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The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Black, DM and Reid, IR and Boonen, S and Bucci-Rechtweg, C and Cauley, JA and Cosman, F and Cummings, SR and Hue, TF and Lippuner, K and Lakatos, P and Leung, PC and Man, Z and Martinez, RLM and Tan, M and Ruzycky, ME and Su, G and Eastell, R (2012) The effect of 3 versus 6 years of Zoledronic acid treatment of osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). Journal of Bone and Mineral Research, 27 (2). 243 - 254. ISSN 0884-0431

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Zoledronic acid 5 mg (ZOL) annually for 3 years reduces fracture risk in postmenopausal women with osteoporosis. To investigate long-term effects of ZOL on bone mineral density (BMD) and fracture risk, the Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) was extended to 6 years. In this international, multicenter, double-blind, placebo-controlled extension trial, 1233 postmenopausal women who received ZOL for 3 years in the core study were randomized to 3 additional years of ZOL (Z6, n = 616) or placebo (Z3P3, n = 617). The primary endpoint was femoral neck (FN) BMD percentage change from year 3 to 6 in the intent-to-treat (ITT) population. Secondary endpoints included other BMD sites, fractures, biochemical bone turnover markers, and safety. In years 3 to 6, FN-BMD remained constant in Z6 and dropped slightly in Z3P3 (between-treatment difference = 1.04%; 95% confidence interval 0.4 to 1.7; p = 0.0009) but remained above pretreatment levels. Other BMD sites showed similar differences. Biochemical markers remained constant in Z6 but rose slightly in Z3P3, remaining well below pretreatment levels in both. New morphometric vertebral fractures were lower in the Z6 (n = 14) versus Z3P3 (n = 30) group (odds ratio = 0.51; p = 0.035), whereas other fractures were not different. Significantly more Z6 patients had a transient increase in serum creatinine >0.5 mg/dL (0.65% versus 2.94% in Z3P3). Nonsignificant increases in Z6 of atrial fibrillation serious adverse events (2.0% versus 1.1% in Z3P3; p = 0.26) and stroke (3.1% versus 1.5% in Z3P3; p = 0.06) were seen. Postdose symptoms were similar in both groups. Reports of hypertension were significantly lower in Z6 versus Z3P3 (7.8% versus 15.1%, p < 0.001). Small differences in bone density and markers in those who continued versus those who stopped treatment suggest residual effects, and therefore, after 3 years of annual ZOL, many patients may discontinue therapy up to 3 years. However, vertebral fracture reductions suggest that those at high fracture risk, particularly vertebral fracture, may benefit by continued treatment. ( identifier: NCT00145327). © 2012 American Society for Bone and Mineral Research.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Black, DM
Reid, IR
Boonen, S
Bucci-Rechtweg, C
Cauley, JAJCauley@edc.pitt.eduJCAULEY
Cosman, F
Cummings, SR
Hue, TF
Lippuner, K
Lakatos, P
Leung, PC
Man, Z
Martinez, RLM
Tan, M
Ruzycky, ME
Su, G
Eastell, R
Date: 1 February 2012
Date Type: Publication
Journal or Publication Title: Journal of Bone and Mineral Research
Volume: 27
Number: 2
Page Range: 243 - 254
DOI or Unique Handle: 10.1002/jbmr.1494
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0884-0431
Date Deposited: 03 Apr 2015 01:24
Last Modified: 02 Feb 2021 18:55


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