Osteoporosis

LOS ANGELES – Longer duration of type 2 diabetes and any use of medication for the disease are risk factors for short-term bone fracture, results from a large community-based study have shown.

“Osteoporotic fractures are a significant public health burden, causing high morbidity, mortality, and associated health care costs,” Elizabeth J. Samelson, PhD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Risk of fractures are higher in patients with type 2 diabetes. Further, outcomes are worse in type 2 diabetes patients, with greater frequency of complications following a fracture.”

Given the projected increase in type 2 diabetes in the U.S. population, Dr. Samelson, an associate scientist at the Marcus Institute for Aging Research at Hebrew SeniorLife and Harvard Medical School, Boston, and colleagues set out to evaluate the short- and long-term risks of bone fractures associated with the disease. They drew from 2,105 women and 1,130 men who participated in the Framingham Original and Offspring Cohorts and whose baseline osteoporosis visit was around 1990. Type 2 diabetes was defined as having a fasting plasma glucose of greater than 125 mg/dL or being on treatment for the disease. Incident fractures excluded finger, toe, skull, face, and pathologic fractures, and the researchers used repeated measures analyses to estimate hazard ratios for the association between type 2 diabetes, type 2 diabetes medication use, and type 2 diabetes duration and incident fracture, adjusted for age, sex, height, and weight.

The mean age of the study participants was 67 years, and the mean follow-up was 9 years. The prevalence of type 2 diabetes in women and men was 7% and 13%, respectively, and 63% and 51% of those were on medication for the disease. The mean duration of diabetes was 8 years.

Dr. Samelson and colleagues found that the cumulative incidence of fracture was 37% in women with type 2 diabetes and 30% in those without the disease. Meanwhile, the cumulative incidence of fracture was 11% in men with type 2 diabetes and 16% in those without the disease. The researchers also found that type 2 diabetes was associated with 1-year fracture risk in women (hazard ratio, 2.23), but not in men.

In the entire study population, longer duration of type 2 diabetes increased the 2-year fracture risk (HR, 1.28), as did the use of any type 2 diabetes medication (HR, 1.70). The researchers observed no statistically significant differences between type 2 diabetes and long-term incidence of fracture.

“Previous studies have contributed to understanding the higher incidence of fractures and worse outcomes in type 2 diabetes, [but] the current study demonstrated that patients [with type 2 diabetes] have 50% to 100% higher short-term [1- to 2-year] risk of fracture independent of clinical risk factors, whereas long-term [10-year] risk of fracture was similar in [patients with] type 2 diabetes and those who do not have [the disease],” Dr. Samelson said. “The current study has some inherent limitations of observational studies, including a lack of definitive determination of causality and that the results are not generalizable to patients with similar demographics. The study, however, is robust in the availability of detailed clinical information, which allows for control of multiple confounding variables.”

Dr. Samelson reported having no financial disclosures. Coauthors Setareh Williams, PhD, and Rich Weiss, MD, are employees and shareholders of Radius Health Inc.

[email protected]

LOS ANGELES – Longer duration of type 2 diabetes and any use of medication for the disease are risk factors for short-term bone fracture, results from a large community-based study have shown.

“Osteoporotic fractures are a significant public health burden, causing high morbidity, mortality, and associated health care costs,” Elizabeth J. Samelson, PhD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Risk of fractures are higher in patients with type 2 diabetes. Further, outcomes are worse in type 2 diabetes patients, with greater frequency of complications following a fracture.”

Given the projected increase in type 2 diabetes in the U.S. population, Dr. Samelson, an associate scientist at the Marcus Institute for Aging Research at Hebrew SeniorLife and Harvard Medical School, Boston, and colleagues set out to evaluate the short- and long-term risks of bone fractures associated with the disease. They drew from 2,105 women and 1,130 men who participated in the Framingham Original and Offspring Cohorts and whose baseline osteoporosis visit was around 1990. Type 2 diabetes was defined as having a fasting plasma glucose of greater than 125 mg/dL or being on treatment for the disease. Incident fractures excluded finger, toe, skull, face, and pathologic fractures, and the researchers used repeated measures analyses to estimate hazard ratios for the association between type 2 diabetes, type 2 diabetes medication use, and type 2 diabetes duration and incident fracture, adjusted for age, sex, height, and weight.

The mean age of the study participants was 67 years, and the mean follow-up was 9 years. The prevalence of type 2 diabetes in women and men was 7% and 13%, respectively, and 63% and 51% of those were on medication for the disease. The mean duration of diabetes was 8 years.

Dr. Samelson and colleagues found that the cumulative incidence of fracture was 37% in women with type 2 diabetes and 30% in those without the disease. Meanwhile, the cumulative incidence of fracture was 11% in men with type 2 diabetes and 16% in those without the disease. The researchers also found that type 2 diabetes was associated with 1-year fracture risk in women (hazard ratio, 2.23), but not in men.

In the entire study population, longer duration of type 2 diabetes increased the 2-year fracture risk (HR, 1.28), as did the use of any type 2 diabetes medication (HR, 1.70). The researchers observed no statistically significant differences between type 2 diabetes and long-term incidence of fracture.

“Previous studies have contributed to understanding the higher incidence of fractures and worse outcomes in type 2 diabetes, [but] the current study demonstrated that patients [with type 2 diabetes] have 50% to 100% higher short-term [1- to 2-year] risk of fracture independent of clinical risk factors, whereas long-term [10-year] risk of fracture was similar in [patients with] type 2 diabetes and those who do not have [the disease],” Dr. Samelson said. “The current study has some inherent limitations of observational studies, including a lack of definitive determination of causality and that the results are not generalizable to patients with similar demographics. The study, however, is robust in the availability of detailed clinical information, which allows for control of multiple confounding variables.”

Dr. Samelson reported having no financial disclosures. Coauthors Setareh Williams, PhD, and Rich Weiss, MD, are employees and shareholders of Radius Health Inc.

[email protected]

LOS ANGELES – Longer duration of type 2 diabetes and any use of medication for the disease are risk factors for short-term bone fracture, results from a large community-based study have shown.

“Osteoporotic fractures are a significant public health burden, causing high morbidity, mortality, and associated health care costs,” Elizabeth J. Samelson, PhD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Risk of fractures are higher in patients with type 2 diabetes. Further, outcomes are worse in type 2 diabetes patients, with greater frequency of complications following a fracture.”

Given the projected increase in type 2 diabetes in the U.S. population, Dr. Samelson, an associate scientist at the Marcus Institute for Aging Research at Hebrew SeniorLife and Harvard Medical School, Boston, and colleagues set out to evaluate the short- and long-term risks of bone fractures associated with the disease. They drew from 2,105 women and 1,130 men who participated in the Framingham Original and Offspring Cohorts and whose baseline osteoporosis visit was around 1990. Type 2 diabetes was defined as having a fasting plasma glucose of greater than 125 mg/dL or being on treatment for the disease. Incident fractures excluded finger, toe, skull, face, and pathologic fractures, and the researchers used repeated measures analyses to estimate hazard ratios for the association between type 2 diabetes, type 2 diabetes medication use, and type 2 diabetes duration and incident fracture, adjusted for age, sex, height, and weight.

The mean age of the study participants was 67 years, and the mean follow-up was 9 years. The prevalence of type 2 diabetes in women and men was 7% and 13%, respectively, and 63% and 51% of those were on medication for the disease. The mean duration of diabetes was 8 years.

Dr. Samelson and colleagues found that the cumulative incidence of fracture was 37% in women with type 2 diabetes and 30% in those without the disease. Meanwhile, the cumulative incidence of fracture was 11% in men with type 2 diabetes and 16% in those without the disease. The researchers also found that type 2 diabetes was associated with 1-year fracture risk in women (hazard ratio, 2.23), but not in men.

