Experimental Hyperhomocysteinemia Reduces Bone Quality in Rats

Herrmann, Markus; Wildemann, Britt; Claes, Lutz; Klohs, Stefan; Ohnmacht, Michael; Taban-Shomal, Omid; Hübner, Ulrich; Pexa, Anette; Umanskaya, Natalia; Herrmann, Wolfgang

doi:10.1373/clinchem.2007.086272

Cited by 56 publications

(39 citation statements)

References 29 publications

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“…32 Another rat study showed that increased homocysteinemia induced by a diet enriched in methiononine or homocysteine -which is likely to interfere with crosslink formation -for 3 months resulted in decreased bone formation, bone volume and bone strength at the distal femur. 33 The impact of an increase of enzymatic crosslinks on bone strength can also be investigated using fetal bovine cortical bone, which is characterized by a low level of these molecules. By incubating bone samples at 37 ° C for 60 days, we showed that the increase in PYD and DPD was positively associated with an increase of ultimate stress and post-yield energy absorption.…”

Section: Collagen Post-translational Modifications and Bone Strengthmentioning

confidence: 99%

The contribution of collagen crosslinks to bone strength

Garnero¹

2012

BoneKEy Reports

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Collagen crosslinking is a major post-translational modification of collagen which has important roles in determining the biomechanical competence of bone. Crosslinks can be divided into enzymatic lysil oxidase-mediated and nonenzymatic glycation-induced (advanced glycation end products, AGE) molecules. In addition, collagen in bone can also undergo spontaneous isomerization and racemization of the aspartic acid residues with the C-telopeptide (CTX), leading to the formation of two isomers namely ␣ (newly formed collagen) and ␤ (matured isomerized collagen) CTX. Several in vitro and ex vivo studies, relating the bone content of these crosslinks with bone strength, have shown that they contributed to the mechanical competence of trabecular and cortical bone -mainly on the post-yield properties -in part independent of the bone mineral content. In addition, AGEs such as pentosidine have been reported to alter the formation and propagation of microdamage by making the bone more brittle. The bone content of AGEs and isomerization can also be modified by antiresorptive and anabolic therapies. They may thus explain part of the antifracture efficacy of these treatments. The main challenge consists in the transposition of these in vitro / ex vivo studies to clinical applications for the development of a non-invasive biomarker, as none of currently identified collagen crosslinks (both enzymatic and nonenzymatic) is bone specific. Nevertheless, serum or urine levels of pentosidine and the ratio of ␣ / ␤ CTX have been reported to predict fracture risk in postmenopausal women, in men and in patients with type 2 diabetes.

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Section: Collagen Post-translational Modifications and Bone Strengthmentioning

confidence: 99%

The contribution of collagen crosslinks to bone strength

Garnero¹

2012

BoneKEy Reports

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“…Hcy is the final degradation product of the methionine pathway and is increased if vitamin B12, folate and/or B6, important co-enzymes of the Hcy degrading re-methylation and trans-sulfuration pathway, are deficient (7). In vivo and in vitro studies suggest that there are direct effects of Hcy and vitamin B12 on bone metabolism (8)(9)(10). In rats, 3 and 5 months of continuous hyperhomocysteinemia causes bone loss and a reduction in bone strength (9).…”

Section: Introductionmentioning

confidence: 99%

“…In vivo and in vitro studies suggest that there are direct effects of Hcy and vitamin B12 on bone metabolism (8)(9)(10). In rats, 3 and 5 months of continuous hyperhomocysteinemia causes bone loss and a reduction in bone strength (9). Cell culture experiments using human osteoclasts and osteoblasts revealed a distinct increase in osteoclast activity in the presence of high tHcy and low vitamin B12, B6, and folate concentrations in the culture medium.…”

