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

Context: This is a study extension to evaluate the efficacy and safety of long-term treatment with denosumab in postmenopausal women with low bone mass. Objective: Our objective was to describe changes in bone mineral density (BMD) and bone turnover markers as well as safety with 6 yr of denosumab treatment. Design: We conducted an ongoing 4-yr, open-label, single-arm, extension study of a dose-ranging phase 2 trial. This paper reports a 2-yr interim analysis representing up to 6 yr of continuous denosumab treatment. Setting: This multicenter study was conducted at 23 U.S. centers. Patients:Of the 262 subjects who completed the parent study, 200 enrolled in the study extension and 178 (89%) completed the first 2 yr. Intervention: All subjects received denosumab 60 mg sc every 6 months. Main Outcome Measures: We evaluated BMD at the lumbar spine, total hip, femoral neck, and one third radius; biochemical markers of bone turnover; and safety, reported as adverse events. Results: Over a period of 6 yr, continuous treatment with denosumab resulted in progressive gains in BMD in postmenopausal women with low bone mass. Reduction in bone resorption was sustained over the course of continuous treatment. Independent of past treatment and discontinuation period, subjects demonstrated responsiveness to denosumab therapy as measured by BMD and bone turnover markers. The safety profile of denosumab did not change over time. Conclusions: In this study, denosumab was well tolerated and effective through 6 yr of continuous treatment in postmenopausal women with low bone mass.