Introduction

Hypocholecalciferolemia, commonly referred to as vitamin D deficiency, is a disorder characterized by inadequate serum concentrations of 25-hydroxyvitamin D [25(OH)D], resulting in impaired calcium and phosphate homeostasis. Persistent deficiency leads to defective bone mineralization, causing rickets in children and osteomalacia in adults. Vitamin D deficiency also contributes to osteoporosis, muscle weakness, falls, and fragility fractures, particularly among older adults.

According to the Endocrine Society, serum 25(OH)D concentrations between 30–60 ng/mL (75–150 nmol/L) are considered sufficient for optimal musculoskeletal health.

Epidemiology

• One of the most common nutritional deficiencies worldwide.

• Particularly common among infants, older adults, pregnant women, and individuals with limited sun exposure.

• Higher prevalence in people with darker skin pigmentation due to reduced cutaneous vitamin D synthesis.

• Common in patients with chronic kidney disease, liver disease, obesity, and malabsorption syndromes.

Etiology

Vitamin D deficiency may result from inadequate intake, reduced skin synthesis, impaired activation, or excessive losses.

Common causes include:

• Inadequate dietary vitamin D intake

• Limited sunlight exposure

• Dark skin pigmentation

• Aging

• Obesity

• Malabsorption syndromes (e.g., celiac disease, inflammatory bowel disease)

• Chronic liver disease

• Chronic kidney disease

• Long-term anticonvulsant therapy

• Glucocorticoid therapy

• Exclusive breastfeeding without vitamin D supplementation

• Bariatric surgery

Risk factors

• Infancy and childhood

• Older age

• Pregnancy and lactation

• Institutionalization

• Limited outdoor activity

• Chronic kidney disease

• Chronic liver disease

• Obesity

• Malabsorption disorders

• Dark skin

• Strict vegan diets without supplementation

• Long-term use of enzyme-inducing anticonvulsants

Pathophysiology

Vitamin D is essential for intestinal absorption of calcium and phosphate. Deficiency reduces intestinal calcium absorption, resulting in hypocalcemia that stimulates secretion of parathyroid hormone (secondary hyperparathyroidism). Elevated parathyroid hormone maintains serum calcium by increasing bone resorption and renal phosphate excretion, leading to hypophosphatemia and defective mineralization of newly formed bone. In adults, this results in osteomalacia, characterized by accumulation of poorly mineralized osteoid, while in growing children impaired mineralization of the growth plate produces rickets with skeletal deformities and impaired linear growth. Persistent deficiency also causes proximal muscle weakness, increasing the risk of falls and fractures.

Classification

According to serum 25-hydroxyvitamin D concentration:

Clinical presentation

Clinical manifestations depend on the severity and duration of deficiency.

Adults

Mild deficiency is often asymptomatic.

Symptoms and signs may include:

• Bone pain and tenderness

• Diffuse musculoskeletal pain

• Proximal muscle weakness

• Difficulty rising from a chair or climbing stairs

• Fatigue

• Increased risk of falls

• Fragility fractures

• Osteomalacia

• Cognitive decline in older adults

• Gait instability

Children

Mild deficiency may be asymptomatic.

Clinical features include:

• Delayed motor milestones

• Bone pain

• Muscle weakness

• Fatigue and malaise

• Delayed growth

• Delayed dentition

• Bowing of the legs

• Widening of wrists and ankles

• Frontal bossing

• Rachitic rosary

• Craniotabes (infants)

• Rickets

• Hypocalcaemic seizures (severe deficiency)

Diagnostic criteria

Vitamin D deficiency is diagnosed by demonstrating:

• Serum 25-hydroxyvitamin D concentration below 20 ng/mL

• Compatible clinical features where present

• Supportive biochemical abnormalities such as hypocalcemia, hypophosphatemia, elevated alkaline phosphatase, and elevated parathyroid hormone

• Radiological evidence of rickets or osteomalacia in symptomatic patients

Investigations

Laboratory investigations

• Serum 25-hydroxyvitamin D [25(OH)D]

• Serum calcium

• Fasting serum phosphate

• Serum alkaline phosphatase

• Parathyroid hormone

• Renal function tests

• Serum magnesium (where available)

• Liver function tests when clinically indicated

Imaging

Dual-energy X-ray absorptiometry (DXA)

May be useful in adults at risk of osteoporosis.

Plain radiographs

Children with rickets may demonstrate:

• Metaphyseal widening

• Metaphyseal cupping

• Fraying of growth plates

• Bowing deformities

Adults with osteomalacia may demonstrate:

• Looser's zones (pseudofractures)

• Generalized osteopenia

Differential diagnosis

• Osteoporosis

• Osteomalacia from other causes

• Hypoparathyroidism

• Chronic kidney disease–mineral bone disorder

• Renal tubular disorders

• Osteogenesis imperfecta

• Hypophosphatasia

• Nutritional calcium deficiency

Management

Treatment aims to:

• Restore normal vitamin D levels

• Correct calcium and phosphate abnormalities

• Improve bone mineralization

• Prevent fractures

• Improve muscle strength

• Prevent recurrence

Non-pharmacological management

Recommended measures include:

• Regular safe sunlight exposure

• Adequate dietary vitamin D intake

• Adequate dietary calcium intake

• Weight-bearing physical activity where appropriate

• Bracing for skeletal deformities when indicated

• Protective walking aids if mobility is impaired

• Isometric and muscle-strengthening exercises

• Fall prevention strategies in older adults

Pharmacological treatment

Children (1–18 years)

Colecalciferol

• 2,000 IU orally once daily for 6 weeks

OR

• 50,000 IU orally once weekly for 6 weeks

Followed by maintenance therapy:

• 600–1,000 IU orally once daily for 3–6 months

Re-evaluate by measuring serum 25(OH)D concentration.

Adults

Colecalciferol

• 6,000 IU orally once daily

OR

• 50,000 IU orally once weekly

for 8 weeks.

Follow with maintenance therapy:

• 1,500–2,000 IU orally daily.

Calcium supplementation

Patients with inadequate dietary calcium intake should receive calcium supplementation alongside vitamin D therapy to optimize bone mineralization.

Monitoring and follow-up

Patients should be reassessed after completion of the loading regimen.

Monitoring should include:

• Serum 25(OH)D concentration

• Serum calcium

• Serum phosphate

• Serum alkaline phosphatase

• Parathyroid hormone when indicated

• Clinical improvement in pain and muscle strength

• Healing of rickets or osteomalacia on imaging when appropriate

Complications

Untreated vitamin D deficiency may result in:

Children

• Rickets

• Permanent skeletal deformities

• Growth retardation

• Delayed motor development

• Hypocalcaemic seizures

Adults

• Osteomalacia

• Osteoporosis

• Fragility fractures

• Chronic musculoskeletal pain

• Recurrent falls

• Muscle weakness

• Reduced quality of life

Prevention

• Adequate sunlight exposure

• Balanced diet containing vitamin D and calcium

• Routine supplementation in high-risk groups

• Vitamin D supplementation for exclusively breastfed infants according to national recommendations

• Early identification and treatment of malabsorption disorders

• Regular monitoring of high-risk individuals

Prognosis

The prognosis is excellent when vitamin D deficiency is identified early and treated appropriately. Most patients experience improvement in muscle strength and bone pain within weeks of treatment, while biochemical abnormalities usually normalize over several months. Children treated promptly recover normal bone mineralization and growth, whereas delayed treatment may result in permanent skeletal deformities. Long-term maintenance therapy and correction of underlying risk factors help prevent recurrence.