This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sanchez, C. P. Articles by Goodman, W. G. Search for Related Content PubMed PubMed Citation Articles by Sanchez, C. P. Articles by Goodman, W. G.

Impaired Growth, Delayed Ossification, and Reduced Osteoclastic Activity in the Growth Plate of Calcium-Supplemented Rats with Renal Failure¹

From the Departments of Pediatrics (C.P.S., B.D.K., I.B.S.) and Medicine (P.A.A., W.G.G.), UCLA School of Medicine, Los Angeles, California 90095; and the Endocrine Unit (H.J.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: William G. Goodman, M.D., Division of Nephrology, 7–155 Factor Building, UCLA Medical Center, 10833 Le Conte Avenue, Los Angeles, California 90095. E-mail: wgoodman{at}ucla.edu

Linear growth is reduced in prepubertal children with adynamic renal osteodystrophy, suggesting that the proliferation and/or differentiation of epiphyseal growth plate chondrocytes is abnormal in this disorder. To examine this issue, in situ hybridization and histochemistry were used to measure selected markers of endochondral bone formation and bone resorption in the proximal tibia of subtotally nephrectomized rats fed a high calcium diet to induce biochemical changes consistent with adynamic osteodystrophy. Blood ionized calcium concentrations were higher and serum PTH levels were lower in nephrectomized, calcium-supplemented rats than in either intact or nephrectomized control animals. Linear growth and tibial length were reduced, but messenger RNA levels for type II collagen, type X collagen, and the PTH/PTHrP receptor did not differ from control values in nephrectomized rats given supplemental calcium. In contrast, both the width of epiphyseal cartilage and the height of the zone of hypertrophic chondrocytes were greater in calcium-supplemented nephrectomized rats. These morphological changes were associated with decreases in histochemical staining for tartrate-resistant acid phosphatase and lower levels of messenger RNA expression for the matrix metalloproteinase MMP-9/gelatinase B immediately adjacent to the epiphyseal growth plate. Diminished chondroclastic/osteoclastic activity alters growth plate morphology and adversely affects linear bone growth in calcium-supplemented, nephrectomized rats.

This article has been cited by other articles:

				V. M. Brandenburg and J. Floege Adynamic bone disease--bone and beyond NDT Plus, June 1, 2008; 1(3): 135 - 147. [Full Text] [PDF]

				K. Olgaard and E. Lewin Can Hyperparathyroid Bone Disease Be Arrested or Reversed? Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 367 - 373. [Abstract] [Full Text] [PDF]

				C. P. Sanchez and Y.-Z. He Growth Hormone Therapy in Calcium-Loaded Rats with Renal Failure Endocrinology, July 1, 2004; 145(7): 3375 - 3385. [Abstract] [Full Text] [PDF]

				R. J. Lund, M. R. Davies, A. J. Brown, and K. A. Hruska Successful Treatment of an Adynamic Bone Disorder with Bone Morphogenetic Protein-7 in a Renal Ablation Model J. Am. Soc. Nephrol., February 1, 2004; 15(2): 359 - 369. [Abstract] [Full Text] [PDF]

				C. P. Sanchez and Y.-Z. He Effects of Thyroparathyroidectomy, Exogenous Calcium, and Short-Term Calcitriol Therapy on the Growth Plate in Renal Failure J. Am. Soc. Nephrol., January 1, 2003; 14(1): 148 - 158. [Abstract] [Full Text] [PDF]

				I. B. SALUSKY and W. G. GOODMAN Adynamic Renal Osteodystrophy: Is There a Problem? J. Am. Soc. Nephrol., September 1, 2001; 12(9): 1978 - 1985. [Full Text] [PDF]