Effects Of Pamidronate Research Articles

Disodium Pamidronate Identifies Differential Osteoclastic Bone Resorption in Metastatic Prostate Cancer

In a controlled trial the effects of the osteoclast inhibitor disodium pamidronate were studied over a 6-month period in men with metastatic bone disease from prostate cancer. Using serial biochemical measurement of metabolic bone activity, and complementary subjective and quantitative bone histology, the effects of pamidronate were evaluated in tumour-free and metastatic regions of the skeleton, enabling analysis of the differential mechanisms of bone destruction in this disease. Following treatment, abnormally high markers of bone breakdown fell significantly (fasting urine hydroxyproline/creatinine (OHP): P less than 0.05; fasting urine calcium excretion (CaE): P less than 0.0001), confirming that activated osteoclasts play an integral role in the osteolytic process. Serial histomorphometry of bone from tumour-free areas showed that pamidronate restored abnormal levels of bone erosion to normal in 93% of cases. Suppression of bone destruction was also evident within metastases, although this was incomplete. The results confirm that osteoclast overactivity is responsible for a significant proportion of the accelerated osteolysis seen in both tumour-free and infiltrated bone in patients with prostate cancer. The differential effects in tumour-free and infiltrated bone suggest that the mechanisms of osteoclast activation may differ in metastatic and non-metastatic regions of the skeleton.

Differential action of pamidronate on trabecular and cortical bone in women with involutional osteoporosis

Since osteoporotic fractures are mainly related to the diminution of the bone mineral density (BMD), the effect of pamidronate (3-amino-1-hydroxy-propylidene) 1,1-bisphosphonate on the BMD of the spine, proximal femur and radius shaft was evaluated in an initial cohort of 35 postmenopausal women with at least one vertebral fracture due to involutional osteoporosis. Pamidronate was given continuously during 18 months in a daily oral dose of 4.8 to 6.0 mg/kg supplemented with calcium (1 g/day). BMD--measured by dual photon absorptiometry--increased after one year 5.3 +/- 1.0% (P less than 0.001) in lumbar spine and 5.3 +/- 1.5% (P less than 0.001) over trochanter. However no significant changes were observed in the BMD of the femoral neck, Ward's triangle or in the cortical bone of the radius shaft measured by single photon absorptiometry. Pamidronate also decreased significantly urinary hydroxyproline-creatinine excretion after 6 months and thereafter maintained a plateau. After 18 months of treatment the diminution was 42.6 +/- 4.9% (P less than 0.001). The differing effects of pamidronate on the BMD of lumbar spine and proximal femur might be ascribed to dissimilarities between the proportions of trabecular and cortical bone in these. These results suggest that pamidronate may be prescribed to prevent fractures in cases of involutional osteoporosis with a significant decrease of BMD in lumbar spine and/or trochanter.

Short-term Effects of Pamidronate on Biochemical Markers of Bone Metabolism in Osteoporosis—a Placebo-controlled Dose-finding Study

The bisphosphonates are potent inhibitors of osteoclastic bone resorption that mainly have been used for treatment of hypercalcaemia secondary to malignancy. We have performed a controlled dose-finding study of oral pamidronate that was given to 60 patients with a history of fracture of the distal forearm, an enhanced bone turnover and a lowered bone mineral density. Different doses of pamidronate, 75 mg and 150 mg daily, or placebo were given to parallel groups. Fasting specimens of blood and urine were collected before the treatment period and at regular intervals. Oral pamidronate caused a dose-related reduction on the biochemical markers of bone resorption, i.e. fasting urinary calcium, hydroxyproline, pyridinoline and deoxypyridinoline that was seen already after the first week. The inhibition was evident during the treatment period and 4 weeks thereafter but not 12 weeks after cessation of therapy. Also the levels of serum osteocalcin, a marker of bone formation, were lowered during treatment with the higher dose.