Article; Osteoporosis, Postmenopausal; Administration, Oral; Aged; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Double-Blind Method; Drug Substitution; Female; Humans; Imidazoles; Middle Aged
Abstract :
[en] Context: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. Objective: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. Design and Setting: This was an international, multicenter, randomized, double-blind trial. Participants:Atotal of 643 postmenopausalwomenwith osteoporosis previously treated with oral bisphosphonates participated in the study. Interventions: Subjects were randomized 1:1 to scdenosumab60mgevery 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. Main Outcome Measures: Changes in BMD and bone turnover markers were measured. Results: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). Conclusions: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greaterBMDincreases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.
Disciplines :
General & internal medicine
Author, co-author :
Miller, P. D.; Colorado Center for Bone Research, 3190 South Wadsworth Boulevard, Lakewood, CO, United States
Pannacciulli, N.; Amgen Inc, Thousand Oaks, CA, United States
Brown, J. P.; Laval University, Centre Hospitalier Universitaire de Québec Research Centre, Québec City, QC, Canada
Czerwinski, E.; Krakow Medical Center, Krakow, Poland
Nedergaard, B. S.; Center for Clinical and Basic Research, Aalborg, Aalborg, Denmark
Bolognese, M. A.; Bethesda Health Research Center, Bethesda, MD, United States
Malouf, J.; Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Bone, H. G.; Michigan Bone and Mineral Clinic, Detroit, MI, United States
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Singer, A.; Georgetown University Medical Center, Washington, DC, United States
Wang, C.; Amgen Inc, Thousand Oaks, CA, United States
Wagman, R. B.; Amgen Inc, Thousand Oaks, CA, United States
Cummings, S. R.; San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA, United States
Sambrook P, Cooper C. Osteoporosis. Lancet. 2006;367:2010-2018.
Recker RR, Gallagher R, MacCosbe PE. Effect of dosing frequency on bisphosphonate medication adherence in a large longitudinal cohort of women. Mayo Clin Proc. 2005;80:856-861.
Silverman SL, Schousboe JT, Gold DT. Oral bisphosphonate compliance and persistence: a matter of choice? Osteoporos Int. 2011; 22:21-26.
Gallagher AM, Rietbrock S, Olson M, van Staa TP. Fracture outcomes related to persistence and compliance with oral bisphosphonates. J Bone Miner Res. 2008;23:1569-1575.
Gold DT, Martin BC, Frytak JR, Amonkar MM, Cosman F. A claims database analysis of persistence with alendronate therapy and fracture risk in post-menopausal women with osteoporosis. Curr Med Res Opin. 2007;23:585-594.
Kanis JA, Cooper C, Hiligsmann M, Rabenda V, Reginster JY, Rizzoli R. Partial adherence: a new perspective on health economic assessment in osteoporosis. Osteoporos Int. 2011;22:2565-2573.
Penning-van Beest FJ, Erkens JA, Olson M, Herings RM. Loss of treatment benefit due to low compliance with bisphosphonate therapy. Osteoporos Int. 2008;19:511-517.
Halpern R, Becker L, Iqbal SU, Kazis LE, Macarios D, Badamgarav E. The association of adherence to osteoporosis therapies with fracture, all-cause medical costs, and all-cause hospitalizations: a retrospective claims analysis of female health plan enrollees with osteoporosis. J Manag Care Pharm. 2011;17:25-39.
Olsen KR, Hansen C, Abrahamsen B. Association between refill compliance to oral bisphosphonate treatment, incident fractures, and health care costs-an analysis using national health databases. Osteoporos Int. 2013;24:2639-2647.
Cramer JA, Gold DT, Silverman SL, Lewiecki EM. A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int. 2007;18:1023-1031.
Cotte FE, Fardellone P, Mercier F, Gaudin AF, Roux C. Adherence to monthly and weekly oral bisphosphonates in women with osteoporosis. Osteoporos Int. 2010;21:145-155.
Gold DT, Safi W, Trinh H. Patient preference and adherence: comparative US studies between two bisphosphonates, weekly risedronate and monthly ibandronate. CurrMedRes Opin. 2006;22:2383-2391.
Lee S, Glendenning P, Inderjeeth CA. Efficacy, side effects and route of administration are more important than frequency of dosing of anti-osteoporosis treatments in determining patient adherence: a critical review of published articles from 1970 to 2009. Osteoporos Int. 2011;22:741-753.
Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. The Horizon Pivotal Fracture Trial. N Engl J Med. 2007;356:1809-1822.
McClung M, Recker R, Miller P, et al. Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. Bone. 2007;41:122-128.
Cummings S, San Martin J, McClung M, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. The FREEDOM Trial. N Engl J Med. 2009;361:756-765.
Kendler D, Roux C, Benhamou C, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res. 2010; 25:72-81.
Recknor C, Czerwinski E, Bone HG, et al. Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol. 2013;121:1291-1299.
Roux C, Hofbauer LC, Ho PR, et al. Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone. 2014;58:48-54.
Bonnick SL, Johnston CC Jr, Kleerekoper M, et al. Importance of precision in bone density measurements. J Clin Densitom. 2001;4: 105-110.
Shane E, Burr D, Abrahamsen B, et al. Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res. 2014;29:1-23.
Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res. 2009;24:153-161.
Seeman E, Libanati C, Austin M, et al. The transitory increase in PTH following denosumab administration is associated with reduced intracortical porosity: a distinctive attribute of denosumab therapy. J Bone Miner Res. 2011;26(suppl 1):S22.
Kostenuik PJ, Ferrari S, Pierroz D, et al. Infrequent delivery of a long-acting PTH-Fc fusion protein has potent anabolic effects on cortical and cancellous bone. J Bone Miner Res. 2007;22:1534-1547.
Atkinson JE, Kostenuik PJ, Smith SY, et al. Four weekly treatments with sustained-duration PTH-Fc increases bone mineral density in cynomolgus monkeys. J Bone Miner Res. 2003;18(suppl 1):S385.
Dempster DW, Zhou H, Recker RR, et al. Differential effects of teriparatide and denosumab on intact PTH and bone formation indices: AVA Osteoporosis Study. J Clin Endocrinol Metab. 2016; 101:1353-1363.
Freemantle N, Satram-Hoang S, Tang ET, et al. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012;23:317-326.
Eastell R, Christiansen C, Grauer A, et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res. 2011;26:530-537.
