The American Journal of Orthopedics

Diabetes mellitus (DM) affects a significant portion of the world’s people, and the problem is increasing in magnitude as the population ages and becomes more obese.¹ An estimated 347 million people have diabetes.¹ In the United States, 26 million (roughly 8% of the population) are affected, making DM a major health issue.² Given the prevalence of diabetes in the general population, it is not surprising that increasing numbers of fracture patients have DM. Unfortunately, for these patients, many relatively simple fractures can have disastrous outcomes. Infections and wound complications occur in disproportionate numbers, healing time is delayed, and risk for nonunion or malunion is substantially higher.³

It is imperative to understand the pathophysiology of DM to appreciate potential interventions and strategies aimed at decreasing complications and improving outcomes of fractures in patients with the disease. In type 1 DM (T1DM), autoimmune destruction of the insulin-secreting β cells in the pancreas results in a complete absence of insulin. Patients with T1DM are dependent on exogenous insulin, and, despite hyperglycemia, most cells in the body are starved for energy. This leads to a catabolic condition, high lipid and protein metabolism, and, in many cases, ketoacidosis. When insulin resistance develops, the β cells are forced to secrete large amounts of insulin; when they fail to keep up, type 2 DM (T2DM) develops. T2DM is often associated with obesity, as excess adipose tissue leads to insulin resistance. Although exogenous insulin may be necessary to treat advanced T2DM, other medications are commonly used to effectively lower blood glucose: Secretagogues (eg, sulfonylureas) facilitate insulin release from β cells, and sensitizers (eg, metformin) increase insulin sensitivity.^4,5

The potential morbidity of fractures in patients with DM can be appreciated with the example of ankle fractures. These typically uncomplicated fractures can have very poor outcomes in the setting of DM. In a prospective study of approximately 1500 patients with ankle fractures treated with open reduction and internal fixation, Wukich and colleagues⁶ found that 9.5% of patients with DM (vs 2.4% of patients without DM) developed surgical site infections. As defined by Jones and colleagues,⁷ major complications of treating ankle fractures in patients with DM include infection, malunion, nonunion, Charcot arthropathy, and amputation. The authors reported major complications in 31% and 17% of patients with and without DM, respectively. Highlighting the importance of glycemic control, Wukich and colleagues⁶ found relative risks of 3.8 for infection, 3.4 for noninfectious complications, and 5.0 for revision in complicated (vs uncomplicated) fractures in patients with DM.

Given the magnitude of problems in the treatment of fractures in patients with DM, we focus our review on the pathobiology of diabetes in terms of bone metabolism and fracture healing, wound healing and vasculopathy, infection, and potential new treatment modalities.

Bone Metabolism and Fracture Healing in Diabetes

Insulin appears to play a role in bone metabolism and fracture healing. Therefore, absence of insulin in T1DM and elevated insulin levels associated with T2DM likely influence these metabolic and fracture-healing processes. Insulin has been hypothesized to have an anabolic effect on bone, and in both human and animal models bone mineral density (BMD) is significantly lower in T1DM. Furthermore, BMD in T2DM has been shown to be normal or even elevated.⁸ Other metabolic effects of insulin on bone metabolism and growth include slower growth rates and lower BMD in pediatric patients with T1DM versus patients without diabetes, and some animal models show bone microarchitecture altered in the absence of insulin (and reversible with insulin supplementation).⁹ These factors seem to contradict the markedly elevated risk for osteoporotic fracture in patients with T2DM, but the mechanisms responsible for this have not been elucidated.⁸

In terms of fracture healing, resorption of cartilage during transition to hard callus appears to be influenced by diabetes. It has been hypothesized that the smaller callus observed in diabetic mice may be secondary to upregulation of osteoclasts. Initial callus size appears not to differ between mice with streptozotocin-induced diabetes, which exhibit a complete absence of insulin, and control mice, but levels of osteoclast and osteoclastogenesis mediators were significantly higher in the diabetic mice.¹⁰ Some investigators think that the reduction in cartilage callus size in diabetic mice is caused by altered mRNA expression and collagen production.¹¹ Diabetic mice, in addition to showing increased resorption by osteoclasts, demonstrate increased chondrocyte apoptosis, which is thought to activate cartilage resorption events. Exogenous insulin effectively reverses this cartilage loss to baseline levels.¹²

Osteoblasts are a crucial component of the fracture-healing cascade, and acute and chronic hyperglycemia, the hallmark of diabetes, has a variety of effects on osteoblasts.¹³ Genes for cell-signal proteins such as osteocalcin, MMP-13, and vascular endothelial growth factor are downregulated in the presence of chronic hyperglycemia, whereas genes for alkaline phosphate are upregulated. Acute hyperglycemia by way of hyperosmolarity is associated with MMP-13 downregulation. Thus, osteoblasts appear to respond to hyperglycemia through 2 different processes: Hyperosmolarity, through osteoblast cell shrinkage, influences the acute response, and hyperglycemia itself, through pathways such as nonenzymatic glycosylation, protein kinase C (PKC) signaling, and the polyol pathway, is the force behind the chronic response.¹⁴ The lineage of osteoblasts from mesenchymal stem cells also can be affected by hyperglycemia, with lower growth rates for mesenchymal stem cells and preferential development toward the adipocyte lineage, while the osteoblast and chondrocyte lineages are downregulated.¹⁵

Increased osteoblast apoptosis has been associated with diabetes through advanced glycation end-products (AGEs), which modify the structure and function of bioactive compounds through AGE receptors that cross-link and bond to amino groups on bioactive molecules.¹⁶ It has been reported that AGEs interfere with osteoblast development and collagen and osteocalcin production.¹⁷ A common AGE, carboxymethyl lysine-modified collagen, has been associated with a significant increase in apoptosis through the mitogen-activated protein kinase (MAPK) pathway. Although most of the literature suggests that osteoblast apoptosis is activated by hypoxia, nitric oxide, or integrins, these factors all have the MAPK pathway in common.¹⁸

Osteoclasts are also influenced by diabetes. Recent work in T1DM demonstrated that osteoclasts are hyperactive and more sensitive to receptor activator of nuclear factor kB ligand (RANKL) compared with osteoclasts from the population without diabetes. It is also known that osteoclasts are under the control of immunologic mediators like lipopolysaccharide (LPS), a surface component of gram-negative bacteria, and various other proinflammatory cytokines. In patients with diabetes, osteoclasts react differently to LPS and other proinflammatory cytokines, at times with opposing effects, including secretion of RANKL to stimulate resorption by the osteoclast, and precursors preventing progression into osteoclasts. In healthy people, high LPS levels not only prevent precursors from producing more osteoclasts, but promote them to mature into immune-like cells that actually phagocytose bacteria. So, in a state of infection, precursors shift from bone-resorbing osteoclasts to protective immune cells. This phenomenon does not occur in patients with diabetes, in whom the osteoclasts instead resorb more bone and stimulate inflammation by releasing cytokines.¹⁹

Interestingly, osteoblasts and osteoclasts are also affected by medications commonly used to treat diabetes. Thiazolidinediones are a class of sensitizers often used to treat patients with T2DM. Thiazolidinediones, particularly rosiglitazone, have been associated with increased bone loss primarily caused by increased bone resorption by osteoclasts.²⁰ In addition, some investigators think that thiazolidinediones induce osteocyte apoptosis, contributing to impaired bone growth.⁸ Metformin, an insulin sensitizer, appears to have a positive effect on bone growth and fracture risk by enhancing osteoblastogenesis and inhibiting osteoclastogenesis, leading to a protective effect on bone.⁸

Peripheral neuropathy, which is often associated with diabetes, appears to play a major role in fracture-healing complications, even more so than hyperglycemia does. A recent clinical paper found that patients with diabetic neuropathy had a 44% risk of foot and ankle fracture-healing complications.²¹ Regardless of the risk, the pathogenesis of diabetic neuropathy can be caused by several mechanisms. Neural tissue does not require insulin for glucose uptake; therefore, in a state of hyperglycemia, aldose reductase shunts glucose to sorbitol while using protective glutathione and generating reactive oxygen species. This oxidative stress results in nerve damage or neuropathy. Microangiopathy, which we discuss in more detail later, also contributes to the development of neuropathy, through compromised flow of blood to neural tissue.²² Another mechanism contributing to diabetic neuropathy involves PKC, which is activated by 1,2-diacylglycerol in the presence of glucose, leading to vascular changes that restrict the flow of blood to peripheral nerves.²³ Finally, AGEs may also participate by altering nerve function after binding to neural tissue.

Charcot neuroarthropathy is a complication associated with diabetes, particularly after injury in which chronic inflammation results in damage to the joint through fracture, dislocation, and osteolytic bony destruction. The pathophysiology is attributed to repeated microtrauma caused by loss of protective sensibility and hyperemia caused by dysregulation.²⁴ Sympathetic and sensory nerve fibers are associated with bone, but a few serve as mechanoreceptors and nociceptors, which can activate substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide—neuropeptides all thought to be involved in the inflammatory process, and in the activation of osteoblasts and osteoclasts. In diabetic neuropathy, many of these neuropeptides show a reduced regulation response, which can lead to impaired fracture healing. In particular, osteoclast activity is upregulated, and consequently bone resorption is increased. In addition to the neuropeptides mentioned, RANKL is one mechanism by which this upregulation occurs.²⁵

It is clear that bone metabolism and fracture healing are complex processes. In the patient with diabetes, many factors are affected, including BMD, bone microarchitecture and bone growth, cartilage resorption during callus formation, osteoblast and osteoclast activation through both altered responses to cell signals and pharmacologic interactions, and, finally, peripheral neuropathy. Given the complex interactions described, it is likely that these factors in combination, as well as those yet undiscovered, negatively affect fracture healing.

Wound Healing and Vasculopathy in Diabetes

Bone healing and soft-tissue healing depend on many of the same factors. Therefore, interactions between neuropathy and vasculopathy can have a tremendous influence on wound healing in patients with diabetes. The vascular pathology that occurs in diabetes depends in part on the fact that endothelial cells do not require insulin for glucose uptake and therefore are more susceptible to damage by hyperglycemia. As already discussed, shunting of glucose through the polyol pathway with the resultant oxidative stress is partly responsible for angiopathy in diabetes.

Also as already discussed, AGEs affect intracellular processes by protein binding and gene regulation and by disrupting the communication between cells and the surrounding matrix. From an extracellular standpoint, AGEs bind to circulating proteins, promoting inflammation and upregulation/downregulation of growth factors, including endothelial nitric oxide synthase, a critical vasodilator. Endothelin 1, on the other hand, is a potent vasoconstrictor. It is upregulated while transforming growth factor b and plasminogen activator inhibitor 1 are upregulated, resulting in further vascular damage.²⁶ The common mechanism for this vasculopathy appears to be superoxide production in the mitochondria, caused by excess glucose oxidation forcing coenzyme Q to donate electrons to oxygen, producing the superoxides. Superoxides in turn inhibit glyceraldehyde 3-phosphate dehydrogenase, which activates the polyol pathway, AGE formation, PKC, and the hexosamine pathway.²⁶ In addition to coenzyme Q, several other enzymes generate reactive oxygen species, including nicotinamide adenine dinucleotide phosphate oxidase, aldehyde oxidase, xanthine oxidase, and glucose oxidase.²⁷ These reactive oxygen species exacerbate oxidative stress, leading to further endothelial cell damage, and cause vascular smooth muscle injury.²⁸

Further influencing the wound-healing environment are the effects of diabetes on blood vessel maintenance and repair as well as angiogenesis in response to local-tissue hypoxia. Vessel-repair mechanisms require endothelial progenitor cells (EPCs), which are released in response to cytokines and neural impulses.²⁹ Bone marrow–derived EPCs have inadequate proliferative and migratory ability in patients with diabetes.^28,30 In a diabetic mouse model, EPCs appear in the bone marrow at normal levels, but levels in circulation are lower than anticipated, because of poor proliferation and mobilization, it is thought. In terms of local-tissue hypoxia, hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that promotes the expression of genes that in turn induce angiogenesis. The mechanism of this response is complex, and hyperglycemia has the potential to interfere in various steps of the cycle. In response to local-tissue hypoxia, the HIF-1a subunit must localize to the target site, where it combines with HIF-1b to create the active dimer, HIF-1.³¹ This active dimer is regulated through degradation of the a subunit in the presence of normal oxygen levels. However, in a state of hypoxia, the molecule is stabilized, promoting angiogenesis and fibroblast migration.³² Recent evidence suggests that hyperglycemia interferes with the dimerization process and that there is a failure of HIF-1a to locate into the nucleus, which is crucial for gene upregulation.^31-33

Infection in Diabetes

Throughout the literature, the risk for infection after fracture is consistently higher in patients with diabetes than without diabetes. There likely are many contributing factors, including diminished blood flow and vasculopathy as well as a dampened immune response as a result of defective granulocytic, phagocytic, and chemotactic functions and defective macrophagic activity. Typically, polymorphonuclear leukocytes (PMNs) migrate to bacteria and initiate bacteriocidal activity, and then macrophages phagocytize PMNs and other damaged cells. PMNs demonstrate impaired function in patients with diabetes—reduced phagocytic response and respiratory burst as well as chemotaxis impairment. The diminished phagocytic potential is substantial, with experiments showing an almost 50% reduction in ingestion of Staphylococcus aureus in a patient with diabetes than in one without diabetes.³⁴ Expression of surface integrins, which mediate PMN adhesion to the basement membrane of the tissue, appears to be negatively altered in both T1DM and T2DM, furthering diminishing the chemotactic response of PMNs.³⁵ Impaired leukocyte function may also be a downstream effect of vasculopathy and associated hypoxia/hypoxemia as PMNs use superoxide radicals and other oxidizing agents to create a bacteriocidal environment that is negatively impacted in a low oxygen state.³ In addition, macrophages are disabled in patients with diabetes. (In rats with streptozotocin-induced diabetes, there is inadequate activation of macrophages in the early stages of healing.³⁶) Furthermore, AGEs similar to those mentioned earlier have a significant negative impact on macrophagic function.³⁷ Thus, both the activation and the activity of macrophages appear to be impeded in the setting of diabetes.

Potential New Treatment Modalities

There is tremendous potential for clinical intervention to prevent pathologic outcomes in patients with diabetes, given the complex tissue, cellular, and molecular interactions, particularly those caused by hyperglycemia. At the bone tissue level, increased osteoclastic activity in patients with diabetes has been associated with many complications, including Charcot arthropathy. RANKL modulates differentiation and activation of osteoclasts; thus, RANKL inhibition is a possible therapeutic target.³⁸ Elevated AGE levels have also been observed in patients with Charcot arthropathy, and RAGE, the receptor for AGE, has been seen at lower than expected levels in patients with diabetes. RAGE appears to provide a protective effect against excessive bone resorption; therefore, treatment that increases RAGE levels—such as angiotensin-converting-enzyme inhibitors, statins, and glitazones—may be capable of mitigating the osteoclastic effects in Charcot arthropathy.³⁹

AGE formation appears to be central to many pathologic processes in diabetes, so it is a logical therapeutic target, particularly for pathologic processes at the vascular tissue level. Aminoguanidine is an anti-AGE agent that was initially used to prevent diabetic retinopathy, but it has also been shown to prevent general vascular complications in diabetic animal models. The terminal amino residue in the compound specifically binds glucose-derived reactive intermediates and prevents cross-linking, which renders them inactive. Disrupting those cross-links is another treatment strategy. N-phenacylthiazolium bromide  and 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711 or alagebrium) are compounds that have been shown to break cross-links in a diabetic rat model.¹⁶

Another tactic for reducing vascular pathology involves mitigating superoxide radicals, as these radicals are generated from the glycolytic intermediates in hyperglycemic states. It has been reasoned that, if the concentration of these intermediates can be decreased, there would be less substrate available for the pathways that lead to radical formation. One approach is to use transketolase, an enzyme that shunts intermediates to pathways that do not produce superoxide radicals. In the treatment of patients with diabetic retinopathy, early data appear promising with benfotiamine, a thiamine derivative, which upregulates transketolase 250%. An additional tactic involves catalytic antioxidants—namely, superoxide dismutase/catalase mimetic, which has been shown to reduce hyperglycemia-induced superoxides. These interventions are appealing because of their nonstoichiometric reactions, which render them potentially more potent antioxidants.²⁶

Potential neurologic interventions include recombinant human nerve growth factor, neurotrophic factors, and gene therapy, all directed toward preventing or regenerating neuropathic tissues in patients with diabetes. Most of these interventions, however, remain theoretical. Few trials have demonstrated clinically significant improvement. In patients with T1DM, however, the absence of circulating C-peptide is thought to contribute to diabetic neuropathy. Results of trials with subcutaneous C-peptide treatment suggest improvement in both sural sensory and vibration perception after only 12 weeks.⁴⁰ These novel treatments further emphasize the potential for intervention at the tissue, cellular, and molecular levels.

Conclusion

Whereas most fractures are uncomplicated in healthy patients, they can have devastating consequences in patients with diabetes. In this review, we have highlighted many of the pathologic processes that can influence outcomes of fractures in patients with diabetes. These problems will become more common as the population ages, age-related risks for osteoporosis and fragility fracture increase, and diabetes becomes nearly epidemic in our increasingly obese, sedentary society. Although some progress has been made, a more thorough intervention strategy is needed to improve both bone and soft-tissue outcomes of fractures in patients with diabetes.

Diabetes mellitus (DM) affects a significant portion of the world’s people, and the problem is increasing in magnitude as the population ages and becomes more obese.¹ An estimated 347 million people have diabetes.¹ In the United States, 26 million (roughly 8% of the population) are affected, making DM a major health issue.² Given the prevalence of diabetes in the general population, it is not surprising that increasing numbers of fracture patients have DM. Unfortunately, for these patients, many relatively simple fractures can have disastrous outcomes. Infections and wound complications occur in disproportionate numbers, healing time is delayed, and risk for nonunion or malunion is substantially higher.³

It is imperative to understand the pathophysiology of DM to appreciate potential interventions and strategies aimed at decreasing complications and improving outcomes of fractures in patients with the disease. In type 1 DM (T1DM), autoimmune destruction of the insulin-secreting β cells in the pancreas results in a complete absence of insulin. Patients with T1DM are dependent on exogenous insulin, and, despite hyperglycemia, most cells in the body are starved for energy. This leads to a catabolic condition, high lipid and protein metabolism, and, in many cases, ketoacidosis. When insulin resistance develops, the β cells are forced to secrete large amounts of insulin; when they fail to keep up, type 2 DM (T2DM) develops. T2DM is often associated with obesity, as excess adipose tissue leads to insulin resistance. Although exogenous insulin may be necessary to treat advanced T2DM, other medications are commonly used to effectively lower blood glucose: Secretagogues (eg, sulfonylureas) facilitate insulin release from β cells, and sensitizers (eg, metformin) increase insulin sensitivity.^4,5

The potential morbidity of fractures in patients with DM can be appreciated with the example of ankle fractures. These typically uncomplicated fractures can have very poor outcomes in the setting of DM. In a prospective study of approximately 1500 patients with ankle fractures treated with open reduction and internal fixation, Wukich and colleagues⁶ found that 9.5% of patients with DM (vs 2.4% of patients without DM) developed surgical site infections. As defined by Jones and colleagues,⁷ major complications of treating ankle fractures in patients with DM include infection, malunion, nonunion, Charcot arthropathy, and amputation. The authors reported major complications in 31% and 17% of patients with and without DM, respectively. Highlighting the importance of glycemic control, Wukich and colleagues⁶ found relative risks of 3.8 for infection, 3.4 for noninfectious complications, and 5.0 for revision in complicated (vs uncomplicated) fractures in patients with DM.

