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Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials.
J Bone Miner Res. 2013 Jun; 28(6):1348-54.JB

Abstract

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.

Authors+Show Affiliations

University of California San Francisco, San Francisco, CA, USA. aschwartz@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 available

Pub Type(s)

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

Language

eng

PubMed ID

23322676

Citation

Schwartz, Ann V., et al. "Effects of Antiresorptive Therapies On Glucose Metabolism: Results From the FIT, HORIZON-PFT, and FREEDOM Trials." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 28, no. 6, 2013, pp. 1348-54.
Schwartz AV, Schafer AL, Grey A, et al. Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Miner Res. 2013;28(6):1348-54.
Schwartz, A. V., Schafer, A. L., Grey, A., Vittinghoff, E., Palermo, L., Lui, L. Y., Wallace, R. B., Cummings, S. R., Black, D. M., Bauer, D. C., & Reid, I. R. (2013). Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 28(6), 1348-54. https://doi.org/10.1002/jbmr.1865
Schwartz AV, et al. Effects of Antiresorptive Therapies On Glucose Metabolism: Results From the FIT, HORIZON-PFT, and FREEDOM Trials. J Bone Miner Res. 2013;28(6):1348-54. PubMed PMID: 23322676.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. AU - Schwartz,Ann V, AU - Schafer,Anne L, AU - Grey,Andrew, AU - Vittinghoff,Eric, AU - Palermo,Lisa, AU - Lui,Li-Yung L, AU - Wallace,Robert B, AU - Cummings,Steven R, AU - Black,Dennis M, AU - Bauer,Douglas C, AU - Reid,Ian R, PY - 2012/08/01/received PY - 2012/12/07/revised PY - 2012/12/17/accepted PY - 2013/1/17/entrez PY - 2013/1/17/pubmed PY - 2013/12/16/medline SP - 1348 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 - 28 IS - 6 N2 - 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. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/23322676/Effects_of_antiresorptive_therapies_on_glucose_metabolism:_results_from_the_FIT_HORIZON_PFT_and_FREEDOM_trials_ L2 - https://doi.org/10.1002/jbmr.1865 DB - PRIME DP - Unbound Medicine ER -