Diagnosis of Osteomalacia
Osteomalacia is diagnosed through a combination of characteristic clinical features (diffuse bone pain, proximal muscle weakness, waddling gait), essential biochemical testing (elevated alkaline phosphatase in 94% of cases, low 25-hydroxyvitamin D, low phosphate, elevated PTH), and radiographic findings (pseudofractures when present are pathognomonic). 1, 2
Clinical Assessment
The diagnostic approach begins with identifying the characteristic clinical triad:
- Diffuse bone pain that is dull and distinct from osteoarthritis-related pain 1, 2
- Proximal muscle weakness with waddling gait and difficulty with ambulation 1, 2
- Increased fall risk particularly in elderly patients 1
In children, additional features include lower limb deformities (varus or valgus), rachitic rosary, and Harrison's groove 1, 2.
Essential Biochemical Testing
The core diagnostic panel should include 1, 2:
- Serum calcium (typically low in advanced stages) 1
- Serum phosphate (typically low) 1
- Alkaline phosphatase (elevated in 94% of cases, making it the most sensitive single marker) 1
- 25-hydroxyvitamin D (best index of vitamin D nutrition; osteomalacia typically occurs when levels fall below 10-12 ng/mL) 3, 4
- Parathyroid hormone (elevated in 41% of cases, typically at upper limit of normal or slightly elevated) 2, 4
Alkaline phosphatase is particularly valuable as it reliably indicates osteomalacia activity and treatment response. 1, 2
For suspected renal phosphate wasting, calculate tubular maximum reabsorption of phosphate per GFR (TmP/GFR) from spot urine samples 2.
Radiographic Evaluation
Plain radiographs should target high-yield sites 1:
- Ribs, scapulae, pubic rami, proximal femurs, and spine to identify pseudofractures (Looser's zones) 1, 2
- Pseudofractures are pathognomonic when present, appearing as radiolucent lines perpendicular to bone cortex 2, 4
In children, radiography of knees, wrists, or ankles is usually sufficient to identify cupped and flared metaphyses with widened, irregular growth plates 1, 2.
Bone Densitometry
Dual-energy X-ray absorptiometry (DXA) of lumbar spine and hip is the gold standard for assessing bone mineral density 5, 1. However, DXA cannot distinguish osteomalacia from osteoporosis, as both show reduced bone mineral density 1. A T-score less than or equal to −2.5 at the hip or spine defines osteoporosis in postmenopausal women and men ≥50 years 5.
Differential Diagnosis Workup
Key conditions to exclude 5, 1, 2:
- Renal Fanconi syndrome: Check for abnormal urinary losses of bicarbonate, amino acids, glucose, uric acid, and low molecular mass proteinuria 1, 2
- X-linked hypophosphatemia: Consider in cases with renal phosphate wasting 1, 2
- Tumor-induced osteomalacia: Evaluate in hypophosphatemic cases 1, 6
- Hypophosphatasia: Low alkaline phosphatase levels (opposite of typical osteomalacia), dental abnormalities 5
- Paget's disease: Raised alkaline phosphatase, mixed osteolytic and osteosclerotic aspect on imaging, age >50 years 5
Proposed Diagnostic Criteria
A diagnosis of osteomalacia can be made non-invasively in the presence of high alkaline phosphatase, high PTH, low dietary calcium intake (<300 mg/day) and/or low serum 25-hydroxyvitamin D (<30 nmol/L). 7 Clinical symptoms or Looser's zone fractures reaffirm the diagnosis 7.
Bone Biopsy
Do not perform routine bone biopsies. 5 Undecalcified transiliac bone biopsy is recommended only in exceptional cases with presumed osteomalacia where the diagnosis remains uncertain after non-invasive testing 5. Histological correlate is reduced or deficient mineralization of newly synthesized extracellular matrix 6.
Monitoring Treatment Response
Track serum alkaline phosphatase as it reliably indicates treatment response and osteomalacia activity 1, 2. Repeat 25-hydroxyvitamin D levels after 3 months of supplementation to ensure adequate response 1.