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Increased low-density lipoprotein cholesterol level is associated with non-vertebral fractures in postmenopausal women

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Abstract

Although a high serum low-density lipoprotein cholesterol (LDL-C) level is an established risk factor for atherosclerosis, it is unclear whether it is associated with osteoporosis. In this study, the associations between the serum LDL-C level and bone mineral density (BMD), bone metabolic markers, and the presence of prevalent vertebral or non-vertebral fractures were examined. A total of 211 healthy postmenopausal women (age range, 46–80 years) who visited a community health center were recruited consecutively. Their radiographic and biochemical characteristics were collected. Prevalent vertebral and non-vertebral fractures were found in 49 (23.2 %) and 36 (17.1 %) subjects, respectively. Simple regression analyses showed that the serum LDL-C level was not significantly correlated with lumbar or femoral BMD or serum levels of total amino-terminal propeptide of type I collagen (PINP) or carboxy-terminal telopeptide of type I collagen (CTX). Logistic regression analyses adjusted for age and BMI showed that the increased serum LDL-C level was selected as an index affecting the presence of prevalent non-vertebral fractures, but not vertebral fractures. This result was still significant after additional adjustments for years since menopause, physical activity, previous cardiovascular events, bone markers, BMD, serum Ca, P, Cr, 25(OH)D, grip strength, tandem gait test, and use of drugs for hyperlipidemia [odds ratio 1.76 (1.13–2.73), p = 0.012]. These findings suggest that a high serum LDL-C level may be a risk factor for prevalent non-vertebral fragility fractures independent of bone turnover, bone mass, vitamin D insufficiency, or frail status in postmenopausal women, and that it may be detrimental to bone, as well as blood vessels.

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References

  1. G.N. Farhat, J.A. Cauley, K.A. Matthews, A.B. Newman, J. Johnston, R. Mackey, D. Edmundowicz, K. Sutton-Tyrrell, Volumetric BMD and vascular calcification in middle-aged women: the Study of Women’s Health Across the Nation. J. Bone Miner. Res. 21(12), 1839–1846 (2006). doi:10.1359/jbmr.060903

    Article  PubMed  Google Scholar 

  2. P. Pennisi, S.S. Signorelli, S. Riccobene, G. Celotta, L. Di Pino, T. La Malfa, C.E. Fiore, Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos. Int. 15(5), 389–395 (2004). doi:10.1007/s00198-003-1550-9

    Article  CAS  PubMed  Google Scholar 

  3. L.B. Tanko, Y.Z. Bagger, C. Christiansen, Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif. Tissue Int. 73(1), 15–20 (2003)

    Article  CAS  PubMed  Google Scholar 

  4. Y.Z. Bagger, L.B. Tanko, P. Alexandersen, G. Qin, C. Christiansen, Radiographic measure of aorta calcification is a site-specific predictor of bone loss and fracture risk at the hip. J. Intern. Med. 259(6), 598–605 (2006)

    Article  CAS  PubMed  Google Scholar 

  5. E. Schulz, K. Arfai, X. Liu, J. Sayre, V. Gilsanz, Aortic calcification and the risk of osteoporosis and fractures. J. Clin. Endocrinol. Metab. 89(9), 4246–4253 (2004)

    Article  CAS  PubMed  Google Scholar 

  6. L.B. Tanko, C. Christiansen, D.A. Cox, M.J. Geiger, M.A. McNabb, S.R. Cummings, Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J. Bone Miner. Res. 20(11), 1912–1920 (2005)

    Article  PubMed  Google Scholar 

  7. M.M. Pinheiro, C.M. Castro, V.L. Szejnfeld, Low femoral bone mineral density and quantitative ultrasound are risk factors for new osteoporotic fracture and total and cardiovascular mortality: a 5-year population-based study of Brazilian elderly women. J. Gerontol. A. Biol. Sci. Med. Sci. 61(2), 196–203 (2006)

    Article  PubMed  Google Scholar 

  8. H.C. Silva, M.M. Pinheiro, P.S. Genaro, C.H. Castro, C.M. Monteiro, F.A. Fonseca, V.L. Szejnfeld, Higher prevalence of morphometric vertebral fractures in patients with recent coronary events independently of BMD measurements. Bone 52(2), 562–567 (2013). doi:10.1016/j.bone.2012.11.004

