Osteomalacia

Question 1

What are the DXA scan ranges?

Answer 1

• T-score of -1.0 or above = normal bone density.
• T-score between -1.0 and -2.5 = low bone density, or osteopenia.
• T-score of -2.5 or lower = osteoporosis.

Question 2

Define osteomalacia. How does it differ from rickets?

Answer 2

Osteomalacia is a metabolic bone disease characterised by incomplete mineralisation of the underlying mature organic bone matrix (osteoid) following growth plate closure in adults.

Rickets is a metabolic bone disease characterised by defective mineralisation of the epiphyseal growth plate cartilage in children –> skeletal deformities and growth retardation.

Question 3

What is the most common cause of osteomalacia/rickets?

Answer 3

Vitamin D deficiency

Question 4

How common is osteomalacia?

Answer 4

• In US/EU >40% of adults over 50yrs are Vitamin D deficient
• Has also been found in Muslim women and their infants perhaps due to body coverage
• ortification of foods with vitamin D and the use of vitamin supplements have greatly reduced the incidence of osteomalacia

Question 5

What are the risk factors for osteomalacia?

Answer 5

• Inadequate Vit D - dietary or sun UV-B exposure
• Dark skin
• Malabsorption - e.g. gastrectomy/coeliac.
• CKD-metabolic bone disorder
• Anticonvulsants - induce Vit D breakdown

Other:

• High dietary phosphate - binds Ca in kidneys and causes excretion of both
• Renal tubular acidosis and inherited/acquired forms of Fanconi’s syndrome
• Inborn errors of metabolism
• Cystic fibrosis - related in part to malnutrition, vit D and Ca deficiencies.
• Chappatis (phytic acid)

Question 6

Summarise the production of vitamin D in the body.

Answer 6

• UVB on the skin forming Vit D3 in liver (cholecalciferol)
• or Vit D2 from diet (ergocalciferol)
• These are converted in the kidney to Calcitriol by 1-ALPHA-HYDROXYLASE (which is regulated by PTH)

Question 7

What are the signs and symptoms of osteomalacia?

Answer 7

Non-specific signs and symptoms

May present as:

• Bone and proximal muscle pain
• Pseudofractures or fractures
• Pain in hips causing a waddling gait
• Rickets:
  
  • bowed legs
  • costochondral swelling
  • widened epiphyses at wrists
  • myopathy

Question 8

What are the biochemical signs of vitamin D deficiency?

Answer 8

1. LOW inactive Vit D in plasma (25(OH)D3)*
2. LOW plasma Ca2+ (but may be normal is secondary hyperparathyroidism has developed)
3. LOW plasma phosphate from reduced gut absorption
4. HIGH PTH - secondary hyperparathyroidism

*(NB we don’t measure 1,25 dihydroxy vitamin D (1,25 (OH)2 D) to assess body vitamin D stores)

Question 9

What investigations would you do for osteomalacia?

Answer 9

• Plasma calcium, phosphate, AlkPhos - low, low, high
• intact PTH - normal
• 25-hydroxyvitamin D - low <25nanomol/L
• renal function tests
• 24hr urinary phosphate and calcium - high and low

Imaging:

• Bone x ray - osteosclerosis (increased bone density) may occur in patients with chronic kidney disease-mineral bone disorder (CKD-MBD)
• DXA scan - performed to confirm the low bone mass and aids in tracking the disease progression or remission. Osteomalacia presents as osteoporosis in 70% of cases
• Biopsy with double tetracycline labelling - rarely necessary

Question 10

How do you manage osteomalacia?

Answer 10

1st line - Calcium plus vitamin D -

• e.g. colecalciferol 50,000 units orally once or twice weekly for 6-12 weeks; or 5000 to 10,000 units orally once daily for 6-12 weeks
• AND calcium carbonate 1-2 g/day orally given in 3-4 divided doses

Monitor 25OH Vit D, urinary calcium excretion, bone density and serum calcium concentration during treatment.

NB: give higher doses of Vit D if patient is taking anticonvulsants or glucocorticoids.

Question 11

What are the complications of osteomalacia?

Answer 11

• Insufficiency fractures or pseudofractures - Looser’s zones or Milkman’s fractures, represent radiolucent bands perpendicular to surface of the bones.
• Secondary hyperparathyroidism - minimise parathyroid stimulation, one of the active metabolites of vitamin D is given in conjunction with phosphate therapy.
• Metastatic calcification in renal failure
• Hypercalcaemia - Aggressive hydration with or without furosemide therapy is required acutely.
• Hypercalciuria and kidney stones - measuring urine calcium:creatinine ratio avoids risk of kidney stones

Question 12

What is the prognosis?

Answer 12

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

Question 13

What is a common XR finding in long-standing vitamin D deficiency?

Answer 13

Looser’s zones (pseudofractures) - wide, transverse lucencies with sclerotic borders traversing partway through a bone, usually perpendicular to the involved cortex,

Question 14

What enzyme is commonly raised in both Paget’s and osteomalacia and why?

Answer 14

ALP - increased activity of osteoclasts

Question 15

What are the consequences of vitamin D excess?

Answer 15

• Hypercalcaemia
• Hypercalciuria (Ca is excreted in urine)

This is due to increased intestinal absorption of Ca.

Question 16

What are the causes of Vitamin D excess?

Answer 16

• Excessive Alfacalcidiol treatment (active metabolites of Vit D)
• Granulomatous disease e.g. sarcoidosis, leprosy, TB (macrophages in granuloma –> 1-alpha hydroxylase production –> 25(OH)D to active 1,25(OH)2D)