What is the pathophysiology of disorders of bone mineralization?

Updated: Jun 19, 2020
  • Author: Horacio B Plotkin, MD, FAAP; Chief Editor: Jatinder Bhatia, MBBS, FAAP  more...
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Calcification of osteoid depends on adequate levels of ionized calcium and phosphate in the extracellular fluid. Vitamin D influences these levels after its dihydroxylation into calcitriol (at the 25 position in the liver and the 1 position in the kidney). If the enzyme that controls either of these steps is deficient because of a mutation, vitamin D function is less than normal. In addition, a renal tubular defect that reduces reabsorption may alter phosphate metabolism. Finally, a genetic absence of the receptor for calcitriol results in deficient calcification.

X-linked hypophosphatemic rickets and autosomal recessive hypophosphatemic rickets are the result of mutations in PHEX (a phosphate-regulating gene with homologies to endopeptidases on the X chromosome) and dentin matrix protein 1 (DMP1), respectively. Degradation of matrix extracellular phosphoglycoprotein (MEPE) and DMP-1 and release of acidic serine-rich and aspartate-rich MEPE-associated motif (ASARM) peptides are chiefly responsible for the hypophosphatemic rickets mineralization defect and changes in osteoblast-osteoclast differentiation. [1]

In patients with oncogenic osteomalacia, intact and C-terminal fibroblast growth factor-23 (FGF-23) levels are elevated, and the tumors responsible for this disease show increased expression of FGF-23 messenger ribonucleic acid (mRNA).

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