Osteomalacia

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Reduced mineralisation of bone matrix (osteoid) is the cardinal feature of all osteomalacic syndromes. Rickets is the form that exclusively occurs in children where there is impaired mineralisation of cartilage matrix (chondroid) with arrest of primary spongiosa formation. Osteomalacia can occur at any age once lamellar bone has formed.

Aetiology

Malabsorption, gastric bypass surgery, caeliac sprue, chronic hepatitis, chronic kidney disease.

Clinical Features

Features include bone pain, tenderness, muscle weakness, difficulty walking, and a waddling gait.

In a report of 17 patients with osteomalacia due to vitamin D depletion on bone biopsy[1]:

  • Bone pain and muscle weakness in 16 (94 percent)
  • Bone tenderness in 15 (88 percent)
  • Fracture in 13 (76 percent)
  • Difficulty walking and waddling gait in four (24 percent)
  • Muscle spasms, cramps, a positive Chvostek's sign, tingling/numbness, and inability to ambulate in one to two (6 to 12 percent)

Bone pain is most pronounced in the lumbar spine, pelvis, and lower extremities where fractures have occurred. There may be tenderness with palpation. The pain is dull, aching, and aggravated by activity and weight bearing.

Fractures can occur without significant trauma. Fractures generally occur in the ribs, vertebrae, and long bone.

The myopathy is generally in a proximal pattern. There may be muscle wasting, reduced tone, and a waddling gait. It is thought that increased PTH and decreased phosphate and calcitriol contribute to the myopathy.

Investigations

Laboratory Findings

Standard investigations include: measurement of serum concentrations of calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, PTH, electrolytes, creatinine, and urea

The findings depend on the underlying cause of osteomalacia. Typical findings of a nutritional osteomalacia are elevated alkaline phosphatase, elevated PTH, decreased calcium, decreased phosphate, and decreased 25-hydroxyvitamin D.

Laboratory findings in different causes of osteomalacia and osteoporosis[2]
Disorder Serum Phosphate Serum calcium Serum ALP PTH Calcidiol Calcitriol
Vitamin D deficiency โ†“ or N โ†“ or N โ†‘ โ†‘ โ†“โ†“ N or โ†‘ or โ†“
Urinary phosphate wasting conditions โ†“โ†“ N N or โ†‘ N N N
Proximal renal tubular acidosis โ†“ N N N N N
Hypophosphatasia N N โ†“ N N N
Osteogenesis imperfecta and axial osteomalacia N N N or โ†‘ N N N
Osteoporosis N N N N N or โ†“ N
Calcidiol: 25-hydroxyvitamin Dโ‚ƒ, calcitriol: 1,25-dihydroxyvitamin D. Testing differences, PTH: parathyroid hormone, ALP: serum alkaline phosphatase, N: normal; โ†“: reduced; โ†“โ†“: very reduced; โ†‘: elevated.

Radiologic Findings

  • Looser pseudofractures, fissures, narrow radiolucent lines.
  • Loss of radiologic distinctness of vertebral body trabeculae and concavity of vertebral bodies, called codfish vertebrae
  • BMD isn't required. Reduced BMD doesn't distinguish osteoporosis from osteomalacia.

Bone Biopsy

Transiliac bone biopsy and histomorphometry with tetracycline labeling should only occur if the diagnosis is in doubt or when the cause of the osteomalacia has not been determined.

Diagnosis

Based on combination of clinical features (bone pain, tenderness, fractures, muscle weakness), laboratory results, radiologic findings. Rarely transiliac bone biopsy is required with double tetracycline labeling.

Differential Diagnosis

Differential diagnosis of bone fractures, bone pain, and reduced BMD
  • Osteoporosis
  • Osteomalacia
  • Malignancy including multiple myeloma
  • Paget disease
  • Hyperparathyroidism

Osteoporosis and osteomalacia may be confused. In osteoporosis there is a decreased apparent density of normally mineralised bone matrix. While in osteomalacia there is an increased, normal, or most commonly decreased mass of insufficiently mineralised bone.[3]

Osteoporosis Osteomalacia
Definition Bone mass decreased

Mineralisation normal

Bone mass variable

Mineralisation decreased

Age of onset Generally elderly, postmenopausal Any age
Aetiology Endocrine abnormality

Age

Idiopathic

Vitamin D deficiency

Abnormality of vitamin D pathway

Hypophosphataemic syndromes

Renal tubular acidosis

Hypophosphatasia

Symptoms Pain referable to fracture site Generalised bone pain
Signs Tenderness at fracture site Tenderness at fracture site and generalised tenderness
Bone mineral density Reduced May be reduced, especially in vitamin D deficiency
Serum Calcium Normal Low or normal (high in hypophosphatasia)
Serum P1 Normal Low or normal (high in renal osteodystrophy)
Alkaline phosphatase Normal Elevated, except on hypophosphatasia
Urinary calcium High or normal Normal or low (high in hypophosphatasia)
Bone biopsy Tetracycline labels normal Tetracycline labels abnormal

Treatment

The treatment depends on the underlying cause.

Osteomalacia secondary to severe vitamin D deficiency

  • Treatment with vitamin D and calcium.
  • Vitamin D treatment normally results in dramatic improvements in pain, bone tenderness, and muscle strength within a few weeks. A common regimen is 50,000 IU once per week for 6-8 weeks, then maintenance dosing.
  • Following vitamin D treatment, monitor serum alkaline phosphate, PTH, calcium, and urinary calcium extretion at one month, three months, then every six to twelve months.
  • Serum calcium concentration measurement allows detection of early hypercalcaemia from excessive dosing.
  • At three to four months measure 25-hydroxyvitamin D levels, and adjust the dose to prevent hyeprcalciuria or hypercalcaemia.
  • Radiologic abnormalities can take up to a year or more to resolve

See Also

References

  1. โ†‘ Basha B, Rao DS, Han ZH, Parfitt AM. Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal malabsorption. Am J Med. 2000 Mar;108(4):296-300. doi: 10.1016/s0002-9343(99)00460-x. PMID: 11014722.
  2. โ†‘ A Cohen et al. Clinical manifestations, diagnosis, and treatment of osteomalacia. UpToDate. June 2021
  3. โ†‘ Orthopaedic Basic Science 2nd edition. Chapter 13. Form and function of bone

Literature Review