Prospective study of effect of fenclofenac on thyroid function tests.

Increases in osteoid volume with sodium fluoride, calcium, and vitamin D treatment are well documented. Small decreases in mineralisation rate have also been reported.2 But osteomalacia in the presence of high plasma 25-OHD concentrations has not been described in patients treated with this regimen. The plasma 1,25-(OH)2D3 concentration in our patient was just below the lower limit of normal, but the total plasma 1,25-(OH)2D (1,25-(OH)2D2-+1,25-(OH)2D3) concentration was probably normal since she was taking vitamin D2 and the radioimmunoassay did not measure plasma 1,25-(OH)2D2. The mechanisms by which fluoride may produce osteomalacia despite high plasma 25-OHD concentrations require further investigation. Possibilities include fluoride-induced end-organ resistance in bone to active vitamin D metabolites or an effect of fluoride on processes of bone mineralisation that are unaffected by vitamin D metabolites. Alternatively, fluoride might affect the metabolism of 25-OHD to other metabolites. Although lack of calcium supplements was probably unimportant in our patient, since the plasma calcium concentration remained above 2 40 mmol,l throughout treatment and dietary calcium intake was adequate, we cannot exclude it as a factor in the development of osteomalacia. Our results indicate that vitamin D in doses that produce high plasma 25-OHD concentrations does not protect against fluoride-induced mineralisation defects and that patients treated with this regimen require careful supervision. Transiliac biopsy provides a sensitive method for diagnosing generalised bone disease such as osteomalacia and may be necessary to detect its development when, as in our patient, plasma biochemical changes are not diagnostic.