Thayu Meena, Leonard Mary B, Hyams Jeffrey S, Crandall Wallace V, Kugathasan Subra, Otley Anthony R, Olson Allan, Johanns Jewel, Marano Colleen W, Heuschkel Robert B, Veereman-Wauters Gigi, Griffiths Anne M, Baldassano Robert N
Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, PA 19014, USA.
Clin Gastroenterol Hepatol. 2008 Dec;6(12):1378-84. doi: 10.1016/j.cgh.2008.07.010.
BACKGROUND & AIMS: Crohn's disease (CD) is associated with altered bone metabolism. This study examined changes in bone formation and resorption after infliximab induction and associations between bone biomarkers, linear growth, and disease activity (Pediatric Crohn's Disease Activity Index [PCDAI]) after 54 weeks of infliximab therapy.
One hundred twelve subjects ages 6-17 years with moderate to severe CD received infliximab induction (5 mg/kg/dose) at weeks 0, 2, and 6; week-10 responders were randomized to infliximab every 8 or every 12 weeks maintenance therapy. Serum bone-specific alkaline phosphatase (BSAP), N-terminal propeptide of type 1 collagen (P1NP), urine C-telopeptide of collagen cross-links (CTX-1), and deoxypyrodinoline (DPD) were collected at baseline and 10 weeks. PCDAI and height z-scores were assessed at baseline and at 10 and 54 weeks.
Models were adjusted for bone age, gender, height, and steroid use. Baseline BSAP and P1NP levels were negatively associated with PCDAI (both P = .01). BSAP and P1NP increased during induction (both P < .001) and were associated with 54-week increases in height z-score (P < .05 and P < .001, respectively). Improvements in P1NP were associated with 54-week decreases in PCDAI (P = .01). CTX-1 and DPD also increased during induction (P < .001 and P = .01, respectively) but were not associated with changes in PCDAI. Changes in CTX-1 were associated with improvements in height z-score (P < .002).
Infliximab therapy is associated with dramatic increases in BSAP and P1NP, consistent with inhibition of tumor necrosis factor-alpha effects on osteoblasts. The increases in CTX-1 and DPD likely reflect coupling of bone formation and resorption and increases in linear growth.
克罗恩病（CD）与骨代谢改变有关。本研究检测了英夫利昔单抗诱导治疗后骨形成和骨吸收的变化，以及英夫利昔单抗治疗54周后骨生物标志物、线性生长和疾病活动度（儿童克罗恩病活动指数[PCDAI]）之间的关联。
112例6至17岁的中重度CD患者在第0、2和6周接受英夫利昔单抗诱导治疗（5mg/kg/剂量）；第10周的缓解者被随机分为每8周或每12周接受英夫利昔单抗维持治疗。在基线和第10周收集血清骨特异性碱性磷酸酶（BSAP）、1型胶原N端前肽（P1NP）、尿胶原交联C端肽（CTX-1）和脱氧吡啶啉（DPD）。在基线、第10周和第54周评估PCDAI和身高z评分。
模型根据骨龄、性别、身高和类固醇使用情况进行了调整。基线时BSAP和P1NP水平与PCDAI呈负相关（均P = 0.01）。诱导治疗期间BSAP和P1NP升高（均P < 0.001），且与54周时身高z评分的增加相关（分别为P < 0.05和P < 0.001）。P1NP的改善与54周时PCDAI的降低相关（P = 0.01）。CTX-1和DPD在诱导治疗期间也升高（分别为P < 0.001和P = 0.01），但与PCDAI的变化无关。CTX-1的变化与身高z评分的改善相关（P < 0.002）。
英夫利昔单抗治疗与BSAP和P1NP显著增加有关，这与抑制肿瘤坏死因子-α对成骨细胞的作用一致。CTX-1和DPD的增加可能反映了骨形成和骨吸收的耦联以及线性生长的增加。
