Noninvasive testing in the diagnosis of osteomalacia.

PURPOSE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.