Session Title: Osteoporosis and Metabolic Bone Disease
Session Type: Abstract Submissions (ACR)
Background/Purpose: During the first 3 years of denosumab 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 denosumab therapy continued to relate to the observed fracture incidence.
Methods: The long-term efficacy and safety of denosumab 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 denosumab every 6 months. For the analyses presented here, women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years. The percentages of women treated with denosumab 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 denosumab 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 denosumab 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 denosumab treatment are shown in Figures 1 and 2, respectively.
Conclusion: Almost all women who received 6 years of denosumab 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 denosumab over time.
M. A. Bolognese,
Lilly, Amgen, Merck,
Lilly, Amgen, Warner-Chilcott,
P. D. Miller,
Procter and Gamble, Sanofi/Aventis, Roche, Eli Lilly, Merck, Novartis, Amgen, Takeda, Radius, GE,
Warner Chilcott, Merck, Eli Lilly, Amgen, Novartis, Roche, GSK, Baxter, Wright,
Warner Chilcott, Amgen, Novartis, Roche,
J. Y. Reginster,
Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GSK, Roche, Merckle, Nycomed, NPS, Theramex, UCB,
Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GSK, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Nycomed, Novo-Nordisk, Nolver,
Bristol-Myers Squibb, Merck Sharp and Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GSK, Amgen, Servier,
Amgen Inc., Biogenidec,
Amgen Inc., Biogenidec,
Amgen, Merck Sharp and Dohme, Novartis, Pfizer, Roche,
Amgen, Eli Lilly, Ipsen, Servier, Roche, Merck, Novartis,
F. G. Hawkins,
D. L. Kendler,
J. R. Zanchetta,
Amgen, Eli Lilly, MSD, Radius Inc,
Amgen, Eli Lilly, MSD, GSK, Pfizer,
R. B. Wagman,
Amgen Inc., Merck Co., Novartis, Eli Lilly, GSK,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-between-changes-in-bone-mineral-density-and-incidence-of-fracture-with-6-years-of-denosumab-treatment/