Osteoporosis

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Abaloparatide/alendronate treatment shows numerically lower risks for wrist fractures compared with placebo/alendronate, suggesting a potential correlation between ultradistal (UD) radius bone mineral density (BMD) and wrist fracture.

Major finding: BMD gains at the UD radius following treatment with abaloparatide in ACTIVE were maintained over the subsequent 24 months of treatment with alendronate in ACTIVExtend (cumulative month 43 treatment difference, 0.89%; P = .20). Conversely, UD radius BMD in the placebo group during ACTIVE decreased to below ACTIVE baseline.

Study details: The data come from a subanalysis of the phase 3 ACTIVExtend trial.

Disclosures: Funding for this study was provided by Radius Health, Inc. NB Watts, RK Dore, and MS LeBoff reported ties with various pharmaceutical companies. B Mitlak and Y Wang were employees of and own company stock in Radius Health, Inc. G Hattersley was a former employee of and a consultant to Radius Health, Inc. TD Rozental is the Editor in Chief of the Journal of Hand Surgery Global Online. S Baim reported no conflicts of interest.

Citation: Watts NB et al. Osteoporos Int. 2020 Sep 15. doi: 10.1007/s00198-020-05555-1.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Use of high-dose inhaled corticosteroids (ICS) significantly increased the risk of osteoporosis and fracture in patients with chronic obstructive pulmonary disease (COPD).

Major finding: Patients with COPD using ICS were at an increased risk for any osteoporosis-related event (high dose: risk ratio [RR], 1.52; 95% confidence interval [CI], 1.24-1.82] and low dose: RR, 1.27; 95% CI, 1.13-1.56) compared with those not using ICS.

Study details: The data come from ARCTIC study of 9,651 patients with COPD and 59,454 matched reference controls.

Disclosures: This study was funded by Novartis Pharma AG, Basel, Switzerland. C Janson, K Lisspers, B Ställberg, G Johansson, and K Larsson reported relationships with various pharmaceutical companies, including Novartis. FS Gutzwiller and K Mezzi are employees of Novartis. L Mindeholm is a consultant to Novartis Institutes for Biomedical Research and holds stocks in Novartis. BK Bjerregaard and L Jorgensen are employees of IQVIA and have received remuneration in relation to statistical analyses.

Citation: Janson C et al. Eur Respir J. 2020 Sep 24. doi: 10.1183/13993003.00515-2020.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: Minodronate demonstrated better efficacy than alendronate, risedronate, raloxifene, or eldecalcitol in patients with osteoporosis.

Major finding: Compared with other drugs, minodronate significantly decreased N-telopeptide of type I collagen/creatinine (weighted mean difference [WMD], −13.669; 95% confidence interval [CI], −23.108 to −4.229), bone alkaline phosphatase (WMD, −1.26; 95% CI: −2.04 to −0.47), and tartrate-resistant acid phosphatase 5b (WMD, −154.11; 95% CI, −277.85 to −30.37).

Study details: A meta-analysis of 13 randomized controlled trials including 3,740 patients with osteoporosis.

Disclosures: This study received no financial support. The authors declared no conflicts of interest.

Citation: Liu Q et al. 2020 Oct 2. doi: 10.1097/MD.0000000000022542.

Key clinical point: The risk for moderate coronary artery calcification (CAC) is inversely and independently associated with bone mineral density (BMD) of the lumbar spine in adults with osteoporosis.

Major finding: After adjustments for significant factors of CAC, BMD of the lumbar spine was significantly and inversely associated with moderate CAC in patients with osteoporosis (odds ratio, 0.38; P = .035). However, no association between CAC and BMD was seen in patients with osteopenia.

Study details: The findings are based on a retrospective medical review study of 246 patients (osteoporosis group, n = 52; osteopenia group, n = 194).

Disclosures: The study was funded by Buddhist Tzu Chi Medical Foundation. The authors declared no conflicts of interest.

Citation: Chuang TL et al. Diagnostics (Basel). 2020 Sep 16. doi: 10.3390/diagnostics10090699.

Key clinical point: The risk for moderate coronary artery calcification (CAC) is inversely and independently associated with bone mineral density (BMD) of the lumbar spine in adults with osteoporosis.

Major finding: After adjustments for significant factors of CAC, BMD of the lumbar spine was significantly and inversely associated with moderate CAC in patients with osteoporosis (odds ratio, 0.38; P = .035). However, no association between CAC and BMD was seen in patients with osteopenia.

Study details: The findings are based on a retrospective medical review study of 246 patients (osteoporosis group, n = 52; osteopenia group, n = 194).

Disclosures: The study was funded by Buddhist Tzu Chi Medical Foundation. The authors declared no conflicts of interest.

Citation: Chuang TL et al. Diagnostics (Basel). 2020 Sep 16. doi: 10.3390/diagnostics10090699.

Key clinical point: The risk for moderate coronary artery calcification (CAC) is inversely and independently associated with bone mineral density (BMD) of the lumbar spine in adults with osteoporosis.

