Osteoporosis

Key clinical point: Both total hip bone mineral density (BMD) change and T-score can serve as surrogates for predicting vertebral fracture risk in patients with osteoporosis receiving denosumab treatment.

Major finding: Total hip BMD change and T-score were strong predictors of subsequent vertebral fracture risk, with total hip BMD change accounting for 73% and T-score accounting for 23% of the treatment effect.

Study details: Post hoc analysis of the DIRECT trial involving 1,011 Japanese postmenopausal women and men who were randomly assigned (2:2:1) to receive denosumab, placebo, or alendronate.

Disclosures: The study was funded by Daiichi Sankyo Co., Ltd., Tokyo, Japan. N Okubo, T Osakabe, K Watanabe, and H Takami were Daiichi Sankyo employees. Other authors reported relationships with various pharmaceutical companies, including Daiichi Sankyo.

Source: Okubo N et al. Calcif Tissue Int. 2020 Aug 25. doi: 10.1007/s00223-020-00750-y.

Key clinical point: Both total hip bone mineral density (BMD) change and T-score can serve as surrogates for predicting vertebral fracture risk in patients with osteoporosis receiving denosumab treatment.

Major finding: Total hip BMD change and T-score were strong predictors of subsequent vertebral fracture risk, with total hip BMD change accounting for 73% and T-score accounting for 23% of the treatment effect.

Study details: Post hoc analysis of the DIRECT trial involving 1,011 Japanese postmenopausal women and men who were randomly assigned (2:2:1) to receive denosumab, placebo, or alendronate.

Disclosures: The study was funded by Daiichi Sankyo Co., Ltd., Tokyo, Japan. N Okubo, T Osakabe, K Watanabe, and H Takami were Daiichi Sankyo employees. Other authors reported relationships with various pharmaceutical companies, including Daiichi Sankyo.

Source: Okubo N et al. Calcif Tissue Int. 2020 Aug 25. doi: 10.1007/s00223-020-00750-y.

Key clinical point: Both total hip bone mineral density (BMD) change and T-score can serve as surrogates for predicting vertebral fracture risk in patients with osteoporosis receiving denosumab treatment.

Major finding: Total hip BMD change and T-score were strong predictors of subsequent vertebral fracture risk, with total hip BMD change accounting for 73% and T-score accounting for 23% of the treatment effect.

Study details: Post hoc analysis of the DIRECT trial involving 1,011 Japanese postmenopausal women and men who were randomly assigned (2:2:1) to receive denosumab, placebo, or alendronate.

Disclosures: The study was funded by Daiichi Sankyo Co., Ltd., Tokyo, Japan. N Okubo, T Osakabe, K Watanabe, and H Takami were Daiichi Sankyo employees. Other authors reported relationships with various pharmaceutical companies, including Daiichi Sankyo.

Source: Okubo N et al. Calcif Tissue Int. 2020 Aug 25. doi: 10.1007/s00223-020-00750-y.

Key clinical point: Diabetic patients with carcinoma in situ (CIS) under metformin therapy presented a lower osteoporosis rate vs. those who were not receiving metformin.

Major finding: The risk of osteoporosis was lower in diabetic patients with CIS who were receiving metformin therapy vs. those who were not receiving metformin (adjusted hazard ratio, 0.82; P = .022).

Study details: This retrospective matched-cohort study included 7,827 diabetic patients with CIS treated with metformin and 23,481 matched controls with no metformin therapy.

Disclosures: The study was funded by the Tri-Service General Hospital Research Foundation, the National Defense Medical Center, Ministry of National Defense-Medical Affairs Bureau, and the Teh-Tzer Study Group for Human Medical Research Foundation. The authors declared no conflicts of interest.

Source: Lu CH et al. J Clin Med. 2020 Sep 2. doi: 10.3390/jcm9092839.

Key clinical point: Diabetic patients with carcinoma in situ (CIS) under metformin therapy presented a lower osteoporosis rate vs. those who were not receiving metformin.

Major finding: The risk of osteoporosis was lower in diabetic patients with CIS who were receiving metformin therapy vs. those who were not receiving metformin (adjusted hazard ratio, 0.82; P = .022).

Study details: This retrospective matched-cohort study included 7,827 diabetic patients with CIS treated with metformin and 23,481 matched controls with no metformin therapy.

Disclosures: The study was funded by the Tri-Service General Hospital Research Foundation, the National Defense Medical Center, Ministry of National Defense-Medical Affairs Bureau, and the Teh-Tzer Study Group for Human Medical Research Foundation. The authors declared no conflicts of interest.

Source: Lu CH et al. J Clin Med. 2020 Sep 2. doi: 10.3390/jcm9092839.

Key clinical point: Diabetic patients with carcinoma in situ (CIS) under metformin therapy presented a lower osteoporosis rate vs. those who were not receiving metformin.

