• 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.