Features of changes in bone mineral density in young patients with inflammatory bowel diseases

Introduction. Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) are chronic relapsing conditions with gastrointestinal mucosa injuries and potential local and systemic complications. The incidence of osteoporosis (OP) in patients with IBD is very variable according to data from different studies.

Aim. To evaluate changes in bone mineral density (BMD) and bone remodelling parameters in young patients with IBD for early detection of changes in the bone tissue.

Materials and methods. The study included 123 patients with verified diagnoses of UC (n = 70) and CD (n = 53), who were observed at the State Autonomous Healthcare Institution Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan from March 2023 to December 2024. All patients underwent a detailed clinical history and physical examination. Bone metabolism and its regulators such as osteocalcin (ng/ml), Beta-Cross Laps (ng/ml), P1NP (ng/ml), and vitamin D levels (ng/ml) were assessed. All patients underwent measurements of BMD using dual-energy X-ray absorptiometry to detect OP.

Results. Of 123 young patients with IBD, 13.8% (17 patients) had bone mass below age-matched reference values based on dual-energy X-ray absorptiometry findings. Bone remodelling parameters assessment revealed changes in 31% (39 patients), and decrease in vitamin D levels in all patients of the study.

Conclusions. Of 123 young patients with IBD examined, 13.8% (17) of patients had bone mass below age-matched reference values. The bone remodelling parameters were changed in a larger percentage of patients (31%). All patients with IBD had low vitamin D levels. The presence of moderate and severe IBD, low body mass index, systemic glucocorticoids in the IBD treatment protocol, as well as acute course of UC and presence of ileocolitis in CD significantly contribute to the decrease in Z-scores, and accordingly, the decrease in BMD.

1. Shelygin YuA, Ivashkin VT, Belousova EA, Reshetov IV, Maev IV, Achkasov SI et al. Ulcerative colitis (K51), adults. Koloproktologia. 2023;22(1):10–44. (In Russ.) https://doi.org/10.33878/2073-7556-2023-22-1-10-44.

2. Shelygin YuA, Ivashkin VT, Achkasov SI, Reshetov IV, Maev IV, Belousova EA et al. Clinical guidelines. Crohn’s disease (К50), adults. Koloproktologia. 2023;22(3):10–49. (In Russ.) https://doi.org/10.33878/2073-7556-2023-22-3-10-49.

3. Ali T, Lam D, Bronze MS, Humphrey MB. Osteoporosis in inflammatory bowel disease. Am J Med. 2009;122(7):599–604. https://doi.org/10.1016/j.amjmed.2009.01.022.

4. Shirazi KM, Somi MH, Rezaeifar P, Fattahi I, Khoshbaten M, Ahmadzadeh M. Bone density and bone metabolism in patients with inflammatory bowel disease. Saudi J Gastroenterol. 2012;18(4):241–247. https://doi.org/10.4103/1319-3767.98428.

5. Romas E. Clinical applications of RANK-ligand inhibition. Intern Med J. 2009;39(2):110–116. https://doi.org/10.1111/j.1445-5994.2008.01732.x.

6. Krela-Kaźmierczak I, Szymczak-Tomczak A, Łykowska-Szuber L, Wysocka E, Michalak M., Stawczyk-Eder et al. Interleukin 6, osteoprotegerin, sRANKL and bone metabolism in inflammatory bowel diseases. Adv Clin Exp Med. 2018;27(4):449–453. https://doi.org/10.17219/acem/75675.

7. Aganov DS, Tyrenko VV, Tsygan EN, Toporkov MM, Bologov SG. The role of cytokine system RANKL/RANK/OPG in the regulation of bone metabolism. Genes and Cells. 2014;9(4):50–52. (In Russ.) Available at: https://elibrary.ru/yrwldr.

8. Bernstein CN, Blanchard JF, Leslie W, Wajda A, Yu BN. The incidence of fracture among patients with inflammatory bowel disease. A population-based cohort study. Ann Intern Med. 2000;133(10):795–799. https://doi.org/10.7326/0003-4819-133-10-200011210-00012.

9. Harbord M, Annese V, Vavricka SR, Allez M, Barreiro-de Acosta M, Boberg KM et al. European Crohn’s and Colitis Organisation. The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease. J Crohns Colitis. 2016;10(3):239–254. https://doi.org/10.1093/ecco-jcc/jjv213.

10. Burisch J, Kiudelis G, Kupcinskas L, Kievit HAL, Andersen KW, Andersen V et al. Natural disease course of Crohn’s disease during the first 5 years after diagnosis in a European population-based inception cohort: an Epi-IBD study. Gut. 2019;68(3):423–433. https://doi.org/10.1136/gutjnl-2017-315568.

11. Burisch J, Katsanos KH, Christodoulou DK, Barros L, Magro F, Pedersen N et al. Natural Disease Course of Ulcerative Colitis During the First Five Years of Follow-up in a European Population-based Inception Cohort-An Epi-IBD Study. J Crohns Colitis. 2019;13(2):198–208. https://doi.org/10.1093/ecco-jcc/jjy154.

