Intermittent Oral Disodium Pamidronate in Established Osteoporosis: A 2 Year Double-Masked Placebo-Controlled Study of Efficacy and Safety

Abstract

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55-75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p < 0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p < 0.01) and total-body BMD for groups A and B (p < 0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p < 0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage.

Changes in bone remodelling and antifracture efficacy of intermittent bisphosphonate therapy: implications from clinical studies with ibandronate

“…30 Nitrogen-containing bisphosphonates have also been given intermittently, usually with drug-free intervals of 3 months. [45][46][47][48][49][50][51] However, in no such study was fracture incidence assessed.…”

Daily Oral Pamidronate in Women and Men With Osteoporosis: A 3-Year Randomized Placebo-Controlled Clinical Trial With a 2-Year Open Extension

“…Pamidronate has been used for many years in Leiden as a model compound to study the action and efficacy of nitrogen‐containing bisphosphonates (9–12) and was the first bisphosphonate of this class to be given to patients with osteoporosis (13,14) . Various modes of administration of oral or intravenous pamidronate were shown to prevent bone loss in patients with postmenopausal, idiopathic and glucocorticoid‐induced osteoporosis in open or controlled studies (13–20) . Early open studies suggested, in addition, that daily oral pamidronate induces a significant increase in bone mineral density of the spine (LS‐BMD) that is not confined to the first 2 years of therapy, as expected from an antiresorptive agent, but continues for at least 4 years of continuous treatment (14,21) .…”

Medical treatment of vertebral osteoporosis

“…Six publications were excluded because they reported on total number of fractures and the number of patients with at least one fracture was not published and could not be derived from published data [34, 46,73,76,80,85]. Sixteen publications were excluded because the duration of observation was less than 36 months [5,7,15 [61] had a median duration of only 21 months, but was kept in the final analysis as it was stopped early by the sponsor.…”