Given the magnitude of problems in the treatment of fractures in patients with DM, we focus our review on the pathobiology of diabetes in terms of bone metabolism and fracture healing, wound healing and vasculopathy, infection, and potential new treatment modalities.

Bone Metabolism and Fracture Healing in Diabetes

Insulin appears to play a role in bone metabolism and fracture healing. Therefore, absence of insulin in T1DM and elevated insulin levels associated with T2DM likely influence these metabolic and fracture-healing processes. Insulin has been hypothesized to have an anabolic effect on bone, and in both human and animal models bone mineral density (BMD) is significantly lower in T1DM. Furthermore, BMD in T2DM has been shown to be normal or even elevated.⁸ Other metabolic effects of insulin on bone metabolism and growth include slower growth rates and lower BMD in pediatric patients with T1DM versus patients without diabetes, and some animal models show bone microarchitecture altered in the absence of insulin (and reversible with insulin supplementation).⁹ These factors seem to contradict the markedly elevated risk for osteoporotic fracture in patients with T2DM, but the mechanisms responsible for this have not been elucidated.⁸

In terms of fracture healing, resorption of cartilage during transition to hard callus appears to be influenced by diabetes. It has been hypothesized that the smaller callus observed in diabetic mice may be secondary to upregulation of osteoclasts. Initial callus size appears not to differ between mice with streptozotocin-induced diabetes, which exhibit a complete absence of insulin, and control mice, but levels of osteoclast and osteoclastogenesis mediators were significantly higher in the diabetic mice.¹⁰ Some investigators think that the reduction in cartilage callus size in diabetic mice is caused by altered mRNA expression and collagen production.¹¹ Diabetic mice, in addition to showing increased resorption by osteoclasts, demonstrate increased chondrocyte apoptosis, which is thought to activate cartilage resorption events. Exogenous insulin effectively reverses this cartilage loss to baseline levels.¹²

Osteoblasts are a crucial component of the fracture-healing cascade, and acute and chronic hyperglycemia, the hallmark of diabetes, has a variety of effects on osteoblasts.¹³ Genes for cell-signal proteins such as osteocalcin, MMP-13, and vascular endothelial growth factor are downregulated in the presence of chronic hyperglycemia, whereas genes for alkaline phosphate are upregulated. Acute hyperglycemia by way of hyperosmolarity is associated with MMP-13 downregulation. Thus, osteoblasts appear to respond to hyperglycemia through 2 different processes: Hyperosmolarity, through osteoblast cell shrinkage, influences the acute response, and hyperglycemia itself, through pathways such as nonenzymatic glycosylation, protein kinase C (PKC) signaling, and the polyol pathway, is the force behind the chronic response.¹⁴ The lineage of osteoblasts from mesenchymal stem cells also can be affected by hyperglycemia, with lower growth rates for mesenchymal stem cells and preferential development toward the adipocyte lineage, while the osteoblast and chondrocyte lineages are downregulated.¹⁵

Increased osteoblast apoptosis has been associated with diabetes through advanced glycation end-products (AGEs), which modify the structure and function of bioactive compounds through AGE receptors that cross-link and bond to amino groups on bioactive molecules.¹⁶ It has been reported that AGEs interfere with osteoblast development and collagen and osteocalcin production.¹⁷ A common AGE, carboxymethyl lysine-modified collagen, has been associated with a significant increase in apoptosis through the mitogen-activated protein kinase (MAPK) pathway. Although most of the literature suggests that osteoblast apoptosis is activated by hypoxia, nitric oxide, or integrins, these factors all have the MAPK pathway in common.¹⁸

Osteoclasts are also influenced by diabetes. Recent work in T1DM demonstrated that osteoclasts are hyperactive and more sensitive to receptor activator of nuclear factor kB ligand (RANKL) compared with osteoclasts from the population without diabetes. It is also known that osteoclasts are under the control of immunologic mediators like lipopolysaccharide (LPS), a surface component of gram-negative bacteria, and various other proinflammatory cytokines. In patients with diabetes, osteoclasts react differently to LPS and other proinflammatory cytokines, at times with opposing effects, including secretion of RANKL to stimulate resorption by the osteoclast, and precursors preventing progression into osteoclasts. In healthy people, high LPS levels not only prevent precursors from producing more osteoclasts, but promote them to mature into immune-like cells that actually phagocytose bacteria. So, in a state of infection, precursors shift from bone-resorbing osteoclasts to protective immune cells. This phenomenon does not occur in patients with diabetes, in whom the osteoclasts instead resorb more bone and stimulate inflammation by releasing cytokines.¹⁹

Interestingly, osteoblasts and osteoclasts are also affected by medications commonly used to treat diabetes. Thiazolidinediones are a class of sensitizers often used to treat patients with T2DM. Thiazolidinediones, particularly rosiglitazone, have been associated with increased bone loss primarily caused by increased bone resorption by osteoclasts.²⁰ In addition, some investigators think that thiazolidinediones induce osteocyte apoptosis, contributing to impaired bone growth.⁸ Metformin, an insulin sensitizer, appears to have a positive effect on bone growth and fracture risk by enhancing osteoblastogenesis and inhibiting osteoclastogenesis, leading to a protective effect on bone.⁸

Peripheral neuropathy, which is often associated with diabetes, appears to play a major role in fracture-healing complications, even more so than hyperglycemia does. A recent clinical paper found that patients with diabetic neuropathy had a 44% risk of foot and ankle fracture-healing complications.²¹ Regardless of the risk, the pathogenesis of diabetic neuropathy can be caused by several mechanisms. Neural tissue does not require insulin for glucose uptake; therefore, in a state of hyperglycemia, aldose reductase shunts glucose to sorbitol while using protective glutathione and generating reactive oxygen species. This oxidative stress results in nerve damage or neuropathy. Microangiopathy, which we discuss in more detail later, also contributes to the development of neuropathy, through compromised flow of blood to neural tissue.²² Another mechanism contributing to diabetic neuropathy involves PKC, which is activated by 1,2-diacylglycerol in the presence of glucose, leading to vascular changes that restrict the flow of blood to peripheral nerves.²³ Finally, AGEs may also participate by altering nerve function after binding to neural tissue.

Charcot neuroarthropathy is a complication associated with diabetes, particularly after injury in which chronic inflammation results in damage to the joint through fracture, dislocation, and osteolytic bony destruction. The pathophysiology is attributed to repeated microtrauma caused by loss of protective sensibility and hyperemia caused by dysregulation.²⁴ Sympathetic and sensory nerve fibers are associated with bone, but a few serve as mechanoreceptors and nociceptors, which can activate substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide—neuropeptides all thought to be involved in the inflammatory process, and in the activation of osteoblasts and osteoclasts. In diabetic neuropathy, many of these neuropeptides show a reduced regulation response, which can lead to impaired fracture healing. In particular, osteoclast activity is upregulated, and consequently bone resorption is increased. In addition to the neuropeptides mentioned, RANKL is one mechanism by which this upregulation occurs.²⁵

It is clear that bone metabolism and fracture healing are complex processes. In the patient with diabetes, many factors are affected, including BMD, bone microarchitecture and bone growth, cartilage resorption during callus formation, osteoblast and osteoclast activation through both altered responses to cell signals and pharmacologic interactions, and, finally, peripheral neuropathy. Given the complex interactions described, it is likely that these factors in combination, as well as those yet undiscovered, negatively affect fracture healing.

Wound Healing and Vasculopathy in Diabetes

Bone healing and soft-tissue healing depend on many of the same factors. Therefore, interactions between neuropathy and vasculopathy can have a tremendous influence on wound healing in patients with diabetes. The vascular pathology that occurs in diabetes depends in part on the fact that endothelial cells do not require insulin for glucose uptake and therefore are more susceptible to damage by hyperglycemia. As already discussed, shunting of glucose through the polyol pathway with the resultant oxidative stress is partly responsible for angiopathy in diabetes.

Also as already discussed, AGEs affect intracellular processes by protein binding and gene regulation and by disrupting the communication between cells and the surrounding matrix. From an extracellular standpoint, AGEs bind to circulating proteins, promoting inflammation and upregulation/downregulation of growth factors, including endothelial nitric oxide synthase, a critical vasodilator. Endothelin 1, on the other hand, is a potent vasoconstrictor. It is upregulated while transforming growth factor b and plasminogen activator inhibitor 1 are upregulated, resulting in further vascular damage.²⁶ The common mechanism for this vasculopathy appears to be superoxide production in the mitochondria, caused by excess glucose oxidation forcing coenzyme Q to donate electrons to oxygen, producing the superoxides. Superoxides in turn inhibit glyceraldehyde 3-phosphate dehydrogenase, which activates the polyol pathway, AGE formation, PKC, and the hexosamine pathway.²⁶ In addition to coenzyme Q, several other enzymes generate reactive oxygen species, including nicotinamide adenine dinucleotide phosphate oxidase, aldehyde oxidase, xanthine oxidase, and glucose oxidase.²⁷ These reactive oxygen species exacerbate oxidative stress, leading to further endothelial cell damage, and cause vascular smooth muscle injury.²⁸

Further influencing the wound-healing environment are the effects of diabetes on blood vessel maintenance and repair as well as angiogenesis in response to local-tissue hypoxia. Vessel-repair mechanisms require endothelial progenitor cells (EPCs), which are released in response to cytokines and neural impulses.²⁹ Bone marrow–derived EPCs have inadequate proliferative and migratory ability in patients with diabetes.^28,30 In a diabetic mouse model, EPCs appear in the bone marrow at normal levels, but levels in circulation are lower than anticipated, because of poor proliferation and mobilization, it is thought. In terms of local-tissue hypoxia, hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that promotes the expression of genes that in turn induce angiogenesis. The mechanism of this response is complex, and hyperglycemia has the potential to interfere in various steps of the cycle. In response to local-tissue hypoxia, the HIF-1a subunit must localize to the target site, where it combines with HIF-1b to create the active dimer, HIF-1.³¹ This active dimer is regulated through degradation of the a subunit in the presence of normal oxygen levels. However, in a state of hypoxia, the molecule is stabilized, promoting angiogenesis and fibroblast migration.³² Recent evidence suggests that hyperglycemia interferes with the dimerization process and that there is a failure of HIF-1a to locate into the nucleus, which is crucial for gene upregulation.^31-33

Infection in Diabetes

Throughout the literature, the risk for infection after fracture is consistently higher in patients with diabetes than without diabetes. There likely are many contributing factors, including diminished blood flow and vasculopathy as well as a dampened immune response as a result of defective granulocytic, phagocytic, and chemotactic functions and defective macrophagic activity. Typically, polymorphonuclear leukocytes (PMNs) migrate to bacteria and initiate bacteriocidal activity, and then macrophages phagocytize PMNs and other damaged cells. PMNs demonstrate impaired function in patients with diabetes—reduced phagocytic response and respiratory burst as well as chemotaxis impairment. The diminished phagocytic potential is substantial, with experiments showing an almost 50% reduction in ingestion of Staphylococcus aureus in a patient with diabetes than in one without diabetes.³⁴ Expression of surface integrins, which mediate PMN adhesion to the basement membrane of the tissue, appears to be negatively altered in both T1DM and T2DM, furthering diminishing the chemotactic response of PMNs.³⁵ Impaired leukocyte function may also be a downstream effect of vasculopathy and associated hypoxia/hypoxemia as PMNs use superoxide radicals and other oxidizing agents to create a bacteriocidal environment that is negatively impacted in a low oxygen state.³ In addition, macrophages are disabled in patients with diabetes. (In rats with streptozotocin-induced diabetes, there is inadequate activation of macrophages in the early stages of healing.³⁶) Furthermore, AGEs similar to those mentioned earlier have a significant negative impact on macrophagic function.³⁷ Thus, both the activation and the activity of macrophages appear to be impeded in the setting of diabetes.

Potential New Treatment Modalities

There is tremendous potential for clinical intervention to prevent pathologic outcomes in patients with diabetes, given the complex tissue, cellular, and molecular interactions, particularly those caused by hyperglycemia. At the bone tissue level, increased osteoclastic activity in patients with diabetes has been associated with many complications, including Charcot arthropathy. RANKL modulates differentiation and activation of osteoclasts; thus, RANKL inhibition is a possible therapeutic target.³⁸ Elevated AGE levels have also been observed in patients with Charcot arthropathy, and RAGE, the receptor for AGE, has been seen at lower than expected levels in patients with diabetes. RAGE appears to provide a protective effect against excessive bone resorption; therefore, treatment that increases RAGE levels—such as angiotensin-converting-enzyme inhibitors, statins, and glitazones—may be capable of mitigating the osteoclastic effects in Charcot arthropathy.³⁹

AGE formation appears to be central to many pathologic processes in diabetes, so it is a logical therapeutic target, particularly for pathologic processes at the vascular tissue level. Aminoguanidine is an anti-AGE agent that was initially used to prevent diabetic retinopathy, but it has also been shown to prevent general vascular complications in diabetic animal models. The terminal amino residue in the compound specifically binds glucose-derived reactive intermediates and prevents cross-linking, which renders them inactive. Disrupting those cross-links is another treatment strategy. N-phenacylthiazolium bromide  and 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711 or alagebrium) are compounds that have been shown to break cross-links in a diabetic rat model.¹⁶

Another tactic for reducing vascular pathology involves mitigating superoxide radicals, as these radicals are generated from the glycolytic intermediates in hyperglycemic states. It has been reasoned that, if the concentration of these intermediates can be decreased, there would be less substrate available for the pathways that lead to radical formation. One approach is to use transketolase, an enzyme that shunts intermediates to pathways that do not produce superoxide radicals. In the treatment of patients with diabetic retinopathy, early data appear promising with benfotiamine, a thiamine derivative, which upregulates transketolase 250%. An additional tactic involves catalytic antioxidants—namely, superoxide dismutase/catalase mimetic, which has been shown to reduce hyperglycemia-induced superoxides. These interventions are appealing because of their nonstoichiometric reactions, which render them potentially more potent antioxidants.²⁶

Potential neurologic interventions include recombinant human nerve growth factor, neurotrophic factors, and gene therapy, all directed toward preventing or regenerating neuropathic tissues in patients with diabetes. Most of these interventions, however, remain theoretical. Few trials have demonstrated clinically significant improvement. In patients with T1DM, however, the absence of circulating C-peptide is thought to contribute to diabetic neuropathy. Results of trials with subcutaneous C-peptide treatment suggest improvement in both sural sensory and vibration perception after only 12 weeks.⁴⁰ These novel treatments further emphasize the potential for intervention at the tissue, cellular, and molecular levels.

Conclusion

Whereas most fractures are uncomplicated in healthy patients, they can have devastating consequences in patients with diabetes. In this review, we have highlighted many of the pathologic processes that can influence outcomes of fractures in patients with diabetes. These problems will become more common as the population ages, age-related risks for osteoporosis and fragility fracture increase, and diabetes becomes nearly epidemic in our increasingly obese, sedentary society. Although some progress has been made, a more thorough intervention strategy is needed to improve both bone and soft-tissue outcomes of fractures in patients with diabetes.

Diabetes mellitus (DM) affects a significant portion of the world’s people, and the problem is increasing in magnitude as the population ages and becomes more obese.¹ An estimated 347 million people have diabetes.¹ In the United States, 26 million (roughly 8% of the population) are affected, making DM a major health issue.² Given the prevalence of diabetes in the general population, it is not surprising that increasing numbers of fracture patients have DM. Unfortunately, for these patients, many relatively simple fractures can have disastrous outcomes. Infections and wound complications occur in disproportionate numbers, healing time is delayed, and risk for nonunion or malunion is substantially higher.³

It is imperative to understand the pathophysiology of DM to appreciate potential interventions and strategies aimed at decreasing complications and improving outcomes of fractures in patients with the disease. In type 1 DM (T1DM), autoimmune destruction of the insulin-secreting β cells in the pancreas results in a complete absence of insulin. Patients with T1DM are dependent on exogenous insulin, and, despite hyperglycemia, most cells in the body are starved for energy. This leads to a catabolic condition, high lipid and protein metabolism, and, in many cases, ketoacidosis. When insulin resistance develops, the β cells are forced to secrete large amounts of insulin; when they fail to keep up, type 2 DM (T2DM) develops. T2DM is often associated with obesity, as excess adipose tissue leads to insulin resistance. Although exogenous insulin may be necessary to treat advanced T2DM, other medications are commonly used to effectively lower blood glucose: Secretagogues (eg, sulfonylureas) facilitate insulin release from β cells, and sensitizers (eg, metformin) increase insulin sensitivity.^4,5

The potential morbidity of fractures in patients with DM can be appreciated with the example of ankle fractures. These typically uncomplicated fractures can have very poor outcomes in the setting of DM. In a prospective study of approximately 1500 patients with ankle fractures treated with open reduction and internal fixation, Wukich and colleagues⁶ found that 9.5% of patients with DM (vs 2.4% of patients without DM) developed surgical site infections. As defined by Jones and colleagues,⁷ major complications of treating ankle fractures in patients with DM include infection, malunion, nonunion, Charcot arthropathy, and amputation. The authors reported major complications in 31% and 17% of patients with and without DM, respectively. Highlighting the importance of glycemic control, Wukich and colleagues⁶ found relative risks of 3.8 for infection, 3.4 for noninfectious complications, and 5.0 for revision in complicated (vs uncomplicated) fractures in patients with DM.

Given the magnitude of problems in the treatment of fractures in patients with DM, we focus our review on the pathobiology of diabetes in terms of bone metabolism and fracture healing, wound healing and vasculopathy, infection, and potential new treatment modalities.

