Document Detail

Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials.
MedLine Citation:
PMID:  23322676     Owner:  NLM     Status:  MEDLINE    
In rodent models, undercarboxylated osteocalcin (ucOC) acts as a hormone that promotes insulin sensitivity and secretion. If ucOC plays a similar role in humans, then antiresorptive therapies, which reduce ucOC levels, may increase the risk of insulin resistance and diabetes. We tested whether antiresorptive therapies result in higher fasting glucose, increased weight, or greater diabetes incidence in post hoc analyses of three randomized, placebo-controlled trials in postmenopausal women: Fracture Intervention Trial (FIT) (N = 6151) of alendronate (4 years), Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly Pivotal Fracture Trial (HORIZON-PFT) (N = 7113) of zoledronic acid (3 years), and Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial (N = 7076) of denosumab (3 years). Fasting glucose was measured annually in FIT and HORIZON in a subset of women, and every 6 months in FREEDOM in all participants. Weight was measured annually in all trials. Incident diabetes was identified from adverse event reports, initiation of diabetes medication, or elevated fasting glucose. Differences in fasting glucose changes from randomization to trial conclusion between treatment and placebo groups were not statistically significant: -0.47 mg/dL in FIT, 0.20 mg/dL in HORIZON-PFT, and 0.09 mg/dL in FREEDOM, all p > 0.6. Weight change differed between treatment and placebo groups in FIT (0.32 kg, p = 0.003) and FREEDOM (0.31 kg, p = 0.023) but not in HORIZON-PFT (0.15 kg, p = 0.132). In the three trials combined, diabetes occurred in 203 and 225 women assigned to treatment or placebo, respectively. Diabetes incidence was not increased in any of the treatment groups or in the pooled estimate (pooled relative risk [RR] = 0.90; 95% confidence interval [CI] 0.74-1.10). Antiresorptive therapy does not have a clinically important effect on fasting glucose, weight, or diabetes risk in postmenopausal women. Contrary to predictions from mouse models, reduced bone turnover does not appear to play a significant role in glucose metabolism in humans.
Ann V Schwartz; Anne L Schafer; Andrew Grey; Eric Vittinghoff; Lisa Palermo; Li-Yung L Lui; Robert B Wallace; Steven R Cummings; Dennis M Black; Douglas C Bauer; Ian R Reid
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  28     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-22     Completed Date:  2013-12-09     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1348-54     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Society for Bone and Mineral Research.
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MeSH Terms
Blood Glucose / metabolism*
Body Weight / drug effects
Bone Density Conservation Agents / administration & dosage*,  adverse effects
Diabetes Mellitus / blood,  chemically induced
Disease Models, Animal
Fasting / blood*
Follow-Up Studies
Fractures, Bone / blood,  epidemiology,  prevention & control*
Insulin Resistance
Middle Aged
Osteoporosis, Postmenopausal / blood*,  drug therapy*,  epidemiology
Time Factors
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/Bone Density Conservation Agents

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