SKELETAL METABOLISM IN PATIENTS WITH OSTEOPOROSIS AFTER DISCONTINUATION OF LONG-TERM TREATMENT WITH ORAL PAMIDRONATE

Bisphosphonates are used with increasing frequency in the treat ment of patients with osteoporosis. Continuous administration of low doses of nitrogen-containing bisphosphonates by mouth is the preferred mode of therapy. The skeletal half-life of bisphosphonates is long, however, and little is known about their long term effects on skeletal metabolism. We examined the changes in biochemical parameters of bone turnover [serum alkaline phosphatase and urinary hydroxyproline (OHP)], in bone mineral density, and in fracture frequency after discontinuation of long term (mean, 6.5 yr; range, 5-9 yr) therapy with oral pamidronate (150 mg/day) in 30 patients with osteoporosis and vertebral fractures. Serum alkaline phosphatase and urinary OHP were significantly lower at the end of long term treatment (90% and 72% of basal values, respectively). Serum alkaline phosphatase had increased to basal values within 6 months of stopping treatment, whereas OHP increased significantly to a maximum average of 92% of pretreatment values. There was no change in the every B-month bone mineral density measurements of the lumbar spine and the femoral neck during the 2 yr after stopping treatment. Spine fracture index, calculated by the method of Raymakers and co-workers, was 0.83 +/- 0.12 before treatment, 0.85 +/- 0.12 at the end of treatment, and 0.85 +/- 0.13 2 yr after stopping treatment (nonsignificant). There was also no significant change in the rate of new vertebral fractures on or up to 2 yr after stopping treatment (48.5 of 1000 and 46.5 of 1000 patient yr, respectively). Our data demonstrate that the sustained suppression of bone turnover induced by long term treatment with pamidronate is readily reversible on stopping treatment. The beneficial effect of this treatment regimen on the skeleton, however, appears to be maintained for at least 2 yr after discontinuation of treatment.