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Published in: Calcified Tissue International 3/2013

01-09-2013 | Original Research

Plasma Level of Homocysteine Associated with Severe Vertebral Fracture in Postmenopausal Women

Authors: Tatsuhiko Kuroda, Shiro Tanaka, Mitsuru Saito, Yumiko Shiraki, Masataka Shiraki

Published in: Calcified Tissue International | Issue 3/2013

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Abstract

The aim of this cross-sectional cohort study was to clarify risk factors for severe vertebral fractures in postmenopausal Japanese women. Subjects were ambulatory volunteers age over 50 years who were recruited from a population of outpatients at a primary care institute. At registration, age, body mass index (BMI), bone mineral density (BMD), and present illness were investigated. Biochemical parameters including urinary levels of type I collagen cross-linked N-telopeptides (NTXs), and pentosidine and plasma levels of homocysteine were measured. Values were compared with different fracture grades (grade 0–3). A total of 1,475 postmenopausal women (66.6 ± 9.0 years) were included in the present study. Distributions of vertebral fracture grades were grade 1, 137 cases (9.3 %); grade 2, 124 cases (8.4 %); and grade 3, 162 cases (11.0 %). Age, BMI, BMD, NTX, pentosidine, and homocysteine were significantly associated with vertebral fracture in unadjusted analysis. In addition, a higher prevalence of hypertension was observed in patients with severe fracture. When comparing vertebral fracture grade 0 versus grade 2–3 by multiple regression analysis, pentosidine and homocysteine levels were a significant risk for moderate/severe vertebral fracture (odds ratio [OR] = 1.17, 95 % confidence interval [CI] 1.00–1.38, p = 0.049; OR = 1.22, 95 % CI 1.03–1.46, p = 0.013). Homocysteine levels were also a significant risk when comparing vertebral fracture grade 0 versus grade 3 (OR = 1.27, 95 % CI 1.04–1.58, p = 0.021). Plasma level of homocysteine was an independent risk for severe vertebral fractures.
Literature
1.
go back to reference NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795CrossRef NIH Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795CrossRef
2.
go back to reference Shiraki M, Kuroda T, Shiraki Y, Aoki C, Sasaki K, Tanaka S (2010) Effects of bone mineral density of the lumbar spine and prevalent vertebral fractures on the risk of immobility. Osteoporos Int 21:1545–1551PubMedCrossRef Shiraki M, Kuroda T, Shiraki Y, Aoki C, Sasaki K, Tanaka S (2010) Effects of bone mineral density of the lumbar spine and prevalent vertebral fractures on the risk of immobility. Osteoporos Int 21:1545–1551PubMedCrossRef
3.
go back to reference Kuroda T, Shiraki M, Tanaka S, Ohta H (2009) Contributions of 25-hydroxyvitamin D, co-morbidities and bone mass to mortality in Japanese postmenopausal women. Bone 44:168–172PubMedCrossRef Kuroda T, Shiraki M, Tanaka S, Ohta H (2009) Contributions of 25-hydroxyvitamin D, co-morbidities and bone mass to mortality in Japanese postmenopausal women. Bone 44:168–172PubMedCrossRef
4.
go back to reference Ross PD, Davis JW, Epstein RS, Wasnich RD (1991) Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 114:919–923PubMedCrossRef Ross PD, Davis JW, Epstein RS, Wasnich RD (1991) Pre-existing fractures and bone mass predict vertebral fracture incidence in women. Ann Intern Med 114:919–923PubMedCrossRef
5.
go back to reference Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739PubMedCrossRef Klotzbuecher CM, Ross PD, Landsman PB, Abbott TA III, Berger M (2000) Patients with prior fractures have an increased risk of future fractures: a summary of the literature and statistical synthesis. J Bone Miner Res 15:721–739PubMedCrossRef
6.
go back to reference Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–382PubMedCrossRef Kanis JA, Johnell O, De Laet C, Johansson H, Oden A, Delmas P et al (2004) A meta-analysis of previous fracture and subsequent fracture risk. Bone 35:375–382PubMedCrossRef
7.
