Abstract
Background: Changes in plasma total homocysteine(tHcy) folic acid, vitamins B12 and B6 in individuals with osteoporosis are reported to impair collagen cross-linking and contribute to low bone mineral density (BMD). There is paucity of information on these associations in osteoporotic patients at risk of bone fractures in Nigeria. The study evaluated plasma tHcy, folic acid, vitamins B12
and B6,in relation to BMD in individuals with osteoporosis.
Methods: Fifty osteoporotic patients age 57.05±1.9 years were selected and fifty non osteoporotic volunteer’s age 54.8±0.9 years were included as controls. The osteoporotic group consisted of 11 males and 39 females (1:3.5) while the controls consisted of 13 males and 37 females (1:2.8) respectively. Bone mineral density, anthropometric indices plasma tHcy, folic acid, vitamins B12 and B6
,were determined using standard procedures.
Results: The results showed remarkably significant increase in plasma tHcy (p<0.001) (180%) compared with the control value. Striking significant decreases were observed in folic acid (62%), vitamins B12 (42%), B6 (59%) and BMI p<0.001) compared with control values. Positive correlation was obtained between vitamin B12 and BMD (r = 0.311, p<0.05).
Conclusion: Significant increase in tHcy with corresponding decreases in folic acid, vitamins B12 and B6 are related to decrease in BMD in osteoporotic patients. These changes could be important risk factors for bone fracture in osteoporotic Nigerians. Supplementation with the B vitamins may be beneficial to the patients.
Keywords: Osteoporosis, Homocysteine, Folic acid, Vitamins B12, B6 and Bone mineral density
Résumé
Introduction: Les variations de l’homocystéine plasmatique totale (tHcy) de l’acide folique, des vitamines B12 et B6 chez les personnes atteintes d’ostéoporose sont présentés à porter atteinte à réticulation du collagène et de contribuer à la faible densité minérale osseuse (DMO).Il y a peu d’informations sur ces associations chez les patients ostéoporotiques risque de fractures osseuses au Nigeria. L’étude a évalué plasma tHcy, acide folique, vitamines B12 et B6 , en ce qui concerne la DMO chez les personnes atteintes d’ostéoporose.
Méthodes: Cinquante patients ostéoporotiques’ âge 57,05 ± 1,9 ans ont été sélectionnés et non cinquante bénévoles ostéoporotiques l’âge 54.8± 0,9 ans ont été inclus comme contrôles. Le groupe de ostéoporotique composée de 11 hommes et 39 femmes (1: 3,5) tandis que les commandes étaient composés de 13 hommes et 37 femmes (1: 2.8) respectivement. La densité osseuse minérale, les indices anthropométriques plasma homocystéine, l’acide folique, des vitamines B12 et B6, ont été déterminés en utilisant des procédures standard.
Résultats: Les résultats ont montré une remarquable augmentation significative dans le plasma tHcy (P<0,001) (180 %) par rapport à la valeur de commande. Frappant diminutions significatives ont été observées en acide folique (62 %), les vitamines B12 (42 %), B6 (59 %) et de BMI P<0.001) par rapport aux valeurs de contrôle. Une corrélation positive a été obtenue entre la vitamine B12 et la densité minérale osseuse (r 0,311, P<0,05).
Conclusion: Une augmentation significative de tHcy avec des réductionsconcordantes en acide folique, vitamines B12 et B6 sont associés à diminuer la DMO chez les patients ostéoporotiques. Ces changements pourraient être d’importants facteurs de risque de fracture de l’OS ostéoporotiques aux Nigérians. Une supplémentation en vitamines B peut être bénéfique pour les patients.
Correspondence: Dr. M.O. Ebesunun, Depart ment of C hemic al P ath ology and Immunology, Faculty of Basic Medical Sciences, Obafemi Awolowo College of Health Sciences Olabisi Onabanjo University, Sagamu Campus, Nigeria. E–mail: onomhaguan25@gmail.com
References
World Health Organization. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis. Report of a WHO Study Group. World Health Organization Tech. Rep. Ser. 1994; 843:1- 129.
Orbandt KJ. Progresis and rehabilitation after hip fracture, Osteopororosis. International (supplement) 1996; S52-S59
Markus H., Thomas W and Wolfgang H. Homocysteine a newly recognized risk factor for osteoporosis (Review) Clin Chem. Lab. Med. 2005; 10: 1111-1117.
Cooper C. Epidemiology of Osteoporosis. Osteoporosis .Int.Supple 1999; 2: S2-S8.
