Effects of Two Administration Schemes of Intramuscular Clodronic Acid on Bone Mineral Density

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 100mg+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% ±f-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 100mg once weekly and 200mg every 2 weeks (two 100mg 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.