go back to reference Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRef Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E et al (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRef
8.
go back to reference Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) investigators. JAMA 282:637–645PubMedCrossRef Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) investigators. JAMA 282:637–645PubMedCrossRef
9.
go back to reference Gallagher JC, Genant HK, Crans GG, Vargas SJ, Krege JH (2005) Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic fractures. J Clin Endocrinol Metab 90:1583–1587PubMedCrossRef Gallagher JC, Genant HK, Crans GG, Vargas SJ, Krege JH (2005) Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic fractures. J Clin Endocrinol Metab 90:1583–1587PubMedCrossRef
10.
go back to reference Gonnelli S, Caffarelli C, Maggi S, Rossi S, Siviero P, Gandolini G, Cisari C, Rossini M, Iolascon G, Letizia Mauro G, Crepaldi G, Nuti R, BREAK Study Group (2013) The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study. Osteoporos Int 24:1151–1159PubMedCrossRef Gonnelli S, Caffarelli C, Maggi S, Rossi S, Siviero P, Gandolini G, Cisari C, Rossini M, Iolascon G, Letizia Mauro G, Crepaldi G, Nuti R, BREAK Study Group (2013) The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study. Osteoporos Int 24:1151–1159PubMedCrossRef
11.
go back to reference Wustrack R, Seeman E, Bucci-Rechtweg C, Burch S, Palermo L, Black DM (2012) Predictors of new and severe vertebral fractures: results from the HORIZON Pivotal Fracture Trial. Osteoporos Int 23:53–58PubMedCrossRef Wustrack R, Seeman E, Bucci-Rechtweg C, Burch S, Palermo L, Black DM (2012) Predictors of new and severe vertebral fractures: results from the HORIZON Pivotal Fracture Trial. Osteoporos Int 23:53–58PubMedCrossRef
12.
go back to reference Shiraki M, Kuroda T, Tanaka S, Saito M, Fukunaga M, Nakamura T (2008) Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts vertebral fractures. J Bone Miner Metab 26:93–100PubMedCrossRef Shiraki M, Kuroda T, Tanaka S, Saito M, Fukunaga M, Nakamura T (2008) Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts vertebral fractures. J Bone Miner Metab 26:93–100PubMedCrossRef
13.
go back to reference Shiraki M, Urano T, Kuroda T, Saito M, Tanaka S, Miyao-Koshizuka M et al (2008) The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures. J Bone Miner Metab 26:595–602PubMedCrossRef Shiraki M, Urano T, Kuroda T, Saito M, Tanaka S, Miyao-Koshizuka M et al (2008) The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures. J Bone Miner Metab 26:595–602PubMedCrossRef
14.
go back to reference Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis the Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–996PubMedCrossRef Genant HK, Jergas M, Palermo L, Nevitt M, Valentin RS, Black D et al (1996) Comparison of semiquantitative visual and quantitative morphometric assessment of prevalent and incident vertebral fractures in osteoporosis the Study of Osteoporotic Fractures Research Group. J Bone Miner Res 11:984–996PubMedCrossRef
15.
go back to reference Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH (2007) Enhanced prediction of fracture risk combining vertebral fracture status and BMD. Osteoporos Int 18:761–770PubMedCrossRef Siris ES, Genant HK, Laster AJ, Chen P, Misurski DA, Krege JH (2007) Enhanced prediction of fracture risk combining vertebral fracture status and BMD. Osteoporos Int 18:761–770PubMedCrossRef
16.
go back to reference Imai E, Horio M, Watanabe T, Iseki K, Yamagata K, Hara S et al (2009) Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol 13:621–630PubMedCrossRef Imai E, Horio M, Watanabe T, Iseki K, Yamagata K, Hara S et al (2009) Prevalence of chronic kidney disease in the Japanese general population. Clin Exp Nephrol 13:621–630PubMedCrossRef
17.
go back to reference Vester B, Rasmussen K (1991) High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Eur J Clin Chem Clin Biochem 29:549–554PubMed Vester B, Rasmussen K (1991) High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Eur J Clin Chem Clin Biochem 29:549–554PubMed
