OBJECTIVE: To compare the efficacy and safety of denosumab to ibandronate in postmenopausal women with low bone mineral density (BMD) previously treated with a bisphosphonate.
METHODS: In a randomized, open-label study, postmenopausal women received 60 mg denosumab subcutaneously every 6 months (n=417) or 150 mg ibandronate orally every month (n=416) for 12 months. End points included percentage change from baseline in total hip, femoral neck, and lumbar spine BMD at month 12 and percentage change from baseline in serum C-telopeptide at months 1 and 6 in a substudy.
RESULTS: At month 12, significantly greater BMD gains from baseline were observed with denosumab compared with ibandronate at the total hip (2.3% compared with 1.1%), femoral neck (1.7% compared with 0.7%), and lumbar spine (4.1% compared with 2.0%; treatment difference P<.001 at all sites). At month 1, median change in serum C-telopeptide from baseline was −81.1% with denosumab and –35.0% with ibandronate (P<.001); the treatment difference remained significant at month 6 (P<.001). Adverse events occurred in 245 (59.6%) denosumab-treated women and 230 (56.1%) ibandronate-treated women (P=.635). The incidence of serious adverse events was 9.5% for denosumab-treated women and 5.4% for ibandronate-treated women (P=.046). No clustering of events in any organ system accounted for the preponderance of these reports. The incidence rates of serious adverse events involving infection and malignancy were similar between treatment groups.
CONCLUSION: In postmenopausal women previously treated with a bisphosphonate and low BMD, denosumab treatment resulted in greater BMD increases than ibandronate at all measured sites. No new safety risks with denosumab treatment were identified.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00936897.
LEVEL OF EVIDENCE: I
Women previously treated with bisphosphonates have greater bone mineral density gains when transitioned to denosumab than to ibandronate.
United Osteoporosis Centers, Gainesville, Georgia; Medical College Jagiellonian University, Krakow, Poland; Michigan Bone and Mineral Clinic, Detroit, Michigan; the Clinical Research Center of North Texas, Denton, Texas; the University of Wisconsin–Madison Osteoporosis Clinical Center and Research Program, Madison, Wisconsin; the Palacios Institute of Woman's Health, Madrid, Spain; OB-GYN Associates of Mid Florida, PA, Leesburg, Florida; Amgen Inc, Thousand Oaks, California; Amgen Ltd, Cambridge, United Kingdom; Ovatech Solutions Ltd, London, United Kingdom; The Bethesda Health Research Center, Bethesda, Maryland; and Institut National de la Santé et de la Recherche Médicale (INSERM) U658, CHR d'Orléans, Orléans, France.
Corresponding author: Chris Recknor, MD, United Osteoporosis Centers, 2350 Limestone Parkway, Gainesville, GA 30501; e-mail: firstname.lastname@example.org.
Funding support Sponsored by Amgen Inc, Thousand Oaks, California.
Financial Disclosure Dr. Recknor has received consulting and advisory fees from Amgen Inc, Eli Lilly, and Novartis, lecture fees from Novartis and Warner Chilcott, a grant from Medi, and is a shareholder in Ion Med Systems. Dr. Czerwinski has received research grants from Amgen Inc, Eli Lilly, Johnson & Johnson, Merck, Serono, Novartis, Pfizer, Roche, and Servier and lecture fees from Amgen Inc, Roche, and Servier. Dr. Bone has received research grants from Amgen Inc, Merck, Novartis, and Tarsa, is a consultant or advisor for Amgen Inc, Merck, and Tarsa, and is a member of the speakers' bureau for Amgen Inc. Dr. Bonnick has received research grants from Amgen Inc, Merck, Takeda, and Wyeth and is a member of the speakers' bureau for Amgen Inc and Novartis. Dr. Binkley has received research grants from Amgen Inc, Eli Lilly, Merck, and Tarsa and is a consultant for Eli Lilly, Merck, and Tarsa. Dr. Palacios has received research grants from Amgen Inc, Gynea, Leon Farma, Merck, Pfizer, PregLem, and Servier and is a consultant or advisor for Abbott, Amgen Inc, Arkopharma, Bioiberica, C Fleet, Ferrer, GlaxoSmithKline, Isdin, Pfizer, Rovi, Servier, and Shionogi. Drs. Siddhanti, Ferreira, Wagman, and Hall are employees of and have stock ownership in Amgen Inc. Mrs Ghelani has received consulting fees from Amgen Inc. D. Bolognese is a consultant for Amgen Inc, Eli Lilly, Roche, and Vivus. Dr. Benhamou has received research grants from Amgen Inc, Eli Lilly, Merck, Novartis, Roche, and Servier and is member of the speakers' bureau for Amgen Inc, Merck, .Novartis, and Servier. Dr. Moffett did not report any potential conflicts of interest.
The authors thank Mandy Suggitt, whose work was funded by Amgen Inc, for medical writing support.
Presented at the American Society for Bone and Mineral Research, Minneapolis, Minnesota, October 12–15, 2012.