The presence of both an energy deficiency and estrogen deficiency exacerbate alterations of bone metabolism in exercising women

Background: Bone loss in amenorrheic athletes has been attributed to energy deficiency-related suppression of bone formation, but not increased resorption despite hypoestrogenism. Objective: To assess the independent and combined effects of energy deficiency and estrogen deficiency on bone turnover markers in exercising women. Design: PINP, osteocalcin, U-CTX-I, TT₃, leptin, and ghrelin were measured repeatedly, and bone mineral density (BMD) was measured once in 44 exercising women. Resting energy expenditure (REE) was used to determine energy status (deficient or replete) and was corroborated with measures of metabolic hormones. Daily levels of urinary estrone and pregnanediol glucuronides (E1G, PdG), were assessed to determine menstrual and estrogen status. Volunteers were then retrospectively categorized into 4 groups: 1) Energy Replete + Estrogen Replete (EnR + E₂R), (n = 22), 2) Energy Replete + Estrogen Deficient (EnR + E₂D), (n = 7), 3) Energy Deficient + Estrogen Replete (EnD + E₂R), (n = 7), and 4) Energy Deficient + Estrogen Deficient (EnD + E₂D), (n = 8). Results: The groups were similar (p > 0.05) with respect to age (24.05 ± 1.75 yrs), weight (57.7 ± 2.2 kg), and BMI (21.05 ± 0.7 kg/m²). By design, REE/FFM (p = 0.028) and REE:pREE (p < 0.001) were lower in the EnD vs. EnR group, and the E₂D group had a lower REE:pREE (p = 0.005) compared to the E₂R group. The EnD + E₂D group had suppressed PINP (p = 0.034), and elevated U-CTX-I (p = 0.052) and ghrelin (p = 0.028) levels compared to the other groups. These same women also had convincing evidence of energy conservation, including TT₃ levels that were 29% lower (p = 0.057) and ghrelin levels that were 44% higher (p = 0.028) than that observed in the other groups. Energy deficiency was associated with suppressed osteocalcin, and TT₃ (p < 0.05), whereas estrogen deficiency was associated with decreased E1G (p < 0.02), and lower L2-L4 BMD (p = 0.033). Leptin was significant in predicting markers of bone formation, but not markers of bone resorption. Conclusions: When the energy status of exercising women was adequate (replete), there were no apparent perturbations of bone formation or resorption, regardless of estrogen status. Estrogen deficiency in exercising women, in the presence of an energy deficiency, was associated with bone loss and involved suppressed bone formation and increased bone resorption. These findings underscore the importance of avoiding energy deficiency, which is associated with hypoestrogenism, to avoid bone health problems.