Response to Letter to the Editor: “Association Between Cortical Bone Microstructure and Statin Use in Older Women”

We welcome Dr. Al-Khazaali and coauthors’ interest in our recent publication (1). They raise some questions about our study on statin use and cortical bone microstructure in older women. Based on previous studies (2, 3), reporting poorer cortical bone microstructure in patients with diabetes, they propose that the higher prevalence of diabetes among women treated with statins could have affected the obtained results of our study, even though we performed statistical adjustments for difference in diabetes prevalence in our analysis. To eliminate this potential bias, they suggest that we exclude women with diabetes from the analysis. In contrast to previous studies (2, 3), we have previously reported that older women with diabetes had lower cortical porosity, at least at the radius, than women without diabetes, in a large subset of the whole SUPERB cohort (4). Therefore, we agree that it is reasonable that diabetes prevalence could have an impact on the associations between statin use and cortical bone microstructure. As a consequence, we tested the associations (by using linear regression analysis with adjustments for confounders) between statin use, cortical volumetric bone mineral density, and cortical porosity in the whole cohort, excluding women with diabetes. In these analyses, statin use was still significantly associated with lower cortical porosity and higher cortical volumetric bone mineral density at both the radius and tibia. The associations were highly similar to those obtained in our previous analysis, in which we adjusted for diabetes prevalence (1). Thus, diabetes prevalence did not influence the association between statin use and cortical bone microstructure in our cohort. Furthermore, Dr. Al-Khazaali and coauthors criticize our suggestion that randomized controlled trials are warranted to determine any possible beneficial effect of statins on the skeleton. We respectfully disagree. Statins are used by a large proportion of the older population, and if positive effects of statins on the skeleton can be confirmed, the threshold for starting statins for other indications could be lowered. On a population level, even small individual effects on bone density could result in fewer fractures in the older population. Using precise measurements capturing the variation of cortical bone characteristics, a randomized controlled trial would not have to be very large and expensive but could still be effective in determining the effect of statins on bone. This strategy was recently shown to be successful in determining the effect of beta-blockers on bone, in a comprehensive study recently presented by Dr. Khosla’s research group at the Mayo Clinic (5). They unraveled potential mechanisms and demonstrated that treatment with selective (for β1-adrenergic receptors) beta-blockers increased bone mineral density at the ultradistal radius in healthy postmenopausal women. Thus, a similar study investigating the effect of statins on especially cortical bone should be feasible.

Acknowledgments

Disclosure Summary: B.A.M.L. has received lecture fees from Bayer. A.G.N. has received lecture fees from Shire and Pfizer. M.L. has received lecture fees from Amgen, Lilly, Meda, Renapharma, and UCB Pharma and consulting fees from Amgen, Radius Health, UCB Pharma, Renapharma, and Consilient Health. K.F.A. has received lecture fees from Meda/Mylan, Lilly, and Amgen. The remaining authors have nothing to disclose.

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