Major finding: The risk of osteoporosis was lower in diabetic patients with CIS who were receiving metformin therapy vs. those who were not receiving metformin (adjusted hazard ratio, 0.82; P = .022).

Study details: This retrospective matched-cohort study included 7,827 diabetic patients with CIS treated with metformin and 23,481 matched controls with no metformin therapy.

Disclosures: The study was funded by the Tri-Service General Hospital Research Foundation, the National Defense Medical Center, Ministry of National Defense-Medical Affairs Bureau, and the Teh-Tzer Study Group for Human Medical Research Foundation. The authors declared no conflicts of interest.

Source: Lu CH et al. J Clin Med. 2020 Sep 2. doi: 10.3390/jcm9092839.

Key clinical point: Teriparatide improves bone formation rate (BFR), bone turnover markers, and spine and hip bone density in premenopausal women with idiopathic osteoporosis (IOP).

Major finding: At 6 months, teriparatide significantly increased lumbar spine (LS) areal bone mineral density (aBMD) vs placebo (percentage change: 5.51% vs. 1.55%; P = .007). At 24 months, teriparatide significantly increased aBMD of LS, total hip, and femoral neck (percentage change: 13.2%, 5.2%, and 5.0%, respectively; P ≤. 001 for all). Cancellous and intracortical BFR increased 3.3-fold (P ≤. 001) and 1.9-fold (P ≤. 001), respectively, in the teriparatide group with no change in placebo group. Serum N-terminal propeptides of procollagen type 1, osteocalcin, and C-telopeptide increased significantly by 3 months with teriparatide treatment.

Study details: The data come from a phase 2 trial of 41 premenopausal women with IOP who were randomly assigned to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6 months, placebo group was switched to teriparatide for 24 months, and the teriparatide group continued the drug for 18 months.

Disclosures: The study was supported by the United States Food and Drug Administration Orphan Products Clinical Trials Grants Program. A Cohen, E Shane, RR Recker, and JM Lappe received research support from Amgen and Eli Lilly. DW Dempster received research support and consulting fees from Amgen, Eli Lilly, and Radius Health.

Source: Cohen A et al. J Clin Endocrinol Metab. 2020 Sep 2. doi: 10.1210/clinem/dgaa489.

Key clinical point: Teriparatide improves bone formation rate (BFR), bone turnover markers, and spine and hip bone density in premenopausal women with idiopathic osteoporosis (IOP).

Major finding: At 6 months, teriparatide significantly increased lumbar spine (LS) areal bone mineral density (aBMD) vs placebo (percentage change: 5.51% vs. 1.55%; P = .007). At 24 months, teriparatide significantly increased aBMD of LS, total hip, and femoral neck (percentage change: 13.2%, 5.2%, and 5.0%, respectively; P ≤. 001 for all). Cancellous and intracortical BFR increased 3.3-fold (P ≤. 001) and 1.9-fold (P ≤. 001), respectively, in the teriparatide group with no change in placebo group. Serum N-terminal propeptides of procollagen type 1, osteocalcin, and C-telopeptide increased significantly by 3 months with teriparatide treatment.

Study details: The data come from a phase 2 trial of 41 premenopausal women with IOP who were randomly assigned to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6 months, placebo group was switched to teriparatide for 24 months, and the teriparatide group continued the drug for 18 months.

Disclosures: The study was supported by the United States Food and Drug Administration Orphan Products Clinical Trials Grants Program. A Cohen, E Shane, RR Recker, and JM Lappe received research support from Amgen and Eli Lilly. DW Dempster received research support and consulting fees from Amgen, Eli Lilly, and Radius Health.

Source: Cohen A et al. J Clin Endocrinol Metab. 2020 Sep 2. doi: 10.1210/clinem/dgaa489.

Key clinical point: Teriparatide improves bone formation rate (BFR), bone turnover markers, and spine and hip bone density in premenopausal women with idiopathic osteoporosis (IOP).

Major finding: At 6 months, teriparatide significantly increased lumbar spine (LS) areal bone mineral density (aBMD) vs placebo (percentage change: 5.51% vs. 1.55%; P = .007). At 24 months, teriparatide significantly increased aBMD of LS, total hip, and femoral neck (percentage change: 13.2%, 5.2%, and 5.0%, respectively; P ≤. 001 for all). Cancellous and intracortical BFR increased 3.3-fold (P ≤. 001) and 1.9-fold (P ≤. 001), respectively, in the teriparatide group with no change in placebo group. Serum N-terminal propeptides of procollagen type 1, osteocalcin, and C-telopeptide increased significantly by 3 months with teriparatide treatment.

Study details: The data come from a phase 2 trial of 41 premenopausal women with IOP who were randomly assigned to either teriparatide 20 mcg (n = 28) or placebo (n = 13). After 6 months, placebo group was switched to teriparatide for 24 months, and the teriparatide group continued the drug for 18 months.

