title: Risk of fracture and the concomitant use of bisphosphonates with osteoporosis-inducing medications.
abstract: OBJECTIVE
  To review the literature on the concomitant use of bisphosphonates and medications that can influence bone metabolism and potentially attenuate bisphosphonate antifracture efficacy.
  
  
  METHODS
  MEDLINE and CINAHL were searched for articles published in English through December 2014 using the following terms: bisphosphonates, bone density conservation agents, acid-suppressive therapy, levothyroxine, thiazolidinediones (TZDs), selective serotonin reuptake inhibitors (SSRIs), bone fractures.
  
  
  METHODS
  Studies were included if they reported results of concomitant use of any listed medications with bisphosphonates and risk of fractures and focused on women. Articles that focused generally on the use of one of the listed medications and fractures without explicitly examining the potential antifracture efficacy or attenuation of bisphosphonates were excluded.
  
  
  RESULTS
  A total of 6 relevant studies were identified. Four epidemiological studies reported a statistically significant dose-dependent increase in the risk of fractures when bisphosphonates and acid-suppressive drugs were used together. One post hoc analysis of clinical trial data suggested no attenuation of the antifracture effects of bisphosphonates when used concomitantly with acid-suppressive therapy. One study involving bisphosphonates and SSRIs noted a statistically significant association between fracture risk and SSRI use. No study examining TZDs or levothyroxine with bisphosphonates was identified.
  
  
  CONCLUSIONS
  Existing research suggests potential attenuation of bisphosphonate antifracture efficacy among patients taking acid-suppressive medications. Based on their pharmacological actions, TZDs, SSRIs, and levothyroxine have similar implications. The paucity of evidence in the literature associating the attenuation of bisphosphonate antifracture efficacy when combined with other medications suggests that further investigation is needed.
authors: Market Access Solutions LLC, Raritan, NJ, USA.
authors: Abner N
authors: AN
authors: Nyandege
authors: Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
authors: Patricia W
authors: PW
authors: Slattum
authors: Midwestern University Chicago College of Pharmacy, Downers Grove, IL, USA sharpe@midwestern.edu.
authors: Spencer E
authors: SE
authors: Harpe
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D010024:Osteoporosis / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D012306:Risk
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: bisphosphonates; drug interactions; drug-induced disorders; medication-induced osteoporosis; osteoporosis; pharmacoepidemiology