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Osteoporosis International

, Volume 26, Issue 6, pp 1747–1753 | Cite as

Decreased bone cortical density at the forearm in subjects with subclinical peripheral arterial disease

  • A. Gaudio
  • F. Muratore
  • V. Fiore
  • R. Rapisarda
  • S. S. Signorelli
  • C. E. FioreEmail author
Original Article

Abstract

Summary

The association between peripheral arterial disease (PAD) and low bone mass is controversial. In our study, peripheral quantitative computed tomography shows a reduction of cortical but not trabecular, bone mineral density (BMD) at the forearm, in patients with subclinical PAD.

Introduction

Some controversy exists regarding the association between peripheral arterial disease (PAD) and low bone mass. Previous studies have evaluated bone mineral density (BMD) in patients with subclinical PAD, with mixed results. Inconsistency of data may depend on the fact that most studies measured areal bone mineral density (aBMD) by Dual-energy-x ray absorptiometry (DXA). Because DXA cannot distinguish between cortical and trabecular compartments, we reasoned that a study aimed to establish whether these compartments were differentially affected by PAD status could give more information on the nature of this association.

Methods

In this cross-sectional study, we used peripheral quantitative computed tomography (pQCT) to examine volumetric cortical and trabecular mineral density at the radius (vBMD) in a cohort of subjects with subclinical PAD as defined by ABI ≤0.90 and compared them with healthy subjects with no evidence of PAD.

Results

Patients with subclinical PAD had significantly reduced cortical density (1101.0 ± 45.4 vs 1156.2 ± 51.3 mg/cm3, p < 0.001) and cortical area (75.0 ± 20.9 vs 99.9 ± 18.2 mm2, p < 0.001) than healthy subjects. Trabecular density (178.1 ± 47.9 vs 165.8 ± 29.6 mg/cm3) was not significantly different in the two groups.

Conclusion

Subclinical PAD induces a selective bone loss at the radius compartment, not identified by standard DXA, which seems to occur primarily at the cortical level.

Keywords

Cortical density PAD pQCT RANKL 

Notes

Conflicts of interest

None.

