Tumor-induced osteomalacia: Clinical and basic studies

Elizabeth Shane, May Parisien, Janet E. Henderson, David W. Dempster, Frieda Feldman, Mark A. Hardy, Jack F. Tohme, Andrew C. Karaplis, Thomas Clemens

Research output: Contribution to journalArticle

Abstract

A patient with classic clinical and biochemical features of tumor- induced osteomalacia (hypophosphatemia, phosphaturia, and undetectable serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)2D]) was studied before and after resection of a benign extraskeletal chondroma from the plantar surface of the foot. Presurgical laboratory evaluation was notable for normal serum concentrations of calcium, intact parathyroid hormone (PTH), parathyroid hormone-related protein (PTHrP), and osteocalcin, increased serum alkaline phosphatase activity, and frankly elevated urinary cyclic adenosine monophosphate (cAMP) and pyridinium cross-link excretion. Quantitative histomorphometry showed severe osteomalacia and deep erosions of the cancellous surface by active osteoclasts. After resection, serum 1,25(OH)2D normalized within 24 h, while renal tubular phosphorus reabsorption and serum phosphorus did not normalize until days 2 and 3, respectively; serum Ca declined slightly, and serum intact PTH, osteocalcin, and urinary pyridinium cross-link excretion increased dramatically. Urinary cAMP excretion declined immediately after resection and then began to increase concomitant with the increase in serum intact PTH. A second bone biopsy taken 3 months after resection demonstrated complete resolution of the osteomalacia, increased mineral apposition rate (1.09 μ/day), resorption surface (9.2%), mineralizing surface (71%), and bone formation rate (0.83 mm3/mm2/day), and marked decreases in cancellous bone volume (13.1%) and trabecular connectivity compared with the first biopsy. Tumor extracts did not affect phosphate transport in renal epithelial cell lines or lα-hydroxylase activity in a myelomonocytic cell line. The patient's course suggests that the abnormal 1,25(OH)2D and phosphorus metabolism is due to a tumor product that may be acting via stimulation of adenylate cyclase activity. Increased bone resorption prior to surgical resection suggests that the tumor may also produce an osteoclast activator. The rise in resorption surface and pyridinium cross-link excretion, increase in serum osteocalcin and bone mineralization, normalization of osteoid width, and fall in cancellous bone volume after resection are consistent with healing of osteomalacia by rapid remodeling.

Original languageEnglish (US)
Pages (from-to)1502-1511
Number of pages10
JournalJournal of Bone and Mineral Research
Volume12
Issue number9
DOIs
StatePublished - Sep 1997
Externally publishedYes

Fingerprint

Serum
Osteomalacia
Osteocalcin
Parathyroid Hormone
Phosphorus
Osteoclasts
Cyclic AMP
Familial Hypophosphatemia
Chondroma
Hypophosphatemia
Kidney
Biopsy
Oncogenic osteomalacia
Clinical Studies
Parathyroid Hormone-Related Protein
Cell Line
Physiologic Calcification
Neoplasms
Bone Resorption
Mixed Function Oxygenases

ASJC Scopus subject areas

  • Surgery

Cite this

Shane, E., Parisien, M., Henderson, J. E., Dempster, D. W., Feldman, F., Hardy, M. A., ... Clemens, T. (1997). Tumor-induced osteomalacia: Clinical and basic studies. Journal of Bone and Mineral Research, 12(9), 1502-1511. https://doi.org/10.1359/jbmr.1997.12.9.1502

Tumor-induced osteomalacia : Clinical and basic studies. / Shane, Elizabeth; Parisien, May; Henderson, Janet E.; Dempster, David W.; Feldman, Frieda; Hardy, Mark A.; Tohme, Jack F.; Karaplis, Andrew C.; Clemens, Thomas.

In: Journal of Bone and Mineral Research, Vol. 12, No. 9, 09.1997, p. 1502-1511.

Research output: Contribution to journalArticle

Shane, E, Parisien, M, Henderson, JE, Dempster, DW, Feldman, F, Hardy, MA, Tohme, JF, Karaplis, AC & Clemens, T 1997, 'Tumor-induced osteomalacia: Clinical and basic studies', Journal of Bone and Mineral Research, vol. 12, no. 9, pp. 1502-1511. https://doi.org/10.1359/jbmr.1997.12.9.1502
Shane E, Parisien M, Henderson JE, Dempster DW, Feldman F, Hardy MA et al. Tumor-induced osteomalacia: Clinical and basic studies. Journal of Bone and Mineral Research. 1997 Sep;12(9):1502-1511. https://doi.org/10.1359/jbmr.1997.12.9.1502
Shane, Elizabeth ; Parisien, May ; Henderson, Janet E. ; Dempster, David W. ; Feldman, Frieda ; Hardy, Mark A. ; Tohme, Jack F. ; Karaplis, Andrew C. ; Clemens, Thomas. / Tumor-induced osteomalacia : Clinical and basic studies. In: Journal of Bone and Mineral Research. 1997 ; Vol. 12, No. 9. pp. 1502-1511.
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