What are the diagnostic features and treatment options for rickets?

Rickets: Diagnostic Features and Treatment

Diagnostic Features

Clinical Presentation

Rickets presents with characteristic skeletal deformities that vary by age, including lower limb bowing (genu varum or valgus), widened wrists and ankles, rachitic rosary (prominent costochondral junctions), Harrison's groove (horizontal indentation along lower ribs), and disproportionate short stature with relatively preserved trunk growth. 1

• In infants and young children, delayed walking, waddling gait, and progressive leg deformities become apparent around 6 months of age 1
• Skull abnormalities including dolichocephaly (elongated head shape) may be present 1
• Dental manifestations include frequent abscesses and poor mineralization, particularly in children over 3 years 1
• Adults with untreated rickets present with bone pain, osteomalacia, pseudofractures, stiffness, and osteoarthritis 1

Radiographic Features

Radiographs demonstrate cupping and flaring of metaphyses at the wrists and knees, fraying and irregularity of growth plates, and widening of the growth plate zone. 2, 1

• Severe cases show marked leg bowing with partial fraying of distal femoral and proximal tibial growth plates 1
• In adults with closed growth plates, Looser's zone fractures may be visible in extreme cases 2
• Bone biopsy can confirm osteomalacia at earlier disease stages when radiographs are inconclusive 2

Biochemical Findings

Elevated alkaline phosphatase (ALP) is the most reliable biomarker of rickets activity, accompanied by hypophosphatemia, elevated parathyroid hormone (PTH), and low 25-hydroxyvitamin D in nutritional rickets. 1, 3

• In children, total ALP can be used as bone-specific ALP represents 80-90% of circulating levels 1
• In adults, bone-specific ALP is preferred since only 50% originates from bone 1
• X-linked hypophosphatemia (XLH) shows hypophosphatemia, elevated ALP, elevated FGF23, and normal or low 25-hydroxyvitamin D 1, 4
• Low serum calcium and phosphate with elevated PTH suggests nutritional rickets 5, 2

Differential Diagnosis

XLH accounts for approximately 80% of hypophosphatemic rickets cases and must be distinguished from nutritional rickets, which improves with vitamin D supplementation. 1

• Consider XLH when hypophosphatemia persists despite vitamin D and calcium supplementation 1
• Genetic testing of the PHEX gene confirms 70-90% of XLH cases 1, 4
• Other causes include vitamin D-dependent rickets (types I and II), familial hypophosphatemic rickets, renal Fanconi syndrome, and tumor-induced osteomalacia 1, 5
• Male-to-male transmission, symptoms after age 2 years, or presence of acidosis/glucosuria suggest alternative diagnoses 1

Treatment Options

Nutritional Rickets

Nutritional rickets requires high-dose vitamin D (cholecalciferol or ergocalciferol) daily for minimum 12 weeks, followed by lifelong maintenance supplementation, plus ensuring adequate calcium intake. 6, 2

• Ergocalciferol is FDA-approved for treatment of refractory rickets and familial hypophosphatemia 6
• Treatment should achieve serum 25-hydroxyvitamin D of at least 20 ng/mL (Institute of Medicine) or preferably 30-60 ng/mL (Endocrine Society) 7
• Adequate dietary calcium is essential for clinical response to vitamin D therapy 6
• Stoss therapy (single high-dose) may be used in exceptional circumstances 2

X-Linked Hypophosphatemia (XLH)

Conventional treatment of XLH combines oral phosphate salts (multiple daily doses) with active vitamin D (calcitriol or alfacalcidol), though burosumab (anti-FGF23 antibody) is now superior and FDA-approved as first-line therapy. 1, 3

• Phosphate supplementation dose: 2.2 mg/kg body weight divided into 4-5 daily doses 3
• Active vitamin D prevents secondary hyperparathyroidism from phosphate therapy 1, 3
• Burosumab has demonstrated superiority over conventional therapy and is approved for XLH treatment 3
• Treatment goals include normalizing ALP, healing rickets radiographically, and improving growth velocity 1

Monitoring During Treatment

Monitor serum ALP, phosphate, calcium, PTH, and urinary calcium every 3-6 months, with radiographs to assess healing and growth velocity measurements in children. 1, 3

• ALP normalization indicates rickets healing; persistently elevated levels suggest undertreatment 1
• Rising urinary calcium suggests excessive active vitamin D relative to phosphate 1
• Suppressed PTH indicates disproportionately high active vitamin D dosing 1
• Watch for treatment complications including hypercalciuria, nephrocalcinosis, nephrolithiasis, and secondary hyperparathyroidism 3
• Height should increase by approximately 1 standard deviation within 2-3 years when treatment initiated in preschool-age children 1

Treatment Precautions

The therapeutic range between effective and toxic vitamin D doses is narrow in vitamin D-resistant rickets, requiring frequent monitoring of serum calcium during high-dose therapy. 6

• Dosage must be individualized and readjusted as clinical improvement occurs 6
• Thiazide diuretics can cause hypercalcemia in hypoparathyroid patients receiving vitamin D 6
• Mineral oil interferes with fat-soluble vitamin absorption including vitamin D 6
• Pregnant women should not exceed 400 IU daily unless specific benefits outweigh risks; lactating women taking 6400 IU daily can provide adequate vitamin D through breast milk 6, 7

Prevention Strategies

All infants and young children should receive vitamin D from fortified formulas/foods or supplementation starting in the first two months of life, with pregnant women taking 1500-2000 IU daily. 7, 5

• Exclusively breastfed infants require vitamin D supplementation to prevent nutritional rickets 5
• Dark-skinned children with limited sun exposure are at particularly high risk 7, 5
• Food fortification with vitamin D and/or calcium is the most cost-effective population-level prevention strategy 2