Fracture Risk and Zoledronic Acid Therapy in Men with Osteoporosis

被引:242
作者
Boonen, Steven [1 ]
Reginster, Jean-Yves [2 ]
Kaufman, Jean-Marc [3 ]
Lippuner, Kurt
Zanchetta, Jose [7 ]
Langdahl, Bente [8 ]
Rizzoli, Rene [5 ]
Lipschitz, Stanley [10 ]
Dimai, Hans Peter [11 ]
Witvrouw, Richard [4 ]
Eriksen, Erik [12 ]
Brixen, Kim [9 ]
Russo, Luis [13 ]
Claessens, Frank [1 ]
Papanastasiou, Philemon [6 ]
Antunez, Oscar [14 ]
Su, Guoqin [14 ]
Bucci-Rechtweg, Christina [14 ]
Hruska, Josef [6 ]
Incera, Elodie [6 ]
Vanderschueren, Dirk [1 ]
Orwoll, Eric [15 ]
机构
[1] Katholieke Univ Leuven, Louvain, Belgium
[2] Univ Liege, Liege, Belgium
[3] Univ Ghent, B-9000 Ghent, Belgium
[4] Ziekenhuis Oost Limburg, Genk, Belgium
[5] Univ Hosp Geneva, Geneva, Switzerland
[6] Novartis Pharmaceut, Basel, Switzerland
[7] Univ Salvador, Buenos Aires, DF, Argentina
[8] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark
[9] Univ So Denmark, Odense, Denmark
[10] Bone Mineral Dens Clin, Johannesburg, South Africa
[11] Med Univ Graz, Graz, Austria
[12] Univ Oslo, Oslo, Norway
[13] Brazil Ctr Clin & Basic Res, Rio De Janeiro, Brazil
[14] Novartis Pharmaceut, E Hanover, NJ USA
[15] Oregon Hlth & Sci Univ, Portland, OR USA
关键词
VERTEBRAL FRACTURES; ORAL ALENDRONATE; HIP FRACTURE; BONE-DENSITY; DOUBLE-BLIND; WOMEN; MORTALITY; RISEDRONATE; PREVALENCE; DENOSUMAB;
D O I
10.1056/NEJMoa1204061
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis. Methods In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months. Results The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P = 0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P = 0.03) and less height loss (P = 0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%). Conclusions Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.)
引用
收藏
页码:1714 / 1723
页数:10
相关论文
共 27 条
[1]  
[Anonymous], 2004, Declaration of Helsinki: Ethical principles for medical research involving human subjects
[2]   Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis [J].
Black, Dennis M. ;
Delmas, Pierre D. ;
Eastell, Richard ;
Reid, Ian R. ;
Boonen, Steven ;
Cauley, Jane A. ;
Cosman, Felicia ;
Lakatos, Peter ;
Leung, Ping Chung ;
Man, Zulema ;
Mautalen, Carlos ;
Mesenbrink, Peter ;
Hu, Huilin ;
Caminis, John ;
Tong, Karen ;
Rosario-Jansen, Theresa ;
Krasnow, Joel ;
Hue, Trisha F. ;
Sellmeyer, Deborah ;
Eriksen, Erik Fink ;
Cummings, Steven R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (18) :1809-1822
[3]   Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures [J].
Black, DM ;
Arden, NK ;
Palermo, L ;
Pearson, J ;
Cummings, SR .
JOURNAL OF BONE AND MINERAL RESEARCH, 1999, 14 (05) :821-828
[4]  
Boonen S, 2009, J BONE MINER RES, V24, P719, DOI [10.1359/jbmr.081214, 10.1359/JBMR.081214]
[5]   Screening for Osteoporosis: US Preventive Services Task Force Recommendation Statement [J].
Calonge, Ned ;
Bibbins-Domingo, Kirsten ;
Cantu, Adelita Gonzales ;
Curry, Susan ;
Dietrich, Allen J. ;
Flores, Glenn ;
Grossman, David ;
Isham, George ;
LeFevre, Michael L. ;
Leipzig, Rosanne M. ;
Melnikow, Joy ;
Melnyk, Bernadette ;
Nicholson, Wanda ;
Reyes, Carolina ;
Schwartz, J. Sanford ;
Wilt, Timothy .
ANNALS OF INTERNAL MEDICINE, 2011, 154 (05) :356-+
[6]   Mortality after all major types of osteoporotic fracture in men and women: an observational study [J].
Center, JR ;
Nguyen, TV ;
Schneider, D ;
Sambrook, PN ;
Eisman, JA .
LANCET, 1999, 353 (9156) :878-882
[7]   PREDICTION OF CREATININE CLEARANCE FROM SERUM CREATININE [J].
COCKCROFT, DW ;
GAULT, MH .
NEPHRON, 1976, 16 (01) :31-41
[8]   Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis [J].
Cummings, Steven R. ;
San Martin, Javier ;
McClung, Michael R. ;
Siris, Ethel S. ;
Eastell, Richard ;
Reid, Ian R. ;
Delmas, Pierre ;
Zoog, Holly B. ;
Austin, Matt ;
Wang, Andrea ;
Kutilek, Stepan ;
Adami, Silvano ;
Zanchetta, Jose ;
Libanati, Cesar ;
Siddhanti, Suresh ;
Christiansen, Claus .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (08) :756-765
[9]   Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial [J].
Delmas, PD ;
Genant, HK ;
Crans, GG ;
Stock, JL ;
Wong, M ;
Siris, E ;
Adachi, JD .
BONE, 2003, 33 (04) :522-532
[10]   The near absence of osteoporosis treatment in older men with fractures [J].
Feldstein, AC ;
Nichols, G ;
Orwoll, E ;
Elmer, PJ ;
Smith, DH ;
Herson, M ;
Aickin, M .
OSTEOPOROSIS INTERNATIONAL, 2005, 16 (08) :953-962