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Re: Bone density loss in Crohn’s disease: Role of TNF and potential for prevention by bupropion.

Dear Editor

We note with interest the demonstration by Card et al. in the February issue of Gut that the increased hip fracture rate in Crohn’s disease, CD, and by inference the diminished bone density commonly noted in CD, is only to minor degree secondary to iatrogenic corticosteroid use.[1] The subject of bone mineral density loss in CD has been recently reviewed - tumor necrosis factor-alpha, TNF, is suspected of being an important mediator of this loss.[2,3] Evidence has been published for localized overproduction of TNF being largely responsible for the bone loss seen in rheumatoid arthritis,[4,5] psoriatic arthritis,[6] multiple myeloma,[7] hip prosthesis loosening,[8] periodontal disease,[9] and spondyloarthropathies.[10] Anti-TNF antibody has been shown to slow the bone loss of spondyloarthropy (10) and rheumatoid arthritis [4,11].

We have found that the commonly used antidepressant bupropion can induce remission in CD [12,13] and have found that bupropion can lower TNF.[14] If bupropion is found effective in CD and to lower TNF in large trials, it might be considered for use in bone loss and osteoporosis in CD or otherwise.

References

1. Card T, West J, Hubbard R, Logan RF. Hip fractures in patients with inflammatory bowel disease and their relationship to corticosteroid use: a population based cohort study. Gut 2004;53;251-55

2. Lichtenstein GR. Evaluation of bone mineral density in IBD: current safty focus. Am J Gastroenterol 2003;98(12 Suppl);S24-30

3. Nanes MS. TNF-alpha:molecular and cellular mechanisms in skeletal pathology. Gene 2003;321;1-15

4. Bingham CO 3rd. The pathogenesis of rheumatoid arthritis: pivotal cytokines involved in bone degradation and inflammation. J Rheum Suppl 2002;65;39

5. Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 2003;42 Suppl 2;ii 11-6

6. Ritchlin CT, Haas-Smith SA, Li P, Hicks DG, Schwarz EM. Mechanism of TNF-alpha and RANKL mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 2003;11l:821-31

7. Jurisic V, Colovic M. Correlation of sera TNF-alpha with petrcentage of bone marrow plasma cells, LDH, beta 2 micro globulin, and clinical stage in multiple myeloma. Med Oncol 2002;19;133-9

8. Campbell PA, Wang M, Amstutz HC, Goodman SB. Positive cytokine production in failed metal on metal total hip replacements. Acta Orthop Scand 2002;73;506-12

9. Graves DT, Cochran D.n The contribution of Il-1 and TNF-alpha to periodontal tissue destruction. J Periodont 2003;74;391-401

10. Allali F, Breban M, Porcher R, Maillefert JF, Dougados M, Roux C. Increase in bone mineral density in patients with spondyloarthropathy treated with anti-TNF-alpha. Ann Rheum Dis 2003;62;347-9

11. Geimold AM. New indications for treatment of chronic inflammation by TNF-alpha blockade. Am J Med Sci 2003;325;75-92

12. Kast RE, Altschuler EL. Remission of Crohn’s disease on bupropion. Gastroenterology 2001;121;1260-1

13. Kane S, Altschuler EL, Kast RE. Crohn’s disease remission on bupropion. Gastroenterology 2003;125;1290