Johanna H M Driessen1,2,3, Hein A W van Onzenoort3,4, Jakob Starup-Linde5,6, Ronald Henry7,8, Cees Neef2,3, Joop van den Bergh9,10, Peter Vestergaard5,11, Frank de Vries1,2,3,12, Andrea M Burden1,2,3. 1. Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands. 2. Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands. 3. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Centre+, Maastricht, The Netherlands. 4. Department of Pharmacy, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. 5. Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. 6. Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 7. Department of Medicine, Maastricht University Medical Centre+, The Netherlands. 8. Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre+, The Netherlands. 9. Department of Internal Medicine, Maastricht University Medical Centre+, The Netherlands. 10. Biomedical Research Institute, University Hasselt, Hasselt, Belgium. 11. Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark. 12. MRC Epidemiology Lifecourse Unit, Southampton General Hospital, Southampton, UK.
Abstract
INTRODUCTION: 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.
INTRODUCTION: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: Johanna H M Driessen; Frank de Vries; Hein van Onzenoort; Nicholas C Harvey; Cees Neef; Joop P W van den Bergh; Peter Vestergaard; Ronald M A Henry Journal: Br J Clin Pharmacol Date: 2016-12-07 Impact factor: 4.335