18.
go back to reference Shiraki M, Kuroda T, Shiraki Y, Tanaka S, Higuchi T, Saito M (2011) Urinary pentosidine and plasma homocysteine levels at baseline predict future fractures in osteoporosis patients under bisphosphonate treatment. J Bone Miner Metab 29:62–70PubMedCrossRef Shiraki M, Kuroda T, Shiraki Y, Tanaka S, Higuchi T, Saito M (2011) Urinary pentosidine and plasma homocysteine levels at baseline predict future fractures in osteoporosis patients under bisphosphonate treatment. J Bone Miner Metab 29:62–70PubMedCrossRef
19.
go back to reference Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M (2007) Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int 18:1617–1624PubMedCrossRef Roux C, Fechtenbaum J, Kolta S, Briot K, Girard M (2007) Mild prevalent and incident vertebral fractures are risk factors for new fractures. Osteoporos Int 18:1617–1624PubMedCrossRef
20.
go back to reference Bennani L, Allali F, Rostom S, Hmamouchi I, Khazzani H, El Mansouri L et al (2009) Relationship between historical height loss and vertebral fractures in postmenopausal women. Clin Rheumatol 28:1283–1289PubMedCrossRef Bennani L, Allali F, Rostom S, Hmamouchi I, Khazzani H, El Mansouri L et al (2009) Relationship between historical height loss and vertebral fractures in postmenopausal women. Clin Rheumatol 28:1283–1289PubMedCrossRef
21.
go back to reference Suzuki N, Ogikubo O, Hansson T (2009) The prognosis for pain, disability, activities of daily living and quality of life after an acute osteoporotic vertebral body fracture: its relation to fracture level, type of fracture and grade of fracture deformation. Eur Spine J 18:77–88PubMedCrossRef Suzuki N, Ogikubo O, Hansson T (2009) The prognosis for pain, disability, activities of daily living and quality of life after an acute osteoporotic vertebral body fracture: its relation to fracture level, type of fracture and grade of fracture deformation. Eur Spine J 18:77–88PubMedCrossRef
22.
go back to reference Crans GG, Silverman SL, Genant HK, Glass EV, Krege JH (2004) Association of severe vertebral fractures with reduced quality of life: reduction in the incidence of severe vertebral fractures by teriparatide. Arthritis Rheum 50:4028–4034PubMedCrossRef Crans GG, Silverman SL, Genant HK, Glass EV, Krege JH (2004) Association of severe vertebral fractures with reduced quality of life: reduction in the incidence of severe vertebral fractures by teriparatide. Arthritis Rheum 50:4028–4034PubMedCrossRef
23.
go back to reference Tanaka S, Kuroda T, Saito M, Shiraki M (2011) Urinary pentosidine improves risk classification using fracture risk assessment tools for postmenopausal women. J Bone Miner Res 26:2778–2784PubMedCrossRef Tanaka S, Kuroda T, Saito M, Shiraki M (2011) Urinary pentosidine improves risk classification using fracture risk assessment tools for postmenopausal women. J Bone Miner Res 26:2778–2784PubMedCrossRef
24.
go back to reference Gineyts E, Munoz F, Bertholon C, Sornay-Rendu E, Chapurlat R (2010) Urinary levels of pentosidine and the risk of fracture in postmenopausal women: the OFELY study. Osteoporos Int 21:243–250PubMedCrossRef Gineyts E, Munoz F, Bertholon C, Sornay-Rendu E, Chapurlat R (2010) Urinary levels of pentosidine and the risk of fracture in postmenopausal women: the OFELY study. Osteoporos Int 21:243–250PubMedCrossRef
25.
go back to reference Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR et al (2009) Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 94:2380–2386PubMedCrossRef Schwartz AV, Garnero P, Hillier TA, Sellmeyer DE, Strotmeyer ES, Feingold KR et al (2009) Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab 94:2380–2386PubMedCrossRef
26.
go back to reference Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019PubMedCrossRef Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T (2008) Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 93:1013–1019PubMedCrossRef
27.
