TY - JOUR
T1 - Follicle-stimulating hormone is associated with low bone mass in postmenopausal women
AU - Mattick, Lindsey J.
AU - Bea, Jennifer W.
AU - Hovey, Kathy M.
AU - Wactawski-Wende, Jean
AU - Cauley, Jane A.
AU - Crandall, Carolyn J.
AU - Tian, Lili
AU - Ochs-Balcom, Heather M.
N1 - Funding Information:
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.
Publisher Copyright:
© 2023, International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.
PY - 2023/4
Y1 - 2023/4
N2 - 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.
AB - 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.
KW - Bone loss
KW - Estradiol
KW - Follicle stimulating hormone
KW - Menopause
KW - Osteoporosis
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U2 - 10.1007/s00198-023-06676-z
DO - 10.1007/s00198-023-06676-z
M3 - Article
C2 - 36692543
AN - SCOPUS:85146780027
SN - 0937-941X
VL - 34
SP - 693
EP - 701
JO - Osteoporosis International
JF - Osteoporosis International
IS - 4
ER -