Definition - 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 Epidemiology - 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
Aetiology - 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
Pathophysiology - 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.
Investigations- 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%
Managementa) conservativeb) 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) surgicalPrognosis |
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