go back to reference Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214PubMedCrossRef Saito M, Marumo K (2010) Collagen cross-links as a determinant of bone quality: a possible explanation for bone fragility in aging, osteoporosis, and diabetes mellitus. Osteoporos Int 21:195–214PubMedCrossRef
28.
go back to reference Lubec B, Fang-Kircher S, Lubec T, Blom HJ, Boers GH (1996) Evidence for McKusick’s hypothesis of deficient collagen cross-linking in patients with homocystinuria. Biochim Biophys Acta 1315:159–162PubMedCrossRef Lubec B, Fang-Kircher S, Lubec T, Blom HJ, Boers GH (1996) Evidence for McKusick’s hypothesis of deficient collagen cross-linking in patients with homocystinuria. Biochim Biophys Acta 1315:159–162PubMedCrossRef
29.
go back to reference Khan M, Yamauchi M, Srisawasdi S, Stiner D, Doty S, Paschalis EP et al (2001) Homocysteine decreases chondrocyte-mediated matrix mineralization in differentiating chick limb-bud mesenchymal cell micro-mass cultures. Bone 28:387–398PubMedCrossRef Khan M, Yamauchi M, Srisawasdi S, Stiner D, Doty S, Paschalis EP et al (2001) Homocysteine decreases chondrocyte-mediated matrix mineralization in differentiating chick limb-bud mesenchymal cell micro-mass cultures. Bone 28:387–398PubMedCrossRef
30.
go back to reference Jakubowski H (2000) Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 275:3957–3962PubMedCrossRef Jakubowski H (2000) Calcium-dependent human serum homocysteine thiolactone hydrolase. A protective mechanism against protein N-homocysteinylation. J Biol Chem 275:3957–3962PubMedCrossRef
31.
go back to reference Herrmann M, Tami A, Wildemann B, Wolny M, Wagner A, Schorr H et al (2009) Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone. Bone 44:467–475PubMedCrossRef Herrmann M, Tami A, Wildemann B, Wolny M, Wagner A, Schorr H et al (2009) Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone. Bone 44:467–475PubMedCrossRef
32.
go back to reference McLean RR, Hannan MT (2007) B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Curr Osteoporos Rep 5:112–119PubMedCrossRef McLean RR, Hannan MT (2007) B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Curr Osteoporos Rep 5:112–119PubMedCrossRef
33.
go back to reference Van Meus J, Dhonukshe-Rutten R, Pluijm S, van der Klift M, deJonge R, Lindemans J et al (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033–2041CrossRef Van Meus J, Dhonukshe-Rutten R, Pluijm S, van der Klift M, deJonge R, Lindemans J et al (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033–2041CrossRef
34.
go back to reference El Maghraoui A, Ghozlani I, Mounach A, Rezqi A, Oumghar K, Achemlal L et al (2012) Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women. J Clin Densitom 15:328–333PubMedCrossRef El Maghraoui A, Ghozlani I, Mounach A, Rezqi A, Oumghar K, Achemlal L et al (2012) Homocysteine, folate, and vitamin B12 levels and vertebral fracture risk in postmenopausal women. J Clin Densitom 15:328–333PubMedCrossRef
35.
go back to reference McCarthy AD, Etcheverry SB, Bruzzone L, Lettieri G, Barrio DA, Cortizo AM (2001) Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic development and oxidative stress. BMC Cell Biol 2:16PubMedCrossRef McCarthy AD, Etcheverry SB, Bruzzone L, Lettieri G, Barrio DA, Cortizo AM (2001) Non-enzymatic glycosylation of a type I collagen matrix: effects on osteoblastic development and oxidative stress. BMC Cell Biol 2:16PubMedCrossRef
36.
go back to reference Saito M, Fujii K, Marumo K (2006) Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 79:160–168PubMedCrossRef Saito M, Fujii K, Marumo K (2006) Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 79:160–168PubMedCrossRef
Metadata
Title
Plasma Level of Homocysteine Associated with Severe Vertebral Fracture in Postmenopausal Women
Authors
Tatsuhiko Kuroda
Shiro Tanaka
Mitsuru Saito
Yumiko Shiraki
Masataka Shiraki
Publication date
01-09-2013
Publisher
Springer US
Published in
Calcified Tissue International / Issue 3/2013
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-013-9754-2

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