ABSTRACT
Bone tissue, one of the body’s most intricate structures, has a unique capacity for spontaneous regeneration and repair under optimal physio logical conditions. Aspirin, a widely used non-steroidal anti-inflammatory drug (NSAID) recognized for its anticoagulant properties, plays a role in bone regeneration by activating cytokines and mediators within osteoclasts, osteoblasts, and progenitor cells at sites of damage. This ac tivation promotes bone repair and stimulates angiogenesis by enhancing endothelial cell migration, which is essential for the formation of new blood vessels necessary for fracture healing. This study analyzed blood samples from 100 Kosovo patients (57 female, 43 male; ages 42–89) with rheumatic osteoporosis who regularly use aspirin. Key biomarkers measured included vitamin D, serum calcium, serum iron, sedimentation rate, glucose, triglycerides, cholesterol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Findings indicated that 37% of these osteoporosis patients exhibited elevated triglyceride levels (>1.7 mmol/L), while nearly 40% had cholesterol levels exceeding 5 mmol/L. Additionally, AST and ALT levels were elevated (>40 IU/L) in 30% of patients, with aspirin users generally showing statistically significant increases across these blood parameters. Body mass index showed no statistically significant correlation with any blood parameter values. However, increasing patient age correlated with reduced vitamin D levels and elevated triglycerides, cholesterol, sedimentation rate, and glucose levels. Understanding the link between diet and osteoporosis is critical for healthcare professionals, including doctors, nutritionists, and researchers, as it supports efforts to prevent and manage osteoporosis. Given this, synthesizing current evidence and conducting further studies on the diet-osteoporosis interaction is essential.
REFERENCES
Abrahamsen, B., Rohold, A., Henriksen, J. E., & Beck-Nielsen, H. (2000). Correlations between insulin sensitivity and bone mineral density in non-diabetic men. Diabetic Medicine, 17(2), 124–129. Adami, S. (2009). Bone health in diabetes: considerations for clinical management. Curr Med Res Opin, 25(5), 1057-1072.
Apostolova, G. (2014). The Influence of Bone Markers in the Assessment of Mineralization of Oral Surgical Bone Defects in Patients with Diabetes Mellitus, University “Ss. Cyril and Methodius,” Faculty of Dentistry – Skopje, Doctoral Dissertation. Bach-Faig, A., Berry, E. M., Lairon, D., Reguant, J., Trichopoulou, A., Dernini, S., Medina, F. X., Battino, M., Belahsen, R., Miranda, G., & Serra-Majem, L.;
Mediterranean Diet Foundation Expert Group. (2011). Mediterranean diet pyramid today: Science and cultural updates. Public Health Nutrition, 14(12A), 2274–2284.
Bauer, D. C., Orwoll, E. S., Fox, K. M., Vogt, T. M., Lane, N. E., Hochberg, M. C., Stone, K., & Nevitt, M. C. (1996). Aspirin and NSAID use in older women: Effect on bone mineral density and fracture risk. Journal of Bone and Mineral Research, 11(1), 29–35.
Bibbins-Domingo, K. (2016). Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. preventive services task force recommendation statement. An nals of Internal Medicine, 164(12), 836–845.
Blasiak, M., Kuska, J., Kokot, F., & Irzyniec, T. (1989). Selected indicators of calcium-phosphate metabolism in patients with diabetes mellitus. Endocrynol Pol, 40(5), 251-262.
Bouillon, R., Bex, M., Van Herck, E., Laureys, J., Dooms, L., Lesaffre, E., & Ravussin, E. (1995). Influence of age, sex, and insulin on osteoblast function: Osteoblast dysfunction in diabetes mellitus. Journal of Clinical Endocrinology & Metabolism, 80(4), 1194–1202.
Brandão, F. R., Vicente, E. J., Daltro, C. H., Sacramento, M., Moreira, A., & Adan, L. (2007). Bone metabolism is linked to disease duration and metabolic control in type 1 diabetes mellitus. Diabetes Research and Clinical Practice, 78(3), 334–339.
Brandi, M.L. (2010). Bone health and diabetes. Medicographia, 32(4), 364-369.
Campos Pastor, M. M., López-Ibarra, P. J., Escobar-Jiménez, F., Serrano Pardo, M. D., & García-Cervigón, A. G. (2000). Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: A prospective study. Osteoporosis International, 11(5), 455–459.
