Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial

• Published in: Osteoporosis international Vol. 24; no. 1; pp. 227 - 235
• Main Authors: McClung, M. R., Lewiecki, E. M., Geller, M. L., Bolognese, M. A., Peacock, M., Weinstein, R. L., Ding, B., Rockabrand, E., Wagman, R. B., Miller, P. D.
• Format: Journal Article
• Language: English
• Published: London Springer-Verlag 01.01.2013; Springer Nature B.V
• Subjects: Aged; Alkaline Phosphatase - blood; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacology; Antibodies, Monoclonal, Humanized - therapeutic use; Biomarkers - blood; Bone density; Bone Density - drug effects; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; Bone Remodeling - drug effects; Collagen Type I - blood; Denosumab; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug therapy; Endocrinology; Female; Hip Joint - physiopathology; Humans; Lumbar Vertebrae - physiopathology; Medicine; Medicine & Public Health; Middle Aged; Original; Original Article; Orthopedics; Osteoporosis; Osteoporosis, Postmenopausal - blood; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - physiopathology; Peptides - blood; Rheumatology; Treatment Outcome; Osteoporosis; RANK ligand; Bone mineral density; Denosumab; Bone turnover markers
• ISSN: 0937-941X; 1433-2965; 1433-2965
• DOI: 10.1007/s00198-012-2052-4

Summary In a phase 2 study, continued denosumab treatment for up to 8 years was associated with continued gains in bone mineral density and persistent reductions in bone turnover markers. Denosumab treatment was well tolerated throughout the 8-year study. Introduction The purpose of this study is to present the effects of 8 years of continued denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTM) from a phase 2 study. Methods In the 4-year parent study, postmenopausal women with low BMD were randomized to receive placebo, alendronate, or denosumab. After 2 years, subjects were reallocated to continue, discontinue, or discontinue and reinitiate denosumab; discontinue alendronate; or maintain placebo for two more years. The parent study was then extended for 4 years where all subjects received denosumab. Results Of the 262 subjects who completed the parent study, 200 enrolled in the extension, and of these, 138 completed the extension. For the subjects who received 8 years of continued denosumab treatment, BMD at the lumbar spine ( N  = 88) and total hip ( N  = 87) increased by 16.5 and 6.8 %, respectively, compared with their parent study baseline, and by 5.7 and 1.8 %, respectively, compared with their extension study baseline. For the 12 subjects in the original placebo group, 4 years of denosumab resulted in BMD gains comparable with those observed during the 4 years of denosumab in the parent study. Reductions in BTM were sustained over the course of continued denosumab treatment. Reductions also were observed when the placebo group transitioned to denosumab. Adverse event profile was consistent with previous reports and an aging cohort. Conclusion Continued denosumab treatment for 8 years was associated with progressive gains in BMD, persistent reductions in BTM, and was well tolerated.