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The nutrition is important for prevention and improvement in bone disorder. Especially osteoporosis associated with nutrition. It has entered the super-aged society in 2007, a further increase in osteoporosis patients are concerned in Japan. Many studies have shown that associated with calcium, vitamin D, vitamin K intake and bone density and fracture. Relationship of osteoporosis and nutrition, despite the general awareness is high, calcium intake is not at all reached the achievement to recommend dietary allowance. In addition, vitamin D deficiency rickets in children, which has been considered in the past of the disorder, there is an increasing trend from such exposure shortage to the infancy of sunlight, vitamin D deficiency in pregnant women, the recommended breastfeeding. Improvement of lifestyle and diet from young age is important for bone disorder prevention.

Renal osteodystrophy is the damage of bone morphology by CKD and treatment and occurred abnormal bone metabolism through renal dysfunction. It demonstrated that the control of P and Ca improves to normalization of mineral metabolism. Protein energy wasting and malnutrition are common in patients with CKD stage 5 and has been associated with life prognosis. In CKD patients, nutritional management is a critical role of treatment. Also it may be important of nutritional management that control P and Ca and improve nutritional status in renal osteodystrophy patients.

In 2003, the NKF K/DOQI released new clinical practice guidelines for bone metabolism and disease in chronic kidney disease, respectively. Target level of phosphate and Ca x Pi products are set at relative low levels in the new guidelines. Prescription of a new phosphate binder, severamer hydrochloride, a widely recommended in this quideline. Other approaches that could prove fruitful include inhibition of intestinal and renal phosphate transporters. Inhibition of the sodium-dependent phosphate transporter by a small molecule would be a desirable method to control serum phosphate levels in patients with chronic renal disease or undergoning dialysis. In this review the progress in the identification of such an agent is discussed.

Abnormalities of the inorganic phosphate (Pi) reabsorption in the kidney result in various disorders. Na(+)-dependent Pi (NaPi) transporters (NaPi- II a and NaPi- II c) in the brush border membrane of proximal tubular cells mediate the rate-limiting step in the overall Pi-reabsorptive process. The PTH (parathyroid hormone) -induced inhibition of Pi reabsorption is mediated by endocytosis of the NaPi- II a transporter from brush border membrane. NaPi- II a is part of the heteromeric protein complexes organized by PDZ ( [PSD-95/Disc-large/ZO-1] -binding proteins) proteins. The NaPi- II c transporter is also regulated by PTH via internalization, but by a vesicular transport pathway distinct from that used by the NaPi- II a transporter. In addition, the importance of the fibrobalst growth factor 23 (FGF23) -klotho axis in regulating mineral ion homeostasis. We will summarize how the FGF23-klotho might regulate renal Pi reabsorption.

Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. Urakawa et al demonstrated that the concerted action of klotho and fibroblast growth factor receptor 1 reconstitutes the fibroblast growth factor 23 (FGF23) receptor (Nature 444,770,2006). We investigated the correlation between hyperphosphatemia and Pi transport activity in klotho mutant mice (kl/kl mice). kl/kl mice displayed hyperphosphatemia, high plasma 1,25 (OH) (2)D(3) levels, increased activity of the renal and intestinal sodium-dependent P (i) cotransporters, and increased levels of the type II a, type II b, and type II c transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type II a/type II c transporter mRNA abundance, but not transcripts levels of type II b transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma FGF23 levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-P (i) diet induced the expression of klotho protein and decreased plasma FGF23 levels in kl/kl mice, whereas colchicine treatment experiments revealed evidence of abnormal membrane trafficking of the type IIa transporter in kl/kl mice. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type II a/ II c transporters rather than to intestinal P (i) uptake.

The hormones currently believe to influence inorganic phosphate (Pi) metabolism are parathyroid hormone (PTH) and the active metabolite to vitamin D. A new class of phosphate-regulating factors, collectively known as the phosphatonins have been shown to be associated with the hypophosphatemic diseases. The reabsorption of Pi in the kidney is a major determinant of the plasma Pi level. Reabsorption is largely regulated by the type II a sodium-dependent Pi cotransporter (NPT2a) that is expressed in renal proximal tubular cells. Phosphatonins cause Pi wasting by controlling the amount of NPT2a on the apical surface of the proximal tubular cell. A recent finding indicates that mutations in NPT2a can contribute to nephrolithiasis and osteoporosis in humans and suggests that changes in NPT2a levels may also cause other human disease. We discuss the roles of phosphatonins and NPT2a in bone formation.

Calcitonin and its receptor are well known for their ability to regulate osteoclast-mediated bone resorption. Calcitonin has been suggested to be a renal Ca(2+) and Mg(2+)-conserving hormone and may share similar signaling mechanisms with PTH. This review describes the characteristics of renal Ca(2+), Mg(2+) and Pi transport pathway and the physiological roles of calcitonin in renal mineral reabsorption.

Changes in the extracellular concentration of inorganic phosphate (Pi) modulate cellular function in a physiologically relevant manner. High serum Pi leads to an increase in PTH secretion, PTH mRNA stability, and parathyroid cell (PT) proliferation. The reduced Pi reabsorption is achieved by a removal of type II a NaPi co-transporter from apical membrane. Acute internalization in response to high dietary Pi-intake or administration of PTH is via clathrin-coated structures and is followed by subsequent lysosomal degradation. In this review, the effects of PTH on the metabolism of Pi are discussed.