Bone Metabolism and Fracture Healing in Diabetes

Insulin appears to play a role in bone metabolism and fracture healing. Therefore, absence of insulin in T1DM and elevated insulin levels associated with T2DM likely influence these metabolic and fracture-healing processes. Insulin has been hypothesized to have an anabolic effect on bone, and in both human and animal models bone mineral density (BMD) is significantly lower in T1DM. Furthermore, BMD in T2DM has been shown to be normal or even elevated.⁸ Other metabolic effects of insulin on bone metabolism and growth include slower growth rates and lower BMD in pediatric patients with T1DM versus patients without diabetes, and some animal models show bone microarchitecture altered in the absence of insulin (and reversible with insulin supplementation).⁹ These factors seem to contradict the markedly elevated risk for osteoporotic fracture in patients with T2DM, but the mechanisms responsible for this have not been elucidated.⁸

In terms of fracture healing, resorption of cartilage during transition to hard callus appears to be influenced by diabetes. It has been hypothesized that the smaller callus observed in diabetic mice may be secondary to upregulation of osteoclasts. Initial callus size appears not to differ between mice with streptozotocin-induced diabetes, which exhibit a complete absence of insulin, and control mice, but levels of osteoclast and osteoclastogenesis mediators were significantly higher in the diabetic mice.¹⁰ Some investigators think that the reduction in cartilage callus size in diabetic mice is caused by altered mRNA expression and collagen production.¹¹ Diabetic mice, in addition to showing increased resorption by osteoclasts, demonstrate increased chondrocyte apoptosis, which is thought to activate cartilage resorption events. Exogenous insulin effectively reverses this cartilage loss to baseline levels.¹²

Osteoblasts are a crucial component of the fracture-healing cascade, and acute and chronic hyperglycemia, the hallmark of diabetes, has a variety of effects on osteoblasts.¹³ Genes for cell-signal proteins such as osteocalcin, MMP-13, and vascular endothelial growth factor are downregulated in the presence of chronic hyperglycemia, whereas genes for alkaline phosphate are upregulated. Acute hyperglycemia by way of hyperosmolarity is associated with MMP-13 downregulation. Thus, osteoblasts appear to respond to hyperglycemia through 2 different processes: Hyperosmolarity, through osteoblast cell shrinkage, influences the acute response, and hyperglycemia itself, through pathways such as nonenzymatic glycosylation, protein kinase C (PKC) signaling, and the polyol pathway, is the force behind the chronic response.¹⁴ The lineage of osteoblasts from mesenchymal stem cells also can be affected by hyperglycemia, with lower growth rates for mesenchymal stem cells and preferential development toward the adipocyte lineage, while the osteoblast and chondrocyte lineages are downregulated.¹⁵

Increased osteoblast apoptosis has been associated with diabetes through advanced glycation end-products (AGEs), which modify the structure and function of bioactive compounds through AGE receptors that cross-link and bond to amino groups on bioactive molecules.¹⁶ It has been reported that AGEs interfere with osteoblast development and collagen and osteocalcin production.¹⁷ A common AGE, carboxymethyl lysine-modified collagen, has been associated with a significant increase in apoptosis through the mitogen-activated protein kinase (MAPK) pathway. Although most of the literature suggests that osteoblast apoptosis is activated by hypoxia, nitric oxide, or integrins, these factors all have the MAPK pathway in common.¹⁸

Osteoclasts are also influenced by diabetes. Recent work in T1DM demonstrated that osteoclasts are hyperactive and more sensitive to receptor activator of nuclear factor kB ligand (RANKL) compared with osteoclasts from the population without diabetes. It is also known that osteoclasts are under the control of immunologic mediators like lipopolysaccharide (LPS), a surface component of gram-negative bacteria, and various other proinflammatory cytokines. In patients with diabetes, osteoclasts react differently to LPS and other proinflammatory cytokines, at times with opposing effects, including secretion of RANKL to stimulate resorption by the osteoclast, and precursors preventing progression into osteoclasts. In healthy people, high LPS levels not only prevent precursors from producing more osteoclasts, but promote them to mature into immune-like cells that actually phagocytose bacteria. So, in a state of infection, precursors shift from bone-resorbing osteoclasts to protective immune cells. This phenomenon does not occur in patients with diabetes, in whom the osteoclasts instead resorb more bone and stimulate inflammation by releasing cytokines.¹⁹

Interestingly, osteoblasts and osteoclasts are also affected by medications commonly used to treat diabetes. Thiazolidinediones are a class of sensitizers often used to treat patients with T2DM. Thiazolidinediones, particularly rosiglitazone, have been associated with increased bone loss primarily caused by increased bone resorption by osteoclasts.²⁰ In addition, some investigators think that thiazolidinediones induce osteocyte apoptosis, contributing to impaired bone growth.⁸ Metformin, an insulin sensitizer, appears to have a positive effect on bone growth and fracture risk by enhancing osteoblastogenesis and inhibiting osteoclastogenesis, leading to a protective effect on bone.⁸

Peripheral neuropathy, which is often associated with diabetes, appears to play a major role in fracture-healing complications, even more so than hyperglycemia does. A recent clinical paper found that patients with diabetic neuropathy had a 44% risk of foot and ankle fracture-healing complications.²¹ Regardless of the risk, the pathogenesis of diabetic neuropathy can be caused by several mechanisms. Neural tissue does not require insulin for glucose uptake; therefore, in a state of hyperglycemia, aldose reductase shunts glucose to sorbitol while using protective glutathione and generating reactive oxygen species. This oxidative stress results in nerve damage or neuropathy. Microangiopathy, which we discuss in more detail later, also contributes to the development of neuropathy, through compromised flow of blood to neural tissue.²² Another mechanism contributing to diabetic neuropathy involves PKC, which is activated by 1,2-diacylglycerol in the presence of glucose, leading to vascular changes that restrict the flow of blood to peripheral nerves.²³ Finally, AGEs may also participate by altering nerve function after binding to neural tissue.

Charcot neuroarthropathy is a complication associated with diabetes, particularly after injury in which chronic inflammation results in damage to the joint through fracture, dislocation, and osteolytic bony destruction. The pathophysiology is attributed to repeated microtrauma caused by loss of protective sensibility and hyperemia caused by dysregulation.²⁴ Sympathetic and sensory nerve fibers are associated with bone, but a few serve as mechanoreceptors and nociceptors, which can activate substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide—neuropeptides all thought to be involved in the inflammatory process, and in the activation of osteoblasts and osteoclasts. In diabetic neuropathy, many of these neuropeptides show a reduced regulation response, which can lead to impaired fracture healing. In particular, osteoclast activity is upregulated, and consequently bone resorption is increased. In addition to the neuropeptides mentioned, RANKL is one mechanism by which this upregulation occurs.²⁵

It is clear that bone metabolism and fracture healing are complex processes. In the patient with diabetes, many factors are affected, including BMD, bone microarchitecture and bone growth, cartilage resorption during callus formation, osteoblast and osteoclast activation through both altered responses to cell signals and pharmacologic interactions, and, finally, peripheral neuropathy. Given the complex interactions described, it is likely that these factors in combination, as well as those yet undiscovered, negatively affect fracture healing.

Wound Healing and Vasculopathy in Diabetes

Bone healing and soft-tissue healing depend on many of the same factors. Therefore, interactions between neuropathy and vasculopathy can have a tremendous influence on wound healing in patients with diabetes. The vascular pathology that occurs in diabetes depends in part on the fact that endothelial cells do not require insulin for glucose uptake and therefore are more susceptible to damage by hyperglycemia. As already discussed, shunting of glucose through the polyol pathway with the resultant oxidative stress is partly responsible for angiopathy in diabetes.

Also as already discussed, AGEs affect intracellular processes by protein binding and gene regulation and by disrupting the communication between cells and the surrounding matrix. From an extracellular standpoint, AGEs bind to circulating proteins, promoting inflammation and upregulation/downregulation of growth factors, including endothelial nitric oxide synthase, a critical vasodilator. Endothelin 1, on the other hand, is a potent vasoconstrictor. It is upregulated while transforming growth factor b and plasminogen activator inhibitor 1 are upregulated, resulting in further vascular damage.²⁶ The common mechanism for this vasculopathy appears to be superoxide production in the mitochondria, caused by excess glucose oxidation forcing coenzyme Q to donate electrons to oxygen, producing the superoxides. Superoxides in turn inhibit glyceraldehyde 3-phosphate dehydrogenase, which activates the polyol pathway, AGE formation, PKC, and the hexosamine pathway.²⁶ In addition to coenzyme Q, several other enzymes generate reactive oxygen species, including nicotinamide adenine dinucleotide phosphate oxidase, aldehyde oxidase, xanthine oxidase, and glucose oxidase.²⁷ These reactive oxygen species exacerbate oxidative stress, leading to further endothelial cell damage, and cause vascular smooth muscle injury.²⁸

Further influencing the wound-healing environment are the effects of diabetes on blood vessel maintenance and repair as well as angiogenesis in response to local-tissue hypoxia. Vessel-repair mechanisms require endothelial progenitor cells (EPCs), which are released in response to cytokines and neural impulses.²⁹ Bone marrow–derived EPCs have inadequate proliferative and migratory ability in patients with diabetes.^28,30 In a diabetic mouse model, EPCs appear in the bone marrow at normal levels, but levels in circulation are lower than anticipated, because of poor proliferation and mobilization, it is thought. In terms of local-tissue hypoxia, hypoxia-inducible factor 1 (HIF-1) is an important transcription factor that promotes the expression of genes that in turn induce angiogenesis. The mechanism of this response is complex, and hyperglycemia has the potential to interfere in various steps of the cycle. In response to local-tissue hypoxia, the HIF-1a subunit must localize to the target site, where it combines with HIF-1b to create the active dimer, HIF-1.³¹ This active dimer is regulated through degradation of the a subunit in the presence of normal oxygen levels. However, in a state of hypoxia, the molecule is stabilized, promoting angiogenesis and fibroblast migration.³² Recent evidence suggests that hyperglycemia interferes with the dimerization process and that there is a failure of HIF-1a to locate into the nucleus, which is crucial for gene upregulation.^31-33

Infection in Diabetes

Throughout the literature, the risk for infection after fracture is consistently higher in patients with diabetes than without diabetes. There likely are many contributing factors, including diminished blood flow and vasculopathy as well as a dampened immune response as a result of defective granulocytic, phagocytic, and chemotactic functions and defective macrophagic activity. Typically, polymorphonuclear leukocytes (PMNs) migrate to bacteria and initiate bacteriocidal activity, and then macrophages phagocytize PMNs and other damaged cells. PMNs demonstrate impaired function in patients with diabetes—reduced phagocytic response and respiratory burst as well as chemotaxis impairment. The diminished phagocytic potential is substantial, with experiments showing an almost 50% reduction in ingestion of Staphylococcus aureus in a patient with diabetes than in one without diabetes.³⁴ Expression of surface integrins, which mediate PMN adhesion to the basement membrane of the tissue, appears to be negatively altered in both T1DM and T2DM, furthering diminishing the chemotactic response of PMNs.³⁵ Impaired leukocyte function may also be a downstream effect of vasculopathy and associated hypoxia/hypoxemia as PMNs use superoxide radicals and other oxidizing agents to create a bacteriocidal environment that is negatively impacted in a low oxygen state.³ In addition, macrophages are disabled in patients with diabetes. (In rats with streptozotocin-induced diabetes, there is inadequate activation of macrophages in the early stages of healing.³⁶) Furthermore, AGEs similar to those mentioned earlier have a significant negative impact on macrophagic function.³⁷ Thus, both the activation and the activity of macrophages appear to be impeded in the setting of diabetes.

Potential New Treatment Modalities

There is tremendous potential for clinical intervention to prevent pathologic outcomes in patients with diabetes, given the complex tissue, cellular, and molecular interactions, particularly those caused by hyperglycemia. At the bone tissue level, increased osteoclastic activity in patients with diabetes has been associated with many complications, including Charcot arthropathy. RANKL modulates differentiation and activation of osteoclasts; thus, RANKL inhibition is a possible therapeutic target.³⁸ Elevated AGE levels have also been observed in patients with Charcot arthropathy, and RAGE, the receptor for AGE, has been seen at lower than expected levels in patients with diabetes. RAGE appears to provide a protective effect against excessive bone resorption; therefore, treatment that increases RAGE levels—such as angiotensin-converting-enzyme inhibitors, statins, and glitazones—may be capable of mitigating the osteoclastic effects in Charcot arthropathy.³⁹

AGE formation appears to be central to many pathologic processes in diabetes, so it is a logical therapeutic target, particularly for pathologic processes at the vascular tissue level. Aminoguanidine is an anti-AGE agent that was initially used to prevent diabetic retinopathy, but it has also been shown to prevent general vascular complications in diabetic animal models. The terminal amino residue in the compound specifically binds glucose-derived reactive intermediates and prevents cross-linking, which renders them inactive. Disrupting those cross-links is another treatment strategy. N-phenacylthiazolium bromide  and 3-phenacyl-4,5-dimethylthiazolium chloride (ALT-711 or alagebrium) are compounds that have been shown to break cross-links in a diabetic rat model.¹⁶

Another tactic for reducing vascular pathology involves mitigating superoxide radicals, as these radicals are generated from the glycolytic intermediates in hyperglycemic states. It has been reasoned that, if the concentration of these intermediates can be decreased, there would be less substrate available for the pathways that lead to radical formation. One approach is to use transketolase, an enzyme that shunts intermediates to pathways that do not produce superoxide radicals. In the treatment of patients with diabetic retinopathy, early data appear promising with benfotiamine, a thiamine derivative, which upregulates transketolase 250%. An additional tactic involves catalytic antioxidants—namely, superoxide dismutase/catalase mimetic, which has been shown to reduce hyperglycemia-induced superoxides. These interventions are appealing because of their nonstoichiometric reactions, which render them potentially more potent antioxidants.²⁶

Potential neurologic interventions include recombinant human nerve growth factor, neurotrophic factors, and gene therapy, all directed toward preventing or regenerating neuropathic tissues in patients with diabetes. Most of these interventions, however, remain theoretical. Few trials have demonstrated clinically significant improvement. In patients with T1DM, however, the absence of circulating C-peptide is thought to contribute to diabetic neuropathy. Results of trials with subcutaneous C-peptide treatment suggest improvement in both sural sensory and vibration perception after only 12 weeks.⁴⁰ These novel treatments further emphasize the potential for intervention at the tissue, cellular, and molecular levels.

Conclusion

Whereas most fractures are uncomplicated in healthy patients, they can have devastating consequences in patients with diabetes. In this review, we have highlighted many of the pathologic processes that can influence outcomes of fractures in patients with diabetes. These problems will become more common as the population ages, age-related risks for osteoporosis and fragility fracture increase, and diabetes becomes nearly epidemic in our increasingly obese, sedentary society. Although some progress has been made, a more thorough intervention strategy is needed to improve both bone and soft-tissue outcomes of fractures in patients with diabetes.

Analyzing the Guidelines: It Can't All Be Level I

The demand for total joint arthroplasty continues to rise, resulting in a steady increase in the number of primary total hip and knee replacements every year. Unfortunately, as these numbers rise, so will the number of periprosthetic joint infections (PJIs). The economic burden and patient morbidity associated with PJI has resulted in the creation of multiple orthopedic societies and committees focused on formulating “best practice” guidelines in order to reduce the rates of PJI as much as possible.

The new guidelines for surgical site infection (SSI) prevention by the Centers for Disease Control and Prevention (CDC) recently forced the orthopedic community to critically analyze the current literature. Dr. Javad Parvizi’s editorial elegantly notes that many areas of infection prevention and treatment are not well evaluated, and many of our day-to-day practices are based on low levels of evidence. Level I studies continue to be a costly and time-consuming challenge due to the already very low SSI rate, and, in order to show an improvement in this rate, thousands of patients are required for study. This makes a multicenter approach necessary to ensure adequate power, and a multicenter study often requires significant resources and funding outlets. These requirements have resulted in many of our practice recommendations being based on retrospective reviews, which have inherent methodological limitations. The retrospective nature of these studies lacks the experimental design necessary to confidently make treatment recommendations; however, they do allow us to look at what strategies have been tried, and in essence, how well they worked. Although level III and IV studies do not allow us to compare treatments head to head, they do give us some insights into viable treatment strategies and should not be completely disregarded. The results of retrospective studies allow us to design prospective experiments based on what we have observed as successful treatment modalities in particular patient cohorts.

An alternative approach for evaluating new and existing treatment strategies is through basic science translational research. Future advancements in PJI diagnosis and treatment will likely be founded upon translational research efforts from clinician scientists testing treatment protocols both on the benchtop and in animal models. The most glaring knowledge gaps in PJI should be identified through the combined efforts of the CDC, the Musculoskeletal Infection Society, the American Academy of Orthopaedic Surgeons, and the Orthopaedic Research Society. Coordinated efforts should be made and strategies executed to systematically fund translational projects that answer these questions. Translational studies will be able to safely and methodically evaluate new and even established treatment protocols for PJI in a cost-effective manner.

We have made great strides in the prevention and treatment of PJI over the past 2 decades. When working together as a cohesive profession, we will undoubtedly continue to advance our knowledge base and improve treatment recommendations for our patients.

Analyzing the Guidelines: It Can't All Be Level I

The demand for total joint arthroplasty continues to rise, resulting in a steady increase in the number of primary total hip and knee replacements every year. Unfortunately, as these numbers rise, so will the number of periprosthetic joint infections (PJIs). The economic burden and patient morbidity associated with PJI has resulted in the creation of multiple orthopedic societies and committees focused on formulating “best practice” guidelines in order to reduce the rates of PJI as much as possible.

The new guidelines for surgical site infection (SSI) prevention by the Centers for Disease Control and Prevention (CDC) recently forced the orthopedic community to critically analyze the current literature. Dr. Javad Parvizi’s editorial elegantly notes that many areas of infection prevention and treatment are not well evaluated, and many of our day-to-day practices are based on low levels of evidence. Level I studies continue to be a costly and time-consuming challenge due to the already very low SSI rate, and, in order to show an improvement in this rate, thousands of patients are required for study. This makes a multicenter approach necessary to ensure adequate power, and a multicenter study often requires significant resources and funding outlets. These requirements have resulted in many of our practice recommendations being based on retrospective reviews, which have inherent methodological limitations. The retrospective nature of these studies lacks the experimental design necessary to confidently make treatment recommendations; however, they do allow us to look at what strategies have been tried, and in essence, how well they worked. Although level III and IV studies do not allow us to compare treatments head to head, they do give us some insights into viable treatment strategies and should not be completely disregarded. The results of retrospective studies allow us to design prospective experiments based on what we have observed as successful treatment modalities in particular patient cohorts.

An alternative approach for evaluating new and existing treatment strategies is through basic science translational research. Future advancements in PJI diagnosis and treatment will likely be founded upon translational research efforts from clinician scientists testing treatment protocols both on the benchtop and in animal models. The most glaring knowledge gaps in PJI should be identified through the combined efforts of the CDC, the Musculoskeletal Infection Society, the American Academy of Orthopaedic Surgeons, and the Orthopaedic Research Society. Coordinated efforts should be made and strategies executed to systematically fund translational projects that answer these questions. Translational studies will be able to safely and methodically evaluate new and even established treatment protocols for PJI in a cost-effective manner.

We have made great strides in the prevention and treatment of PJI over the past 2 decades. When working together as a cohesive profession, we will undoubtedly continue to advance our knowledge base and improve treatment recommendations for our patients.

