A 1-year prospective study of the effect of infliximab on bone metabolism in inflammatory bowel disease patients.

OBJECTIVES: Infliximab (IFX) treatment has shown potentially beneficial effects on bone metabolism in inflammatory bowel disease (IBD) patients. We aimed to prospectively evaluate the impact of IFX treatment on bone metabolism in antitumour necrosis factor (TNF)-α-naive IBD patients using established bone metabolism markers and an in-vitro osteoblast model. MATERIALS AND METHODS: A total of 37 anti-TNFα-naive IBD patients and 20 healthy controls were included. All measurements were performed at baseline and repeated in IBD patients following IFX therapy. Bone mineral density was measured by dual-energy X-ray absorptiometry. Parathyroid hormone, vitamin D, osteoprotegerin, soluble receptor activator of nuclear factor B ligand and proinflammatory and anti-inflammatory cytokines were measured. Bone formation was measured using osteocalcin (OC) and procollagen type 1N propeptide, and bone resorption was measured using serum type 1 collage c-telopeptide. The effect of control and IBD patient sera on human osteoblast viability and differentiation was analysed. RESULTS: OC level was higher in controls than IBD patients (P=0.018). After IFX, OC and procollagen type 1N propeptide increased significantly (P=0.002 and 0.011) and (P<0.001 and P=0.016) at weeks 6 and 30 after treatment, respectively. There was a nonsignificant decrease in serum type 1 collage c-telopeptide. After IFX therapy, proinflammatory cytokines TNF-α, interleukin-6 and interleukin-13 decreased significantly (P=0.016, week 54; P=0.005, week 6 and P=0.025, week 6), respectively. Sera from IBD patients before IFX showed increased osteoblast viability compared with the controls (P=0.003 to P<0.005), but induced reduced osteoblast differentiation. After IFX, viability reduced to control levels, but osteoblast differentiation increased (P=0.041). CONCLUSION: IFX treatment induced beneficial effects on bone metabolism. Osteoblast culture results suggest that IBD patients may have increased osteoblast viability, but reduced differentiation, which has implications for bone strength.

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 < 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.

Hot avulsion: a modification of an existing technique for management of nonlifting areas of a polyp (with video).

BACKGROUND: Endoscopic management of the nonlifting areas of a colonic polyp is a significant challenge. The traditional approach has been to use ablative techniques with mixed long-term results. OBJECTIVE: To evaluate the safety and efficacy of hot avulsion (HA), a modification in the use of hot biopsy forceps in the management of the nonlifting areas of a colonic polyp. DESIGN: Retrospective review of data from a prospectively maintained colonic Endoscopic Mucosal Resection database. SETTING: Tertiary referral hospital. PATIENTS AND INTERVENTION: Twenty patients in whom HA was used as part of the polypectomy technique. MAIN OUTCOME MEASUREMENTS: Location and size of polyp, reasons for nonlifting, immediate success, residual rates, and adverse events. RESULTS: In our 20 patients studied, the main reasons for nonlifting were scarring from previous EMR attempts in 55% and scarring from previous biopsy in 35%. Mean size of avulsion was 4.4 mm (range, 1-15 mm). At the index procedure, HA was successful in removing macroscopic adenomatous tissue in all patients. At follow-up examinations, 85% (17/20) had no macroscopic or microscopic neoplasia residual and 15% (3/20) had a small area of residual that was easily treated with repeat HA. There were no immediate or long-term adverse events. LIMITATIONS: Nonrandomized, single-center experience. CONCLUSIONS: HA appears to be a safe and effective adjunct treatment to snare polypectomy for nonlifting areas of a colonic polyp. Further randomized multicenter studies are required with direct comparison to established techniques.

Duodenal gastric heterotopia: further evidence of an association with fundic gland polyps.

Duodenal gastric heterotopia (DGH) is a common incidental finding at endoscopy, generally assumed to be congenital in origin. A recent study has suggested a possible association with gastric fundal gland polyps (FGPs). In this review of 37 patients with histologically confirmed DGH, the background to our present understanding of the DGH lesion is reviewed, the clinical and pathological associations of the condition in our cohort are identified, and the histological and immunohistochemical features of the DGH lesion are described. An association with the presence of FGPs is again demonstrated, whereas an inverse relationship with Helicobacter pylori is also shown. Immunohistochemical staining demonstrates that the fundic-type glands of DGH express the proton pump antigen (H(+)K(+)ATPase), whereas the overlying surface mucosa expresses the mucin profile of normal gastric-type mucosa (mucin-5AC positive, mucin-2 negative). DGH may represent a further component of the iatrogenic hypergastrinemia-related hypothesis for FGP development, although further study is required to confirm this.

Infliximab-associated alveolitis after treatment for severe left-sided ulcerative colitis.

Here we describe a patient with ulcerative colitis who developed alveolitis after infliximab therapy. With earlier case reports of development of alveolitis in rheumatoid arthritis patients after infliximab infusion, the temporal relationship between the infliximab therapy and the development of alveolitis in this case, raises the possibility that the two might be causally related. With an increasing trend towards treating moderate to severely active ulcerative colitis patients with infliximab as a rescue therapy, clinicians should be aware of this potentially serious complication.