Effects of the selective oestrogen receptor modulator-raloxifene-on calcium and PTH secretory dynamics in women with osteoporosis.

OBJECTIVES

A possible mechanism for the maintenance of bone mass by oestrogens and the selective oestrogen receptor modulator (SERM)-raloxifene-is an interaction with calciotropic hormones. We studied the effects of raloxifene on calcium-PTH homeostasis.

PATIENTS AND MEASUREMENTS: Calcium and EDTA infusions were performed in 32 post-menopausal women with osteoporosis (BMD T score < - 2.5). This cross-sectional study was performed in the third year of the MORE (Multiple Outcomes of Raloxifene Evaluation) trial, a double-blind, placebo-controlled study. After an overnight fast, calcium glubionate (5 mg/kg BW*h), and after 2.5 h of test-free interval, Na3EDTA (40 mg/kg BW*h) were given intravenously. The duration of infusions was based on individual plasma total calcium before the calcium infusion (t = 0), the target calcium (2.60 and 1.95 mmol/l, respectively), and desired mean calcium change (0.010 mmol/L*min). Blood samples were taken at 0 and every 5 minutes of both infusions. Plasma PTH levels were fitted into an inversed sigmoidal relation with plasma calcium. The effect of raloxifene on calcium-PTH homeostasis was tested in linear regression models adjusted for age and BMI. Nine patients used placebo, 13 raloxifene 60 mg/day and 10 raloxifene 120 mg/day.

RESULTS

Raloxifene use was associated with lower plasma albumin (40.7 +/- 1.8 vs. 38.0 +/- 2.0 and 38.5 +/- 2.3 g/l, for placebo, raloxifene 60 mg/day and raloxifene 120 mg/day, respectively, P = 0.01), lower plasma total calcium at t = 0 (2.28 vs. 2.24 and 2.21; +/- 0.07 mmol/L; P = 0.03), lower plasma total calcium at 50% of maximal PTH secretion (PTH set-point: 2.23 +/- 0.06 vs. 2.18 +/- 0.07 and 2.16 +/- 0.08 mmol/l, P = 0.06), and lower plasma non-suppressible PTH (0.84 +/- 0.19 vs. 0.75 +/- 0.10 and 0.73 +/- 0.05 pmol/l, P = 0.02). After correction for plasma albumin, the differences for plasma calcium at t = 0 and at PTH set-point were no longer significant. In contrast, the difference in PTH suppression during calcium load was not explained either by differences in plasma albumin or calcium.

CONCLUSION

Raloxifene did not have any detectable effect on the PTH set-point. An effect on non-suppressible PTH secretion cannot be excluded.