Major finding: After adjustments for significant factors of CAC, BMD of the lumbar spine was significantly and inversely associated with moderate CAC in patients with osteoporosis (odds ratio, 0.38; P = .035). However, no association between CAC and BMD was seen in patients with osteopenia.

Study details: The findings are based on a retrospective medical review study of 246 patients (osteoporosis group, n = 52; osteopenia group, n = 194).

Disclosures: The study was funded by Buddhist Tzu Chi Medical Foundation. The authors declared no conflicts of interest.

Citation: Chuang TL et al. Diagnostics (Basel). 2020 Sep 16. doi: 10.3390/diagnostics10090699.

Key clinical point: Metabolic syndrome (MetS) is associated with an increased risk for low bone mineral density (BMD) in women examined by dual-energy X-ray absorptiometry (DXA) for suspected osteoporosis.

Major finding: MetS was associated with an increased risk for low BMD (odds ratio [OR], 1.19; P = .001). Among MetS components, hypertension significantly correlated with an increased risk for low BMD (OR, 1.23; P = .002), whereas high fasting glucose level/diabetes correlated with a reduced occurrence of low BMD (OR, 0.84; P = .003).

Study details: The data come from a cross-sectional study of 13,182 free-living Caucasian women in Italy (mean age, 62.8 years) who underwent diagnostic assessment of BMD by DXA and of all MetS constitutive elements.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Citation: Rendina D et al. J Endocrinol Invest. 2020 Sep 22. doi: 10.1007/s40618-020-01428-w.

Key clinical point: Metabolic syndrome (MetS) is associated with an increased risk for low bone mineral density (BMD) in women examined by dual-energy X-ray absorptiometry (DXA) for suspected osteoporosis.

Major finding: MetS was associated with an increased risk for low BMD (odds ratio [OR], 1.19; P = .001). Among MetS components, hypertension significantly correlated with an increased risk for low BMD (OR, 1.23; P = .002), whereas high fasting glucose level/diabetes correlated with a reduced occurrence of low BMD (OR, 0.84; P = .003).

Study details: The data come from a cross-sectional study of 13,182 free-living Caucasian women in Italy (mean age, 62.8 years) who underwent diagnostic assessment of BMD by DXA and of all MetS constitutive elements.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Citation: Rendina D et al. J Endocrinol Invest. 2020 Sep 22. doi: 10.1007/s40618-020-01428-w.

Key clinical point: Metabolic syndrome (MetS) is associated with an increased risk for low bone mineral density (BMD) in women examined by dual-energy X-ray absorptiometry (DXA) for suspected osteoporosis.

Major finding: MetS was associated with an increased risk for low BMD (odds ratio [OR], 1.19; P = .001). Among MetS components, hypertension significantly correlated with an increased risk for low BMD (OR, 1.23; P = .002), whereas high fasting glucose level/diabetes correlated with a reduced occurrence of low BMD (OR, 0.84; P = .003).

Study details: The data come from a cross-sectional study of 13,182 free-living Caucasian women in Italy (mean age, 62.8 years) who underwent diagnostic assessment of BMD by DXA and of all MetS constitutive elements.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Citation: Rendina D et al. J Endocrinol Invest. 2020 Sep 22. doi: 10.1007/s40618-020-01428-w.

Key clinical point: Higher serum vitamin K1 (phylloquinone) concentration is associated with a reduced risk for fracture in women with postmenopausal osteoporosis (PMO).

Major finding: Serum vitamin K1 was significantly lower in women with prevalent fractures vs. those without (0.53 μg/L vs. 0.65 μg/L; P = .04). Vitamin K1 inversely correlated with fracture risk (adjusted odds ratio per μg/L increase in serum vitamin K1, 0.550; P = .042). Hip geometry and mechanical strength parameters including cross-sectional area, cross-sectional moment of inertia, and section modulus ‘Z’ at the narrow neck of femur were positively associated with vitamin K1.

Study details: The data come from a cross-sectional study of 374 women with PMO (mean age, 68.7 years).

Disclosures: The study was funded, in part, by the Royal Osteoporosis Society, U.K. The authors declared no conflicts of interest.

Citation: Moore AE et al. Bone. 2020 Sep 10. doi: 10.1016/j.bone.2020.115630.

Key clinical point: Higher serum vitamin K1 (phylloquinone) concentration is associated with a reduced risk for fracture in women with postmenopausal osteoporosis (PMO).

Major finding: Serum vitamin K1 was significantly lower in women with prevalent fractures vs. those without (0.53 μg/L vs. 0.65 μg/L; P = .04). Vitamin K1 inversely correlated with fracture risk (adjusted odds ratio per μg/L increase in serum vitamin K1, 0.550; P = .042). Hip geometry and mechanical strength parameters including cross-sectional area, cross-sectional moment of inertia, and section modulus ‘Z’ at the narrow neck of femur were positively associated with vitamin K1.

Study details: The data come from a cross-sectional study of 374 women with PMO (mean age, 68.7 years).

Disclosures: The study was funded, in part, by the Royal Osteoporosis Society, U.K. The authors declared no conflicts of interest.