Analyzing the Guidelines: It Can't All Be Level I

The demand for total joint arthroplasty continues to rise, resulting in a steady increase in the number of primary total hip and knee replacements every year. Unfortunately, as these numbers rise, so will the number of periprosthetic joint infections (PJIs). The economic burden and patient morbidity associated with PJI has resulted in the creation of multiple orthopedic societies and committees focused on formulating “best practice” guidelines in order to reduce the rates of PJI as much as possible.

The new guidelines for surgical site infection (SSI) prevention by the Centers for Disease Control and Prevention (CDC) recently forced the orthopedic community to critically analyze the current literature. Dr. Javad Parvizi’s editorial elegantly notes that many areas of infection prevention and treatment are not well evaluated, and many of our day-to-day practices are based on low levels of evidence. Level I studies continue to be a costly and time-consuming challenge due to the already very low SSI rate, and, in order to show an improvement in this rate, thousands of patients are required for study. This makes a multicenter approach necessary to ensure adequate power, and a multicenter study often requires significant resources and funding outlets. These requirements have resulted in many of our practice recommendations being based on retrospective reviews, which have inherent methodological limitations. The retrospective nature of these studies lacks the experimental design necessary to confidently make treatment recommendations; however, they do allow us to look at what strategies have been tried, and in essence, how well they worked. Although level III and IV studies do not allow us to compare treatments head to head, they do give us some insights into viable treatment strategies and should not be completely disregarded. The results of retrospective studies allow us to design prospective experiments based on what we have observed as successful treatment modalities in particular patient cohorts.

An alternative approach for evaluating new and existing treatment strategies is through basic science translational research. Future advancements in PJI diagnosis and treatment will likely be founded upon translational research efforts from clinician scientists testing treatment protocols both on the benchtop and in animal models. The most glaring knowledge gaps in PJI should be identified through the combined efforts of the CDC, the Musculoskeletal Infection Society, the American Academy of Orthopaedic Surgeons, and the Orthopaedic Research Society. Coordinated efforts should be made and strategies executed to systematically fund translational projects that answer these questions. Translational studies will be able to safely and methodically evaluate new and even established treatment protocols for PJI in a cost-effective manner.

We have made great strides in the prevention and treatment of PJI over the past 2 decades. When working together as a cohesive profession, we will undoubtedly continue to advance our knowledge base and improve treatment recommendations for our patients.

According to a new study, total knee arthroplasty is highly effective in reducing clinically relevant knee pain to a greater extent than other subjective health-related quality-of-life indicies in patients with rheumatoid arthritis, although this improvement is less marked as compared to outcomes in patients with osteoarthritis. These study findings were published online ahead of print July 20 in Arthritis & Rheumatology.

The study included patients with rheumatologist-diagnosed arthritis undergoing primary total knee arthroplasty during 1999 to 2012. Indices of pain knee, and health-related quality of life were obtained in 3 consecutive 6-month intervals: preoperative, perioperative, and postoperative. Descriptive statistics and 1-way analysis of variance were used to compare total knee arthroplasty outcomes by diagnosis. Effect sizes and standardized response means were calculated between baseline and recovery.

Of the participating 18,897 patients, 834 people with rheumatoid arthritis, and 315 people with osteoarthritis had undergone index total knee arthroplasty at mean ages 65 and 68. Post total knee arthroplasty, significant improvements were observed for most domains of pain, function, and health-related quality of life within both disease groups, with greater impact in osteoarthritis. Based on the standardized response means, the maximum improvement was shown in index knee pain.

The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive health-related quality of life indices in detecting post-total knee arthroplasty improvement in rheumatoid arthritis. A diagnosis of rheumatoid arthritis, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following total knee arthroplasty.

Senior author Kaleb D. Michaud, PhD, Associate Professor in the Division of Rheumatology and Immunology at the University of Nebraska Medical Center in Omaha, and colleagues said that total knee replacement can serve as a “time machine” by which patients can return to a less disabled lifestyle, before the arthritic process catches up.

“A new knee can give osteoarthritis patients 10 to 20 years of painless use, whereas rheumatoid arthritis continues to affect the joint soon afterward,” the researchers said. “It’s an important and effective treatment, but patients with rheumatoid arthritis shouldn’t expect the same, often dramatic results experienced by their osteoarthritis counterparts,” Dr. Michaud said.

According to a new study, total knee arthroplasty is highly effective in reducing clinically relevant knee pain to a greater extent than other subjective health-related quality-of-life indicies in patients with rheumatoid arthritis, although this improvement is less marked as compared to outcomes in patients with osteoarthritis. These study findings were published online ahead of print July 20 in Arthritis & Rheumatology.

The study included patients with rheumatologist-diagnosed arthritis undergoing primary total knee arthroplasty during 1999 to 2012. Indices of pain knee, and health-related quality of life were obtained in 3 consecutive 6-month intervals: preoperative, perioperative, and postoperative. Descriptive statistics and 1-way analysis of variance were used to compare total knee arthroplasty outcomes by diagnosis. Effect sizes and standardized response means were calculated between baseline and recovery.

Of the participating 18,897 patients, 834 people with rheumatoid arthritis, and 315 people with osteoarthritis had undergone index total knee arthroplasty at mean ages 65 and 68. Post total knee arthroplasty, significant improvements were observed for most domains of pain, function, and health-related quality of life within both disease groups, with greater impact in osteoarthritis. Based on the standardized response means, the maximum improvement was shown in index knee pain.

The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive health-related quality of life indices in detecting post-total knee arthroplasty improvement in rheumatoid arthritis. A diagnosis of rheumatoid arthritis, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following total knee arthroplasty.

Senior author Kaleb D. Michaud, PhD, Associate Professor in the Division of Rheumatology and Immunology at the University of Nebraska Medical Center in Omaha, and colleagues said that total knee replacement can serve as a “time machine” by which patients can return to a less disabled lifestyle, before the arthritic process catches up.

“A new knee can give osteoarthritis patients 10 to 20 years of painless use, whereas rheumatoid arthritis continues to affect the joint soon afterward,” the researchers said. “It’s an important and effective treatment, but patients with rheumatoid arthritis shouldn’t expect the same, often dramatic results experienced by their osteoarthritis counterparts,” Dr. Michaud said.

According to a new study, total knee arthroplasty is highly effective in reducing clinically relevant knee pain to a greater extent than other subjective health-related quality-of-life indicies in patients with rheumatoid arthritis, although this improvement is less marked as compared to outcomes in patients with osteoarthritis. These study findings were published online ahead of print July 20 in Arthritis & Rheumatology.

The study included patients with rheumatologist-diagnosed arthritis undergoing primary total knee arthroplasty during 1999 to 2012. Indices of pain knee, and health-related quality of life were obtained in 3 consecutive 6-month intervals: preoperative, perioperative, and postoperative. Descriptive statistics and 1-way analysis of variance were used to compare total knee arthroplasty outcomes by diagnosis. Effect sizes and standardized response means were calculated between baseline and recovery.

Of the participating 18,897 patients, 834 people with rheumatoid arthritis, and 315 people with osteoarthritis had undergone index total knee arthroplasty at mean ages 65 and 68. Post total knee arthroplasty, significant improvements were observed for most domains of pain, function, and health-related quality of life within both disease groups, with greater impact in osteoarthritis. Based on the standardized response means, the maximum improvement was shown in index knee pain.

The Health Assessment Questionnaire II and the Short Form 36 physical component summary were the most responsive health-related quality of life indices in detecting post-total knee arthroplasty improvement in rheumatoid arthritis. A diagnosis of rheumatoid arthritis, lower income, and preoperative anxiety were independently associated with a lower degree of improvement in index knee pain following total knee arthroplasty.

Senior author Kaleb D. Michaud, PhD, Associate Professor in the Division of Rheumatology and Immunology at the University of Nebraska Medical Center in Omaha, and colleagues said that total knee replacement can serve as a “time machine” by which patients can return to a less disabled lifestyle, before the arthritic process catches up.

“A new knee can give osteoarthritis patients 10 to 20 years of painless use, whereas rheumatoid arthritis continues to affect the joint soon afterward,” the researchers said. “It’s an important and effective treatment, but patients with rheumatoid arthritis shouldn’t expect the same, often dramatic results experienced by their osteoarthritis counterparts,” Dr. Michaud said.

Postmenopausal women with kidney or bladder stones are not at increased risk for osteoporosis, but they do have about a 15% increased risk of another painful stone, according to a study published online ahead of print May 19 in the Journal of Bone and Mineral Research.

Researchers examined data on approximately 150,000 postmenopausal women and found, despite the 2 conditions being clearly associated in men, the same did not hold true for women. “We know in men that if you have a kidney stone, you are more likely to have osteoporosis,” said Laura D. Carbone, MD, MS, Division Chief Chief of Rheumatology in the Department of Medicine at the Medical College of Georgia at Georgia Regents University in Augusta. What Dr. Carbone and colleagues found was that “unlike what has been reported in men, a woman having a kidney stone is not a risk factor for osteoporosis. However, having one urinary tract stone does put women at increased risk for a second stone.”

Data came from participants in the National Institutes of Health Women’s Health Initiative. Out of more than 150,000 women followed in the Women’s Health Initiative, 9,856 women reported urinary tract stones at the start of or over the course of the study. The women were followed for about 8 years, on average.

Dr. Carbone and colleagues looked at the data several different ways, adjusting for factors that could also influence outcome, such as physical inactivity. Investigators only looked at whether urinary tract stones increased the risk of osteoporosis, not the reverse. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (hazard ratio, 1.10) However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in bone mineral density at any skeletal site or to incident fractures.

The Osteoporotic Fractures in Men study, which looked at nearly 6,000 men with a mean age of 73.7 to determine risk factors for osteoporosis, identified urinary tract stones are a risk factor.

One link between the seemingly disparate conditions of stones and weak bones is an excess of calcium in the urine, which tends to be more common in men, Dr. Carbone said. Sodium and calcium share a common transport mechanism in the kidney, the researchers pointed out, and sodium affects reabsorption of calcium by that organ. When sodium levels are high, more calcium in eliminated in the urine. “Overactivity of the parathyroid glands, which regulate levels of calcium in the blood, is associated with both urinary tract stones and fractures of the vertebra in the spine,” the researchers said.

Some treatments for osteoporosis, including calcium supplementation, can increase the risk of stones. Conversely, individuals who’ve already experienced a urinary tract stone might avoid calcium to help avoid another a subsequent stone and inadvertently increase their osteoporosis risk, the researchers wrote.

“Women with a stone likely should work with their physician to reduce their increased risk of a subsequent stone,” the physicians said, noting that low water and fluid intake, and a high-salt, high-calorie diet are common stone risks.

Postmenopausal women with kidney or bladder stones are not at increased risk for osteoporosis, but they do have about a 15% increased risk of another painful stone, according to a study published online ahead of print May 19 in the Journal of Bone and Mineral Research.

Researchers examined data on approximately 150,000 postmenopausal women and found, despite the 2 conditions being clearly associated in men, the same did not hold true for women. “We know in men that if you have a kidney stone, you are more likely to have osteoporosis,” said Laura D. Carbone, MD, MS, Division Chief Chief of Rheumatology in the Department of Medicine at the Medical College of Georgia at Georgia Regents University in Augusta. What Dr. Carbone and colleagues found was that “unlike what has been reported in men, a woman having a kidney stone is not a risk factor for osteoporosis. However, having one urinary tract stone does put women at increased risk for a second stone.”

Data came from participants in the National Institutes of Health Women’s Health Initiative. Out of more than 150,000 women followed in the Women’s Health Initiative, 9,856 women reported urinary tract stones at the start of or over the course of the study. The women were followed for about 8 years, on average.

Dr. Carbone and colleagues looked at the data several different ways, adjusting for factors that could also influence outcome, such as physical inactivity. Investigators only looked at whether urinary tract stones increased the risk of osteoporosis, not the reverse. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (hazard ratio, 1.10) However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in bone mineral density at any skeletal site or to incident fractures.

The Osteoporotic Fractures in Men study, which looked at nearly 6,000 men with a mean age of 73.7 to determine risk factors for osteoporosis, identified urinary tract stones are a risk factor.

One link between the seemingly disparate conditions of stones and weak bones is an excess of calcium in the urine, which tends to be more common in men, Dr. Carbone said. Sodium and calcium share a common transport mechanism in the kidney, the researchers pointed out, and sodium affects reabsorption of calcium by that organ. When sodium levels are high, more calcium in eliminated in the urine. “Overactivity of the parathyroid glands, which regulate levels of calcium in the blood, is associated with both urinary tract stones and fractures of the vertebra in the spine,” the researchers said.

Some treatments for osteoporosis, including calcium supplementation, can increase the risk of stones. Conversely, individuals who’ve already experienced a urinary tract stone might avoid calcium to help avoid another a subsequent stone and inadvertently increase their osteoporosis risk, the researchers wrote.

“Women with a stone likely should work with their physician to reduce their increased risk of a subsequent stone,” the physicians said, noting that low water and fluid intake, and a high-salt, high-calorie diet are common stone risks.

Postmenopausal women with kidney or bladder stones are not at increased risk for osteoporosis, but they do have about a 15% increased risk of another painful stone, according to a study published online ahead of print May 19 in the Journal of Bone and Mineral Research.

Researchers examined data on approximately 150,000 postmenopausal women and found, despite the 2 conditions being clearly associated in men, the same did not hold true for women. “We know in men that if you have a kidney stone, you are more likely to have osteoporosis,” said Laura D. Carbone, MD, MS, Division Chief Chief of Rheumatology in the Department of Medicine at the Medical College of Georgia at Georgia Regents University in Augusta. What Dr. Carbone and colleagues found was that “unlike what has been reported in men, a woman having a kidney stone is not a risk factor for osteoporosis. However, having one urinary tract stone does put women at increased risk for a second stone.”

Data came from participants in the National Institutes of Health Women’s Health Initiative. Out of more than 150,000 women followed in the Women’s Health Initiative, 9,856 women reported urinary tract stones at the start of or over the course of the study. The women were followed for about 8 years, on average.

Dr. Carbone and colleagues looked at the data several different ways, adjusting for factors that could also influence outcome, such as physical inactivity. Investigators only looked at whether urinary tract stones increased the risk of osteoporosis, not the reverse. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (hazard ratio, 1.10) However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in bone mineral density at any skeletal site or to incident fractures.

The Osteoporotic Fractures in Men study, which looked at nearly 6,000 men with a mean age of 73.7 to determine risk factors for osteoporosis, identified urinary tract stones are a risk factor.

One link between the seemingly disparate conditions of stones and weak bones is an excess of calcium in the urine, which tends to be more common in men, Dr. Carbone said. Sodium and calcium share a common transport mechanism in the kidney, the researchers pointed out, and sodium affects reabsorption of calcium by that organ. When sodium levels are high, more calcium in eliminated in the urine. “Overactivity of the parathyroid glands, which regulate levels of calcium in the blood, is associated with both urinary tract stones and fractures of the vertebra in the spine,” the researchers said.

Some treatments for osteoporosis, including calcium supplementation, can increase the risk of stones. Conversely, individuals who’ve already experienced a urinary tract stone might avoid calcium to help avoid another a subsequent stone and inadvertently increase their osteoporosis risk, the researchers wrote.

“Women with a stone likely should work with their physician to reduce their increased risk of a subsequent stone,” the physicians said, noting that low water and fluid intake, and a high-salt, high-calorie diet are common stone risks.

Total knee replacements can effectively treat degeneration caused by Blount disease, according to a study published online ahead of print July 11 in the Journal of Arthroplasty.

Middle-aged patients with Blount disease who underwent joint replacements on 1 or both knees were found to have stable knees, excellent range of motion, and no need for pain medications, according to the study conducted at Loyola University Medical Center in Illinois.

“With proper attention paid to technical details, patients with Blount or Blount-like deformity can undergo successful total knee arthroplasty,” said Harold Rees, MD, Assistant Professor of Reconstructive Surgery and Joint Replacement at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois, and colleagues.

For the study, Dr. Rees and colleagues reviewed the records of 5 patients with Blount disease. Three patients had replacements on both knees and 2 patients had replacements on 1 knee. Four patients were African American and 4 were male. All were obese. The average age at the time of the knee replacements was 49.9. Patients were followed-up an average of 75.2 months after their knee replacements.

Mean proximal tibial metaphyseal-diaphyseal angle was 20.75 degrees. Each patient had substantial posteromedial tibial bony defects and 6 knees required extensive medial releases. Two knees required increased constraint at index procedure. One patient underwent bilateral revision surgery with rotating hinge prostheses.

The researchers used a scoring system, devised by the Knee Society, that combines clinical, functional, and satisfaction scores. The mean Knee Society score was 212.5, out of a maximum possible score of 255. Patients also were rated on the Western Ontario and McMaster Universities Osteoarthritis Index.

“The main purpose was to highlight surgical considerations in performing total knee arthroplasty in patients with Blount disease or Blount-like deformity. Despite a challenging patient population in which to perform total knee arthroplasty, we show that it can be done with a low risk of complication and reasonable medium-term results,” said the study authors. “Surgeons should be prepared to address posteromedial tibial bony defects and consider constrained arthroplasty at the index procedure,” they said.

Total knee replacements can effectively treat degeneration caused by Blount disease, according to a study published online ahead of print July 11 in the Journal of Arthroplasty.

Middle-aged patients with Blount disease who underwent joint replacements on 1 or both knees were found to have stable knees, excellent range of motion, and no need for pain medications, according to the study conducted at Loyola University Medical Center in Illinois.

“With proper attention paid to technical details, patients with Blount or Blount-like deformity can undergo successful total knee arthroplasty,” said Harold Rees, MD, Assistant Professor of Reconstructive Surgery and Joint Replacement at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois, and colleagues.

For the study, Dr. Rees and colleagues reviewed the records of 5 patients with Blount disease. Three patients had replacements on both knees and 2 patients had replacements on 1 knee. Four patients were African American and 4 were male. All were obese. The average age at the time of the knee replacements was 49.9. Patients were followed-up an average of 75.2 months after their knee replacements.

Mean proximal tibial metaphyseal-diaphyseal angle was 20.75 degrees. Each patient had substantial posteromedial tibial bony defects and 6 knees required extensive medial releases. Two knees required increased constraint at index procedure. One patient underwent bilateral revision surgery with rotating hinge prostheses.

The researchers used a scoring system, devised by the Knee Society, that combines clinical, functional, and satisfaction scores. The mean Knee Society score was 212.5, out of a maximum possible score of 255. Patients also were rated on the Western Ontario and McMaster Universities Osteoarthritis Index.

“The main purpose was to highlight surgical considerations in performing total knee arthroplasty in patients with Blount disease or Blount-like deformity. Despite a challenging patient population in which to perform total knee arthroplasty, we show that it can be done with a low risk of complication and reasonable medium-term results,” said the study authors. “Surgeons should be prepared to address posteromedial tibial bony defects and consider constrained arthroplasty at the index procedure,” they said.

