New Biologic Treatment Increases Bone Mass in Postmenopausal Women

Denosumab can increase bone mass in post menopausal women, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.

Postmenopausal women have markedly reduced levels of estrogen, leading to loss of bone and damage to bone quality. Currently, there are more than 10 million people—eight million of which are women—with osteoporosis who are susceptible to fractures. Those over the age of 50 are at greatest risk of developing osteoporosis and suffering related fractures. In this age group, one in two women will suffer an osteoporosis-related fracture at some point in her life.

Researchers recently compared the effectiveness and safety of denosumab, a biologic inhibitor of the activation of bone-resorbing osteoclasts that is administered just twice a year, with alendronate (FOSAMAX®), a drug commonly used in the prevention and treatment of osteoporosis in postmenopausal women.

They followed 1,189 postmenopausal women with low bone mass over one year’s time in a randomized double blind trial. Participants, with an average age of 64 years and whose average bone mineral density results in the lumbar spine were a T-score of 2.6—(the level at which a person is diagnosed with osteoporosis is -2.5)—were randomly assigned to one of two groups. The first group received a 60 mg injection of denosumab every six months and a weekly oral placebo. The second group received an injection of placebo every six months plus 70 mgs of alendronate, orally, each week. All participants took at least 500 mg of calcium and at least 400 mg of vitamin D daily.

Researchers evaluated changes in bone mass and substances found in the blood and urine that that reflect the rates of bone turnover, as well as drug safety over 12 months. Participants taking denosumab showed greater bone mass gains than those on alendronate. At the end of the study, more participants on denosumab had gained at least three percent of bone mass at the hip and lumbar spine than those on alendronate. In addition, denosumab suppressed serum markers of bone turnover, suggesting effective suppression of bone resorption.

Researchers found that side effects were similar between patients taking both denosumab and alendronate.

“The fact that bone density changes were greater than the most commonly used antiresorptive agent, alendronate, shows that denosumab is an effective agent,” explains Chad Deal, MD; head, Center for Osteoporosis and Metabolic Bone Disease, Cleveland Clinic, Cleveland, OH, and lead investigator in the study.

Patients should talk to their rheumatologists to determine their best course of treatment.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see

Editor’s Notes: Dr. Deal will present this research during the ACR Annual Scientific Meeting at the Moscone Center from 11:15 – 11:30 AM on Wednesday, October 29, in Room 130. Dr. Deal will be available for media questions and briefing at 1:30 PM on Sunday, October 26 in the on-site press conference room, 114.

Presentation Number: 2102

Direct Comparison of Changes in Bone Density and Bone Turnover Markers in Postmenopausal Women With Low Bone Mass Treated With 6-monthly Denosumab or Weekly Alendronate (Fosamax®)

C. Deal1, J. P. Brown2, R. Recker3, R. Prince4, D. P. Kiel5, J. M. Álvaro-Gracia6, L. H. de Gregorio7, P. Hadji8, L. C. Hofbauer9, H. Wang10, M. Austin10, R. Newmark10, C. Libanati10, R. B. Wagman11, J. San Martin10, H. G. Bone12. 1Cleveland Clinic, Cleveland, OH; 2CHUQ Laval University, Quebec, QC, Canada; 3Creighton University, Omaha, NE; 4Sir Charles Gairdner Hospital, University of Western Australia, Perth, Australia; 5Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, MA; 6Hospital de la Princesa, Madrid, Spain; 7SYNARC/CCBR, Rio de Janerio, Brazil; 8Philipps-University of Marburg, Marburg, Germany; 9Technical University Medical Center, Dresden, Germany; 10Amgen Inc., Thousand Oaks, CA; 11Amgen Inc. and Stanford University School of Medicine, San Francisco and Stanford, CA; 12Michigan Bone and Mineral Clinic, Detroit, MI

Purpose: We directly compared the efficacy and safety of denosumab, a RANKL inhibitor, with alendronate (ALN) in postmenopausal women with low bone mass in a randomized, blinded, phase 3 trial.

