1. We studied the effect of mineral supplementation and its duration is osteoporosis by analysing the calcium and phosphorus balances of 49 treated osteoporotic patients whose median length of calcium treatment was 19 weeks with a range of 8 days to over 4 years. Forty-four studies satisfied statistical criteria of reproducibility and included 35 women (10 also receiving oestrogen replacement therapy) and nine men. 2. Mean calcium balance was positive in women taking calcium supplements alone, +1.9 ± 2.5 mmol daily ( P < 0.002), and was significantly more positive ( P < 0.05) in women also taking oestrogens, +4.2 ± 2.1 mmol daily. Calcium balance was not significantly positive in men. 3. Calcium balance correlated negatively with duration of supplementation, but, significantly, only when duration of supplementation was expressed logarithmically ( r = −0.401, P < 0.01) giving the regression equation y = 4.2–1.6 log x , where y = calcium balance in mol/day and x = duration of supplementation in weeks. Theoretical net calcium retention, without allowance for dermal loss, could be calculated by integration. 4. Mean phosphorus balance was significantly positive in both groups of women and in the whole population. Although its correlation with duration of supplementation did not reach statistical significance ( P < 0.1), the ratio of the regression slopes for calcium and phosphorus, 1.5:1, corresponded to their molar ratio in bone. 5. These statistics are, we believe, the first to describe an exponential decline in calcium balance during mineral treatment of osteoporosis, but they firmly suggest that such treatment, with or without oestrogen therapy, conveys temporary benefit.

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.