Bone mass and metabolism in women aged 45–55

OBJECTIVE Changes in calcium homeostasis and bone mass around the climacteric are poorly understood. We examined relations between endocrine factors and indices of bone mass and metabolism in healthy women approaching the menopause. DESIGN Cross-section study. PATIENTS Sixty-eight spontaneously menstruating women aged 45–55. MEASUREMENTS Bone density measured at lumbar spine (LS) and femoral neck (FN) using dual energy X-ray absorptiometry and distal non-dominant forearm using peripheral quantitative computed tomography. We recorded menstrual history, physical activity and dietary calcium, and measured serum calcium, phosphate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH, FSH and oestradiol (E₂), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion. RESULTS Using serum FSH level as a marker of ovarian function, 63 subjects could be classified into one of three groups: group A (serum FSH <10 U/l, n = 29), group B (10–35 U/l, n = 27) and group C (>35 U/l, n = 7). Bone density fell with declining ovarian function at the LS, FN and forearm trabecular (but not cortical) sites. Serum PTH was lower in group A vs B (mean (SD) 2.68 (0.97) vs 3.52 (1.17) pmol/l, P < 0.05), but similar to group C (2.90 (1.09) pmol/l, P = NS). Serum phosphate was elevated in group C compared to groups A and B (1.17 (0.15) vs 1.04 (0.11) and 1.05 (0.13) mmol/l, P < 0.05), and urinary PYD (61.1 (8.0) vs 50.4 (11.6) and 43.9 (8.1) μmol/mol creatinine) and DPD (15.9 (3.9) vs 12.0 (3.6) and 11.4 (3.6) μmol/mol creatinine) excretion were also increased. There were no significant differences in vitamin D metabolites or osteocalcin. Multivariate analysis suggested serum osteocalcin was positively related to physical activity and serum 1,25-dihydroxycholecalciferol levels. Serum free T3 was positively correlated with urinary DPD excretion, and inversely related to serum PTH. In all subjects, serum PTH was related to body weight (r = 0.38, P = 0.002). CONCLUSIONS Declining ovarian function before menopause is accompanied by reductions in bone mass and altered calcium metabolism. Free T3 may regulate bone resorption and indirectly modulate PTH release.     

Expression of α5 (CD49e) and α6 (CD49f) Integrin Subunits on T Cells in the Circulation and the Lamina Propria of Normal and Inflammatory Bowel Disease Colonic Mucosa

Intestinal lamina propria T cells are believed to be derived, via the systemic circulation, from gut-associated lymphoid tissue. After migration into the lamina propria, T cells are capable of luminally directed migration following the loss of surface epithelial cells. For adhesion and migration within the extracellular matrix, T cells are likely to utilize the integrin family of adhesion molecules. The aim of this study was to quantitatively and qualitatively investigate the expression of α₅ and α₆ integrin subunits on the surface of human T cells that: (a) migrated out of the lamina propria, (b) remained resident within the matrix and (c) were present in the circulation. In both subpopulations of CD4 and CD8-positive T cells, from both normal and inflamed (inflammatory bowel disease) colonic mucosa, there were significantly fewer α₅ and α₆-positive cells than in the peripheral blood. In addition, there were significantly fewer α₆ integrin molecules on the surface of CD4 and CD8-positive lamina propria T-cell subpopulations, compared with those in the circulation. Our studies suggest that, following migration into the lamina propria, there is down-regulation of α₅ and α₆ integrin-subunit expression on the surface of T cells. Molecules other than members of very late activation antigen-5 (VLA-5) (α₅β₁) and VLA-6 (α₆β₁) families of adhesion molecules are likely to be important in interactions with extracellular components in the lamina propria of normal and inflamed human colonic mucosa.     

The early effects of radioiodine therapy for hyperthyroidism on biochemical indices of bone turnover

OBJECTIVE We investigated the early changes following radioiodine therapy for hyperthyroidism, in biochemical indices of bone synthesis and degradation, and their relationship to circulating thyroid hormone concentrations. DESIGN Prospective follow-up over the first 12 weeks after radioiodine therapy. PATIENTS Six women with clinical and biochemical evidence of hyperthyroidism. MEASUREMENTS Serum Concentrations of T4, free T3 and osteocalcin, and urinary excretion of the pyridinium cross-links, pyridinaline and deoxypyridinaline, measured before and weekly for 12 weeks after administration of radioiodine therapy. RESULTS Biochemical indices of bone metabolism were elevated prior to treatment. There was a brisk reduction in circulating thyroid hormones levels paralleled by a similar fall In pyridinlum cross-llnk excretion, which had returned to normal in five patients by the end of the study. There was a positive correlation between pyridinium cross-link excretion and thyroid hormone concentrations. There was no significant change in serum osteocalcin. CONCLUSIONS Treatment of hyperthyroidism results in prompt correction of the associated increased rate of bone collagen degradation suggesting that effective early correction of hyperthyroidism is desirable to limit its detrimental effect on skeletal mass.     

7-ribosyl-3-deazaguanine—Mechanism of antibacterial action

The mechanism by which 7-ribosyl-3-deazaguanine $\text{[7}\text{R}\text{3}\text{DG}\text{, 6-}\text{amino}\text{-3-β-}\text{d}\text{-}\text{ribofuranosylimidazo}\text{[4,5-c]}\text{pyridin}\text{-4(5H)-}\text{one}\text{]}$ exerts its antibacterial effect was examined. Escherichia coli was found to contain an enzyme that exhibited the properties of a nucleoside phosphorylase and that converted 7R3DG to 3-deazaguanine (3DG, 6-aminoimidazo[4,5-c]pyridin-4(5H)-one], but no mammalian system that was examined (Erilch ascites, rat liver and human liver) was able to convert 7R3DG to 3DG. The 3DG arising from the phosphorolysis of 7R3DG was converted to 3-deaza-GMP [3DGMP, 6-amino-l-β-D-riboluranosylimidazo [4,5-c]pyridin-4(5H)-one-5′-phosphate] by the guanine phosphoribosyltransferase present in E. coli. A strain of E. coli, resistant to 7R3DG, was found to lack this enzyme and, therefore, was unable to convert 3DG to 3DGMP.