Effects of two administration schemes of intramuscular clodronic acid on bone mineral density: a randomized, open-label, parallel-group study.

BACKGROUND: Clodronic acid is a bisphosphonate used in the prevention and treatment of postmenopausal bone loss. Previous evidence suggests a direct dose-response relationship for the densitometric effect of clodronic acid. Therefore, as it is widely accepted that a reduction in the dosing frequency of bisphosphonates may improve adherence and therefore therapeutic outcomes, an increase in the interval between consecutive administrations of clodronic acid might be associated with a concomitant increase in the overall bisphosphonate dose received. However, to our knowledge, a direct comparison of the effects of intramuscular clodronic acid 100 mg once weekly with a regimen consisting of a higher dose and a longer interval between two consecutive administrations is still lacking. OBJECTIVE: This study compared the increase in bone mineral density (BMD) achieved with two different administration schemes of intramuscular clodronic acid (100 mg once weekly and 200 mg every 2 weeks) in patients with postmenopausal osteoporosis. STUDY DESIGN AND SETTING: This randomized, open-label, parallel-group trial was conducted in the Osteoporosis and Instrumental Diagnosis Center 'OsteoArticolar' (University of Siena, Siena, Italy) between January 2007 and December 2009. PATIENTS: Consecutive women aged 50-80 years with postmenopausal osteoporosis, diagnosed ≥5 years prior to inclusion in the study, were eligible for participation in this study. INTERVENTION: Patients were randomized to receive either intramuscular clodronic acid (Clasteon®) 100 mg (group A) + lidocaine (lignocaine) once weekly or intramuscular clodronic acid 100 mg + lidocaine for two consecutive days every 2 weeks (group B), for 2 years. RESULTS: In total, 30 patients were randomized to group A and 30 patients to group B. Significant increases in mean ± SD BMD of the lumbar spine versus baseline values were observed in both groups at 1 and 2 year(s) from treatment initiation (group A - year 1: +2.8% ± 1.7%, p < 0.05; year 2: +3.5% ± 2.2%, p < 0.01; group B - year 1: +2.7% ± 2.1%, p < 0.05; year 2: +3.9% ± 2.2%, p < 0.01). Mean ± SD BMD at the femoral neck also significantly increased versus baseline in group A at both timepoints (year 1: +2.3% ± 1.9%, p < 0.05; year 2: +2.5% ± 1.9%, p < 0.05), while the increase reported in group B was significant only after 2 years of treatment (year 1: +1.9% ± 2.2%; year 2: +2.8% ± 1.8%; p < 0.05). Significant mean ± SD increases in total femur BMD were observed only in group A at 2 years (+2.4% ± 1.9, p < 0.05). No differences between study groups were reported. Two non-traumatic vertebral fractures were observed in group A (6.6%) and three in group B (10.0%). Treatment was well tolerated; mild pain at injection site was observed in three patients (one in group A, 3.3%; two in group B, 6.6%). CONCLUSION: This randomized study suggests, for the first time to the author's knowledge, a similar effect of intramuscular clodronic acid 100 mg once weekly and 200 mg every 2 weeks (two 100 mg administrations on two consecutive days) on BMD in women with postmenopausal osteoporosis. The administration of intramuscular clodronic acid 200 mg every 2 weeks may therefore represent a new therapeutic option in the treatment of postmenopausal osteoporosis.