    Article  PubMed  Google Scholar 

  9. N. Bucay, I. Sarosi, C.R. Dunstan, S. Morony, J. Tarpley, C. Capparelli, S. Scully, H.L. Tan, W. Xu, D.L. Lacey, W.J. Boyle, W.S. Simonet, osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes. Dev. 12(9), 1260–1268 (1998)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. M. Kuro-o, Y. Matsumura, H. Aizawa, H. Kawaguchi, T. Suga, T. Utsugi, Y. Ohyama, M. Kurabayashi, T. Kaname, E. Kume, H. Iwasaki, A. Iida, T. Shiraki-Iida, S. Nishikawa, R. Nagai, Y.I. Nabeshima, Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390(6655), 45–51 (1997). doi:10.1038/36285

    Article  CAS  PubMed  Google Scholar 

  11. K. Tamai, M. Semenov, Y. Kato, R. Spokony, C. Liu, Y. Katsuyama, F. Hess, J.P. Saint-Jeannet, X. He, LDL-receptor-related proteins in Wnt signal transduction. Nature 407(6803), 530–535 (2000). doi:10.1038/35035117

    Article  CAS  PubMed  Google Scholar 

  12. R. Baron, G. Rawadi, S. Roman-Roman, Wnt signaling: a key regulator of bone mass. Curr. Top. Dev. Biol. 76, 103–127 (2006). doi:10.1016/S0070-2153(06)76004-5

    Article  CAS  PubMed  Google Scholar 

  13. A. Mani, J. Radhakrishnan, H. Wang, A. Mani, M.A. Mani, C. Nelson-Williams, K.S. Carew, S. Mane, H. Najmabadi, D. Wu, R.P. Lifton, LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315(5816), 1278–1282 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. M.S. Huang, J. Lu, Y. Ivanov, A.P. Sage, W. Tseng, L.L. Demer, Y. Tintut, Hyperlipidemia impairs osteoanabolic effects of PTH. J. Bone Miner. Res. 23(10), 1672–1679 (2008). doi:10.1359/jbmr.080513

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. A.P. Sage, J. Lu, E. Atti, S. Tetradis, M.G. Ascenzi, D.J. Adams, L.L. Demer, Y. Tintut, Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids. J. Bone Miner. Res. 26(6), 1197–1206 (2011). doi:10.1002/jbmr.312

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. F. Parhami, S.M. Jackson, Y. Tintut, V. Le, J.P. Balucan, M. Territo, L.L. Demer, Atherogenic diet and minimally oxidized low density lipoprotein inhibit osteogenic and promote adipogenic differentiation of marrow stromal cells. J. Bone Miner. Res. 14(12), 2067–2078 (1999). doi:10.1359/jbmr.1999.14.12.2067

    Article  CAS  PubMed  Google Scholar 

  17. F. Parhami, Y. Tintut, W.G. Beamer, N. Gharavi, W. Goodman, L.L. Demer, Atherogenic high-fat diet reduces bone mineralization in mice. J. Bone Miner. Res. 16(1), 182–188 (2001). doi:10.1359/jbmr.2001.16.1.182

    Article  CAS  PubMed  Google Scholar 

  18. T. Majima, A. Shimatsu, Y. Komatsu, N. Satoh, A. Fukao, K. Ninomiya, T. Matsumura, K. Nakao, Increased bone turnover in patients with hypercholesterolemia. Endocr. J. 55(1), 143–151 (2008)

    Article  CAS  PubMed  Google Scholar 

  19. T. Yamaguchi, T. Sugimoto, S. Yano, M. Yamauchi, H. Sowa, Q. Chen, K. Chihara, Plasma lipids and osteoporosis in postmenopausal women. Endocr. J. 49(2), 211–217 (2002)

    Article  CAS  PubMed  Google Scholar 

  20. Y.H. Hsu, S.A. Venners, H.A. Terwedow, Y. Feng, T. Niu, Z. Li, N. Laird, J.D. Brain, S.R. Cummings, M.L. Bouxsein, C.J. Rosen, X. Xu, Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women. Am. J. Clin. Nutr. 83(1), 146–154 (2006)

