Intramuscular clodronate in nonresponders to oral alendronate therapy for osteoporosis.

OBJECTIVE

Oral alendronate is effective in increasing bone mineral density (BMD) and in reducing fracture incidence. However, a large proportion of patients under treatment do not show significant changes in BMD, or even bone loss. Incorrect administration, low intestinal absorption, and poor compliance are among factors that may account for this effect. In this subgroup of patients we evaluated whether intramuscular (im) clodronate increased the number of responders.

METHODS

Using an open case-control design we studied 60 postmenopausal osteoporotic women (mean age 58.9 years +/- 4.8 SD) after one year of therapy with oral alendronate who had an increase in BMD that was lower than the in vivo densitometry measurement error (2%). Subjects were divided into 2 groups: the first continued aledronate treatment (AL group); the second began weekly im injections of clodronate 100 mg (CL group). BMD measurements were performed at the right femoral neck by the same operator, using dual energy x-ray absorptiometry.

RESULTS

After 12 months of therapy the prevalence of responders (increase in BMD > 2%) was 40% in the AL group and 66% in the CL group (prevalence rate ratio = 1.65; 95% CI 1.25-2.04). The treatment group was the only variable that showed a significant correlation with being a responder (beta = 1.13; p = 0.03), as analyzed by multiple logistic regression to account for the effect of confounding factors. In the CL group the difference in the mean value of BMD between time T0 and time T+12 was greater than in the AL group, but did not reach statistical significance. The mean percentage variation of BMD was significantly greater in the CL group (+3.21%) compared to the AL group (+0.98%) (p < 0.001, t test) (f value = 8.4; p < 0.01, by multiple linear regression analysis using the same covariates).

CONCLUSION

Treatment with weekly intramuscular injection of clodronate in nonresponders to oral alendronate showed a higher number of subjects with a significant increase in BMD, compared to continuation of therapy with alendronate.