Adalimumab Therapy Has a Beneficial Effect on Bone Metabolism in Patients with Crohn's Disease

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 2015 Mar 4

PMID 25732718

Citations 5

Authors

Sundaram G Veerappan

Martin Healy

Bernard J Walsh

Colm A OMorain

Jacqueline S Daly

Barbara M Ryan

Affiliations

Soon will be listed here.

Abstract

Background: Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn's disease (CD) although as yet the exact mechanisms have not been fully elucidated.

Aim: To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model.

Methods: Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients' and pre- and post-treatment CD patients' sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed.

Results: There was a significant increase in bone formation markers osteocalcin (P < 0.05) and procollagen type 1 N-terminal propeptide (P < 0.01) at 1 and 3 months post-treatment. Moreover, there was a sustained but not significant fall in serum CTx, a bone resorption marker. No significant change was seen over time with other parameters measured. Serum from CD patients pre-treated with adalimumab showed increased osteoblast viability compared with that of post-treated patients at 6 months (P = 0.002) and controls. However, post-adalimumab treatment sera at 6 months appeared to increase osteoblast differentiation (P = 0.001), which is likely to be important in new bone formation.

Conclusions: This first study evaluating the role of adalimumab as a possible bone protector in Crohn's disease patients has shown that similar to infliximab, adalimumab has complex and potentially beneficial effects on bone metabolism.

Citing Articles

Serum N-terminal telopeptide of type I collagen as a biomarker for predicting bone density loss in patients with Crohn disease.

Ishida N, Higuchi T, Miyazu T, Tamura S, Suzuki S, Tani S PLoS One. 2021; 16(4):e0250658.

PMID: 33905438 PMC: 8078791. DOI: 10.1371/journal.pone.0250658.

The Interplay between Immune System and Microbiota in Osteoporosis.

Locantore P, Del Gatto V, Gelli S, Paragliola R, Pontecorvi A Mediators Inflamm. 2020; 2020:3686749.

PMID: 32184701 PMC: 7061131. DOI: 10.1155/2020/3686749.

Bone alterations in inflammatory bowel diseases.

Sgambato D, Gimigliano F, De Musis C, Moretti A, Toro G, Ferrante E World J Clin Cases. 2019; 7(15):1908-1925.

PMID: 31423424 PMC: 6695530. DOI: 10.12998/wjcc.v7.i15.1908.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

Szulc P, Naylor K, Hoyle N, Eastell R, Leary E Osteoporos Int. 2017; 28(9):2541-2556.

PMID: 28631236 DOI: 10.1007/s00198-017-4082-4.

The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

Barreira S, Fonseca J Clin Rev Allergy Immunol. 2016; 51(1):100-9.

PMID: 27166684 DOI: 10.1007/s12016-016-8547-6.

References

Harris S, Enger R, Riggs B, Spelsberg T . Development and characterization of a conditionally immortalized human fetal osteoblastic cell line. J Bone Miner Res. 1995; 10(2):178-86. DOI: 10.1002/jbmr.5650100203. View

Lamb E, Wong T, Smith D, Simpson D, Coakley A, Moniz C . Metabolic bone disease is present at diagnosis in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2002; 16(11):1895-902. DOI: 10.1046/j.1365-2036.2002.01363.x. View

Ryan B, Russel M, Schurgers L, Wichers M, Sijbrandij J, Stockbrugger R . 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(8):851-7. DOI: 10.1111/j.1365-2036.2004.02097.x. View

Plevy S, Landers C, Prehn J, Carramanzana N, Deem R, Shealy D . A role for TNF-alpha and mucosal T helper-1 cytokines in the pathogenesis of Crohn's disease. J Immunol. 1998; 159(12):6276-82. View

Ammann P, Rizzoli R, Bonjour J, Bourrin S, Meyer J, Vassalli P . Transgenic mice expressing soluble tumor necrosis factor-receptor are protected against bone loss caused by estrogen deficiency. J Clin Invest. 1997; 99(7):1699-703. PMC: 507990. DOI: 10.1172/JCI119333. View

