Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Ferrari, S.; Adachi, J.; Lippuner, K.; Zapalowski, C.; Miller, P.; Reginster, J.-Y.; Törring, O.; Kendler, D.; Daizadeh, N.; Wang, A.; O'Malley, C.; Wagman, R.; Libanati, C.; Lewiecki, E.
• Is Part Of: Osteoporosis international. Volume 26:Issue 12(2015)
• Page Start: 2763
• Page End: 2771
• Publication Date: 2015-12
• Subjects: Denosumab -- Fracture threshold -- Hip bone mineral density -- Long-term osteoporosis therapy -- Nonvertebral fracture -- Treatment to goal; Osteoporosis -- Periodicals; Bones -- Metabolism -- Disorders -- Periodicals; 616.716005
• DOI: 10.1007/s00198-015-3179-x
• Languages: English
• ISSNs: 0937-941X

Abstract

Abstract Summary Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4–7 versus years 1–3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. Introduction This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. Methods Participants who completed the 3-year placebo-controlledF ractureRE ductionE valuation ofD enosumab inO steoporosis every 6M onths (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4, 074 postmenopausal women with osteoporosis (n = 2, 343 long-term;n = 1, 731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1–3 of denosumab with that of the fourth year and with the rate during years 4–7 was evaluated. Results For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1–3 were compared to years 4–7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). Conclusions Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.