Abstract | BACKGROUND: METHODS: These studies assessed the efficacy of the 1,25(OH)2D3 analog, 19-Nor-1,25(OH)2D2 (19-Nor), in the prevention (protocol I) and treatment (protocol II) of SH and renal osteodystrophy in uremic rats. In protocol I, normal and uremic rats were fed a high phosphorus diet for 2 months; uremic rats were administered intraperitoneal injections of either vehicle or 19-Nor (200 ng three times a week). In protocol II, normal and uremic rats were fed a high phosphorus diet for 4 months; 2 months after the onset of uremia, rats were administered either intraperitoneal vehicle or 19-Nor (200 ng three times a week). Serum PTH and bone histology were used to assess the degree of SH. RESULTS: 19-Nor was effective in preventing (protocol I) and suppressing (protocol II) the significant SH induced by uremia and further enhanced by a high phosphorus diet. In protocol I, bone histology in uremic controls showed a threefold increase in the cancellous bone mass compared to normal rats. This expansion in unmineralized bone was accompanied by 5-, 1.5-, and 7-fold increases in eroded surface, mineralization lag time (MLT), and bone formation rate (BFR/BS), respectively. Moreover, cortical bone porosity in untreated uremic rats increased 267-fold compared to normal animals. 19-Nor ameliorated these changes in cancellous and cortical bone. In protocol II, the reported indices worsened even further. In contrast, 2 months of 19-Nor treatment improved bone histology by reducing cortical bone porosity, woven bone formation, MLT, and BFR/BS. CONCLUSION: In an experimental model of chronic renal failure (CRF), 19-Nor prevents SH and ameliorates the histomorphometric changes induced by uremia and high phosphorus diet. In addition, 19-Nor suppresses serum PTH and improves bone histology in uremic rats with established severe SH. Further studies in patients with CRF are necessary to define the clinical applicability of 19-Nor on bone histology in humans.
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Authors | Eduardo Slatopolsky, Mario Cozzolino, Yan Lu, Jane Finch, Andriana Dusso, Marc Staniforth, Yoo Wein, Jee Webster |
Journal | Kidney international
(Kidney Int)
Vol. 63
Issue 6
Pg. 2020-7
(Jun 2003)
ISSN: 0085-2538 [Print] United States |
PMID | 12753289
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Ergocalciferols
- Parathyroid Hormone
- Phosphorus, Dietary
- paricalcitol
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Topics |
- Animals
- Bone Diseases
(drug therapy, etiology, prevention & control)
- Ergocalciferols
(pharmacology)
- Female
- Hyperparathyroidism
(drug therapy, etiology, prevention & control)
- Kidney Failure, Chronic
(complications)
- Parathyroid Hormone
(blood, metabolism)
- Phosphorus, Dietary
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Uremia
(complications)
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