What laboratory tests should be ordered for a 41-year-old man with rickets?

Laboratory Workup for a 41-Year-Old Male with Rickets

Order a comprehensive metabolic panel including serum phosphate, calcium, alkaline phosphatase, creatinine, bicarbonate, 25(OH) vitamin D, 1,25(OH)₂ vitamin D, PTH, and spot urine for phosphate, calcium, creatinine, amino acids, glucose, and low-molecular-weight proteins to differentiate between calcipenic and phosphopenic rickets and identify the underlying etiology. 1

Initial Serum Tests

The diagnostic approach begins with blood work to establish the rickets subtype:

• Serum phosphate – Low levels indicate phosphopenic rickets, which is the most common form in adults with hereditary disease 1, 2
• Serum calcium – Typically low-normal or normal in phosphopenic rickets; low in calcipenic (vitamin D deficiency) rickets 1, 2, 3
• Alkaline phosphatase (ALP) – Elevated in all active rickets types and serves as a reliable biomarker of disease activity 2, 3
• 25(OH) vitamin D – Low in nutritional rickets; normal in phosphopenic rickets 2, 3
• 1,25(OH)₂ vitamin D – Low or inappropriately normal in phosphopenic rickets despite hypophosphatemia 1, 2, 3
• Parathyroid hormone (PTH) – Upper limit of normal or slightly elevated in phosphopenic rickets; markedly elevated in calcipenic rickets 1, 2
• Creatinine – Essential to assess renal function and calculate TmP/GFR 1
• Bicarbonate – Must exclude metabolic acidosis suggesting Fanconi syndrome 1

Urine Studies

A spot urine sample (or 24-hour collection) is critical to differentiate renal phosphate wasting from other causes:

• Urinary phosphate and creatinine – Calculate TmP/GFR (tubular maximum reabsorption of phosphate per GFR) to confirm renal phosphate wasting 1
• Urinary calcium and creatinine – Low urinary calcium is typical in active rickets; helps distinguish from hereditary hypophosphatemic rickets with hypercalciuria 1
• Urinary amino acids, glucose, and low-molecular-weight proteins – Essential to exclude Fanconi syndrome, which causes non-selective tubular wasting 1

Advanced Testing Based on Initial Results

If Phosphopenic Rickets is Confirmed (Low Phosphate, Normal Vitamin D):

• Intact FGF23 levels – Non-suppressed or elevated FGF23 in the setting of hypophosphatemia suggests X-linked hypophosphatemia (XLH) or other FGF23-mediated disorders, which account for approximately 80% of hereditary phosphopenic rickets 1
• Genetic testing for PHEX gene – Recommended to confirm XLH diagnosis 1
• Consider genetic testing for other genes (DMP1, ENPP1, FGF23) if PHEX is negative 1

If Calcipenic Rickets is Suspected (Low Calcium, Low Vitamin D):

• Nutritional history – Assess dietary vitamin D and calcium intake 4, 5
• Consider malabsorption workup if dietary intake appears adequate 4

Critical Diagnostic Pitfalls

Do not rely on FGF23 for routine diagnosis or monitoring – FGF23 levels vary considerably by assay and are influenced by phosphate intake, vitamin D therapy, and treatment status 1, 2, 3

Always exclude Fanconi syndrome – The presence of glucosuria, aminoaciduria, or low-molecular-weight proteinuria indicates non-selective tubular dysfunction rather than isolated phosphate wasting 1

Consider acquired causes in adults – Tumor-induced osteomalacia, alcohol-induced FGF23 syndrome, and medication effects (particularly intravenous iron causing "6H-syndrome") must be excluded in adult-onset cases 1

Screen for complications – In confirmed XLH or other hereditary forms, additional workup should assess for dental abscesses, enthesopathies, spinal stenosis, pseudofractures, and early osteoarthritis 1

Algorithmic Approach

1. First-line labs: Phosphate, calcium, ALP, 25(OH) vitamin D, PTH, creatinine, bicarbonate 1
2. If phosphate is low with normal/high-normal vitamin D: Add 1,25(OH)₂ vitamin D, spot urine for phosphate/calcium/creatinine (calculate TmP/GFR), and urine amino acids/glucose/protein 1
3. If isolated renal phosphate wasting confirmed: Measure intact FGF23 and pursue genetic testing 1
4. If vitamin D is low: Treat nutritionally and reassess; consider malabsorption workup if refractory 4, 5