Five years of denosumab exposure in women with postmenopausal osteoporosis:​ results from the first two years of the FREEDOM extension

Papapoulos, Socrates; Chapurlat, Roland; Libanati, Cesar; Brandi, Maria Luisa; Brown, Jacques P.; Czerwiński, Edward; Krieg, Marc-Antoine; Man, Zulema; Mellström, Dan; Radominski, Sebastião C.; Reginster, Jean-Yves; Resch, Heinrich; Ivorra, José A. Román; Roux, Christian; Vittinghoff, Eric; Austin, Matthew; Daizadeh, Nadia; Bradley, Michelle N.; Grauer, Andreas; Cummings, Steven R.; Bone, Henry G.

Affiliations

¹Department of Endocrinology & Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands

²INSERM UMR 1033, Université de Lyon, Lyon, France

³Amgen Inc., Thousand Oaks, CA, USA

⁴Department of Internal Medicine, University of Florence, Florence, Italy

⁵Department of Medicine, Laval University and Rheumatology Division, CHUQ Research Centre, Laval University, Quebec City, QC, Canada

⁶Krakow Medical Center, Krakow, Poland

⁷Bone and Joint Department, University Hospital of Lausanne, Lausanne, Switzerland

⁸Endocrinology Division, Centro TIEMPO, Buenos Aires, Argentina

⁹Osteoporosis Clinic, Center for Bone Research, Sahlgrenska University Hospital, Göteborg, Sweden

¹⁰Department of Internal Medicine, Universidade Federal do Paraná, Curitiba, Brazil

¹¹Bone and Cartilage Metabolism Unit, University of Liège, Liège, Belgium

¹²Medical Department II, St. Vincent Hospital, Vienna, Austria

¹³Rheumatology Unit, Hospital Universitario La Fe, Valencia, Spain

¹⁴Department of Rheumatology, Cochin Hospital, Paris Descartes University, Paris, France

¹⁵Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

¹⁶San Francisco Coordinating Center, CPMC Research Institute, and University of California San Francisco, San Francisco, CA, USA

¹⁷Michigan Bone and Mineral Clinic, Detroit, MI, USA

Abstract and keywords

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial 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), fracture 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. 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.

Keywords: BONE MINERAL DENSITY; BONE TURNOVER MARKERS; DENOSUMAB; FRACTURE; PIVOTAL FRACTURE TRIAL EXTENSION

Links

DOI: 10.1002/jbmr.1479

PubMed: 22113951

WoS: 000300682500021

History

Received: 2011-07-11

Revised: 2011-10-26

Accepted: 2011-11-17

Online: 2011-11-23

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