Introduction. Atherosclerosis and osteoporosis share an age-independent bidirectional correlation. Rheumatoid arthritis (RA) represents a risk factor for both conditions. Objectives. The study aims to evaluate the connection between the estimated cardiovascular risk (CVR) and the loss of bone tissue in RA patients. Methods. The study has a prospective cross-sectional design and it includes female in-patients with RA or without autoimmune diseases; bone tissue was measured using whole body dual X-ray absorptiometry (wbDXA); CVR was estimated using SCORE charts and PROCAM applications. Results. There were 75？RA women and 66 normal women of similar age. The wbDXA bone indices correlate significantly, negatively, and age-independently with the estimated CVR. The whole body bone percent (wbBP) was a significant predictor of estimated CVR, explaining 26% of SCORE variation along with low density lipoprotein ( ) and 49.7% of PROCAM variation along with glycemia and menopause duration ( ). Although obese patients had less bone relative to body composition (wbBP), in terms of quantity their bone content was significantly higher than that of nonobese patients. Conclusions. Female patients with RA and female patients with cardiovascular morbidity have a lower whole body bone percent. Obese female individuals have higher whole body bone mass than nonobese patients. 1. Introduction Atherosclerosis and osteoporosis share an age-independent bidirectional correlation [1, 2], although they were considered to be independent pathologies. On one hand, low bone mass is associated with subclinical [3] and clinical atherosclerosis, manifested as cardiovascular morbidity [4, 5] and mortality [6]. On the other hand, cardiovascular disease is associated with low bone mass and with a higher risk of fragility fractures [7]. There is no unifying theory which can explain a deterministic link between atherosclerosis and osteoporosis, if any. Certainly, bone modeling and vascular calcification have common biological processes and risk factors (e.g., smoking, inactivity, and inflammation) [8]. We can cite RA among these factors, as a crossroad of atherosclerosis and osteoporosis. The main cause of mortality in RA is the cardiovascular pathology [9, 10]. Adding to the classical cardiovascular risk (CVR) factor, chronic inflammation [11, 12] and disease duration [12] contribute decisively to the excess cardiovascular mortality in RA. The background of this observation is the inflammatory pathogenesis of RA which is associated with accelerated atherosclerosis [13], both clinically and
References
[1]
D. den Uyl, M. T. Nurmohamed, L. H. D. van Tuyl, H. G. Raterman, and W. F. Lems, “(Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk, a systematic review of the association between cardiovascular disease and osteoporosis,” Arthritis Research and Therapy, vol. 13, no. 1, article R5, 2011.
[2]
G. N. Farhat and J. A. Cauley, “The link between osteoporosis and cardiovascular disease,” Clinical Cases in Mineral and Bone Metabolism, vol. 5, no. 1, pp. 19–34, 2008.
[3]
D. P. Kiel, L. I. Kauppila, L. A. Cupples, M. T. Hannan, C. J. O'Donnell, and P. W. F. Wilson, “Bone loss and the progression of abdominal aortic calcification over 25 year period: the Framingham Heart Study,” Calcified Tissue International, vol. 68, no. 5, pp. 271–276, 2001.
[4]
G. N. Farhat, A. B. Newman, K. Sutton-Tyrrell et al., “The association of bone mineral density measures with incident cardiovascular disease in older adults,” Osteoporosis International, vol. 18, no. 7, pp. 999–1008, 2007.
[5]
J. H. Magnus and D. L. Broussard, “Relationship between bone mineral density and myocardial infarction in US adults,” Osteoporosis International, vol. 16, no. 12, pp. 2053–2062, 2005.
[6]
M. E. Mussolino, J. H. Madans, and R. F. Gillum, “Bone mineral density and mortality in women and men: the NHANES I epidemiologic follow-up study,” Annals of Epidemiology, vol. 13, no. 10, pp. 692–697, 2003.
[7]
J. S. Chen, C. Hogan, G. Lyubomirsky, and P. N. Sambrook, “Women with cardiovascular disease have increased risk of osteoporotic fracture,” Calcified Tissue International, vol. 88, no. 1, pp. 9–15, 2011.
[8]
A. Fisher, W. Srikusalanukul, M. Davis, et al., “Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links,” Journal of Clinical Interventions in Aging, vol. 8, pp. 239–256, 2013.
[9]
H. Maradit-Kremers, P. J. Nicola, C. S. Crowson, K. V. Ballman, and S. E. Gabriel, “Cardiovascular death in rheumatoid arthritis: a population-based study,” Arthritis and Rheumatism, vol. 52, no. 3, pp. 722–732, 2005.
[10]
J. A. Avi？a-Zubieta, H. K. Choi, M. Sadatsafavi, M. Etminan, J. M. Esdaile, and D. Lacaille, “Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies,” Arthritis Care and Research, vol. 59, no. 12, pp. 1690–1697, 2008.
[11]
S. W？llberg-Jonsson, H. Johansson, M. L. ？hman, and S. Rantap？？-Dahlqvist, “Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset,” Journal of Rheumatology, vol. 26, no. 12, pp. 2562–2571, 1999.
[12]
I. del Rincón, D. H. O'Leary, G. L. Freeman, and A. Escalante, “Acceleration of atherosclerosis during the course of rheumatoid arthritis,” Atherosclerosis, vol. 195, no. 2, pp. 354–360, 2007.
[13]
M. A. Gonzalez-Gay, C. Gonzalez-Juanatey, and J. Martin, “Rheumatoid arthritis: a disease associated with accelerated atherogenesis,” Seminars in Arthritis and Rheumatism, vol. 35, no. 1, pp. 8–17, 2005.
