Vitamin D Deficiency and Osteomalacia

Question 1

Define

Answer 1

Osteomalacia is a disorder of mineralization of bone matrix (osteoid)

Normal amount of bone but its mineral content is low (there is excess uncalcified osteoid and cartilage)

Rickets is the result if this process occurs during the period of bone growth
Osteomalacia is the result if it occurs after fusion of the epiphyses

Question 2

Causes

Answer 2

Vitamin D deficiency: malabsorption (SB disease), poor diet, or lack of sunlight

 Renal osteodystrophy: Renal failure leads to 1,25(OH)2- vitamin D deficiency

 Drug-induced: Anticonvulsants induce liver enzymes → increased breakdown of 25-hydroxy-vitamin D

 Liver disease: reduced hydroxylation of vit D and malabsorption of vit D, e.g. in cirrhosis

 Vitamin D resistance: mutation in vit D receptor gene

 Tumour-induced osteomalacia (oncogenic hypophosphatemia): mediated by ↑ tumour production of phosphatonin FGF-23 which causes hyperphosphaturia, ↓serum PO43−, myalgia and weakness

Question 3

Risk factors

Answer 3

Risk Factors for Vitamin D Deficiency

• Lack of exposure to sunlight
• Dietary deficiency
• Malabsorption
• Decreased 25-hydroxylation of vitamin D (due to liver disease, anticonvulsants)
• Decrease 1a-hydroxylation of vitamin D (due to chronic kidney disease, hypoparathyroidism)
• Vitamin D resistance

Renal Phosphate Wasting

• Fanconi’s syndrome - characterised by:
  
  • Phosphaturia
  • Glycosuria
  • Amino aciduria
• Renal tubular acidosis (type 2)
• Hereditary hypophosphataemic rickets (X-linked or autosomal dominant)
• Tumour induced osteomalacia

Question 4

Epidemiology

Answer 4

COMMON in industrialised countries

More common in FEMALES

Question 5

Symptoms

Answer 5

Osteomalacia

• Bone pain (mainly in the axial skeleton)
• Weakness
• Malaise

Rickets

• Hypotonia
• Growth retardation
• Skeletal deformities

Question 6

Signs

Answer 6

Osteomalacia

• Bone tenderness
• Proximal muscle weakness
• Waddling gait

Signs of hypocalcaemia:

Trousseau’s sign - inflation of a blood pressure cuff to above the systolic pressure for > 3 mins causes tetanic spasm of the wrist and fingers

Chvostek’s sign - tapping over the facial nerve causes twitching of the ipsilateral facial muscles

Rickets

• Bossing of frontal and parietal bones
• Swelling of costochondral junctions (rickety rosary)
• Bow legs in early childhood
• ‘Knock knees’ in later childhood
• Short stature

Question 7

Investigations

Answer 7

Bloods

• Low or normal Ca2+
• Low phosphate
• High ALP
• Low 25-hydroxy vitamin D
• High PTH (secondary hyperparathyroidism)
• Check U&Es
• Check ABGs (for renal tubular acidosis)
• Increased phosphate excreting (in renal phosphate wasting)

Radiographs

May appear normal

May show osteopaenia

Looser’s zones = wide, transverse lucencies traversing part way through a bone, usually at right angles to the involved cortex and are associated most frequently with osteomalacia and rickets (AKA pseudofractures)

Bone biopsy after double tetracycline labelling

• Tetracycline is deposited at the mineralisation front as a band
• After two course of tetracycline (separated by a few days), the distance between the bands of deposited tetracycline is reduced in osteomalacia
• Not usually necessary for the diagnosis of osteomalacia

Question 8

Management

Answer 8

Vitamin D and calcium replacement

Monitor 24 hr urinary calcium

Also monitor:

• Serum calcium
• Phosphate
• ALP
• PTH
• Vitamin D

Treat the underlying CAUSE

Question 9

Complcations

Answer 9

Bone deformities

Hypocalcaemia can cause epileptic seizures

Cardiac arrhythmias

Hypocalcaemic tetany

Depression

Hypocalcaemia symptoms = CATs go NUMB

• Convulsions
• Arrhythmias
• Tetany
• NUMBness/paraesthesia

Question 10

Prognosis

Answer 10

Symptoms and radiological appearances improve with vitamin D treatment

Bone deformities in children tend to be permanent