[en] The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for treatment of postmenopausal women with osteoporosis. Participants who completed FREEDOM were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fractures rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a "virtual untreated twin" cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw (ONJ). Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile. (c) 2011 American Society for Bone and Mineral Research.
Disciplines :
General & internal medicine
Author, co-author :
Papapoulos, S.
Chapurlat, R.
Libanati, C.
Brandi, M.
Brown, J.
Czerwinski, E.
Krieg, M. A.
Man, Z.
Mellstrom, D.
Radominski, S.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Cummings SR, San Martin J, McClung MR, Siris ES, Eastell R, Reid IR, Delmas P, Zoog HB, Austin M, Wang A, Kutilek S, Adami S, Zanchetta J, Libanati C, Siddhanti S, Christiansen C., Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361: 756-65.
Eastell R, Christiansen C, Grauer A, Kutilek S, Libanati C, McClung MR, Reid IR, Resch H, Siris E, Uebelhart D, Wang A, Weryha G, Cummings SR., Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res. 2011; 3: 530-7.
Genant HK, Wu CY, van Kuijk C, Nevitt MC., Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 1993; 8: 1137-48.
Thomas D, Carriere P, Jacobs I., Safety of denosumab in giant-cell tumour of bone. Lancet Oncol. 2010; 11: 815.
Longford NT., Random coefficient models. New York: Oxford University Press; 1993.
Kenward MG, Roger JH., Small sample inference for fixed effects from restricted maximum likelihood. Biometrics. 1997; 53: 983-97.
Vittinghoff E, McCulloch CE, Woo C, Cummings SR., Estimating long-term effects of treatment from placebo-controlled trials with an extension period, using virtual twins. Stat Med. 2010; 29: 1127-36.
Hochberg MC, Greenspan S, Wasnich RD, Miller P, Thompson DE, Ross PD., Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. J Clin Endocrinol Metab. 2002; 87: 1586-92.
Stein CM, Ray WA., The ethics of placebo in studies with fracture end points in osteoporosis. N Engl J Med. 2010; 363: 1367-70.
Rosen CJ, Khosla S., Placebo-controlled trials in osteoporosis-proceeding with caution. N Engl J Med. 2010; 363: 1365-7.
Endocrinologic and Metabolic Drugs Advisory Committee. Meeting Minutes, September 25-27, 2002. [Internet]. Silver Spring, MD: Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration. [cited 2011 Nov 24]. Available from:.
Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, Rodriguez-Portales JA, Downs RW, Gupta J, Santora AC, Liberman UA., Ten years' experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med. 2004; 350: 1189-99.