Disclosures: The study was supported by the United States Food and Drug Administration Orphan Products Clinical Trials Grants Program. A Cohen, E Shane, RR Recker, and JM Lappe received research support from Amgen and Eli Lilly. DW Dempster received research support and consulting fees from Amgen, Eli Lilly, and Radius Health.

Source: Cohen A et al. J Clin Endocrinol Metab. 2020 Sep 2. doi: 10.1210/clinem/dgaa489.

Key clinical point: Denosumab treatment was safe and increased bone mineral density (BMD), suppressed bone turnover, and improved bone quality marker levels in chronic liver disease (CLD) patients with osteoporosis.

Major finding: At 12 months, denosumab significantly improved BMD at the lumbar spine, femoral neck, and total hip regardless of age, gender, and presence/absence of liver cirrhosis (+4.44%, +3.71%, and +4.03%, respectively; P less than .001 for all). Denosumab significantly decreased serum levels of tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide (P less than .001 for both) and also plasma pentosidine level (P = .010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

Study details: The data come from a retrospective study of 60 CLD patients with osteoporosis who were subcutaneously administered denosumab once every 6 months.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Saeki C et al. World J Gastroenterol. 2020 Sep 7. doi: 10.3748/wjg.v26.i33.4960.

Key clinical point: Denosumab treatment was safe and increased bone mineral density (BMD), suppressed bone turnover, and improved bone quality marker levels in chronic liver disease (CLD) patients with osteoporosis.

Major finding: At 12 months, denosumab significantly improved BMD at the lumbar spine, femoral neck, and total hip regardless of age, gender, and presence/absence of liver cirrhosis (+4.44%, +3.71%, and +4.03%, respectively; P less than .001 for all). Denosumab significantly decreased serum levels of tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide (P less than .001 for both) and also plasma pentosidine level (P = .010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

Study details: The data come from a retrospective study of 60 CLD patients with osteoporosis who were subcutaneously administered denosumab once every 6 months.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Saeki C et al. World J Gastroenterol. 2020 Sep 7. doi: 10.3748/wjg.v26.i33.4960.

Key clinical point: Denosumab treatment was safe and increased bone mineral density (BMD), suppressed bone turnover, and improved bone quality marker levels in chronic liver disease (CLD) patients with osteoporosis.

Major finding: At 12 months, denosumab significantly improved BMD at the lumbar spine, femoral neck, and total hip regardless of age, gender, and presence/absence of liver cirrhosis (+4.44%, +3.71%, and +4.03%, respectively; P less than .001 for all). Denosumab significantly decreased serum levels of tartrate-resistant acid phosphatase-5b and procollagen type I N-terminal propeptide (P less than .001 for both) and also plasma pentosidine level (P = .010). No patients experienced fractures and moderate-to-severe adverse events, except for transient hypocalcemia.

Study details: The data come from a retrospective study of 60 CLD patients with osteoporosis who were subcutaneously administered denosumab once every 6 months.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.

Source: Saeki C et al. World J Gastroenterol. 2020 Sep 7. doi: 10.3748/wjg.v26.i33.4960.

Romosozumab is a novel osteoporosis treatment agent that stimulates bone formation and inhibits bone resorption. Due to concerns for adverse cardiovascular effects, this medication is generally reserved for patients with severe osteoporosis despite multiple previous treatments. However, the influence of previous osteoporosis pharmacotherapy on romosozumab’s skeletal efficacy remains poorly studied, especially in real world clinical scenarios. In a prospective non-randomized study of 130 patients treated with romosozumab in Japan, the effects of romosozumab treatment on bone turnover markers and bone mineral density (BMD) was assessed based on previous treatment with either no osteoporosis medication, bisphosphonates, denosumab, or teriparatide. In general, treatment-naïve individuals experienced superior spine BMD and bone turnover marker gains versus patients who had previously received osteoporosis pharmacotherapy. Notably, prior treatment with the potent anti-resorptive agent denosumab was associated with suboptimal spine BMD response to romosozumab. These results highlight the potential impact of previous anti-resorptive treatment on romosozumab efficacy and indicate that careful consideration of treatment sequence is warranted when deciding amongst the multiple osteoporosis agents that are currently available.

Denosumab is a potent anti-resorptive osteoporosis agent that works by neutralizing RANKL, the key cytokine that drives osteoclast differentiation. While effective at suppressing bone resorption, increasing BMD, and preventing fragility fractures when administered every 6 months, rapid discontinuation of denosumab has been associated with an increased risk of vertebral compression fractures. In routine clinical practice, denosumab injection delays are common. However, risks of vertebral fractures associated with such injection delays remain unknown. In this study of a UK population-based cohort of 2,594 patients, a large electronic database was used to assess the relationship between denosumab dosing intervals (defined as ‘on time’, ‘short delay’, and ‘long delay’) and fractures in the 6 month window after the recommended treatment date. Compared with ‘on time’ denosumab treatment, individuals who received delayed denosumab injections showed an increased risk of interval vertebral fractures. Notably, the delay time was associated with fracture risk. This powerful study design further underscores the importance of timely (every 6 months) denosumab injections. Given current health care delivery challenges associated with the COVID-19 pandemic, these results should be considered when selecting initial osteoporosis treatment agents and in management of patients currently receiving denosumab. 

