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Premature osteoporosis is a frequent problem in female athletes. Current concepts suggest that a disruption of the hypothalamic-pituitary axis leads to hypoestrogenism, which then causes amenorrhea and osteoporosis. However, the underlying mechanisms have been insufficiently investigated. Osteoprotegerin (OPG) and soluble TNF-α receptor antagonist ligand (sRANKL) regulate the balance of osteoblasts and osteoclasts. Their role in the pathogenesis of osteoporosis in female athletes has not been studied yet.We measured OPG and sRANKL in relation to biochemical bone markers [osteocalcin (OC), bone alkaline phosphatase (BAP), serum β-crosslaps (CTx)] and female sex hormones [estradiol (E2) and luteinizing hormone (LH)] in fastening blood samples from 25 female elite endurance athletes and 25 matched controls.Athletes exhibited significantly higher levels of the bone resorption marker CTx than controls (0.61±0.26 vs. 0.44±0.15 ng/ml). OPG and sRANKL were not changed. Subgroup analysis revealed that athletes using oral contraceptives [A-OCC(−)] had significantly higher levels of CTx (0.82 ± 0.20 vs. 0.50 ± 0.14 ng/ml), BAP [37.3 (23.2–54.4) U/l vs. 25.2 (20.3–35.6) U/l] and OPG (3.4 ± 0.8 vs. 2.7 ± 0.8 ng/ml) than controls who did not use oral contraceptives [C- OCC(−)]. While the difference for CTx exceeded the least significant change in this marker by approximately 30%, the differences for the bone formation markers OC and BAP were close to the least significant change. In athletes using oral contraceptives [A- OCC(+)] we found no differences compared to controls.A-OCC(−) athletes have increased bone turnover with a particular stimulation of bone resorption. The increased bone resorption is not accompanied by a shift of the OPG/sRANKL relationship towards an osteoclastogenic constellation. Since increased bone resorption was not detectable in A-OCC(+) athletes, it can be suggested that OCC use might protect bone health in female athletes.