Vitamin D deficiency: rickets and osteomalacia

Effect · 25(OH)D low ALP high

Too little substrate reaches the 1-alpha-hydroxylase, so gut calcium absorption falls and PTH rises to hold serum calcium up, wasting phosphate as it does so. Osteoid is laid down but not mineralised: rickets at the growth plate in children, osteomalacia in adults.

Traced from the start

  1. Fall in ionised calciumRise in ionised calcium
  2. Calcium-sensing receptor on parathyroid chief cells
  3. Phosphate load and hyperphosphataemia
  4. Osteocyte phosphate sensing
  5. Cholecalciferol from skin and diet
  6. Hepatic 25-hydroxylation
  7. Parathyroid hormoneFibroblast growth factor 2325-hydroxyvitamin D (calcifediol)
  8. Thyroid parafollicular (C) cells
  9. Calcitonin
  10. Renal proximal tubule: 1-alpha-hydroxylaseBone: osteoblast-osteoclast coupling
  11. Vitamin D deficiency: rickets and osteomalacia

Detail

Biochemistry
25(OH)D low, calcium low or low-normal, phosphate low, PTH high, alkaline phosphatase high; calcitriol is often normal because the high PTH drives what substrate remains
Rickets in children
Bowed legs, widened wrists and costochondral junctions (the rachitic rosary), craniotabes, delayed fontanelle closure, delayed dentition and hypocalcaemic seizures
Osteomalacia in adults
Diffuse bone pain and tenderness, proximal myopathy with a waddling gait and difficulty rising from a chair, and Looser zones (pseudofractures) on x-ray
Treatment
Cholecalciferol, a loading dose then maintenance, with calcium if dietary intake is poor; recheck calcium afterwards in case coexisting primary hyperparathyroidism is unmasked

When it goes wrong

Low 25(OH)D with a high PTH, low phosphate and raised alkaline phosphatase

Vitamin D deficiency with secondary hyperparathyroidism: the pattern to separate from primary hyperparathyroidism, where the calcium is high rather than low

Hypophosphataemic rickets that does not respond to cholecalciferol

Think X-linked hypophosphataemia from FGF23 excess, or vitamin D-dependent rickets, rather than simple deficiency

Practise this structure

1 question in the bank tagged Vitamin D.