Clinical Endocrinology

Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features*

Authors

  • Bart L. Clarke,

    1. Endocrine Research Unit Division of Endocrinology
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    • Current Address: The University of Chicago Medical Center, Department of Medicine, Section of Endocrinology, 5841 S. Maryland Avenue, Chicago, IL 60637.

  • Alan G. Wynne,

    1. Endocrine Research Unit Division of Endocrinology
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    • §

      Current Address: Cotton-ONeill Clinic, P.A., 901 Garfield, Topeka, KS 66606.

  • David M. Wilson,

    1. Division of Nephrology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA
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  • Lorraine A. Fitzpatrick

    Corresponding author
    1. Endocrine Research Unit Division of Endocrinology
      Dr L. A. Fitzpatrick, Endocrine Research Unit, Mayo Clinic, 5–164 West Joseph Building, St Mary's Hospital, Rochester, MN 55905, USA.
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  • *

    Previously presented as B. L. Clarke, A. G. Wynne and D. M. Wilson, Osteomalacia associated with adult Fanconi's syndrome: clinical and diagnostic features in 7 patients. The Endocrine Society 73rd Annual Meeting, Washington, DC, 18–23 June 1991.

Dr L. A. Fitzpatrick, Endocrine Research Unit, Mayo Clinic, 5–164 West Joseph Building, St Mary's Hospital, Rochester, MN 55905, USA.

Summary

OBJECTIVE Osteomalacia associated with adult acquired Fanconi's syndrome is thought to result from hypophosphataemia and relative 1,25-dihydroxy vitamin 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 osteomaiacia 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 parameters, 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 ail 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, mlnerallzation lag time was prolonged at 111 days (normal 19.2±1.0 days). Hypophosphataemia, inappropriately low 1,25-dihydroxyvltamin 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 Regardless of the underlying cause, osteomalacia associated with adult acquired Fanconi's syndrome appears to respond well to calcium, phosphate, and vitamin D replacement. These patients do not appear to necessarily require 1,25-dihydroxyvitamin D replacement.

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