Citation: Moore AE et al. Bone. 2020 Sep 10. doi: 10.1016/j.bone.2020.115630.

Key clinical point: Higher serum vitamin K1 (phylloquinone) concentration is associated with a reduced risk for fracture in women with postmenopausal osteoporosis (PMO).

Major finding: Serum vitamin K1 was significantly lower in women with prevalent fractures vs. those without (0.53 μg/L vs. 0.65 μg/L; P = .04). Vitamin K1 inversely correlated with fracture risk (adjusted odds ratio per μg/L increase in serum vitamin K1, 0.550; P = .042). Hip geometry and mechanical strength parameters including cross-sectional area, cross-sectional moment of inertia, and section modulus ‘Z’ at the narrow neck of femur were positively associated with vitamin K1.

Study details: The data come from a cross-sectional study of 374 women with PMO (mean age, 68.7 years).

Disclosures: The study was funded, in part, by the Royal Osteoporosis Society, U.K. The authors declared no conflicts of interest.

Citation: Moore AE et al. Bone. 2020 Sep 10. doi: 10.1016/j.bone.2020.115630.

Key clinical point: Patients with osteoporosis with age-related macular degeneration (AMD) are at a significantly higher risk of developing spine and hip fractures.

Major finding: The AMD vs. non-AMD group had a significantly higher risk for spine and hip fractures (hazard ratio [HR], 1.09; P less than .001 and HR, 1.18; P = .001; respectively). The risk for mortality was significantly higher in patients with osteoporosis with older age, male sex, and all types of comorbidities (P less than .05), except for hyperthyroidism (P = .200).

Study details: This Taiwanese nationwide study included 1,206,247 patients with osteoporosis using insurance claims data. After propensity score matching, 13,548 and 54,336 patients were analyzed in the AMD and non-AMD groups, respectively.

Disclosures: The study was supported by Chang Gung Medical Research Foundation. The authors declared no conflicts of interest.

Citation: Sun CC et al. BMJ Open. 2020 Sep 17. doi: 10.1136/bmjopen-2020-037028.

Key clinical point: Patients with osteoporosis with age-related macular degeneration (AMD) are at a significantly higher risk of developing spine and hip fractures.

Major finding: The AMD vs. non-AMD group had a significantly higher risk for spine and hip fractures (hazard ratio [HR], 1.09; P less than .001 and HR, 1.18; P = .001; respectively). The risk for mortality was significantly higher in patients with osteoporosis with older age, male sex, and all types of comorbidities (P less than .05), except for hyperthyroidism (P = .200).

Study details: This Taiwanese nationwide study included 1,206,247 patients with osteoporosis using insurance claims data. After propensity score matching, 13,548 and 54,336 patients were analyzed in the AMD and non-AMD groups, respectively.

Disclosures: The study was supported by Chang Gung Medical Research Foundation. The authors declared no conflicts of interest.

Citation: Sun CC et al. BMJ Open. 2020 Sep 17. doi: 10.1136/bmjopen-2020-037028.

Key clinical point: Patients with osteoporosis with age-related macular degeneration (AMD) are at a significantly higher risk of developing spine and hip fractures.

Major finding: The AMD vs. non-AMD group had a significantly higher risk for spine and hip fractures (hazard ratio [HR], 1.09; P less than .001 and HR, 1.18; P = .001; respectively). The risk for mortality was significantly higher in patients with osteoporosis with older age, male sex, and all types of comorbidities (P less than .05), except for hyperthyroidism (P = .200).

Study details: This Taiwanese nationwide study included 1,206,247 patients with osteoporosis using insurance claims data. After propensity score matching, 13,548 and 54,336 patients were analyzed in the AMD and non-AMD groups, respectively.

Disclosures: The study was supported by Chang Gung Medical Research Foundation. The authors declared no conflicts of interest.

Citation: Sun CC et al. BMJ Open. 2020 Sep 17. doi: 10.1136/bmjopen-2020-037028.

Denosumab boosted bone mineral density (BMD) over 12 months to a greater extent than did alendronate in a randomized, 12-month study. The investigator-initiated research compared BMD at the lumbar spine and elsewhere among people with systemic lupus erythematosus (SLE) and other autoimmune conditions. Long-term glucocorticoid therapy places some people in this group at higher risk for adverse effects of bone density loss.

“Glucocorticoids remain the mainstay of treatment of rheumatic diseases, but [they are] a major risk factor for osteoporosis and fracture,” study author Chi Chiu Mok, MD, said in an interview.

Compared with baseline, adults randomly assigned to denosumab had a 3.5% increase in lumbar spine BMD at 12 months, compared with 2.5% among those taking alendronate, a significant difference. Dr. Mok, a consultant and honorary associate professor in the department of medicine and nuclear medicine at Tuen Mun Hospital in Hong Kong, presented the study results at the virtual annual meeting of the American College of Rheumatology.

“Given the knowledge that denosumab is more effective than alendronate in raising spinal BMD in chronic users of GCs without increasing adverse events, this drug may be considered as an alternative first-line therapy in higher-risk patients and in those who are contraindicated for the oral bisphosphonates,” he said.
 