    CAS  PubMed  Google Scholar 

  21. I.K. Jeong, S.W. Cho, S.W. Kim, H.J. Choi, K.S. Park, S.Y. Kim, H.K. Lee, S.H. Cho, B.H. Oh, C.S. Shin, Lipid profiles and bone mineral density in pre- and postmenopausal women in Korea. Calcif. Tissue Int. 87(6), 507–512 (2010). doi:10.1007/s00223-010-9427-3

    Article  CAS  PubMed  Google Scholar 

  22. D.H. Solomon, J. Avorn, C.F. Canning, P.S. Wang, Lipid levels and bone mineral density. Am. J. Med. 118(12), 1414 (2005)

    Article  Google Scholar 

  23. W.T. Friedewald, R.I. Levy, D.S. Fredrickson, Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18(6), 499–502 (1972)

    CAS  PubMed  Google Scholar 

  24. P. Garnero, P. Vergnaud, N. Hoyle, Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis. Clin. Chem. 54(1), 188–196 (2008). doi:10.1373/clinchem.2007.094953

    Article  CAS  PubMed  Google Scholar 

  25. H. Schmidt-Gayk, E. Spanuth, J. Kotting, R. Bartl, D. Felsenberg, J. Pfeilschifter, F. Raue, H.J. Roth, Performance evaluation of automated assays for beta-CrossLaps, N-MID-Osteocalcin and intact parathyroid hormone (BIOROSE Multicenter Study). Clin. Chem. Lab. Med. 42(1), 90–95 (2004). doi:10.1515/CCLM.2004.017

    Article  CAS  PubMed  Google Scholar 

  26. A. Leino, U. Turpeinen, P. Koskinen, Automated measurement of 25-OH vitamin D3 on the Roche Modular E170 analyzer. Clin. Chem. 54(12), 2059–2062 (2008). doi:10.1373/clinchem.2008.111732

    Article  CAS  PubMed  Google Scholar 

  27. D. Nakaoka, T. Sugimoto, T. Kobayashi, T. Yamaguchi, A. Kobayashi, K. Chihara, Prediction of bone mass change after parathyroidectomy in patients with primary hyperparathyroidism. J. Clin. Endocrinol. Metab. 85(5), 1901–1907 (2000)

    CAS  PubMed  Google Scholar 

  28. H.K. Genant, C.Y. Wu, C. van Kuijk, M.C. Nevitt, Vertebral fracture assessment using a semiquantitative technique. J. Bone Miner. Res. 8(9), 1137–1148 (1993). doi:10.1002/jbmr.5650080915

    Article  CAS  PubMed  Google Scholar 

  29. E.M. Lewiecki, A.J. Laster, Clinical review: clinical applications of vertebral fracture assessment by dual-energy x-ray absorptiometry. J. Clin. Endocrinol. Metab. 91(11), 4215–4222 (2006). doi:10.1210/jc.2006-1178

    Article  CAS  PubMed  Google Scholar 

  30. T. Fuerst, C. Wu, H.K. Genant, G. von Ingersleben, Y. Chen, C. Johnston, M.J. Econs, N. Binkley, T.J. Vokes, G. Crans, B.H. Mitlak, Evaluation of vertebral fracture assessment by dual X-ray absorptiometry in a multicenter setting. Osteoporos. Int. 20(7), 1199–1205 (2009). doi:10.1007/s00198-008-0806-9

    Article  CAS  PubMed  Google Scholar 

  31. P.D. Delmas, H.K. Genant, G.G. Crans, J.L. Stock, M. Wong, E. Siris, J.D. Adachi, Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33(4), 522–532 (2003)

    Article  CAS  PubMed  Google Scholar 

  32. P. Garnero, F. Munoz, E. Sornay-Rendu, P.D. Delmas, Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study. Bone 40(3), 716–722 (2007). doi:10.1016/j.bone.2006.09.026

    Article  CAS  Google Scholar 

  33. M. Janghorbani, R.M. Van Dam, W.C. Willett, F.B. Hu, Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am. J. Epidemiol. 166(5), 495–505 (2007). doi:10.1093/aje/kwm106

    Article  PubMed  Google Scholar 

  34. P. Vestergaard, Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos. Int. 18(4), 427–444 (2007). doi:10.1007/s00198-006-0253-4

    Article  CAS  PubMed  Google Scholar 

  35. L. Dukas, E. Schacht, H.B. Stahelin, In elderly men and women treated for osteoporosis a low creatinine clearance of <65 ml/min is a risk factor for falls and fractures. Osteoporos. Int. 16(12), 1683–1690 (2005). doi:10.1007/s00198-005-1903-7

