MP372USE OF DENUSUMAB IN END STAGE RENAL DISEASE

Abstract

Introduction and Aims: Osteoporosis is a common disease that is characterized by low bone mass with microarchitectural disruption and skeletal fragility resulting increased risk of fracture. In CKD patients the diagnosis and the treatment especially in ESRD remains a challenging area. The current methods of diagnosing osteoporosis on the basis of bone mineral density (BMD) criteria (T score of 2.5 standart deviations or more below the young adult mean BMD) by dual energy X-ray absorptiometry (DEXA) have not been validated in CKD. Denosumab is a powerful and reversible inhibitor of bone turnover that induces a transient complete loss of the histomorphometric appearance of osteoclasts on biopsy. It has been used in CKD stage III patients with remarkable results. Methods: In our study 10 patients (female:male 6:4) in hemodialysis (mean duration 7.3years in HD) with either osteoporosis (diagnosed by BMD) or pathologic fracture were given a single dose of denusumab 60mg sc and followed up for 6months. The patients were monitored closely (weekly) concerning Calcium(Ca) and Phosphorus levels and PTH was checked at baseline, month 3 and 6. Consent form was signed from the patients as the given drug has not been aproved for ESRD . Patients with adynamic bone disease were excluded. Results: Markedly hypocalcemia and hypophosphatemia was avoided by increasing the Ca concentration in dialysate, discontinuation of cinacalcet and reduction of phosphate binders and use calcium tablets instead for a short period of time. BMD showed an improvement although it might too early to exclude conclusions. Remarkably all the patients mentioned improvement of their diffuse myalgias without any adverse event. Conclusions: Another aspect on treatment of osteoporosis in hemodialysis patients is denosumab that showed promising results especially an improvement of myalgias and an increase in BMD in a short period of time after treatment. Increased attention is needed in careful monitoring of calcium and phosphorus the first few weeks after treatment as significant hypo-calcemia and -phosphatemia may occur. Concerning PTH it also showed improvent but further long term follow up is necessary in order to define this favorable outcome. Larger prospective trials are needed to examine the relationship between denosumab use and vascular calcification.