Cost considerations

Denosumab is a human monoclonal antibody administered as a subcutaneous injection, available under the brand names Prolia and Xgeva. Alendronate is an oral agent available as both generic and brand name formulations.

“Yes, denosumab is more expensive, more costly than oral alendronate, but our study shows efficacy is better for steroid users,” Dr. Mok said in answer to a question about cost disparity between the two agents during his presentation at the meeting. “For patients who are contraindicated or have low compliance for bisphosphonate, or are high-risk patients, I recommend first-line use of denosumab.”

Researchers previously studied these agents, including a smaller study by Dr. Mok and colleagues that showed a BMD benefit after switching people on an oral bisphosphonate to denosumab. However, he said, “There is a paucity of data regarding comparative efficacy of denosumab and the bisphosphonates in long-term steroid users.”

To explore any differences in a larger patient population, the investigators randomly assigned adults with SLE and other autoimmune conditions to the two treatments: denosumab 60 mg subcutaneoulsy every 6 months or oral alendronate 70 mg/week. All patients also received 3,000 mg calcium and 1,000 IU vitamin D₃ (cholecalciferol) each day.

After three discontinuations in denosumab cohort and four in the alendronate group, the researchers evaluated 69 people taking denosumab and 70 others taking alendronate. The discontinuations were caused by noncompliance, Dr. Mok said, not by adverse events.

Adverse events were reported, but the rate did not differ significantly between groups. Dr. Mok highlighted some notable differences, including more minor infections and arthralgias reported in the denosumab cohort. Chest discomfort was reported in one denosumab recipient versus no patients in the alendronate group. Dyspepsia/upper GI symptoms and dizziness/vertigo occurred more often in the alendronate group.

Women were 96% of the study population, and mean age was 50 years. A majority, 81%, had underlying SLE. Other diagnoses included rheumatoid arthritis, myositis, antineutrophil cytoplasmic antibody–associated vasculitis, and polymyalgia rheumatica. The mean dose of prednisolone at study entry was 5.1 mg/day.
 

Key BMD and biomarker findings

BMD increased significantly in the spine, hip, and femoral neck in both treatment groups by 12 months. However, after adjustment for baseline BMD and covariates including age, menopause, and history of fracture, the gains in the denosumab group were significantly higher.

The increase in lumbar spine BMD at 12 months of 3.5% in the denosumab group versus 2.5% in the alendronate group was statistically significant (P = .045). Less significant was a 0.9% increase at the hip in the denosumab patients versus 1.6% in the alendronate group (P = .10), as well as femoral neck BMD gains of 1% in the denosumab group versus 1.5% in the alendronate group (P = .86).

Furthermore, “denosumab was more potent in suppressing the bone markers at 12 months,” Dr. Mok said.

Specifically, the percentage decrease in serum PINP (procollagen type I N-terminal propeptide) levels in the denosumab group was significantly greater than in the alendronate group (P = .001). Likewise, the decrease in CTX (C-terminal telopeptide of type I collagen) was significantly greater in the denosumab cohort versus the alendronate cohort (P < .001).

“Dr. Mok’s study was a well-controlled investigation. The superiority of denosumab was impressive, especially given the small group sizes of 69 and 70,” session comoderator Gregg Silverman, MD, professor in the department of internal medicine and the department of pathology at New York University, said when asked for comment.

“However, bone density measurements may not tell the whole story. These results support a bigger and much larger-scale study to confirm that rates of fracture on denosumab are also reduced.”

No new symptomatic fractures occurred in either group during the study. The investigators are evaluating for any new radiologic fractures, with results pending.

Dr. Mok said “results of our study in Asian patients are largely confirmatory” of a previous 2018 comparison study and a 2019 comparison study, each sponsored by Amgen.

A small sample size, short duration of treatment, and the open-label design were limitations of the study.

The trial was an investigator-initiated study. Dr. Mok and colleagues had no relevant financial disclosures. Dr. Silverman had no relevant financial disclosures.

SOURCE: Mok CC et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract 1442.

Denosumab boosted bone mineral density (BMD) over 12 months to a greater extent than did alendronate in a randomized, 12-month study. The investigator-initiated research compared BMD at the lumbar spine and elsewhere among people with systemic lupus erythematosus (SLE) and other autoimmune conditions. Long-term glucocorticoid therapy places some people in this group at higher risk for adverse effects of bone density loss.

“Glucocorticoids remain the mainstay of treatment of rheumatic diseases, but [they are] a major risk factor for osteoporosis and fracture,” study author Chi Chiu Mok, MD, said in an interview.

Compared with baseline, adults randomly assigned to denosumab had a 3.5% increase in lumbar spine BMD at 12 months, compared with 2.5% among those taking alendronate, a significant difference. Dr. Mok, a consultant and honorary associate professor in the department of medicine and nuclear medicine at Tuen Mun Hospital in Hong Kong, presented the study results at the virtual annual meeting of the American College of Rheumatology.

“Given the knowledge that denosumab is more effective than alendronate in raising spinal BMD in chronic users of GCs without increasing adverse events, this drug may be considered as an alternative first-line therapy in higher-risk patients and in those who are contraindicated for the oral bisphosphonates,” he said.
 

