The effect of intermittent slow-release sodium fluoride and continuous calcium citrate therapy on calcitropic hormones, biochemical markers of 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 calcium citrate (400 mg Ca B.I.D.) (n = 36) or intermittent slow-release sodium fluoride (SRNaF, 25 mg B.I.D.) plus calcium citrate (n = 39). After 2 years of therapy, a significant reduction in serum immunoreactive 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 < 0.0001 for both groups). Serum 1,25(OH)₂D significantly fell in placebo-treated patients (91 ± 31-75 ± 34 pmol/liter, P = 0.001) but did not change for SRNaF-treated patients. This difference in response between placebo and SRNaF-treated groups was significant, P = 0.005. Urinary hydroxyproline significantly declined during treatment in both groups (130 ± 61-76 ± 38 μmol/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 (118 ± 38-101 ± 36 μg/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 bone 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 placebo and treated groups was significant (P = 0.007). There were no significant changes within or between treatment groups for blood hematology 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 resorption in both groups, indicated by a decline in serum PTH, urinary hydroxyproline, and N-telopeptide. A low turnover state of bone may have been produced in the placebo group taking calcium citrate alone, since serum PICP, BS-ALPase, and 1,25(OH)₂D also decreased. The addition of SRNaF prevented serum 1,25(OH)₂D from falling by an unknown mechanism. However, its anabolic action on the skeleton was best reflected by changes in BS-ALPase. Moreover, SRNaF appeared to exert no deleterious effects on blood chemistries or hematology during 2 years of administration.