In the entire study population, longer duration of type 2 diabetes increased the 2-year fracture risk (HR, 1.28), as did the use of any type 2 diabetes medication (HR, 1.70). The researchers observed no statistically significant differences between type 2 diabetes and long-term incidence of fracture.

“Previous studies have contributed to understanding the higher incidence of fractures and worse outcomes in type 2 diabetes, [but] the current study demonstrated that patients [with type 2 diabetes] have 50% to 100% higher short-term [1- to 2-year] risk of fracture independent of clinical risk factors, whereas long-term [10-year] risk of fracture was similar in [patients with] type 2 diabetes and those who do not have [the disease],” Dr. Samelson said. “The current study has some inherent limitations of observational studies, including a lack of definitive determination of causality and that the results are not generalizable to patients with similar demographics. The study, however, is robust in the availability of detailed clinical information, which allows for control of multiple confounding variables.”

Dr. Samelson reported having no financial disclosures. Coauthors Setareh Williams, PhD, and Rich Weiss, MD, are employees and shareholders of Radius Health Inc.

[email protected]

Long-term use of alendronate and zoledronic acid for more than 3 years reduces the rate of vertebral fracture in treatment-naive postmenopausal women with notable, yet rare, adverse events, but too little evidence exists to make determinations on the long-term benefit/risk profile of other bisphosphonates or other osteoporosis drugs besides raloxifene and oral hormone therapy, according to a report coming out of a recent National Institutes of Health workshop.

This situation leaves a large research gap that authors of an accompanying position paper hope to bridge with recommendations for studying therapy discontinuation and drug holidays during long-term osteoporosis drug treatment.

The NIH’s Pathways to Prevention (P2P) Workshop: Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention outlined the findings of the systematic review of long-term osteoporosis drug treatment (ODT), which was commissioned by the NIH Office of Disease Prevention. The systematic review and a position paper summarizing the workshop were published April 23 in Annals of Internal Medicine.

“Clinicians and patients need increased information on benefits and risks to inform shared decision making about the use of these treatments, taking into account patients’ values and preferences,” Albert Siu, MD, of the Brookdale Department of Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai in New York, and his colleagues wrote in the position paper (Ann Intern Med. 2019 Apr 23. doi: 10.7326/M19-0961). “The research ... is urgently needed to advance prevention of osteoporosis-related mortality and morbidity.”

In the systematic review, by a group of researchers separate from the workshop, 48 studies were identified (35 trials, 13 observational studies) that compared men and postmenopausal women 50 years or older who used treatments such as alendronate, raloxifene, zoledronic acid, and hormone therapy. The researchers found that use of alendronate for 4 years reduced the rate of clinical fractures (hazard ratio, 0.64; 95% confidence interval, 0.50-0.82) and radiographic vertebral fractures (HR, 0.50; 95% CI, 0.31-0.82) in women with osteoporosis. Raloxifene use for 4 years reduced the rate of clinical vertebral fractures (relative risk, 0.58; 95% CI, 0.43-0.79) and radiographic vertebral fractures (RR, 0.64; 95% CI, 0.53-0.76) but not nonvertebral fractures. Zoledronic acid use for 6 years was associated with a lower rate of nonvertebral fractures (HR, 0.66; 95% CI, 0.51-0.85) and clinical vertebral fractures (HR, 0.41; 95% CI, 0.22-0.75) in women with both osteoporosis and osteopenia. Estrogen-progestin use for 5.6 years and unopposed estrogen for 7 years was associated with clinical fracture reduction in women with unspecified osteoporosis and osteopenia when compared with placebo (Ann Intern Med. 2019 April 23. doi: 10.7326/M19-0533).

Controlled observational studies collectively show that long-term use of alendronate and of bisphosphonates as a class increased risk for radiologically confirmed atypical femoral fracture but by a small absolute amount, with less evidence for risks of subtrochanteric or femoral shaft fractures without radiologically confirmed atypical femoral fracture features and osteonecrosis of the jaw. However, there were no eligible observational studies with long-term use of zoledronic acid that evaluated risk for these adverse events.

Long-term raloxifene therapy was associated with a threefold increased risk for deep venous thrombosis and a three- to fourfold increased risk for pulmonary embolism, although not all results were statistically significant, the researchers said. In two long-term trials, both estrogen and estrogen-progestin compared with placebo increased risk for cardiovascular disease and cognitive impairment. Estrogen-progestin also increased risk for invasive breast cancer.

The researchers also studied abaloparatide, denosumab, ibandronate, risedronate, and teriparatide, but noted there were insufficient data to show the long-term effects of their use on fractures and other harms.

Dr. Siu and coauthors on the position paper made the following recommendations with regard to future research on long-term ODT:

• Using “innovative designs and approaches” for new research such as modeling studies, clinical trials, and observational studies of existing and potential treatments.

• Evaluating new agents or multicomponent interventions, such as fracture liaison services and oral care, that do not carry the downsides of antiresorptive therapies.

• Researching and preventing atypical femoral fracture and osteonecrosis of the jaw, particularly when associated with long-term denosumab or bisphosphonate use.

• Determining which patients are indicated for drug holidays, sequential therapies, and strategies for avoiding serious adverse events.

• Studying barriers to ODT.

“When we have information on these outcomes, such as how medication use after a fragility fracture is linked to future fractures or survival rates, we need to understand how to convey that information to patients so they can make more informed decisions about their care,” noted Dr. Siu and colleagues.

In an editorial related to both the position paper and the systematic review, Carolyn J. Crandall, MD, of the University of California, Los Angeles, agreed that clinical trial data do not answer questions about shared decision making for women with multiple comorbid conditions, the long-term effects of ODT with regard to rare fracture risk, and which patients are well-suited for drug holidays.

“The National Institutes of Health should support research to answer these high-impact clinical questions, in addition to encouraging approaches for clinicians to determine which individual patients are at greater risk for harms related to long-term bisphosphonate use,” she said. “The need to rigorously study patient preferences in the context of ODT is pressing because of the complex dosing instructions of oral bisphosphonates and the dramatic underutilization of ODT among persons who have already had a vertebral or hip fracture.”

The systematic review was funded by the National Institutes of Health and the Agency for Healthcare Research and Quality. The authors of the position paper and Dr. Crandall reported no conflicts of interest.

SOURCE: Siu A et al. Ann Intern Med. 2019 April 23. doi: 10.7326/M19-0961.

Long-term use of alendronate and zoledronic acid for more than 3 years reduces the rate of vertebral fracture in treatment-naive postmenopausal women with notable, yet rare, adverse events, but too little evidence exists to make determinations on the long-term benefit/risk profile of other bisphosphonates or other osteoporosis drugs besides raloxifene and oral hormone therapy, according to a report coming out of a recent National Institutes of Health workshop.

This situation leaves a large research gap that authors of an accompanying position paper hope to bridge with recommendations for studying therapy discontinuation and drug holidays during long-term osteoporosis drug treatment.

The NIH’s Pathways to Prevention (P2P) Workshop: Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention outlined the findings of the systematic review of long-term osteoporosis drug treatment (ODT), which was commissioned by the NIH Office of Disease Prevention. The systematic review and a position paper summarizing the workshop were published April 23 in Annals of Internal Medicine.

“Clinicians and patients need increased information on benefits and risks to inform shared decision making about the use of these treatments, taking into account patients’ values and preferences,” Albert Siu, MD, of the Brookdale Department of Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai in New York, and his colleagues wrote in the position paper (Ann Intern Med. 2019 Apr 23. doi: 10.7326/M19-0961). “The research ... is urgently needed to advance prevention of osteoporosis-related mortality and morbidity.”

