New insights into the pathogenesis of bone loss in recurrent calcium stone formers

Abstract

Background/aims: Urolithiasis is one of the leading social and economical problems of modern society. It is estimated that 10% of males and 4 % of females between 30 and 50 years of age have urinary tract stone disease. Recurrence rate of urolithiasis is 75% at 15 years with no treatment. Calcium is the major calculus component since 75-80% of renal stones are composed of calcium oxalate, while idiopathic metabolic hypercalciuria is one of the most frequent causes of recurrent calcium urolithiasis. Numerous studies showed that urolithiasis patients have higher rate of bone resorption and lower bone mineral content as well as bone mineral density, which is more evident in idiopathic calcium stone formers. However, mechanisms of action and factors involved in bone loss in these patients are still unknown. Increased production of cytokines such as IL-1, IL-6, TNF as well as osteopontin (OPN), osteoprotegerin (OPG) and RANKL (receptor activator of NF-kappaB ligand) may enhance bone resorption and therefore lower bone mass in patients with idiopathic calcium urolithiasis. Aim of this study is to assess changes of cytokines involved in bone turnover and increased bone resorption, as that might play role in bone loss in recurrent calcium stone formers. Methods: 49 recurrent calcium stone formers were involved in the study and compared to healthy age and sex matched controls. Anthropometrical measurements and metabolic evaluation were performed. Bone mineral density (BMD ; g/cm2) was assessed by dual-energy x-ray absorptiometry (« Lunar Prodigy» ). BMD measurements were performed at the lumbar spine, femoral neck, forearm and total body. Results are presented as bone mineral content (BMC ; g) and bone area (BA ; cm2). Ca2+, Mg2+, P, creatinine, Na+, K+, Cl-, proteins, uric acid, alkaline phosphatase, osteocalcin, calcitonin, PTH, 25-OH D vitamin and 1, 25-OH D vitamin were assessed by standard biochemical serum analysis. IL-1, IL-6, TNF-α , OPG, RANKL and OPN serum levels were determined by quantitive enzyme-linked immunosorbent assay (ELISA) according to manufacture’ s protocol (Quantikine, R&D Systems, Inc., Minneapolis, USA). Results: The frequency of low BMD between male and female recurrent calcium stone formers was 36.4% to 45.8%, respectiveley. Different calcium excretion levels influenced the frequency of low BMD and ranged from 31.6% in normocalciuric patients to 50% in patients with hypercalciuria, respectiveley. The frequency of increased bone turnover markers showed differences between recurent stone formers with and without low BMD as well as between male and female participants. PTH was increased in 54.5% female participants with low BMD and in 25%