Effects of unfractionated heparin and low-molecular-weight heparin on bone metabolism in a rat model of renal failure

Yoshiyuki Hanba, Masahide Mizobuchi, Ken Kunimoto, Fumie Saji, Kazuhiro Shiizaki, Toshifumi Sakaguchi, Shigeo Negi, Takashi Shigematsu, Tadao Akizawa

Research output: Contribution to journalArticle

Abstract

Background: Anticoagulants such as unfractionated heparin (UH) and low-molecularweight heparin (LMWH) are indispensable to the performance of hemodialysis, but it has been suggested that long-term heparin administration affects bone metabolism and may cause heparin-induced osteoporosis. On the other hand, renal failure patients are known to develop secondary hyperparathyroidism as a result of abnormal calcium and phosphorus metabolism, vitamin D deficiency, etc., and to have bone metabolism abnormalities due to renal osteodystrophy. Although LMWH has been reported to have less of an effect on bone metabolism than UH does, the effects of LMWH and UH on the bones of renal failure patients have not been adequately studied. Objective: To investigate the effects of LMWH and UH on bone metabolism under renal failure conditions by using bone morphometry methods in renal failure rats. Methods: Seven-week-old male Sprague-Dawley rats were 5/6-nephrectomized and randomized to receive LMWH (1000 U/kg: group L), UH (1000 U/kg: group H) or no treatment (group Nx). Sham-operated rats of the same strain and age served as normal controls. After 8 weeks, the rats were killed and blood biochemistry and morphologic changes in the femoral secondary substantia spongiosa were examined. Results: All of the renal failure rats had elevated blood parathyroid hormone (PTH) levels. Bone morphometry revealed lower bone formation parameters in both the H group and the L group than in the Nx group, and they were markedly lower in the H group. In addition, the bone resorption parameters tended to be lower in both the H group and the L group than in the Nx group. Conclusions: Both UH and LMWH inhibited bone formation in the presence of elevated blood PTH levels, and they did not promote bone resorption. In addition, the effects of LMWH were milder than those of heparin, and it seemed to have less effect on bone metabolism. Because the results suggested the possibility that both UH and LMWH either directly or indirectly inhibit bone metabolic turnover in renal failure by some sort of mechanism of action, further study will be necessary in the future.

Original languageEnglish (US)
Pages (from-to)102-107
Number of pages6
JournalJournal of the Wakayama Medical Society
Volume60
Issue number3
StatePublished - Sep 2009

Fingerprint

Low Molecular Weight Heparin
Renal Insufficiency
Heparin
Bone and Bones
Bone Resorption
Parathyroid Hormone
Osteogenesis
Chronic Kidney Disease-Mineral and Bone Disorder
Secondary Hyperparathyroidism
Vitamin D Deficiency
Bone Remodeling
Thigh

Keywords

  • Heparin
  • Hyperparathyroidism
  • Low-molecular-weight heparin (LMWH)
  • Osteoporosis
  • Renal failure

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hanba, Y., Mizobuchi, M., Kunimoto, K., Saji, F., Shiizaki, K., Sakaguchi, T., ... Akizawa, T. (2009). Effects of unfractionated heparin and low-molecular-weight heparin on bone metabolism in a rat model of renal failure. Journal of the Wakayama Medical Society, 60(3), 102-107.

Effects of unfractionated heparin and low-molecular-weight heparin on bone metabolism in a rat model of renal failure. / Hanba, Yoshiyuki; Mizobuchi, Masahide; Kunimoto, Ken; Saji, Fumie; Shiizaki, Kazuhiro; Sakaguchi, Toshifumi; Negi, Shigeo; Shigematsu, Takashi; Akizawa, Tadao.

In: Journal of the Wakayama Medical Society, Vol. 60, No. 3, 09.2009, p. 102-107.

Research output: Contribution to journalArticle

Hanba, Y, Mizobuchi, M, Kunimoto, K, Saji, F, Shiizaki, K, Sakaguchi, T, Negi, S, Shigematsu, T & Akizawa, T 2009, 'Effects of unfractionated heparin and low-molecular-weight heparin on bone metabolism in a rat model of renal failure', Journal of the Wakayama Medical Society, vol. 60, no. 3, pp. 102-107.
Hanba, Yoshiyuki ; Mizobuchi, Masahide ; Kunimoto, Ken ; Saji, Fumie ; Shiizaki, Kazuhiro ; Sakaguchi, Toshifumi ; Negi, Shigeo ; Shigematsu, Takashi ; Akizawa, Tadao. / Effects of unfractionated heparin and low-molecular-weight heparin on bone metabolism in a rat model of renal failure. In: Journal of the Wakayama Medical Society. 2009 ; Vol. 60, No. 3. pp. 102-107.
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abstract = "Background: Anticoagulants such as unfractionated heparin (UH) and low-molecularweight heparin (LMWH) are indispensable to the performance of hemodialysis, but it has been suggested that long-term heparin administration affects bone metabolism and may cause heparin-induced osteoporosis. On the other hand, renal failure patients are known to develop secondary hyperparathyroidism as a result of abnormal calcium and phosphorus metabolism, vitamin D deficiency, etc., and to have bone metabolism abnormalities due to renal osteodystrophy. Although LMWH has been reported to have less of an effect on bone metabolism than UH does, the effects of LMWH and UH on the bones of renal failure patients have not been adequately studied. Objective: To investigate the effects of LMWH and UH on bone metabolism under renal failure conditions by using bone morphometry methods in renal failure rats. Methods: Seven-week-old male Sprague-Dawley rats were 5/6-nephrectomized and randomized to receive LMWH (1000 U/kg: group L), UH (1000 U/kg: group H) or no treatment (group Nx). Sham-operated rats of the same strain and age served as normal controls. After 8 weeks, the rats were killed and blood biochemistry and morphologic changes in the femoral secondary substantia spongiosa were examined. Results: All of the renal failure rats had elevated blood parathyroid hormone (PTH) levels. Bone morphometry revealed lower bone formation parameters in both the H group and the L group than in the Nx group, and they were markedly lower in the H group. In addition, the bone resorption parameters tended to be lower in both the H group and the L group than in the Nx group. Conclusions: Both UH and LMWH inhibited bone formation in the presence of elevated blood PTH levels, and they did not promote bone resorption. In addition, the effects of LMWH were milder than those of heparin, and it seemed to have less effect on bone metabolism. Because the results suggested the possibility that both UH and LMWH either directly or indirectly inhibit bone metabolic turnover in renal failure by some sort of mechanism of action, further study will be necessary in the future.",
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T1 - Effects of unfractionated heparin and low-molecular-weight heparin on bone metabolism in a rat model of renal failure