In the systematic review, by a group of researchers separate from the workshop, 48 studies were identified (35 trials, 13 observational studies) that compared men and postmenopausal women 50 years or older who used treatments such as alendronate, raloxifene, zoledronic acid, and hormone therapy. The researchers found that use of alendronate for 4 years reduced the rate of clinical fractures (hazard ratio, 0.64; 95% confidence interval, 0.50-0.82) and radiographic vertebral fractures (HR, 0.50; 95% CI, 0.31-0.82) in women with osteoporosis. Raloxifene use for 4 years reduced the rate of clinical vertebral fractures (relative risk, 0.58; 95% CI, 0.43-0.79) and radiographic vertebral fractures (RR, 0.64; 95% CI, 0.53-0.76) but not nonvertebral fractures. Zoledronic acid use for 6 years was associated with a lower rate of nonvertebral fractures (HR, 0.66; 95% CI, 0.51-0.85) and clinical vertebral fractures (HR, 0.41; 95% CI, 0.22-0.75) in women with both osteoporosis and osteopenia. Estrogen-progestin use for 5.6 years and unopposed estrogen for 7 years was associated with clinical fracture reduction in women with unspecified osteoporosis and osteopenia when compared with placebo (Ann Intern Med. 2019 April 23. doi: 10.7326/M19-0533).

Controlled observational studies collectively show that long-term use of alendronate and of bisphosphonates as a class increased risk for radiologically confirmed atypical femoral fracture but by a small absolute amount, with less evidence for risks of subtrochanteric or femoral shaft fractures without radiologically confirmed atypical femoral fracture features and osteonecrosis of the jaw. However, there were no eligible observational studies with long-term use of zoledronic acid that evaluated risk for these adverse events.

Long-term raloxifene therapy was associated with a threefold increased risk for deep venous thrombosis and a three- to fourfold increased risk for pulmonary embolism, although not all results were statistically significant, the researchers said. In two long-term trials, both estrogen and estrogen-progestin compared with placebo increased risk for cardiovascular disease and cognitive impairment. Estrogen-progestin also increased risk for invasive breast cancer.

The researchers also studied abaloparatide, denosumab, ibandronate, risedronate, and teriparatide, but noted there were insufficient data to show the long-term effects of their use on fractures and other harms.

Dr. Siu and coauthors on the position paper made the following recommendations with regard to future research on long-term ODT:

• Using “innovative designs and approaches” for new research such as modeling studies, clinical trials, and observational studies of existing and potential treatments.

• Evaluating new agents or multicomponent interventions, such as fracture liaison services and oral care, that do not carry the downsides of antiresorptive therapies.

• Researching and preventing atypical femoral fracture and osteonecrosis of the jaw, particularly when associated with long-term denosumab or bisphosphonate use.

• Determining which patients are indicated for drug holidays, sequential therapies, and strategies for avoiding serious adverse events.

• Studying barriers to ODT.

“When we have information on these outcomes, such as how medication use after a fragility fracture is linked to future fractures or survival rates, we need to understand how to convey that information to patients so they can make more informed decisions about their care,” noted Dr. Siu and colleagues.

In an editorial related to both the position paper and the systematic review, Carolyn J. Crandall, MD, of the University of California, Los Angeles, agreed that clinical trial data do not answer questions about shared decision making for women with multiple comorbid conditions, the long-term effects of ODT with regard to rare fracture risk, and which patients are well-suited for drug holidays.

“The National Institutes of Health should support research to answer these high-impact clinical questions, in addition to encouraging approaches for clinicians to determine which individual patients are at greater risk for harms related to long-term bisphosphonate use,” she said. “The need to rigorously study patient preferences in the context of ODT is pressing because of the complex dosing instructions of oral bisphosphonates and the dramatic underutilization of ODT among persons who have already had a vertebral or hip fracture.”

The systematic review was funded by the National Institutes of Health and the Agency for Healthcare Research and Quality. The authors of the position paper and Dr. Crandall reported no conflicts of interest.

SOURCE: Siu A et al. Ann Intern Med. 2019 April 23. doi: 10.7326/M19-0961.

Long-term use of alendronate and zoledronic acid for more than 3 years reduces the rate of vertebral fracture in treatment-naive postmenopausal women with notable, yet rare, adverse events, but too little evidence exists to make determinations on the long-term benefit/risk profile of other bisphosphonates or other osteoporosis drugs besides raloxifene and oral hormone therapy, according to a report coming out of a recent National Institutes of Health workshop.

This situation leaves a large research gap that authors of an accompanying position paper hope to bridge with recommendations for studying therapy discontinuation and drug holidays during long-term osteoporosis drug treatment.

The NIH’s Pathways to Prevention (P2P) Workshop: Appropriate Use of Drug Therapies for Osteoporotic Fracture Prevention outlined the findings of the systematic review of long-term osteoporosis drug treatment (ODT), which was commissioned by the NIH Office of Disease Prevention. The systematic review and a position paper summarizing the workshop were published April 23 in Annals of Internal Medicine.

“Clinicians and patients need increased information on benefits and risks to inform shared decision making about the use of these treatments, taking into account patients’ values and preferences,” Albert Siu, MD, of the Brookdale Department of Geriatrics and Palliative Medicine at the Icahn School of Medicine at Mount Sinai in New York, and his colleagues wrote in the position paper (Ann Intern Med. 2019 Apr 23. doi: 10.7326/M19-0961). “The research ... is urgently needed to advance prevention of osteoporosis-related mortality and morbidity.”

In the systematic review, by a group of researchers separate from the workshop, 48 studies were identified (35 trials, 13 observational studies) that compared men and postmenopausal women 50 years or older who used treatments such as alendronate, raloxifene, zoledronic acid, and hormone therapy. The researchers found that use of alendronate for 4 years reduced the rate of clinical fractures (hazard ratio, 0.64; 95% confidence interval, 0.50-0.82) and radiographic vertebral fractures (HR, 0.50; 95% CI, 0.31-0.82) in women with osteoporosis. Raloxifene use for 4 years reduced the rate of clinical vertebral fractures (relative risk, 0.58; 95% CI, 0.43-0.79) and radiographic vertebral fractures (RR, 0.64; 95% CI, 0.53-0.76) but not nonvertebral fractures. Zoledronic acid use for 6 years was associated with a lower rate of nonvertebral fractures (HR, 0.66; 95% CI, 0.51-0.85) and clinical vertebral fractures (HR, 0.41; 95% CI, 0.22-0.75) in women with both osteoporosis and osteopenia. Estrogen-progestin use for 5.6 years and unopposed estrogen for 7 years was associated with clinical fracture reduction in women with unspecified osteoporosis and osteopenia when compared with placebo (Ann Intern Med. 2019 April 23. doi: 10.7326/M19-0533).

Controlled observational studies collectively show that long-term use of alendronate and of bisphosphonates as a class increased risk for radiologically confirmed atypical femoral fracture but by a small absolute amount, with less evidence for risks of subtrochanteric or femoral shaft fractures without radiologically confirmed atypical femoral fracture features and osteonecrosis of the jaw. However, there were no eligible observational studies with long-term use of zoledronic acid that evaluated risk for these adverse events.

Long-term raloxifene therapy was associated with a threefold increased risk for deep venous thrombosis and a three- to fourfold increased risk for pulmonary embolism, although not all results were statistically significant, the researchers said. In two long-term trials, both estrogen and estrogen-progestin compared with placebo increased risk for cardiovascular disease and cognitive impairment. Estrogen-progestin also increased risk for invasive breast cancer.

The researchers also studied abaloparatide, denosumab, ibandronate, risedronate, and teriparatide, but noted there were insufficient data to show the long-term effects of their use on fractures and other harms.

Dr. Siu and coauthors on the position paper made the following recommendations with regard to future research on long-term ODT:

• Using “innovative designs and approaches” for new research such as modeling studies, clinical trials, and observational studies of existing and potential treatments.

• Evaluating new agents or multicomponent interventions, such as fracture liaison services and oral care, that do not carry the downsides of antiresorptive therapies.