Cost considerations

Denosumab is a human monoclonal antibody administered as a subcutaneous injection, available under the brand names Prolia and Xgeva. Alendronate is an oral agent available as both generic and brand name formulations.

“Yes, denosumab is more expensive, more costly than oral alendronate, but our study shows efficacy is better for steroid users,” Dr. Mok said in answer to a question about cost disparity between the two agents during his presentation at the meeting. “For patients who are contraindicated or have low compliance for bisphosphonate, or are high-risk patients, I recommend first-line use of denosumab.”

Researchers previously studied these agents, including a smaller study by Dr. Mok and colleagues that showed a BMD benefit after switching people on an oral bisphosphonate to denosumab. However, he said, “There is a paucity of data regarding comparative efficacy of denosumab and the bisphosphonates in long-term steroid users.”

To explore any differences in a larger patient population, the investigators randomly assigned adults with SLE and other autoimmune conditions to the two treatments: denosumab 60 mg subcutaneoulsy every 6 months or oral alendronate 70 mg/week. All patients also received 3,000 mg calcium and 1,000 IU vitamin D₃ (cholecalciferol) each day.

After three discontinuations in denosumab cohort and four in the alendronate group, the researchers evaluated 69 people taking denosumab and 70 others taking alendronate. The discontinuations were caused by noncompliance, Dr. Mok said, not by adverse events.

Adverse events were reported, but the rate did not differ significantly between groups. Dr. Mok highlighted some notable differences, including more minor infections and arthralgias reported in the denosumab cohort. Chest discomfort was reported in one denosumab recipient versus no patients in the alendronate group. Dyspepsia/upper GI symptoms and dizziness/vertigo occurred more often in the alendronate group.

Women were 96% of the study population, and mean age was 50 years. A majority, 81%, had underlying SLE. Other diagnoses included rheumatoid arthritis, myositis, antineutrophil cytoplasmic antibody–associated vasculitis, and polymyalgia rheumatica. The mean dose of prednisolone at study entry was 5.1 mg/day.
 

Key BMD and biomarker findings

BMD increased significantly in the spine, hip, and femoral neck in both treatment groups by 12 months. However, after adjustment for baseline BMD and covariates including age, menopause, and history of fracture, the gains in the denosumab group were significantly higher.

The increase in lumbar spine BMD at 12 months of 3.5% in the denosumab group versus 2.5% in the alendronate group was statistically significant (P = .045). Less significant was a 0.9% increase at the hip in the denosumab patients versus 1.6% in the alendronate group (P = .10), as well as femoral neck BMD gains of 1% in the denosumab group versus 1.5% in the alendronate group (P = .86).

Furthermore, “denosumab was more potent in suppressing the bone markers at 12 months,” Dr. Mok said.

Specifically, the percentage decrease in serum PINP (procollagen type I N-terminal propeptide) levels in the denosumab group was significantly greater than in the alendronate group (P = .001). Likewise, the decrease in CTX (C-terminal telopeptide of type I collagen) was significantly greater in the denosumab cohort versus the alendronate cohort (P < .001).

“Dr. Mok’s study was a well-controlled investigation. The superiority of denosumab was impressive, especially given the small group sizes of 69 and 70,” session comoderator Gregg Silverman, MD, professor in the department of internal medicine and the department of pathology at New York University, said when asked for comment.

“However, bone density measurements may not tell the whole story. These results support a bigger and much larger-scale study to confirm that rates of fracture on denosumab are also reduced.”

No new symptomatic fractures occurred in either group during the study. The investigators are evaluating for any new radiologic fractures, with results pending.

Dr. Mok said “results of our study in Asian patients are largely confirmatory” of a previous 2018 comparison study and a 2019 comparison study, each sponsored by Amgen.

A small sample size, short duration of treatment, and the open-label design were limitations of the study.

The trial was an investigator-initiated study. Dr. Mok and colleagues had no relevant financial disclosures. Dr. Silverman had no relevant financial disclosures.

SOURCE: Mok CC et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract 1442.

Denosumab boosted bone mineral density (BMD) over 12 months to a greater extent than did alendronate in a randomized, 12-month study. The investigator-initiated research compared BMD at the lumbar spine and elsewhere among people with systemic lupus erythematosus (SLE) and other autoimmune conditions. Long-term glucocorticoid therapy places some people in this group at higher risk for adverse effects of bone density loss.

“Glucocorticoids remain the mainstay of treatment of rheumatic diseases, but [they are] a major risk factor for osteoporosis and fracture,” study author Chi Chiu Mok, MD, said in an interview.

Compared with baseline, adults randomly assigned to denosumab had a 3.5% increase in lumbar spine BMD at 12 months, compared with 2.5% among those taking alendronate, a significant difference. Dr. Mok, a consultant and honorary associate professor in the department of medicine and nuclear medicine at Tuen Mun Hospital in Hong Kong, presented the study results at the virtual annual meeting of the American College of Rheumatology.

