What is the appropriate evaluation and management for a child under five years old with suspected rickets (bowing of the legs, frontal bossing, and rachitic rosary)?

Evaluation and Management of Rickets in Children Under Five Years

Initial Clinical Assessment

For a child under five presenting with bowing of legs, frontal bossing, and rachitic rosary, immediately obtain serum 25-hydroxyvitamin D, calcium, phosphate, alkaline phosphatase, and parathyroid hormone levels to differentiate nutritional rickets from hereditary forms, then initiate treatment with high-dose vitamin D (2,000 IU daily for 12 weeks) plus calcium supplementation (250-500 mg elemental calcium daily) if nutritional rickets is confirmed. 1

Key History Elements to Obtain

• Feeding history: Exclusive breastfeeding without vitamin D supplementation is a critical risk factor for nutritional rickets 2, 1
• Sun exposure and skin pigmentation: Dark-skinned children with limited sunlight exposure are at substantially higher risk 1, 3
• Dietary calcium intake: Assess whether intake is below 300 mg/day (normal requirement is 1,250 mg/day for ages 9-18) 4
• Prematurity history: Extreme prematurity (≤28 weeks or ≤1500 g) predisposes to metabolic bone disease 1
• Mobility status: Mobile infants with rickets have higher fracture risk; fractures in rickets typically occur only after children become mobile (8-19 months) 2, 1
• Family history: X-linked hypophosphatemia represents 80% of hereditary hypophosphatemic rickets and may present after age 2 years 2, 4

Physical Examination Findings

• Classic skeletal deformities: Swollen wrists and ankles, rachitic rosary (costochondral beading), frontal bossing, soft skull, leg bowing (genu varum or valgum) 5, 6
• Measure intercondylar/intermalleolar distance: Quantifies severity of varus or valgus deformities 2
• Growth parameters: Document height and growth velocity; appropriate treatment should increase height by ~1 standard deviation within 2-3 years 2
• Proximal muscle weakness and bone pain: Common features suggesting active rickets 1, 5
• Life-threatening complications: Assess for hypocalcemic seizures or signs of dilated cardiomyopathy (heart failure) in severe cases 5

Diagnostic Laboratory Evaluation

Essential Initial Tests

• 25-hydroxyvitamin D: Deficiency defined as <20 ng/mL; severe deficiency <10-12 ng/mL 1, 7
• Serum calcium and phosphate: Low levels characteristic of nutritional rickets 1, 8
• Alkaline phosphatase: Elevated ALP is a reliable biomarker of rickets activity; total ALP can be used in children as bone-specific ALP represents 80-90% of total 2, 1
• Parathyroid hormone: Typically elevated in nutritional rickets 1, 8

Additional Tests When Hereditary Forms Suspected

• Serum phosphate with renal tubular reabsorption of phosphate (TmP/GFR): Essential if X-linked hypophosphatemia or other hereditary hypophosphatemic rickets is suspected 2, 8
• Extended molecular genetic analysis: Helpful in unclear cases of hypophosphatemic rickets to establish definitive diagnosis 2, 8

Radiographic Evaluation

Characteristic Findings in Nutritional Rickets

• Metaphyseal changes: Widening with irregular, frayed, and cupped edges; loss of zone of provisional calcification 2, 1
• Generalized demineralization: Diffuse osteopenia throughout skeleton 1
• Fracture pattern if present: Metaphyseal fractures occur closer to the diaphysis (not the classic juxtaphyseal corner/bucket-handle pattern seen in abuse) 2, 1

Important Diagnostic Pitfall

Vitamin D insufficiency alone does NOT cause multiple fractures, rib fractures, or classic metaphyseal lesions (CMLs). Studies show no association between vitamin D insufficiency and these high-specificity indicators of abuse 2, 1. In a study of 40 healthy infants with vitamin D insufficiency, fracture prevalence was zero 2. When fractures do occur in rickets, they are seen only in mobile children (8-19 months) and involve long bones, ribs, or metatarsals in the background of florid rachitic changes 2.

Treatment Protocol for Nutritional Rickets

Vitamin D Replacement

Loading regimen options (choose one):

• 2,000 IU vitamin D₃ daily for 12 weeks 1
• 50,000 IU every other week for 12 weeks 1

Avoid active vitamin D analogs (calcitriol) for nutritional rickets; cholecalciferol (vitamin D₃) is preferred due to higher bioefficacy compared with ergocalciferol (vitamin D₂) 1.

Calcium Supplementation

• 250-500 mg elemental calcium daily during treatment phase 1
• Ensure adequate dietary calcium intake or provide supplementation to reach recommended levels 5

Follow-Up and Monitoring

• Repeat 25-OH-D after 12 weeks: Target level >20 ng/mL (Institute of Medicine) or preferably 30-60 ng/mL (Endocrine Society) 1, 7
• Expected healing time: 3-9 months for radiographic and clinical improvement 4
• Maintenance therapy: 600 IU vitamin D₃ daily for children aged 1-18 years after loading phase 1
• Monitor alkaline phosphatase: Should normalize as rickets heals 2
• Assess limb deformity improvement: Reduction in intercondylar/intermalleolar distance indicates response 2

Management of Hereditary Forms

X-Linked Hypophosphatemia (Most Common Hereditary Form)

• Conventional therapy: Phosphate supplementation combined with active vitamin D treatment 2
• Multidisciplinary care: Requires expert in metabolic bone diseases coordinating with orthopedic surgeons, physical therapists, dentists, and other specialists 2
• Orthopedic evaluation: Patients with substantial limb deformities need assessment by orthopedic surgeon experienced in metabolic bone disease 2
• Dental surveillance: Twice-yearly dental examinations after tooth eruption; orthodontic evaluation around age 12 years 2
• Craniosynostosis screening: Consider in children up to age 5 years with insufficient head circumference increase or abnormal head shape 2

Vitamin D-Dependent Rickets

• Type I: Treated with vitamin D supplementation 3, 8
• Type II: Management more challenging due to defective vitamin D receptors 3, 8

Prevention Strategies

For Breastfed Infants

All exclusively breastfed infants should receive vitamin D supplementation beginning in the first two months of life to prevent nutritional rickets 3. Alternatively, if lactating women take approximately 6,400 IU of vitamin D daily, they provide enough vitamin D in breast milk to satisfy infant requirements 7.

For Pregnant Women

Pregnant women unable to obtain adequate vitamin D from sunlight and diet should take 1,500-2,000 IU daily, as 600 IU daily will not maintain circulating 25-hydroxyvitamin D of at least 20 ng/mL in most pregnant women 7.

Population-Level Approaches

• Food fortification: Most cost-effective preventative strategy with vitamin D and/or calcium 5
• Targeted supplementation: Focus on at-risk groups (dark skin, reduced sun exposure, infants, pregnant/lactating women) 5

Critical Complications Requiring Urgent Management

• Hypocalcemic seizures: Life-threatening complication requiring immediate calcium replacement 5
• Dilated cardiomyopathy with heart failure: Can occur in severe infantile rickets 5
• Severe skeletal deformities: May ultimately require surgical intervention if not treated early 3, 6

When to Suspect Non-Nutritional Causes

• Lack of response to standard vitamin D/calcium therapy: Consider hereditary forms 2, 8
• Persistent hypophosphatemia despite treatment: Suggests X-linked hypophosphatemia or other phosphate-wasting disorders 2, 8
• Family history of rickets or consanguinity: Increases likelihood of hereditary forms 8, 6
• Coexistence with other systemic features: Hair abnormalities, renal disease, or malabsorption syndromes point to specific genetic or secondary causes 1, 8