Total knee replacements can effectively treat degeneration caused by Blount disease, according to a study published online ahead of print July 11 in the Journal of Arthroplasty.

Middle-aged patients with Blount disease who underwent joint replacements on 1 or both knees were found to have stable knees, excellent range of motion, and no need for pain medications, according to the study conducted at Loyola University Medical Center in Illinois.

“With proper attention paid to technical details, patients with Blount or Blount-like deformity can undergo successful total knee arthroplasty,” said Harold Rees, MD, Assistant Professor of Reconstructive Surgery and Joint Replacement at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois, and colleagues.

For the study, Dr. Rees and colleagues reviewed the records of 5 patients with Blount disease. Three patients had replacements on both knees and 2 patients had replacements on 1 knee. Four patients were African American and 4 were male. All were obese. The average age at the time of the knee replacements was 49.9. Patients were followed-up an average of 75.2 months after their knee replacements.

Mean proximal tibial metaphyseal-diaphyseal angle was 20.75 degrees. Each patient had substantial posteromedial tibial bony defects and 6 knees required extensive medial releases. Two knees required increased constraint at index procedure. One patient underwent bilateral revision surgery with rotating hinge prostheses.

The researchers used a scoring system, devised by the Knee Society, that combines clinical, functional, and satisfaction scores. The mean Knee Society score was 212.5, out of a maximum possible score of 255. Patients also were rated on the Western Ontario and McMaster Universities Osteoarthritis Index.

“The main purpose was to highlight surgical considerations in performing total knee arthroplasty in patients with Blount disease or Blount-like deformity. Despite a challenging patient population in which to perform total knee arthroplasty, we show that it can be done with a low risk of complication and reasonable medium-term results,” said the study authors. “Surgeons should be prepared to address posteromedial tibial bony defects and consider constrained arthroplasty at the index procedure,” they said.

Applying for a residency program can be a stressful process for medical students. It is a combination of applying for a job in the “real world” and applying to a college or medical school. In certain fields of medicine or surgery, there may be over 600 residency applications for 40 to 80 interviewee slots. Different specialties, as well as programs within a given specialty, take a different number of residents per year. This can vary from 1 to over 20 available spots, depending on the field of medicine or surgery as well as the specific program. Orthopedic surgery residencies, for example, can match between 2 and 12 residents each year. During the 2013–2014 academic year at our institution, there were over 600 applications received for approximately 50 interview slots for a class of 5 orthopedic surgery residents. Nationally, according to publicly available 2013 National Resident Matching Program (NRMP) data, a total of 1038 applicants (833 US medical school seniors) applied for 693 spots in orthopedic surgery, of which 692 were filled, indicating that orthopedic surgery remains one of the most desired fields among medical school seniors.¹ Looking at the statistics provided by the NRMP data, orthopedic applicants remain some of the most competitive, with proportionally higher board scores, publication numbers, and grades, among other factors.¹

Each individual program has its own method for sifting through the applications. At some institutions, the individual “in charge” of the selection committee may look through all applications initially, narrow them down, and then distribute them to the other members of the selection committee to determine the final interviewee list. At other institutions, the initial group of applications may be divided and distributed to the committee members so that each member reviews the applications and ultimately decides upon the interview candidates.

The Electronic Residency Application Service (ERAS) application includes the applicant’s name, birth city, current place of residence, education history, standardized test scores, grades achieved during medical school, letters of recommendation, personal statement, extracurricular activities, volunteer activities, research experience, and languages spoken, along with several other pieces of data, all intended to be able to give the committee a better understanding of the applicant. Interestingly, however, the application also includes a photograph of the applicant.

Countless authors have demonstrated that we make assumptions and reach conclusions without even being aware that this is occurring. This is the theory of “unconscious bias.”^2-5 Unconscious bias applies to how we perceive other people, and occurs when subconscious beliefs or unrecognized stereotypes about specific characteristics, including gender, ethnicity, religion, socioeconomic status, age, and sexual orientation, result in an automatic and unconscious reaction and/or behavior.⁶ Unconscious bias has the ability to affect everything from how health care is delivered to how employees are hired.^7-12 We are all biased, and becoming aware of our biases will help us mitigate them in the workplace.

Title VII of the Civil Rights Act of 1964 requires that employers rely solely on job-related qualifications, and not physical characteristics, in their interviewing and hiring process. The US Equal Employment Opportunity Commission (EEOC), the federal agency that enforces Title VII, includes asking for photographs during the application stage on its list of prohibited practices for employers.¹³ It is our belief that including a photograph in the ERAS application, prior to the selection of interview candidates, may produce unconscious bias in the decision for granting (or not granting) an interview, and this component of the application should be eliminated.

Using a wide spectrum of cultural backgrounds in employers, Dion and colleagues¹⁴ demonstrated that the “what is beautiful is good” bias is present in all cultures when prospective employees are closely matched in qualification. Attractive individuals are thought to have better professional lives and stable marital relationships and personalities, according to previous studies.¹⁴ There has been much research aimed at determining if physical attractiveness is a factor in hiring, and the evidence suggests that the more attractive the applicant is, the greater the chances of being hired.¹⁵ Specifically, Watkins and Johnston¹⁵ have found that attractive people are thought to have better personalities than less attractive people, and that a photograph can influence the hiring decision process.

Bradley Ruffle at Ben-Gurion University and Ze’ev Shtudiner at Ariel University looked at what happens when job hunters include photographs with their curricula vitae (CV), as is the norm in much of Europe and Asia.¹⁶ For over 2500 job postings, they sent 2 identical résumés: one with a photograph and one without a photograph. An equal number of male and female applicants were sent to each posting, as were an equal number of attractive and plain-looking photographs; applications without photographs were also sent as a control group. For men, the results were as expected: CVs of “attractive” men were more likely to elicit a response from the employer (19.7%) compared with those of no-picture men (13.7%) and plain-looking men (9.2%). Interestingly, men who were viewed as “plain-looking” were better off not including a photograph. For the female applicants, however, the results were unexpected: CVs of women without a picture elicited the highest response rate (16.6%), while CVs of “plain-looking” women (13.6%) and of “attractive” women (12.8%) were less likely to receive a response.¹⁶

It is an unfortunate reality that personal preference, bias, and, in some cases, discriminatory hiring practices all factor into the selection process.¹⁷ This is why, as described above, the EEOC includes asking for photographs during the application stage on its list of prohibited practices for employers.¹³ The EEOC website also states: “If needed for identification purposes, a photograph may be obtained after an offer of employment is made and accepted.”¹³ In the residency application scenario, once an applicant has been granted an interview, a photograph can be taken on the day of the interview. With so many interviewees, this may help the interviewers to remember the interviewee. At this point in the process, the applicant has already been granted the interview. The bias associated with merely looking at a photograph is thus eliminated. This is in accordance with Title VII and is clearly different than including a photograph in the initial application, which directly violates Title VII.

Reviewers of applicants may have an unconscious bias due to the applicant’s attractiveness, race, sex, ethnicity, etc. Other, subtler forms of bias may also be present. Without realizing it, people may judge the quality of the photograph, or even what the applicant was wearing in the photograph. In orthopedic surgery, for example, there may be bias in the “size” of the applicant regardless of sex. Reviewers may unconsciously think how is he/she going to hold the leg, cut a rod, reduce a hip, etc. Without even realizing it, this may sway the person reviewing the application to choose one applicant over another. This may occur regardless of the applicant’s actual qualifications as based on the previously described factors, including test scores, grades during medical school, letters of recommendation, personal statement, extracurricular activities, volunteer activities, and research experience.

Unconscious bias is present in everyone. In an ideal world, one would be able to eliminate all sources of unconscious bias in the application process. Bias due to attending an Ivy League school versus a state school, bias due to where the applicant is from, bias due to who wrote the letter of recommendation, along with various other sources of unconscious bias, would be able to be eliminated. Unfortunately, this is not possible. What is possible, however, is to remove the photograph from the application process and to comply with Title VII of the Civil Rights Act of 1964.

Applying for a residency program can be a stressful process for medical students. It is a combination of applying for a job in the “real world” and applying to a college or medical school. In certain fields of medicine or surgery, there may be over 600 residency applications for 40 to 80 interviewee slots. Different specialties, as well as programs within a given specialty, take a different number of residents per year. This can vary from 1 to over 20 available spots, depending on the field of medicine or surgery as well as the specific program. Orthopedic surgery residencies, for example, can match between 2 and 12 residents each year. During the 2013–2014 academic year at our institution, there were over 600 applications received for approximately 50 interview slots for a class of 5 orthopedic surgery residents. Nationally, according to publicly available 2013 National Resident Matching Program (NRMP) data, a total of 1038 applicants (833 US medical school seniors) applied for 693 spots in orthopedic surgery, of which 692 were filled, indicating that orthopedic surgery remains one of the most desired fields among medical school seniors.¹ Looking at the statistics provided by the NRMP data, orthopedic applicants remain some of the most competitive, with proportionally higher board scores, publication numbers, and grades, among other factors.¹

Each individual program has its own method for sifting through the applications. At some institutions, the individual “in charge” of the selection committee may look through all applications initially, narrow them down, and then distribute them to the other members of the selection committee to determine the final interviewee list. At other institutions, the initial group of applications may be divided and distributed to the committee members so that each member reviews the applications and ultimately decides upon the interview candidates.

The Electronic Residency Application Service (ERAS) application includes the applicant’s name, birth city, current place of residence, education history, standardized test scores, grades achieved during medical school, letters of recommendation, personal statement, extracurricular activities, volunteer activities, research experience, and languages spoken, along with several other pieces of data, all intended to be able to give the committee a better understanding of the applicant. Interestingly, however, the application also includes a photograph of the applicant.

Countless authors have demonstrated that we make assumptions and reach conclusions without even being aware that this is occurring. This is the theory of “unconscious bias.”^2-5 Unconscious bias applies to how we perceive other people, and occurs when subconscious beliefs or unrecognized stereotypes about specific characteristics, including gender, ethnicity, religion, socioeconomic status, age, and sexual orientation, result in an automatic and unconscious reaction and/or behavior.⁶ Unconscious bias has the ability to affect everything from how health care is delivered to how employees are hired.^7-12 We are all biased, and becoming aware of our biases will help us mitigate them in the workplace.

Title VII of the Civil Rights Act of 1964 requires that employers rely solely on job-related qualifications, and not physical characteristics, in their interviewing and hiring process. The US Equal Employment Opportunity Commission (EEOC), the federal agency that enforces Title VII, includes asking for photographs during the application stage on its list of prohibited practices for employers.¹³ It is our belief that including a photograph in the ERAS application, prior to the selection of interview candidates, may produce unconscious bias in the decision for granting (or not granting) an interview, and this component of the application should be eliminated.

Using a wide spectrum of cultural backgrounds in employers, Dion and colleagues¹⁴ demonstrated that the “what is beautiful is good” bias is present in all cultures when prospective employees are closely matched in qualification. Attractive individuals are thought to have better professional lives and stable marital relationships and personalities, according to previous studies.¹⁴ There has been much research aimed at determining if physical attractiveness is a factor in hiring, and the evidence suggests that the more attractive the applicant is, the greater the chances of being hired.¹⁵ Specifically, Watkins and Johnston¹⁵ have found that attractive people are thought to have better personalities than less attractive people, and that a photograph can influence the hiring decision process.

Bradley Ruffle at Ben-Gurion University and Ze’ev Shtudiner at Ariel University looked at what happens when job hunters include photographs with their curricula vitae (CV), as is the norm in much of Europe and Asia.¹⁶ For over 2500 job postings, they sent 2 identical résumés: one with a photograph and one without a photograph. An equal number of male and female applicants were sent to each posting, as were an equal number of attractive and plain-looking photographs; applications without photographs were also sent as a control group. For men, the results were as expected: CVs of “attractive” men were more likely to elicit a response from the employer (19.7%) compared with those of no-picture men (13.7%) and plain-looking men (9.2%). Interestingly, men who were viewed as “plain-looking” were better off not including a photograph. For the female applicants, however, the results were unexpected: CVs of women without a picture elicited the highest response rate (16.6%), while CVs of “plain-looking” women (13.6%) and of “attractive” women (12.8%) were less likely to receive a response.¹⁶

It is an unfortunate reality that personal preference, bias, and, in some cases, discriminatory hiring practices all factor into the selection process.¹⁷ This is why, as described above, the EEOC includes asking for photographs during the application stage on its list of prohibited practices for employers.¹³ The EEOC website also states: “If needed for identification purposes, a photograph may be obtained after an offer of employment is made and accepted.”¹³ In the residency application scenario, once an applicant has been granted an interview, a photograph can be taken on the day of the interview. With so many interviewees, this may help the interviewers to remember the interviewee. At this point in the process, the applicant has already been granted the interview. The bias associated with merely looking at a photograph is thus eliminated. This is in accordance with Title VII and is clearly different than including a photograph in the initial application, which directly violates Title VII.

Reviewers of applicants may have an unconscious bias due to the applicant’s attractiveness, race, sex, ethnicity, etc. Other, subtler forms of bias may also be present. Without realizing it, people may judge the quality of the photograph, or even what the applicant was wearing in the photograph. In orthopedic surgery, for example, there may be bias in the “size” of the applicant regardless of sex. Reviewers may unconsciously think how is he/she going to hold the leg, cut a rod, reduce a hip, etc. Without even realizing it, this may sway the person reviewing the application to choose one applicant over another. This may occur regardless of the applicant’s actual qualifications as based on the previously described factors, including test scores, grades during medical school, letters of recommendation, personal statement, extracurricular activities, volunteer activities, and research experience.

Unconscious bias is present in everyone. In an ideal world, one would be able to eliminate all sources of unconscious bias in the application process. Bias due to attending an Ivy League school versus a state school, bias due to where the applicant is from, bias due to who wrote the letter of recommendation, along with various other sources of unconscious bias, would be able to be eliminated. Unfortunately, this is not possible. What is possible, however, is to remove the photograph from the application process and to comply with Title VII of the Civil Rights Act of 1964.

Applying for a residency program can be a stressful process for medical students. It is a combination of applying for a job in the “real world” and applying to a college or medical school. In certain fields of medicine or surgery, there may be over 600 residency applications for 40 to 80 interviewee slots. Different specialties, as well as programs within a given specialty, take a different number of residents per year. This can vary from 1 to over 20 available spots, depending on the field of medicine or surgery as well as the specific program. Orthopedic surgery residencies, for example, can match between 2 and 12 residents each year. During the 2013–2014 academic year at our institution, there were over 600 applications received for approximately 50 interview slots for a class of 5 orthopedic surgery residents. Nationally, according to publicly available 2013 National Resident Matching Program (NRMP) data, a total of 1038 applicants (833 US medical school seniors) applied for 693 spots in orthopedic surgery, of which 692 were filled, indicating that orthopedic surgery remains one of the most desired fields among medical school seniors.¹ Looking at the statistics provided by the NRMP data, orthopedic applicants remain some of the most competitive, with proportionally higher board scores, publication numbers, and grades, among other factors.¹

Each individual program has its own method for sifting through the applications. At some institutions, the individual “in charge” of the selection committee may look through all applications initially, narrow them down, and then distribute them to the other members of the selection committee to determine the final interviewee list. At other institutions, the initial group of applications may be divided and distributed to the committee members so that each member reviews the applications and ultimately decides upon the interview candidates.

The Electronic Residency Application Service (ERAS) application includes the applicant’s name, birth city, current place of residence, education history, standardized test scores, grades achieved during medical school, letters of recommendation, personal statement, extracurricular activities, volunteer activities, research experience, and languages spoken, along with several other pieces of data, all intended to be able to give the committee a better understanding of the applicant. Interestingly, however, the application also includes a photograph of the applicant.

Countless authors have demonstrated that we make assumptions and reach conclusions without even being aware that this is occurring. This is the theory of “unconscious bias.”^2-5 Unconscious bias applies to how we perceive other people, and occurs when subconscious beliefs or unrecognized stereotypes about specific characteristics, including gender, ethnicity, religion, socioeconomic status, age, and sexual orientation, result in an automatic and unconscious reaction and/or behavior.⁶ Unconscious bias has the ability to affect everything from how health care is delivered to how employees are hired.^7-12 We are all biased, and becoming aware of our biases will help us mitigate them in the workplace.

Title VII of the Civil Rights Act of 1964 requires that employers rely solely on job-related qualifications, and not physical characteristics, in their interviewing and hiring process. The US Equal Employment Opportunity Commission (EEOC), the federal agency that enforces Title VII, includes asking for photographs during the application stage on its list of prohibited practices for employers.¹³ It is our belief that including a photograph in the ERAS application, prior to the selection of interview candidates, may produce unconscious bias in the decision for granting (or not granting) an interview, and this component of the application should be eliminated.

Using a wide spectrum of cultural backgrounds in employers, Dion and colleagues¹⁴ demonstrated that the “what is beautiful is good” bias is present in all cultures when prospective employees are closely matched in qualification. Attractive individuals are thought to have better professional lives and stable marital relationships and personalities, according to previous studies.¹⁴ There has been much research aimed at determining if physical attractiveness is a factor in hiring, and the evidence suggests that the more attractive the applicant is, the greater the chances of being hired.¹⁵ Specifically, Watkins and Johnston¹⁵ have found that attractive people are thought to have better personalities than less attractive people, and that a photograph can influence the hiring decision process.

Bradley Ruffle at Ben-Gurion University and Ze’ev Shtudiner at Ariel University looked at what happens when job hunters include photographs with their curricula vitae (CV), as is the norm in much of Europe and Asia.¹⁶ For over 2500 job postings, they sent 2 identical résumés: one with a photograph and one without a photograph. An equal number of male and female applicants were sent to each posting, as were an equal number of attractive and plain-looking photographs; applications without photographs were also sent as a control group. For men, the results were as expected: CVs of “attractive” men were more likely to elicit a response from the employer (19.7%) compared with those of no-picture men (13.7%) and plain-looking men (9.2%). Interestingly, men who were viewed as “plain-looking” were better off not including a photograph. For the female applicants, however, the results were unexpected: CVs of women without a picture elicited the highest response rate (16.6%), while CVs of “plain-looking” women (13.6%) and of “attractive” women (12.8%) were less likely to receive a response.¹⁶

It is an unfortunate reality that personal preference, bias, and, in some cases, discriminatory hiring practices all factor into the selection process.¹⁷ This is why, as described above, the EEOC includes asking for photographs during the application stage on its list of prohibited practices for employers.¹³ The EEOC website also states: “If needed for identification purposes, a photograph may be obtained after an offer of employment is made and accepted.”¹³ In the residency application scenario, once an applicant has been granted an interview, a photograph can be taken on the day of the interview. With so many interviewees, this may help the interviewers to remember the interviewee. At this point in the process, the applicant has already been granted the interview. The bias associated with merely looking at a photograph is thus eliminated. This is in accordance with Title VII and is clearly different than including a photograph in the initial application, which directly violates Title VII.

