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Clinical Chemistry 53: 1455-1461, 2007. First published June 22, 2007; 10.1373/clinchem.2007.086272
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(Clinical Chemistry. 2007;53:1455-1461.)
© 2007 American Association for Clinical Chemistry, Inc.

Endocrinology and Metabolism

Experimental Hyperhomocysteinemia Reduces Bone Quality in Rats

Markus Herrmann1, Britt Wildemann2,2, Lutz Claes3,2, Stefan Klohs2, Michael Ohnmacht3, Omid Taban-Shomal1, Ulrich Hübner1, Anette Pexa4, Natalia Umanskaya1 and Wolfgang Herrmann1,a

1 Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, Homburg/Saar, Germany.
2 Center for Musculoskeletal Surgery, Charité-Universitätsmedizin, Berlin, Germany.
3 Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany.
4 Institute of Physiology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.

aAddress correspondence to this author at: Department of Clinical Chemistry and Laboratory Medicine, University Hospital of Saarland, D-66421 Homburg/Saar, Germany. Fax 496841-1630703; e-mail kchwher{at}uniklinik-saarland.de.

Background: Recently, hyperhomocysteinemia (HHCY) has been suggested as a new risk factor for osteoporosis. This study investigated if HHCY is a causal osteoporotic factor in vivo.

Methods: We used 3 groups of rats: a control group (n = 20), a moderate HHCY group (induced by a 2.4% methionine-enriched diet, n = 10), and an intermediate HHCY group (induced by a 2% homocystine-enriched diet, n = 10). We measured bone fragility [maximum force of an axial compression test (Fmax)], bone area as percentage of total area (BAr/TAr, histomorphometry), and biochemical bone turnover markers [osteocalcin (OC) and collagen I C-terminal crosslaps (CTx)].

Results: Compared with controls, 3 months of moderate or intermediate HHCY increased mean (SD) bone fragility at the femoral neck by 18% (6%) in methionine-fed (P = 0.001) and 36% (13%) in homocystine-fed rats (P <0.001). Mean (SD) BAr/TAr at the distal femur in methionine and homocystine groups was decreased by 45% (21%; P = 0.001) and 93% (9%; P = 0.001), respectively. At the femoral neck, BAr/TAr was decreased by 19% (11%; P <0.001) and 55% (19%; P <0.001). At the lumbar spine, the reduction of BAr/TAr was 17% (23%; P = 0.099) and 44% (19%; P <0.001). Plasma OC (bone formation marker) was decreased by 23% (20%; P = 0.006) and 34% (21%; P <0.001). Plasma CTx (bone resorption marker) did not differ between groups.

Conclusion: Bone quality is consistently decreased in the presence of increased circulating homocysteine. The results provide evidence that HHCY is a causal osteoporotic factor.




The following articles in journals at HighWire Press have cited this article:


Home page
 IBMS BoneKEyHome page
P. Garnero
New Biochemical Markers of Bone Turnover
IBMS BoneKEy, March 1, 2008; 5(3): 84 - 102.
[Abstract] [Full Text] [PDF]


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