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

Osteoporos Int. 1999;9(4):351-7. doi: 10.1007/s001980050158.


There is controversy as to whether the rise in urinary calcium at the menopause 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 biochemical variables in 102 premenopausal volunteers (mean age 37 years; range 21-52) and 86 apparently normal postmenopausal women (mean age 55 years; range 40-60). We measured the fasting serum calcium, creatinine, proteins, electrolytes and intact parathyroid hormone (PTH), and the urinary calcium and creatinine both after an overnight fast and in a 24-h collection. We calculated serum calcium fractions, creatinine clearance and the notional tubular maximum reabsorptive capacity for calcium. Creatinine excretion and clearance were lower in the post- than in the premenopausal women after correction for surface area and age. Total serum calcium was higher in the post- than in the premenopausal women but this was accounted for by the higher ligand 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 former's higher filtered load of calcium (due to their higher serum complexed calcium) but mainly to their reduced tubular reabsorption of calcium despite their slightly raised serum PTH. Our analysis resolves the rise in urinary calcium at the menopause into its two components: increased filtered load and reduced tubular reabsorption. The changes in these two variables, neither of which can be attributed to increased bone resorption, produce an increase in calcium requirement that is sufficient to account for postmenopausal bone loss. However, the translation of this menopausal increase in calcium requirement into an increase in bone resorption at near-normal serum PTH levels requires some menopause-dependent change in the responsiveness of the bone to calcium demand. We suggest that this change may occur at the level of the osteoclasts and that estrogen may modify the calcium feedback setpoint in these cells in a manner analogous to calcitonin. This model resolves the apparent conflict between the estrogen and calcium hypotheses and explains the synergism between these two treatment modalities.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Bone Resorption / metabolism
  • Calcium / blood
  • Calcium / urine*
  • Creatinine / blood
  • Creatinine / urine
  • Estrogens / metabolism*
  • Female
  • Humans
  • Kidney / metabolism
  • Metabolic Clearance Rate
  • Middle Aged
  • Parathyroid Hormone / blood
  • Postmenopause / metabolism*
  • Premenopause / metabolism*


  • Estrogens
  • Parathyroid Hormone
  • Creatinine
  • Calcium