Reviewers of applicants may have an unconscious bias due to the applicant’s attractiveness, race, sex, ethnicity, etc. Other, subtler forms of bias may also be present. Without realizing it, people may judge the quality of the photograph, or even what the applicant was wearing in the photograph. In orthopedic surgery, for example, there may be bias in the “size” of the applicant regardless of sex. Reviewers may unconsciously think how is he/she going to hold the leg, cut a rod, reduce a hip, etc. Without even realizing it, this may sway the person reviewing the application to choose one applicant over another. This may occur regardless of the applicant’s actual qualifications as based on the previously described factors, including test scores, grades during medical school, letters of recommendation, personal statement, extracurricular activities, volunteer activities, and research experience.

Unconscious bias is present in everyone. In an ideal world, one would be able to eliminate all sources of unconscious bias in the application process. Bias due to attending an Ivy League school versus a state school, bias due to where the applicant is from, bias due to who wrote the letter of recommendation, along with various other sources of unconscious bias, would be able to be eliminated. Unfortunately, this is not possible. What is possible, however, is to remove the photograph from the application process and to comply with Title VII of the Civil Rights Act of 1964.

Osteochondromas are common benign bone tumors composed of a bony protrusion with an overlying cartilage cap.¹ This lesion constitutes 24% to 40% of all benign bone tumors, and the great majority arise from the metaphyseal region of long bones.² The scapula accounts for only 3% to 5% of all osteochondromas; however, this lesion is the most common benign bone tumor to involve the scapula.³

In contrast, cutaneous bronchogenic cyst of the scapula is an exceedingly rare pathology. The bronchogenic cyst is a congenital cystic mass lined by tracheobronchial structures and respiratory epithelium.⁴ These are most commonly located in the thorax, although numerous remote locations have also been described, including cutaneous cysts.⁵ The overall incidence of bronchogenic cysts is thought to be 1 in 42,000 to 1 in 68,000.⁶ There are only 15 case reports of cutaneous bronchogenic cysts in the scapular region.⁷

We report the case of a novel dual lesion of both an osteochondroma and a contiguous cutaneous bronchogenic cyst in the scapula. The patient’s guardian provided written informed consent for print and electronic publication of this case report.

Case Report

A 12-month-old boy presented to our clinic with the complaint of a mass over the left scapula. The mass was first noted incidentally several weeks earlier during bathing. Examination revealed a firm, subcutaneous, nontender mass measuring 1×2 cm located over the spine of the scapula. There were no overlying skin changes, and there was normal function of the ipsilateral upper extremity. Anteroposterior and lateral chest radiographs revealed no abnormality. Magnetic resonance imaging (MRI) showed an exostosis projecting from the scapular spine measuring 2×6×7 mm with an adjacent cystic mass measuring 5×8×9 mm that was thought to represent bursitis (Figure 1). The decision was made to observe the mass. 

The patient returned to clinic at age 31 months with a new complaint of scant drainage of serous fluid from a pinprick-sized hole located just superolateral to the scapular mass. The child’s mother reported daily manual expression of fluid from the mass via the hole, without which the mass would enlarge. There were no local or systemic signs of infection. A repeat MRI again revealed an exostosis with an adjacent cystic mass with interval enlargement of the cyst (Figure 2). At age 4.5 years, the decision was made to proceed with excision of the osteochondroma and adjacent cystic mass.

The mass was approached via a 2-cm incision designed to excise the tract to the skin. Dissection revealed a sinus tract connecting to a well-defined cystic sac. This sac was attached to the underlying exostosis. The exostosis and attached cyst were excised en bloc. The cyst was opened, revealing foul-smelling, cloudy white fluid that was sent for culture; the specimen was sent for pathology.

The fluid culture grew mixed flora, with no Staphylococcus aureus, group A streptococcus, or Pseudomonas aeruginosa identified. The pathologic examination identified bone with a cartilaginous cap, consistent with osteochondroma (Figure 3), as well as a cyst lined by respiratory epithelium with patchy areas of squamous epithelium and surrounding mucus glands, consistent with bronchogenic cyst (Figure 4). Figure 5 shows the contiguous nature of the 2 lesions.

The postoperative course was uneventful. The patient returned to full use of the left upper extremity and had resolution of all drainage. 

Discussion

Osteochondromas are thought to arise from aberrant growth of the epiphyseal growth plate cartilage. A small portion of the physis herniates past the groove of Ranvier and grows parallel to the normal physis with medullary continuity. This can occur idiopathically or, more rarely, secondary to an identified injury to the growth plate.¹

The formation of bronchogenic cysts is most often attributed to anomalous budding of the ventral foregut during fetal development,⁴ hence the alternative designation of these cysts as foregut cysts. An extrathoracic location of the cyst has been postulated to stem from 2 possible events: a preexisting cyst may migrate out of the thorax prior to closure of the sternal plates, or sternal plate closure may itself pinch off the cyst.^8,9 An alternative explanation is in situ metaplastic development of respiratory epithelium.¹⁰ When located near the skin, these cysts often drain clear fluid.¹¹

Scapular osteochondromas are known to cause various pathologies of the shoulder girdle, including snapping scapula syndrome, chest wall deformity, shoulder impingement, and bursa formation.^12-17 This case, however, is the first known finding of a scapular osteochondroma with a contiguous cutaneous bronchogenic cyst. A putative explanation for their co-occurrence is that local disturbances caused by one lesion stimulated the formation of the second. The direct connection between the bronchogenic cyst and the bone, as has been reported in 3 cases,^7,9,18 seems to favor this explanation. Definitive conclusions regarding any causal relationship are beyond the scope of this single case report.

Definitive management of bronchogenic cysts is complete excision, although the diagnosis is often not made until histopathologic examination has been completed.¹⁹ Osteochondromas are managed with observation unless they are symptomatic.² Malignant degeneration is a rare but documented occurrence in both lesions.^2,20

Conclusion

In approaching the pediatric patient with a cystic mass over the scapula, a cutaneous bronchogenic cyst may be included in the differential diagnosis. This lesion can occur in isolation or can be found with another pathology, such as osteochondroma, as reported here.

Osteochondromas are common benign bone tumors composed of a bony protrusion with an overlying cartilage cap.¹ This lesion constitutes 24% to 40% of all benign bone tumors, and the great majority arise from the metaphyseal region of long bones.² The scapula accounts for only 3% to 5% of all osteochondromas; however, this lesion is the most common benign bone tumor to involve the scapula.³

In contrast, cutaneous bronchogenic cyst of the scapula is an exceedingly rare pathology. The bronchogenic cyst is a congenital cystic mass lined by tracheobronchial structures and respiratory epithelium.⁴ These are most commonly located in the thorax, although numerous remote locations have also been described, including cutaneous cysts.⁵ The overall incidence of bronchogenic cysts is thought to be 1 in 42,000 to 1 in 68,000.⁶ There are only 15 case reports of cutaneous bronchogenic cysts in the scapular region.⁷

We report the case of a novel dual lesion of both an osteochondroma and a contiguous cutaneous bronchogenic cyst in the scapula. The patient’s guardian provided written informed consent for print and electronic publication of this case report.

Case Report

A 12-month-old boy presented to our clinic with the complaint of a mass over the left scapula. The mass was first noted incidentally several weeks earlier during bathing. Examination revealed a firm, subcutaneous, nontender mass measuring 1×2 cm located over the spine of the scapula. There were no overlying skin changes, and there was normal function of the ipsilateral upper extremity. Anteroposterior and lateral chest radiographs revealed no abnormality. Magnetic resonance imaging (MRI) showed an exostosis projecting from the scapular spine measuring 2×6×7 mm with an adjacent cystic mass measuring 5×8×9 mm that was thought to represent bursitis (Figure 1). The decision was made to observe the mass. 

The patient returned to clinic at age 31 months with a new complaint of scant drainage of serous fluid from a pinprick-sized hole located just superolateral to the scapular mass. The child’s mother reported daily manual expression of fluid from the mass via the hole, without which the mass would enlarge. There were no local or systemic signs of infection. A repeat MRI again revealed an exostosis with an adjacent cystic mass with interval enlargement of the cyst (Figure 2). At age 4.5 years, the decision was made to proceed with excision of the osteochondroma and adjacent cystic mass.

The mass was approached via a 2-cm incision designed to excise the tract to the skin. Dissection revealed a sinus tract connecting to a well-defined cystic sac. This sac was attached to the underlying exostosis. The exostosis and attached cyst were excised en bloc. The cyst was opened, revealing foul-smelling, cloudy white fluid that was sent for culture; the specimen was sent for pathology.

The fluid culture grew mixed flora, with no Staphylococcus aureus, group A streptococcus, or Pseudomonas aeruginosa identified. The pathologic examination identified bone with a cartilaginous cap, consistent with osteochondroma (Figure 3), as well as a cyst lined by respiratory epithelium with patchy areas of squamous epithelium and surrounding mucus glands, consistent with bronchogenic cyst (Figure 4). Figure 5 shows the contiguous nature of the 2 lesions.

The postoperative course was uneventful. The patient returned to full use of the left upper extremity and had resolution of all drainage. 

Discussion

Osteochondromas are thought to arise from aberrant growth of the epiphyseal growth plate cartilage. A small portion of the physis herniates past the groove of Ranvier and grows parallel to the normal physis with medullary continuity. This can occur idiopathically or, more rarely, secondary to an identified injury to the growth plate.¹

The formation of bronchogenic cysts is most often attributed to anomalous budding of the ventral foregut during fetal development,⁴ hence the alternative designation of these cysts as foregut cysts. An extrathoracic location of the cyst has been postulated to stem from 2 possible events: a preexisting cyst may migrate out of the thorax prior to closure of the sternal plates, or sternal plate closure may itself pinch off the cyst.^8,9 An alternative explanation is in situ metaplastic development of respiratory epithelium.¹⁰ When located near the skin, these cysts often drain clear fluid.¹¹

Scapular osteochondromas are known to cause various pathologies of the shoulder girdle, including snapping scapula syndrome, chest wall deformity, shoulder impingement, and bursa formation.^12-17 This case, however, is the first known finding of a scapular osteochondroma with a contiguous cutaneous bronchogenic cyst. A putative explanation for their co-occurrence is that local disturbances caused by one lesion stimulated the formation of the second. The direct connection between the bronchogenic cyst and the bone, as has been reported in 3 cases,^7,9,18 seems to favor this explanation. Definitive conclusions regarding any causal relationship are beyond the scope of this single case report.

Definitive management of bronchogenic cysts is complete excision, although the diagnosis is often not made until histopathologic examination has been completed.¹⁹ Osteochondromas are managed with observation unless they are symptomatic.² Malignant degeneration is a rare but documented occurrence in both lesions.^2,20

Conclusion

In approaching the pediatric patient with a cystic mass over the scapula, a cutaneous bronchogenic cyst may be included in the differential diagnosis. This lesion can occur in isolation or can be found with another pathology, such as osteochondroma, as reported here.

Osteochondromas are common benign bone tumors composed of a bony protrusion with an overlying cartilage cap.¹ This lesion constitutes 24% to 40% of all benign bone tumors, and the great majority arise from the metaphyseal region of long bones.² The scapula accounts for only 3% to 5% of all osteochondromas; however, this lesion is the most common benign bone tumor to involve the scapula.³

In contrast, cutaneous bronchogenic cyst of the scapula is an exceedingly rare pathology. The bronchogenic cyst is a congenital cystic mass lined by tracheobronchial structures and respiratory epithelium.⁴ These are most commonly located in the thorax, although numerous remote locations have also been described, including cutaneous cysts.⁵ The overall incidence of bronchogenic cysts is thought to be 1 in 42,000 to 1 in 68,000.⁶ There are only 15 case reports of cutaneous bronchogenic cysts in the scapular region.⁷

We report the case of a novel dual lesion of both an osteochondroma and a contiguous cutaneous bronchogenic cyst in the scapula. The patient’s guardian provided written informed consent for print and electronic publication of this case report.

Case Report

A 12-month-old boy presented to our clinic with the complaint of a mass over the left scapula. The mass was first noted incidentally several weeks earlier during bathing. Examination revealed a firm, subcutaneous, nontender mass measuring 1×2 cm located over the spine of the scapula. There were no overlying skin changes, and there was normal function of the ipsilateral upper extremity. Anteroposterior and lateral chest radiographs revealed no abnormality. Magnetic resonance imaging (MRI) showed an exostosis projecting from the scapular spine measuring 2×6×7 mm with an adjacent cystic mass measuring 5×8×9 mm that was thought to represent bursitis (Figure 1). The decision was made to observe the mass. 

The patient returned to clinic at age 31 months with a new complaint of scant drainage of serous fluid from a pinprick-sized hole located just superolateral to the scapular mass. The child’s mother reported daily manual expression of fluid from the mass via the hole, without which the mass would enlarge. There were no local or systemic signs of infection. A repeat MRI again revealed an exostosis with an adjacent cystic mass with interval enlargement of the cyst (Figure 2). At age 4.5 years, the decision was made to proceed with excision of the osteochondroma and adjacent cystic mass.

The mass was approached via a 2-cm incision designed to excise the tract to the skin. Dissection revealed a sinus tract connecting to a well-defined cystic sac. This sac was attached to the underlying exostosis. The exostosis and attached cyst were excised en bloc. The cyst was opened, revealing foul-smelling, cloudy white fluid that was sent for culture; the specimen was sent for pathology.

The fluid culture grew mixed flora, with no Staphylococcus aureus, group A streptococcus, or Pseudomonas aeruginosa identified. The pathologic examination identified bone with a cartilaginous cap, consistent with osteochondroma (Figure 3), as well as a cyst lined by respiratory epithelium with patchy areas of squamous epithelium and surrounding mucus glands, consistent with bronchogenic cyst (Figure 4). Figure 5 shows the contiguous nature of the 2 lesions.

The postoperative course was uneventful. The patient returned to full use of the left upper extremity and had resolution of all drainage. 

Discussion

Osteochondromas are thought to arise from aberrant growth of the epiphyseal growth plate cartilage. A small portion of the physis herniates past the groove of Ranvier and grows parallel to the normal physis with medullary continuity. This can occur idiopathically or, more rarely, secondary to an identified injury to the growth plate.¹

The formation of bronchogenic cysts is most often attributed to anomalous budding of the ventral foregut during fetal development,⁴ hence the alternative designation of these cysts as foregut cysts. An extrathoracic location of the cyst has been postulated to stem from 2 possible events: a preexisting cyst may migrate out of the thorax prior to closure of the sternal plates, or sternal plate closure may itself pinch off the cyst.^8,9 An alternative explanation is in situ metaplastic development of respiratory epithelium.¹⁰ When located near the skin, these cysts often drain clear fluid.¹¹

Scapular osteochondromas are known to cause various pathologies of the shoulder girdle, including snapping scapula syndrome, chest wall deformity, shoulder impingement, and bursa formation.^12-17 This case, however, is the first known finding of a scapular osteochondroma with a contiguous cutaneous bronchogenic cyst. A putative explanation for their co-occurrence is that local disturbances caused by one lesion stimulated the formation of the second. The direct connection between the bronchogenic cyst and the bone, as has been reported in 3 cases,^7,9,18 seems to favor this explanation. Definitive conclusions regarding any causal relationship are beyond the scope of this single case report.

Definitive management of bronchogenic cysts is complete excision, although the diagnosis is often not made until histopathologic examination has been completed.¹⁹ Osteochondromas are managed with observation unless they are symptomatic.² Malignant degeneration is a rare but documented occurrence in both lesions.^2,20

Conclusion

In approaching the pediatric patient with a cystic mass over the scapula, a cutaneous bronchogenic cyst may be included in the differential diagnosis. This lesion can occur in isolation or can be found with another pathology, such as osteochondroma, as reported here.

Posterior spinal fusion for adolescent idiopathic scoliosis is a relatively common procedure. However, intestinal obstruction is a possible complication in the case of an asthenic adolescent with weight loss after surgery. We present the case of a 12-year-old girl who underwent an uncomplicated posterior spinal fusion with instrumentation for scoliosis and who developed nausea, emesis, and abdominal pain. We also discuss the origins, epidemiology, diagnosis, and treatment of superior mesenteric artery syndrome (SMAS), a rare condition. The patient’s parents provided written informed consent for print and electronic publication of this case report.

Case Report

The patient was a 12-year-old girl with juvenile idiopathic scoliosis. She was seen by a pediatric orthopedist at age 8 after her primary care physician noticed a curve in her back during her physical examination. Given her age and primary curve of 25º, magnetic resonance imaging was ordered, which was negative for syrinx, tethered cord, or bony abnormalities. An underarm thoracolumbosacral orthosis (Boston Brace) was prescribed to be worn 23 hours/day. There was inconsistent follow-up over the next 4 years, and her curve progressed to 55º (right thoracic) and 47º in the lumbar spine (Figures 1, 2). Given the magnitude of the curves, surgical intervention was recommended, because bracing would no longer be beneficial. 

The patient was healthy and appeared vibrant with no medical issues. She weighed 49 kg and her height was 162 cm (body mass index [BMI], 18.6; normal). She underwent segmental posterior spinal instrumentation, and a fusion was performed from T4 to L4 using a cobalt chrome rod. Postoperatively, there were no problems. Her diet was slowly advanced from clear liquids to regular food over 3 days. She was discharged on postoperative day 4. She had no abdominal distention, pain, or nausea. The family was instructed about pain medication (oxycodone liquid, 5 mg every 4 hours as needed) and how to prevent and treat constipation. 

Three days after discharge, her mother called to inquire about positioning because the patient was uncomfortable owing to back pain. There were no abdominal complaints, and she was taking her pain medicine every 4 hours. She was instructed to lie in a comfortable position and to ambulate several times daily. The patient took little food or fluids because of a lack of appetite and back pain. On postoperative day 8, she presented to the emergency department with complaints of generalized abdominal pain and 1 day’s emesis. The patient had not had a bowel movement postoperatively. An acute abdominal series (AAS) was obtained (Figure 3), which noted a nonobstructive bowel gas pattern, with some increased colonic fecal retention. The patient was given intravenous (IV) fluids and an IV anti-emetic, and was admitted for observation. The pediatric surgical team evaluated her and concluded her symptoms resulted from constipation. Her symptoms improved over 2 to 3 days, and she had several bowel movements on day 2 after taking polyethylene glycol, sennosides, and bisacodyl suppositories. At discharge, she was noted to be passing gas, and her abdominal examination revealed no tenderness or guarding. She had mild distention, but it had improved from the previous day. She ate breakfast and ambulated several times. She had no complaints of abdominal pain and was released home with her parents. Staff reiterated instructions regarding constipation, diet, and follow-up. Her discharge weight was 48 kg (down 1 kg) and her BMI was 17.2 (down 1.4; underweight). Her height was now 165 cm (up 3 cm). Postoperative radiographs noted stable fixation with corrected curves (Figures 4, 5).