Abaloparatide, a synthetic analog of parathyroid hormone related peptide (PTHrP) is a bone anabolic osteoporosis treatment agent. In the ACTIVE study, abaloparatide increased bone mineral density and reduced fracture risk compared to both placebo and teriparatide. Although abaloparatide is generally well-tolerated, non-serious adverse events have been reported such as dizziness and palpitations. PTHrP can act in a paracrine manner to cause vasodilation. Therefore, in this post hoc drug safety study, the effects of abaloparatide on blood pressure, pulse, and cardiovascular adverse events were assessed in detail in subjects from the ACTIVE study (one hour post treatment) plus an additional group of 55 subjects for more detailed hemodynamic assessment. Compared to placebo injection, both abaloparatide and teriparatide treatment caused mild and transient increases in pulse and decreases in systolic blood pressure. These mild hemodynamic changes were not associated with an increased risk of adverse cardiovascular events. In general, these data are reassuring and support the cardiac safety of PTH analogs for osteoporosis. However, the transient hemodynamic changes observed should be considered for patients with cardiovascular comorbidities or baseline problems with orthostasis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Romosozumab is a novel osteoporosis treatment agent that stimulates bone formation and inhibits bone resorption. Due to concerns for adverse cardiovascular effects, this medication is generally reserved for patients with severe osteoporosis despite multiple previous treatments. However, the influence of previous osteoporosis pharmacotherapy on romosozumab’s skeletal efficacy remains poorly studied, especially in real world clinical scenarios. In a prospective non-randomized study of 130 patients treated with romosozumab in Japan, the effects of romosozumab treatment on bone turnover markers and bone mineral density (BMD) was assessed based on previous treatment with either no osteoporosis medication, bisphosphonates, denosumab, or teriparatide. In general, treatment-naïve individuals experienced superior spine BMD and bone turnover marker gains versus patients who had previously received osteoporosis pharmacotherapy. Notably, prior treatment with the potent anti-resorptive agent denosumab was associated with suboptimal spine BMD response to romosozumab. These results highlight the potential impact of previous anti-resorptive treatment on romosozumab efficacy and indicate that careful consideration of treatment sequence is warranted when deciding amongst the multiple osteoporosis agents that are currently available.

Denosumab is a potent anti-resorptive osteoporosis agent that works by neutralizing RANKL, the key cytokine that drives osteoclast differentiation. While effective at suppressing bone resorption, increasing BMD, and preventing fragility fractures when administered every 6 months, rapid discontinuation of denosumab has been associated with an increased risk of vertebral compression fractures. In routine clinical practice, denosumab injection delays are common. However, risks of vertebral fractures associated with such injection delays remain unknown. In this study of a UK population-based cohort of 2,594 patients, a large electronic database was used to assess the relationship between denosumab dosing intervals (defined as ‘on time’, ‘short delay’, and ‘long delay’) and fractures in the 6 month window after the recommended treatment date. Compared with ‘on time’ denosumab treatment, individuals who received delayed denosumab injections showed an increased risk of interval vertebral fractures. Notably, the delay time was associated with fracture risk. This powerful study design further underscores the importance of timely (every 6 months) denosumab injections. Given current health care delivery challenges associated with the COVID-19 pandemic, these results should be considered when selecting initial osteoporosis treatment agents and in management of patients currently receiving denosumab. 

