Journal of Clinical Endocrinology & Metabolism, Vol 72, 229-235, Copyright © 1991 by Endocrine Society

ARTICLES

Osteomalacia in hereditary hypophosphatemic rickets with hypercalciuria: a correlative clinical-histomorphometric study

D Gazit, M Tieder, UA Liberman, L Passi-Even and IA Bab
Division of Oral Pathology and Bone Laboratory, Hebrew University- Hadassah Faculty of Dental Medicine, Jerusalem, Israel.

We characterized the bone disease of transilial biopsy specimens from children with hereditary hypophosphatemic rickets with hypercalciuria (HHRH) and genetically related asymptomatic hypercalciuric subjects. All HHRH patients showed irregular mineralization fronts, markedly elevated osteoid surface and seam width, increased number of osteoid lamellae, and prolonged mineralization lag time. These findings are consistent with a mineralization defect and indicate unambiguously that the bone disease in HHRH is osteomalacia. The only abnormality seen in the asymptomatic hypercalciuric subjects was slightly extended osteoid surface. Parametric and nonparametric statistical analyses performed on a pooled sample of HHRH patients and asymptomatic hypercalciuric subjects revealed a very high inverse correlation and a tight linear relationship between serum phosphorus and osteoid parameters. Serum 1,25-dihydroxyvitamin D, which is low in other forms of hereditary hypophosphatemia and osteomalacia, is elevated in HHRH and correlated positively with osteoid parameters and the mineralization lag time. Serum alkaline phosphatase showed similar relationships. These results as well as the clinical, biochemical, and radiological remission of bone disease consequent to phosphate therapy strongly suggest that in HHRH 1) hypophosphatemia alone is sufficient to cause osteomalacia; and 2) the elevation of 1,25-dihydroxyvitamin D reflects the degree of the primary renal phosphate leak, but is not involved in the pathogenesis of the bone disease.

This article has been cited by other articles:

				H. Segawa, S. Yamanaka, A. Onitsuka, Y. Tomoe, M. Kuwahata, M. Ito, Y. Taketani, and K.-i. Miyamoto Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter Am J Physiol Renal Physiol, January 1, 2007; 292(1): F395 - F403. [Abstract] [Full Text] [PDF]

				M. R. Carpinelli, I. P. Wicks, N. A. Sims, K. O'Donnell, K. Hanzinikolas, R. Burt, S. J. Foote, M. Bahlo, W. S. Alexander, and D. J. Hilton An Ethyl-Nitrosourea-Induced Point Mutation in Phex Causes Exon Skipping, X-Linked Hypophosphatemia, and Rickets Am. J. Pathol., November 1, 2002; 161(5): 1925 - 1933. [Abstract] [Full Text] [PDF]

				A. O. JONES, J. TZENOVA, D. FRAPPIER, M. J. CRUMLEY, N. M. ROSLIN, C. H. KOS, M. TIEDER, C. B. LANGMAN, W. PROESMANS, T. O. CARPENTER, et al. Hereditary Hypophosphatemic Rickets with Hypercalciuria Is Not Caused by Mutations in the Na/Pi Cotransporter NPT2 Gene J. Am. Soc. Nephrol., March 1, 2001; 12(3): 507 - 514. [Abstract] [Full Text]

				H. Murer, N. Hernando, I. Forster, and J. Biber Proximal Tubular Phosphate Reabsorption: Molecular Mechanisms Physiol Rev, October 1, 2000; 80(4): 1373 - 1409. [Abstract] [Full Text] [PDF]

				L. Beck, A. C. Karaplis, N. Amizuka, A. S. Hewson, H. Ozawa, and H. S. Tenenhouse Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities PNAS, April 28, 1998; 95(9): 5372 - 5377. [Abstract] [Full Text] [PDF]