Abstract
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 [median age (25th–75th percentile), 67 (57–75) years]. 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 NF-κB ligand (sRANKL) were studied. Results: According to BMD subjects were classified as normal (n=24), osteopenic (n=51) or osteoporotic (n=68). Median Hcy did not differ between normal, osteopenic and osteoporotic subjects (p=0.647). Partial correlation analysis, controlling for the major confounders, age, creatinine, menopause and previous fractures, revealed significant correlations between Hcy and DPD (r=0.193, p=0.022), as well as between Hcy and Ca (r=0.170, p=0.045). 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 relation between Hcy and bone resorption was not dependent on OPG or sRANKL.
References
1. Ray NF, Chan JK, Thamer M, Melton LJ III. Medical expenditures for the treatment of osteoporotic fractures inthe United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res 1997; 12:24–35.10.1359/jbmr.1997.12.1.24Search in Google Scholar
2. Melton LJ III. Adverse outcomes of osteoporotic fractures in the general population. J Bone Miner Res 2003; 18:1139–41.10.1359/jbmr.2003.18.6.1139Search in Google Scholar
3. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 1999; 353:878–82.10.1016/S0140-6736(98)09075-8Search in Google Scholar
4. Chrischilles E, Shireman T, Wallace R. Costs and health effects of osteoporotic fractures. Bone 1994; 15:377–86.10.1016/8756-3282(94)90813-3Search in Google Scholar
5. Kanis JA, Jonsson B. Economic evaluation of interventions for osteoporosis. Osteoporos Int 2002; 13:765–7.10.1007/s001980200106Search in Google Scholar PubMed
6. Walker-Bone K, Walter G, Cooper C. Recent developments in the epidemiology of osteoporosis. Curr Opin Rheumatol 2002; 14:411–5.10.1097/00002281-200207000-00014Search in Google Scholar PubMed
7. Kanis JA, Black D, Cooper C, Dargent P, Dawson-Hughes B, De Laet C, et al. A new approach to the development of assessment guidelines for osteoporosis. Osteoporos Int 2002; 13:527–36.10.1007/s001980200069Search in Google Scholar PubMed
8. Eisman J, Clapham S, Kehoe L. Osteoporosis prevalence and levels of treatment in primary care: the Australian Bone Care Study. J Bone Miner Res 2004; 19:1969–75.10.1359/jbmr.040905Search in Google Scholar
9. Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris DW, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract 2003; 9:544–64.10.4158/EP.9.6.544Search in Google Scholar PubMed
10. McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004; 350:2042–9.10.1056/NEJMoa032739Search in Google Scholar PubMed
11. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004; 350:2033–41.10.1056/NEJMoa032546Search in Google Scholar
12. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. J Am Med Assoc 2005; 293:1082–8.10.1001/jama.293.9.1082Search in Google Scholar
13. Cagnacci A, Baldassari F, Rivolta G, Arangino S, Volpe A. Relation of homocysteine, folate, and vitamin B12 to bone mineral density of postmenopausal women. Bone 2003; 33:956–9.10.1016/j.bone.2003.07.001Search in Google Scholar
14. Golbahar J, Hamidi A, Aminzadeh MA, Omrani GR. Association of plasma folate, plasma total homocysteine, but not methylenetetrahydrofolate reductase C667T polymorphism, with bone mineral density in postmenopausal Iranian women: a cross-sectional study. Bone 2004; 35:760–5.10.1016/j.bone.2004.04.018Search in Google Scholar
15. Morris MS, Jacques PF, Selhub J. Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 2005; 37:234–42.10.1016/j.bone.2005.04.017Search in Google Scholar
16. Lenchik L, Kiebzak GM, Blunt BA. What is the role of serial bone mineral density measurements in patient management? J Clin Densitom 2002; 5(Suppl):S29–38.10.1385/JCD:5:3S:S29Search in Google Scholar
17. Bonnick SL. Current controversies in bone densitometry. Curr Opin Rheumatol 2002; 14:416–20.10.1097/00002281-200207000-00015Search in Google Scholar
18. Deal CL. Using bone densitometry to monitor therapy in treating osteoporosis: pros and cons. Curr Rheumatol Rep 2001; 3:233–9.10.1007/s11926-001-0023-4Search in Google Scholar PubMed
19. Delmas PD, Eastell R, Garnero P, Seibel MJ, Stepan J. The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int 2000; 11(Suppl 6):S2–17.10.1007/s001980070002Search in Google Scholar PubMed
20. Stepan JJ. Prediction of bone loss in postmenopausal women. Osteoporos Int 2000; 11(Suppl 6):S45–54.10.1007/s001980070005Search in Google Scholar PubMed
21. Bode MK, Laitinen P, Risteli J, Uusimaa P, Juvonen T. Atherosclerosis, type 1 collagen cross-linking and homocysteine. Atherosclerosis 2000; 152:531–2.10.1016/S0021-9150(00)00548-7Search in Google Scholar
22. Miyao M, Morita H, Hosoi T, Kurihara H, Inoue S, Ho-shino S, et al. Association of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women. Calcif Tissue Int 2000; 66:190–4.10.1007/s002230010038Search in Google Scholar
23. Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, Lips P, Smit JH, van Staveren WA. Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 2005; 20:921–9.10.1359/JBMR.050202Search in Google Scholar
24. Njeh CF, Apple K, Temperton DH, Boivin CM. Radiological assessment of a new bone densitometer – the Lunar EXPERT. Br J Radiol 1996; 69:335–40.10.1259/0007-1285-69-820-335Search in Google Scholar
25. Meunier PJ, Delmas PD, Eastell R, McClung MR, Papapoulos S, Rizzoli R, et al. Diagnosis and management of osteoporosis in postmenopausal women: clinical guidelines. International Committee for Osteoporosis Clinical Guidelines. Clin Ther 1999; 21:1025–44.10.1016/S0149-2918(99)80022-8Search in Google Scholar
26. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry: scientific review. J Am Med Assoc 2002; 288:1889–97.10.1001/jama.288.15.1889Search in Google Scholar
27. Grieco AJ. Homocystinuria: pathogenetic mechanisms. Am J Med Sci 1977; 273:120–32.10.1097/00000441-197703000-00001Search in Google Scholar
28. Morreels CL Jr, Fletcher BD, Weilbaecher RG, Dorst JP. The roentgenographic features of homocystinuria. Radiology 1968; 90:1150–8.10.1148/90.6.1150Search in Google Scholar
29. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985; 37:1–31.Search in Google Scholar
30. McKusick V. Heritable disorders of connective tissue, 3rd ed. St Louis, MO: Mosby, 2004.Search in Google Scholar
31. Kang AH, Trelstad RL. A collagen defect in homocystinuria. J Clin Invest 1973; 52:2571–8.10.1172/JCI107449Search in Google Scholar
32. Lubec B, Fang-Kircher S, Lubec T, Blom HJ, Boers GH. Evidence for McKusick's hypothesis of deficient collagen cross-linking in patients with homocystinuria. Biochim Biophys Acta 1996; 1315:159–62.10.1016/0925-4439(95)00119-0Search in Google Scholar
33. Herrmann M, Widmann T, Colaianni G, Colucci S, Zallone A, Herrmann W. Increased osteoclast activity in the presence of elevated homocysteine levels. Clin Chem. In press.Search in Google Scholar
34. Hofbauer LC, Kuhne CA, Viereck V. The OPG/RANKL/RANK system in metabolic bone diseases. J Musculoskelet Neuronal Interact 2004; 4:268–75.Search in Google Scholar
35. Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular diseases. J Am Med Assoc 2004; 292:490–5.10.1001/jama.292.4.490Search in Google Scholar PubMed
36. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 2002; 22:549–53.10.1161/01.ATV.0000012303.37971.DASearch in Google Scholar
37. Khosla S. Minireview: the OPG/RANKL/RANK system. Endocrinology 2001; 142:5050–5.10.1210/endo.142.12.8536Search in Google Scholar PubMed
©2005 by Walter de Gruyter Berlin New York
