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

backgroundClodronic 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.

objectiveThis 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

settingThis 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.

interventionPatients 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.

resultsIn 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%).

conclusionThis 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.