title: Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study.
abstract: OBJECTIVE
  Hypoglycemic treatments could modulate the risk for fractures in many ways. Most studies have not explored the effect on the incidence of bone fractures of individual oral hypoglycemic agents, rather all oral treatments as a whole. The aim of this case-control study, nested within a retrospective cohort, is the assessment of the risk for bone fractures associated with exposure to insulin or different oral hypoglycemic agents.
  
  
  METHODS
  A case-control study nested within a cohort of 1,945 diabetic outpatients with a follow-up of 4.1 +/- 2.3 years was performed, comparing 83 case subjects of bone fractures and 249 control subjects matched for age, sex, duration of diabetes, BMI, A1C, comorbidity, smoking, and alcohol abuse. Exposure to hypoglycemic drugs during the 10 years preceding the event (or matching index date) was assessed.
  
  
  RESULTS
  In a model including treatment with insulin secretagogues metformin and insulin for at least 36 months during the previous 10 years, no significant association was observed between bone fractures and medications. In an alternative model considering treatments at the time of fracture, insulin treatment was significantly associated with bone fractures in men (OR 3.20 [95% CI 1.32-7.74]) but not in women (1.41 [0.73-2.73]).
  
  
  CONCLUSIONS
  Insulin-sensitizing treatment with metformin is not associated with a higher incidence of bone fractures, suggesting that the negative effect of thiazolidinediones is due to a specific action on bone metabolism rather a reduction of insulinemia. Conversely, current treatment with insulin increases the risk of fractures; at the same time, exposure to this agent in the longer term does not appear to affect bone frailty.
authors.affiliation: Department of Critical Care Medicine and Surgery, Unit of Geriatrics, University of Florence and Azienda Ospedaliero-Universitaria Careggi, via delle Oblate 4, 50134 Florence, Italy. mmonami@libero.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Monami
authors.forename: Barbara
authors.initials: B
authors.lastname: Cresci
authors.forename: Angela
authors.initials: A
authors.lastname: Colombini
authors.forename: Laura
authors.initials: L
authors.lastname: Pala
authors.forename: Daniela
authors.initials: D
authors.lastname: Balzi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gori
authors.forename: Veronica
authors.initials: V
authors.lastname: Chiasserini
authors.forename: Niccolò
authors.initials: N
authors.lastname: Marchionni
authors.forename: Carlo Maria
authors.initials: CM
authors.lastname: Rotella
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
mesh_terms: D000368:Aged; D001794:Blood Pressure; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000453:epidemiology* / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008019:Life Style; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents