Professorial Surgical Unit, Trinity Centre for Health Sciences, Tallaght Hospital, Trinity College Dublin, Dublin, Ireland.
Metabolism Laboratory, St Vincent's University Hospital, Dublin, Ireland.
Am J Gastroenterol. 2015 Feb;110(2):336-45. doi: 10.1038/ajg.2014.430. Epub 2015 Jan 27.
Because of deteriorating exocrine function, malabsorption renders chronic pancreatitis (CP) patients at risk of osteoporosis and fracture. However, the pathogenesis of low bone mineral density (BMD) has not been characterized. We hypothesized that bone turnover is elevated in CP, and we sought to investigate an association between bone metabolism and systemic inflammation.
Twenty-nine CP patients and twenty-nine matched controls were recruited. Bone-turnover markers procollagen 1 amino-terminal propeptide (P1NP), OC (osteocalcin; bone formation markers), and carboxy-terminal telopeptide of type I collagen (CTX-I; bone resorption marker) were measured along with vitamin D (25-hydroxyvitamin D, 25OHD), parathyroid hormone (PTH), interleukin 6 (IL-6), high-sensitivity (hs) C-reactive protein (CRP), and sex/thyroid hormones. BMD was measured by dual-energy X-ray absorptiometry. Smoking status was noted.
Of the CP patients, 31% had osteoporosis and 44.8% osteopenia (controls: 6.9 and 51.7%, respectively; P=0.019). BMD was lower for patients at the lumbar spine (P=0.014) and femoral neck (P=0.029). Patients had elevated bone formation (P1NP (P=0.0068), OC (P=0.033)) and bone resportion (CTX-I (P=0.016)) compared with controls. Patients had lower 25OHD compared with controls (P=0.0126) and higher inflammatory markers (hsCRP, P=0.0013). Sex and thyroid hormone levels were similar. Patients with lowest 25OHD levels had highest P1NP. In a multivariable model, age, PTH, and smoking were predictive of 25OHD. Patients with osteoporosis had higher P1NP, PTH, and IL-6 and lower 25OHD. Using analysis of variance, inflammation (hsCRP) was highest in those with lowest 25OHD and lowest BMD.
For the first time, bone turnover was shown to be abnormal in CP, and importantly, an association between low 25-OHD, smoking, and systematic inflammation was identified. Moreover, those with osteoporosis had the highest systemic inflammation. Together these factors provide an avenue for potential modification of risk factors, which may ultimately reduce bone loss and avert fractures in this group.
由于外分泌功能恶化,吸收不良使慢性胰腺炎(CP)患者有发生骨质疏松症和骨折的风险。然而,低骨密度(BMD)的发病机制尚未明确。我们假设 CP 患者的骨转换率升高,我们试图研究骨代谢与全身炎症之间的关系。
招募了 29 名 CP 患者和 29 名匹配的对照者。同时测量了骨转换标志物原胶原 1 氨基末端前肽(P1NP)、OC(骨形成标志物)和 I 型胶原羧基末端肽(CTX-I;骨吸收标志物),以及维生素 D(25-羟维生素 D,25OHD)、甲状旁腺激素(PTH)、白细胞介素 6(IL-6)、高敏(hs)C 反应蛋白(CRP)和性激素/甲状腺激素。采用双能 X 线吸收法测量 BMD。记录吸烟情况。
CP 患者中,31%患有骨质疏松症,44.8%患有骨质疏松症(对照组:分别为 6.9%和 51.7%;P=0.019)。患者的腰椎(P=0.014)和股骨颈(P=0.029)的 BMD 较低。与对照组相比,患者的骨形成标志物(P1NP(P=0.0068)、OC(P=0.033))和骨吸收标志物(CTX-I(P=0.016))更高。与对照组相比,患者的 25OHD 水平较低(P=0.0126),炎症标志物(hsCRP,P=0.0013)较高。性激素和甲状腺激素水平相似。25OHD 水平最低的患者 P1NP 最高。在多变量模型中,年龄、PTH 和吸烟是 25OHD 的预测因素。骨质疏松症患者的 P1NP、PTH 和 IL-6 较高,25OHD 较低。使用方差分析,最低 25OHD 和最低 BMD 患者的炎症(hsCRP)最高。
这是首次表明 CP 患者的骨转换异常,重要的是,我们发现低 25-OHD、吸烟和全身炎症之间存在关联。此外,骨质疏松症患者的全身炎症水平最高。这些因素共同为潜在的危险因素改变提供了途径,这可能最终减少该组患者的骨质流失并避免骨折。