Bone mineral density and metabolism at an early stage of menopause when estrogen and calcium supplement are not used and without the interference of major confounding variables.

OBJECTIVES: To measure bone mineral density (BMD) and to screen for early biochemical abnormalities in bone mineral metabolism in the first five years of natural menopause when estrogen and calcium supplement are not used and in the absence of major confounding variables. SETTING: Two homogeneous and comparable groups (n = 30) of healthy pre- and postmenopausal Caucasian women living in a northern region (latitude 46 degrees N) were recruited during the mid-Spring/Summer season in a cross-sectional design. METHODS: Volumetric apparent BMAD (g/cm(3)) was calculated from areal BMD (g/cm(2)) which was evaluated by dual energy X-ray absorptiometry (Lunar) at both axial and peripheric (femur) sites using two sets of reference values (WHO criterion expressed as T-score and absolute values of areal density) in combination to bone specific biochemical measurements. RESULTS: BMD and BM(A)D were significantly lower in postmenopausal women for all lumbar sites, but not for Ward's triangle and any other femoral sites whereas free deoxypyridinoline (Dpd), urinary biochemical marker of bone resorption, was markedly (p < 0.0001) greater. Their serum calcium and phosphate were significantly higher without a difference in 1,25(OH)(2)D(3) and PTH. The prevalence of osteopenia in pre- and postmenopausal women was about 2-fold lower in both groups (26.6 and 46.9%, respectively) when lumbar (L) spine and femur neck were combined and using the criteria based on reference values of areal density instead of T-scores. CONCLUSIONS: The present study showed that the negative effects of estrogen deficiency on BMD and bone metabolism in early menopause occurred independently of the effect of major calcitropic hormones. Bone loss affects a non negligible proportion of premenopausal women. The prevalence of osteopenia in pre- and postmenopausal women varied according to the criterion used and anatomic site.

Chemical and biomechanical characterization of hyperhomocysteinemic bone disease in an animal model.

BACKGROUND: Classical homocystinuria is an autosomal recessive disorder caused by cystathionine beta-synthase (CBS) deficiency and characterized by distinctive alterations of bone growth and skeletal development. Skeletal changes include a reduction in bone density, making it a potentially attractive model for the study of idiopathic osteoporosis. METHODS: To investigate this aspect of hyperhomocysteinemia, we supplemented developing chicks (n = 8) with 0.6% dl-homocysteine (hCySH) for the first 8 weeks of life in comparison to controls (n = 10), and studied biochemical, biomechanical and morphologic effects of this nutritional intervention. RESULTS: hCySH-fed animals grew faster and had longer tibiae at the end of the study. Plasma levels of hCySH, methionine, cystathionine, and inorganic sulfate were higher, but calcium, phosphate, and other indices of osteoblast metabolism were not different. Radiographs of the lower limbs showed generalized osteopenia and accelerated epiphyseal ossification with distinct metaphyseal and suprametaphyseal lucencies similar to those found in human homocystinurics. Although biomechanical testing of the tibiae, including maximal load to failure and bone stiffness, indicated stronger bone, strength was proportional to the increased length and cortical thickness in the hCySH-supplemented group. Bone ash weights and IR-spectroscopy of cortical bone showed no difference in mineral content, but there were higher Ca2+/PO4(3-) and lower Ca2+/CO3(2-) molar ratios than in controls. Mineral crystallization was unchanged. CONCLUSION: In this chick model, hyperhomocysteinemia causes greater radial and longitudinal bone growth, despite normal indices of bone formation. Although there is also evidence for an abnormal matrix and altered bone composition, our finding of normal biomechanical bone strength, once corrected for altered morphometry, suggests that any increase in the risk of long bone fracture in human hyperhomocysteinemic disease is small. We also conclude that the hCySH-supplemented chick is a promising model for study of the connective tissue abnormalities associated with homocystinuria and an important alternative model to the CBS knock-out mouse.