Search

Vitamin D deficiency rickets is characterized by mineralization impairment in bone and cartilage of children caused by vitamin D deficiency in the body due to limited sunlight exposure and vitamin D intake. Vitamin D supplementation is recommended in developed countries. Low calcium intake is a risk factor for vitamin D deficiency rickets. For treatment, native vitamin D is used in developed countries, while active vitamin D is used in Japan.

Rickets is characterized by mineralization defect in bone and cartilage. X-linked hypophosphatemic rickets (XLH) is the most common form of inherited rickets. Mineralization defect is observed in dentin as well as in bone and cartilage in XLH. The dominant feature is the occurrence of infectious periradicular abscesses on deciduous and permanent teeth, not associated with trauma or decay. Dental care including the maintenance of good oral hygiene and periodical examinations should be performed. A preventive sealing of occlusal surfaces can be considered. Endodontic treatment or extraction are carried out in the presence of periradicular abscesses. Further studies are necessary for elucidating mechanisms of dentin mineralization defect and the occurrence of periradicular abscesses and for developing preventive and curative measures in XLH.

Wnt signaling pathway components have been shown to be involved in bone biology since mutations in the LRP5 gene proved to cause osteoporosis-pseudoglioma syndrome and high bone mass trait. Genome wide association studies have indicated that single nucleotide polymorphisms of various components in Wnt signaling pathways are associated with bone mineral density and risk for low-trauma fracture. Mouse genetic studies have demonstrated that multiple components in Wnt signaling pathways play significant roles in skeletal development and bone mass maintenance. Here we review several components in Wnt signaling pathways with their association with bone mineral density in humans.

The enzymes, such as TNSALP regulate bone mineralization, and the mineralization inhibitor inorganic pyrophosphate (PPi) plays a central role in the process. NPP1 and ANK increase PPi concentration in the extracellular matrix, while TNSALP hydrolyzes PPi. The analyses using knock-out mice demonstrated that NPP1 and ANK, and TNSALP are antagonistic regulators for PPi. Concerted regulation of PPi by TNSALP, NPP1, and ANK, leads bone mineralization to be regulated strictly.

Osteoporosis is the most common metabolic bone disease and caused by multiple nutritional, environmental and genetical factors. Bone mineral density (BMD) is rather strongly under genetical control. A number of candidate genes have been studied with respect to the impact on BMD. Also, gene loci of susceptibility genes for osteoporosis have been identified by family-based association and linkage approaches. In particular, LRP5 is an important molecule involved in the determination of BMD, because its abnormality is associated with osteoporosis-pseudoglioma syndrome or autosomal dominant syndrome characterized by high bone density. These findings may contribute to new strategy to teat patients with osteoporosis.