2 YEARS EFFECTIVENESS OF INTRAVENOUS PAMIDRONATE (APD) VERSUS ORAL FLUORIDE FOR OSTEOPOROSIS OCCURRING IN THE POSTMENOPAUSE

Bisphosphonates seem to be effective as antiresorptive agents in the prevention and treatment of osteoporosis. However, the optimal dose and route of administration as well as the specific effects on cortical or trabecular bone have not been clarified. To compare pamidronate (APD) with fluoride (F) in the therapy of postmenopausal osteoporosis, 32 osteoporotic women were treated for 2 years either with APD (30 mg as a single intravenous infusion over 1 h every 3 months, n = 16, mean age 65 years) or with fluoride orally (20-30 mg F/day, n = 16, mean age 67 years) in an open study. Both groups received 1 g calcium and 1000 U vitamin D per day, but no estrogens or other drugs acting on bone. Both groups showed the same initial mean number of fractures per patient (2.8 and 2.7). Bone densitometry was performed every 6 months at three sites: lumbar spine and hip with dual-energy X-ray absorptiometry (BMD), distal forearm with single photon absorptiometry and lumbar spine with quantitative computed tomography. Biochemical assessment was performed in blood and urine every 3 months. Lumbar BMD (g/cm2, mean +/- SEM) increased from 0.632 (+/- 0.030) at time 0 to 0.696 (+/- 0.028) at 24 months in the APD group (p < 0.001), and from 0.684 (+/- 0.025) to 0.769 (+/- 0.028) in the fluoride group (p < 0.001). Femoral neck BMD increased significantly from 0.558 (+/- 0.025) to 0.585 (+/- 0.025) (p < 0.01) in the APD group, whereas it did not change in the fluoride group. Forearm SPA (g/cm) increased from 0.90 (+/- 0.08) to 0.97 (+/- 0.10) (p < 0.01) in the APD group, whereas it decreased from 0.94 +/- (0.06) to 0.90 (+/- 0.06) (p < 0.05) in the fluoride group. Plasma calcium, parathormone and creatinine did not change in any group. Urinary hydroxyproline/creatinine, serum osteocalcin and alkaline phosphatase decreased significantly with APD, but did not change with fluoride, except for an increase in osteocalcin. Two new vertebral fractures occurred with APD and 6 with fluoride, plus 1 hip fracture. Side effects were a transient fever with flu-like symptoms in 5 patients after the first infusion of APD, rigors and mild phlebitis in 1 patient. Fluoride was associated with 5 transient arthralgias and 4 mild gastric intolerances, and treatment was interrupted in 2 patients with distal stress fractures. While fluoride increased only lumbar BMD, intermittent intravenous APD increased lumbar, hip and radial BMD in postmenopausal osteoporosis and was well tolerated.