Uninterrupted oral bisphosphonate (pamidronate) therapy of patients with osteoporosis is not associated with chronic stimulation of parathyroid hormone secretion.

We have previously reported that long-term uninterrupted treatment of patients with osteoporosis with oral pamidronate is associated with increases in bone mineral content (BMC) of the lumbar spine which could not be explained by the antiresorptive action of the drug alone, raising the possibility of an additional effect of the treatment on skeletal tissue. Administration of suppressive doses of the bisphosphonate to patients with excessive osteoclastic resorption is followed by transient decreases in serum calcium and increases in parathyroid hormone (PTH) concentrations. It is possible, therefore, that chronic pamidronate therapy may stimulate PTH secretion, which in turn has been previously shown to have anabolic effects on the skeleton. To test this hypothesis we examined the changes in serum calcium. PTH and phosphate concentrations every 6 months in 33 patients with vertebral osteoporosis and no biochemical evidence of increased bone turnover, treated with oral pamidronate 150 mg daily. Serum alkaline phosphatase and urinary hydroxyproline excretion decreased significantly by 20% and 28%, respectively, after 6 months of treatment and remained at this level for the following 18 months. These changes were associated with significant increases in spinal BMC, as expected. Serum calcium, PTH and phosphate did not change from baseline values either in the whole group or when the patients were divided according to the use or not of calcium supplements. Our results exclude chronic stimulation of PTH secretion as a factor contributing to long-term increases in bone mass in patients with osteoporosis and adequate calcium intake during continuous oral pamidronate therapy.

Recovery of serum calcium concentrations following acute hypocalcemia in patients with osteoporosis on long-term oral therapy with the bisphosphonate pamidronate.

Bisphosphonates, synthetic compounds that are taken up preferentially by the skeleton and that suppress bone resorption, are currently used in the management of patients with osteoporosis. Long-term uninterrupted administration of low oral doses is the preferred mode of treatment in current clinical trials with newer bisphosphonates. These compounds have, however, a long residence time in the skeleton, and there is no information about their long-term effects on blood calcium homeostasis. We examined the effect of long-term therapy with oral bisphosphonate on blood calcium homeostasis following an acute hypocalcemic stimulus. Twenty patients with vertebral osteoporosis (10 untreated controls and 10 treated with oral pamidronate, 150 mg/day for at least 5 yr) were given intravenous infusions of sodium EDTA, and the concentrations of calcium and PTH in blood were followed for 24 h. Serum calcium concentrations decreased similarly in both groups (maximum decrease 0.21 mmol/L and 0.22 mmol/L, respectively). The recovery of serum calcium concentrations was identical in both groups, and all patients had normal concentrations at 24 h. Plasma PTH increased to a peak of 17.3 +/- 2.5 pmol/L in the control group and to 17.0 +/- 3.1 pmol/L in the pamidronate-treated patients. During the whole study period, there was no difference in either the peak PTH response or in the recovery of plasma PTH values between the two groups. However, when only PTH responses between 60 min and 24 h were examined, there were differences between the two groups. Plasma PTH values, although strictly within the normal range, were significantly higher in the pamidronate-treated patients (P = 0.001). There were no differences in the calcemic responses during this period. Further, there were no detectable changes in immunoreactive PTH-related protein in either group after the EDTA infusions. In conclusion, our study showed that longterm therapy with oral pamidronate does not affect the calcemic response to an acute hypocalcemic stimulus in patients with osteoporosis.