AU - Hanba, Yoshiyuki

AU - Mizobuchi, Masahide

AU - Kunimoto, Ken

AU - Saji, Fumie

AU - Shiizaki, Kazuhiro

AU - Sakaguchi, Toshifumi

AU - Negi, Shigeo

AU - Shigematsu, Takashi

AU - Akizawa, Tadao

PY - 2009/9

Y1 - 2009/9

N2 - Background: Anticoagulants such as unfractionated heparin (UH) and low-molecularweight heparin (LMWH) are indispensable to the performance of hemodialysis, but it has been suggested that long-term heparin administration affects bone metabolism and may cause heparin-induced osteoporosis. On the other hand, renal failure patients are known to develop secondary hyperparathyroidism as a result of abnormal calcium and phosphorus metabolism, vitamin D deficiency, etc., and to have bone metabolism abnormalities due to renal osteodystrophy. Although LMWH has been reported to have less of an effect on bone metabolism than UH does, the effects of LMWH and UH on the bones of renal failure patients have not been adequately studied. Objective: To investigate the effects of LMWH and UH on bone metabolism under renal failure conditions by using bone morphometry methods in renal failure rats. Methods: Seven-week-old male Sprague-Dawley rats were 5/6-nephrectomized and randomized to receive LMWH (1000 U/kg: group L), UH (1000 U/kg: group H) or no treatment (group Nx). Sham-operated rats of the same strain and age served as normal controls. After 8 weeks, the rats were killed and blood biochemistry and morphologic changes in the femoral secondary substantia spongiosa were examined. Results: All of the renal failure rats had elevated blood parathyroid hormone (PTH) levels. Bone morphometry revealed lower bone formation parameters in both the H group and the L group than in the Nx group, and they were markedly lower in the H group. In addition, the bone resorption parameters tended to be lower in both the H group and the L group than in the Nx group. Conclusions: Both UH and LMWH inhibited bone formation in the presence of elevated blood PTH levels, and they did not promote bone resorption. In addition, the effects of LMWH were milder than those of heparin, and it seemed to have less effect on bone metabolism. Because the results suggested the possibility that both UH and LMWH either directly or indirectly inhibit bone metabolic turnover in renal failure by some sort of mechanism of action, further study will be necessary in the future.

AB - Background: Anticoagulants such as unfractionated heparin (UH) and low-molecularweight heparin (LMWH) are indispensable to the performance of hemodialysis, but it has been suggested that long-term heparin administration affects bone metabolism and may cause heparin-induced osteoporosis. On the other hand, renal failure patients are known to develop secondary hyperparathyroidism as a result of abnormal calcium and phosphorus metabolism, vitamin D deficiency, etc., and to have bone metabolism abnormalities due to renal osteodystrophy. Although LMWH has been reported to have less of an effect on bone metabolism than UH does, the effects of LMWH and UH on the bones of renal failure patients have not been adequately studied. Objective: To investigate the effects of LMWH and UH on bone metabolism under renal failure conditions by using bone morphometry methods in renal failure rats. Methods: Seven-week-old male Sprague-Dawley rats were 5/6-nephrectomized and randomized to receive LMWH (1000 U/kg: group L), UH (1000 U/kg: group H) or no treatment (group Nx). Sham-operated rats of the same strain and age served as normal controls. After 8 weeks, the rats were killed and blood biochemistry and morphologic changes in the femoral secondary substantia spongiosa were examined. Results: All of the renal failure rats had elevated blood parathyroid hormone (PTH) levels. Bone morphometry revealed lower bone formation parameters in both the H group and the L group than in the Nx group, and they were markedly lower in the H group. In addition, the bone resorption parameters tended to be lower in both the H group and the L group than in the Nx group. Conclusions: Both UH and LMWH inhibited bone formation in the presence of elevated blood PTH levels, and they did not promote bone resorption. In addition, the effects of LMWH were milder than those of heparin, and it seemed to have less effect on bone metabolism. Because the results suggested the possibility that both UH and LMWH either directly or indirectly inhibit bone metabolic turnover in renal failure by some sort of mechanism of action, further study will be necessary in the future.

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