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 oestrog ens and the selective oestrogen receptor modulator (SERM)-raloxifene-is an interaction with calciotropic hormones. We studied the effects of raloxifen e on calcium-PTH homeostasis. PATIENTS AND MEASUREMENTS Calcium and EDTA infusions were performed in 32 p ost-menopausal women with osteoporosis (BMD T score < - 2.5). This cross-se ctional study was performed in the third year of the MORE (Multiple Outcome s 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, Na(3)EDTA (40 mg/kg BW*h) were given intravenousl y. The duration of infusions was based on individual plasma total calcium b efore 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 r egression models adjusted for age and BMI. Nine patients used placebo, 13 r aloxifene 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 cal cium at t = 0 (2.28 vs. 2.24 and 2.21; +/- 0.07 mmol/L; P = 0.03), lower pl asma 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 plas ma 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. I n contrast, the difference in PTH suppression during calcium load was not e xplained either by differences in plasma albumin or calcium. CONCLUSION Raloxifene did not have any detectable effect on the PTH set-poi nt. An effect on non-suppressible PTH secretion cannot be excluded.