Biochemical variables in pre- and postmenopausal women: Reconciling the calcium and estrogen hypotheses

There is controversy as to whether the rise in urinary calcium at the menop ause is the cause or the result of the rise in bone resorption at that time . In an attempt to resolve this issue, we have compared the relevant bioche mical variables in 102 premenopausal volunteers (mean age 37 years; range 2 1-52) and 86 apparently normal postmenopausal women (mean age 55 years; ran ge 40-60). We measured the fasting serum calcium, creatinine, proteins, ele ctrolytes and intact parathyroid hormone (PTH), and the urinary calcium and creatinine both after an overnight fast and in a 24-h collection. We calcu lated serum calcium fractions, creatinine clearance and the notional tubula r maximum reabsorptive capacity for calcium. Creatinine excretion and clear ance were lower in the post- than in the premenopausal women after correcti on for surface area and age. Total serum calcium was higher in the post- th an in the premenopausal women but this was accounted for by the higher liga nd concentrations in the former. Fasting and 24-h urinary calcium were also higher in the post- than in the premenopausal women due in part to the for mer's higher filtered load of calcium (due to their higher serum complexed calcium) but mainly to their reduced tubular reabsorption of calcium despit e their slightly raised serum PTH. Our analysis resolves the rise in urinar y calcium at the menopause into its two components: increased filtered load and reduced tubular reabsorption. The changes in these two variables, neit her of which can be attributed to increased bone resorption, produce an inc rease in calcium requirement that is sufficient to account for postmenopaus al bone loss. However, the translation of this menopausal increase in calci um requirement into an increase in bone resorption at near-normal serum PTH levels requires some menopause-dependent change in the responsiveness of t he bone to calcium demand. We suggest that this change may occur at the lev el of the osteoclasts and that estrogen may modify the calcium feedback set point in these cells in a manner analogous to calcitonin. This model resolv es the apparent conflict between the estrogen and calcium hypotheses and ex plains the synergism between these two treatment modalities.