Idiopathic osteoporosis in premenopausal women

Although osteoporosis predominantly affects older postmenopausal women, low bone mineral density also occurs in men and younger women. In men, it is often unexplained by recognized secondary causes. These men with idiopathic osteoporosis have reductions in serum IGF-I as well as indices of reduced bone formation. Younger women also experience bone loss of unknown etiology (IOP). Whether premenopausal women with IOP have similar decreases in IGF-I levels and reduced indices of bone formation is unknown. We prospectively evaluated a group of premenopausal women with unexplained low bone mass and compared them to normal premenopausal women with respect to serum concentrations of IGF-I. Thirteen premenopausal women (34.2±2.3 years) with low bone density (mean lumbar spine T-score −2.26±0.20) were compared with 13 premenopausal women (35.7±1.7 years) with normal bone density of similar age, height and ethnic composition. Body mass index (BMI) was lower in subjects than controls (20.5±0.7 versus 25.2±1.1 kg/m2, P<0.01). A family history of osteoporosis and a history of fragility fractures were found more frequently in subjects than controls (P≤0.05). Calciotropic hormones did not differ between the two groups. In contrast to our observations in men with idiopathic osteoporosis, mean serum IGF-I concentrations did not differ between subjects and controls (subjects: 22.5±2.2 nmol/l versus controls: 20.8±1.6 nmol/l; NS). Moreover, serum IGF-I levels did not correlate significantly with serum estradiol or with BMD at either the lumbar spine or femoral neck. However, lower follicular phase serum estradiol levels among non-oral contraceptive users were found in subjects as compared to controls (subjects: 124.1±13 pmol/l versus controls 194.9±24 pmol/l, P=0.06). Calculated free, bioavailable estradiol levels were significantly lower overall in subjects than controls (0.6±0.1 versus 1.2±0.2 pmol/l, P<0.05). Total serum estradiol levels correlated with BMD at the femoral neck (r=+0.50; P<0.05). Free, bioavailable estradiol correlated with BMD and BMAD at the lumbar spine (r=+0.54, P<0.01 and r=+0.54, P<0.05, respectively) and femoral neck (r=+0.60 and r=+0.55 respectively, both P<0.01). Urinary NTX excretion, although within the normal premenopausal range, was 45% higher in subjects than controls (41.6±5.9 nmol BCE/l versus 28.3±2.4 nmol BCE/l; P<0.05). Bone-specific alkaline phosphatase activity was also higher (17.4±1.6 ng/ml versus 14.7±0.8 ng/ml), although the difference was not statistically significant. These results suggest differences in the pathogenesis of idiopathic osteoporosis in women as compared to men with IOP.