Abstract | UNLABELLED: We demonstrate a reduction in enzymatic divalent immature and trivalent pyridinium cross-links and an increase in the nonenzymatic cross-link, pentosidine (Pen), in rabbits with methionine (Met)-induced hyperhomocysteinemia. Such detrimental cross-link formation in bone was ameliorated by raloxifene (RLX) treatment. INTRODUCTION:
Collagen cross-links are determinants of bone quality. Homocysteine (Hcys) interferes with collagen cross-linking. Because RLX is thought to ameliorate bone quality, we investigated whether RLX ameliorated hyperhomocysteinemia-induced cross-link abnormalities using a Met-rich diet rabbit model. METHODS: We divided New Zealand white rabbits into six groups (n = 6 per group): baseline control, sham operation, sham + 1% Met diet, ovariectomy (OVX), 1% Met diet + OVX, OVX + RLX (10 mg/kg/day), and 1% Met diet + OVX + RLX. RLX was administered for 16 weeks. We measured the amount of enzymatic immature and mature pyridinium cross-links and the nonenzymatic cross-link, Pen, and correlated the cross-link content to bone strength. RESULTS: Hcys levels were significantly higher in the Met diet groups than in the normal diet groups. Met-fed rabbits with or without OVX showed a significant reduction of enzymatic cross-links, whereas an increase in Pen was observed in Met-fed rabbits with OVX. The cross-link content of the RLX-treated Met-fed rabbits with OVX was restored to similar levels as the sham group, accompanied by an improvement of bone strength. CONCLUSION: These results demonstrate that hyperhomocysteinemia reduced bone strength via a reduction of enzymatic cross-links and an increase of nonenzymatic cross-links. RLX may ameliorate hyperhomocysteinemia-induced detrimental cross-linking in rabbits with OVX and may improve bone strength via the amelioration of collagen cross-links.
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Authors | M Saito, K Marumo, S Soshi, Y Kida, C Ushiku, A Shinohara |
Journal | Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
(Osteoporos Int)
Vol. 21
Issue 4
Pg. 655-66
(Apr 2010)
ISSN: 1433-2965 [Electronic] England |
PMID | 19484165
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bone Density Conservation Agents
- Glycation End Products, Advanced
- Raloxifene Hydrochloride
- Collagen
- Arginine
- Methionine
- pentosidine
- Lysine
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Topics |
- Animals
- Arginine
(analogs & derivatives, metabolism)
- Bone Density
(drug effects)
- Bone Density Conservation Agents
(therapeutic use)
- Bone and Bones
(physiopathology)
- Collagen
(metabolism)
- Disease Models, Animal
- Drug Evaluation, Preclinical
(methods)
- Female
- Glycation End Products, Advanced
(metabolism)
- Hyperhomocysteinemia
(chemically induced, complications, metabolism, physiopathology)
- Lysine
(analogs & derivatives, metabolism)
- Methionine
- Osteoporosis
(etiology, metabolism, prevention & control)
- Rabbits
- Raloxifene Hydrochloride
(therapeutic use)
- Stress, Mechanical
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