At home, the patient ate little but continued to drink fluids. On postdischarge day 3, she developed nausea, bilious emesis, and generalized abdominal pain. She returned to the emergency department. At this point, the patient weighed 44.5 kg (down 6.6 kg since the initial surgery) and her BMI was 16.1 (down 2.5; underweight). She was admitted, and IV fluids were initiated. She had more than 1300 mL of bilious emesis. A nasogastric (NG) tube was inserted. Initial laboratory findings were unremarkable other than an increase in serum lipase of 261 U/L. Her amylase level was within normal limits. An AAS was again completed and showed a distended stomach and loop of small bowel below the liver with an air fluid level. There were also distended loops of bowel in the pelvis (Figure 6). 

A pediatric surgical consultant examined her the next morning. An upper gastrointestinal series (UGI) was obtained and showed air fluid levels in the stomach with prompt gastric emptying into a normal caliber duodenal bulb. However, with supine positioning, there was significant dilatation of the second portion of the duodenum with abrupt vertical cutoff just to the right of the spine, compatible with SMAS (Figure 7). There was reflux of contrast material into the stomach from the duodenum, with no passage of barium into the distal duodenum. After the UGI, a nasojejunal (NJ) feeding tube was placed. The tip was left at the beginning of the fourth part of the duodenum. Repeated attempts to pass the NJ feeding tube beyond the fourth part of the duodenum were unsuccessful because of massive gastric distention. The patient was taken to the operating room for placement of a Stamm gastrostomy feeding tube with insertion of a transgastric jejunal (G-J) feeding tube under fluoroscopy (Figure 5). The patient had the G-J feeding tube in place for 6 weeks to augment her enteral nutrition. As she gained weight, her duodenal emptying improved. She gradually transitioned to normal oral intake. She has done well since the G-J feeding tube was removed. 

Discussion

Von Rokitansky first described SMAS in the mid-1800s.¹ The exact pathology was further defined 60 years later when vascular involvement was determined to be the definitive mechanism of obstruction.^2-4 Superior mesenteric artery syndrome is caused by the superior mesenteric vessels compressing the third portion of the duodenum, resulting in an extrinsic obstruction. This syndrome is also commonly called Wilkie disease, after Dr. David Wilkie, who first published in 1927 results of a comprehensive series of 75 patients.¹ The syndrome is also known as arteriomesenteric duodenal compression, aortomesenteric syndrome, chronic duodenal ileus, megaduodenum, and cast syndrome.^1,4,5 The term cast syndrome was derived from events in 1878, when Willet applied a body cast to a scoliosis patient who died after what was termed “fatal vomiting.”³

Epidemiology, Incidence, and Prevalence

While not unheard of, SMAS is an uncommon disorder. There have been only 400 documented reports in the English-language literature since 1980.^5-8 Studies have stated that the incidence of the affected population is less than 0.4%.^5,7,9,10 However, SMAS has been reported to have a mortality rate as high as 33% because of the uncommon nature of the disease and prolonged duration between onset of symptoms and diagnosis.^7,9,11,12 The incidence of SMAS is higher after surgical procedures to correct spinal deformities, with rates between 0.5% and 4.7%.^10,12,13 Females are affected more frequently than males (3:2 ratio).^1,9,14 One large study with 80 patients that spanned 10 years reported that female incidence was 66%, and another study with 75 patients also observed that two-thirds of the patients were women.^1,7 This syndrome commonly affects patients who are tall and thin with an asthenic body habitus.^1,6,11,12 Superior mesenteric artery syndrome develops more commonly in younger patients. Previous studies noted that two-thirds of patients were between ages 10 and 39 years.^1,8 However, given the right set of medical conditions, it can occur in patients of any age.^2,9,15,16 In young, thin patients with scoliosis, the risk of developing SMAS after spinal fusion with instrumentation increases, given their already low weight coupled with the surgical intervention at the height of their longitudinal growth spurt.^1,11,12 

Other patients also at increased risk for developing SMAS include those with anorexia nervosa, psychiatric/emotional disorders, or drug addiction. It can also be found in persons on prolonged bedrest, those who have increased their activity and lost weight volitionally, or patients with illness or injuries, such as burns, trauma, or significant postoperative complications that decrease caloric intake and keep them in a supine position.^2,6,17 The syndrome can be acute or chronic in its presentation.

Anatomy and Physiology

The superior mesenteric artery (SMA) comes off the right anterolateral portion of the abdominal aorta, which is just anterior to the L1 vertebra. It passes over the third part of the duodenum, generally at the L2 level (Figure 8A). The duodenum passes across the aorta at the level of the L3 vertebral body and is suspended between the aorta and the SMA by the ligament of Treitz (Figure 8B).³ The angle between the aorta and SMA (aortomesenteric angle) typically ranges from 25º to 60º with an average of 45º (Figure 8A). The distance between the aorta and SMA at the level of the duodenum is called the aortomesenteric distance, and it normally measures from 10 mm to 28 mm. Obstruction is usually observed at 2 mm to 8 mm (Figure 8C).^1,3

Compression and outlet obstruction from narrowing of the SMA aortomesenteric angle can be caused by a multitude of problems.^3,5,9,17 In chronic conditions, narrowing of the aorto-mesenteric angle could be the result of a shortened ligament, or a low origin of the SMA on the aorta, or a high insertion of the duodenum at the ligament of Treitz. Postoperatively, any change in anatomy caused by adhesions could result in compression as well. Most commonly, however, in those with significant weight loss, such as postoperative spinal fusion patients, there is loss of retroperitoneal fat, which normally acts as a cushion around the duodenum. This allows the SMA to move posteriorly obstructing the duodenum. Lying in a recumbent position along with weight loss also puts patients at risk after surgery.^3,5,9,17 SMAS should be distinguished from other conditions that can cause duodenal obstruction, such as duodenal hematomas and congenital webs. 

Symptoms and Patient Presentation

Whether SMAS is acute or chronic, most patients with SMAS present in a similar fashion. Almost all patients with acute SMAS complain of abdominal pain, nausea, and emesis (usually bilious) that usually occur after eating. Early satiety is commonly observed, resulting from delayed gastric emptying. Abdominal pain may improve when patients lie prone and are in the knee-chest, or lateral decubitus, position. These patients frequently have upper abdominal distention because of massive retention of gastric contents.^4,6,16,18,19 Most spinal fusion patients present with these symptoms 7 to 10 days after surgery.^11-13

Diagnosis

Our first diagnostic tool is a comprehensive history and physical examination. Once that is complete, many radiologic tests can be used to confirm the anatomic abnormality. The first test ordered is a simple AAS, which may show a “double bubble sign” (Figure 6), indicative of duodenal obstruction.⁴ There are several other tests, and each facility and surgeon has a preference as to which is considered the “gold standard.” Upper gastrointestinal (GI) barium studies are the simplest and most reliable. The barium test shows foregut anatomy and, to some extent, function. In SMAS patients, one should see duodenal dilatation and failure of the contrast to flow past the third section of the duodenum, along with an abrupt termination of the barium column as the duodenum crosses the vertebrae. This is the traditional method of diagnosis. There is minimal radiation, and the cost is less than that of many other tests, but it can be uncomfortable for the patient.^1-4

At some institutions, an upper GI barium study is combined with angiography, which can be used to measure aortomesenteric angle and distance.^1,3 Other practitioners prefer computed tomography (CT) with 3-dimensional reconstruction, which allows for measurement of the aortomesenteric angle and distance. In 1 study, CT was found to have an extremely high sensitivity and specificity for these measurements.¹⁰ CT angiography also identifies the obstruction with increased sensitivity, but it is rarely necessary and provides more radiation exposure and increased cost.^1,6,14,19 Abdominal ultrasound has been used to measure the angle of the SMA and the aortomesenteric distance. When combined with endoscopy, this offers an alternative way to diagnose SMAS and decreases radiation exposure. However, it may require sedation or anesthesia.^7,15,17 Overall, 3 criteria are used to define whether a patient has SMAS: duodenal dilatation, an aortomesenteric angle that is less than 25º, and an SMA that is shown to be compressing the third part of the duodenum.⁵

Treatment

Conservative treatment of SMAS usually starts by removing any precipitating factors present, such as a splint or cast that was applied for scoliosis, or ending activity associated with significant weight loss. Medical management consists of IV hydration, anti-emetics, oral feeding restriction, posture therapy, and placement of an NG tube for decompression. In most cases, patients will need to have an NJ feeding tube passed distal to the site of obstruction. This provides access for enteral feeding, and patients will gradually gain weight, repleting their retroperitoneal fat stores, which pushes the SMA forward and relieves the pressure on the duodenum. Electrolyte balance should be closely monitored along with weight gain. A nutritionist is often consulted to prevent underfeeding, which can produce a slow return to weight gain, poor wound healing, and loss of lean body muscle mass; or overfeeding, which can result in hyperglycemia and respiratory failure. Once patients are stable on enteral feedings, they can begin a slow return to oral intake.^2-4,7,12 Total parental nutrition may be needed in some cases, but the risks associated with IV feeding usually outweigh the benefits.⁴ Almost all cases of acute SMAS can be successfully treated medically if diagnosed in a timely manner and supportive treatment begins promptly.⁷

Surgical intervention is rarely necessary for acute SMAS, but when conservative measures fail (after a 4- to 6-week trial), or in the presence of peptic ulcer disease or pancreatitis, this may become an appropriate option. In our patient, multiple attempts at passing an NJ feeding tube were unsuccessful, and she needed an operative procedure for insertion of a G-J feeding tube.  

Further surgical intervention is usually reserved for those patients with long-standing SMAS for whom medical management has failed or other issues, such as pancreatitis, colitis, or megaduodenum, have arisen. Many operations are described in the literature. A duodenojejunostomy to bypass the site of the obstruction is one option. Another is duodenal derotation (Strong procedure) to alter the aortomesenteric angle and place the third and fourth duodenal portions to the right of the SMA. Other procedures include a Roux-en-Y duodenojejunostomy and duodenal uncrossing. A lateral duodenojejunostomy between the second portion of the duodenum and the jejunum is considered the simplest surgical technique. It achieves successful outcomes in 90% of cases.^2-5,14 With regards to SMAS and scoliosis, it is extremely rare that this kind of surgical intervention would be necessary.

Conclusion

When planning operative spinal correction in scoliosis patients (especially females) who have a low BMI at the time of surgery and who have increased thoracic stiffness, be alert for signs and symptoms of SMAS. This rare complication can develop, and timely diagnosis and medical management will decrease morbidity and shorten the length of time needed for nutritional rehabilitation.

Posterior spinal fusion for adolescent idiopathic scoliosis is a relatively common procedure. However, intestinal obstruction is a possible complication in the case of an asthenic adolescent with weight loss after surgery. We present the case of a 12-year-old girl who underwent an uncomplicated posterior spinal fusion with instrumentation for scoliosis and who developed nausea, emesis, and abdominal pain. We also discuss the origins, epidemiology, diagnosis, and treatment of superior mesenteric artery syndrome (SMAS), a rare condition. The patient’s parents provided written informed consent for print and electronic publication of this case report.

Case Report

The patient was a 12-year-old girl with juvenile idiopathic scoliosis. She was seen by a pediatric orthopedist at age 8 after her primary care physician noticed a curve in her back during her physical examination. Given her age and primary curve of 25º, magnetic resonance imaging was ordered, which was negative for syrinx, tethered cord, or bony abnormalities. An underarm thoracolumbosacral orthosis (Boston Brace) was prescribed to be worn 23 hours/day. There was inconsistent follow-up over the next 4 years, and her curve progressed to 55º (right thoracic) and 47º in the lumbar spine (Figures 1, 2). Given the magnitude of the curves, surgical intervention was recommended, because bracing would no longer be beneficial. 

The patient was healthy and appeared vibrant with no medical issues. She weighed 49 kg and her height was 162 cm (body mass index [BMI], 18.6; normal). She underwent segmental posterior spinal instrumentation, and a fusion was performed from T4 to L4 using a cobalt chrome rod. Postoperatively, there were no problems. Her diet was slowly advanced from clear liquids to regular food over 3 days. She was discharged on postoperative day 4. She had no abdominal distention, pain, or nausea. The family was instructed about pain medication (oxycodone liquid, 5 mg every 4 hours as needed) and how to prevent and treat constipation. 

Three days after discharge, her mother called to inquire about positioning because the patient was uncomfortable owing to back pain. There were no abdominal complaints, and she was taking her pain medicine every 4 hours. She was instructed to lie in a comfortable position and to ambulate several times daily. The patient took little food or fluids because of a lack of appetite and back pain. On postoperative day 8, she presented to the emergency department with complaints of generalized abdominal pain and 1 day’s emesis. The patient had not had a bowel movement postoperatively. An acute abdominal series (AAS) was obtained (Figure 3), which noted a nonobstructive bowel gas pattern, with some increased colonic fecal retention. The patient was given intravenous (IV) fluids and an IV anti-emetic, and was admitted for observation. The pediatric surgical team evaluated her and concluded her symptoms resulted from constipation. Her symptoms improved over 2 to 3 days, and she had several bowel movements on day 2 after taking polyethylene glycol, sennosides, and bisacodyl suppositories. At discharge, she was noted to be passing gas, and her abdominal examination revealed no tenderness or guarding. She had mild distention, but it had improved from the previous day. She ate breakfast and ambulated several times. She had no complaints of abdominal pain and was released home with her parents. Staff reiterated instructions regarding constipation, diet, and follow-up. Her discharge weight was 48 kg (down 1 kg) and her BMI was 17.2 (down 1.4; underweight). Her height was now 165 cm (up 3 cm). Postoperative radiographs noted stable fixation with corrected curves (Figures 4, 5).

At home, the patient ate little but continued to drink fluids. On postdischarge day 3, she developed nausea, bilious emesis, and generalized abdominal pain. She returned to the emergency department. At this point, the patient weighed 44.5 kg (down 6.6 kg since the initial surgery) and her BMI was 16.1 (down 2.5; underweight). She was admitted, and IV fluids were initiated. She had more than 1300 mL of bilious emesis. A nasogastric (NG) tube was inserted. Initial laboratory findings were unremarkable other than an increase in serum lipase of 261 U/L. Her amylase level was within normal limits. An AAS was again completed and showed a distended stomach and loop of small bowel below the liver with an air fluid level. There were also distended loops of bowel in the pelvis (Figure 6). 

A pediatric surgical consultant examined her the next morning. An upper gastrointestinal series (UGI) was obtained and showed air fluid levels in the stomach with prompt gastric emptying into a normal caliber duodenal bulb. However, with supine positioning, there was significant dilatation of the second portion of the duodenum with abrupt vertical cutoff just to the right of the spine, compatible with SMAS (Figure 7). There was reflux of contrast material into the stomach from the duodenum, with no passage of barium into the distal duodenum. After the UGI, a nasojejunal (NJ) feeding tube was placed. The tip was left at the beginning of the fourth part of the duodenum. Repeated attempts to pass the NJ feeding tube beyond the fourth part of the duodenum were unsuccessful because of massive gastric distention. The patient was taken to the operating room for placement of a Stamm gastrostomy feeding tube with insertion of a transgastric jejunal (G-J) feeding tube under fluoroscopy (Figure 5). The patient had the G-J feeding tube in place for 6 weeks to augment her enteral nutrition. As she gained weight, her duodenal emptying improved. She gradually transitioned to normal oral intake. She has done well since the G-J feeding tube was removed. 

Discussion

Von Rokitansky first described SMAS in the mid-1800s.¹ The exact pathology was further defined 60 years later when vascular involvement was determined to be the definitive mechanism of obstruction.^2-4 Superior mesenteric artery syndrome is caused by the superior mesenteric vessels compressing the third portion of the duodenum, resulting in an extrinsic obstruction. This syndrome is also commonly called Wilkie disease, after Dr. David Wilkie, who first published in 1927 results of a comprehensive series of 75 patients.¹ The syndrome is also known as arteriomesenteric duodenal compression, aortomesenteric syndrome, chronic duodenal ileus, megaduodenum, and cast syndrome.^1,4,5 The term cast syndrome was derived from events in 1878, when Willet applied a body cast to a scoliosis patient who died after what was termed “fatal vomiting.”³

Epidemiology, Incidence, and Prevalence

While not unheard of, SMAS is an uncommon disorder. There have been only 400 documented reports in the English-language literature since 1980.^5-8 Studies have stated that the incidence of the affected population is less than 0.4%.^5,7,9,10 However, SMAS has been reported to have a mortality rate as high as 33% because of the uncommon nature of the disease and prolonged duration between onset of symptoms and diagnosis.^7,9,11,12 The incidence of SMAS is higher after surgical procedures to correct spinal deformities, with rates between 0.5% and 4.7%.^10,12,13 Females are affected more frequently than males (3:2 ratio).^1,9,14 One large study with 80 patients that spanned 10 years reported that female incidence was 66%, and another study with 75 patients also observed that two-thirds of the patients were women.^1,7 This syndrome commonly affects patients who are tall and thin with an asthenic body habitus.^1,6,11,12 Superior mesenteric artery syndrome develops more commonly in younger patients. Previous studies noted that two-thirds of patients were between ages 10 and 39 years.^1,8 However, given the right set of medical conditions, it can occur in patients of any age.^2,9,15,16 In young, thin patients with scoliosis, the risk of developing SMAS after spinal fusion with instrumentation increases, given their already low weight coupled with the surgical intervention at the height of their longitudinal growth spurt.^1,11,12 

Other patients also at increased risk for developing SMAS include those with anorexia nervosa, psychiatric/emotional disorders, or drug addiction. It can also be found in persons on prolonged bedrest, those who have increased their activity and lost weight volitionally, or patients with illness or injuries, such as burns, trauma, or significant postoperative complications that decrease caloric intake and keep them in a supine position.^2,6,17 The syndrome can be acute or chronic in its presentation.

Anatomy and Physiology

The superior mesenteric artery (SMA) comes off the right anterolateral portion of the abdominal aorta, which is just anterior to the L1 vertebra. It passes over the third part of the duodenum, generally at the L2 level (Figure 8A). The duodenum passes across the aorta at the level of the L3 vertebral body and is suspended between the aorta and the SMA by the ligament of Treitz (Figure 8B).³ The angle between the aorta and SMA (aortomesenteric angle) typically ranges from 25º to 60º with an average of 45º (Figure 8A). The distance between the aorta and SMA at the level of the duodenum is called the aortomesenteric distance, and it normally measures from 10 mm to 28 mm. Obstruction is usually observed at 2 mm to 8 mm (Figure 8C).^1,3

Compression and outlet obstruction from narrowing of the SMA aortomesenteric angle can be caused by a multitude of problems.^3,5,9,17 In chronic conditions, narrowing of the aorto-mesenteric angle could be the result of a shortened ligament, or a low origin of the SMA on the aorta, or a high insertion of the duodenum at the ligament of Treitz. Postoperatively, any change in anatomy caused by adhesions could result in compression as well. Most commonly, however, in those with significant weight loss, such as postoperative spinal fusion patients, there is loss of retroperitoneal fat, which normally acts as a cushion around the duodenum. This allows the SMA to move posteriorly obstructing the duodenum. Lying in a recumbent position along with weight loss also puts patients at risk after surgery.^3,5,9,17 SMAS should be distinguished from other conditions that can cause duodenal obstruction, such as duodenal hematomas and congenital webs. 

