title: Diabetes Mellitus and Bone Regeneration: A Systematic Review and Meta-Analysis of Animal Studies.
abstract: The regeneration of bone defects resulting from trauma, resection of tumors, infection, or congenital disease is a challenge, and bone grafts are utilized in a wide array of clinical settings to augment bone repair and regeneration. Diabetes mellitus (DM) is a chronic metabolic disease, which affects 8.3% of the world population, summing ∼387 million individuals. The consequences of the disease, for example, hyperglycemia, have been associated to a reduced capacity to form bone and poor bone quality, influencing bone healing. Our aim was to systematically review the literature to the effect of diabetic condition on bone regeneration in animal models, when using bone substitute materials from different origins, and perform a meta-analysis to quantitatively study the effect of DM on bone regeneration.
  
  
  
  An extensive search strategy was carried out through PubMed and EMBASE to identify the potential relevant studies published from database inception until July 1, 2015. Initially, the title and abstract of 1409 studies were screened, after which inclusion criteria sorted 29 studies for full-text evaluation. After using exclusion criteria, a final number of seven studies could be included in the review.
  
  
  
  The seven included studies that passed our inclusion/exclusion criteria were all type 1 diabetes, comprising a total of 189 animals and 14 intrastudy comparisons. These studies presented a consistent and reduced risk of bias and showed a significant average effect size of -6.87% of bone formation for diabetes type 1 versus healthy condition [95% confidence interval: -10.55 to -3.18; I2= 87.4%; p = 0.0003].
  
  
  
  These findings prove that DM type 1 negatively influences bone formation compared with a healthy condition, irrespective of the bone substitute material used.
authors.affiliation: 1 Department of Biomaterials (309), Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Winston A
authors.initials: WA
authors.lastname: Camargo
authors.affiliation: 2 Systematic Review Centre for Laboratory Animal Experimentation, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Rob
authors.initials: R
authors.lastname: de Vries
authors.affiliation: 2 Systematic Review Centre for Laboratory Animal Experimentation, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Judith
authors.initials: J
authors.lastname: van Luijk
authors.affiliation: 1 Department of Biomaterials (309), Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Hoekstra
authors.affiliation: 1 Department of Biomaterials (309), Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Ewald M
authors.initials: EM
authors.lastname: Bronkhorst
authors.affiliation: 1 Department of Biomaterials (309), Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: John A
authors.initials: JA
authors.lastname: Jansen
authors.affiliation: 1 Department of Biomaterials (309), Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Jeroen J J P
authors.initials: JJJP
authors.lastname: van den Beucken
mesh_terms: D000818:Animals; D001861:Bone Regeneration; D003920:Diabetes Mellitus / Q000503:physiopathology*; D006801:Humans; D010012:Osteogenesis; D017063:Outcome Assessment, Health Care; D019919:Prosthesis Implantation; D017594:Publication Bias
keywords: animal studies; bone formation; bone regeneration; bone substitutes; bone transplantation; diabetes mellitus