Review article: the effects of antitumour necrosis factor-α on bone metabolism in inflammatory bowel disease.

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis. A number of studies have emerged in recent years indicating that tumour necrosis factor (TNF) blockade appears to have a beneficial effect on bone mineral density (BMD) in IBD patients. AIMS: To provide a review of the available data regarding the effect of the currently licensed anti-TNF-α therapies on bone metabolism and BMD in IBD patients. METHODS: A Medline search was performed using the search terms \u27infliximab\u27, \u27bone metabolism\u27, \u27IBD\u27, \u27BMD\u27, \u27bone markers\u27, \u27adalimumab\u27, \u27bone disease\u27, \u27Crohn\u27s disease\u27 and \u27ulcerative colitis\u27. RESULTS: Infliximab has a beneficial effect on bone turnover markers in Crohn\u27s disease (CD) patients in the short term. The longest study to date comprising 24 CD patients showed an overall improvement in two bone formation markers - b-alkaline phosphatase (P = 0.022) and osteocalcin (P = 0.008) at 4 months post-treatment. Moreover, the largest study to date comprising 71 CD patients showed significant improvement in sCTx, a bone resorption marker (P = 0.04) at week-8 post-treatment. There is little data looking at the effect of anti-TNF-α therapy on bone metabolism in ulcerative colitis. Moreover, the long-term effects of anti-TNF-α therapy on bone structure and fracture risk in IBD patients are currently not known. The effect of cessation of anti-TNF-α therapy on bone metabolism is also unknown. CONCLUSION: Properly controlled long-term trials are needed to fully evaluate the impact of TNF blockade on bone mineral density

Anti tumour necrosis factor - alpha : does it rescue bone loss in inflammatory bowel disease patients?

I. I inflammatory Bowe1 Disease I. I. I General Overview Inflammatory bowel disease (IBD) is a group of disorders of the gastrointestinal tract characterized by intestinal inflammation and a chronic relapsing course. IBD has traditionally been categorized as either ulcerative colitis (UC) or Crohn's disease (CD) on the basis of clinical, radiological, endoscopic and histological criteria [I], (Figure 1.1 and Figure 1.2). About 10 % of colitis cases show overlapping features of the two major forms and are designated intermediate colitis [I]. Both UC and CD are commonly characterized by a series of clinical exacerbations and remissions requiring long term use of medications, and frequently necessitating surgical interventions. Figure 1.1: Endoscopic appearance of Ulcerative colitis [2] - marked by diffuse, superficial inflammation of the colonic mucosa, beginning in the rectum and extending proximally to involve any contiguous length of colon. Figure 1.2: Endoscopic appearance of Crohn's colitis [2] - marked by transmural nflammation of the colonic mucosa. see figures in thesis. Although the etiology of IBD remains to be defined, recent experimental and clinical studies suggests that the initiation and pathogenesis of these diseases are multi-factorial, involving interactions between genetic, environmental and immune factors [3]. I. I.2 Prevalence and Incidence IBD is not evenly distributed world-wide. There is a clear tendency to a higher incidence in developed countries compared with less developed countries [4]. North America, the United Kingdom and Scandinavia have the highest rates [4]. In areas in which data are available over a number of years, the incidence of UC has remained relatively constant [S-81. Unlike UC, the incidence of CD has risen progressively since its original description [9-131. In a European study the reported incidence rates for UC and CD in Ireland were 14.8 and 5.9 per 100,000 populations over a two year period 1991-1993 [14]. UC and CD are most commonly diagnosed in late adolescence and early adulthood, but the diagnosis may occur at all ages.</p

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

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 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.</p