“Given the knowledge that denosumab is more effective than alendronate in raising spinal BMD in chronic users of GCs without increasing adverse events, this drug may be considered as an alternative first-line therapy in higher-risk patients and in those who are contraindicated for the oral bisphosphonates,” he said.
 

Cost considerations

Denosumab is a human monoclonal antibody administered as a subcutaneous injection, available under the brand names Prolia and Xgeva. Alendronate is an oral agent available as both generic and brand name formulations.

“Yes, denosumab is more expensive, more costly than oral alendronate, but our study shows efficacy is better for steroid users,” Dr. Mok said in answer to a question about cost disparity between the two agents during his presentation at the meeting. “For patients who are contraindicated or have low compliance for bisphosphonate, or are high-risk patients, I recommend first-line use of denosumab.”

Researchers previously studied these agents, including a smaller study by Dr. Mok and colleagues that showed a BMD benefit after switching people on an oral bisphosphonate to denosumab. However, he said, “There is a paucity of data regarding comparative efficacy of denosumab and the bisphosphonates in long-term steroid users.”

To explore any differences in a larger patient population, the investigators randomly assigned adults with SLE and other autoimmune conditions to the two treatments: denosumab 60 mg subcutaneoulsy every 6 months or oral alendronate 70 mg/week. All patients also received 3,000 mg calcium and 1,000 IU vitamin D₃ (cholecalciferol) each day.

After three discontinuations in denosumab cohort and four in the alendronate group, the researchers evaluated 69 people taking denosumab and 70 others taking alendronate. The discontinuations were caused by noncompliance, Dr. Mok said, not by adverse events.

Adverse events were reported, but the rate did not differ significantly between groups. Dr. Mok highlighted some notable differences, including more minor infections and arthralgias reported in the denosumab cohort. Chest discomfort was reported in one denosumab recipient versus no patients in the alendronate group. Dyspepsia/upper GI symptoms and dizziness/vertigo occurred more often in the alendronate group.

Women were 96% of the study population, and mean age was 50 years. A majority, 81%, had underlying SLE. Other diagnoses included rheumatoid arthritis, myositis, antineutrophil cytoplasmic antibody–associated vasculitis, and polymyalgia rheumatica. The mean dose of prednisolone at study entry was 5.1 mg/day.
 

Key BMD and biomarker findings

BMD increased significantly in the spine, hip, and femoral neck in both treatment groups by 12 months. However, after adjustment for baseline BMD and covariates including age, menopause, and history of fracture, the gains in the denosumab group were significantly higher.

The increase in lumbar spine BMD at 12 months of 3.5% in the denosumab group versus 2.5% in the alendronate group was statistically significant (P = .045). Less significant was a 0.9% increase at the hip in the denosumab patients versus 1.6% in the alendronate group (P = .10), as well as femoral neck BMD gains of 1% in the denosumab group versus 1.5% in the alendronate group (P = .86).

Furthermore, “denosumab was more potent in suppressing the bone markers at 12 months,” Dr. Mok said.

Specifically, the percentage decrease in serum PINP (procollagen type I N-terminal propeptide) levels in the denosumab group was significantly greater than in the alendronate group (P = .001). Likewise, the decrease in CTX (C-terminal telopeptide of type I collagen) was significantly greater in the denosumab cohort versus the alendronate cohort (P < .001).

“Dr. Mok’s study was a well-controlled investigation. The superiority of denosumab was impressive, especially given the small group sizes of 69 and 70,” session comoderator Gregg Silverman, MD, professor in the department of internal medicine and the department of pathology at New York University, said when asked for comment.

“However, bone density measurements may not tell the whole story. These results support a bigger and much larger-scale study to confirm that rates of fracture on denosumab are also reduced.”

No new symptomatic fractures occurred in either group during the study. The investigators are evaluating for any new radiologic fractures, with results pending.

Dr. Mok said “results of our study in Asian patients are largely confirmatory” of a previous 2018 comparison study and a 2019 comparison study, each sponsored by Amgen.

A small sample size, short duration of treatment, and the open-label design were limitations of the study.

The trial was an investigator-initiated study. Dr. Mok and colleagues had no relevant financial disclosures. Dr. Silverman had no relevant financial disclosures.

SOURCE: Mok CC et al. Arthritis Rheumatol. 2020;72(suppl 10). ACR 2020, Abstract 1442.

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Osteoporosis is frequently underdiagnosed and undertreated in men before and even after they have experienced a fracture, according to research presented at the virtual annual meeting of the American College of Rheumatology.

“This is an important public health concern,” as fractures contribute significantly to morbidity and mortality, said Jeffrey Curtis, MD, MS, MPH, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham.

Men are often overlooked, he said, “because it’s misconstrued as a disease that mainly, if not only, affects Caucasian women,” despite the fact that 20%-25% of fractures occur in men.

Emerging evidence suggests that men who have bone fractures have worse outcomes than women, Dr. Curtis said.
 

Guidelines lacking

Consistent guidelines for osteoporosis screening among men are also lacking, leading to ambiguity and increased disease burden.

