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Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment?
J Clin Endocrinol Metab. 2014 Dec; 99(12):4546-54.JC

Abstract

CONTEXT

Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period.

OBJECTIVE

To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups.

DESIGN

This study is based on data from the 3 year extension of HORIZON.

SETTING

Subjects were in the ZOL arm of the Multicenter HORIZON trial.

PARTICIPANTS

One thousand two hundred thirty three women who previously received 3 ZOL treatments during the Core trial.

INTERVENTION

Randomization to three additional annual ZOL (Z6, n = 616) or placebo infusions (Z3P3, n = 617).

MAIN OUTCOMES

The risk of morphometric vertebral fractures (MorphVertFx) and clinical nonvertebral fractures (NVF).

RESULTS

The incidence of MorphVertFx in Z3P3 was predicted by femoral neck (FN) t-score ≤-2.5 [OR 3.3 (1.4, 8.0), p = .008], total hip (TH) t-score ≤-2.5 [OR 4.0 (1.8, 9.0), p = .0007], and incident MorphVertFx during Core [OR 4.75 (1.4, 16.8), p < .015]. Incidence of NVF was predicted by TH t-score [for 1 decline, HR 1.7 (1.2, 2.6), p = .008], incident NVF during Core [HR 2.5 (1.2, 5.3), p = .014], and prevalent vertebral fracture [HR 3.0 (1.4, 6.3), p = .005]. For MorphVertFx, there were no significant treatment subgroup interactions; absolute fracture reductions with continued ZOL were greatest in high-risk subgroups. For NVF, there were no significant treatment reductions overall or in subgroups and no significant interactions.

CONCLUSIONS

After 3 years of ZOL, in women who have a TH t-score above -2.5, no recent incident fracture and no more than one risk factor (almost 55% of the population), risk for subsequent fracture (over three additional years) is low if treatment is discontinued (for MorphVertFx, average risk 3.2% and for NVF, average risk 5.8%). In these patients, discontinuation for up to 3 years is reasonable.

Authors+Show Affiliations

Helen Hayes Hospital (F.C.), West Haverstraw, New York 10993; Department of Medicine (F.C.), Columbia University College of Physicians and Surgeons, New York, New York 10032; Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; Academic Unit of Bone Metabolism (R.E.), University of Sheffield, Sheffield, United Kingdon, S5 7AU; Department of Experimental Medicine (S.B.); Leuven University Hospital, Leuven, B-3000 Belgium; Department of Epidemiology and Department of Biostatistics (L.P., S.R.C., D.M.B.), University of California San Francisco, San Francisco, California 94107; and Faculty of Medical and Health Sciences (I.R.R.), University of Auckland, Auckland, New Zealand, 1023.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

25215556

Citation

Cosman, Felicia, et al. "Reassessment of Fracture Risk in Women After 3 Years of Treatment With Zoledronic Acid: when Is It Reasonable to Discontinue Treatment?" The Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 12, 2014, pp. 4546-54.
Cosman F, Cauley JA, Eastell R, et al. Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? J Clin Endocrinol Metab. 2014;99(12):4546-54.
Cosman, F., Cauley, J. A., Eastell, R., Boonen, S., Palermo, L., Reid, I. R., Cummings, S. R., & Black, D. M. (2014). Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? The Journal of Clinical Endocrinology and Metabolism, 99(12), 4546-54. https://doi.org/10.1210/jc.2014-1971
Cosman F, et al. Reassessment of Fracture Risk in Women After 3 Years of Treatment With Zoledronic Acid: when Is It Reasonable to Discontinue Treatment. J Clin Endocrinol Metab. 2014;99(12):4546-54. PubMed PMID: 25215556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: when is it reasonable to discontinue treatment? AU - Cosman,Felicia, AU - Cauley,Jane A, AU - Eastell,Richard, AU - Boonen,Steven, AU - Palermo,Lisa, AU - Reid,Ian R, AU - Cummings,Steven R, AU - Black,Dennis M, PY - 2014/9/13/entrez PY - 2014/9/13/pubmed PY - 2015/10/8/medline SP - 4546 EP - 54 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 99 IS - 12 N2 - CONTEXT: Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period. OBJECTIVE: To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups. DESIGN: This study is based on data from the 3 year extension of HORIZON. SETTING: Subjects were in the ZOL arm of the Multicenter HORIZON trial. PARTICIPANTS: One thousand two hundred thirty three women who previously received 3 ZOL treatments during the Core trial. INTERVENTION: Randomization to three additional annual ZOL (Z6, n = 616) or placebo infusions (Z3P3, n = 617). MAIN OUTCOMES: The risk of morphometric vertebral fractures (MorphVertFx) and clinical nonvertebral fractures (NVF). RESULTS: The incidence of MorphVertFx in Z3P3 was predicted by femoral neck (FN) t-score ≤-2.5 [OR 3.3 (1.4, 8.0), p = .008], total hip (TH) t-score ≤-2.5 [OR 4.0 (1.8, 9.0), p = .0007], and incident MorphVertFx during Core [OR 4.75 (1.4, 16.8), p < .015]. Incidence of NVF was predicted by TH t-score [for 1 decline, HR 1.7 (1.2, 2.6), p = .008], incident NVF during Core [HR 2.5 (1.2, 5.3), p = .014], and prevalent vertebral fracture [HR 3.0 (1.4, 6.3), p = .005]. For MorphVertFx, there were no significant treatment subgroup interactions; absolute fracture reductions with continued ZOL were greatest in high-risk subgroups. For NVF, there were no significant treatment reductions overall or in subgroups and no significant interactions. CONCLUSIONS: After 3 years of ZOL, in women who have a TH t-score above -2.5, no recent incident fracture and no more than one risk factor (almost 55% of the population), risk for subsequent fracture (over three additional years) is low if treatment is discontinued (for MorphVertFx, average risk 3.2% and for NVF, average risk 5.8%). In these patients, discontinuation for up to 3 years is reasonable. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/25215556/Reassessment_of_fracture_risk_in_women_after_3_years_of_treatment_with_zoledronic_acid:_when_is_it_reasonable_to_discontinue_treatment L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2014-1971 DB - PRIME DP - Unbound Medicine ER -