OSTEOMALACIA ASSOCIATED WITH ADULT FANCONIS-SYNDROME - CLINICAL AND DIAGNOSTIC FEATURES

OBJECTIVE Osteomalacia associated with adult acquired Fanconi's syndro me is thought to result from hypophosphataemia and relative 1,25-dihyd roxyvitamin 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 w ith calcium, phosphate and vitamin D. DESIGN Retrospective Mayo Clinic case-note review from 1975 to 1994 and prospective follow-up study, c ombined with literature review, PATIENTS Eleven patients (7 male, 4 fe male) were identified who satisfied criteria for diagnosis of osteomal acia and adult Fanconi's syndrome. Twenty-five additional patients wer e identified in a literature review from 1954 to the present. METHODS Clinical history and physical examination, serum and urine bone and mi neral parameters, X-ray radiography and iliac crest bone histomorphome try, RESULTS All patients presented with typical symptoms of osteomala cia, including lower extremity or low back bone pain, and all had frac tures, pseudofractures, and/or bone demineralization on X-ray radiogra phy. Osteomalacia and Fanconi's syndrome were diagnosed concurrently i n 10 patients, whereas osteomalacia preceded diagnosis of Fanconi's sy ndrome by 5 years in one patient, Pretreatment bone biopsies in 9 of t he 11 patients demonstrated increased osteoid surface, volume and widt h. In the one patient labelled with tetracycline prior to biopsy, mine ralization lag time was prolonged at 111 days (normal 19.2+/-1.0 days) . Hypophosphataemia, inappropriately low 1,25-dihydroxyvitamin D level s, renal insufficiency, and chronic acidosis due to bicarbonate leak a nd uraemia, contributed to the osteomalacia in these patients, Seconda ry hyperparathyroidism was present in two patients, Eight of the 11 pa tients with osteomalacia associated with Fanconi's syndrome had monocl onal disorders, including multiple myeloma or lymphoma, many of them m anifest by light-chain proteinuria. Over a mean patient follow-up peri od of 46 months (range 1-239 months), patients responded symptomatical ly to calcium, phosphate, and vitamin D replacement typically within 1 -6 months, In 8 patients in whom follow-up data were available, post-t reatment serum phosphate and 1,25-dihydroxyvitamin D levels improved i n the setting of stable mild renal insufficiency; only one patient dev eloped end-stage renal failure after 20 years, suggesting that these p atients do not invariably progress rapidly to renal failure. CONCLUSIO NS Regardless of the underlying cause, osteomalacia associated with ad ult acquired Fanconi's syndrome appears to respond well to calcium, ph osphate, and vitamin D replacement. These patients do not appear to ne cessarily require 1,25-dihydroxyvitamin D replacement.