    Article  CAS  PubMed  Google Scholar 

  36. K.E. Ensrud, L.Y. Lui, B.C. Taylor, A. Ishani, M.G. Shlipak, K.L. Stone, J.A. Cauley, S.A. Jamal, D.M. Antoniucci, S.R. Cummings, Renal function and risk of hip and vertebral fractures in older women. Arch. Intern. Med. 167(2), 133–139 (2007). doi:10.1001/archinte.167.2.133

    Article  PubMed  Google Scholar 

  37. L.H. Cui, M.H. Shin, E.K. Chung, Y.H. Lee, S.S. Kweon, K.S. Park, J.S. Choi, Association between bone mineral densities and serum lipid profiles of pre- and post-menopausal rural women in South Korea. Osteoporos. Int. 16(12), 1975–1981 (2005)

    Article  CAS  PubMed  Google Scholar 

  38. I.K. Jeong, S.W. Cho, S.W. Kim, H.J. Choi, K.S. Park, S.Y. Kim, H.K. Lee, S.H. Cho, B.H. Oh, C.S. Shin, Lipid profiles and bone mineral density in pre- and postmenopausal women in Korea. Calcif. Tissue Int. 87(6), 507–512 (2010). doi:10.1007/s00223-010-9427-3

    Article  CAS  PubMed  Google Scholar 

  39. F. Sivas, E. Alemdaroglu, E. Elverici, T. Kulug, K. Ozoran, Serum lipid profile: its relationship with osteoporotic vertebrae fractures and bone mineral density in Turkish postmenopausal women. Rheumatol. Int. 29(8), 885–890 (2009). doi:10.1007/s00296-008-0784-4

    Article  CAS  PubMed  Google Scholar 

  40. P. Trimpou, A. Oden, T. Simonsson, L. Wilhelmsen, K. Landin-Wilhelmsen, High serum total cholesterol is a long-term cause of osteoporotic fracture. Osteoporos. Int. 22(5), 1615–1620 (2011). doi:10.1007/s00198-010-1367-2

    Article  CAS  PubMed  Google Scholar 

  41. Y.Z. Bagger, H.B. Rasmussen, P. Alexandersen, T. Werge, C. Christiansen, L.B. Tanko, Links between cardiovascular disease and osteoporosis in postmenopausal women: serum lipids or atherosclerosis per se? Osteoporos. Int. 18(4), 505–512 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. F. Parhami, L.L. Demer, Arterial calcification in face of osteoporosis in ageing: can we blame oxidized lipids? Curr. Opin. Lipidol. 8(5), 312–314 (1997)

    Article  CAS  PubMed  Google Scholar 

  43. Y. Tintut, F. Parhami, A. Tsingotjidou, S. Tetradis, M. Territo, L.L. Demer, 8-Isoprostaglandin E2 enhances receptor-activated NFkappa B ligand (RANKL)-dependent osteoclastic potential of marrow hematopoietic precursors via the cAMP pathway. J. Biol. Chem. 277(16), 14221–14226 (2002). doi:10.1074/jbc.M111551200

    Article  CAS  PubMed  Google Scholar 

  44. J.A. Cauley, A.Z. Lacroix, L. Wu, M. Horwitz, M.E. Danielson, D.C. Bauer, J.S. Lee, R.D. Jackson, J.A. Robbins, C. Wu, F.Z. Stanczyk, M.S. LeBoff, J. Wactawski-Wende, G. Sarto, J. Ockene, S.R. Cummings, Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann. Intern. Med. 149(4), 242–250 (2008)

    Article  PubMed Central  PubMed  Google Scholar 

  45. M. Yamauchi, H. Kaji, K. Nawata, S. Takaoka, T. Yamaguchi, T. Sugimoto, Role of parathyroid hormone in bone fragility of postmenopausal women with vitamin D insufficiency. Calcif. Tissue Int. 88(5), 362–369 (2011). doi:10.1007/s00223-011-9464-6

    Article  CAS  PubMed  Google Scholar 

  46. C. Mattila, P. Knekt, S. Mannisto, H. Rissanen, M.A. Laaksonen, J. Montonen, A. Reunanen, Serum 25-hydroxyvitamin D concentration and subsequent risk of type 2 diabetes. Diabetes Care 30(10), 2569–2570 (2007). doi:10.2337/dc07-0292

