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An Increased Serum N-Terminal Telopeptide of Type I Collagen, a Biochemical Marker of Increased Bone Resorption, Is Associated with Infliximab Therapy in Patients with Crohn’s Disease

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Abstract

Background

Osteopenia and osteoporosis are considered to be extra-intestinal manifestations of inflammatory bowel disease (IBD). Anti-tumor necrosis factor (TNF)-α biologics have been introduced as novel medications for an active IBD. However, it is still not well documented whether anti-TNF-α affects the frequency of bone loss or abnormality of bone mineral markers among patients with IBD.

Aims

This study was to investigate the biochemical basis of low bone mineral density (BMD) and increased turnover in IBD during infliximab (IFX) therapy.

Methods

Forty patients with Crohn’s disease (CD), 80 patients with ulcerative colitis (UC), and 65 age- and gender-matched controls were included. BMD was measured with dual-energy X-ray absorptiometry, and vitamins K and D were measured as serum undercarboxylated osteocalcin (ucOC) and 1,25-(OH)2D, respectively. Bone formation and resorption were based on measuring bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx), respectively.

Results

Significantly lower BMD was found in patients with UC and CD as compared to controls (P < 0.05). BAP, 1,25-(OH)2D, ucOC, and NTx were significantly higher in CD patients, but not in UC patients as compared to controls (P < 0.05). Further, serum NTx level was significantly higher in CD patients who were receiving IFX as compared to CD patients who were not receiving IFX (P < 0.01).

Conclusions

A lower BMD and higher bone metabolism markers were found in CD patients as compared to controls or UC patients. A significant increased serum level of NTx, a biochemical marker of increased bone resorption, was observed in CD patients during IFX therapy.

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Abbreviations

BAP:

Bone-specific alkaline phosphatase

BMD:

Bone mineral density

CD:

Crohn’s disease

DEXA:

Dual-energy X-ray absorptiometry

IBD:

Inflammatory bowel diseases

IFX:

Infliximab

NTx:

N-terminal telopeptide of type I collagen

SD:

Standard deviation

TNF:

Tumour necrosis factor

ucOC:

Undercarboxylated osteocalcin

UC:

Ulcerative colitis

References

  1. Bischoff SC, Herrmann A, Göke M, Manns MP, von zur Mühlen A, Brabant G. Altered bone metabolism in inflammatory bowel disease. Am J Gastroenterol. 1997;92:1157–1163.

  2. Ali T, Lam D, Bronze MS, Humphrey MB. Osteoporosis in inflammatory bowel disease. Am J Med. 2009;122:599–604.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Lewiecki EM, Borges JL. Bone density testing in clinical practice. Arq Bras Endocrinol Metabol. 2006;50:586–595.

    PubMed  Google Scholar 

  4. NIH Consensus Development Panel on Osteoporosis Prevention. Diagnosis, and therapy. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785–795.

    Article  Google Scholar 

  5. Genant HK, Engelke K, Fuerst T, et al. Noninvasive assessment of bone mineral and structure: state of the art. J Bone Miner Res. 1996;11:707–730.

    Article  CAS  PubMed  Google Scholar 

  6. Couttenye MM, D’Haese PC, Van Hoof VO, et al. Low serum levels of alkaline phosphatase of bone origin: a good marker of adynamic bone disease in haemodialysis patients. Nephrol Dial Transpl. 1996;11:1065–1072.

    Article  CAS  Google Scholar 

  7. Eastell R, Mallinak N, Weiss S, et al. Biological variability of serum and urinary N-telopeptides of type I collagen in postmenopausal women. J Bone Miner Res. 2000;15:594–598.

    Article  CAS  PubMed  Google Scholar 

  8. Szulc P, Meunier PJ. Is vitamin K deficiency a risk factor for osteoporosis in Crohn’s disease? Lancet. 2001;357:1995–1996.

    Article  CAS  PubMed  Google Scholar 

  9. Miheller P, Muzes G, Hritz I, et al. Comparison of the effects of 1,25 dihydroxyvitamin D and 25 hydroxyvitamin D on bone pathology and disease activity in Crohn’s disease patients. Inflamm Bowel Dis. 2009;15:1656–1662.

