title: Predictors of fracture while on treatment with oral bisphosphonates: a population-based cohort study.
abstract: Although oral bisphosphonates (BPs) are highly effective in preventing fractures, some patients will fracture while on treatment. We identified predictors of such fractures in a population-based cohort of incident users of oral BPs. We screened the Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP) database to identify new users of oral BPs in 2006-2007. SIDIAP includes pharmacy invoice data and primary care electronic medical records for a representative 5 million people in Catalonia (Spain). Exclusion criteria were the following: Paget disease; <40 years of age; and any antiosteoporosis treatment in the previous year. A priori defined risk factors included age, gender, body mass index, vitamin D deficiency, smoking, alcohol drinking, preexisting comorbidities, and medications. Fractures were considered if they appeared at least 6 months after treatment initiation. "Fractures while on treatment" were defined as those occurring among participants persisting for at least 6 months and with an overall high compliance (medication possession ratio ≥80%). Fine and Gray survival models accounting for competing risk with therapy discontinuation were fitted to identify key predictors. Only 7449 of 21,385 (34.8%) participants completed >6 months of therapy. Incidence of fracture while on treatment was 3.4/100 person-years (95% confidence interval [CI], 3.1-3.7). Predictors of these among patients persisting and adhering to treatment included: older age (subhazard ratio [SHR] for 60 to <80 years, 2.18 [95% CI, 1.70-2.80]; for ≥80 years, 2.5 [95% CI, 1.82-3.43]); previous fracture (1.75 [95% CI, 1.39-2.20] and 2.49 [95% CI, 1.98-3.13], in the last 6 months and longer, respectively); underweight, 2.11 (95% CI, 1.14-3.92); inflammatory arthritis, 1.46 (95% CI, 1.02-2.10); use of proton pump inhibitors (PPIs), 1.22 (95% CI, 1.02-1.46); and vitamin D deficiency, 2.69 (95% CI, 1.27-5.72). Even among high compliers, 3.4% of oral BP users will fracture every year. Older age, underweight, vitamin D deficiency, PPI use, previous fracture, and inflammatory arthritides increase risk. Monitoring strategies and/or alternative therapies should be considered for these patients.
authors.affiliation: Unitat de Recerca en Fisiopatologia Òssia i Articular (URFOA-IMIM) and Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), Parc de Salut Mar, Barcelona, Spain; National Institute for Health Research (NIHR) Biomedical Research Unit, Musculoskeletal Epidemiology Group, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK; Grup de Recerca en Malalties Prevalents de l'Aparell Locomotor (GREMPAL) Research Group, Institut d'Investigació en Atenció Primària (IDIAP) Jordi Gol Primary Care Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Medical Research Council (MRC) Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Prieto-Alhambra
authors.forename: Aina
authors.initials: A
authors.lastname: Pagès-Castellà
authors.forename: Gemma
authors.initials: G
authors.lastname: Wallace
authors.forename: M Kassim
authors.initials: MK
authors.lastname: Javaid
authors.forename: Andrew
authors.initials: A
authors.lastname: Judge
authors.forename: Xavier
authors.initials: X
authors.lastname: Nogués
authors.forename: Nigel K
authors.initials: NK
authors.lastname: Arden
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.forename: Adolfo
authors.initials: A
authors.lastname: Diez-Perez
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015331:Cohort Studies; D016208:Databases, Factual; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000517:prevention & control; D006620:Hip Fractures / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D054328:Proton Pump Inhibitors / Q000009:adverse effects; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D013851:Thinness; D014808:Vitamin D Deficiency / Q000150:complications
chemical_list: D004164:Diphosphonates; D054328:Proton Pump Inhibitors
keywords: BISPHOSPHONATES; BONE; EPIDEMIOLOGY; FRACTURES