title: An association between abnormal bone turnover, systemic inflammation, and osteoporosis in patients with chronic pancreatitis: a case-matched study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Professorial Surgical Unit, Trinity Centre for Health Sciences, Tallaght Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: Sinead N
authors.initials: SN
authors.lastname: Duggan
authors.affiliation: Professorial Surgical Unit, Trinity Centre for Health Sciences, Tallaght Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: Christina
authors.initials: C
authors.lastname: Purcell
authors.affiliation: Metabolism Laboratory, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Kilbane
authors.affiliation: Metabolism Laboratory, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Myra
authors.initials: M
authors.lastname: O'Keane
authors.affiliation: Metabolism Laboratory, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Malachi
authors.initials: M
authors.lastname: McKenna
authors.affiliation: Department of Biochemistry, Tallaght Hospital, Dublin, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Gaffney
authors.affiliation: Professorial Surgical Unit, Trinity Centre for Health Sciences, Tallaght Hospital, Trinity College Dublin, Dublin, Ireland.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Ridgway
authors.affiliation: Department of Biochemistry, Tallaght Hospital, Dublin, Ireland.
authors.forename: Gerard
authors.initials: G
authors.lastname: Boran
authors.affiliation: Professorial Surgical Unit, Tallaght Hospital, St Vincent's University Hospital Dublin, Trinity College Dublin, Dublin, Ireland.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Conlon
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D024042:Collagen Type I / Q000378:metabolism; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis; D010024:Osteoporosis / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000150:complications / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011347:Procollagen / Q000378:metabolism; D011446:Prospective Studies; D012907:Smoking; D013963:Thyroid Hormones / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D012739:Gonadal Steroid Hormones; C508600:IL6 protein, human; D015850:Interleukin-6; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011347:Procollagen; D013963:Thyroid Hormones; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D014807:Vitamin D; D002097:C-Reactive Protein; C104450:25-hydroxyvitamin D