Methods: Ambulatory postmenopausal women with a T-score

< -2.0 at the lumbar spine or total hip were randomized (1:1) to receive a subcutaneous (SC) denosumab injection (60 mg) every 6 months (Q6M) plus oral placebo weekly or SC placebo injection Q6M plus oral ALN (70 mg, Merck) weekly. All subjects received daily calcium (≥ 500 mg) and vitamin D (≥ 400 IU) supplements. Changes in bone mineral density (BMD) and biochemical markers of bone turnover, and safety were evaluated over 12 months.

Results: In total, 1189 subjects were enrolled (594 denosumab; 595 ALN) with a mean (SD) age of 64 (9) yrs and a mean (SD) lumbar spine T-score of -2.6 (0.8). Denosumab resulted in greater BMD gains than ALN at all measured skeletal sites (Table). More denosumab subjects gained >

3% BMD at the total hip (62% vs 39%) and lumbar spine (77% vs 65%) than alendronate subjects at month 12 (P < 0.0001 for both). With denosumab, suppression of serum type 1 C-telopeptide from baseline levels was rapid (month 1: -89% vs -61% ALN; P <0.0001) and sustained (month 12: -74% vs -76% ALN; P = 0.5). Procollagen type 1 N-propeptide levels decreased within one month of denosumab treatment (-26% vs -11% for ALN; P < 0.0001) and remained decreased through month 12 (-72% vs -65% ALN, P < 0.0001). Adverse events, including infections and neoplasms, were similar between both groups. No denosumab subjects (n = 592 tested) developed anti-denosumab antibodies.

Conclusions: Denosumab increased BMD at all measured skeletal sites and decreased BTM more than ALN among the subjects in this study. Similar safety profiles were observed for both groups. Ongoing clinical trials will further assess the efficacy and safety of denosumab.

Disclosure Block: C. Deal, Amgen, 2; Lilly, 2; Novartis, 2; GlaxoSmithKline, 2; Amgen, 5; Amgen, 8; Lilly, 8; Novartis, 8; Procter & Gamble, 8; GlaxoSmithKline, 8; Amgen, 9; Lilly, 9; Novartis, 9; J.P. Brown, Amgen, 2; Novartis, 8; Amgen, 9; Procter & Gamble, 9; Sanofi-Aventis, 9; Merck, 9; Procter & Gamble, 2; Sanofi-Aventis, 2; Merck, 2; Novartis, 2; Procter & Gamble, 5; Sanofi-Aventis, 5; Novartis, 5; Procter & Gamble, 8; Sanofi-Aventis, 8; Merck, 8; Novartis, 9; R. Recker, Allelix, 5; Amgen, 5; Lilly, 5; Merck, 5; Novartis, 5; NPS, 5; Procter & Gamble, 5; Roche, 5; GlaxoSmithKline, 5; Wyeth, 5; R. Prince, Lilly, 2; Novartis, 2; Servier, 2; Merck, 5; D.P. Kiel, Amgen, 2; Merck, 2; Amgen, 5; Merck, 5; Merck, 8; J.M. Álvaro-Gracia, None; L.H. de Gregorio, Amgen, 2; Merck, 2; Roche, 2; P. Hadji, None; L.C. Hofbauer, None; H. Wang, Amgen, 1; Amgen, 3; M. Austin, Amgen, 1; Amgen, 3; R. Newmark, Amgen, 1; Amgen, 3; C. Libanati, Amgen, 1; Amgen, 3; R.B. Wagman, Amgen, 1; Amgen, 3; J. San Martin, Amgen, 1; Amgen, 3; H.G. Bone, Amgen, 2; Merck, 2; Eli Lilly, 2; Amgen, 5; Novartis, 5; Merck, 5; Merck, 9.

Source: American College of Rheumatology (ACR)

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