Further Nonvertebral Fracture Reduction Beyond 3 Years for up to 10 Years of Denosumab Treatment.
J Clin Endocrinol Metab. 2019 May 24;: Authors: Ferrari S, Butler PW, Kendler DL, Miller PD, Roux C, Wang AT, Huang S, Wagman RB, Lewiecki EM
CONTEXT: Evidence for further nonvertebral fracture (NVF) reductions with long-term antiresorptive therapy in osteoporosis is lacking. OBJECTIVE: To evaluate NVF risk reduction in subjects who received up to 10 years of denosumab treatment. DESIGN: Phase 3, randomized, placebo-controlled, 3-year FREEDOM trial (NCT00089791) and its open-label 7-year Extension (NCT00523341). SETTING: 214 study centers worldwide; subjects from this analysis came from 172 centers. PATIENTS: Women aged 60-90 years with BMD T-score <-2.5 at the lumbar spine or total hip but ≥-4.0 at both sites. INTERVENTIONS: Randomized 1:1 to denosumab 60 mg SC Q6M (long-term group) or placebo (cross-over group) in FREEDOM; eligible subjects could enroll in Extension to receive denosumab 60 mg SC Q6M. MAIN OUTCOME MEASURES: Exposure-adjusted subject incidence (per 100 subject-years) of NVF during denosumab treatment years 1-3 and 4-7 (all subjects) and years 4-10 (long-term group only), and rate ratios for years 4-7 or 4-10 vs 1-3. RESULTS: Among 4074 subjects in this analysis (2343 long-term; 1731 cross-over), NVF rates (95% CI) in all subjects were 2.15 (1.90-2.43) during years 1-3 and 1.53 (1.34-1.75) during years 4-7 of denosumab treatment (rate ratio [95% CI]=0.72 [0.61-0.86]; P<0.001). NVF rates in the long-term denosumab subjects only were 1.98 (1.67-2.34) during years 1-3 and 1.44 (1.24-1.66) during years 4-10 (rate ratio=0.74 [0.60-0.93]; P=0.008). The combined osteonecrosis of the jaw and atypical femoral fracture rate was 0.06. CONCLUSIONS: Long-term denosumab treatment, beyond 3 and up to 10 years, was associated with further reductions in NVF rates vs the first 3 years. PMID: 31125092 [PubMed - as supplied by publisher]