References

  1. 1.
    Tankò LB, Christiansen C, Cox DA, Geiger MJ, McNabb MA, Cummings SR (2005) Relationship between osteoporosis and cardiovascular disease in postmenopausal women. J Bone Miner Res 20:1912–20PubMedCrossRefGoogle Scholar
  2. 2.
    Farhat GN, Strotmeyer ES, Newman AB, Sutton-Tyrrel K, Bauer DC, Harris T, Johnson KC, Toaffe DR, Cauley JA (2006) Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: the health, aging, and bone composition study. Calcif Tissue Int 79:102–11PubMedCrossRefGoogle Scholar
  3. 3.
    Fisher A, Srikusalanukul W, Davis M, Smith P (2013) Cardiovascular disease in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links. Clin Interv Aging 3:239–56CrossRefGoogle Scholar
  4. 4.
    Hampson G, Edwards S, Conroy S, Blake GM, Fogelman I, Frost ML (2013) The relationship between inhibitors of the Wnt signaling pathway (Dickkopf-1 (DKK1) and Sclerostin), bone mineral density, vascular calcification and arterial stiffness in post-menopausal women. Bone 56:42–7PubMedCrossRefGoogle Scholar
  5. 5.
    Criqui MH, Langer RD, Fronek A, Feigelson HS, Klauber MR, McCann TJ, Browner D (1992) Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 326:381–6PubMedCrossRefGoogle Scholar
  6. 6.
    Collins TC, Ewing SK, Diem SJ, Taylor BC, Orwoll ES, Cummings SR, Strotmeyer ES, Ensrud KE, Osteoporotic Fractures in Men (MrOS) Study Group (2009) Peripheral arterial disease is associated with higher rates of hip bone loss and increased fracture risk in older men. Circulation 119(17):2305–12PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Vogt MT, Cauley JA, Kuller LH, Nevitt MC (1997) Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res 12:283–9PubMedCrossRefGoogle Scholar
  8. 8.
    Fowkes FG, Housley E, Macintyre CC, Prescott RJ, Ruckley CV (1998) Variability of ankle and brachial systolic pressure in the measurement of atherosclerotic peripheral arterial disease. J Epidemiol Community Health 42:128–33CrossRefGoogle Scholar
  9. 9.
    Von MÜhlen D, Allison M, Jassel SK, Barret-Connor E (2009) Peripheral arterial disease and osteoporosis in older adults: the Rancho Bernardo study. Osteoporos Int 20:2071–8CrossRefGoogle Scholar
  10. 10.
    London GM, Marchais SJ, Guérin AP, de Vernejoul MC (2014) Ankle-brachial index and bone turnover in patients on dialysis. J Am Soc Nephrol. 2014 Sep 17. pii: ASN.2014020169Google Scholar
  11. 11.
    Van der Klift M, Pols HA, Hak AE, Witteman JC, Hofman A, de Laet CE (2002) Bone mineral density and the risk of peripheral arterial disease: the Rotterdam Study. Calcif Tissue Int 70:443–9PubMedCrossRefGoogle Scholar
  12. 12.
    Mangiafico RA, Russo E, Riccobene S, Pennisi P, Mangiafico M, D’Amico F, Fiore CE (2006) Increased prevalence of peripheral arterial disease in osteoporotic postmenopausal women. J Bone Miner Metab 24:125–31PubMedCrossRefGoogle Scholar
  13. 13.
    Wong SY, Kwok T, Woo J, Lynn H, Griffith JF, Leung J (2005) Bone mineral density and the risk of peripheral arterial disease in men and women: results from Mr and Ms Os, Hong Kong. Osteoporos Int 16:1933–8PubMedCrossRefGoogle Scholar
  14. 14.
    Fiore CE, Pennisi P, Tinè M (2008) Therapeutic perspectives. Clin Cases Miner Bone Metab 5(1):45–8PubMedCentralPubMedGoogle Scholar
  15. 15.
    Khosla S (2001) Minireview: the OPG/RANKL/RANK system. Endocrinology 142(12):5050–5PubMedCrossRefGoogle Scholar
  16. 16.
    Hofbauer LC, Brueck CC, Shanahan CM, Schoppet M, Dobnig H (2007) Vascular calcification and osteoporosis: from clinical observation towards molecular understanding. Osteoporos Int 18:251–9PubMedCrossRefGoogle Scholar
  17. 17.
    Ali Z, Ellington AA, Mosley TH Jr, Kullo IJ (2009) Association of serum osteoprotegerin with ankle-brachial index and urine albumin: creatinine ratio in African-Americans and non-Hispanic whites. Atherosclerosis 206:575–80PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Pennisi P, Russo E, Gaudio A, Veca R, D’Amico F, Mangiafico RA, Laspina M, Tringali G, Signorelli SS, Fiore CE (2010) The association between carotid or femoral atheriosclerosis and low bone mass in postmenopausal women referred for osteoporosis screening. Does osteoprotegerin play a role? Maturitas 67:358–62PubMedCrossRefGoogle Scholar
