Osteomalacia

Osteomalacia is a disease characterized by the softening of the bones caused by impaired bone metabolism primarily due to inadequate levels of available phosphate, calcium, and vitamin D, or because of resorption of calcium. The impairment of bone metabolism causes inadequate bone mineralization. Osteomalacia in children is known as rickets, and because of this, use of the term "osteomalacia" is often restricted to the milder, adult form of the disease. Signs and symptoms can include diffuse body pains, muscle weakness, and fragility of the bones. In addition to low systemic levels of circulating mineral ions (for example, caused by vitamin D deficiency or renal phosphate wasting) that result in decreased bone and tooth mineralization, accumulation of mineralization-inhibiting proteins and peptides (such as osteopontin and ASARM peptides), and small inhibitory molecules (such as pyrophosphate), can occur in the extracellular matrix of bones and teeth, contributing locally to cause matrix hypomineralization (osteomalacia/odontomalacia). A relationship describing local, physiologic double-negative (inhibiting inhibitors) regulation of mineralization has been termed the Stenciling Principle of mineralization, whereby enzyme-substrate pairs imprint mineralization patterns into the extracellular matrix (most notably described for bone) by degrading mineralization inhibitors (e.g. TNAP/TNSALP/ALPL enzyme degrading the pyrophosphate inhibition, and PHEX enzyme degrading the osteopontin inhibition). The Stenciling Principle for mineralization is particularly relevant to the osteomalacia and odontomalacia observed in hypophosphatasia (HPP) and X-linked hypophosphatemia (XLH). The most common cause of osteomalacia is a deficiency of vitamin D, which is normally derived from sunlight exposure and, to a lesser extent, from the diet. The most specific screening test for vitamin D deficiency in otherwise healthy individuals is a serum 25(OH)D level. Less common causes of osteomalacia can include hereditary deficiencies of vitamin D or phosphate (which would typically be identified in childhood) or malignancy. Vitamin D and calcium supplements are measures that can...