    Article  PubMed  Google Scholar 

  10. Jahnsen J, Falch JA, Aadland E, Mowinckel P. Bone mineral density is reduced in patients with Crohn’s disease but not in patients with ulcerative colitis: a population based study. Gut. 1997;40:313–319.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ghosh S, Cowen S, Hannan WJ, Ferguson A. Low bone mineral density in Crohn’s disease, but not in ulcerative colitis, at diagnosis. Gastroenterology. 1994;107:1031–1039.

    CAS  PubMed  Google Scholar 

  12. Ardizzone S, Bollani S, Bettica P, Bevilacqua M, Molteni P, Bianchi Porro G. Altered bone metabolism in inflammatory bowel disease: there is a difference between Crohn’s disease and ulcerative colitis. J Intern Med. 2000;247:63–70.

  13. Targownik LE, Bernstein CN, Nugent Z, Leslie WD. Inflammatory bowel disease has a small effect on bone mineral density and risk for osteoporosis. Clin Gastroenterol Hepatol. 2013;11:278–285.

    Article  PubMed  Google Scholar 

  14. Sinnott BP, Licata AA. Assessment of bone and mineral metabolism in inflammatory bowel disease: case series and review. Endocr Pract. 2006;12:622–629.

    Article  PubMed  Google Scholar 

  15. Loftus EV Jr, Achenbach SJ, Sandborn WJ, Tremaine WJ, Oberg AL, Melton LJ 3rd. Risk of fracture in ulcerative colitis: a population-based study from Olmsted County, Minnesota. Clin Gastroenterol Hepatol. 2003;1:465–473.

    Article  PubMed  Google Scholar 

  16. Leichtmann GA, Bengoa JM, Bolt MJ, Sitrin MD. Intestinal absorption of cholecalciferol and 25-hydroxycholecalciferol in patients with both Crohn’s disease and intestinal resection. Am J Clin Nutr. 1991;54:548–552.

    CAS  PubMed  Google Scholar 

  17. Azzopardi N, Ellul P. Risk factors for osteoporosis in Crohn’s disease: infliximab, corticosteroids, body mass index, and age of onset. Inflamm Bowel Dis. 2013;19:1173–1178.

    Article  PubMed  Google Scholar 

  18. Carter MJ, Lobo AJ, Travis SP. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2004;53:V1–V16.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Abreu MT, Kantorovich V, Vasiliauskas EA, et al. Measurement of vitamin D levels in inflammatory bowel disease patients reveals a subset of Crohn’s disease patients with elevated 1,25-dihydroxyvitamin D and low bone mineral density. Gut. 2004;53:1129–1136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nakajima S, Iijima H, Egawa S, et al. Association of vitamin K deficiency with bone metabolism and clinical disease activity in inflammatory bowel disease. Nutrition. 2011;27:1023–1028.

    Article  CAS  PubMed  Google Scholar 

  21. Gilman J, Shanahan F, Cashman KD. Altered levels of biochemical indices of bone turnover and bone-related vitamins in patients with Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2006;23:1007–1016.

    Article  CAS  PubMed  Google Scholar 

  22. Riggs BL, Melton LJ 3rd, O’Fallon WM. Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. Bone. 1996;18:197S–201S.

    Article  CAS  PubMed  Google Scholar 

  23. Garnero P, Sornay-Rendu E, Duboeuf F, Delmas PD. Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study. J Bone Miner Res. 1999;14:1614–1621.

    Article  CAS  PubMed  Google Scholar 

  24. Chesnut CH 3rd, Bell NH, Clark GS, et al. Hormone replacement therapy in postmenopausal women: urinary N-telopeptide of type I collagen monitors therapeutic effect and predicts response of bone mineral density. Am J Med. 1997;102:29–37.

    Article  CAS  PubMed  Google Scholar 

  25. Eastell R, Barton I, Hannon RA, Chines A, Garnero P, Delmas PD. Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate. J Bone Miner Res. 2003;18:1051–1056.

    Article  CAS  PubMed  Google Scholar 

  26. Ciucci T, Ibáñez L, Boucoiran A, et al. Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD. Gut. 2014. doi:10.1136/gutjnl-2014-306947.

  27. Franchimont N, Putzeys V, Collette J, et al. Rapid improvement of bone metabolism after infliximab treatment in Crohn’s disease. Aliment Pharmacol Ther. 2004;20:607–614.

    Article  CAS  PubMed  Google Scholar 

  28. Ryan BM, Russel MG, Schurgers L, et al. Effect of antitumour necrosis factor-alpha therapy on bone turnover in patients with active Crohn’s disease: a prospective study. Aliment Pharmacol Ther. 2004;20:851–857.

