Association between activated renin angiotensin system and bone formation in hemodialysis patients:: Is the bone mass genetically determined by ACE gene polymorphism?

Background. Angiotensin II (ang II) receptor subtype I binding sites has been recently demonstrated on bone cell precursors. Ang II stimulates DNA and collagen synthesis in human adult bone cells. The aim of this study is to evaluate the role of renin angiotensin system in the bone metabolism and to address the genetic influence of angiotensin converting enzyme (ACE) gene polymorphism on bone mass in hemodialysis patients. Methods. Forty-eight end-stage renal disease patients (28 male, 20 female mean age 42+/-13 years,) on maintenance hemodialysis were included in the study. Bone mineral density (BMD) was estimated at lumbar spine and T score worse than -1.5 were considered as osteopenia. Serum parathyroid hormone (iPTH) and osteocalcin (OC), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type 1 collagen (PICP) levels were measured as markers of bone metabolism. Plasma renin activity (PRA), serum ACE activity and ACE gene polymorphism (II, ID, DD) were determined. Results. Bone mineral density and T score of the hemodialysis patients were 0.92+/-0.17 g/cm(2) and -1.36+/-1.50, respectively. Twenty-one patients (43,7%) were osteopenic (T score worse than -1.5) and mean T score of osteopenic patients was -2.72+/-0.72. T score of nonosteopenic group was -0.29+/-0.99. Serum calcium, serum, phosphorus, serum OC, serum bAP, serum PCIP, serum PTH levels were similar in osteopenics and nonosteopenics. No difference was observed in predialysis PRA and in both pre- and postdialysis serum ACE activity of patients in both groups. PRA after hemodialysis in nonosteopenic group was higher than osteopenics (p<0.05). Percent increment in PRA in hemodialysis patients was correlated with T score (R=0.48 p<0.05). Serum ACE activity was positively correlated with serum iPTH (R=0.29, p=0.02), serum OC (R=0.35, p=0.01), serum bAP (R=0.34, p=0.01), serum PCIP (R=0.36, p=0.01). T score (-0.7+/-1.5, vs -1.7+/-1.3 p<0.05) was higher in DD group (n=19) compared to II+ID group (n=29). Conclusions. Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an evidence for the involvement of this system in the regulation of bone metabolism.