Carbone, L. D., Tylavsky, F. A., Cauley, J. A., Harris, T. B., Lang, T. F., Bauer, D. C., Barrow, K. D., & Kritchevsky, S. B. (2003). Association between bone mineral density and the use of non steroidal anti-inflammatory drugs and aspirin: Impact of cyclooxygenase selectivity. Jour nal of Bone and Mineral Research, 18(10), 1795–1802.
Chaudhary, P., Janmeda, P., Docea, A.O., Yeskaliyeva, B., Abdull Razis, A.F., Modu, B., Calina, D., & Sharifi-Rad, J. (2023). Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Front Chem, 11, 1158198.
hen, D., Shen, J., Zhao, W., Wang, T., Han L., Hamilton, J.L., & Im, H.-J. (2017). Osteoarthritis: Toward a comprehensive understanding of pathological mechanism. Bone Res, 5, 16044.
Chin, K.Y., & Ima-Nirwana, S. (2018). The role of vitamin E in preventing and treating osteoar thritis—A review of the current evidence. Front Pharmacol, 9, 946.
77 IJTNS International Journal of Technical and Natural Sciences Cicuttini, F.M., & Spector, T.D. (1996). Genetics of osteoarthritis. Ann Rheum Dis, 55, 665–667.
Dehmer, S.P., Maciosek, M.V., Flottemesch, T.J., LaFrance, A.B., & Whitlock, E.P. (2016). Aspirin for the primary prevention of cardiovascular disease and colorectal cancer: a decision analysis for the U.S. preventive services task force. Annals of Internal Medicine, 164(12), 777–786.
DeLuca, H.F. (1986). The metabolism and functions of vitamin D. Adv Exp Med Biol, 196, 361–375.
Deng, W., Yi, Z., Yin, E., Lu, R., You, H., & Yuan, X. (2023). Effect of omega-3 polyunsaturated fatty acids supplementation for patients with osteoarthritis: A meta-analysis. J Orthop Surg Res, 18, 381.
Downey, P.A., & Siegel, M.I. (2006). Bone biology and the clinical implications for osteoporosis. Phys Ther, 86(1), 77-91.
Dunlap, B., Patterson, G.T., Kumar, S., Vyavahare, S., Mishra, S., Isales, C., & Fulzele, S. (2021). Vitamin C supplementation for the treatment of osteoarthritis: Perspectives on the past, present, and future. Ther Adv Chronic Dis, 12.
Ekegren, C. L., Edwards, E. R., Page, R., Hau, R., de Steiger, R., Bucknill, A., Liew, S., Oppy, A., & Gabbe, B. J. (2016). Twelve-month mortality and functional outcomes in hip fracture pa tients under 65 years of age. Injury, 47(10), 2182–2188.
Epstein, F.H., & Harris, E.D. (1990). Rheumatoid arthritis: pathophysiology and implications for therapy. N Engl J Med, 322, 1277-1289.
Feng, X., & McDonald, J.M. (2011). Disorders of bone remodeling. Annual Review of Pathology: Mechanisms of Disease, 6, 121–145. Furst, D.E., Ulrich, R.W., & Prakash, S. (2012). Nonsteroidal anti-inflammatory drugs, dis ease-modifying antirheumatic drugs, nonopioid analgesics, & drugs used in gout. In Basic and Clinical Pharmacology, 12th edition, chapter 36. McGraw-Hill, New York, NY.
Fuster, V., & Sweeny, J.M. (2011). Aspirin: a historical and contemporary therapeutic overview. Circulation, 123(7), 768–775.
Gambari, L., Cellamare, A., Grassi, F., Grigolo, B., Panciera, A., Ruffilli, A., Faldini, C., & Desan do, G. (2023). Targeting the inflammatory hallmarks of obesity-associated osteoarthritis: towards nutraceutical-oriented preventive and complementary therapeutic strategies based on n-3 polyunsaturated fatty acids. Int J Mol Sci, 24, 9340.
Gil, A. (2002). Polyunsaturated fatty acids and inflammatory diseases. Biomed Pharmacother, 56, 388–396.
Gupte, P.A., Giramkar, S.A., Harke, S.M., Kulkarni, S.K., Deshmukh, A.P., Hingorani, L.L., Maha jan, M.P., & Bhalerao, S.S. (2019). Evaluation of the efficacy and safety of capsule longvida® optimized curcumin (solid lipid curcumin particles) in knee osteoarthritis: A pilot clinical study. J Inflamm Res, 12, 145–152.
