Low Calcium-Phosphate Intakes Modulate the Low-Protein Diet-Related Effect on Peak Bone Mass Acquisition: A Hormonal and Bone Strength Determinants Study in Female Growing Rats

Abstract

Peak bone mass acquisition is influenced by environmental factors including dietary intake. A low-protein diet delays body and skeletal growth in association with a reduction in serum IGF-1 whereas serum FGF21 is increased by selective amino acid deprivation. Calcium (Ca) and phosphorous (P) are also key nutrients for skeletal health, and inadequate intakes reduce bone mass accrual in association with calciotropic hormone modulation. Besides, the effect of calcium supplementation on bone mass in prepubertal children appears to be influenced by protein intake. To further explore the interaction of dietary protein and Ca-P intake on bone growth, 1-month-old female rats were fed with an isocaloric 10%, 7.5%, or 5% casein diet containing normal or low Ca-P for an 8-week period (6 groups). Changes in tibia geometry, mineral content, microarchitecture, strength, and intrinsic bone quality were analyzed. At the hormonal level, serum IGF-1, fibroblast growth factor 21 (FGF21), PTH, 1,25-dihydroxyvitamin D3 (calcitriol), and FGF23 were investigated as well as the Ghr hepatic gene expression. In normal dietary Ca-P conditions, bone mineral content, trabecular and cortical bone volume, and bone strength were lower in the 5% casein group in association with a decrease in serum IGF-1 and an increase in FGF21 levels. Unexpectedly, the low-Ca-P diet attenuated the 5% casein diet-related reduction of serum IGF-1 and Ghr hepatic gene expression, as well as the low-protein diet-induced decrease in bone mass and strength. However, this was associated with lower cortical bone material level properties. The low-Ca-P diet increased serum calcitriol but decreased FGF23 levels. Calcitriol levels positively correlated with Ghr hepatic mRNA levels. These results suggest that hormonal modulation in response to a low-Ca-P diet may modify the low-protein diet-induced effect on Ghr hepatic mRNA levels and consequently the impact of low protein intakes on IGF-1 circulating levels and skeletal growth.

Regulation of fibroblast growth factor 23 (FGF23) in health and disease

“…Dietary Ca 2+ stimulates FGF23 production , and a Ca 2+ deficit lowers FGF23 . Ca 2+ ‐dependent regulation of FGF23 seems to be independent of PTH/vitamin D and possibly be due to a direct effect on Fgf23 gene expression via calcium channels .…”

Homeostatic sensing of dietary protein restriction: A case for FGF21

“…In fact, restricting energy intake without restricting protein decreased FGF21 expression. Subsequent work by multiple groups has confirmed that FGF21 is robustly increased by dietary protein restriction (Fournier et al, 2014; Ozaki et al, 2015; Chalvon-Demersay et al, 2016; Gosby et al, 2016; Maida et al, 2016; Pezeshki et al, 2016; Solon-Biet et al, 2016; Larson et al, 2017; Pereira et al, 2017a). This effect to increase FGF21 also extends to other situations of amino acid restriction, including the restriction of leucine, methionine/cysteine, the depletion asparagine, and the restriction of multiple non-essential amino acids (De Sousa-Coelho et al, 2012; Wanders et al, 2015; Wilson et al, 2015; Maida et al, 2016; Wanders et al, 2017).…”

Spirulina Enhances Bone Modeling in Growing Male Rats by Regulating Growth-Related Hormones

“…Chronic protein deficiency has been reported to delay skeletal growth and bone maturity and cause fatty infiltration of the liver in infants and young children, conditions that are often associated with chronic malnutrition, a major factor affecting child morbidity and mortality in developing countries [10,11]. It has been reported that a low-protein diet reduces tibia length and diameter, and bone mineral content (BMC) in growing rats [12] and children [13]. Also low levels of circulating IGF-1 and the presence of a fatty liver are conditions frequently observed in children with a protein-deficient diet [14].…”