An observational study of musculoskeletal pain among patients receiving bisphosphonate therapy.
OBJECTIVE
To seek evidence for the association of bisphosphonate use with diffuse musculoskeletal pain (MSKP) in a large national cohort, controlling for conditions associated with MSKP.


METHODS
This retrospective cohort study enrolled all US veterans aged 65 years or older with a vertebral or hip fracture who were treated for at least 1 year between October 1, 1998, and September 30, 2006 (N=26,545). All International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes, demographics, and pharmaceutical data were obtained from national databases. A composite end point, based on ICD-9-CM codes compatible with diffuse MSKP, was constructed. The primary outcome was time until MSKP. We performed regression analysis using the Cox proportional hazards model, controlling for age, sex, race, alcoholism, depression, anxiety, smoking, recent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use, rheumatic disease, and comorbidity score.


RESULTS
The univariate regression identified an association of bisphosphonate exposure and MSKP (hazard ratio, 1.22; 95% confidence interval, 1.04-1.44). In the multivariate regression, however, patients prescribed a bisphosphonate were not more likely to be assigned an ICD-9-CM code compatible with diffuse MSKP (hazard ratio, 1.10; 95% confidence interval, 0.93-1.30). Consistent with prior studies, we found that female sex, depression, anxiety, comorbidity score, and the presence of a rheumatic disease were all associated with a greater risk of a diagnosis of diffuse MSKP. There was no demonstrable association with statin exposure.


CONCLUSIONS
Bisphosphonate use was not associated with a statistically higher rate of MSKP in this cohort. Individual patients may rarely report MSKP while taking bisphosphonates; however, for our studied cohort, incident MSKP does not appear to explain bisphosphonate discontinuation rates.
Department of Medicine, Denver Veterans Affairs Medical Center, University of Colorado Denver, Denver, CO 80045, USA. liron.caplan@ucdenver.edu
Liron
L
Caplan
Cory B
CB
Pittman
Angelique L
AL
Zeringue
Jeffrey F
JF
Scherrer
Kent R
KR
Wehmeier
Francesca E
FE
Cunningham
Seth A
SA
Eisen
Jay R
JR
McDonald
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006620:Hip Fractures / Q000188:drug therapy; D006801:Humans; D008297:Male; D009140:Musculoskeletal Diseases / Q000139:chemically induced* / Q000453:epidemiology; D010024:Osteoporosis / Q000188:drug therapy; D010146:Pain / Q000139:chemically induced* / Q000453:epidemiology; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
D050071:Bone Density Conservation Agents; D004164:Diphosphonates