• Metabolic bone disease characterised by incomplete mineralisation of the underlying mature organic bone matrix (osteoid) following growth plate closure in adults
  • In contrast, rickets is a metabolic bone disease characterised by defective mineralisation of the epiphyseal growth plate cartilage in children, resulting in skeletal deformities and growth retardation
  • Rickets and osteomalacia are different manifestations of the same underlying pathological process
Risk Factors
  • dietary vitamin D deficiency
  • chronic kidney disease
  • inherited disorders of vitamin D and bone metabolism
  • hypophosphatasia
  • dietary calcium deficiency
  • anticonvulsant therapy
  • mesenchymal tumours
  • Fanconi's syndrome
Differential diagnosis
  • In the US and Europe, more than 40% of the adult population older than age 50 are vitamin D deficient, this being the most prominent cause of osteomalacia.
  • In developing countries, such as Tibet and Mongolia, vitamin D deficiency leading to clinical rickets is described in 60% of infants
  • In the Middle East, a high prevalence of rickets and osteomalacia has been described in Muslim women and their infants, perhaps due to increased clothing coverage of the skin
  • Fortification of foods with vitamin D and the use of vitamin supplements have greatly reduced the incidence of osteomalacia in the western world
    • Despite this, vitamin D-related osteomalacia still occurs with the consumption of unfortified foods, especially in the setting of limited sunlight exposure
  • Vitamin D deficiency is the primary cause of osteomalacia in the western world
    • Inadequate endogenous production of vitamin D3 in the skin related to suboptimal UV-B sunlight exposure and the use of sunscreen
    • Insufficient dietary supplementation
    • Inability of the small intestine to absorb adequate amounts of dietary vitamin D
    • Resistance to the effects of vitamin D can result from the use of drugs that antagonise vitamin D action or cause alterations in vitamin D metabolism
  • Malabsorption of vitamin D and calcium are major causes of osteomalacia in the US, with gastrectomy and coeliac disease accounting for up to 66% of all cases of osteomalacia
    • Malabsorption of vitamin D and calcium related to bariatric procedures for weight loss is emerging as a common cause of vitamin D deficiency and consequently osteomalacia
  • Renal osteodystrophy is a global term applied to all pathological features of bone in patients with chronic renal failure
    • Clinical symptoms of bone disease are present in fewer than 10% of patients with end-stage renal disease (ESRD)
    • However, x-ray abnormalities are observed in about 35%, and histological abnormalities are observed in about 90%
  • Hypophosphataemia, related to increased urinary phosphate excretion, is the predominant cause of osteomalacia in disorders of vitamin D metabolism
    • Acquired mesenchymal tumours can cause a tumour-induced osteomalacia with phosphate wasting secondary to a phosphatonin, FGF-23
    • Hypophosphataemia is also a feature of X-linked hypophosphatemic rickets, alcohol abuse, poorly controlled diabetes, metabolic acidosis, and diuretic use. 
  • Osteomalacia may be a feature of proximal (type 2) renal tubular acidosis
  • Bone mineralisation may be inhibited by bisphosphonates, aluminium-containing phosphate binders, prolonged total parenteral nutrition, or dietary fluoride
  • Inborn errors of metabolism:
    • Underactive tissue-non-specific isoenzymes of alkaline phosphatase in the serum and bone are associated with the development of osteomalacia and severe periodontal disease
    • There are multiple modes of inheritance, and a variable spectrum of disease manifestations
    • Diagnosis is based on elevated levels of phosphoethanolamine and pyrophosphate in the blood and urine. 
    • Patients with cystic fibrosis have a high prevalence of low bone mass (including osteomalacia
Clinical features
  • elderly
  • vitamin D-deficient diet
  • fractures
  • malabsorption syndromes
  • diffuse bone pain and tenderness
  • proximal muscle weakness
  • lack of sunlight exposure
  • family history of osteomalacia
  • waddling gait
  • anticonvulsant therapy
  • steatorrhoea
  • Osteomalacia results from defective bone mineralisation
  • This is a result of a lack of one or more of the factors necessary for osteogenesis
    • Normal extracellular concentration of calcium and phosphate
    • Normal pH at the site of calcification
  • Normal mineralisation depends on interdependent factors that supply adequate calcium and phosphate to the bones
  • Vitamin D maintains calcium and phosphate homeostasis through its actions on the GI tract, the kidneys, bone, and the parathyroid glands
    • Vitamin D is obtained from the diet or it can be produced from a sterol precursor (7-dehydroergosterol) in the skin following exposure to UV-B light
    • Sequential hydroxylation of vitamin D is required to produce the metabolically-active form of vitamin D
    • Hydroxylation occurs first in the liver and then in the kidneys, and produces vitamin D 1,25(OH)
    • Dysfunction in any of these metabolic steps results in osteomalacia and secondary hyperparathyroidism in adults
    • The active metabolite of vitamin D 1,25(OH)2D is essential for maintaining normocalcaemia through ensuring adequate intestinal calcium absorption
    • Inadequate intestinal calcium absorption leads to a fall in blood ionised calcium and secondary hyperparathyroidism
    • Low 1,25(OH)2D levels may contribute to secondary hyperparathyroidism through a reduction in the suppressive effects of 1,25(OH)2D on PTH gene transcription
    • PTH decreases urinary calcium excretion and increases renal tubular phosphate loss
      • Therefore, serum phosphate levels are reduced, despite an increase in phosphate release from bone
    • Osteopenia results from increased bone resorption, occurring through an indirect effect of PTH, which increases both osteoclast numbers and activity. 
  • A number of drugs interfere with the normal metabolism of vitamin D to 25OHD and 1,25(OH)2D, leading to alterations in calcium homeostasis
  • Rickets or osteomalacia result from the increased catabolism of vitamin D and its metabolites via the induction of hepatic cytochrome P450 enzymes.
  • Hyperphosphataemia in renal osteodystrophy directly induces hypocalcaemia and decreases the efficacy of 1-alpha-hydroxylase in the kidney
    • This, in turn, decreases active vitamin D metabolites and thus the ability of the gut to absorb calcium
    • Subsequently, secondary hyperparathyroidism develops.
  • With hypophosphataemia, low calcitriol levels lead to a reduction in calcium absorption and the subsequent development of secondary hyperparathyroidism and urinary phosphate wasting.

  • serum calcium level
  • serum vitamin D 25OH level
  • serum phosphate level
  • serum urea and creatinine
  • intact PTH
  • serum alkaline phosphatase
  • 24-hour urinary calcium
  • bone x-rays
  • 24-hour urinary phosphate
  • DEXA scan
  • iliac crest biopsy with double tetracycline labeling
    • reduced distance between tetracycline bands
    • unmineralised matrix appears as widened osteoid seam (>15 microns)
    • osteoid volume >10%

a) conservative

b) medical
  • calcium plus vitamin D
  • calcium plus vitamin D metabolite or dihydrotachysterol (DHT)
    • Vitamin D metabolites are utilised in patients who remain vitamin deficient after treatment with vitamin D or who have renal disease
    • They are also used in those with vitamin D-dependent rickets type 1 who have an inactivating mutation in the 1-alpha-hydroxylase gene
  • Phosphate supplementation is indicated only in patients who are symptomatic or who have a renal tubular defect leading to chronic phosphate loss.
c) surgical

  • The clinical outcome is dependent on the underlying cause and compliance with therapies.