title: The effect of hyperglycaemia on osseointegration: a review of animal models of diabetes mellitus and titanium implant placement.
abstract: Patients with type 2 diabetes mellitus have a higher risk of dental and/or orthopaedic implant failure. However, the mechanism behind this phenomenon is unclear, and animal studies may prove useful in shedding light on the processes involved. This review considers the available literature on rat models of diabetes and titanium implantation.
  
  
  
  The process of osseointegration whereby direct contact is achieved between bone and an implant surface depends on healthy bone metabolism. Collective evidence suggests that hyperglycaemia adversely affects bone turnover and the quality of the organic matrix resulting in an overall deterioration in the quality, resilience and structure of the bone tissue. This in turn results in compromised osseointegration in patients receiving dental and orthopaedic implants. The incidence of diabetes mellitus (DM), which is a chronic metabolic disorder resulting in hyperglycaemia, is rising. Of particular significance is the rising incidence of adult onset type 2 diabetes mellitus (T2DM) in an ageing population. Understanding the effects of hyperglycaemia on osseointegration will enable clinicians to manage health outcomes for patients receiving implants. Much of our understanding of how hyperglycaemia affects osseointegration comes from animal studies.
  
  
  
  In this review, we critically analyse the current animal studies.
  
  
  
  Our review has found that most studies used a type 1 diabetes mellitus (T1DM) rodent model and looked at a young male population of rodents. The pathophysiology of T1DM is however very different to that of T2DM and is not representative of T2DM, the incidence of which is rising in the ageing adult population. Genetically modified rats have been used to model T2DM, but none of these studies have included female rats and the metabolic changes in bone for some of these models used are not adequately characterized.
  
  
  
  Therefore, the review suggests that the study population needs to be broadened to include both T1DM and T2DM models, older rats as well as young rats, and importantly animals from both sexes to reflect more accurately clinical practice.
authors.affiliation: Faculty of Dentistry, University of Sydney, Sydney, Australia.
authors.forename: Shalinie
authors.initials: S
authors.lastname: King
authors.affiliation: Faculty of Dentistry, University of Sydney, Sydney, Australia.
authors.forename: Iven
authors.initials: I
authors.lastname: Klineberg
authors.affiliation: Clinical Exercise Science Research Program, Institute of Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Australia.
authors.forename: Itamar
authors.initials: I
authors.lastname: Levinger
authors.affiliation: Department of Physiology and Bosch Institute for Medical Research, University of Sydney, Sydney, NSW, 2006, Australia. tara.speranza@sydney.edu.au.
authors.forename: Tara C
authors.initials: TC
authors.lastname: Brennan-Speranza
mesh_terms: D000818:Animals; D035843:Biomedical Research / Q000379:methods / Q000592:standards; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D019544:Equipment Failure Analysis; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D016348:Osseointegration / Q000502:physiology*; D019736:Prostheses and Implants / Q000009:adverse effects*; D011475:Prosthesis Failure / Q000209:etiology*; D058996:Quality Improvement; D051381:Rats; D014025:Titanium / Q000627:therapeutic use
chemical_list: D014025:Titanium
keywords: Animal models; Biochemical markers of bone turnover; Implants