Komatsu M, Kobayashi D, Saito K, Furuya D, Yagihashi A, Araake H . Tumor necrosis factor-alpha in serum of patients with inflammatory bowel disease as measured by a highly sensitive immuno-PCR. Clin Chem. 2001; 47(7):1297-301. View

Card T, West J, Hubbard R, Logan R . Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study. Gut. 2004; 53(2):251-5. PMC: 1774916. DOI: 10.1136/gut.2003.026799. View

Krieckaert C, Nurmohamed M, Wolbink G, Lems W . Changes in bone mineral density during long-term treatment with adalimumab in patients with rheumatoid arthritis: a cohort study. Rheumatology (Oxford). 2012; 52(3):547-53. DOI: 10.1093/rheumatology/kes320. View

Pollak R, Karmeli F, Eliakim R, Ackerman Z, Tabb K, Rachmilewitz D . Femoral neck osteopenia in patients with inflammatory bowel disease. Am J Gastroenterol. 1998; 93(9):1483-90. DOI: 10.1111/j.1572-0241.1998.468_q.x. View

10.

Lanfranchi G, Tragnone A . Serum and faecal tumour necrosis factor-alpha as marker of intestinal inflammation. Lancet. 1992; 339(8800):1053. DOI: 10.1016/0140-6736(92)90573-l. View

11.

Murch S, Lamkin V, Savage M, Walker-Smith J, MacDonald T . Serum concentrations of tumour necrosis factor alpha in childhood chronic inflammatory bowel disease. Gut. 1991; 32(8):913-7. PMC: 1378961. DOI: 10.1136/gut.32.8.913. View

12.

Silvennoinen J, Karttunen T, Niemela S, Manelius J, Lehtola J . A controlled study of bone mineral density in patients with inflammatory bowel disease. Gut. 1995; 37(1):71-6. PMC: 1382771. DOI: 10.1136/gut.37.1.71. View

13.

Mauro M, Radovic V, Armstrong D . Improvement of lumbar bone mass after infliximab therapy in Crohn's disease patients. Can J Gastroenterol. 2007; 21(10):637-42. PMC: 2658130. DOI: 10.1155/2007/216162. View

14.

Miheller P, Muzes G, Racz K, Blazovits A, Lakatos P, Herszenyi L . Changes of OPG and RANKL concentrations in Crohn's disease after infliximab therapy. Inflamm Bowel Dis. 2007; 13(11):1379-84. DOI: 10.1002/ibd.20234. View

15.

Bernstein M, Irwin S, Greenberg G . Maintenance infliximab treatment is associated with improved bone mineral density in Crohn's disease. Am J Gastroenterol. 2005; 100(9):2031-5. DOI: 10.1111/j.1572-0241.2005.50219.x. View

16.

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(2):228-33. PMC: 1027054. DOI: 10.1136/gut.40.2.228. View

17.

Hyams J, Wyzga N, Kreutzer D, Justinich C, Gronowicz G . Alterations in bone metabolism in children with inflammatory bowel disease: an in vitro study. J Pediatr Gastroenterol Nutr. 1997; 24(3):289-95. DOI: 10.1097/00005176-199703000-00011. View

18.

Bernstein C, Sargent M, Leslie W . Serum osteoprotegerin is increased in Crohn's disease: a population-based case control study. Inflamm Bowel Dis. 2005; 11(4):325-30. DOI: 10.1097/01.mib.0000164015.60795.ca. View

19.

Lin C, Moniz C, Chambers T, Chow J . Colitis causes bone loss in rats through suppression of bone formation. Gastroenterology. 1996; 111(5):1263-71. DOI: 10.1053/gast.1996.v111.pm8898640. View

20.

Oelzner P, Franke S, Muller A, Hein G, Stein G . Relationship between soluble markers of immune activation and bone turnover in post-menopausal women with rheumatoid arthritis. Rheumatology (Oxford). 1999; 38(9):841-7. DOI: 10.1093/rheumatology/38.9.841. View