Contribution of Bone Tissue to Regulation of Calcium and Phosphate Metabolism. Role of FGF23 and Klotho Protein.

Bone tissue actively contributes to the regulation of systemic homoeostasis, and particularly the maintenance of calcium-phosphate balance. The parathyroid hormone-vitamin D feedback axis is balanced by the recently discovered bone-FGF23-kidney hormonal axis. An active complex consisting of FGF23, a receptor and Klotho protein blocks phosphate reabsorption in the proximal tubules, increasing urine phosphate levels and decreasing blood phosphate levels. Mutations of the gene mediating FGF23 transcription lead to a number of diseases, examples including autosomal dominant hypophosphataemic rickets. Klotho protein is a cofactor for FGF23 displaying cardio-, vaso- and nephroprotective activity. It increases calcium reabsorption in the kidneys and inhibits phosphate reabsorption. It also exerts antioxidative and anti-insulin effects and inhibits tissue calcification and apoptosis. As an inhibitor of bone resorption, osteoprotegerin becomes an important contributor to bone remodelling, while RANK/RANKL signalling inhibition is used in the treatment of postmenopausal osteoporosis. Osteocalcin plays an important role in energy metabolism in the human body. Sclerostin exerts a strong catabolic effect on bone tissue. Newly identified contributors to the regulation of calcium and phosphate homoeostasis suggest that bone tissue plays a complex role in the systemic metabolism.

Evaluation of Selected Parameters of Calcium and Phosphate Metabolism in Children with Adolescent Idiopathic Scoliosis.

BACKGROUND: The multifactor aetiology of adolescent idiopathic scoliosis is commonly acknowledged. Both multivariate analyses of large study groups and the search for causes of adolescent idiopathic scoliosis and its progression in individual patients indicate that the aetiopathogenesis of this disorder is remarkably complex. The discovery of novel bone turnover markers, such as Klotho protein and FGF-23, means that their role in this condition also has to be considered. The aim of this paper is to evaluate the FGF-23 and Klotho protein concentration profiles as new contributors to the regulation of calcium and phosphate metabolism in children with adolescent idiopathic scoliosis and compare them with the values seen in healthy children. MATERIAL AND METHODS: The study assessed a total of 70 children, including 35 children treated at the postural defects clinic of the Health Care Facility in Olesno following a diagnosis of adolescent idiopathic scoliosis and 35 healthy children who constituted a control group. The levels of classic bone turnover markers, such as calcium and phosphorus concentration, alkaline phosphatase, 25-OH-D, and parathyroid hormone (PTH) activity, and of newly discovered contributors to calcium and phosphate metabolism regulation, namely Klotho protein and FGF-23, were determined in both groups. RESULTS: There were statistically significant differences in the levels of basic parameters of calcium and phosphate metabolism between children with scoliosis and the control group, with scoliotic patients showing elevated calcium and 25-OH-D levels and reduced parathyroid hormone levels. Klotho protein levels in children with scoliosis were significantly lower than in the control group. Moreover, the scoliotic patients showed a marked trend towards higher FGF-23 levels as compared to the control group. CONCLUSIONS: 1. Adolescent idiopathic scoliosis is characterised by multi-level abnormalities of calcium and phosphate metabolism. 2. The increased FGF-23 levels and reduced Klotho protein concentrations found in serum samples collected from children with ado-lescent idiopathic scoliosis may suggest that these hormones play a role in the aetiopathogenesis of the disorder.