Rickets and Osteomalacia – Vitamin D-Sensitive and -Resistant States

Bone mineralization is a complex process requiring a complex interplay between different hormones, enzymes, and minerals. Mineralization defects are underrated metabolic bone diseases, often not recognized and unproperly treated. Rickets and osteomalacia are disorders of mineralization occurring in the developing and adult skeleton, respectively, sharing common pathogenetic mechanisms. Vitamin D deficiency is still today one of the major causes of rickets and osteomalacia. Besides vitamin D-sensitive states, vitamin D-resistant states are conditions in which therapy with vitamin D metabolites at replacement doses does not correct the mineral and skeletal abnormalities. The distinction in vitamin D-sensitive and vitamin D-resistant forms is of key importance, in order to undertake proper treatment. The characterization of some forms of inherited rickets has brought to the discovery of key actors in mineral metabolism, such as the phosphaturic hormone fibroblast growth factor 23 (FGF23), and key actions of alkaline phosphatase and pyrophosphate. Although clinical, radiologic, and histologic features can be aspecific, biochemical characterization of each form of rickets/osteomalacia leads to correct diagnosis, which is preliminary to targeted treatment.