Association between phosphate removal and markers of bone turnover in haemodialysis patients.

BACKGROUND: As the main mineral reservoir, bone acts as a calcium (Ca) and phosphate buffering system. Accordingly, phosphate removal by haemodialysis (HD) might be theoretically influenced by bone turnover, as well as by the interaction of regulatory molecules, such as PTH and osteoprotegerin (OPG). The present study investigated the relationship between these variables and phosphate removal by HD. METHODS: Blood samples for serum Ca, phosphate, bicarbonate, intact PTH, PTH (1-84), bone alkaline phosphatase, tartrate-resistant acid phosphatase 5b, OPG and receptor activator of nuclear factor-kappaB ligand (RANKL) were obtained in 28 HD patients. Phosphate removal was measured by a continuous collection of the dialysate. RESULTS: Pre-dialysis serum phosphate concentration is the critical factor in determining dialytic phosphate removal. However, multiple regression analysis reveals that phosphate removal is better explained by a combination of factors than by phosphate concentration alone. In this model, the PTH/OPG ratio is an additional positive factor, whereas age and vitamin D treatment are negative factors. Patients with pre-HD bicarbonate higher than 20 mEq/l had higher serum phosphate and, accordingly, higher phosphate removal; of interest, these individuals also have significant differences in RANKL/OPG. Mean (SD) OPG levels were significantly higher than that in the healthy population (16.2 (12.5) pmol/l; these values correlated with age (r = 0.4, P<0.04). Mean serum RANKL (1.03 (1.02) pmol/l) was within the range of normal individuals. CONCLUSIONS: Dialytic phosphate removal has a crucial, direct relationship with pre-HD plasma phosphate levels. However, the phenomenon of phosphate removal is more precisely explained using a more complex relationship, defined by the interaction between serum phosphate, PTH/OPG, age and vitamin D administration. Serum RANKL levels are first reported in HD patients, and are not different from the normal population.

Comparative effects of bicalutamide (Casodex) versus orchidectomy on bone mineral density, bone remodelling, and bone biomechanics in healthy rats.

INTRODUCTION: The aim of this work was to analyze the effects produced on bone mineral density (BMD) by the administration of bicalutamide and to compare them with those produced by orchidectomy. Bone formation rate (serum osteocalcin), bone resorption (serum carboxyterminal telopeptide of collagen I; CTX), and biomechanical properties of bone were also studied. METHODS: Thirty-eight male Wistar rats were used: (1) Sham group, rats sham operated at 16 weeks of age; (2) OQX group, rats orchidectomized at 16 weeks of age, and (3) Bic group, rats sham operated at 16 weeks of age and treated during 6 weeks with bicalutamide. The rats were sacrificed at 22 weeks of age, and the BMD in femur and lumbar spine was determined. Serum osteocalcin and serum CTX were also analyzed. Biomechanical parameters related to torsion assay were also studied. RESULTS: The OQX group showed a significant decrease in femoral BMD with respect to Sham rats, whereas bicalutamide treatment did not produce any significant change in BMD. Both Sham and Bic groups showed similar serum osteocalcin and CTX values, whereas OQX rats presented higher osteocalcin and CTX levels than the Sham group. The OQX group showed a significant decrease in femoral thickness. No significant differences were observed in the rest of the biomechanical parameters between groups. CONCLUSION: These results indicate that bicalutamide treatment, in spite of its anti-androgenic properties, does not affect bone remodelling nor BMD in male healthy rats, suggesting that this compound may function as a selective androgen receptor modulator for effects on bone remodelling in the osteoblasts.