Bisphosphonate therapy improves BMD and lowers the fracture risk in general population. The large randomized trials excluded patients with known renal dysfunction. Only post hoc studies on the subjects with an estimated eGFR lower than 60 have shown that the fracture reduction was similar to subjects with a normal eGFR. This study was done to evaluate efficacy and safety of bisphosphonates in subjects with various degrees of renal function impairment. Eighty patients of CKD stage 3- 5D with age > 18 yrs with informed consent were randomized to placebo versus 35 mg of alendronate, taken once a week for 12 months. Patients with age <18 or > 70 years, h/o of previous use antiresorbtive therapy or steroids in last 6 months, with PTH < 200 and/or bSAP < 30 and renal transplant recipients were excluded. Primary outcomes of study were assessed with help of DEXA scan for improvement in mean T score, Z score and BMD at level of lumbar spine, femur neck and total hip, done at baseline, at 6 month and 12 month and X rays for evidence of fractures and vascular calcification. Secondary out comes were assessed by looking for any adverse reactions related to treatment during each follow up visit and improvement in biochemical parameters like PTH, calcium, phosphorous and ALP levels. A total of 150 patients of CKD age 3-5D presenting to Nephrology ward, OPD and/or dialysis unit were initially screened for the study. A total of 80 patients with T score < -1SD on DEXA scan, meeting inclusion criteria finally completed the study period duration and were included for final analysis. There was improvement in mean T score, Z score and BMD at level of lumbar spine, femur neck and total hip at 6 and 12 months in patients, who received oral alendronate compared to controls. This change in mean of T score, Z score and BMD was statistically significant between two groups at 6 and 12 month irrespective of CKD stage. There was no difference in overall mean ALP level at baseline, 3, 6 and 12 months between control and case group in CKD 3, 4 and 5. But there was statistically significance difference in mean PTH level between control and cases at 12 month (P=0.047) when analyzed as combined irrespective of CKD stage. But this difference was not seen for individual CKD sub stage. There was no increase in base line proteinuria for various CKD stages between case or control group at the end of the study. 2 patients in control group and one in case group had fracture. There was no significant difference in the incidence of fractures between treatment and control arm. The benefit of the treatment was independent of the degree of renal impairment. Five patients had initially GI intolerance to alendronate, one had osteonecrosis of jaw, one had dermatological reaction to alendronate, but none of them required stoppage of drug due to side effects. Our study demonstrated the efficacy and safety of antiresorptive therapy in patients with CKD stage 3-5D. Low-dose alendronate, administered for longer duration, appears to be well tolerated in CKD 3-5D patients without major adverse effects. The BMD, T-scores and Z score declined in the placebo group over 12 months, while there was improvement in the treatment group, suggesting a bone-preserving effect of alendronate. There were no major adverse effects of therapy except for mild GIT intolerance.
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Open Access
Jun 18, 2021
Jun Iwamoto + 3
