A longitudinal study of bone-related biochemical changes at the menopause.

OBJECTIVE: To evaluate the effects of the menopause on bone-related biochemical variables in a longitudinal study.
DESIGN: Recruitment by advertisement of premenopausal women over the age of 44 for measurement of selected variables and collection of blood and urine samples for deep freezing, followed by annual check of menopausal status and repeat collection of blood and urine samples for deep freezing after the menopausal transition. PATIENTS: A total of 104 women with confirmed premenopausal status and on no treatment likely to affect calcium or bone metabolism were admitted to the study over a period of 2 years. After 8 years, 43 of the volunteers had passed through the menopause and the study was closed. MEASUREMENTS: Radiocalcium absorption was measured at the first attendance and again after the menopausal transition. Calcium and other relevant variables were measured consecutively on paired thawed-out samples of blood and urine.
RESULTS: The data were complete in 34 subjects. In these women, there were highly significant correlations between the first and second measurements of most variables - serum calcium and fractions, radiocalcium absorption, vitamin D metabolites, PTH and others - indicating significant 'tracking' of these variables across the menopause. Within that framework there were significant rises in serum total and calculated ionized calcium (both P < 0.001) without change in mean serum parathyroid hormone (PTH). Radiocalcium absorption fell (P < 0.001) without change in serum 1,25D. There was a rise in fasting urinary calcium (P < 0.001) which could not be explained by the rise in filtered load and therefore represented a fall in TmCa (P < 0.001). There were significant rises in urinary bone resorption markers, pyridinoline and deoxypyridinoline (P < 0.001).
CONCLUSIONS: We conclude that the menopausal rise in calculated serum ionized calcium without fall in PTH, indicates a change in PTH set-point, and that the falls in gastrointestinal absorption and renal tubular reabsorption of calcium reflect the loss of an oestrogen action at these two sites. Although these changes are sufficient to explain the rise in calcium requirement at the menopause, the association of high bone resorption with normal serum PTH suggests also an increased sensitivity of bone to the action of parathyroid hormone. There is significant 'tracking' of many variables across the menopause despite very significant changes in their absolute values.