Rickets and osteomalacia

Abstract

Rickets and osteomalacia are consequences of impaired mineralization of the paediatric and adult skeleton, respectively. Softened bone leads to deformity during growth and fractures during adult life. Radiographs show widened growth plates in rickets, whereas fractures and pseudofractures characterize osteomalacia. Vitamin D deficiency from impaired biosynthesis of cholecalciferol (vitamin D3) from insufficient exposure to sunlight, without dietary supplementation using cholecalciferol or ergocalciferol (vitamin D2), is the most common cause of rickets, but calcium malabsorption from hepatobiliary, pancreatic or gastrointestinal disease can be an additional explanation for these disorders. Rarely, patients have heritable impairment of vitamin D bioactivation or resistance to its hormonal form, 1,25-dihydroxyvitamin D (calcitriol). All of these conditions feature secondary hyperparathyroidism from hypocalcaemia causing hypophosphataemia from renal phosphate wasting. Other patients manifest renal loss of phosphate from kidney tubule defects or damage, or circulating ‘phosphatonins’ engendered by certain genetic diseases or sometimes elaborated by benign neoplasms. In these disorders, suppression of calcitriol formation with inappropriately normal or low (rather than high) circulating levels is a typical biochemical finding. Hypophosphatasia features paradoxically low levels of serum alkaline phosphatase activity because of deactivating mutation of the gene encoding the isoenzyme expressed in bone, and accumulation of pyrophosphate – an inhibitor of mineralization. Therapy of rickets or osteomalacia requires clinical expertise and close patient monitoring, because potent vitamin D pharmaceuticals and mineral supplements can be effective, but excessive dosing can cause hypercalciuria and hypercalcaemia with renal damage from nephrocalcinosis or nephrolithiasis.