    Article  CAS  PubMed  Google Scholar 

  47. M. Leu, E. Giovannucci, Vitamin D: epidemiology of cardiovascular risks and events. Best Pract Res Clin Endocrinol Metab 25(4), 633–646 (2011). doi:10.1016/j.beem.2011.04.001

    Article  CAS  PubMed  Google Scholar 

  48. T. Skaaby, L.L. Husemoen, C. Pisinger, T. Jorgensen, B.H. Thuesen, M. Fenger, A. Linneberg, Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 43(3), 618–625 (2013). doi:10.1007/s12020-012-9805-x

    Article  CAS  PubMed  Google Scholar 

  49. W. Saliba, O. Barnett, H.S. Rennert, G. Rennert, The risk of all-cause mortality is inversely related to serum 25(OH)D levels. J. Clin. Endocrinol. Metab. 97(8), 2792–2798 (2012). doi:10.1210/jc.2012-1747

    Article  CAS  PubMed  Google Scholar 

  50. C. Gagnon, Z.X. Lu, D.J. Magliano, D.W. Dunstan, J.E. Shaw, P.Z. Zimmet, K. Sikaris, P.R. Ebeling, R.M. Daly, Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: ausDiab). J. Clin. Endocrinol. Metab. 97(6), 1953–1961 (2012). doi:10.1210/jc.2011-3187

    Article  CAS  PubMed  Google Scholar 

  51. J.Y. Chung, S.H. Hong, Vitamin D status and its association with cardiometabolic risk factors in Korean adults based on a 2008-2010 Korean National Health and Nutrition Examination Survey. Nutr. Res. Pract. 7(6), 495–502 (2013). doi:10.4162/nrp.2013.7.6.495

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. M.P. Ponda, X. Huang, M.A. Odeh, J.L. Breslow, H.W. Kaufman, Vitamin D may not improve lipid levels: a serial clinical laboratory data study. Circulation 126(3), 270–277 (2012). doi:10.1161/CIRCULATIONAHA.111.077875

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  53. L.H. Li, X.Y. Yin, C.Y. Yao, X.C. Zhu, X.H. Wu, Serum 25-hydroxyvitamin D, parathyroid hormone, and their association with metabolic syndrome in Chinese. Endocrine 44(2), 465–472 (2013). doi:10.1007/s12020-013-9885-2

    Article  CAS  PubMed  Google Scholar 

  54. K.S. Sarkis, L.A. Martini, V.L. Szejnfeld, M.M. Pinheiro, Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL-cholesterol are associated with high bone mineral density in women: a cross-sectional study with control group. Lipids. Health. Dis. 11, 37 (2012). doi:10.1186/1476-511X-11-37

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  55. D.C. Bauer, G.R. Mundy, S.A. Jamal, D.M. Black, J.A. Cauley, K.E. Ensrud, M. van der Klift, H.A. Pols, Use of statins and fracture: results of 4 prospective studies and cumulative meta-analysis of observational studies and controlled trials. Arch. Intern. Med. 164(2), 146–152 (2004). doi:10.1001/archinte.164.2.146

    Article  CAS  PubMed  Google Scholar 

  56. K. Esposito, A. Capuano, L. Sportiello, A. Giustina, D. Giugliano, Should we abandon statins in the prevention of bone fractures? Endocrine 44(2), 326–333 (2013). doi:10.1007/s12020-013-9924-z

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by Grants-in-Aid Scientific Research (C) No. 23590882 (to M. Yamauchi) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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  1. Internal Medicine 1, Faculty of Medicine, Shimane University, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan

    Mika Yamauchi, Toru Yamaguchi, Kiyoko Nawata, Ken-ichiro Tanaka, Shin Takaoka & Toshitsugu Sugimoto

  2. Health and Nutrition, The University of Shimane, Izumo, Japan

    Kiyoko Nawata

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  1. Mika Yamauchi
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Yamauchi, M., Yamaguchi, T., Nawata, K. et al. Increased low-density lipoprotein cholesterol level is associated with non-vertebral fractures in postmenopausal women. Endocrine 48, 279–286 (2015). https://doi.org/10.1007/s12020-014-0292-0

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