1. To determine the relationships between parathyroid hormone activity and long-term sodium fluoride therapy in osteoporosis, cytochemical bioassays (for biologically active parathyroid hormone) were performed in 22 osteoporotic control patients and in 18 patients after 15 ± 10 months of treatment (60 mg of sodium fluoride daily). Ten patients were studied longitudinally by repeated metabolic balances and were therefore common to both groups. All patients were receiving mineral supplements.

2. Cross-sectional data showed a fourfold mean increase in biologically active parathyroid hormone on fluoride treatment (P < 0.005) together with a 51% increase in serum alkaline phosphatase (P < 0.005). Longitudinal data showed, in addition, a significant increase in the calcium balance of 2.4 ± 1.2 (sem) mmol daily (P < 0.05) and the development of a positive phosphorus balance (P < 0.02).

3. Fluoride-treated patients were then analysed in two groups according to the level of biologically active parathyroid hormone. Thirty-two per cent of values were above the upper limit of normal (18 pg/ml). The mean serum alkaline phosphatase level in this group showed no elevation above that of the control patients, the overall rise being accounted for entirely by patients with normal levels of biologically active parathyroid hormone. High levels of biologically active parathyroid hormone were also associated with relative hypophosphataemia (P < 0.01), relative hypercalciuria (P < 0.05) and an increased urine/faecal calcium ratio (P < 0.025).

4. Results show that long-term fluoride and calcium therapy increase biologically active parathyroid hormone in osteoporosis and that excessive parathyroid hormone activity may account for certain features of the refractory state.

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