Noninvasive testing in the diagnosis of osteomalacia

Osteomalacia is associated with many clinical, radiographic, and biochemical abnormalities. Unfortunately, none of these are pathognomonic of the disorder, and histologic examination of a bone biopsy specimen is often necessary to confirm the diagnosis. Noninvasive methods of diagnosis would be preferable to decrease patient morbidity and increase cost-effectiveness. Previous studies addressing the adequacy of these methods were performed prior to the widespread availability of 1,25-dihydroxycalcitriol (1,25-(OH)2D3) and parathyroid hormone (PTH) levels. Therefore, we reviewed our experience with patients with biopsy-proven osteomalacia to determine if PTH or 1,25(OH)2D3 levels would serve a useful role in establishing the diagnosis of osteomalacia.

We retrospectively studied 17 patients who had biopsy-proven osteomalacia (defined as an osteoid volume greater than 10% and an osteoid width greater than 15 microns) in order to ascertain if their clinical presentation, biochemical profile, and radiographic features were sufficient to establish a diagnosis of osteomalacia.

We found that 94% of our patients exhibited symptoms of osteomalacia, and all patients had at least one demonstrable sign of osteomalacia on examination. Biochemically, the patients presented a heterogeneous picture: 94% had an elevated alkaline phosphatase level; 47% had either a low serum calcium or phosphate (12% had both) level; urinary calcium excretion was low in 18%; and 25-(OH)D3 concentration was low in 29%. Levels of 1,25-(OH)2D3 were measured in eight patients; three had low values despite normal 25-(OH)D3 levels. PTH levels were elevated in 41% of patients in the absence of histologic evidence of hyperparathyroidism; however, these patients were noted to have multiple other abnormal clinical, biochemical, or radiograph features. Radiographically, 18% of patients had pseudofractures; the rest had nonspecific findings suggestive of osteomalacia. In summary, all patients had at least two of the following abnormalities: low calcium, low phosphate, elevated alkaline phosphatase, or a radiographic finding suggestive of osteomalacia.

We conclude: (1) a careful history and physical examination remain important in the evaluation of potential osteomalacia patients; (2) PTH offered no apparent benefit as a screening test in our patients; (3) 1,25-(OH)2D3 was low in three patients with normal levels of 25-(OH)D3; (4) decreased urinary calcium excretion had low sensitivity for detecting osteomalacia; and (5) serum calcium, phosphate, alkaline phosphatase, and radiographic examination may be adequate screening tests in patients who have a clinical presentation suggestive of osteomalacia.