Key Facts

Vitamin D is essential for calcium and phosphate homeostasis and bone health. It is synthesised in the skin through UVB exposure and obtained from dietary sources. Deficiency is extremely prevalent in the UK due to limited sunlight exposure, particularly in northern latitudes.

Epidemiology

• 20% of UK adults have serum 25-OH-D <25 nmol/L
• Higher prevalence in Scotland and Northern England
• More common in South Asian, African, and Caribbean ethnic groups in the UK
• Seasonal variation: lowest levels in January–March
• UK is at latitude 50-60°N – insufficient UVB for vitamin D synthesis from October to March

Aetiology

• Reduced sunlight exposure: housebound, institutionalised, covered skin, northern latitude
• Dietary insufficiency: limited oily fish, egg yolks, fortified foods
• Malabsorption: coeliac disease, Crohn's disease, short bowel syndrome
• Increased catabolism: anticonvulsants (carbamazepine, phenytoin), rifampicin
• Reduced synthesis: chronic kidney disease (impaired 1-alpha-hydroxylation), liver disease
• Obesity: vitamin D sequestered in adipose tissue

Pathophysiology

• Vitamin D3 (cholecalciferol) is hydroxylated in the liver to 25-OH-D then in the kidneys to active 1,25-(OH)2-D (calcitriol)
• Calcitriol increases intestinal calcium and phosphate absorption
• Deficiency leads to secondary hyperparathyroidism, increased bone resorption, and impaired mineralisation
• Results in rickets (children) or osteomalacia (adults)

Asymptomatic

• Many patients are asymptomatic; diagnosed on incidental blood testing

Musculoskeletal Symptoms

• Diffuse bone pain and tenderness, particularly pelvis, lower back, and legs
• Proximal muscle weakness – difficulty rising from a chair, climbing stairs
• Increased fracture risk, particularly in the elderly
• Myalgia and generalised aches

Severe Deficiency (Osteomalacia)

• Bone pain with characteristic waddling gait
• Looser zones (pseudofractures) on X-ray – pathognomonic
• Pathological fractures

In Children (Rickets)

• Bowing of legs (genu varum)
• Widened wrists and ankles – metaphyseal expansion
• Rachitic rosary – enlarged costochondral junctions
• Craniotabes – softening of skull bones
• Delayed fontanelle closure, delayed dentition

Red Flags

• Severe hypocalcaemia with tetany, seizures, or laryngospasm
• Pathological fracture in a young patient
• Failure to thrive or developmental delay in children

Bedside

• Assess risk factors: skin colour, diet, sun exposure, BMI
• Assess for proximal myopathy (sit-to-stand test)

Bloods

• Serum 25-hydroxyvitamin D (25-OH-D): gold standard
  • <25 nmol/L: deficient
  • 25-50 nmol/L: insufficient

  • 50 nmol/L: sufficient

• Adjusted calcium: may be low or low-normal
• Phosphate: may be low
• ALP: elevated (indicates increased bone turnover)
• PTH: elevated (secondary hyperparathyroidism)
• Consider coeliac screen (tTG antibodies) if malabsorption suspected

Imaging

• X-ray: Looser zones (pseudofractures) – pathognomonic of osteomalacia; widened growth plates/metaphyseal cupping in rickets
• DEXA scan: may show reduced bone density (often misdiagnosed as osteoporosis)

Special Tests

• Bone biopsy: rarely needed; shows increased osteoid volume and reduced mineralisation
• 24-hour urinary calcium: low in vitamin D deficiency

Non-pharmacological

• Dietary advice: oily fish (salmon, mackerel), egg yolks, fortified foods (cereals, margarine)
• Safe sun exposure: 10-15 minutes of midday sun exposure to arms/face (March–September)
• Address underlying causes (e.g., coeliac disease, malabsorption)

Pharmacological

• Treatment of deficiency (<25 nmol/L) per NICE CKS:
  • Colecalciferol (D3) loading: 50,000 IU weekly for 6 weeks (or 4,000 IU daily for 10 weeks)
  • Followed by maintenance: 800-2,000 IU (20-50 mcg) daily
• Insufficiency (25-50 nmol/L): 800-4,000 IU daily
• Prevention per SACN/PHE:
  • All adults and children >4 years: 400 IU (10 mcg) daily, especially October–March
  • Breastfed infants from birth: 340-400 IU daily
  • Formula-fed infants taking <500ml/day: 340-400 IU daily
  • At-risk groups: year-round supplementation
• Ergocalciferol (D2): less effective than D3, used mainly in vegans
• Alfacalcidol or calcitriol: for CKD-related deficiency (impaired 1-alpha-hydroxylation)
• Correct hypocalcaemia with calcium supplements if present

Referral Criteria

• Refractory deficiency despite adequate supplementation → consider malabsorption
• CKD stage 4-5 → nephrology for alfacalcidol management
• Rickets in children → paediatric endocrinology
• Suspected genetic causes (vitamin D-dependent rickets)

• Excellent prognosis with appropriate supplementation
• Biochemical improvement typically seen within 4-6 weeks of loading dose
• Bone pain and myopathy usually improve within 3-6 months
• Rickets changes reversible with treatment in most cases
• Chronic deficiency increases risk of osteoporotic fractures, particularly in elderly
• Association with increased risk of falls in the elderly (due to proximal myopathy)

Vitamin D Status Classification

Treatment Doses Summary