• Researching and preventing atypical femoral fracture and osteonecrosis of the jaw, particularly when associated with long-term denosumab or bisphosphonate use.

• Determining which patients are indicated for drug holidays, sequential therapies, and strategies for avoiding serious adverse events.

• Studying barriers to ODT.

“When we have information on these outcomes, such as how medication use after a fragility fracture is linked to future fractures or survival rates, we need to understand how to convey that information to patients so they can make more informed decisions about their care,” noted Dr. Siu and colleagues.

In an editorial related to both the position paper and the systematic review, Carolyn J. Crandall, MD, of the University of California, Los Angeles, agreed that clinical trial data do not answer questions about shared decision making for women with multiple comorbid conditions, the long-term effects of ODT with regard to rare fracture risk, and which patients are well-suited for drug holidays.

“The National Institutes of Health should support research to answer these high-impact clinical questions, in addition to encouraging approaches for clinicians to determine which individual patients are at greater risk for harms related to long-term bisphosphonate use,” she said. “The need to rigorously study patient preferences in the context of ODT is pressing because of the complex dosing instructions of oral bisphosphonates and the dramatic underutilization of ODT among persons who have already had a vertebral or hip fracture.”

The systematic review was funded by the National Institutes of Health and the Agency for Healthcare Research and Quality. The authors of the position paper and Dr. Crandall reported no conflicts of interest.

SOURCE: Siu A et al. Ann Intern Med. 2019 April 23. doi: 10.7326/M19-0961.

Although stroke is a risk factor for osteoporosis, falls, and fractures, very few people who have experienced a recent stroke are either screened for osteoporosis or treated, research suggests.

Writing in Stroke, researchers presented an analysis of Ontario registry data from 16,581 patients who were aged 65 years or older and presented with stroke between 2003 and 2013.

Overall, just 5.1% of patients underwent bone mineral density testing. Of the 1,577 patients who had experienced a prior fracture, 71 (4.7%) had bone mineral density testing, and only 2.9% of those who had not had prior bone mineral density testing were tested after their stroke. Bone mineral density testing was more likely in patients who were younger, who were female, and who experienced a low-trauma fracture in the year after their stroke.

In total, 15.5% of patients were prescribed osteoporosis drugs in the first year after their stroke. However, only 7.8% of those who had fractures before the stroke and 14.8% of those with fractures after the stroke received osteoporosis treatment after the stroke. Patients who were female, had prior osteoporosis, had experienced prior fracture, had previously undergone bone mineral density testing, or had experienced a fracture or fall after their stroke were more likely to receive osteoporosis pharmacotherapy.

The authors found that the neither the severity of stroke nor the presence of other comorbidities was associated with an increased likelihood of screening or treatment of osteoporosis after the stroke.

Stroke is associated with up to a fourfold increased risk of osteoporosis and fracture, compared with healthy controls, most probably because of reduced mobility and an increased risk of falls, wrote Eshita Kapoor of the department of medicine at the University of Toronto and her coauthors.

“Screening and treatment may be particularly low poststroke because of under-recognition of osteoporosis as a consequence of stroke, a selective focus on the management of cardiovascular risk and stroke recovery, or factors such as dysphagia precluding use of oral bisphosphonates,” the authors wrote.

While the association is noted in U.S. stroke guidelines, there are few recommendations for treatment aside from fall prevention strategies, which the authors noted was a missed opportunity for prevention.

“Use of a risk prediction score to identify those at particularly high short-term risk of fractures after stroke may help to prioritize patients for osteoporosis testing and treatment,” they suggested.

The study was funded by the Heart and Stroke Foundation of Canada and was supported by ICES (Institute for Clinical Evaluative Sciences) and the Ontario Ministry of Health and Long-Term Care. One author declared consultancies for the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Kapoor E et al. Stroke. 2019 April 25. doi: 10.1161/STROKEAHA.118.024685
 

Although stroke is a risk factor for osteoporosis, falls, and fractures, very few people who have experienced a recent stroke are either screened for osteoporosis or treated, research suggests.

Writing in Stroke, researchers presented an analysis of Ontario registry data from 16,581 patients who were aged 65 years or older and presented with stroke between 2003 and 2013.

Overall, just 5.1% of patients underwent bone mineral density testing. Of the 1,577 patients who had experienced a prior fracture, 71 (4.7%) had bone mineral density testing, and only 2.9% of those who had not had prior bone mineral density testing were tested after their stroke. Bone mineral density testing was more likely in patients who were younger, who were female, and who experienced a low-trauma fracture in the year after their stroke.

In total, 15.5% of patients were prescribed osteoporosis drugs in the first year after their stroke. However, only 7.8% of those who had fractures before the stroke and 14.8% of those with fractures after the stroke received osteoporosis treatment after the stroke. Patients who were female, had prior osteoporosis, had experienced prior fracture, had previously undergone bone mineral density testing, or had experienced a fracture or fall after their stroke were more likely to receive osteoporosis pharmacotherapy.

The authors found that the neither the severity of stroke nor the presence of other comorbidities was associated with an increased likelihood of screening or treatment of osteoporosis after the stroke.

Stroke is associated with up to a fourfold increased risk of osteoporosis and fracture, compared with healthy controls, most probably because of reduced mobility and an increased risk of falls, wrote Eshita Kapoor of the department of medicine at the University of Toronto and her coauthors.

“Screening and treatment may be particularly low poststroke because of under-recognition of osteoporosis as a consequence of stroke, a selective focus on the management of cardiovascular risk and stroke recovery, or factors such as dysphagia precluding use of oral bisphosphonates,” the authors wrote.

While the association is noted in U.S. stroke guidelines, there are few recommendations for treatment aside from fall prevention strategies, which the authors noted was a missed opportunity for prevention.

“Use of a risk prediction score to identify those at particularly high short-term risk of fractures after stroke may help to prioritize patients for osteoporosis testing and treatment,” they suggested.

The study was funded by the Heart and Stroke Foundation of Canada and was supported by ICES (Institute for Clinical Evaluative Sciences) and the Ontario Ministry of Health and Long-Term Care. One author declared consultancies for the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Kapoor E et al. Stroke. 2019 April 25. doi: 10.1161/STROKEAHA.118.024685
 

Although stroke is a risk factor for osteoporosis, falls, and fractures, very few people who have experienced a recent stroke are either screened for osteoporosis or treated, research suggests.

Writing in Stroke, researchers presented an analysis of Ontario registry data from 16,581 patients who were aged 65 years or older and presented with stroke between 2003 and 2013.

Overall, just 5.1% of patients underwent bone mineral density testing. Of the 1,577 patients who had experienced a prior fracture, 71 (4.7%) had bone mineral density testing, and only 2.9% of those who had not had prior bone mineral density testing were tested after their stroke. Bone mineral density testing was more likely in patients who were younger, who were female, and who experienced a low-trauma fracture in the year after their stroke.

In total, 15.5% of patients were prescribed osteoporosis drugs in the first year after their stroke. However, only 7.8% of those who had fractures before the stroke and 14.8% of those with fractures after the stroke received osteoporosis treatment after the stroke. Patients who were female, had prior osteoporosis, had experienced prior fracture, had previously undergone bone mineral density testing, or had experienced a fracture or fall after their stroke were more likely to receive osteoporosis pharmacotherapy.

The authors found that the neither the severity of stroke nor the presence of other comorbidities was associated with an increased likelihood of screening or treatment of osteoporosis after the stroke.

Stroke is associated with up to a fourfold increased risk of osteoporosis and fracture, compared with healthy controls, most probably because of reduced mobility and an increased risk of falls, wrote Eshita Kapoor of the department of medicine at the University of Toronto and her coauthors.

