What tests should be done for a patient with suspected rickets and vitamin D deficiency?

Diagnostic Tests for Suspected Rickets and Vitamin D Deficiency

For patients with suspected rickets and vitamin D deficiency, a comprehensive diagnostic workup should include serum measurements of phosphate, calcium, alkaline phosphatase, parathyroid hormone, 25(OH) vitamin D, and 1,25(OH)2 vitamin D, along with urinary calcium and phosphate levels to calculate renal phosphate wasting. 1, 2

Initial Laboratory Tests

Essential Blood Tests:

• Serum phosphate (to assess hypophosphatemia)
• Serum calcium (total and ionized)
• Alkaline phosphatase (ALP) - elevated in active rickets
• Parathyroid hormone (PTH) - to assess secondary hyperparathyroidism
• 25-hydroxyvitamin D [25(OH)D] - primary indicator of vitamin D status
• 1,25-dihydroxyvitamin D [1,25(OH)2D] - active form of vitamin D
• Serum creatinine - to assess renal function

Urinary Tests:

• Spot urine calcium and phosphate with creatinine
• Calculate tubular maximum reabsorption of phosphate per glomerular filtration rate (TmP/GFR) 1
• Urinary calcium:creatinine ratio

Specialized Tests to Consider

For Renal Phosphate Wasting:

• Evaluate for non-selective renal tubular phosphate wasting (Fanconi syndrome) by testing for:
  • Urinary bicarbonate
  • Urinary amino acids
  • Urinary glucose
  • Urinary uric acid
  • Low molecular mass proteinuria 1

For Vitamin D Assessment:

• When measuring vitamin D levels, use an assay that measures both 25(OH)D2 and 25(OH)D3 1
• If using an assay that separates these compounds (HPLC or LC/MS-MS), report the sum as the main result
• Avoid gel tubes for sample collection until more data are available 1

Radiological Evaluation

• Wrist and/or knee and/or ankle radiographs to assess for signs of rickets 1
• Look for:
  • Metaphyseal fraying and widening of growth plates
  • Cupping and flaring of metaphyses
  • Osteopenia 3

Additional Considerations

For Genetic Forms of Rickets:

• Consider genetic testing for PHEX gene mutations in cases of suspected X-linked hypophosphatemic rickets, especially with family history 1, 2
• Measure intact FGF23 levels in cases with negative family history 1

For Secondary Causes:

• Thyroid function tests to rule out hypothyroidism 1
• In cases of suspected malabsorption, consider additional tests for celiac disease or other gastrointestinal disorders

Monitoring After Diagnosis

• After initiating vitamin D supplementation, measure 25(OH)D levels after at least 3 months to allow plateau to be reached 1
• For intermittent regimens, measure levels just prior to the next dose
• Monitor serum calcium, phosphate, ALP, and PTH levels regularly during treatment
• Monitor urinary calcium excretion to avoid hypercalciuria during treatment 1

Important Pitfalls to Avoid

• Do not rely solely on serum calcium levels to rule out vitamin D deficiency, as they may remain normal despite deficiency 1
• Avoid misinterpreting radiologic features of rickets as fractures 4
• Remember that vitamin D deficiency rickets can occasionally mimic pseudohypoparathyroidism with hypocalcemia and hyperphosphatemia 5
• Do not overlook the possibility of vitamin D-resistant forms of rickets when standard supplementation fails 6

By following this systematic diagnostic approach, clinicians can accurately identify rickets and vitamin D deficiency, determine its severity, and guide appropriate treatment decisions to prevent long-term complications.