Abaloparatide, a synthetic analog of parathyroid hormone related peptide (PTHrP) is a bone anabolic osteoporosis treatment agent. In the ACTIVE study, abaloparatide increased bone mineral density and reduced fracture risk compared to both placebo and teriparatide. Although abaloparatide is generally well-tolerated, non-serious adverse events have been reported such as dizziness and palpitations. PTHrP can act in a paracrine manner to cause vasodilation. Therefore, in this post hoc drug safety study, the effects of abaloparatide on blood pressure, pulse, and cardiovascular adverse events were assessed in detail in subjects from the ACTIVE study (one hour post treatment) plus an additional group of 55 subjects for more detailed hemodynamic assessment. Compared to placebo injection, both abaloparatide and teriparatide treatment caused mild and transient increases in pulse and decreases in systolic blood pressure. These mild hemodynamic changes were not associated with an increased risk of adverse cardiovascular events. In general, these data are reassuring and support the cardiac safety of PTH analogs for osteoporosis. However, the transient hemodynamic changes observed should be considered for patients with cardiovascular comorbidities or baseline problems with orthostasis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Romosozumab is a novel osteoporosis treatment agent that stimulates bone formation and inhibits bone resorption. Due to concerns for adverse cardiovascular effects, this medication is generally reserved for patients with severe osteoporosis despite multiple previous treatments. However, the influence of previous osteoporosis pharmacotherapy on romosozumab’s skeletal efficacy remains poorly studied, especially in real world clinical scenarios. In a prospective non-randomized study of 130 patients treated with romosozumab in Japan, the effects of romosozumab treatment on bone turnover markers and bone mineral density (BMD) was assessed based on previous treatment with either no osteoporosis medication, bisphosphonates, denosumab, or teriparatide. In general, treatment-naïve individuals experienced superior spine BMD and bone turnover marker gains versus patients who had previously received osteoporosis pharmacotherapy. Notably, prior treatment with the potent anti-resorptive agent denosumab was associated with suboptimal spine BMD response to romosozumab. These results highlight the potential impact of previous anti-resorptive treatment on romosozumab efficacy and indicate that careful consideration of treatment sequence is warranted when deciding amongst the multiple osteoporosis agents that are currently available.

Denosumab is a potent anti-resorptive osteoporosis agent that works by neutralizing RANKL, the key cytokine that drives osteoclast differentiation. While effective at suppressing bone resorption, increasing BMD, and preventing fragility fractures when administered every 6 months, rapid discontinuation of denosumab has been associated with an increased risk of vertebral compression fractures. In routine clinical practice, denosumab injection delays are common. However, risks of vertebral fractures associated with such injection delays remain unknown. In this study of a UK population-based cohort of 2,594 patients, a large electronic database was used to assess the relationship between denosumab dosing intervals (defined as ‘on time’, ‘short delay’, and ‘long delay’) and fractures in the 6 month window after the recommended treatment date. Compared with ‘on time’ denosumab treatment, individuals who received delayed denosumab injections showed an increased risk of interval vertebral fractures. Notably, the delay time was associated with fracture risk. This powerful study design further underscores the importance of timely (every 6 months) denosumab injections. Given current health care delivery challenges associated with the COVID-19 pandemic, these results should be considered when selecting initial osteoporosis treatment agents and in management of patients currently receiving denosumab. 

Abaloparatide, a synthetic analog of parathyroid hormone related peptide (PTHrP) is a bone anabolic osteoporosis treatment agent. In the ACTIVE study, abaloparatide increased bone mineral density and reduced fracture risk compared to both placebo and teriparatide. Although abaloparatide is generally well-tolerated, non-serious adverse events have been reported such as dizziness and palpitations. PTHrP can act in a paracrine manner to cause vasodilation. Therefore, in this post hoc drug safety study, the effects of abaloparatide on blood pressure, pulse, and cardiovascular adverse events were assessed in detail in subjects from the ACTIVE study (one hour post treatment) plus an additional group of 55 subjects for more detailed hemodynamic assessment. Compared to placebo injection, both abaloparatide and teriparatide treatment caused mild and transient increases in pulse and decreases in systolic blood pressure. These mild hemodynamic changes were not associated with an increased risk of adverse cardiovascular events. In general, these data are reassuring and support the cardiac safety of PTH analogs for osteoporosis. However, the transient hemodynamic changes observed should be considered for patients with cardiovascular comorbidities or baseline problems with orthostasis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Key clinical point: Teriparatide may have better therapeutic effects than denosumab in glucocorticoid-induced osteoporosis (GIO) patients previously treated with bisphosphonates.

Major finding: Teriparatide group showed a significantly greater improvement in the bone mineral density (BMD) of lumbar spine (P less than .01) and femoral neck (P less than .05) vs. denosumab group at 12 months, but not at 24 months. At 24 months, BMD of lumbar spine had significantly increased from baseline in both the groups, whereas BMD of femoral neck had increased only in the teriparatide group.

Study details: A prospective, open-label, nonrandomized, single-center study including 47 patients with GIO assigned to either teriparatide group (n = 23) or denosumab group (n = 24).

Disclosures: The study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Hirooka Y et al. Bone Rep. 2020 Jul 4. doi: 10.1016/j.bonr.2020.100293.

Key clinical point: Teriparatide may have better therapeutic effects than denosumab in glucocorticoid-induced osteoporosis (GIO) patients previously treated with bisphosphonates.

Major finding: Teriparatide group showed a significantly greater improvement in the bone mineral density (BMD) of lumbar spine (P less than .01) and femoral neck (P less than .05) vs. denosumab group at 12 months, but not at 24 months. At 24 months, BMD of lumbar spine had significantly increased from baseline in both the groups, whereas BMD of femoral neck had increased only in the teriparatide group.