“Screening and treatment may be particularly low poststroke because of under-recognition of osteoporosis as a consequence of stroke, a selective focus on the management of cardiovascular risk and stroke recovery, or factors such as dysphagia precluding use of oral bisphosphonates,” the authors wrote.

While the association is noted in U.S. stroke guidelines, there are few recommendations for treatment aside from fall prevention strategies, which the authors noted was a missed opportunity for prevention.

“Use of a risk prediction score to identify those at particularly high short-term risk of fractures after stroke may help to prioritize patients for osteoporosis testing and treatment,” they suggested.

The study was funded by the Heart and Stroke Foundation of Canada and was supported by ICES (Institute for Clinical Evaluative Sciences) and the Ontario Ministry of Health and Long-Term Care. One author declared consultancies for the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Kapoor E et al. Stroke. 2019 April 25. doi: 10.1161/STROKEAHA.118.024685
 

A treat-to-target approach using total hip T scores could help guide decisions about how long women with osteoporosis should stay on bone-building therapy, according to Serge Ferrari, MD, and his colleagues.

Using 10 years of follow-up data from 1,343 women who took denosumab in the FREEDOM trial, Dr. Ferrari and his colleagues determined that a T score of at least –2.5 would be an appropriate target for this decision.

“A T-score unit increase of 1.0 was associated with a significant reduction in fracture risk for T scores up to, but no greater than, –2.0, suggesting that a T-score threshold of at least –2.0 would be an appropriate target for therapy to maximize treatment,” said Dr. Ferrari of the University of Geneva and his colleagues. “Further improvements in bone mineral density were not associated with major additional changes in 1-year nonvertebral fracture incidence.”

The findings “highlight the importance of the relationship between hip T score and fracture risk, which is maintained during long-term therapy with denosumab. Regular monitoring of bone mineral density during therapy may be useful to determine when fracture risk has reached a minimal threshold; treatment could therefore be suspended and/or consolidated, as in the case of a reversible therapy such as denosumab.”

[email protected]

SOURCE: Ferrari S et al. J Bone Miner Res. 2019 Mar 28. doi: 10.1002/jbmr.3722.

A treat-to-target approach using total hip T scores could help guide decisions about how long women with osteoporosis should stay on bone-building therapy, according to Serge Ferrari, MD, and his colleagues.

Using 10 years of follow-up data from 1,343 women who took denosumab in the FREEDOM trial, Dr. Ferrari and his colleagues determined that a T score of at least –2.5 would be an appropriate target for this decision.

“A T-score unit increase of 1.0 was associated with a significant reduction in fracture risk for T scores up to, but no greater than, –2.0, suggesting that a T-score threshold of at least –2.0 would be an appropriate target for therapy to maximize treatment,” said Dr. Ferrari of the University of Geneva and his colleagues. “Further improvements in bone mineral density were not associated with major additional changes in 1-year nonvertebral fracture incidence.”

The findings “highlight the importance of the relationship between hip T score and fracture risk, which is maintained during long-term therapy with denosumab. Regular monitoring of bone mineral density during therapy may be useful to determine when fracture risk has reached a minimal threshold; treatment could therefore be suspended and/or consolidated, as in the case of a reversible therapy such as denosumab.”

[email protected]

SOURCE: Ferrari S et al. J Bone Miner Res. 2019 Mar 28. doi: 10.1002/jbmr.3722.

A treat-to-target approach using total hip T scores could help guide decisions about how long women with osteoporosis should stay on bone-building therapy, according to Serge Ferrari, MD, and his colleagues.

Using 10 years of follow-up data from 1,343 women who took denosumab in the FREEDOM trial, Dr. Ferrari and his colleagues determined that a T score of at least –2.5 would be an appropriate target for this decision.

“A T-score unit increase of 1.0 was associated with a significant reduction in fracture risk for T scores up to, but no greater than, –2.0, suggesting that a T-score threshold of at least –2.0 would be an appropriate target for therapy to maximize treatment,” said Dr. Ferrari of the University of Geneva and his colleagues. “Further improvements in bone mineral density were not associated with major additional changes in 1-year nonvertebral fracture incidence.”

The findings “highlight the importance of the relationship between hip T score and fracture risk, which is maintained during long-term therapy with denosumab. Regular monitoring of bone mineral density during therapy may be useful to determine when fracture risk has reached a minimal threshold; treatment could therefore be suspended and/or consolidated, as in the case of a reversible therapy such as denosumab.”

[email protected]

SOURCE: Ferrari S et al. J Bone Miner Res. 2019 Mar 28. doi: 10.1002/jbmr.3722.

SAN FRANCISCO – Falls figured prominently in the elevated fracture risk of SLE patients in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.

Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.

“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.

“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.

The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.

Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.

In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.

“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.

She reported having no financial conflicts regarding her study, carried out free of commercial support.

[email protected]

SAN FRANCISCO – Falls figured prominently in the elevated fracture risk of SLE patients in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.

Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.

“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.

“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.

The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.

Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.

In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.

“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.

She reported having no financial conflicts regarding her study, carried out free of commercial support.

[email protected]

SAN FRANCISCO – Falls figured prominently in the elevated fracture risk of SLE patients in a Dutch prospective longitudinal study, Irene E.M. Bultink, MD, PhD, reported at an international congress on systemic lupus erythematosus.

Bruce Jancin/MDedge News

“I think we should focus on fall risk and fall events in lupus. I think that’s a neglected area,” according to Dr. Bultink, a rheumatologist at the University of Amsterdam.

Contrary to the conventional wisdom, in her study, cumulative corticosteroid dose, average daily dosage, and bone loss were not significantly related to fracture risk in these SLE patients. That’s because Dr. Bultink and her fellow rheumatologists took steps to mitigate steroid-induced bone loss.

“We know steroids are very important for bone loss in lupus, but we demonstrated in our long-term follow-up study that it’s very dose dependent. If you use steroids below 7.5 mg daily and you protect your patient with calcium and vitamin D and, if possible, with bisphosphonates, the bone loss is restricted. I think fracture risk in lupus is more related to fall risk and fall incidence than to bone loss and steroid use. That’s what we demonstrated in our study,” she said in an interview.

“Unfortunately, until now, no studies on fall risk and fall events in lupus have been published. It’s not investigated very well. I think that fall risk in lupus patients might be greatly increased, compared to healthy controls,” Dr. Bultink added.

The study included 145 Dutch SLE patients with a mean age of 41 years at baseline. Ninety percent were women; 69% were white. Bone mineral density measurements by dual x-ray bone densitometry and x-rays of the lumbar and thoracic spine were obtained at entry and again after a median of 5 years.

Forty-two incident fractures occurred during a median of 7.2 years of follow-up. This equated to an incidence rate of 2.2 peripheral and 2.0 vertebral fractures per 100 person-years, rates double those in the Dutch general population.

In a logistic regression analysis, white ethnicity was independently associated with a 13.2-fold increased risk of fractures overall. Postmenopausal status conferred a fourfold increased risk. Older age was another important determinant. And patients with a prior stroke were at 15.5-fold greater risk of peripheral fractures.

“The prior stroke subgroup is especially vulnerable. In an earlier population-based study using data from the U.K. we also demonstrated that fractures happened more frequently in SLE patients who had already suffered a stroke (Osteoporos Int. 2014 Apr;25[4]:1275-83). So those are patients who are at very high risk for falling and fractures. But I think there are many reasons why patients with SLE would have an elevated fall risk. They have fatigue. They have muscle weakness, which might be due to vitamin D deficiency or prednisone use or inactivity. And they often have balance problems due to neuropathy or medication,” the rheumatologist observed.

She reported having no financial conflicts regarding her study, carried out free of commercial support.

[email protected]

The Food and Drug Administration approved romosozumab-aqqg (Evenity) for treating osteoporosis in postmenopausal women who are at high risk for fracture.

“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.

The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.

The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.

Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.

