Intramuscular clodronate therapy in postmenopausal osteoporosis

Long-term daily administration of oral bisphosphonates has been effective i n the treatment of postmenopausal osteoporosis, but the duration, mode and cost of the therapy may sometimes affect patient compliance. In Italy, the bisphosphonate clodronate is also available via the intramuscular (i.m.) ro ute of administration, and the present study was performed to test its effi cacy in postmenopausal osteoporosis, Ninety osteoporotic postmenopausal wom en were enrolled in a randomized, controlled 3 year study. The diet of all patients was adjusted to provide 1200-1300 mg of calcium daily, eventually by administration of supplements. Patients were randomly assigned to no the rapy (30 patients) or to receive clodronate 100 mg i.m. either every 2 week s (30 patients) or 1 week (30 patients). The i.m. injection caused substant ial pain at the site of injection, which led to treatment withdrawal in alm ost 50% of the patients receiving weekly dosing. In control patients, a pro gressive, slow decline in spine and femoral bone mineral density (BMD), whi ch became statistically significant at the end of the second year of observ ation, was observed. In the patients given weekly i.m. clodronate, spinal B MD rose by 3.8% (+/-7.3 SD) within 6 months. A slight, nonsignificant incre ase was observed thereafter, such that, at the completion of 3 years of obs ervation, the mean gain was 4.5% (+/-6.3). In the patients treated with inj ections of 100 mg of clodronate every two weeks the increase in BMD was som ewhat lower and slower, becoming significant only at month 24 (2.9 +/- 4.6% ), In none of the two active groups was the femoral neck BMD changed signif icantly during the 3 years of the study. A significant increase in trochant er and Ward's triangle BMD was observed at month 12 only in the patients on the highest dose of clodronate, In both groups treated, the hip BMD change s were significantly different from those observed in control patients. The biochemical markers of bone turnover were suppressed in both clodronate gr oups. These results indicate that intermittent i.m. clodronate administrati on can provide clinically relevant benefits to skeletal bone density in ost eoporotic postmenopausal women, but the in situ pain may limit its extensiv e use. (Bone 24:125-129; 1999) (C) 1999 by Elsevier Science Inc. All rights reserved.