THE EFFECT OF INTERMITTENT SLOW-RELEASE SODIUM-FLUORIDE AND CONTINUOUS CALCIUM CITRATE THERAPY ON CALCITROPIC HORMONES, BIOCHEMICAL MARKERSOF BONE METABOLISM, AND BLOOD-CHEMISTRY IN POSTMENOPAUSAL OSTEOPOROSIS

A detailed examination of calcitropic hormones and biochemical markers of bone turnover, serum chemistry, and blood hematology was performed in 75 postmenopausal women allocated to two groups: placebo plus calc ium citrate (400 mg Ca B.I.D.) (n = 36) or intermittent slow-release s odium fluoride (SRNaF, 25 mg B.I.D.) plus calcium citrate (n = 39). Af ter 2 years of therapy, a significant reduction in serum immunoreactiv e parathyroid hormone (PTH) was seen for both groups (43 +/- 18 SD-30 +/- 11 ng/liter, in placebo and 46 +/- 24-36 +/- 10, in SRNaF P < 0.00 01 for both groups). Serum 1,25(OH)(2)D significantly fell in placebo- treated patients (91 +/- 31-75 +/- 34 pmol/liter, P = 0.001) but did n ot change for SRNaF-treated patients. This difference in response betw een placebo and SRNaF-treated groups was significant, P = 0.005. Urina ry hydroxyproline significantly declined during treatment in both grou ps (130 +/- 61-76 +/- 38 mu mol/day, for placebo and 138 +/- 84-84 +/- 38 for SRNaF, P = 0.001). Similar decreases in urinary N-telopeptide of type I collagen were also observed for both groups (305 +/- 192-252 +/- 197 nmoles BCE/day for placebo and 356 +/- 230-220 +/- 197, P = 0 .0001 for SRNaF). Serum carboxyterminal propeptide of type I collagen (PICP) declined significantly in both the placebo and SRNaF groups (11 8 +/- 38-101 +/- 36 mu g/liter, and 116 +/- 47-105 +/- 39, P = 0.0027) . Serum osteocalcin did not change significantly for either group, but bone-specific alkaline phosphatase (BS-ALPase), another marker of bon e formation, demonstrated a significant fall in the placebo group at 2 years of therapy (16.2 +/- 6.7 U/liter-12.1 +/- 3.5, P = 0.009) and a small increase in the SRNaF-treated patients (13.0 +/- 4.1-15.0 +/- 4 .5). The observed difference in response of BS-ALPase between the plac ebo and treated groups was significant (P = 0.007). There were no sign ificant changes within or between treatment groups for blood hematolog y or serum chemistries. Mean values for all parameters remained within established normal ranges. These findings suggest that administration of calcium citrate inhibited PTH secretion and thereby reduced bone r esorption in both groups, indicated by a decline in serum PTH, urinary hydroxyproline, and N-telopeptide. A low turnover state of bone may h ave been produced in the placebo group taking calcium citrate alone, s ince serum PICP, BS-ALPase, and 1,25(OH)(2)D also decreased. The addit ion of SRNaF prevented serum 1,25(OH)(2)D from falling by an unknown m echanism. However, its anabolic action on the skeleton was best reflec ted by changes in BS-ALPase. Moreover, SRNaF appeared to exert no dele terious effects on blood chemistries or hematology during 2 years of a dministration.