Pathophysiology of rickets

Rickets is defective mineralisation of the growth plate in the growing skeleton, with failure of normal endochondral ossification and usually accompanying osteomalacia—defective mineralisation of osteoid Haffner et al. 2021.

The central mechanism is insufficient phosphate availability at the growth plate: low extracellular phosphate impairs terminal differentiation and apoptosis of hypertrophic chondrocytes, causing persistence and disorganisation of these cells, growth-plate widening and impaired cartilage mineralisation Haffner et al. 2021.

Two principal pathways lead to this defect:

• Calcipenic rickets: vitamin D deficiency or inadequate dietary calcium reduces calcium availability; vitamin D normally promotes intestinal absorption of calcium and phosphate NICE CKS. The resulting tendency towards hypocalcaemia stimulates secondary hyperparathyroidism, which helps preserve serum calcium but increases renal phosphate loss, producing hypophosphataemia and rickets Haffner et al. 2021. Consequently, serum calcium may remain normal despite significant skeletal disease Haffner et al. 2021.
• Phosphopenic rickets: phosphate deficiency arises directly from inadequate intake or bioavailability, or from renal phosphate wasting Haffner et al. 2021. In FGF23-mediated disorders, including X-linked hypophosphataemia associated with PHEX mutations, excess FGF23 activity reduces proximal tubular phosphate reabsorption and suppresses calcitriol production, further reducing phosphate availability Haffner et al. 2021.

Less common causes include inherited defects in vitamin D synthesis or receptor signalling, and impaired vitamin D activation in severe liver or kidney disease NICE CKS Acar et al. 2018.

The skeletal consequences are impaired growth, widened metaphyses and mechanically weak, poorly mineralised bone, producing wrist enlargement, leg bowing and other deformities NICE CKS Haffner et al. 2021. Rickets requires open growth plates; after growth-plate closure, defective bone-matrix mineralisation manifests as osteomalacia rather than rickets Filho et al. 2006.