Osteomalacia associated with adult acquired Fanconi's syndrome is thought to result from hypophosphataemia and relative
1,25-dihydroxyvitamin D deficiency. We have followed the clinical and diagnostic features of patients with
osteomalacia associated with adult Fanconi's syndrome, with particular emphasis on their responses to treatment with
calcium, phosphate and
vitamin D.
DESIGN: Retrospective Mayo Clinic case-note review from 1975 to 1994 and prospective follow-up study, combined with literature review.
PATIENTS: Eleven patients (7 male, 4 female) were identified who satisfied criteria for diagnosis of
osteomalacia and adult Fanconi's syndrome. Twenty-five additional patients were identified in a literature review from 1954 to the present.
METHODS: Clinical history and physical examination, serum and urine bone and
mineral parameter, X-ray radiography and iliac crest bone histomorphometry.
RESULTS: All patients presented with typical symptoms of
osteomalacia, including lower extremity or low back bone
pain, and all had fractures, pseudofractures, and/or bone demineralization on X-ray radiography.
Osteomalacia and Fanconi's syndrome were diagnosed concurrently in 10 patients, whereas
osteomalacia preceded diagnosis of Fanconi's syndrome by 5 years in one patient. Pre-treatment bone biopsies in 9 of the 11 patients demonstrated increased osteoid surface, volume and width. In the one patient labelled with
tetracycline prior to biopsy, mineralization lag time was prolonged at 111 days (normal 19.2 +/- 1.0 days). Hypophosphataemia, inappropriately low
1,25-dihydroxyvitamin D levels,
renal insufficiency, and chronic
acidosis due to
bicarbonate leak and uraemia, contributed to the
osteomalacia in these patients.
Secondary hyperparathyroidism was present in two patients. Eight of the 11 patients with
osteomalacia associated with Fanconi's syndrome had monoclonal disorders, including
multiple myeloma or
lymphoma, many of them manifest by light-chain
proteinuria. Over a mean patient follow-up period of 46 months (range 1-239 months), patients responded symptomatically to
calcium, phosphate, and
vitamin D replacement typically within 1-6 months. In 8 patients in whom follow-up data were available, post-treatment serum
phosphate and
1,25-dihydroxyvitamin D levels improved in the setting of stable mild
renal insufficiency; only one patient developed
end-stage renal failure after 20 years, suggesting that these patients do not invariably progress rapidly to
renal failure.
CONCLUSIONS: