Idiopathic osteoporosis in premenopausal women

Abstract

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/m(2), P<0.01). A family history of osteoporosis and a history of fragility fractures were found more frequently in subjects than controls (P< or =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.

TBS reflects trabecular microarchitecture in premenopausal women and men with idiopathic osteoporosis and low-traumatic fractures

“…As shown in Fig. 2, we observed relationships between cancellous bone microarchitecture and serum markers of osteocyte, osteoblast and osteoclast activity, but these serum markers were within normal ranges for both genders [29,32]. After adjusting for the multiple models, BTMs (P1NP and CTX, but not sclerostin) were only significant for Tb.N, which resulted in an improvement of the predictability; this was not found for the three other cancellous μCT parameters.…”

“…Based on recent animal model data, BTMs can be used to differentiate early and late stages of primary or secondary osteoporosis [27]. The literature indicates a direct relationship between circulating sclerostin levels and age as well as positive correlations between sclerostin levels with trabecular density, number and thickness in both genders, but also gender differences in bone-specific serum values with regard to possible differences in the pathogenesis of idiopathic osteoporosis [28,29]. Particularly for nonosteoporotic young men (age ≤43 years), higher sclerostin levels are associated with higher aBMD and better bone microarchitecture as assessed by HR-pQCT.…”

Aspectos genéticos, influência do eixo GH/IGF1 e novas possibilidades terapêuticas na osteoporose idiopática

“…A história de osteoporose em familiares, principalmente de primeiro grau, é comum entre os pacientes com osteoporose idiopática, tanto homens (30) quanto mulheres (31) . Assim, o risco de osteoporose no jovem é maior quando o pai do paciente masculino ou a mãe da paciente feminina teve osteoporose na juventude.…”

“…Homens com osteoporose idiopática podem apresentar exacerbada reabsorção óssea, com aumento da excreção urinária de deoxipiridinolina e do peptídeo carboxiterminal do colágeno tipo I (CTX), associado a baixos níveis séricos de estradiol e testosterona livre, com SHBG (globulina de ligação dos hormônios sexuais) aumentada tendo correlação positiva com piridinolina e excreção de NTX (32) . Quadro laboratorial semelhante foi recentemente descrito em mulheres com osteoporose idiopática, as quais não apresentavam deficiência de IGF1 (31) . Entretanto, muitos pacientes com osteoporose idiopática não apresentam aumento nos marcadores bioquímicos de reabsorção, mas apenas menor capacidade de formação óssea, por vezes associada à hipercalciúria (33) .…”

ETIOLOGIYa I PATOGENEZ SNIZhENIYa KOSTNOYMASSY U ZhENShchIN MOLODOGO VOZRASTA (Obzor literatury)

“…Рост, масса тела и уровень физической активности опреде-ляют примерно 17-20% вариабельности пиковой костной мас-сы [70]. Показано, что костный метаболизм зависит от массы тела при рождении [6,13].…”