Hadjidakis, D.J., & Androulakis, I.I. (2006). Bone remodeling. Ann N.Y. Acad Sci, 1092, 385-396.
Hagen, K.B., Byfuglien, M.G., Falzon, L., Olsen, S.U., & Smedslund, G. (2009). Dietary interven tions for rheumatoid arthritis. Cochrane Database Syst Rev.
Hofbauer, L.C., Brueck, C.C., Singh, S.K., & Dobnig, H. (2007). Review: Osteoporosis in patients with diabetes mellitus. J Bone Mineral Res, 22(9), 1317-1328.
Ide, Y., & Agematsu, H. (2007). Structure of jaw bone. Clin Calcium, 17(2), 164-171. 78
Dren Zhubi and Valentina Pavlova Blood Analysis of Patients with Rheumatoid Disease from Kosovo Using Non-Steroidal Anti-Inflammatory Drug – Aspirin International Osteoporosis Foundation.
(2006). Invest in your bones. Bone Appétit − The role of food and nutrition in building and maintaining strong bones. Available from: http://www. iofbonehealth.org/publications/bone-appetit.html.
Kalfas, I.H. (2001). Principles of bone healing. Neurosurg Focus, 10(4), 7-10.
Kini, U., & Nandeesh, B.N. (2012). Physiology of bone formation, remodeling, and metabolism. In Radionuclide and Hybrid Bone Imaging, 29-57. Springer, Berlin, Heidelberg. Lawrence, T. (2009). The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Per spect Biol, 1(6), a001651.
Lee, S.H., Chen, I.J., Li, Y.H., Fan Chiang, C.Y., Chang, C.H., & Hsieh, P.H. (2016). Incidence of second hip fractures and associated mortality in Taiwan: A nationwide population-based study of 95,484 patients during 2006–2010. Acta Orthop Traumatol Turc, 50(4), 437–442.
Liput, K.P., Lepczynski, A., Ogluszka, M., Nawrocka, A., Polawska, E., Grzesiak, A., Slaska, B., Pareek, C.S., Czarnik, U., & Pierzchala, M. (2021). Effects of dietary n–3 and n–6 polyun saturated fatty acids in inflammation and cancerogenesis. Int J Mol Sci, 22, 6965.
Mecevska, J.J. (2010). Comparative study of biochemical markers of bone metabolism in post menopausal women with primary osteoporosis: effects of bisphosphonate therapy. Biochem Med, 20(1), 52-60.
Meier, C., & Kraenzlin, M.E. (2020). Antiresorptive drug-related osteonecrosis of the jaw: risks and p 39.
Mecevska, J.J. (2010). Komparativna studija na biohemiskite marker na kosken metabolizam kaj postmenopauzalni zeni so primarna osteoporoza: efekti od bifosfonatna terapija (doktorska disertacija) Skopje, Makedonija. Prirodno matematicki fakultet, 2010, 11-13.
Paez Espinosa, E. V., Murad, J. P., & Khasawneh, F. T. (2012). Aspirin: pharmacology and clinical applications, Thrombosis, 2012, Article ID 173124, 15 pages.
Papaioannou, A., Kennedy, C. C., Ioannidis, G., Sawka, A., Hopman, W. M., Pickard, L., Brown, J. P., Josse, R. G., Kaiser, S., Anastassiades, T., Goltzman, D., Papadimitropoulos, M., Tenen house, A., Prior, J. C., Olszynski, W. P., & Adachi, J. D.; CaMos Study Group. (2009). The im pact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study. Osteoporosis International, 20(5), 703–714.
Park, C.Y. (2019). Vitamin D in the prevention and treatment of osteoarthritis: From clinical interventions to cellular evidence, Nutrients, 11, 243.
Patterson, E., Wall, R., Fitzgerald, G.F., Ross, R.P., Stanton, C. (2012). Health implications of high dietary omega-6 polyunsaturated fatty acids, J. Nutr. Metab, 2012, 539426.
Portune, K.J., Benitez-Paez, A., Del Pulgar, E.M.G., Cerrudo, V., & Sanz, Y. (2017). Gut microbi ota, diet, and obesity-related disorders—The good, the bad, and the future challenges, Mol. Nutr. Food Res., 61, 1600252.
Prolo, D. J. (1990). Biology of bone fusion. Clin Neurosurg, 36, 135–146.