Symptoms and Patient Presentation

Whether SMAS is acute or chronic, most patients with SMAS present in a similar fashion. Almost all patients with acute SMAS complain of abdominal pain, nausea, and emesis (usually bilious) that usually occur after eating. Early satiety is commonly observed, resulting from delayed gastric emptying. Abdominal pain may improve when patients lie prone and are in the knee-chest, or lateral decubitus, position. These patients frequently have upper abdominal distention because of massive retention of gastric contents.^4,6,16,18,19 Most spinal fusion patients present with these symptoms 7 to 10 days after surgery.^11-13

Diagnosis

Our first diagnostic tool is a comprehensive history and physical examination. Once that is complete, many radiologic tests can be used to confirm the anatomic abnormality. The first test ordered is a simple AAS, which may show a “double bubble sign” (Figure 6), indicative of duodenal obstruction.⁴ There are several other tests, and each facility and surgeon has a preference as to which is considered the “gold standard.” Upper gastrointestinal (GI) barium studies are the simplest and most reliable. The barium test shows foregut anatomy and, to some extent, function. In SMAS patients, one should see duodenal dilatation and failure of the contrast to flow past the third section of the duodenum, along with an abrupt termination of the barium column as the duodenum crosses the vertebrae. This is the traditional method of diagnosis. There is minimal radiation, and the cost is less than that of many other tests, but it can be uncomfortable for the patient.^1-4

At some institutions, an upper GI barium study is combined with angiography, which can be used to measure aortomesenteric angle and distance.^1,3 Other practitioners prefer computed tomography (CT) with 3-dimensional reconstruction, which allows for measurement of the aortomesenteric angle and distance. In 1 study, CT was found to have an extremely high sensitivity and specificity for these measurements.¹⁰ CT angiography also identifies the obstruction with increased sensitivity, but it is rarely necessary and provides more radiation exposure and increased cost.^1,6,14,19 Abdominal ultrasound has been used to measure the angle of the SMA and the aortomesenteric distance. When combined with endoscopy, this offers an alternative way to diagnose SMAS and decreases radiation exposure. However, it may require sedation or anesthesia.^7,15,17 Overall, 3 criteria are used to define whether a patient has SMAS: duodenal dilatation, an aortomesenteric angle that is less than 25º, and an SMA that is shown to be compressing the third part of the duodenum.⁵

Treatment

Conservative treatment of SMAS usually starts by removing any precipitating factors present, such as a splint or cast that was applied for scoliosis, or ending activity associated with significant weight loss. Medical management consists of IV hydration, anti-emetics, oral feeding restriction, posture therapy, and placement of an NG tube for decompression. In most cases, patients will need to have an NJ feeding tube passed distal to the site of obstruction. This provides access for enteral feeding, and patients will gradually gain weight, repleting their retroperitoneal fat stores, which pushes the SMA forward and relieves the pressure on the duodenum. Electrolyte balance should be closely monitored along with weight gain. A nutritionist is often consulted to prevent underfeeding, which can produce a slow return to weight gain, poor wound healing, and loss of lean body muscle mass; or overfeeding, which can result in hyperglycemia and respiratory failure. Once patients are stable on enteral feedings, they can begin a slow return to oral intake.^2-4,7,12 Total parental nutrition may be needed in some cases, but the risks associated with IV feeding usually outweigh the benefits.⁴ Almost all cases of acute SMAS can be successfully treated medically if diagnosed in a timely manner and supportive treatment begins promptly.⁷

Surgical intervention is rarely necessary for acute SMAS, but when conservative measures fail (after a 4- to 6-week trial), or in the presence of peptic ulcer disease or pancreatitis, this may become an appropriate option. In our patient, multiple attempts at passing an NJ feeding tube were unsuccessful, and she needed an operative procedure for insertion of a G-J feeding tube.  

Further surgical intervention is usually reserved for those patients with long-standing SMAS for whom medical management has failed or other issues, such as pancreatitis, colitis, or megaduodenum, have arisen. Many operations are described in the literature. A duodenojejunostomy to bypass the site of the obstruction is one option. Another is duodenal derotation (Strong procedure) to alter the aortomesenteric angle and place the third and fourth duodenal portions to the right of the SMA. Other procedures include a Roux-en-Y duodenojejunostomy and duodenal uncrossing. A lateral duodenojejunostomy between the second portion of the duodenum and the jejunum is considered the simplest surgical technique. It achieves successful outcomes in 90% of cases.^2-5,14 With regards to SMAS and scoliosis, it is extremely rare that this kind of surgical intervention would be necessary.

Conclusion

When planning operative spinal correction in scoliosis patients (especially females) who have a low BMI at the time of surgery and who have increased thoracic stiffness, be alert for signs and symptoms of SMAS. This rare complication can develop, and timely diagnosis and medical management will decrease morbidity and shorten the length of time needed for nutritional rehabilitation.

Posterior spinal fusion for adolescent idiopathic scoliosis is a relatively common procedure. However, intestinal obstruction is a possible complication in the case of an asthenic adolescent with weight loss after surgery. We present the case of a 12-year-old girl who underwent an uncomplicated posterior spinal fusion with instrumentation for scoliosis and who developed nausea, emesis, and abdominal pain. We also discuss the origins, epidemiology, diagnosis, and treatment of superior mesenteric artery syndrome (SMAS), a rare condition. The patient’s parents provided written informed consent for print and electronic publication of this case report.

Case Report

The patient was a 12-year-old girl with juvenile idiopathic scoliosis. She was seen by a pediatric orthopedist at age 8 after her primary care physician noticed a curve in her back during her physical examination. Given her age and primary curve of 25º, magnetic resonance imaging was ordered, which was negative for syrinx, tethered cord, or bony abnormalities. An underarm thoracolumbosacral orthosis (Boston Brace) was prescribed to be worn 23 hours/day. There was inconsistent follow-up over the next 4 years, and her curve progressed to 55º (right thoracic) and 47º in the lumbar spine (Figures 1, 2). Given the magnitude of the curves, surgical intervention was recommended, because bracing would no longer be beneficial. 

The patient was healthy and appeared vibrant with no medical issues. She weighed 49 kg and her height was 162 cm (body mass index [BMI], 18.6; normal). She underwent segmental posterior spinal instrumentation, and a fusion was performed from T4 to L4 using a cobalt chrome rod. Postoperatively, there were no problems. Her diet was slowly advanced from clear liquids to regular food over 3 days. She was discharged on postoperative day 4. She had no abdominal distention, pain, or nausea. The family was instructed about pain medication (oxycodone liquid, 5 mg every 4 hours as needed) and how to prevent and treat constipation. 

Three days after discharge, her mother called to inquire about positioning because the patient was uncomfortable owing to back pain. There were no abdominal complaints, and she was taking her pain medicine every 4 hours. She was instructed to lie in a comfortable position and to ambulate several times daily. The patient took little food or fluids because of a lack of appetite and back pain. On postoperative day 8, she presented to the emergency department with complaints of generalized abdominal pain and 1 day’s emesis. The patient had not had a bowel movement postoperatively. An acute abdominal series (AAS) was obtained (Figure 3), which noted a nonobstructive bowel gas pattern, with some increased colonic fecal retention. The patient was given intravenous (IV) fluids and an IV anti-emetic, and was admitted for observation. The pediatric surgical team evaluated her and concluded her symptoms resulted from constipation. Her symptoms improved over 2 to 3 days, and she had several bowel movements on day 2 after taking polyethylene glycol, sennosides, and bisacodyl suppositories. At discharge, she was noted to be passing gas, and her abdominal examination revealed no tenderness or guarding. She had mild distention, but it had improved from the previous day. She ate breakfast and ambulated several times. She had no complaints of abdominal pain and was released home with her parents. Staff reiterated instructions regarding constipation, diet, and follow-up. Her discharge weight was 48 kg (down 1 kg) and her BMI was 17.2 (down 1.4; underweight). Her height was now 165 cm (up 3 cm). Postoperative radiographs noted stable fixation with corrected curves (Figures 4, 5).

At home, the patient ate little but continued to drink fluids. On postdischarge day 3, she developed nausea, bilious emesis, and generalized abdominal pain. She returned to the emergency department. At this point, the patient weighed 44.5 kg (down 6.6 kg since the initial surgery) and her BMI was 16.1 (down 2.5; underweight). She was admitted, and IV fluids were initiated. She had more than 1300 mL of bilious emesis. A nasogastric (NG) tube was inserted. Initial laboratory findings were unremarkable other than an increase in serum lipase of 261 U/L. Her amylase level was within normal limits. An AAS was again completed and showed a distended stomach and loop of small bowel below the liver with an air fluid level. There were also distended loops of bowel in the pelvis (Figure 6). 

A pediatric surgical consultant examined her the next morning. An upper gastrointestinal series (UGI) was obtained and showed air fluid levels in the stomach with prompt gastric emptying into a normal caliber duodenal bulb. However, with supine positioning, there was significant dilatation of the second portion of the duodenum with abrupt vertical cutoff just to the right of the spine, compatible with SMAS (Figure 7). There was reflux of contrast material into the stomach from the duodenum, with no passage of barium into the distal duodenum. After the UGI, a nasojejunal (NJ) feeding tube was placed. The tip was left at the beginning of the fourth part of the duodenum. Repeated attempts to pass the NJ feeding tube beyond the fourth part of the duodenum were unsuccessful because of massive gastric distention. The patient was taken to the operating room for placement of a Stamm gastrostomy feeding tube with insertion of a transgastric jejunal (G-J) feeding tube under fluoroscopy (Figure 5). The patient had the G-J feeding tube in place for 6 weeks to augment her enteral nutrition. As she gained weight, her duodenal emptying improved. She gradually transitioned to normal oral intake. She has done well since the G-J feeding tube was removed. 

Discussion

Von Rokitansky first described SMAS in the mid-1800s.¹ The exact pathology was further defined 60 years later when vascular involvement was determined to be the definitive mechanism of obstruction.^2-4 Superior mesenteric artery syndrome is caused by the superior mesenteric vessels compressing the third portion of the duodenum, resulting in an extrinsic obstruction. This syndrome is also commonly called Wilkie disease, after Dr. David Wilkie, who first published in 1927 results of a comprehensive series of 75 patients.¹ The syndrome is also known as arteriomesenteric duodenal compression, aortomesenteric syndrome, chronic duodenal ileus, megaduodenum, and cast syndrome.^1,4,5 The term cast syndrome was derived from events in 1878, when Willet applied a body cast to a scoliosis patient who died after what was termed “fatal vomiting.”³

Epidemiology, Incidence, and Prevalence

While not unheard of, SMAS is an uncommon disorder. There have been only 400 documented reports in the English-language literature since 1980.^5-8 Studies have stated that the incidence of the affected population is less than 0.4%.^5,7,9,10 However, SMAS has been reported to have a mortality rate as high as 33% because of the uncommon nature of the disease and prolonged duration between onset of symptoms and diagnosis.^7,9,11,12 The incidence of SMAS is higher after surgical procedures to correct spinal deformities, with rates between 0.5% and 4.7%.^10,12,13 Females are affected more frequently than males (3:2 ratio).^1,9,14 One large study with 80 patients that spanned 10 years reported that female incidence was 66%, and another study with 75 patients also observed that two-thirds of the patients were women.^1,7 This syndrome commonly affects patients who are tall and thin with an asthenic body habitus.^1,6,11,12 Superior mesenteric artery syndrome develops more commonly in younger patients. Previous studies noted that two-thirds of patients were between ages 10 and 39 years.^1,8 However, given the right set of medical conditions, it can occur in patients of any age.^2,9,15,16 In young, thin patients with scoliosis, the risk of developing SMAS after spinal fusion with instrumentation increases, given their already low weight coupled with the surgical intervention at the height of their longitudinal growth spurt.^1,11,12 

Other patients also at increased risk for developing SMAS include those with anorexia nervosa, psychiatric/emotional disorders, or drug addiction. It can also be found in persons on prolonged bedrest, those who have increased their activity and lost weight volitionally, or patients with illness or injuries, such as burns, trauma, or significant postoperative complications that decrease caloric intake and keep them in a supine position.^2,6,17 The syndrome can be acute or chronic in its presentation.

Anatomy and Physiology

The superior mesenteric artery (SMA) comes off the right anterolateral portion of the abdominal aorta, which is just anterior to the L1 vertebra. It passes over the third part of the duodenum, generally at the L2 level (Figure 8A). The duodenum passes across the aorta at the level of the L3 vertebral body and is suspended between the aorta and the SMA by the ligament of Treitz (Figure 8B).³ The angle between the aorta and SMA (aortomesenteric angle) typically ranges from 25º to 60º with an average of 45º (Figure 8A). The distance between the aorta and SMA at the level of the duodenum is called the aortomesenteric distance, and it normally measures from 10 mm to 28 mm. Obstruction is usually observed at 2 mm to 8 mm (Figure 8C).^1,3

Compression and outlet obstruction from narrowing of the SMA aortomesenteric angle can be caused by a multitude of problems.^3,5,9,17 In chronic conditions, narrowing of the aorto-mesenteric angle could be the result of a shortened ligament, or a low origin of the SMA on the aorta, or a high insertion of the duodenum at the ligament of Treitz. Postoperatively, any change in anatomy caused by adhesions could result in compression as well. Most commonly, however, in those with significant weight loss, such as postoperative spinal fusion patients, there is loss of retroperitoneal fat, which normally acts as a cushion around the duodenum. This allows the SMA to move posteriorly obstructing the duodenum. Lying in a recumbent position along with weight loss also puts patients at risk after surgery.^3,5,9,17 SMAS should be distinguished from other conditions that can cause duodenal obstruction, such as duodenal hematomas and congenital webs. 

Symptoms and Patient Presentation

Whether SMAS is acute or chronic, most patients with SMAS present in a similar fashion. Almost all patients with acute SMAS complain of abdominal pain, nausea, and emesis (usually bilious) that usually occur after eating. Early satiety is commonly observed, resulting from delayed gastric emptying. Abdominal pain may improve when patients lie prone and are in the knee-chest, or lateral decubitus, position. These patients frequently have upper abdominal distention because of massive retention of gastric contents.^4,6,16,18,19 Most spinal fusion patients present with these symptoms 7 to 10 days after surgery.^11-13

Diagnosis

Our first diagnostic tool is a comprehensive history and physical examination. Once that is complete, many radiologic tests can be used to confirm the anatomic abnormality. The first test ordered is a simple AAS, which may show a “double bubble sign” (Figure 6), indicative of duodenal obstruction.⁴ There are several other tests, and each facility and surgeon has a preference as to which is considered the “gold standard.” Upper gastrointestinal (GI) barium studies are the simplest and most reliable. The barium test shows foregut anatomy and, to some extent, function. In SMAS patients, one should see duodenal dilatation and failure of the contrast to flow past the third section of the duodenum, along with an abrupt termination of the barium column as the duodenum crosses the vertebrae. This is the traditional method of diagnosis. There is minimal radiation, and the cost is less than that of many other tests, but it can be uncomfortable for the patient.^1-4

At some institutions, an upper GI barium study is combined with angiography, which can be used to measure aortomesenteric angle and distance.^1,3 Other practitioners prefer computed tomography (CT) with 3-dimensional reconstruction, which allows for measurement of the aortomesenteric angle and distance. In 1 study, CT was found to have an extremely high sensitivity and specificity for these measurements.¹⁰ CT angiography also identifies the obstruction with increased sensitivity, but it is rarely necessary and provides more radiation exposure and increased cost.^1,6,14,19 Abdominal ultrasound has been used to measure the angle of the SMA and the aortomesenteric distance. When combined with endoscopy, this offers an alternative way to diagnose SMAS and decreases radiation exposure. However, it may require sedation or anesthesia.^7,15,17 Overall, 3 criteria are used to define whether a patient has SMAS: duodenal dilatation, an aortomesenteric angle that is less than 25º, and an SMA that is shown to be compressing the third part of the duodenum.⁵

Treatment

Conservative treatment of SMAS usually starts by removing any precipitating factors present, such as a splint or cast that was applied for scoliosis, or ending activity associated with significant weight loss. Medical management consists of IV hydration, anti-emetics, oral feeding restriction, posture therapy, and placement of an NG tube for decompression. In most cases, patients will need to have an NJ feeding tube passed distal to the site of obstruction. This provides access for enteral feeding, and patients will gradually gain weight, repleting their retroperitoneal fat stores, which pushes the SMA forward and relieves the pressure on the duodenum. Electrolyte balance should be closely monitored along with weight gain. A nutritionist is often consulted to prevent underfeeding, which can produce a slow return to weight gain, poor wound healing, and loss of lean body muscle mass; or overfeeding, which can result in hyperglycemia and respiratory failure. Once patients are stable on enteral feedings, they can begin a slow return to oral intake.^2-4,7,12 Total parental nutrition may be needed in some cases, but the risks associated with IV feeding usually outweigh the benefits.⁴ Almost all cases of acute SMAS can be successfully treated medically if diagnosed in a timely manner and supportive treatment begins promptly.⁷

Surgical intervention is rarely necessary for acute SMAS, but when conservative measures fail (after a 4- to 6-week trial), or in the presence of peptic ulcer disease or pancreatitis, this may become an appropriate option. In our patient, multiple attempts at passing an NJ feeding tube were unsuccessful, and she needed an operative procedure for insertion of a G-J feeding tube.  

Further surgical intervention is usually reserved for those patients with long-standing SMAS for whom medical management has failed or other issues, such as pancreatitis, colitis, or megaduodenum, have arisen. Many operations are described in the literature. A duodenojejunostomy to bypass the site of the obstruction is one option. Another is duodenal derotation (Strong procedure) to alter the aortomesenteric angle and place the third and fourth duodenal portions to the right of the SMA. Other procedures include a Roux-en-Y duodenojejunostomy and duodenal uncrossing. A lateral duodenojejunostomy between the second portion of the duodenum and the jejunum is considered the simplest surgical technique. It achieves successful outcomes in 90% of cases.^2-5,14 With regards to SMAS and scoliosis, it is extremely rare that this kind of surgical intervention would be necessary.

Conclusion

When planning operative spinal correction in scoliosis patients (especially females) who have a low BMI at the time of surgery and who have increased thoracic stiffness, be alert for signs and symptoms of SMAS. This rare complication can develop, and timely diagnosis and medical management will decrease morbidity and shorten the length of time needed for nutritional rehabilitation.