Section: Introductionmentioning

confidence: 99%

Enhanced bone metabolism in vegetarians – the role of vitamin B12 deficiency

Herrmann

Obeid²,

Schorr³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: Vitamin B12 deficiency and bone fractures are common in vegetarians. However, a direct relationship between vitamin B12 status and bone metabolism in vegetarians has not been tested sufficiently. Methods: Our study included 96 vegetarians (23 German vegans, and 54 German and 19 Indian lacto-, lacto-ovo-vegetarians) and 89 omnivores (Germans and Asian-Indian immigrants in Oman). Blood concentrations of total vitamin B12, holotranscobalamin (holoTC), 25OH-vitamin D (25(OH)D), total homocysteine (tHcy), methylmalonic acid (MMA), and the bone turnover markers (BTMs) bone alkaline phosphatase (BAP), osteocalcin (OC), pro-collagen type I N-terminal peptide (PINP) and C-terminal telopeptides of collagen I (CTx) were measured. Results: Vegetarians from both population groups exhibited significantly higher concentrations of tHcy, MMA, folate, and BAP, but lower concentrations of holoTC and cobalamin compared with omnivores from the same population. Additionally, German vegetarians had higher circulating activities of BAP as well as higher CTx, OC, and PINP compared with their omnivorous controls. HoloTC and MMA were correlated with OC, CTx and BAP. Subjects with low vitamin B12 status (holoTC F35 pmol/L and MMA

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“…First experimental evidence for an osteoporotic potency of chronic hyperhomocysteinemia (HHCY) comes from two recent animal studies. (7,8) After 3 and 5 mo of HHCY, healthy adult rats exhibited a distinct loss of cancellous bone and a reduction in bone strength. The adverse effects of HHCY on bone were accompanied by a bonespecific accumulation of HCY, S-adenosyl-homocysteine (SAH), and S-adenosyl-methionine (SAM).…”

Section: Introductionmentioning

confidence: 99%

Experimental Folate and Vitamin B12 Deficiency Does Not Alter Bone Quality in Rats

Herrmann

Wildemann

Wagner

et al. 2009

Journal of Bone and Mineral Research

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Hyperhomocysteinemia (HHCY) has been linked to fragility fractures and osteoporosis. Folate and vitamin B 12 deficiencies are among the main causes of HHCY. However, the impact of these vitamins on bone health has been poorly studied. This study analyzed the effect of folate and vitamin B 12 deficiency on bone in rats. We used two groups of rats: a control group (Co, n = 10) and a vitamin-deficient group (VitDef, n = 10). VitDef animals were fed for 12 wk with a folate-and vitamin B 12 -free diet. Co animals received an equicaloric control diet. Tissue and plasma concentrations of homocysteine (HCY), S-adenosyl-homocysteine (SAH), and S-adenosyl-methionine (SAM) were measured. Bone quality was assessed by biomechanical testing (maximum force of an axial compression test; F max ), histomorphometry (bone area/total area; B.Ar./ T.Ar.], and the measurement of biochemical bone turnover markers (osteocalcin, collagen I C-terminal crosslaps [CTX]). VitDef animals developed significant HHCY (Co versus VitDef: 6.8 ± 2.7 versus 61.1 ± 12.8 mM, p < 0.001) that was accompanied by a high plasma concentration of SAH (Co versus VitDef: 24.1 ± 5.9 versus 86.4 ± 44.3 nM, p < 0.001). However, bone tissue concentrations of HCY, SAH, and SAM were similar in the two groups. Fmax, B.Ar./T.Ar., OC, and CTX did not differ between VitDef and Co animals, indicating that bone quality was not affected. Folate and vitamin B 12 deficiency induces distinct HHCY but has no effect on bone health in otherwise healthy adult rats. The unchanged HCY metabolism in bone is the most probable explanation for the missing effect of the vitamin-free diet on bone.

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Experimental Hyperhomocysteinemia Reduces Bone Quality in Rats

Cited by 56 publications

References 29 publications

The contribution of collagen crosslinks to bone strength

The contribution of collagen crosslinks to bone strength

Enhanced bone metabolism in vegetarians – the role of vitamin B12 deficiency

Experimental Folate and Vitamin B12 Deficiency Does Not Alter Bone Quality in Rats

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