title: Use of dipeptidyl peptidase-4 inhibitors for type 2 diabetes mellitus and risk of fracture.
abstract: BACKGROUND
  Although patients with type 2 diabetes mellitus have an increased bone mineral density as compared to healthy patients, their risk of fracture is elevated. Incretins, new anti-diabetic drugs, may have a protective effect on bone mineral density. However, data on the effect of incretins on fracture risk are limited. Therefore the aim of this study was to investigate the association between the use of DPP4-I and the risk of fracture.
  
  
  METHODS
  A retrospective population based cohort study, using data from the Clinical Practice Research Datalink (CPRD) database (2007-2012), was conducted. Patients (N=216,816) with at least one prescription for a non-insulin anti-diabetic drug (NIAD), aged 18+ during data collection, were matched to one control patient. Cox proportional hazards models were used to estimate the hazard ratio of any fracture in DPP4 inhibitor (DPP4-I) users versus controls and versus other NIAD patients. Time-dependent adjustments were made for age, sex, life style, comorbidity and drug use.
  
  
  RESULTS
  The actual duration of DPP4-I use was 1.3years. There was no different risk of fracture comparing current DPP4-I users to controls (adjusted hazard ratio (adj. HR) 0.89, 95% confidence interval (CI) 0.71-1.13). There was also no increased risk comparing current DPP4-I users to other NIAD users, adj. HR 1.03 (95% CI 0.92-1.15).
  
  
  CONCLUSIONS
  DPP4-I use was not associated with fracture risk compared to controls and to other NIAD users. However, the duration of DPP4-I use in our database might have been too short to show an association with fracture risk.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands; Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Johanna H M
authors.initials: JH
authors.lastname: Driessen
authors.affiliation: Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands; Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Hein A W
authors.initials: HA
authors.lastname: van Onzenoort
authors.affiliation: Department of Medicine, Maastricht University Medical Centre+, The Netherlands; Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre+, The Netherlands.
authors.forename: Ronald M A
authors.initials: RM
authors.lastname: Henry
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Arief
authors.initials: A
authors.lastname: Lalmohamed
authors.affiliation: Department of Internal Medicine, Viecuri Medical Centre, Venlo, The Netherlands; Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands; Biomedical Research Institute, University Hasselt, Hasselt, Belgium.
authors.forename: Joop P
authors.initials: JP
authors.lastname: van den Bergh
authors.affiliation: Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands; Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Neef
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands.
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands; Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands; MRC Epidemiology Lifecourse Unit, Southampton General Hospital, Southampton UK. Electronic address: f.devries@uu.nl.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
keywords: CPRD; Cohort-study; DPP; Diabetes mellitus type 2; Fracture