title: Use of dipeptidyl peptidase 4 inhibitors and fracture risk compared to use of other anti-hyperglycemic drugs.
abstract: BACKGROUND
  Dipeptidyl peptidase-4 inhibitors (DPP4-Is) are a new class of anti-hyperglycemic drugs which might have a potential beneficial effect on bone metabolism. Data on the effect of DPP4-I use and fracture risk is limited and conflicting. The aim of the present study was to investigate the association between use of DPP4-Is and fracture risk.
  
  
  METHODS
  A case-control study was conducted using data from the Danish National Health Service. Cases were those who sustained a fracture, and controls were those without a fracture during the study period (2007-2011), all aged 18 years and older. Conditional logistic regression estimated the odds ratios of fracture with current use of DPP4-I use. Analyses were adjusted for comorbidities and recent drug use.
  
  
  RESULTS
  Among the cases there were 6993 current non-insulin anti-diabetic drug (NIAD) users (excluding incretin users) and 643 DPP4-I users. There were 7209 NIAD users (excluding incretin users) among the controls and 707 DPP4-I users. Current DPP4-I use was not associated with risk of any fracture (adjusted [adj.] OR: 0.97, 95% CI: 0.79-1.18) or major osteoporotic fracture (adj. OR: 0.96, 95% CI: 0.72-1.28). Stratification of current DPP4-I use to cumulative and average daily dose did not show an association.
  
  
  CONCLUSIONS
  In a population-based case-control study we identified that short-term use of DPP4-I was not associated with fracture risk as compared to users of other anti-hyperglycemic drugs. Additionally, results suggest that increasing daily dose and cumulative DPP4-I exposure were not associated with fracture risk. However, more research is needed to assess the effect of long-term DPP4-I use on the risk of fracture.
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 Clinical Medicine, Aalborg University, Aalborg, Denmark.|Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Starup-Linde
authors.affiliation: Department of Medicine, Maastricht University Medical Centre+, The Netherlands.|Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre+, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Henry
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: Department of Internal Medicine, Maastricht University Medical Centre+, The Netherlands.|Biomedical Research Institute, University Hasselt, Hasselt, Belgium.
authors.forename: Joop
authors.initials: J
authors.lastname: van den Bergh
authors.affiliation: Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.|Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Vestergaard
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.
authors.forename: Frank
authors.initials: F
authors.lastname: de Vries
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: Andrea M
authors.initials: AM
authors.lastname: Burden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D003718:Denmark / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000453:epidemiology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000209:etiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012306:Risk; D013997:Time Factors; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
keywords: DPP4-I; case-control; fracture; pharmacoepidemiology; type 2 diabetes mellitus