title: Biochemical markers of bone turnover in diabetes patients--a meta-analysis, and a methodological study on the effects of glucose on bone markers.
abstract: This study examined whether markers of bone turnover differ between individuals with and without diabetes. Bone markers showed heterogeneity between studies and were discrepant for markers of bone creation and markers of bone degradation. Bone markers may be of lesser value in diabetes due to heterogeneity.
  
  
  BACKGROUND
  The aim of this meta-analysis was to compare existing literature regarding changes in bone markers among diabetics compared to healthy controls. To exclude that blood glucose levels among diabetes patients could influence the assays used for determining bone turnover markers, a methodological study was performed.
  
  
  METHODS
  Medline at Pubmed Embase, Cinahl, Svemed+, Cochrane library, and Bibliotek.dk was searched in August 2012. The studies should examine biochemical bone turnover among diabetes patients in comparison to controls in an observational design. In the methodological study, fasting blood samples were drawn from two individuals. Glucose was added to the blood samples in different concentrations and OC, CTX, and procollagen type 1 amino terminal propeptide were measured after 0, 1, 2, and 3 h.
  
  
  RESULTS
  Twenty-two papers fulfilled the criteria for the meta-analysis. From the pooled data in the meta-analysis, the bone markers osteocalcin (OC) (-1.15 ng/ml [-1.78,-0.52]) and C-terminal cross-linked telopeptide (CTX) (-0.14 ng/ml [-0.22, -0.05]) were significantly lower among diabetes patients than non-diabetes patients, however other markers did not differ. All markers displayed very high heterogeneity by I2 statistics. In the methodological study, the addition of glucose did not significantly change the bone markers neither by level of glucose nor with increasing incubation time.
  
  
  CONCLUSIONS
  The dissociative pattern of biochemical bone markers of bone formation and bone resorption present in diabetes patients is thus not caused by glucose per se but may be modulated by unknown factors associated with diabetes mellitus.
authors.affiliation: Clinical Institute, Aalborg University, Fredrik Bajers vej 7, 9220, Aalborg, Denmark, jakolind@rm.dk.
authors.forename: J
authors.initials: J
authors.lastname: Starup-Linde
authors.forename: S A
authors.initials: SA
authors.lastname: Eriksen
authors.forename: S
authors.initials: S
authors.lastname: Lykkeboe
authors.forename: A
authors.initials: A
authors.lastname: Handberg
authors.forename: P
authors.initials: P
authors.lastname: Vestergaard
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D024042:Collagen Type I / Q000097:blood / Q000187:drug effects; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D015675:Osteocalcin / Q000097:blood / Q000187:drug effects; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D010455:Peptides / Q000097:blood / Q000187:drug effects; D011347:Procollagen / Q000097:blood / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D005947:Glucose