Rickets (Osteomalacia): Test and Diagnosis

1st-order laboratory parameters-obligatory laboratory tests.

  • Calcium* [n/↓]
  • Phosphate* [n/↓]
  • Alkaline phosphatase (AP)* [↑] – typical in osteomalacia, but not specific DD bone metastases.
  • Parathyroid hormone (PTH)* [↑- ↑↑]
  • 25-hydroxyvitamin D (25(OH)-vitamin D3 ; 25-OH-D3), plasma [↓-↓↓]
  • 1,25-(OH)2-vitamin D (1,25-OH-D3), plasma [n-↑]Note: 1,25(OH)2-vitamin D3 levels ↓ + normal 25(OH)-vitamin D3 → synthesis disorder of vitamin D3.
  • Histological examination of a bone biopsy/bone punch (generous indication).

* Critical laboratory parameters for follow-up.

Laboratory parameters 2nd order – depending on the results of the history, physical examination and the obligatory laboratory parameters – for differential diagnostic clarification.

  • CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate).
  • Differential blood count
  • Alanine aminotransferase (ALT, GPT), aspartate aminotransferase (AST, GOT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (gamma-GT, GGT), alkaline phosphatase, bilirubin.
  • Blood gas analysis (BGA)
  • Urine diagnostics
    • Urine status and serum glucose [glucose in urine (glucosuria) with normal serum glucose → e.g., Fanconi syndrome; alkaline urine → e.g., renal tubular partial disorder].
    • Urinary alpha-1 microglobulin (marker for tubular proteinuria; restriction of tubular reabsorptive function) [tubular damage e.g. as part of Fanconi syndrome or in nephritides, nephropathies, renal involvement].
  • Urea, creatinine, if necessary cystatin C or creatinine clearance [creatinine clearance: differential diagnosis renal osteopathy].
  • Gamma-glutamyl transferase (GGT) – for differential diagnosis of hepatic AP elevation, indication of celiac disease or alcohol abuse (risk of falls), hepatic osteodystrophy.
  • Wg. hypophosphatemia [decrease in blood phosphate level <0.8 mmol/l]
    • Phosphate clearance [In hypophosphatemic form of osteomalacia: ↑ ]
    • Fibroblast growth factor 23 (FGF23 – in hypophosphatemic form of osteomalacia: to exclude an FGF23-producing tumor[If positive: octreotide scintigraphy or positron emission tomography-computed tomography (PET-CT)]
  • Serum protein electrophoresis, immunofixation in serum and urine – for differential diagnosis of monoclonal gammopathy or hypogammaglobulinemia as evidence of monoclonal gammopathy of unclear significance (MGUS) or plasmacytoma (multiple myeloma) or systemic inflammatory disease.
Disease or cause Ca Phosphate AP PTH 25-OH-D3 1,25-OH-D3
Vitamin D deficiency + decreased 25-hydroxylation. ↑↑ ↑-↑↑ N-(↑) and (↓), respectively.
Decreased 1α-hydroxylation: vitamin D-dependent rickets type I (VDDR-1). ↑↑ N-↓ ↓↓
Decreased 1α-hydroxylation: renal insufficiency. ↑-↑↑ ↑-↑↑ N
Hypophosphatemia N ↓↓ ↑↑ N N N-↓
Mineralization defect: hypophosphatasia (synonyms: Rathbun syndrome, phosphatase deficiency rickets). N N ↓-↓↓ ↓-u.N. N N
Target organ resistance:vitamin D-dependent rickets type II (VDDR-2). ↓-↓↓ ↑↑ N-↓ ↑-N