[14]
N. Rexhepaj, G. Bajraktari, I. Berisha et al., “Left and right ventricular diastolic functions in patients with rheumatoid arthritis without clinically evident cardiovascular disease,” International Journal of Clinical Practice, vol. 60, no. 6, pp. 683–688, 2006.
[15]
C. P. Chung, J. T. Giles, M. Petri et al., “Prevalence of traditional modifiable cardiovascular risk factors in patients with rheumatoid arthritis: Comparison with control subjects from the multi-ethnic study of atherosclerosis,” Seminars in Arthritis and Rheumatism, vol. 41, no. 4, pp. 535–544, 2012.
[16]
M. J. Peters, D. P. Symmons, D. McCarey et al., “EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis,” Annals of the Rheumatic Diseases, vol. 69, no. 2, pp. 325–331, 2010.
[17]
M. J. L. Peters, V. P. van Halm, A. E. Voskuyl et al., “Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study,” Arthritis Care and Research, vol. 61, no. 11, pp. 1571–1579, 2009.
[18]
G. Haugeberg, T. Uhlig, J. A. Falch, et al., “Bone mineral density and frequency of osteoporosis in female patients with rheumatoid arthritis: results from 394 patients in the Oslo County Rheumatoid Arthritis register,” Arthritis & Rheumatology, vol. 43, no. 3, pp. 522–530, 2000.
[19]
L. Sinigaglia, A. Nervetti, Q. Mela et al., “A multicenter cross sectional study on bone mineral density in rheumatoid arthritis,” Journal of Rheumatology, vol. 27, no. 11, pp. 2582–2589, 2000.
[20]
A. Gough, P. Sambrook, J. Devlin et al., “Osteoclastic activation is the principal mechanism leading to secondary osteoporosis in rheumatoid arthritis,” Journal of Rheumatology, vol. 25, no. 7, pp. 1282–1289, 1998.
[21]
S. Xu, Y. Wang, J. Lu, et al., “Osteoprotegerin and RANKL in the pathogenesis of rheumatoid arthritis-induced osteoporosis,” Rheumatology International, vol. 32, no. 11, pp. 3397–3403, 2012.
[22]
R. E. ？rstavik, G. Haugeberg, T. Uhlig et al., “Incidence of vertebral deformities in 255 female rheumatoid arthritis patients measured by morphometric X-ray absorptiometry,” Osteoporosis International, vol. 16, no. 1, pp. 35–42, 2005.
[23]
T. M. Huusko, M. Korpela, P. Karppi, V. Avikainen, H. Kautiainen, and R. Sulkava, “Threefold increased risk of hip fractures with rheumatoid arthritis in central Finland,” Annals of the Rheumatic Diseases, vol. 60, no. 5, pp. 521–522, 2001.
[24]
H. L. Hunter and T. R. Nagy, “Body composition in a seasonal model of obesity: Longitudinal measures and validation of DXA,” Obesity Research, vol. 10, no. 11, pp. 1180–1187, 2002.
[25]
D. Aletaha, T. Neogi, A. J. Silman, et al., “2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative,” Arthritis & Rheumatology, vol. 62, no. 9, pp. 2569–2581, 2010.
[26]
G. Mancia, R. Fagard, K. Narkiewicz, et al., “2013 ESH/ESC Guidelines for the management of arterial hypertension,” Blood Press, vol. 22, no. 4, pp. 193–278, 2013.
[27]
S. D. Fihn, J. M. Gardin, J. Abrams, et al., “2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons,” Circulation, vol. 126, no. 25, pp. e354–e471, 2012.
[28]
P. S. Jellinger, D. A. Smith, A. E. Mehta et al., “American association of clinical endocrinologists' guidelines for management of dyslipidemia and prevention of atherosclerosis,” Endocrine Practice, vol. 18, supplement 1, pp. 1–78, 2012.
[29]
“Diagnosis and classification of diabetes mellitus,” Diabetes Care, vol. 36, supplement 1, pp. S67–S74, 2013.
[30]
K. G. M. M. Alberti and P. Zimmet, “Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation,” Diabetic Medicine, vol. 23, no. 5, pp. 469–480, 2006.
[31]
J. Perk, G. De Backer, H. Gohlke, et al., “European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The 5th Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts),” European Heart Journal, vol. 33, no. 13, pp. 1635–1701, 2012.
[32]
P. Cullen, H. Schulte, and G. Assmann, “The Munster Heart Study (PROCAM): total mortality in middle-aged men is increased at low total and LDL cholesterol concentrations in smokers but not in nonsmokers,” Circulation, vol. 96, no. 7, pp. 2128–2136, 1997.
[33]
K. Shibuya, H. Hagino, Y. Morio, and R. Teshima, “Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis,” Clinical Rheumatology, vol. 21, no. 2, pp. 150–158, 2002.
[34]
C. S. Chang, Y. F. Chang, M. W. Wang, et al., “Inverse relationship between central obesity and osteoporosis in osteoporotic drug naive elderly females: the Tianliao Old People (TOP) Study,” Journal of Clinical Densitometry, vol. 16, no. 2, pp. 204–211, 2013.
[35]
S. Migliaccio, E. A. Greco, R. Fornari, et al., “Is obesity in women protective against osteoporosis?” Diabetes, Metabolic Syndrome and Obesity, vol. 4, pp. 273–282, 2011.
[36]
E. A. Greco, R. Fornari, F. Rossi et al., “Is obesity protective for osteoporosis? Evaluation of bone mineral density in individuals with high body mass index,” International Journal of Clinical Practice, vol. 64, no. 6, pp. 817–820, 2010.
