Bone Abstracts

Low protein diet (LPD) impairs body growth, decreases serum IGF1 and increases serum FGF21, two hepatokines influencing bone growth. Low calcium-phosphate diet (LCaPiD) increases serum calcitriol. We hypothesized that LPD effects on bone growth may differ according to calcium and phosphate intakes through the hormonal modulation of calcitriol, IGF1 and FGF21. One-month old rats were fed isocaloric diets containing 10 or 5% casein (10Prot, 5Prot), with 1.0% calcium and 0.8% phosphorus (normal; NCaPi) or 0.2% calcium and 0.16% phosphorus (low; LCaPi) for 8 weeks. Tibia bone microarchitecture was analyzed by microCT, BMC by DXA, tibia midshaft and proximal strength by flexion and compression tests, respectively, and cortical tissue hardness by nanoindentation. Independently of CaPi intakes, LPD led to body growth retardation. In NCaPi, LPD decreased bone strength and altered microstructure in association with higher serum FGF21 (+466%, P<0.01), lower serum IGF1 (−24% P<0.05) and reduced hepatic GH receptor (GHR) gene expression (−48% P<0.01). In LCaPi, LPD-related effects were attenuated in association with a lower decrease in serum IGF1 (−11%, vs 10ProtLCaPi, P=0.14) and hepatic GHR mRNA levels (−30% vs 10ProtLCaPi, P<0.01). The latter was however higher than 5ProtNCaPi (+48% vs 5ProtNCaPi, P<0.05). In LCaPi, LPD still maintained high serum FGF21. Cortical tissue hardness was not affected in 5ProtNCaPiD, while it was lower in 5ProtLCaPiD (−15% vs 10ProtLCaPi; P<0.01). Positive correlations were observed between serum IGF1 and midshaft Ct.BV (r=0.73, P<0.01) and proximal BV/TV (r=0.52, P<0.01). In LCaPi groups, normocalcemia and normophosphatemia were maintained together with increased serum calcitriol. In conclusion, LCaPiD attenuated the LPD–related alteration of bone growth by reducing hepatic GH resistance, however at the expense of cortical tissue hardness. Our results suggest that a factor induced by LCaPiD could act at the liver level to attenuate the LPD effects.