Rondanelli, М., Perdoni, F., Peroni, G., Caporali, R., Gasparri, C., Riva, A., Petrangolini, G., Faliva, M.A., Infantino, V., Naso, M., Perna, S., & Rigon, C. (2021). Ideal food pyramid for patients with rheumatoid arthritis: A narrative review. Clinical Nutrition 40, 661-689.
Ronn, K., Reischl, N., Gautier, E., & Jacobi, M. (2011). Current Surgical Treatment of Knee Oste oarthritis. Arthritis 2011, 454873. 79 IJTNS International Journal of Technical and Natural Sciences
Sanghi, D., Mishra, A., Sharma, A.C., Singh, A., Natu, S.M., Agarwal, S., & Srivastava, R.N. (2013). Does vitamin D improve osteoarthritis of the knee: A randomized controlled pilot trial, Clin. Orthop. Relat. Res., 471, 3556–3562.
Sandor, G. K. B., Lindholm, T. C., & Clokie, C. M. L. (2003). Bone regeneration of the cranio-maxillofa cial and dento-alveolar skeletons in the framework of tissue engineering. In N. Ashammakhi & P. Ferretti (Eds.), Topics in tissue engineering (pp. [page numbers]). University of Oulu.
Schott, E. M., Farnsworth, C. W., Grier, A., Lillis, J. A., Soniwala, S., Dadourian, G. H., Bell, R. D., Doolittle, M. L., Villani, D. A., Awad, H., Ketz, J. P., Kamal, F., Ackert-Bicknell, C., Ashton, J. M., Gill, S. R., Mooney, R. A., & Zuscik, M. J. (2018). Targeting the gut microbiome to treat the osteoarthritis of obesity. JCI Insight, 3(8), e95997.
Shep, D., Khanwelkar, C., Gade, P., & Karad, S. (2019). Safety and efficacy of curcumin versus di clofenac in knee osteoarthritis: A randomized open-label parallel-arm study, Trials, 20, 214.
Sophocleous, A. (2023). The Role of Nutrition in Osteoarthritis Development, Nutrients, 15, 4336. https://doi.org/10.3390/ nu15204336
Suda, K., Udagawa, N., Sato, N., Takami, M., Itoh, K., Woo, J. T., Takahashi, N., & Nagai, K. (2004). Suppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation. Journal of Immunology, 172(4), 2504 2510.
Suzuki, K., Sugimoto, C., Takizawa, M., Ishizuka, S., Kikuyama, M., Togawa, H., Taguchi, Y., Nosaka, K., Seino, Y., & Ishida, H. (2000). Correlations between bone mineral density and circulating bone metabolic markers in diabetic patients. Diabetes Research and Clinical Practice, 48(3), 185–191.
Symmons, DPM. (2003). Environmental factors and the outcome of rheumatoid arthritis. Best Pract Res Clin Rheumatol, 17, 717e27.
Tak, P. P. & Firestein, G. S. (2001). NF-𝜅B: a key role in inflammatory diseases, The Journal of Clinical Investigation, 107, (1), pp. 7–11.
Van Coeverden, MC. (2002). Bone metabolism markers and bone mass in healthy pubertal boys and girls, Clinical Endocrinology, 57, 107–116.
Vestergaard, P., Hermann, P., Jensen, J.-E. B., Eiken, P., & Mosekilde, L. (2012). Effects of par acetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish osteoporosis prevention study (dops), Osteoporosis International, 23, (4), 1255–1265.
Vestergaard, P., Steinberg, T. H., Schwarz, P., & Jørgensen, N. R. (2012). Use of the oral platelet inhibitors dipyridamole and acetylsalicylic acid is associated with increased risk of fracture, International Journal of Cardiology, 160, 1, 36–40.
Zeng, Y. P., Yang, C., Li, Y. (2016). Aspirin inhibits osteoclastogenesis by suppressing the activa tion of NF-𝜅B and MAPKs in RANKL-induced RAW264.7 cells, MolecularMedicine Reports, 14, (3), 1957–1962.
Zhubi, D., Pavlova, V., Zhubi, M., Tahiri, A., Kovaci, I., Blazhevska, T., Knights, V., Pavlovska Dim kovski, M., & Srbinoska, M. (2024). Recommendations and use of calcium, vitamin D, and appropriate nutrition in patients with rheumatoid diseases, Journal of Hygienic Engineer ing and Design, 47, 103-110.