  19. 19.
    Fahrleitner-Pammer A, Obernosterer A, Pilger E, Dobnig H, Dimai HP, Leb G (2005) Hypovitaminosis D, impaired bone turnover and low bone mass are common in patients with peripheral arterial disease. Osteoporos Int 16:319–24PubMedCrossRefGoogle Scholar
  20. 20.
    Tankò LB, Bagger YZ, Christiansen C (2003) Low bone mineral density in the hip as marker of advanced atherosclerosis in elderly women. Calcif Tissue Int 73:15–20PubMedCrossRefGoogle Scholar
  21. 21.
    Grampp S, Lang PL, Jergas M, GlÜer CC, Mathur A, Engelke K, Genant HK (1995) Assessment of the skeletal status by peripheral quantitative computed tomography of the forearm: short-term precision in vivo and comparison to dual X-ray absorptiometry. J Bone Miner Res 10:1566–76PubMedCrossRefGoogle Scholar
  22. 22.
    Patsch JM, Burghardt A, Yap SP, Baum T, Schwartz AV, Joseph GB, Link TM (2013) Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res 28:313–24PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Jamal SA, Gilbert J, Gordon C, Bauer DC (2006) Cortical pQCT measures are associated with fractures in dialysis patients. J Bone Miner Res 21:543–8PubMedCrossRefGoogle Scholar
  24. 24.
    Wetzsteon RJ, Shults J, Zemel BS, Gupta PU, Burnham JM, Herskontz RM, Howard KM, Leonard MB (2009) Divergent effects of glucocorticoids on cortical and trabecular compartment BMD in Childhood nephrotic syndrome. J Bone Miner Res 24:503–13PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Stein EM, Carrelli A, Young P, Bucovsky M, Zhang C, Schrope B, Bessler M, Zhou B, Wang J, Guo E, McMahon DJ, Silverberg SJ (2013) Bariatric surgery results in cortical bone loss. J Clin Endocrinol Metab 98:541–9PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Winterhalder L, Eser P, Widmer J, Villiger PM, Aeberli D (2012) Changes in volumetric BMD of radius and tibia upon antidepressants drug administration in young depressive patients. J Muskuloskelet Neuronal Interact 12:224–9Google Scholar
  27. 27.
    Gaudio A, Pennisi P, Muratore F, Bertino G, Ardiri A, Pulvirenti I, Tringali G, Fiore CE (2012) Reduction of volumetric bone mineral density in postmenopausal women with hepatitis C virus-correlated chronic liver disease: a peripheral quantitative computerized tomography (pQCT) study. Eur J Int Med 23:656–60CrossRefGoogle Scholar
  28. 28.
    Fowkes FG (1988) The measurement of atherosclerotic peripheral arterial disease in epidemiological surveys. Int J Epidemiol 17:248–54PubMedCrossRefGoogle Scholar
  29. 29.
    Hiatt WR (2001) Medical treatment of peripheral arterial disease and claudication. N Engl J Med 344:1608–21PubMedCrossRefGoogle Scholar
  30. 30.
    Augat P, Gordon CL, Lang TF, Iida H, Genant HK (1998) Accuracy of cortical and trabecular bone measurements with peripheral quantitative computed tomography (pQCT). Pys Med Biol 43:2873–83CrossRefGoogle Scholar
  31. 31.
    Kassanos D, Trakakis E, Baltos CS, Papakonstantinou O, Simeonidis G, Salamalakis G, Grammatikakis I, Basios G, Labos G, Skarantavos G, Balanika A (2010) Augmentation of cortical bone mineral density in women with polycystic ovary syndrome: a peripheral quantitative computed tomography (pQCT) study. Human Rep 25:2107–14CrossRefGoogle Scholar
  32. 32.
    Turner CH, Burr DB (1993) Basic biomechanical measurements of bone. A tutorial Bone 14:595–608CrossRefGoogle Scholar
  33. 33.
    Sievänen H, Koskue V, Rauhio A, Kannus P, Heinonen A, Vuori I (1998) Peripheral quantitative computed tomography in human long bones: evaluation of in vitro and in vivo precision. J Bone Miner Res 13:871–82PubMedCrossRefGoogle Scholar
  34. 34.
    Hasegawa K, Hasegawa Y, Nagano A (2004) Estimation of bone mineral density and architectural parameters of the distal radius in hemodialysis patients using peripheral quantitative computed tomography. J Biomech 37:751–6PubMedCrossRefGoogle Scholar
