"Twice-a-month" clodronate 200 mg IM: a new dosing regimen and improved therapy adherence in the treatment of postmenopausal osteoporosis.
BACKGROUND
The identification of therapeutic strategies aimed both at preventing and treating osteoporosis and osteoporotic fractures has become increasingly important; in particular, it is essential to promote adequate patient adherence to treatment. The primary aim of this study was to evaluate the effects on lumbar and femoral bone mass density (BMD) after two different intramuscular (IM) dosing regimens of clodronate (CLD), a bisphosphonate shown to be efficacious in reducing the incidence of both vertebral and nonvertebral fractures. Secondary aims were the assessments of bone resorption markers, safety, tolerability, pain, and patient compliance.


METHODS
Sixty women with postmenopausal osteoporosis were randomized to two groups: group A (CLD 100 mg IM weekly for 12 months), and group B (CLD 200 mg IM every 2 weeks for 12 months). All patients received 1 g of calcium supplemented with 800 IU vitamin D(3), orally, once daily for 12 months Lumbar and femoral BMD, measured by DEXA Norland XR-36 (Norland Co., Fort Atkinson, WI), and bone turnover markers were assessed at baseline and at 12 months. Each patient was administered a visual analog scale of pain at baseline and after 6 and 12 months of treatment.


RESULTS
A significant increase of BMD in both groups and in both skeletal sites was observed at 12 months versus baseline. In group A (n=28), lumbar BMD increased by 3.5% and femoral BMD by 2.1%; in group B (n=32), lumbar and femoral BMD rose by 3.4% and 2.2%, respectively. No difference was observed between groups. Bone resorption markers significantly reduced from baseline. Pain significantly improved as early as after 6 months of therapy and even more after 12 months, although no significant difference between the two groups was observed. The most common side effect was pain at the injection site, particularly in group B. Six patients in group A discontinued treatment and failed adherence to the therapeutic protocol. Conversely, no patient from group B discontinued therapy.


CONCLUSIONS
In agreement with published data, in our two groups of patients, therapy with IM CLD at the doses of 100 mg/week and 200 mg/2 weeks was shown to be effective in increasing BMD, without differences between the two dosing regimens in all assessed efficacy parameters. Therefore, the "twice-a-month" regimen with 200 mg IM CLD may well promote an improved adherence with the same clinical efficacy and safety profile.
Muratore
M
M
U.O. Rheumatology, Hospital Galateo, 73016 San Cesario di Lecce (LE), Italy. mamuratore@libero.it
Quarta
L
L
Calcagnile
F
F
Quarta
E
E
D000368:Aged; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001862:Bone Resorption; D004002:Clodronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005269:Femur; D006801:Humans; D008159:Lumbar Vertebrae; D055118:Medication Adherence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D010146:Pain / Q000188:drug therapy
D050071:Bone Density Conservation Agents; D004002:Clodronic Acid