OBJECTIVE Changes in calcium homeostasis and bone mass around the clim
acteric are poorly understood. We examined relations between endocrine
factors and indices of bone mass and metabolism in healthy women appr
oaching the menopause. DESIGN Cross-section study. PATIENTS Sixty-eigh
t spontaneously menstruating women aged 45-55. MEASUREMENTS Bone densi
ty measured at lumbar spine (LS) and femoral neck (FN) using dual ener
gy X-ray absorptiometry and distal non-dominant forearm using peripher
al quantitative computed tomography. We recorded menstrual history, ph
ysical activity and dietary calcium, and measured serum calcium, phosp
hate, alkaline phosphatase, osteocalcin, vitamin D, fT3, T4, TSH, PTH,
FSH and oestradiol (E(2)), and urinary pyridinoline (PYD) and deoxypy
ridinoline (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 o
varian 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) pm
ol/l, P = NS). Serum phosphate was elevated in group C compared to gro
ups 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) mu mol/
mol creatinine) and DPD (15.9 (3.9) vs 12.0 (3.6) and 11.4 (3.6) mu mo
l/mol creatinine) excretion were also increased. There were no signifi
cant differences in vitamin D metabolites or osteocalcin. Multivariate
analysis suggested serum osteocalcin was positively related to physic
al activity and serum 1,25-dihydroxycholecalciferol levels. Serum free
T3 was positively correlated with urinary DPD excretion, and inversel
y 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 indirect
ly modulate PTH release.