Clodronic Acid in the Treatment of Postmenopausal Osteoporosis

Abstract

Clodronic acid, a first-generation bisphosphonate, has been successfully used in the treatment of high bone turnover states, Paget's disease and osteolytic bone metastases. However, controversies remain over its optimal dosage and method of administration in the treatment of postmenopausal osteoporosis. In this study we aimed to evaluate the effect of clodronic acid treatment for 3 years on bone mineral density (BMD) in women with postmenopausal osteoporosis. This was a prospective, open-label, randomised, controlled study that was conducted in an outpatient clinic at the Bone Metabolism Unit of a tertiary referral centre university hospital. Thirty postmenopausal women (age range 48-73 years) with osteoporosis and a control group of 49 osteoporotic women (age range 47-74 years) received randomised therapy. The clodronic acid group of participants received oral doses of clodronic acid 800 mg plus elemental calcium 500 mg and 400 IU of vitamin D daily, while the control group was treated with calcium and vitamin D only. BMD was measured by dual energy x-ray absorptiometry at yearly intervals. Biochemical markers of bone turnover were also measured. In this clinical study of postmenopausal women with osteoporosis, 36 months of clodronic acid treatment significantly increased average femoral neck BMD by 3.2 +/- 2.9%, trochanter BMD by 2.2 +/- 2.9% and lumbar spine BMD by 3.1 +/- 3%. In the control group, femoral neck, trochanter and lumbar spine BMD decreased by -6 +/- 2.7%, -7.3 +/- 2.5% and -5.4 +/- 2%, respectively (p<0.01, p<0.05 and p<0.05 for clodronic acid vs control, respectively). There was a significant decrease in urinary hydroxyproline (-38.3%) over 3 years in the clodronic acid group compared with baseline (p<0.05), while no significant change occurred in the control group. Clodronic acid was well tolerated and compliance was good. There were no clinically meaningful differences in the incidence of individual adverse events between the groups. These results indicate that daily oral administration of clodronic acid 800 mg provides benefits to skeletal bone density in osteoporotic postmenopausal women. Calcium and vitamin D supplementation alone did not prevent further bone loss.