Veerappan Sundaram G, Healy Martin, Walsh Bernard, O'Morain Colm A, Daly Jacqueline S, Ryan Barbara M
aDeparment of Gastroenterology, Adelaide & Meath Hospital, Tallaght, Dublin 24 Departments of bBiochemistry cGerontology, St James's Hospital, Dublin 8 dDepartment of Anatomy, Divison of Biology, Royal College of Surgeons in Ireland, Dublin 2, Republic of Ireland.
Eur J Gastroenterol Hepatol. 2016 Nov;28(11):1335-44. doi: 10.1097/MEG.0000000000000719.
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.
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.
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).
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.
英夫利昔单抗（IFX）治疗已显示出对炎症性肠病（IBD）患者骨代谢具有潜在的有益作用。我们旨在使用既定的骨代谢标志物和体外成骨细胞模型，前瞻性评估IFX治疗对未使用过抗肿瘤坏死因子（TNF）-α的IBD患者骨代谢的影响。
共纳入37例未使用过抗TNFα的IBD患者和20名健康对照者。所有测量均在基线时进行，并在IFX治疗后的IBD患者中重复测量。采用双能X线吸收法测量骨密度。检测甲状旁腺激素、维生素D、骨保护素、核因子κB受体活化因子配体可溶性受体以及促炎和抗炎细胞因子。使用骨钙素（OC）和I型前胶原N端前肽测量骨形成，使用血清I型胶原C端肽测量骨吸收。分析对照者和IBD患者血清对人成骨细胞活力和分化的影响。
对照组的OC水平高于IBD患者（P = 0.018）。IFX治疗后，治疗后第6周和第30周时，OC和I型前胶原N端前肽分别显著升高（P = 0.002和0.011）以及（P < 0.001和P = 0.016）。血清I型胶原C端肽有非显著性下降。IFX治疗后，促炎细胞因子TNF-α、白细胞介素-6和白细胞介素-13分别显著下降（第54周，P = 0.016；第6周，P = 0.005；第6周，P = 0.025）。IFX治疗前IBD患者的血清与对照组相比，显示出成骨细胞活力增加（P = 0.003至P < 0.005），但诱导成骨细胞分化降低。IFX治疗后，活力降至对照水平，但成骨细胞分化增加（P = 0.041）。
IFX治疗对骨代谢产生有益影响。成骨细胞培养结果表明，IBD患者可能有成骨细胞活力增加，但分化降低，这对骨强度有影响。