Study details: A prospective, open-label, nonrandomized, single-center study including 47 patients with GIO assigned to either teriparatide group (n = 23) or denosumab group (n = 24).

Disclosures: The study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Hirooka Y et al. Bone Rep. 2020 Jul 4. doi: 10.1016/j.bonr.2020.100293.

Key clinical point: Teriparatide may have better therapeutic effects than denosumab in glucocorticoid-induced osteoporosis (GIO) patients previously treated with bisphosphonates.

Major finding: Teriparatide group showed a significantly greater improvement in the bone mineral density (BMD) of lumbar spine (P less than .01) and femoral neck (P less than .05) vs. denosumab group at 12 months, but not at 24 months. At 24 months, BMD of lumbar spine had significantly increased from baseline in both the groups, whereas BMD of femoral neck had increased only in the teriparatide group.

Study details: A prospective, open-label, nonrandomized, single-center study including 47 patients with GIO assigned to either teriparatide group (n = 23) or denosumab group (n = 24).

Disclosures: The study did not receive any specific funding. The authors declared no conflicts of interest.

Source: Hirooka Y et al. Bone Rep. 2020 Jul 4. doi: 10.1016/j.bonr.2020.100293.

Key clinical point: Psoriatic arthritis (PsA) is associated with the risk for low bone mineral density (BMD), but this association is partially mediated by treatment with methotrexate or ciclosporin. Psoriasis excluding PsA in the absence of a secondary condition is not a risk factor for osteoporosis.

Major finding: PsA was associated with low BMD (β-coefficient = −0.014; P = .0006). However, the association became nonsignificant when patients were treated with methotrexate or ciclosporin (β-coefficient = −0.005; P = .28). Psoriasis without arthritis was not associated with low BMD or osteoporosis.

Study details: The data come from a cross-sectional study of 432,513 participants from the UK Biobank dataset.

Disclosures: The study was supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Xia J et al. Ann Rheum Dis. 2020 Jul 31. doi: 10.1136/annrheumdis-2020-217892.

Key clinical point: Psoriatic arthritis (PsA) is associated with the risk for low bone mineral density (BMD), but this association is partially mediated by treatment with methotrexate or ciclosporin. Psoriasis excluding PsA in the absence of a secondary condition is not a risk factor for osteoporosis.

Major finding: PsA was associated with low BMD (β-coefficient = −0.014; P = .0006). However, the association became nonsignificant when patients were treated with methotrexate or ciclosporin (β-coefficient = −0.005; P = .28). Psoriasis without arthritis was not associated with low BMD or osteoporosis.

Study details: The data come from a cross-sectional study of 432,513 participants from the UK Biobank dataset.

Disclosures: The study was supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Xia J et al. Ann Rheum Dis. 2020 Jul 31. doi: 10.1136/annrheumdis-2020-217892.

Key clinical point: Psoriatic arthritis (PsA) is associated with the risk for low bone mineral density (BMD), but this association is partially mediated by treatment with methotrexate or ciclosporin. Psoriasis excluding PsA in the absence of a secondary condition is not a risk factor for osteoporosis.

Major finding: PsA was associated with low BMD (β-coefficient = −0.014; P = .0006). However, the association became nonsignificant when patients were treated with methotrexate or ciclosporin (β-coefficient = −0.005; P = .28). Psoriasis without arthritis was not associated with low BMD or osteoporosis.

Study details: The data come from a cross-sectional study of 432,513 participants from the UK Biobank dataset.

Disclosures: The study was supported by the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars of China and the National Natural Science Foundation of China. The authors declared no conflicts of interest.

Source: Xia J et al. Ann Rheum Dis. 2020 Jul 31. doi: 10.1136/annrheumdis-2020-217892.

Key clinical point: Treatment with abaloparatide is associated with a transient increase in heart rate (HR) and a small decrease in post-dose blood pressure (BP) in postmenopausal women with osteoporosis.

Major finding: Abaloparatide showed a significantly higher mean HR change from pretreatment to 1 hour posttreatment on day 1 vs. placebo (mean [standard deviation]: 7.9 [8.5] vs. 1.2 [7.1] beats per minute; P less than .0001). Abaloparatide showed a significantly higher change in systolic and diastolic blood pressure from pre-dose to 1 hour post-dose vs. placebo (−2.7/−3.6 vs. −1.5/−2.3 mmHg; P less than .05). These changes were not associated with an increased risk of serious cardiac adverse events, major adverse cardiovascular events, and heart failure.

Study details: The findings are based on a post-hoc analysis from the ACTIVE and ACTIVExtend trials including 2,460 postmenopausal women with osteoporosis.

Disclosures: Dr. Felicia Cosman, Dr. Steven R Cummings, Dr. Linda R Peterson, and Dr. Dwight A Towler consulted for/received research grants from pharmaceutical companies/research institutes including Amgen; Radius Health, Inc.; and the National Institutes of Health. Dr. Bruce Mitlak and Dr. Yamei Wang are employees of and hold equity in Radius Health, Inc.