[email protected]

The Food and Drug Administration approved romosozumab-aqqg (Evenity) for treating osteoporosis in postmenopausal women who are at high risk for fracture.

“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.

The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.

The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.

Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.

[email protected]

The Food and Drug Administration approved romosozumab-aqqg (Evenity) for treating osteoporosis in postmenopausal women who are at high risk for fracture.

“These are women who have a history of osteoporotic fracture or multiple risk factors or have failed other treatments for osteoporosis,” according to a news release from the agency.

The monthly treatment of two injections (given one after the other at one visit) mainly works by increasing new bone formation, but these effects wane after 12 doses. If patients still need osteoporosis therapy after that maximum of 12 doses, it’s recommended they are put on treatments that reduce bone breakdown. Romosozumab-aqqg is “a monoclonal antibody that blocks the effects of the protein sclerostin,” according to the news release.

The treatment’s efficacy and safety was evaluated in two clinical trials of more than 11,000 women with postmenopausal osteoporosis. In one trial, women received 12 months of either romosozumab-aqqg or placebo. The treatment arm had a 73% lower risk of vertebral fracture than did the placebo arm, and this benefit was maintained over a second year when both groups were switched to denosumab, another osteoporosis therapy. In the second trial, one group received romosozumab-aqqg for 1 year and then a year of alendronate, and the other group received 2 years of alendronate, another osteoporosis therapy, according to the news release. In this trial, the romosozumab-aqqg arm had 50% less risk of vertebral fractures than did the alendronate-only arm, as well as reduced risk of nonvertebral fractures.

Romosozumab-aqqg was associated with higher risks of cardiovascular death, heart attack, and stroke in the alendronate trial, so the treatment comes with a boxed warning regarding those risks and recommends that the drug not be used in patients who have had a heart attack or stroke within the previous year, according to the news release. Common side effects include joint pain and headache, as well as injection-site reactions.

[email protected]

NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.

“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.

The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.

“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.


The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).

The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).

In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.

However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.


Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.

Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.

He reported having no relevant financial relationships.

NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.

“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.

The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.

“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.


The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).

The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).

In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.

However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.


Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.

Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.

He reported having no relevant financial relationships.

NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.

“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.

The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.

“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.


The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).

The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).

In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.

However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.


Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.

Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.

He reported having no relevant financial relationships.

NEW ORLEANS – Falls consume an estimated 6% of Medicare expenditures each year, but the risk can be meaningfully reduced in individuals over the age of 65 years when risk assessment justifies strength and neuromuscular training, according to an update on this field at the annual meeting at the Endocrine Society.

“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.

There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.

“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.

Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.

As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.

In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.

Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.

There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.

Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.

“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.

Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.

Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.

Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.

Dr. Kaufman reported no relevant financial relationships to disclose.

NEW ORLEANS – Falls consume an estimated 6% of Medicare expenditures each year, but the risk can be meaningfully reduced in individuals over the age of 65 years when risk assessment justifies strength and neuromuscular training, according to an update on this field at the annual meeting at the Endocrine Society.

“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.

There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.

“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.

Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.

As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.

In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.

Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.

There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.

Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.

“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.

Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.

Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.

Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.

Dr. Kaufman reported no relevant financial relationships to disclose.

NEW ORLEANS – Falls consume an estimated 6% of Medicare expenditures each year, but the risk can be meaningfully reduced in individuals over the age of 65 years when risk assessment justifies strength and neuromuscular training, according to an update on this field at the annual meeting at the Endocrine Society.

“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.

There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.

“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.

Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.

As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.

In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.

Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.

There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.

Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.

“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.

Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.

Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.

Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.

Dr. Kaufman reported no relevant financial relationships to disclose.

MAUI, HAWAII – Industry-funded randomized, controlled clinical trials published in the three top-rated rheumatology journals during the past 20 years are of significantly higher overall quality than the nonindustry-funded ones, Michael Putman, MD, said at the 2019 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Putman, a second-year rheumatology fellow at Northwestern University, Chicago, analyzed all randomized, controlled trials (RCTs) of pharmacotherapy featuring a comparator – either placebo or an active agent – published in 1998, 2008, and 2018 in Annals of the Rheumatic Diseases, Rheumatology, and Arthritis & Rheumatology.

His main takeaway: “Rheumatologic interventions seem to work pretty well. The mean absolute risk reduction in the trials is 17.5%, so the average number of patients who need to be treated with a rheumatologic intervention is about five. This is why it’s such a great specialty to be a part of: A lot of our patients get better.”

He created an RCT quality rating scale that captured the strength of study design, methodology, and findings based upon whether a randomized trial used a double-blind design; identified a prespecified primary outcome; and featured patient-reported outcomes, power calculations, sensitivity analysis, adjustment for multiple hypotheses, and intention-to-treat analysis. He then applied the rating scale to the 85 published RCTs in the three study years.

Of note, 84% of the trials published in 2018 were industry funded, up from 74% in 2008 and 1998.

“Industry funds the vast majority of studies. Industry studies are significantly more likely to be appropriately double blinded, report patient-reported outcome measures, use intention to treat, and they have a higher overall quality,” according to Dr. Putman.

Indeed, the industry-funded studies averaged a 66% score on his quality grading scale, compared with 45% for nonindustry-funded studies.

Utilization of most of the quality metrics remained stable over time. The exceptions: Incorporation of intent-to-treat analysis increased from 58% in 1998 to 87% in 2018, and sensitivity analysis was employed in just 5% of the trials published in 1998, compared with 37% in 2008 and 26% in 2018.

The most important change over the past 2 decades, in his view, has been the shrinking proportion of RCTs featuring an active-drug, head-to-head comparator arm. In 1998, 42% of studies featured that design; for example, comparing methotrexate to sulfasalazine. By 2018, that figure had dropped to just 13%.

“Most of our trials today compare an active compound, such an interleukin-17 inhibitor, to a placebo. I think that’s a big change in how we do things,” Dr. Putman observed. “With 84% of our studies being funded by industry, the incentives in medicine right now don’t support active comparator research. It’s harder to show a difference between two things that work than it is to show a difference between something and nothing.”

However, he’d welcome a revival of head-to-head active comparator trials.

“I’d really love to have that happen,” he said. “We have basic questions we haven’t answered yet about a lot of our basic drugs: Like in myositis, should you start with Imuran [azathioprine], CellCept [mycophenolate mofetil], or methotrexate?”

Another striking change over time has been the dwindling proportion of published trials with a statistically significant finding for the primary outcome: 79% in 1998, 46% in 2008, and 36% last year. Dr. Putman suspects the explanation lies in the steady improvement in the effectiveness of standard background therapy for many conditions, which makes it tougher to show a striking difference between the add-on study drug and add-on placebo.

“We’re a victim of our own success,” he commented.

In any event, many key secondary outcomes in the RCTs were positive, even when the primary endpoint wasn’t, according to Dr. Putman, and there was a notable dearth of completely negative clinical RCTs published in the three top journals.

“The more cynical interpretation is there’s an incredible amount of publication bias, where we’re only publishing studies that show an effect and the journals or investigators are censoring the ones that don’t. The more charitable explanation, which is probably also true, is that by the time you get to putting on an RCT you kind of think, ‘This thing works.’ You’re not testing random stuff, so your pretest probability of a drug being effective when it enters into an RCT is probably shifted toward effectiveness,” Dr. Putman speculated.

He reported having no financial conflicts regarding his study.

[email protected]

MAUI, HAWAII – Industry-funded randomized, controlled clinical trials published in the three top-rated rheumatology journals during the past 20 years are of significantly higher overall quality than the nonindustry-funded ones, Michael Putman, MD, said at the 2019 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Putman, a second-year rheumatology fellow at Northwestern University, Chicago, analyzed all randomized, controlled trials (RCTs) of pharmacotherapy featuring a comparator – either placebo or an active agent – published in 1998, 2008, and 2018 in Annals of the Rheumatic Diseases, Rheumatology, and Arthritis & Rheumatology.

