The effect of exercise and estrogen on osteoprotegerin in premenopausal women

BackgroundThe benefits of exercise are widely recognized, however physically active women can develop exercise associated menstrual cycle disturbances such as amenorrhea (i.e., estrogen deficiency) secondary to a chronic energy deficiency.ObjectiveTo assess the effects of exercise status and estrogen deficiency on osteoprotegerin (OPG) and its relationship to bone resorption in premenopausal exercising women.DesignCross-sectional study of serum OPG, urinary c-telopeptides (uCTX), urinary estrone 3-glucuronide (E1G), urinary pregnanediol 3-glucuronide (PdG) and bone mineral density (BMD) measured on multiple occasions in 67 women. Volunteers were retrospectively grouped: 1) sedentary menstruating group (SedMen n = 8), 2) exercising menstruating group (ExMen, n = 36), and 3) exercising amenorrheic group (ExAmen, n = 23). One-way ANOVAs were performed, and LSD post-hoc tests were performed when differences were detected.ResultsSubjects were similar with respect to age (24.2 ± 1.0 years), weight (57.8 ± 1.7 kg), and height (164.3 ± 1.3 cm) (p > 0.05). ExMen and ExAmen groups were more aerobically fit (p = 0.003) and had less body fat (p = 0.002) than the SedMen group. Resting energy expenditure/fat free mass was lowest (p = 0.001) in the ExAmen groups. Mean E1G across the measurement period (p < 0.001) and overall E1G exposure as assessed by E1G area under the curve (AUC) (p < 0.001) were lower in the ExAmen group vs. the SedMen and ExMen groups. U-CTX-I was elevated (p = 0.033) in the ExAmen group (281.8 ± 40.3 μg/L/mmCr), compared with the SedMen and ExMen groups (184.5 ± 22.4, 197.2 ± 14.7 μg/L/mmCr, respectively). OPG was suppressed (p = 0.005) in the ExAmen group (4.6 ± 0.2 pmol/L) vs. ExMen group (5.2 ± 0.2 pmol/L), and OPG was lower in the SedMen group (4.1 ± 0.3 pmol/L) compared with the ExMen group. Findings were translated to BMD; the ExAmen group had suppressed total body BMD (p = 0.014) and L2–L4 BMD (p = 0.015) vs. the ExMen group.ConclusionsOur results suggest that OPG responds to the bone loading effect of exercise, and that suppressed OPG may play a role in the etiology of increased bone resorption observed in exercising women with chronic estrogen deficiency secondary to hypothalamic amenorrhea.