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Follicle-stimulating hormone is associated with low bone mass in postmenopausal women

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Abstract

Summary

We evaluated the influence of two endogenous hormones on bone health in older women. Higher FSH was associated with bone disease, especially in lower estradiol environments. FSH attenuated the relationship between estradiol and bone. This may provide a mechanism through which future clinical research intervenes on bone loss.

Introduction/purpose

Despite preclinical evidence for an inverse association of follicle-stimulating hormone (FSH) and bone mineral density (BMD), no large epidemiologic studies have evaluated the separate and joint influences of FSH and estradiol on bone in postmenopausal women.

Methods

In a cross-sectional study of 675 postmenopausal women, we evaluated associations of serum FSH and dual X-ray absorptiometry (DXA)-classified areal BMD as well as low bone mass or osteoporosis (T-score <  − 1.0) of the femoral neck and total hip. We stratified this analysis by serum estradiol (cut at the median). We tested whether FSH mediates the association of estradiol and BMD using the Sobel test.

Results

In linear regression models, there was a significant inverse association of serum FSH with both femoral neck and total hip BMD (both p < 0.01) when adjusted for age, hormone therapy (HT) use, and diabetes. In fully adjusted logistic regression models, women in the highest FSH tertile had higher odds of low bone mass/osteoporosis at the femoral neck (OR = 2.98; 95% CI = 1.86–4.77) and at the total hip (OR = 1.74; 95% CI = 1.06–2.84) compared to those in the lowest FSH tertile. We report evidence of effect modification by estradiol in stratified models and an interaction term. FSH met all criteria of a mediator, including an estimated 70% attenuation of the estradiol-BMD relationship (Sobel p value < 0.001).

Conclusions

FSH is associated with higher odds of having low bone mass/osteoporosis even after accounting for HT use. FSH is a mediator of the relationship between estradiol and BMD in healthy postmenopausal women. Larger, prospective studies of FSH concentrations and bone health are needed.

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Funding

This work was supported by the National Ruth L Kirschstein National Research Service Award Predoctoral Fellowship 1F31AG071241-01. Additional support was provided by the Breast Cancer Research and Education Fund through New York State Department of Health Contract #C34926GG. Additional grants include NHLBI-CSB-WH-2016–01-CM, DOD #OS950077, and NIH R01 DE13505. The WHI program is funded by the National Heart, Lung, and Blood Institute through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. The WHI program is also funded by the National Heart, Lung, and Blood Institute through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005.

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Authors and Affiliations

  1. Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY, USA

    Lindsey J. Mattick, Kathy M. Hovey, Jean Wactawski-Wende & Heather M. Ochs-Balcom

  2. Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, USA

    Jennifer W. Bea

  3. Department of Medicine, University of Arizona, Tucson, AZ, USA

    Jennifer W. Bea

  4. Department of Epidemiology, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Jane A. Cauley

  5. Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Carolyn J. Crandall

  6. Department of Biostatistics, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY, USA

    Lili Tian

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  1. Lindsey J. Mattick
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Correspondence to Lindsey J. Mattick.

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Mattick, L.J., Bea, J.W., Hovey, K.M. et al. Follicle-stimulating hormone is associated with low bone mass in postmenopausal women. Osteoporos Int 34, 693–701 (2023). https://doi.org/10.1007/s00198-023-06676-z

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  • DOI: https://doi.org/10.1007/s00198-023-06676-z

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