Effects of fasting, feeding, and bisphosphonate administration on serum calcitriol levels in phosphate-deprived rats

Background. In a recent study, we showed in phosphate deprived rats that mo rning feeding decreased serum phosphate and increased serum calcium values as compared with similar rats: fasted overnight, and high doses of bisphosp honates did not reduce the magnitude of hypercalcemia. In the present study , we evaluated in phosphate-deprived rats whether serum calcitriol values w ere: (I) affected by the differences in serum phosphate induced by morning feeding and overnight fasting, (2) correlated with changes in serum phospha te levels, and (3) influenced by bisphosphonate administration. Methods. Four groups of rats were studied: (I) low-phosphate diet (LPD; P < 0.05%), (2) LPD + the bisphosphonate pamidronate (APD): (3) normal diet (N D: P 0.6%), and (4) ND + APD, Both diets contained 0.6% calcium. In rats re ceiving APD, high doses (0.8 mg/kg) were given subcutaneously four times du ring the study. On day 11, rats were sacrificed after an overnight fast or two to four hours after morning feeding. Results. In the fed phosphate-deprived rats (LPD and LPD + APD), serum phos phate levels were less (P < 0.05) and serum calcium levels were greater (P < 0.05) than in similar rats fasted overnight. In rats on the ND (ND and ND + APD), no differences were observed between fed and fasted rats. In phosp hate-deprived rats, serum calcitriol levels were greater (LPD, P < 0.05) or tended to be greater (LPD + APD, P = 0.10) in the fed than in the fasted g roups. In APD-treated rats. serum calcitriol values were greater than in ra ts not given APD whether rats were (I) fed or fasted, or (2) on an LPD dr N D. An inverse correlation was present between serum phosphate and serum cal citriol (r = -0.58, P = 0.001). In a stepwise regression model in which ser um calcitriol was the dependent variable and independent variables were APD administration and serum calcium, phosphate, ind PTH. serum phosphate (r = 0.003) had an inverse and APD (P < 0.001) administration a direct effect o n serum calcitriol (r(2) = 0.59). Conclusion. Calcitriol synthesis is rapidly inducible in rats during chroni c phosphate deprivation, and the increase in serum calcitriol values is bes t attributed to feeding-induced decreases in serum phosphate. APD administr ation independently increases serum calcitriol levels in rats on normal and phosphate-deprived diets. Finally, whether our results in the rat are appl icable to the clinical setting should be evaluated because in previous huma n studies of dietary phosphate restriction, serum calcitriol measurements w ere performed the morning after an overnight fast.