FP435EFFECTS ON BONE TISSUE OF 12 MONTHS’ COMBINED TREATMENT WITH ALFACALCIDOL AND STRONTIUM RANELATE IN PATIENTS WITH MILD TO MODERATE CHRONIC RENAL FAILURE

Abstract

Introduction and Aims: Renal osteodystrophy is a serious complication of chronic kidney disease (CKD) which leads to worsening of the quality of life, disability and increased mortality in patients with renal pathology. Therefore, further development of new methods of treatment in early stages of renal impairment is needed. The present study examined the safety and the effect of low-dose of alphacalcidol and strontium ranelate combined therapy on bone metabolism and bone density in pre-dialysis chronic renal failure patients with renal osteodystrophy. Methods: Subjects: 64 patients aged 21-67 years with mild to moderate chronic renal failure (creatinine clearance 30-89 ml/min), elevated parathyroid hormone (PTH) and serum cross-linked C-terminal telopeptide of type I collagen (s-CTx) concentration and reduced bone mineral density (BMD). BMD was measured with dual energy X-ray absorptiometry (LUNAR DPX) at baseline and after 12 months of therapy in all patients at the lumbar spine (L1-L4) and femoral neck levels. Measurements of the serum levels of calcium, ionized calcium, phosphorus, bone specific alkaline phosphatase (bAP), PTH and s-CTx were perfomed at 3 months' intervals. Patients were randomized into two groups with similar baseline characteristics. First group (31 patients) was administered low phosphate diet, alfacalcidol in a dose of 0,25 mcg on alternate days and strontium ranelate in a dose 2,0 g befor sleep daily. Second group (34 patients) was administered a low phosphate diet and alfacalcidol in a dose of 0,25 mcg on alternate days. Low dose of alfacalcidol was used to maintain PTH levels at target values to avoid the risk of adynamic bone disease. Results: In both groups the mean PTH level decreased significantly and achieved target levels for respective CKD stage. Concentration of ionized calcium increased and the level of phosphorus, s-CTx and bone specific alkaline phosphatase decreased significantly after 12 months of treatment in both groups. The reduction of PTH and s-CTx levels was more expressed in first group. No patients had episodes of hypercalcemia and reduction PTH, bAP and s-CTX levels below the target level or other side effects of the therapy. In first group after 1 year of alfacalcidol and strontium ranelate therapy, lumbar spine BMD significantly improved (increased in 7,3±0,64 % (p<0,01) from baseline) whereas femoral neck BMD increased in 4,3±0,39 % ( p<0,01) from baseline. In second group after 12 months of therapy lumbar spine and femoral neck BMD did not change significantly. Conclusions: Administration of strontium ranelate in combination with low doses of alfacalcidol safely and effectively corrects the mineral metabolism and promotes bone mass increase in pre-dialysis CKD patients with renal osteodystrophy.