Increased Osteoclast Activity in the Presence of Increased Homocysteine Concentrations

Herrmann, Markus; Widmann, Thomas; Colaianni, Graziana; Colucci, Silvia; Zallone, Alberta; Herrmann, Wolfgang

doi:10.1373/clinchem.2005.053363

Cited by 116 publications

(62 citation statements)

References 41 publications

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“…This conclusion is supported by cell culture experiments with human osteoclasts showing a dose-dependent increase in osteoclast activity with increasing Hcy concentrations in the culture medium (33).…”

Section: Discussionmentioning

confidence: 70%

Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women

Herrmann¹,

Kraenzlin²,

Pape³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background: Recently, increased plasma homocysteine (Hcy) has been suggested as an independent risk factor for osteoporotic fractures. Therefore, it is tempting to speculate that Hcy adversely affects bone metabolism. This study aimed to analyze the relation between Hcy and biochemical markers of bone metabolism and bone mineral density (BMD). Materials and methods: We investigated 143 peri-and post-menopausal women wmedian age (25th-75th percentile), 67 (57-75) yearsx. All subjects underwent a detailed medical examination, measurement of bone mineral density at lumbar spine (BMD-LS) and total hip (BMD-HIP), and fasting venous blood and urine sampling. Osteocalcin (OC), serum calcium (Ca), urinary desoxypyridinoline cross-links (DPD), osteoprotegerin (OPG) and soluble receptor activator of NFkB ligand (sRANKL) were studied. Results: According to BMD subjects were classified as normal (ns24), osteopenic (ns51) or osteoporotic (ns68). Median Hcy did not differ between normal, osteopenic and osteoporotic subjects (ps0.647). Partial correlation analysis, controlling for the major confounders, age, creatinine, menopause and previous fractures, revealed significant correlations between Hcy and DPD (rs0.193, ps0.022), as well as between Hcy and Ca (rs0.170, ps0.045). After adjustment for the same confounders, subsequent regression analysis confirmed significant associations of Hcy with DPD and Ca. No significant relations could be observed between Hcy and BMD-LS, BMD-HIP, OC, OPG or sRANKL. Conclusion: Our results demonstrate weak, but significant, relations between Hcy and markers of organic and inorganic bone resorption, suggesting a mechanistic role of Hcy in bone metabolism. The rela-

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Section: Discussionmentioning

confidence: 70%

Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women

Herrmann¹,

Kraenzlin²,

Pape³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…(17,28,29) In experimental settings, Hcy has been reported to affect both osteoclasts and osteoblasts. (10,11) High Hcy levels may inhibit collagen cross-linking. (6,7) The most evident correlation between Hcy and a bone marker was noted for S-CTX.…”

Section: Figmentioning

confidence: 99%

“…(1,8,9) Experimental data suggest that high Hcy levels affect both osteoclasts and osteoblasts. (10,11) If a high Hcy level is the cause of an increased fracture risk or simply a bystander is not known. (12,13) A high Hcy level could also be caused by poor nutrition, which could affect fracture risk.…”

mentioning

confidence: 99%

Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women

Gerdhem

Ivaska

Isaksson

et al. 2007

Journal of Bone and Mineral Research

107

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Homocysteine has been suggested to be a risk factor for fracture, but the causal relationship is not clear. In 996 women from the OPRA study, high homocysteine level was associated with high bone marker levels and low BMD at baseline. During a mean 7-year follow-up, high homocysteine level was associated with mortality, but no clear association to fracture risk existed.Introduction: Recently, the association between high serum homocysteine (Hcy) levels and an increased risk of fracture has been described. Materials and Methods: Hcy levels were measured at baseline in 996 women, all 75 years old. Vitamin B 12 , folate, serum cross-linking telopeptide of type I collagen (CTX), serum TRACP5b, serum osteocalcin, urine deoxypyridinoline, PTH, areal BMD (aBMD), calcaneal quantitative ultrasound (QUS), and physical performance were assessed at baseline. Fractures and mortality were recorded during a mean follow-up of 7.0 years. Results: Bone marker levels were higher in women with Hcy in the highest quartile compared with all other women (p < 0.05). The most evident correlation between Hcy and a bone marker was seen with CTX (r ‫ס‬ 0.19, p < 0.001). aBMD (hip) was 4% lower, QUS was up to 2% lower, and gait speed was 11% slower among women with Hcy in the highest quartile compared with the other women (p < 0.05). During the follow-up, 267 women sustained at least one low-energy fracture (including 69 hip fractures). When women in the highest Hcy quartile were compared with all other women, the hazard ratios (HRs) for sustaining any type of fracture was 1.18 (95% CI, 0.89-1.36) and for hip fracture was 1.50 (95% CI, 0.91-1.94). For the same group of women, the mortality risk was 2.16 (95% CI, 1.58-2.55). Adjustments for confounders did not substantially change these associations. Adjustment for PTH increased the HR for hip fracture to 1.67 (95% CI, 1.01-2.17). Low vitamin B 12 or folate was not associated with increased fracture risk or mortality. Conclusions: High Hcy levels were associated with higher bone turnover, poor physical performance, and lower BMD. There was no clear association to fracture risk. The increased mortality among women with high Hcy levels indicates that a high Hcy level may be a marker of frailty.

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“…Treatment with vitamin B12 and folate, which lower Hcy levels, has been found to markedly decrease the risk of hip fracture in stroke patients (Sato et al, 2005), indicating that Hcy may play an important role in the development of osteoporosis. Although the precise mechanisms of Hcy-induced osteoporosis has not been determined, interfering with collagen cross-linking (Lubec et al, 1996), increased osteoclastic bone resorption (Herrmann et al, 2005) and decreased osteoblastic bone formation (Kim et al, 2006), have been reported to contribute to the development of Hcy-induced osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

Kim

Park²,

Koh³

et al. 2006

Exp Mol Med

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Homocysteine (Hcy) is thought to play an important role in the development of osteoporosis and fracture. Methionine synthase reductase (MTRR) is an enzyme involved in the conversion of Hcy to methionine. We hypothesized that certain genetic polymorphisms of MTRR leading to reduced enzyme activity may cause hyperhomocysteinemia and affect bone metabolism. We therefore examined the associations of the A66G and C524T polymorphisms of the MTRR gene with bone mineral density (BMD) and serum osteocalcin levels in postmenopausal women. Although we did not detect any significant associations between MTRR polymorphisms and BMD or serum osteocalcin levels, we found that the 66G/524C haplotype, which has reduced enzyme activity, was significantly associated with serum osteocalcin levels in a gene-dose dependent manner (P = 0.002). That is, the highest osteocalcin levels (34.5 ± 16.8 ng/ml) were observed in subjects bearing two copies, intermediate osteocalcin levels (32.6 ± 14.4 ng/ml) were observed in subjects bearing one copy, and the lowest levels of osteocalcin (28.8 ± 10.9 ng/ml) were observed in subjects bearing no copies. These results suggest that the 66G/524C haplotype of the MTRR gene affect bone turn over rate.

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Increased Osteoclast Activity in the Presence of Increased Homocysteine Concentrations

Cited by 116 publications

References 41 publications

Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women

Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women

Associations Between Homocysteine, Bone Turnover, BMD, Mortality, and Fracture Risk in Elderly Women

Methionine synthase reductase polymorphisms are associated with serum osteocalcin levels in postmenopausal women

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