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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).
J Bone Miner Res. 2012 Feb; 27(2):243-54.JB

Abstract

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.

Authors+Show Affiliations

Department of Epidemiology and Biostastistics, University of California, San Francisco, CA 94107, USA. dblack@psg.ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22161728

Citation

Black, Dennis M., et al. "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 : the Official Journal of the American Society for Bone and Mineral Research, vol. 27, no. 2, 2012, pp. 243-54.
Black DM, Reid IR, Boonen S, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27(2):243-54.
Black, D. M., Reid, I. R., Boonen, S., Bucci-Rechtweg, C., Cauley, J. A., Cosman, F., Cummings, S. R., Hue, T. F., Lippuner, K., Lakatos, P., Leung, P. C., Man, Z., Martinez, R. L., Tan, M., Ruzycky, M. E., Su, G., & 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 : the Official Journal of the American Society for Bone and Mineral Research, 27(2), 243-54. https://doi.org/10.1002/jbmr.1494
Black DM, et al. The Effect of 3 Versus 6 Years of Zoledronic Acid Treatment of Osteoporosis: a Randomized Extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res. 2012;27(2):243-54. PubMed PMID: 22161728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). AU - Black,Dennis M, AU - Reid,Ian R, AU - Boonen,Steven, AU - Bucci-Rechtweg,Christina, AU - Cauley,Jane A, AU - Cosman,Felicia, AU - Cummings,Steven R, AU - Hue,Trisha F, AU - Lippuner,Kurt, AU - Lakatos,Peter, AU - Leung,Ping Chung, AU - Man,Zulema, AU - Martinez,Ruvie Lou Maria, AU - Tan,Monique, AU - Ruzycky,Mary Ellen, AU - Su,Guoqin, AU - Eastell,Richard, PY - 2011/12/14/entrez PY - 2011/12/14/pubmed PY - 2012/6/14/medline SP - 243 EP - 54 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 27 IS - 2 N2 - 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. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/22161728/The_effect_of_3_versus_6_years_of_zoledronic_acid_treatment_of_osteoporosis:_a_randomized_extension_to_the_HORIZON_Pivotal_Fracture_Trial__PFT__ L2 - https://doi.org/10.1002/jbmr.1494 DB - PRIME DP - Unbound Medicine ER -