title: MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover - a systematic review and meta-analysis.
abstract: OBJECTIVE
  To investigate the differences in bone turnover between diabetic patients and controls.
  
  
  METHODS
  A systematic review and meta-analysis.
  
  
  METHODS
  A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers.
  
  
  RESULTS
  A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (-0.10 ng/mL (-0.12, -0.08)) and the bone formation markers osteocalcin (-2.51 ng/mL (-3.01, -2.01)) and procollagen type 1 amino terminal propeptide (-10.80 ng/mL (-12.83, -8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (-0.31 U/L (-0.56, -0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)).
  
  
  CONCLUSIONS
  Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus C, Denmark.
authors.forename: Katrine
authors.initials: K
authors.lastname: Hygum
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus C, Denmark.|Department of Infectious DiseasesAarhus University Hospital, Aarhus N, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Starup-Linde
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus C, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Harsløf
authors.affiliation: Department of Clinical Medicine and EndocrinologyAalborg University Hospital, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
authors.affiliation: Department of Endocrinology and Internal MedicineAarhus University Hospital, Aarhus C, Denmark.
authors.forename: Bente L
authors.initials: BL
authors.lastname: Langdahl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D016022:Case-Control Studies; D024043:Collagen Type II / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D005819:Genetic Markers; D006801:Humans; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D000071681:Tartrate-Resistant Acid Phosphatase / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C000590554:C-terminal cross-linking telopeptide of type II collagen, human; D024043:Collagen Type II; D005819:Genetic Markers; D053244:Osteoprotegerin; D010446:Peptide Fragments; D011347:Procollagen; C422903:SOST protein, human; C047202:procollagen Type I N-terminal peptide; D015675:Osteocalcin; D000071681:Tartrate-Resistant Acid Phosphatase