The 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. To assess the effects of exercise status and estrogen deficiency on osteoprotegerin (OPG) and its relationship to bone resorption in premenopausal exercising women. Cross-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. Subjects 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 microg/L/mmCr), compared with the SedMen and ExMen groups (184.5+/-22.4, 197.2+/-14.7 microg/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. Our 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.
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