Short-Term Effect of Estrogen on Human Bone Marrow Fat

Abstract

Bone marrow fat, an unique component of the bone marrow cavity increases with aging and menopause and is inversely related to bone mass. Sex steroids may be involved in the regulation of bone marrow fat, because men have higher bone marrow fat than women and clinical observations have suggested that the variation in bone marrow fat fraction is greater in premenopausal compared to postmenopausal women and men. We hypothesized that the menstrual cycle and/or estrogen affects the bone marrow fat fraction. First, we measured vertebral bone marrow fat fraction with Dixon Quantitative Chemical Shift MRI (QCSI) twice a week during 1 month in 10 regularly ovulating women. The vertebral bone marrow fat fraction increased 0.02 (95% CI, 0.00 to 0.03) during the follicular phase (p ¼ 0.033), and showed a nonsignificant decrease of 0.02 (95% CI, -0.01 to 0.04) during the luteal phase (p ¼ 0.091). To determine the effect of estrogen on bone marrow fat, we measured vertebral bone marrow fat fraction every week for 6 consecutive weeks in 6 postmenopausal women before, during, and after 2 weeks of oral 17-b estradiol treatment (2 mg/day). Bone marrow fat fraction decreased by 0.05 (95% CI, 0.01 to 0.09) from 0.48 (95% CI, 0.42 to 0.53) to 0.43 (95% CI, 0.34 to 0.51) during 17-b estradiol administration (p < 0.001) and increased again after cessation. During 17-b estradiol administration the bone formation marker procollagen type I N propeptide (P1NP) increased (p ¼ 0.034) and the bone resorption marker C-terminal crosslinking telopeptides of collagen type I (CTx) decreased (p < 0.001). In conclusion, we described the variation in vertebral bone marrow fat fraction among ovulating premenopausal women. And among postmenopausal women, we demonstrated that 17-b estradiol rapidly reduces the marrow fat fraction, suggesting that 17-b estradiol regulates bone marrow fat independent of bone mass.

Daily leptin blunts marrow fat but does not impact bone mass in calorie-restricted mice

“…In addition, there may be crosstalk between leptin, estrogen and the GH-IGF-1 axis, both of which are suppressed in CR in humans and animal models (Devlin et al 2010; Misra and Klibanski 2011; Mobbs, et al 2001). Postmenopausal estrogen deficiency in women is associated with MAT expansion, and estrogen replacement increases serum leptin and decreases marrow adiposity (Limonard, et al 2015; Syed, et al 2008). GH deficiency leads to expansion of MAT that is attenuated by GH replacement in dwarf ( dw/dw) rats (Gevers, et al 2002) and in hypophysectomized mice and rats (Menagh, et al 2010).…”

Quantitative MRI and spectroscopy of bone marrow

“…Regarding the mineralized component, bone marrow characterization remains an important aspect of better understanding the pathophysiology of bone loss induced by both primary and secondary osteoporosis. In addition to the relationship between bone marrow fat fraction and BMD in primary osteoporosis, bone marrow fat changes have been also reported in secondary osteoporosis patients, like patients with chronic kidney disease, in prostate cancer patients treated with androgen deprivation therapy, and in women receiving estrogen …”

Bone–Fat Interaction

“…61 The changes in marrow adiposity are most evident in the axial skeleton and it has been reported that the increase in MAT can occur quickly after withdrawal of estrogen or decrease rapidly in response to exogenous estrogen. 62 Furthermore, the fatty acid composition of MAT in postmenopausal women also follows a similar profile demonstrating lower saturated fatty acids and increased monounsaturated fatty acids, particularly in participants with previous fracture. 63 This is particularly interesting given the opposite observation in T2DM.…”