Source: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Key clinical point: Treatment with abaloparatide is associated with a transient increase in heart rate (HR) and a small decrease in post-dose blood pressure (BP) in postmenopausal women with osteoporosis.

Major finding: Abaloparatide showed a significantly higher mean HR change from pretreatment to 1 hour posttreatment on day 1 vs. placebo (mean [standard deviation]: 7.9 [8.5] vs. 1.2 [7.1] beats per minute; P less than .0001). Abaloparatide showed a significantly higher change in systolic and diastolic blood pressure from pre-dose to 1 hour post-dose vs. placebo (−2.7/−3.6 vs. −1.5/−2.3 mmHg; P less than .05). These changes were not associated with an increased risk of serious cardiac adverse events, major adverse cardiovascular events, and heart failure.

Study details: The findings are based on a post-hoc analysis from the ACTIVE and ACTIVExtend trials including 2,460 postmenopausal women with osteoporosis.

Disclosures: Dr. Felicia Cosman, Dr. Steven R Cummings, Dr. Linda R Peterson, and Dr. Dwight A Towler consulted for/received research grants from pharmaceutical companies/research institutes including Amgen; Radius Health, Inc.; and the National Institutes of Health. Dr. Bruce Mitlak and Dr. Yamei Wang are employees of and hold equity in Radius Health, Inc.

Source: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Key clinical point: Treatment with abaloparatide is associated with a transient increase in heart rate (HR) and a small decrease in post-dose blood pressure (BP) in postmenopausal women with osteoporosis.

Major finding: Abaloparatide showed a significantly higher mean HR change from pretreatment to 1 hour posttreatment on day 1 vs. placebo (mean [standard deviation]: 7.9 [8.5] vs. 1.2 [7.1] beats per minute; P less than .0001). Abaloparatide showed a significantly higher change in systolic and diastolic blood pressure from pre-dose to 1 hour post-dose vs. placebo (−2.7/−3.6 vs. −1.5/−2.3 mmHg; P less than .05). These changes were not associated with an increased risk of serious cardiac adverse events, major adverse cardiovascular events, and heart failure.

Study details: The findings are based on a post-hoc analysis from the ACTIVE and ACTIVExtend trials including 2,460 postmenopausal women with osteoporosis.

Disclosures: Dr. Felicia Cosman, Dr. Steven R Cummings, Dr. Linda R Peterson, and Dr. Dwight A Towler consulted for/received research grants from pharmaceutical companies/research institutes including Amgen; Radius Health, Inc.; and the National Institutes of Health. Dr. Bruce Mitlak and Dr. Yamei Wang are employees of and hold equity in Radius Health, Inc.

Source: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Key clinical point: Women with a previous fracture or who had an inflammatory rheumatic disease were more likely to start antiosteoporotic drugs (AODs) within 1 year from glucocorticoid (GC) initiation. However, the proportions starting an AOD were much lower than clinically indicated.

Major finding: Women with vs. without previous fracture were twice as likely to start an AOD within 1 year after initiating GC treatment, but the cumulative incidences were low: 9.1% vs. 4.6%, respectively. Women with a diagnosis of rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start an AOD compared with women with other diagnoses.

Study details: This Norwegian population-based study evaluated the initiation of osteoporosis prophylaxis with AOD in women starting treatment with oral GC (n=105,477; age, 55 years or older).

Disclosures: Open Access funding was provided by the University of Bergen. Astrid Lunde is involved in the Denosumab Global Safety Study. Department of Clinical Epidemiology, Aarhus University receives an institutional research funding from several pharmaceutical companies, some of which manufacture AOD. None of these companies was involved in the current study. Vera Ehrenstein is a salaried employee of the Aarhus University. Ellen M Apalset, Mari Hoff, and Grethe S Tell declared no conflicts of interest.

Source: Apalset EM et al. Arch Osteoporos. 2020 Aug 5. doi: 10.1007/s11657-020-00783-8.

Key clinical point: Women with a previous fracture or who had an inflammatory rheumatic disease were more likely to start antiosteoporotic drugs (AODs) within 1 year from glucocorticoid (GC) initiation. However, the proportions starting an AOD were much lower than clinically indicated.

Major finding: Women with vs. without previous fracture were twice as likely to start an AOD within 1 year after initiating GC treatment, but the cumulative incidences were low: 9.1% vs. 4.6%, respectively. Women with a diagnosis of rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start an AOD compared with women with other diagnoses.

Study details: This Norwegian population-based study evaluated the initiation of osteoporosis prophylaxis with AOD in women starting treatment with oral GC (n=105,477; age, 55 years or older).