  35. 35.
    Russo C, Taccetti G, Caneva P, Mannarino A, Maranghi P, Ricca M (1998) Volumetric bone density and geometry assessed by peripheral quantitative computed tomography in uremic patients on maintenance hemodialysis. Osteoporos Int 8:443–8PubMedCrossRefGoogle Scholar
  36. 36.
    Laroche M, Pouilles JM, Ribot C, Bendajan P, Bernard J, Boccalon H (1994) Comparison of the bone mineral content of the lower limbs in men with ischaemic atherosclerotic disease. Clin Rheumatol 13:611–4PubMedCrossRefGoogle Scholar
  37. 37.
    De Schutter TM, Neven E, Persy VP, Behets GJ, Postnov AA, De Clerck NM, D'Haese PC (2011) Vascular calcification is associated with cortical bone loss in chronic renal failure rats with and without ovariectomy: the calcification paradox. Am J Nephrol 34(4):356–66PubMedCrossRefGoogle Scholar
  38. 38.
    Kuipers AL, Zmuda JM, Carr JT, Terry JG, Patrick AL, Gey Y, Hightower RC, Bunker CH, Miljkovic I (2014) Association of volumetric bone mineral density with abdominal aortic calcification in African ancestry men. Osteoporos Int 25:1063–9PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Kiechl S, Werner P, Knoflach M, Furtner M, Willeit J, Schett G (2006) The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease. Expert Rev Cardiovasc Ther 4:801–11PubMedCrossRefGoogle Scholar
  40. 40.
    Schoppet M, Preissner KT, Hofbauer LC (2002) RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 22:549–53PubMedCrossRefGoogle Scholar
  41. 41.
    Browner WS, Lui LY, Cummings SR (2001) Association of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86:631–7PubMedGoogle Scholar
  42. 42.
    Kiechl S, Schett G, Schwaiger J, Seppi K, Eder P, Egger G, Santer P, Mayr A, Xu Q, Willeit J (2007) Soluble receptor activator of nuclear factor-kappa B ligand and risk for cardiovascular disease. Circulation 116:385–91PubMedCrossRefGoogle Scholar
  43. 43.
    Schoppet M, Schaefer JR, Hofbauer LC (2003) Low serum levels of soluble RANK ligand are associated with the presence of coronary artery disease in men. Circulation 107:e76PubMedCrossRefGoogle Scholar
  44. 44.
    Crisafulli A, Micari A, Altavilla D, Saporito F, Sardella A, Passaniti M, Raffa S, D’Anneo G, Mioni F, Arrigo F, Squadrito F (2005) Serum levels of osteoprotegerin and RANKL inpatients with ST elevation acute myocardial infarction. Clin Sci (London) 209:389–95Google Scholar
  45. 45.
    Xiong J, O’Brien CA (2012) Osteocyte RANKL: new insights in the control of bone remodeling. J Bone Miner Res 27:499–505PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ (2011) Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. Plos ONE 6:e25900PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Rhee Y, Lee E, Lezcano V, Ronda AC, Condon KK, Allen MR, Plotkin LI, Bellido T (2013) Resorption controls bone anabolism driven by PTH receptor signaling in osteocytes. J Biol Chem 288:29809–20PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Weinstein RS (2010) Glucocorticoids, osteocytes, and skeletal fragility: the role of bone vascularity. Bone 46:564–70PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Knothe Tate ML, Niederer P, Nnothe U (1998) In vivo tracer transport through the lacuno-canalicular system of rat bone in an environment devoid of mechanical loading. Bone 22:107–17PubMedCrossRefGoogle Scholar
  50. 50.
    Beveridge LA, Witham MD (2013) Vitamin D and cardiovascular system. Osteoporos Int 24:2168–80CrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • A. Gaudio
    • 1
  • F. Muratore
    • 1
  • V. Fiore
    • 2
  • R. Rapisarda
    • 1
  • S. S. Signorelli
    • 2
  • C. E. Fiore
    • 1
    Email author
  1. 1.Department of Clinical and Experimental Medicine, Section of Metabolic Bone DiseaseUniversity of CataniaCataniaItaly
  2. 2.Department of Clinical and Experimental Medicine, Section of Vascular Medicine, Medical Angiology UnitUniversity of CataniaCataniaItaly

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