Three-year oral clodronate treatment does not impair mineralization of newly formed bone--a histomorphometric study

Bisphosphonates have been used successfully in the treatment of malignant hypercalcemia and skeletal metastases. Recently, clodronate has been studied in adjuvant settings in primary breast cancer. However, long-term effect of adjuvant clodronate on bone histology has not been reported, whereas bone mineral density studies have been published. The aim of this study was to examine the effect and safety of long-term clodronate treatment on bone quality as measured by histomorphometric techniques from bone biopsies. A total of 299 patients with early stage breast cancer were randomized to receive adjuvant oral clodronate (1.6 g/day) or to a control group for 3 years. All patients had adjuvant treatment: premenopausal women had six cycles of chemotherapy and postmenopausal women had antiestrogen for 3 years. Trabecular bone quality was examined in transiliac bone biopsy specimens by using histomorphometric techniques in 28 clodronate treated and 35 control patients who were disease-free at 3 years and who allowed the biopsy specimen to be obtained. No statistically significant differences were found in the values of osteoid, mineral apposition rate, or mineralization lag time in bone biopsies between the clodronate and the control groups. Postmenopausal women who received two antiresorptive drugs, antiestrogen and clodronate, developed features of secondary hyperparathyroidism with increased eroded surface and osteoclast number. In premenopausal, women clodronate with adjuvant chemotherapy, which induced early menopause and rapid bone loss in most of the patients, seemed to conduct slight depression in bone formation. Three-year oral clodronate treatment does not impair mineralization of newly formed bone: however, clodronate with different adjuvant breast cancer treatments has a diverse impact on bone histomorphometry depending on the type of therapy.