Disclosures: Open Access funding was provided by the University of Bergen. Astrid Lunde is involved in the Denosumab Global Safety Study. Department of Clinical Epidemiology, Aarhus University receives an institutional research funding from several pharmaceutical companies, some of which manufacture AOD. None of these companies was involved in the current study. Vera Ehrenstein is a salaried employee of the Aarhus University. Ellen M Apalset, Mari Hoff, and Grethe S Tell declared no conflicts of interest.

Source: Apalset EM et al. Arch Osteoporos. 2020 Aug 5. doi: 10.1007/s11657-020-00783-8.

Key clinical point: Women with a previous fracture or who had an inflammatory rheumatic disease were more likely to start antiosteoporotic drugs (AODs) within 1 year from glucocorticoid (GC) initiation. However, the proportions starting an AOD were much lower than clinically indicated.

Major finding: Women with vs. without previous fracture were twice as likely to start an AOD within 1 year after initiating GC treatment, but the cumulative incidences were low: 9.1% vs. 4.6%, respectively. Women with a diagnosis of rheumatoid arthritis or another inflammatory rheumatic disease were more likely to start an AOD compared with women with other diagnoses.

Study details: This Norwegian population-based study evaluated the initiation of osteoporosis prophylaxis with AOD in women starting treatment with oral GC (n=105,477; age, 55 years or older).

Disclosures: Open Access funding was provided by the University of Bergen. Astrid Lunde is involved in the Denosumab Global Safety Study. Department of Clinical Epidemiology, Aarhus University receives an institutional research funding from several pharmaceutical companies, some of which manufacture AOD. None of these companies was involved in the current study. Vera Ehrenstein is a salaried employee of the Aarhus University. Ellen M Apalset, Mari Hoff, and Grethe S Tell declared no conflicts of interest.

Source: Apalset EM et al. Arch Osteoporos. 2020 Aug 5. doi: 10.1007/s11657-020-00783-8.

Key clinical point: Delaying denosumab doses by more than 16 weeks is associated with an increased risk of vertebral fracture in patients with osteoporosis vs. on-time injections. However, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with a long delay.

Major finding: Compared with on-time injections (within 4 weeks after the recommended date), short delay (by 4-16 weeks) had a hazard ratio (HR) of 1.03 and long delay (by more than 16 weeks) an HR of 1.44 (P for trend = .093) for composite fracture. For vertebral fractures, short delay had an HR of 1.48 and long delay an HR of 3.91 (P for trend = .005).

Study details: This U.K. population-based cohort study included 2,594 patients (age, 45 years or older) who initiated denosumab therapy for osteoporosis.

Disclosures: The study was supported by a grant from the National Institutes of Health and by the internal resources from the National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation (Beijing) and Xiangya Hospital, Central South University. The authors declared no conflicts of interest in relation to the subject of the study. Three of the authors reported receiving grants from 1 or more pharma companies, outside the submitted work.

Source: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.

Key clinical point: Delaying denosumab doses by more than 16 weeks is associated with an increased risk of vertebral fracture in patients with osteoporosis vs. on-time injections. However, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with a long delay.

Major finding: Compared with on-time injections (within 4 weeks after the recommended date), short delay (by 4-16 weeks) had a hazard ratio (HR) of 1.03 and long delay (by more than 16 weeks) an HR of 1.44 (P for trend = .093) for composite fracture. For vertebral fractures, short delay had an HR of 1.48 and long delay an HR of 3.91 (P for trend = .005).

Study details: This U.K. population-based cohort study included 2,594 patients (age, 45 years or older) who initiated denosumab therapy for osteoporosis.

Disclosures: The study was supported by a grant from the National Institutes of Health and by the internal resources from the National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation (Beijing) and Xiangya Hospital, Central South University. The authors declared no conflicts of interest in relation to the subject of the study. Three of the authors reported receiving grants from 1 or more pharma companies, outside the submitted work.

Source: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.

Key clinical point: Delaying denosumab doses by more than 16 weeks is associated with an increased risk of vertebral fracture in patients with osteoporosis vs. on-time injections. However, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with a long delay.

Major finding: Compared with on-time injections (within 4 weeks after the recommended date), short delay (by 4-16 weeks) had a hazard ratio (HR) of 1.03 and long delay (by more than 16 weeks) an HR of 1.44 (P for trend = .093) for composite fracture. For vertebral fractures, short delay had an HR of 1.48 and long delay an HR of 3.91 (P for trend = .005).

Study details: This U.K. population-based cohort study included 2,594 patients (age, 45 years or older) who initiated denosumab therapy for osteoporosis.

Disclosures: The study was supported by a grant from the National Institutes of Health and by the internal resources from the National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation (Beijing) and Xiangya Hospital, Central South University. The authors declared no conflicts of interest in relation to the subject of the study. Three of the authors reported receiving grants from 1 or more pharma companies, outside the submitted work.

Source: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.