12. Lunney PC, Kariyawasam VC, Wang RR, Middleton KL, Huang T, Selinger CP et al. Smoking prevalence and its influence on disease course and surgery in Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2015;42(1):61–70. https://doi.org/10.1111/apt.13239.

13. Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68(Suppl 3):s1–s106. https://doi.org/10.1136/gutjnl-2019-318484.

14. Yoon V, Maalouf NM, Sakhaee K. The effects of smoking on bone metabolism. Osteoporos Int. 2012;23(8):2081–2092. https://doi.org/10.1007/s00198-012-1940-y.

15. Karban A, Eliakim R. Effect of smoking on inflammatory bowel disease: Is it disease or organ specific? World J Gastroenterol. 2007;13(15):2150–2152. Available at: https://www.wjgnet.com/1007-9327/full/v13/i15/2150.htm.

16. Belaya ZE, Belova KYu, Biryukova EV, Dedov II, Dzeranova LK, Drapkina OM et al. Federal clinical guidelines for diagnosis, treatment and prevention of osteoporosis. Osteoporosis and Bone Diseases. 2021;24(2):4–47. (In Russ.) https://doi.org/10.14341/osteo12930.

17. Leslie WD, Miller N, Rogala L, Bernstein CN. Body mass and composition affect bone density in recently diagnosed inflammatory bowel disease: the Manitoba IBD Cohort Study. Inflamm Bowel Dis. 2009;15(1):39–46. https://doi.org/10.1002/ibd.20541.

18. Albulova EA, Parfenov AI, Drozdov VN. Metabolism of vitamin D and its active metabolites in celiac disease. Experimental and Clinical Gastroenterology. 2010;(3):15–17. (In Russ.) Available at: https://elibrary.ru/mvaipn.

19. Schouten BJ, Doogue MP, Soule SG, Hunt PJ. Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem. 2009;46(Pt 2):167–169. https://doi.org/10.1258/acb.2008.008151.

20. Mailyan EA. Multifactorial pathogenesis of osteoporosis and the role of genes of canonical Wnt-signaling pathway. Osteoporosis and Bone Diseases. 2015;18(2):15–19. (In Russ.) https://doi.org/10.14341/osteo2015215-19.

21. Mbalaviele G, Sheikh S, Stains JP, Salazar VS, Cheng SL, Chen D, Civitelli R. Beta-catenin and BMP-2 synergize to promote osteoblast differentiation and new bone formation. J Cell Biochem. 2005;94(2):403–418. https://doi.org/10.1002/jcb.20253.

22. Mani LY, Nseir G, Venetz JP, Pascual M. Severe hypophosphatemia after intravenous administration of iron carboxymaltose in a stable renal transplant recipient. Transplantation. 2010;90(7):804–805. https://doi.org/10.1097/TP.0b013e3181f00a18.

23. Giustina A, di Filippo L, Allora A, Bikle DD, Cavestro GM, Feldman D et al. Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship? Rev Endocr Metab Disord. 2023;24(2):121–138. https://doi.org/10.1007/s11154-023-09792-7.

24. Tulewicz-Marti EM, Lewandowski K, Rydzewska G. Bone Metabolism Alteration in Patients with Inflammatory Bowel Disease. J Clin Med. 2022;11(14):4138. https://doi.org/10.3390/jcm11144138.

25. Lewandowski K, Kaniewska M, Więcek M, Szwarc P, Panufnik P, Tulewicz-Marti E et al. Risk Factors for Osteoporosis among Patients with Inflammatory Bowel Disease – Do We Already Know Everything? Nutrients. 2023;15(5):1151. https://doi.org/10.3390/nu15051151.

26. Darlow SJ, Mandal A, Pick B, Thomas T, Mayberry JF, Robinson RJ. The shortterm effects of Eudragit-L-coated prednisolone metasulphobenzoate (Predocol) on bone formation and bone mineral density in acute ulcerative colitis. Eur J Gastroenterol Hepatol. 2004;16(11):1173–1176. https://doi.org/10.1097/00042737-200411000-00015.

27. Koutroubakis IE, Zavos C, Damilakis J, Papadakis GZ, Neratzoulakis J, Karkavitsas N, Kouroumalis EA. Low bone mineral density in Greek patients with inflammatory bowel disease: prevalence and risk factors. Ann Gastroenterol. 2011;24(1):41–46. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC3959460/.

28. Drozdov VN. Vitamin D deficiency as a factor polymorbidity. Experimental and Clinical Gastroenterology. 2015;118(6):82–88. (In Russ.) Available at: https://elibrary.ru/uhynnh.

29. Pappa HM, Grand RJ, Gordon CM. Report on the vitamin D status of adult and pediatric patients with inflammatory bowel disease and its significance for bone health and disease. Inflamm Bowel Dis. 2006;12(12):1162–1174. https://doi.org/10.1097/01.mib.0000236929.74040.b0.

30. Abitbol V, Roux C, Chaussade S, Guillemant S, Kolta S, Dougados M et al. Metabolic bone assessment in patients with inflammatory bowel disease. Gastroenterology. 1995;108(2):417–422. https://doi.org/10.1016/0016-5085(95)90068-3.