Vanderjagt DJ, Bond B, Dulai A, et al. Assessment of bone status of Nigerian women by ultrasound and biochemical markers. Calcified Tissue International 2001; 68: 5: 271–272
Walsh JS, Henry YM, Fatayerji D and Eastell R. Lumbar spine peak bone mass and bone turnover in men and women: a longitudinal study. Osteoporosis Int. 2009; 20:355–362.
Van Meurs B, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004; 350: 2033-2041.
Pérez-López FR., Chedraui P and Cuadros-López JL. Bone Mass Gain During Puberty and Adolescence: Deconstructing Gender Characteristics. Current Medicinal Chemistry 2010; 17: 240-254.
McLean RR, Jacques PF, Selhub J, et al. Homocysteine as a predictive factor of hip fracture in older Persons. New England Journal of Medicine 2004; 350: 20:2042-2049
Deloughery TG, Evans A, Sadeghi A, et. al. Common mutation in methylenetetrahydrofolate reductase. Correlation with homocysteine metabolism and late onset vascular disease. Circulation. 1996; 94:3074-3078
Gjesdal CG, Vollset SE, Ueland PM, et al. Plasma total Homocysteine Study. Arch Intern Med 2006; 166: 88-94.
Saito M. Elevated plasma concentration of homocysteine, low level of vitamin B6 pyridoxal, and vitamin D insufficiency in patients with hip fracture: a possible explanation for detrimental cross-link pattern in bone collagen. Clin Calcium. 2006; 16:1974 -1984.
Kim DJ. Lee OS and Koh JM. Homocysteine enhances apoptosis via ROS-mediated mitochondrial pathway in human bone marrow stromal cells: a possible mechanism for homocysteine-mediated bone loss. J Bone Miner Res. 2005; 20: S242.
McNulty H, McKinley MC and Wilson B. Impaired functioning of thermolabile methy- lenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements. Am. J. Clin. Nutr 2002;76:436-441.
Morris MS, Jacques PF and Selhub J. Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 2005; 37: 234-242.
Frantzer F, Faaren M, Atherm J and Nirdhil AK. Enzyme conversion immune assay for determination of total homocysteine in plasma or serum. Chin Chann 1998; 44: 311 – 316.
Ebesunun MO, Evurulobi HU, Olagunji T and Owoeye OA. Elevated plasma homocysteine in association with decreased vitamin B12 folate serotonin lipids and lipoprotiens in depressed patients. African Journal of Psychiatry 2 012;.15: 25-29.
Ebesunun MO and Obajobi EO. Elevated plasma homocysteine in type 2 diabetes mellitus: a risk factor for cardiovascular diseases. Pan Afr Med J. 2012; 12:48.
Ibukun-olu Alade. Classification of Nigerian Foods: A review, United Nation University http://unu.edu
Martha SM , Paul FJ and Selhub J. Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 2005.37; 2: 234-242.
McLean R.R. Jacques P.F, Selhub J.et al. Bone loss and hip fracture in elderly men and women J. Clin Endocrinol Metab. 2008; 93: 6:2206-2212.
Cagnacci A, Baldassari F, Rivolta G, et al. Relation of homocysteine, folate and vitamin B12 to bone mineral density of postmenopausal women. Bone. 2003; 33: 956-959.
McLean RR and Hannan MT. B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Curr Osteoporosis Rep. 2007; 5:112–119.
Kang AH, Trelstad RL A collagen defect in homocystinuria. J Clin Invest 1973; 52:2571–2578.
Carlos L, Krumdieck C and Prince W. Mechanisms of Homocysteine Toxicity on Connective Tissues: Implications for the Morbidity of Aging. American J Nutrition 2000;
Roman T, Marlies A, Silvia S, et al. Homocysteine Suppresses the Expression of the Collagen Cross- linker Lysyl Oxidase Involving IL-6, Fli1, and Epigenetic DNA Methylation. J. Biol Chem. 2011; 286:(7) 5578–5588.
Baran DT, Faulkner KG, Genant HK, et al. Diagnosis and management of osteoporosis: guidelines for the utilization of bone densitometry. Calcif Tissue Int . 1997; 61: 6: 433-440.
Ouzzif Z. Oumghar K, Sbai K, et al. A Relation of plasma total homocysteine, folate and vitamin B12 levels to bone mineral density in Moroccan healthy postmenopausal women. Rheumatol Int. 2012; 32:(1): 123-128.
Jakubowski H. The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease. Journal of physiology and pharmacology suppl 2008; 9: 155-167.