Researchers studied records for a 5% random sample of male Medicare fee-for-service beneficiaries (n = 9,876) aged at least 65 years with a closed fragility fracture between January 2010 and September 2014. Average age for the men with fractures was 77.9 years, and the most common sites of the fracture were the spine, hip, and ankle.

They looked back to see whether these men had been effectively screened and treated.

Very few had.

“We found that 92.8% of them did not have any diagnosis or treatment of osteoporosis at baseline,” Curtis said. On top of that, less than 6% of men had undergone any dual-energy x-ray absorptiometry (DEXA) or bone mineral testing in the 2 years prior to their fracture.

Even men who had high-risk factors for falls, such as those using beta-blockers, mobility impairment, or a history of opioid use, were unlikely to be screened, he said.

Dr. Curtis’s data show there was actually a decline in DEXA scans from 2012 to 2014, and that decline was particularly high in men aged 75 years and older who are more likely to be at risk for fracture.

In addition to underscreening and undertreating before the fracture, Dr. Curtis said, “The treatment patterns after the fracture were not much better.” In the year after the fracture, “only about 10% of these men had BMD [bone mineral density] testing. Only 9% were treated with an osteoporosis medication.”

“Importantly, about 7% of the men in this large cohort went on to have one or more fractures in the next year,” he added.

Reasons for undertreatment

Reasons for the poor rates of diagnosis and treatment may begin with patients not having symptoms. Therefore, they aren’t coming into doctors’ offices asking to be screened. “Even if they break bones, they may not know enough to ask how to prevent the next fracture,” Dr. Curtis said.

There’s a financial obstacle as well, Dr. Curtis explained. “U.S. legislation that provides population screening for Medicare patients really, for men, is quite dissimilar to the near-universal coverage for women. So many clinicians worry they won’t get reimbursed if they order DEXA in men for screening.”

Additionally, postfracture quality-of-care guidelines that are reimbursed as part of the Medicare Access and CHIP Reauthorization Act of 2015 and the Merit-based Incentive Payment System program specifically exclude men, he noted.

Better management of male osteoporosis, including early identification of at-risk individuals is clearly warranted, he said, so they can be screened and put on effective therapy.

Sonali Khandelwal, MD, a rheumatologist with Rush University Medical Center, Chicago, who was not part of the research, agreed.

She said in an interview that part of the problem is that diagnosis and treatment could come from a variety of specialists – endocrinologists, rheumatologists, orthopedists, and primary care physicians – and each may think it falls in another’s realm.

At Rush and some other sites nationally, she said, an alert is registered in electronic medical records flagging any patient who may need bone density screening based on age, medications, or history.

Rush University also has a fracture liaison service under which everyone hospitalized there who may have had a history of a fracture or is admitted with a fracture gets followed up with screening and treatment, “to capture those patients who may not have come through the system otherwise.”

She said guidelines have called for DEXA screening for men at age 70, but she said clinical screening should start younger – as young as 50 – for patients with conditions such as lupus, rheumatoid arthritis, hypogonadism, or those on chronic steroids.

Dr. Khandelwal said that, even when an insurance company doesn›t typically cover bone density screening for men, physicians can often make a case for reimbursement if the patient has a history of falls or fractures.

“In the long run, preventing a fracture is saving so much more money than when you get a fracture and end up in a hospital and have to go to a nursing home,” she said.

Dr. Curtis reported relationships with AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Gilead Sciences, and Sanofi. Dr. Khandelwal reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.

Timing is everything when it comes to the use of the anabolic agent romosozumab (Evenity) for the treatment of advanced osteoporosis, a review of clinical trials suggests.

In four studies with treatment sequences in which romosozumab was administered either before or following the use of an antiresorptive agent, initial treatment with 1 year of romosozumab produced substantial bone mineral density (BMD) gains in the total hip and lumbar spine.

Transition from romosozumab to a potent resorptive agent, either alendronate or denosumab (Prolia) augmented the initial gains, reported Felicia Cosman, MD, professor of clinical medicine at Columbia University, New York.

Romosozumab was the third approved agent in its class, following teriparatide in 2002, and abaloparatide (Tymlos) in 2017, both of which have been shown to produce rapid reductions in fracture risk and large improvements in BMD when they were administered up front, followed by an antiresorptive agent.

“But since romosozumab has a very different mechanism of action compared to both teriparatide and abaloparatide, we didn’t know if treatment sequence would be as important for this agent as it was for teriparatide,” she said during a press briefing prior to her presentation of the data in an oral abstract session at the virtual annual meeting of the American College of Rheumatology.

Two-for-one

Romosozumab is unique in that it both increases bone formation and decreases bone resorption, and has been shown in treatment-naive postmenopausal women with osteoporosis to significantly improve BMD and reduce fracture risk, compared with either placebo or alendronate. Romosozumab has also been studied as sequential therapy in patients treated initially with either alendronate or denosumab.

To see whether treatment sequence could have differential effects on clinical outcomes for patients with osteoporosis, Dr. Cosman and colleagues looked at results from four clinical trials, using levels of bone turnover markers (procollagen type I N-terminal propeptide [PINP] and beta-isomer of the C-terminal telopeptide of type I collagen [beta-CTX]) and BMD gains in the total hip and spine as outcomes.