His main takeaway: “Rheumatologic interventions seem to work pretty well. The mean absolute risk reduction in the trials is 17.5%, so the average number of patients who need to be treated with a rheumatologic intervention is about five. This is why it’s such a great specialty to be a part of: A lot of our patients get better.”

He created an RCT quality rating scale that captured the strength of study design, methodology, and findings based upon whether a randomized trial used a double-blind design; identified a prespecified primary outcome; and featured patient-reported outcomes, power calculations, sensitivity analysis, adjustment for multiple hypotheses, and intention-to-treat analysis. He then applied the rating scale to the 85 published RCTs in the three study years.

Of note, 84% of the trials published in 2018 were industry funded, up from 74% in 2008 and 1998.

“Industry funds the vast majority of studies. Industry studies are significantly more likely to be appropriately double blinded, report patient-reported outcome measures, use intention to treat, and they have a higher overall quality,” according to Dr. Putman.

Indeed, the industry-funded studies averaged a 66% score on his quality grading scale, compared with 45% for nonindustry-funded studies.

Utilization of most of the quality metrics remained stable over time. The exceptions: Incorporation of intent-to-treat analysis increased from 58% in 1998 to 87% in 2018, and sensitivity analysis was employed in just 5% of the trials published in 1998, compared with 37% in 2008 and 26% in 2018.

The most important change over the past 2 decades, in his view, has been the shrinking proportion of RCTs featuring an active-drug, head-to-head comparator arm. In 1998, 42% of studies featured that design; for example, comparing methotrexate to sulfasalazine. By 2018, that figure had dropped to just 13%.

“Most of our trials today compare an active compound, such an interleukin-17 inhibitor, to a placebo. I think that’s a big change in how we do things,” Dr. Putman observed. “With 84% of our studies being funded by industry, the incentives in medicine right now don’t support active comparator research. It’s harder to show a difference between two things that work than it is to show a difference between something and nothing.”

However, he’d welcome a revival of head-to-head active comparator trials.

“I’d really love to have that happen,” he said. “We have basic questions we haven’t answered yet about a lot of our basic drugs: Like in myositis, should you start with Imuran [azathioprine], CellCept [mycophenolate mofetil], or methotrexate?”

Another striking change over time has been the dwindling proportion of published trials with a statistically significant finding for the primary outcome: 79% in 1998, 46% in 2008, and 36% last year. Dr. Putman suspects the explanation lies in the steady improvement in the effectiveness of standard background therapy for many conditions, which makes it tougher to show a striking difference between the add-on study drug and add-on placebo.

“We’re a victim of our own success,” he commented.

In any event, many key secondary outcomes in the RCTs were positive, even when the primary endpoint wasn’t, according to Dr. Putman, and there was a notable dearth of completely negative clinical RCTs published in the three top journals.

“The more cynical interpretation is there’s an incredible amount of publication bias, where we’re only publishing studies that show an effect and the journals or investigators are censoring the ones that don’t. The more charitable explanation, which is probably also true, is that by the time you get to putting on an RCT you kind of think, ‘This thing works.’ You’re not testing random stuff, so your pretest probability of a drug being effective when it enters into an RCT is probably shifted toward effectiveness,” Dr. Putman speculated.

He reported having no financial conflicts regarding his study.

[email protected]

MAUI, HAWAII – Industry-funded randomized, controlled clinical trials published in the three top-rated rheumatology journals during the past 20 years are of significantly higher overall quality than the nonindustry-funded ones, Michael Putman, MD, said at the 2019 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Dr. Putman, a second-year rheumatology fellow at Northwestern University, Chicago, analyzed all randomized, controlled trials (RCTs) of pharmacotherapy featuring a comparator – either placebo or an active agent – published in 1998, 2008, and 2018 in Annals of the Rheumatic Diseases, Rheumatology, and Arthritis & Rheumatology.

His main takeaway: “Rheumatologic interventions seem to work pretty well. The mean absolute risk reduction in the trials is 17.5%, so the average number of patients who need to be treated with a rheumatologic intervention is about five. This is why it’s such a great specialty to be a part of: A lot of our patients get better.”

He created an RCT quality rating scale that captured the strength of study design, methodology, and findings based upon whether a randomized trial used a double-blind design; identified a prespecified primary outcome; and featured patient-reported outcomes, power calculations, sensitivity analysis, adjustment for multiple hypotheses, and intention-to-treat analysis. He then applied the rating scale to the 85 published RCTs in the three study years.

Of note, 84% of the trials published in 2018 were industry funded, up from 74% in 2008 and 1998.

“Industry funds the vast majority of studies. Industry studies are significantly more likely to be appropriately double blinded, report patient-reported outcome measures, use intention to treat, and they have a higher overall quality,” according to Dr. Putman.

Indeed, the industry-funded studies averaged a 66% score on his quality grading scale, compared with 45% for nonindustry-funded studies.

Utilization of most of the quality metrics remained stable over time. The exceptions: Incorporation of intent-to-treat analysis increased from 58% in 1998 to 87% in 2018, and sensitivity analysis was employed in just 5% of the trials published in 1998, compared with 37% in 2008 and 26% in 2018.

The most important change over the past 2 decades, in his view, has been the shrinking proportion of RCTs featuring an active-drug, head-to-head comparator arm. In 1998, 42% of studies featured that design; for example, comparing methotrexate to sulfasalazine. By 2018, that figure had dropped to just 13%.

“Most of our trials today compare an active compound, such an interleukin-17 inhibitor, to a placebo. I think that’s a big change in how we do things,” Dr. Putman observed. “With 84% of our studies being funded by industry, the incentives in medicine right now don’t support active comparator research. It’s harder to show a difference between two things that work than it is to show a difference between something and nothing.”

However, he’d welcome a revival of head-to-head active comparator trials.

“I’d really love to have that happen,” he said. “We have basic questions we haven’t answered yet about a lot of our basic drugs: Like in myositis, should you start with Imuran [azathioprine], CellCept [mycophenolate mofetil], or methotrexate?”

Another striking change over time has been the dwindling proportion of published trials with a statistically significant finding for the primary outcome: 79% in 1998, 46% in 2008, and 36% last year. Dr. Putman suspects the explanation lies in the steady improvement in the effectiveness of standard background therapy for many conditions, which makes it tougher to show a striking difference between the add-on study drug and add-on placebo.

“We’re a victim of our own success,” he commented.

In any event, many key secondary outcomes in the RCTs were positive, even when the primary endpoint wasn’t, according to Dr. Putman, and there was a notable dearth of completely negative clinical RCTs published in the three top journals.

“The more cynical interpretation is there’s an incredible amount of publication bias, where we’re only publishing studies that show an effect and the journals or investigators are censoring the ones that don’t. The more charitable explanation, which is probably also true, is that by the time you get to putting on an RCT you kind of think, ‘This thing works.’ You’re not testing random stuff, so your pretest probability of a drug being effective when it enters into an RCT is probably shifted toward effectiveness,” Dr. Putman speculated.

He reported having no financial conflicts regarding his study.

[email protected]

PHILADELPHIA – While a potential effect can’t be ruled out, the evidence to date is inconsistent in terms of whether proton pump inhibitors increase risk of osteoporotic fractures, an expert said at the Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.

“These associations are possible,” said David C. Metz, MD, professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.

However, Dr. Metz cautioned attendees to “be cognizant of the limitations of epidemiological data,” and highlighted a recent randomized, double-blind trial he recently published with colleagues showing a lack of proton pump inhibitors (PPI) effect on bone homeostasis in healthy, postmenopausal women.

Taking all the evidence into consideration, Dr. Metz recommended judicious use of PPIs: “Don’t deny therapy because of concerns about long-term side effects. If the patient deserves the drug, they work. Use the lowest effective long-term maintenance dose, depending on the indication.”

