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Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial.
JAMA. 2016 Aug 16; 316(7):722-33.JAMA

Abstract

IMPORTANCE

Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.

OBJECTIVE

To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.

DESIGN, SETTING, AND PARTICIPANTS

The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll.

INTERVENTIONS

Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months.

MAIN OUTCOMES AND MEASURES

Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants.

RESULTS

Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text].

CONCLUSIONS AND RELEVANCE

Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01343004.

Authors+Show Affiliations

Colorado Center for Bone Research, Lakewood.Radius Health, Waltham, Massachusetts.Nordic Bioscience, Copenhagen, Denmark.Radius Health, Waltham, Massachusetts.Center for Health & Medical Research, Hong Kong, People's Republic of China.Center for Clinical and Basic Research, Rio de Janeiro, Brazil.Center for Clinical and Basic Research, Vejle, Denmark.Centro Paulista de Investigação Clinica; São Paulo, Brazil.Radius Health, Waltham, Massachusetts.Radius Health, Waltham, Massachusetts.Radius Health, Waltham, Massachusetts.Clinical Research Center, Helen Hayes Hospital, West Haverstraw, New York.Nordic Bioscience, Copenhagen, Denmark.No affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27533157

Citation

Miller, Paul D., et al. "Effect of Abaloparatide Vs Placebo On New Vertebral Fractures in Postmenopausal Women With Osteoporosis: a Randomized Clinical Trial." JAMA, vol. 316, no. 7, 2016, pp. 722-33.
Miller PD, Hattersley G, Riis BJ, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016;316(7):722-33.
Miller, P. D., Hattersley, G., Riis, B. J., Williams, G. C., Lau, E., Russo, L. A., Alexandersen, P., Zerbini, C. A., Hu, M. Y., Harris, A. G., Fitzpatrick, L. A., Cosman, F., & Christiansen, C. (2016). Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA, 316(7), 722-33. https://doi.org/10.1001/jama.2016.11136
Miller PD, et al. Effect of Abaloparatide Vs Placebo On New Vertebral Fractures in Postmenopausal Women With Osteoporosis: a Randomized Clinical Trial. JAMA. 2016 Aug 16;316(7):722-33. PubMed PMID: 27533157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. AU - Miller,Paul D, AU - Hattersley,Gary, AU - Riis,Bente Juel, AU - Williams,Gregory C, AU - Lau,Edith, AU - Russo,Luis Augusto, AU - Alexandersen,Peter, AU - Zerbini,Cristiano A F, AU - Hu,Ming-yi, AU - Harris,Alan G, AU - Fitzpatrick,Lorraine A, AU - Cosman,Felicia, AU - Christiansen,Claus, AU - ,, PY - 2016/8/18/entrez PY - 2016/8/18/pubmed PY - 2016/9/14/medline SP - 722 EP - 33 JF - JAMA JO - JAMA VL - 316 IS - 7 N2 - IMPORTANCE: Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor. OBJECTIVE: To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture. DESIGN, SETTING, AND PARTICIPANTS: The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll. INTERVENTIONS: Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months. MAIN OUTCOMES AND MEASURES: Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants. RESULTS: Among 2463 women (mean age, 69 years [range, 49-86]), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006). [table: see text]. CONCLUSIONS AND RELEVANCE: Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01343004. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/27533157/Effect_of_Abaloparatide_vs_Placebo_on_New_Vertebral_Fractures_in_Postmenopausal_Women_With_Osteoporosis:_A_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2016.11136 DB - PRIME DP - Unbound Medicine ER -