The two trials of romosozumab in treatment-naive women were the ARCH trial comparing romosozumab with alendronate in a double-blind phase for 1 year, followed by 1 year of open-label alendronate, and the FRAME trial, in which romosozumab was compared with placebo in a 1-year double-blind phase, followed by 1-year of open-label denosumab.

The two trials of romosozumab in women treated initially with antiresorptive agents were the STRUCTURE trial in which patients on oral bisphosphonates for at least 3 years or alendronate 70 mg weekly for 1 year were randomized to receive either romosozumab or teriparatide, and a phase 2 trial (NCT00896532) that included a 24-month romosozumab or placebo treatment phase followed by rerandomization to a 12-month extension phase with denosumab or placebo, followed by a 12-month retreatment phase with romosozumab, followed by a 24-month follow-on phase with zoledronic acid or no intervention.

Total hip BMD gains

In the ARCH trial, total hip BMD increased 6.2% with 1 year of romosozumab, and a cumulative total of 7.1% with the 2-year romosozumab/alendronate sequence. In the FRAME trial, patients gained 6.8% in total hip BMD after 1 year of romosozumab and a total of 8.8% after 2 years of romosozumab followed by denosumab.

In contrast, in the STRUCTURE trial, patients treated for 1 year or longer with alendronate and then with 1 year of romosozumab had a 2.9% BMD gain in the total hip. In the phase 2 trial, 1 year of romosozumab following 1 year of denosumab yielded a 0.9% BMD gain, for a total gain of 3.8% with the denosumab sequence.
 

Lumbar spine BMD gains

In ARCH, lumbar spine BMD increased 13.7% with 1 year of romosozumab, and a total of 15.2% with the 2-year sequence of romosozumab followed by alendronate. Similarly, in FRAME, patients gained 13.3% in BMD after a year of romosozumab, and total of 17.6% by the end of the 2-year romosozumab/denosumab sequence.

In contrast, in STRUCTURE, patients who had previously been on alendronate for at least 1 year had a gain of 9.8% after 1 year of romosozumab, and in the phase 2 study, patients who had been on denosumab for 1 year had an increase in lumbar spine BMD of 5.3% after 1 year on romosozumab, and a total gain of 11.5% at the end of the 2-year sequence.
 

Serum PINP and beta-CTX

Looking at the markers of bone turnover, the investigators saw that, in both ARCH and FRAME, PINP peaked at over 80% of baseline at 1 month, and then continued to steadily decline past 1 year. The beta-CTX nadir was 40%-50% below baseline at 1 year.

At the end of year 2, the PINP nadir was –67% with follow-on alendronate, and –69% with denosumab, and the beta-CTX nadir was –72% and –92%, respectively.

In the two trials where romosozumab was the follow-on therapy, however, the trends were distinctly different. In STRUCTURE, for example, PINP peaked at 141% of baseline at 1 month, and then returned toward baseline, whereas beta-CTX remained largely unchanged.

In the phase 2 trial, PINP peaked at 28% above baseline at 9 months, and then only slightly declined, and beta-CTX peaked at 211% at the end of 1 year of romosozumab.

Best used up front

“This study is important, because it suggests that for the three bone-building drugs that the best effects will really be attained on bone strength if the agents are used as initial therapy in very-high-risk patients. Those are people who have sustained fractures within the preceding 2 years, who had multiple fractures at any point in their adulthood, and who present with very low BMD, particularly if they have any associated clinical risk factors such as family history or other underlying diseases or medications that have detrimental effects on bone,” Dr. Cosman said at the briefing.

Marcy Bolster, MD, from the division of rheumatology, allergy, and immunology at Massachusetts General Hospital, Boston, and associate professor of medicine at Harvard Medical School in Boston, who was not involved in the study, commented that the study provides important information for clinicians who treat patients with osteoporosis.

“We have an increasing number of medications available for use in the treatment of patients with osteoporosis, and as we consider the importance of reducing fracture risk, the duration of therapy, the timing of a bisphosphonate holiday, it is essential that we consider any advantages to the order or sequence of our medications,” she said when asked for comment.

“This study provides evidence supporting the concept of the ‘anabolic window’ in which there is a demonstrated advantage in treating patients with an anabolic agent prior to treatment with an antiresorptive agent, and while gains in bone mineral density were achieved with either order of medication use, the gains were more dramatic with treatment with romosozumab as the first agent,” she added.

Dr. Bolster also noted it will be important to demonstrate reduction in fracture risk as well as gain in BMD.

The study was sponsored by Amgen, Astellas, and UCB. Dr. Cosman disclosed grants/research support from Amgen, and consulting fees and speaker activities for Amgen and Radius Health. Dr. Bolster disclosed relationships with AbbVie, Corbus, Cumberland, Gilead, Johnson & Johnson, and Pfizer.

SOURCE: Cosman F et al. Arthritis Rheumatol. 2020;72(suppl 10), Abstract 1973.