Relationship Between Changes in Bone Mineral Density and Incidence of Fracture With 6 Years of Denosumab

MILLER PD; STEVEN CUMMIMGS; REGINSTER JY; FRANCHIMONT N; BIANCHI G; MICHAEL BOLOGNESE; CHAPURLAT R; FEDERICO HAWKINS; DANIEL KENDLER; OLIVERI B; JOSÉ ZANCHETTA; ZAPALOWSKI C; DAIZADEH N; WANG A; WANGMAN R; PAPAPOULOS S

Congreso; Annual Meeting American Society for Bone and Mineral Research; 2012

Purpose: During the first 3 years of denosumab (DMAb) treatment in FREEDOM, there were continued increases in bone mineral density (BMD) and a robust reduction in fracture risk (Cummings et al., NEJM 2009). The changes in total hip BMD explained a considerable proportion of the reduction in new or worsening vertebral and nonvertebral fracture risk (Austin et al., JBMR 2011). Here, we conducted a BMD responder analysis and explored if the progressive BMD gains with 6 years of DMAb therapy continued to relate to the observed fracture incidence. Methods: The long-term efficacy and safety of DMAb for up to 10 years is being investigated in the open-label extension of the 3-year FREEDOM trial. During the extension, all participants receive 60 mg DMAb every 6 months. For the analyses presented here, women from the FREEDOM DMAb group received 3 more years of DMAb for a total of 6 years. The percentages of women treated with DMAb who achieved BMD increases from FREEDOM baseline at the lumbar spine, total hip, and femoral neck were determined. A logistic regression model was used to examine the relationship between change in total hip BMD and new or worsening vertebral fracture. A comparable approach was employed for nonvertebral fracture using the Cox proportional hazards model. Results: For women who received 3 additional years of DMAb treatment (N=2343 enrolled), further significant increases in BMD occurred for cumulative 6 year mean gains of 15.2% (lumbar spine), 7.5% (total hip), and 6.7% (femoral neck). At year 6, almost all women treated with DMAb had gains in BMD at the lumbar spine (98%), total hip (96%), and femoral neck (91%). Additionally, 99% of women had gains in BMD at any of these sites, and of these, the gains were >3% in 98% of women and >6% in 95% of women. Fracture incidence remained low during the extension. The relationships between total hip BMD gains and new or worsening vertebral and nonvertebral fractures with 6 years of DMAb treatment are shown in Figures 1 and 2, respectively. Conclusion: Almost all women who received 6 years of DMAb treatment had gains in BMD at the lumbar spine, total hip, or femoral neck; and those gains were >6% in 95% of them. While on denosumab treatment, the risk of new or worsening vertebral fracture and nonvertebral fracture decreased with increasing percentage change in total hip BMD over 6 years. This association provides clinical relevance to the progressive and continued BMD gains reported with DMAb over time.