    Article  CAS  PubMed  Google Scholar 

  29. Abreu MT, Geller JL, Vasiliauskas EA, et al. Treatment with infliximab is associated with increased markers of bone formation in patients with Crohn’s disease. J Clin Gastroenterol. 2006;40:55–63.

    Article  CAS  PubMed  Google Scholar 

  30. Miheller P, Muzes G, Zagoni T, Toth M, Racz K, Tulassay Z. Infliximab therapy improves the bone metabolism in fistulizing Crohn’s disease. Dig Dis. 2006;24:201–206.

    Article  PubMed  Google Scholar 

  31. Bernstein M, Irwin S, Greenberg GR. Maintenance infliximab treatment is associated with improved bone mineral density in Crohn’s disease. Am J Gastroenterol. 2005;100:2031–2035.

    Article  CAS  PubMed  Google Scholar 

  32. Compston JE, Judd D, Crawley EO, et al. Osteoporosis in patients with inflammatory bowel disease. Gut. 1987;28:410–415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Bjarnason I, Macpherson A, Mackintosh C, Buxton-Thomas M, Forgacs I, Moniz C. Reduced bone density in patients with inflammatory bowel disease. Gut. 1997;40:228–233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pollak RD, Karmeli F, Eliakim R, Ackerman Z, Tabb K, Rachmilewitz D. Femoral neck osteopenia in patients with inflammatory bowel disease. Am J Gastroenterol. 1998;93:1483–1490.

    Article  CAS  PubMed  Google Scholar 

  35. Pigot F, Roux C, Chaussade S, et al. Low bone mineral density in patients with inflammatory bowel disease. Dig Dis Sci. 1992;37:1396–1403.

    Article  CAS  PubMed  Google Scholar 

  36. Robinson RJ, al-Azzawi F, Iqbal SJ, et al. Osteoporosis and determinants of bone density in patients with Crohn’s disease. Dig Dis Sci. 1998;43:2500–2506.

  37. Melek J, Sakuraba A. Efficacy and safety of medical therapy for low bone mineral density in patients with inflammatory bowel disease: a meta-analysis and systematic review. Clin Gastroenterol Hepatol. 2014;12:32–44.

    Article  PubMed  Google Scholar 

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Acknowledgments

No external funding was used to carry out this study.

Authors’ Contributions

K. Sugimoto, H. Hanai, K. Ikeya, T. Iida, F. Watanabe: study concept and design; K. Sugimoto, S. Kawasaki, O. Arai, K. Umehara, S. Tani, S. Oishi, S. Osawa, T. Yamamoto, H. Hanai: acquisition of data, statistical analyses, and interpretation of data; K. Sugimoto, H. Hanai: drafting of the manuscript; K. Sugimoto, K. Ikeya, T. Iida, S. Kawasaki, O. Arai, K. Umehara, F. Watanabe, S. Tani, S. Oishi, S. Osawa, T. Yamamoto, H. Hanai: critical revision of the manuscript for important intellectual content, and approval of the final manuscript version.

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Authors and Affiliations

  1. First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, 431-3192, Japan

    Ken Sugimoto, Shinya Tani & Shinji Oishi

  2. Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, Hamamatsu, 430-0846, Japan

    Kentaro Ikeya, Takayuki Iida, Shinsuke Kawasaki, Osamu Arai, Fumitoshi Watanabe & Hiroyuki Hanai

  3. Orthopedics Unit, Hamamatsu South Hospital, Hamamatsu, 430-0846, Japan

    Keita Umehara

  4. Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu, 431-3192, Japan

    Satoshi Osawa

  5. Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Mie, 510-0016, Japan

    Takayuki Yamamoto

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  1. Ken Sugimoto
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Correspondence to Ken Sugimoto.

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The authors hereby declare having no conflict of interest or funding interest in connection with the publication of this manuscript.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Sugimoto, K., Ikeya, K., Iida, T. et al. An Increased Serum N-Terminal Telopeptide of Type I Collagen, a Biochemical Marker of Increased Bone Resorption, Is Associated with Infliximab Therapy in Patients with Crohn’s Disease. Dig Dis Sci 61, 99–106 (2016). https://doi.org/10.1007/s10620-015-3838-y

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