Diagnosis of vitamin D deficiency/insufficiency in adults

Mainstay in the diagnosis of vitamin D deficiency, apart from being alert to it as a potential cause of non-specific musculoskeletal symptoms, is measurement of serum concentrations of 25-hydroxycholecalciferol (25OHD) (1)

• however, no consensus about the definition of a replete or deficient vitamin state with respect to 25OHD concentrations
  • the UK National Osteoporosis Society recommends the following vitamin D thresholds for UK practitioners in respect to bone health
    • serum 25OHD < 30 nmol/L is deficient
    • serum 25OHD of 30- 50 nmol/L may be inadequate in some people
    • serum 25OHD > 50 nmol/L is sufficient for almost the whole population (1)
• if serum 25-hydroxyvitamin D (25[OH]D) levels are less than 25 nmol/L (2,3)
  • the following investigations should be considered (depending on clinical presentation and clinical judgment) to aid the diagnosis of vitamin D deficiency and to exclude differential diagnoses:
    • bone profile (calcium, phosphate, and alkaline phosphatase [ALP]), to assess for hypocalcaemia and markers of bone disease
      • note though that serum calcium and phosphate concentrations only fall in longstanding, symptomatic, vitamin D deficiency
      • there is an increase in levels of alkaline phosphatase (total and bone-specific) increase early in vitamin D deficiency - this is a non-specific finding, but may be helpful in diagnosing individuals with otherwise unexplained elevations in alkaline phosphatase
    • renal, liver, and thyroid function tests
    • parathyroid hormone (PTH) levels
    • full blood count and ferritin, B12/folate (to identify other possible vitamin deficiencies/malabsorptive states)
    • rheumatoid and other autoimmune screening
    • inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP], to exclude other inflammatory disorders)
• radiological assessment is not routinely indicated in asymptomatic individuals
• Xrays of locally painful or tender areas, and of the ribs, lumbar spine and pelvis may suggest longstanding, symptomatic deficiency by identifying Looser's zones, cortical thinning and reduced mineralisation
  • Xrays also help in excluding other conditions
  • in vitamin D deficiency there may be general skeletal deformity that may include vertebral crush fractures, trefoil pelvis, and spontaneous fractures of the ribs, pubic rami or femoral neck
• bone biopsy is rarely used now that immunoassays of serum 25OHD are available

Notes:

• if the 25OHD concentration is below around 25nmol/L (10 µg/L) then this is probably consistent with vitamin D deficiency, which may be associated with osteomalacia (2)
• if the 25OHD concentration is 30-50nmol/L (12-20 µg/L) then this is generally considered evidence of vitamin D insufficiency, in which there may be biochemical disturbances with or without non-specific musculoskeletal symptoms

Reference:

1. National Osteoporosis Society (NOS) 2018. Vitamin D and Bone Health: A Practical Clinical Guideline for Patient Management
2. Drug and Therapeutics Bulletin 2006;44 (4);25-9.
3. Consensus Vitamin D position statement, (represents the unified views of the British Association of Dermatologists, Cancer Research UK, Diabetes UK, the Multiple Sclerosis Society, the National Heart Forum, the National Osteoporosis Society and the Primary Care Dermatology Society) - December 2010