Dr. Metz was senior author on a frequently cited 2006 report in JAMA linking long-term PPI therapy to increased hip fracture risk, particularly when given at high doses. That study “opened up a cottage industry” of researchers examining positive or negative associations with PPI therapy, he said.

In a 2016 meta-analysis including 18 studies, investigators reported in Osteoporosis International that PPIs “modestly increased” risk of hip fracture (relative risk, 1.26; 95% confidence interval, 1.16-1.36), along with similar risk increases for spine or any-site fracture. However, many of the studies incorporated into that analysis did not conclusively associate PPIs with fractures, according to Dr. Metz.

Moreover, there had been no randomized, prospective, double-blind trials on the subject published until this month, according to Dr. Metz, when he and his coauthors reported in Gastroenterology that dexlansoprazole and esomeprazole did not affect bone homeostasis in healthy, postmenopausal women. The randomized, 26-week study, mandated by the Food and Drug Administration to evaluate long-term PPI risks, was “essentially a negative study,” Dr. Metz said in his presentation.

“I think it gives us comfort in knowing to use the drug appropriately when indicated,” he said.

In the randomized study, there were no significant differences between the PPI and placebo groups in bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or calcium absorption. There were significant increases in markers of bone turnover in women receiving PPIs versus women receiving placebo, but the levels remained within the normal limits, according to the investigators.

Nevertheless, he said that clinicians do need to be mindful of a potential risk of fracture associated with PPIs, even if studies to date are inconclusive. “I don’t think that PPIs really have a biological explanation yet at this point as to why they may make your parents a little bit more fracturable, if you happen to be a postmenopausal female who’s at risk for that.”

Dr. Metz reported receiving grant/research support from AAA, Ipsen, Lexicon, and Wren Laboratories, consulting for Takeda, and serving as a board member for the North American Neuroendocrine Tumor Society. The study was funded by Takeda, which was responsible for and sponsored the study design, data collection, data interpretation, and writing of the manuscript appearing in Gastroenterology.

This news organization and Global Academy for Medical Education are owned by the same parent company.

PHILADELPHIA – While a potential effect can’t be ruled out, the evidence to date is inconsistent in terms of whether proton pump inhibitors increase risk of osteoporotic fractures, an expert said at the Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.

“These associations are possible,” said David C. Metz, MD, professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.

However, Dr. Metz cautioned attendees to “be cognizant of the limitations of epidemiological data,” and highlighted a recent randomized, double-blind trial he recently published with colleagues showing a lack of proton pump inhibitors (PPI) effect on bone homeostasis in healthy, postmenopausal women.

Taking all the evidence into consideration, Dr. Metz recommended judicious use of PPIs: “Don’t deny therapy because of concerns about long-term side effects. If the patient deserves the drug, they work. Use the lowest effective long-term maintenance dose, depending on the indication.”

Dr. Metz was senior author on a frequently cited 2006 report in JAMA linking long-term PPI therapy to increased hip fracture risk, particularly when given at high doses. That study “opened up a cottage industry” of researchers examining positive or negative associations with PPI therapy, he said.

In a 2016 meta-analysis including 18 studies, investigators reported in Osteoporosis International that PPIs “modestly increased” risk of hip fracture (relative risk, 1.26; 95% confidence interval, 1.16-1.36), along with similar risk increases for spine or any-site fracture. However, many of the studies incorporated into that analysis did not conclusively associate PPIs with fractures, according to Dr. Metz.

Moreover, there had been no randomized, prospective, double-blind trials on the subject published until this month, according to Dr. Metz, when he and his coauthors reported in Gastroenterology that dexlansoprazole and esomeprazole did not affect bone homeostasis in healthy, postmenopausal women. The randomized, 26-week study, mandated by the Food and Drug Administration to evaluate long-term PPI risks, was “essentially a negative study,” Dr. Metz said in his presentation.

“I think it gives us comfort in knowing to use the drug appropriately when indicated,” he said.

In the randomized study, there were no significant differences between the PPI and placebo groups in bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or calcium absorption. There were significant increases in markers of bone turnover in women receiving PPIs versus women receiving placebo, but the levels remained within the normal limits, according to the investigators.

Nevertheless, he said that clinicians do need to be mindful of a potential risk of fracture associated with PPIs, even if studies to date are inconclusive. “I don’t think that PPIs really have a biological explanation yet at this point as to why they may make your parents a little bit more fracturable, if you happen to be a postmenopausal female who’s at risk for that.”

Dr. Metz reported receiving grant/research support from AAA, Ipsen, Lexicon, and Wren Laboratories, consulting for Takeda, and serving as a board member for the North American Neuroendocrine Tumor Society. The study was funded by Takeda, which was responsible for and sponsored the study design, data collection, data interpretation, and writing of the manuscript appearing in Gastroenterology.

This news organization and Global Academy for Medical Education are owned by the same parent company.

PHILADELPHIA – While a potential effect can’t be ruled out, the evidence to date is inconsistent in terms of whether proton pump inhibitors increase risk of osteoporotic fractures, an expert said at the Digestive Diseases: New Advances conference jointly provided by Rutgers and Global Academy for Medical Education.

“These associations are possible,” said David C. Metz, MD, professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.

However, Dr. Metz cautioned attendees to “be cognizant of the limitations of epidemiological data,” and highlighted a recent randomized, double-blind trial he recently published with colleagues showing a lack of proton pump inhibitors (PPI) effect on bone homeostasis in healthy, postmenopausal women.

Taking all the evidence into consideration, Dr. Metz recommended judicious use of PPIs: “Don’t deny therapy because of concerns about long-term side effects. If the patient deserves the drug, they work. Use the lowest effective long-term maintenance dose, depending on the indication.”

Dr. Metz was senior author on a frequently cited 2006 report in JAMA linking long-term PPI therapy to increased hip fracture risk, particularly when given at high doses. That study “opened up a cottage industry” of researchers examining positive or negative associations with PPI therapy, he said.

In a 2016 meta-analysis including 18 studies, investigators reported in Osteoporosis International that PPIs “modestly increased” risk of hip fracture (relative risk, 1.26; 95% confidence interval, 1.16-1.36), along with similar risk increases for spine or any-site fracture. However, many of the studies incorporated into that analysis did not conclusively associate PPIs with fractures, according to Dr. Metz.

Moreover, there had been no randomized, prospective, double-blind trials on the subject published until this month, according to Dr. Metz, when he and his coauthors reported in Gastroenterology that dexlansoprazole and esomeprazole did not affect bone homeostasis in healthy, postmenopausal women. The randomized, 26-week study, mandated by the Food and Drug Administration to evaluate long-term PPI risks, was “essentially a negative study,” Dr. Metz said in his presentation.

“I think it gives us comfort in knowing to use the drug appropriately when indicated,” he said.

In the randomized study, there were no significant differences between the PPI and placebo groups in bone mineral density, parathyroid hormone levels, serum or urine levels of minerals, or calcium absorption. There were significant increases in markers of bone turnover in women receiving PPIs versus women receiving placebo, but the levels remained within the normal limits, according to the investigators.

Nevertheless, he said that clinicians do need to be mindful of a potential risk of fracture associated with PPIs, even if studies to date are inconclusive. “I don’t think that PPIs really have a biological explanation yet at this point as to why they may make your parents a little bit more fracturable, if you happen to be a postmenopausal female who’s at risk for that.”

Dr. Metz reported receiving grant/research support from AAA, Ipsen, Lexicon, and Wren Laboratories, consulting for Takeda, and serving as a board member for the North American Neuroendocrine Tumor Society. The study was funded by Takeda, which was responsible for and sponsored the study design, data collection, data interpretation, and writing of the manuscript appearing in Gastroenterology.

This news organization and Global Academy for Medical Education are owned by the same parent company.