Nutritional Rickets

Nutritional rickets is impaired mineralisation of the growth plate and osteoid in children, caused by vitamin D deficiency, calcium deficiency or both. Osteomalacia occurs in the same condition after growth plate closure.

It is most common in infants and toddlers, especially exclusively breastfed infants without vitamin D supplements, children with dark skin and limited sunlight exposure, covered clothing, northern latitudes, and children on diets low in calcium, which is common in parts of Africa and Asia.

Maternal vitamin D deficiency in pregnancy increases the risk in the infant. Severe disease can cause hypocalcaemic seizures, tetany, cardiomyopathy, deformity and delayed motor development.

Pathophysiology.

Vitamin D deficiency lowers intestinal calcium absorption, causing hypocalcaemia and secondary hyperparathyroidism. Parathyroid hormone raises serum calcium at the cost of phosphaturia, so serum phosphate falls.

Low phosphate impairs apoptosis of hypertrophic chondrocytes, causing growth plate widening, and osteoid fails to mineralise. In calcium deficiency, vitamin D concentrations may be normal but calcitriol levels are high.

• Delayed motor milestones, irritability, muscle weakness and a protuberant abdomen.
• Craniotabes, delayed fontanelle closure, frontal bossing, delayed dentition and enamel defects.
• Widened wrists and ankles, rachitic rosary (costochondral swelling), Harrison sulcus, and bowed legs or knock knees after walking.
• Hypocalcaemic seizures, tetany, laryngospasm, or heart failure from dilated cardiomyopathy, especially at 2 to 6 months.

Red flags.

• Seizures, tetany, stridor or cardiac failure from hypocalcaemia.
• Short stature, severe asymmetric deformity or family history, suggesting hypophosphataemic or vitamin D-dependent rickets.
• Fractures in a young child, requiring consideration of abuse.

• Radiographs of the wrist or knee: metaphyseal widening, cupping and fraying, widened growth plate, osteopenia and bowing.
• Biochemistry: raised alkaline phosphatase, low or normal calcium, low phosphate (in vitamin D deficiency), raised parathyroid hormone, and 25-hydroxyvitamin D under 30 nmol/L as deficiency.
• Urea, creatinine, bicarbonate and urine pH if renal causes are suspected. Dietary history of calcium and vitamin D, and maternal vitamin D status.

Differential diagnosis. X-linked hypophosphataemic rickets (low phosphate with normal calcium and parathyroid hormone), vitamin D-dependent rickets, renal tubular disorders, chronic kidney disease, hypophosphatasia, metaphyseal chondrodysplasia, osteogenesis imperfecta, Blount disease and abuse.

Emergency hypocalcaemia. Calcium gluconate 10%, 0.5 mL/kg (50 mg/kg) IV over 5 to 10 minutes with ECG monitoring, followed by oral calcium.

Vitamin D replacement.

• Daily vitamin D3 for 12 weeks: 2000 units daily for infants under 12 months, and 3000 to 6000 units daily for older children.
• Alternatively a single high dose (stoss therapy) where adherence is uncertain: 50 000 units in infants under 3 months, 150 000 units at 3 to 12 months and 300 000 units in children over 12 months, followed by maintenance.
• Calcium: oral elemental calcium 500 mg daily in divided doses for 12 weeks, or 50 mg/kg/day, in addition to vitamin D. Use dietary or supplement calcium in calcium deficiency rickets.
• Maintenance after treatment: vitamin D 400 units daily under 12 months and 600 units daily after.

Monitoring. Calcium, phosphate, alkaline phosphatase and parathyroid hormone at 4 weeks, and radiographs at 3 months. Biochemical improvement is expected in 2 to 4 weeks, and radiographic healing in 1 to 3 months. Check urinary calcium for hypercalciuria on high dose treatment, and serum calcium for hypercalcaemia.

Referral and escalation. Refer to a paediatric endocrinologist or bone specialist for failure to respond after 3 months, persistent hypophosphataemia, or suspected genetic disease. Refer to orthopaedics for persistent deformity after the age of 3.

Special groups. Breastfed infants need vitamin D 400 units daily from birth. Mothers with deficiency need treatment, and siblings should be screened.