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SAPC 2013 , Nottingham

Exposure to bisphosphonates and risk of non-gastrointestinal cancers: nested case-control studies . Yana Vinogradova , Carol Coupland, Julia Hippisley-Cox. SAPC 2013 , Nottingham. Background. Bone loss and bisphosphonates Laboratory linkages with reduced cancer risk

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SAPC 2013 , Nottingham

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  1. Exposure to bisphosphonates and risk of non-gastrointestinal cancers: nested case-control studies Yana Vinogradova, Carol Coupland, Julia Hippisley-Cox SAPC 2013 , Nottingham

  2. Background Bone loss and bisphosphonates Laboratory linkages with reduced cancer risk Anti-tumor properties, accumulation in different organs Treatment for osteoporosis and cancer risk • Reduced risk of breast cancer • Chlebowski (2010) 1993-1998 • Newcomb (2010) 2003-2006 • Rennert (2010) 2000-2006 • Vestergaard (2011) 1996-2006 • No associations for other cancers • Cardwell (2011) 1996-2006

  3. QResearch • EMIS • 660 GP practices • Clinical Practice Research Datalink • Main (EHR)-IT • 643 GP practices Patient level data from GP clinical records Anonymised Longitudinal data for 20+ years Validated externally and internally Industry independent

  4. Methods: Study design Nested case control study Study period Jan 1997 – July 2011 Aged 50 – 100 At least 2 years of records Up to 5 controls matched by Age Sex Practice Calendar year

  5. Methods: Assessment of Exposure excluding 6 months before the index date use: at least 1 script short-term (<12m), long-term users different types of bisphosphonates

  6. Methods: Confounding factors BMI, ethnicity, smoking, alcohol Osteoporosis Morbidities (rheumatoid arthritis, diabetes, benign breast disease, GI disorders, hypertension) Family history of cancers Other medications (NSAIDs, corticosteroids, acid-lowering drugs, vitamin D, HRT)

  7. Methods: Statistical analysis Multiple imputations Conditional logistic regression Combined analysis Odds ratios + 95% CI 1% significance level

  8. QRESEARCH CPRD 4.2% users 4.2% users • Cases: exposed total • Breast 1304 24,489 • Prostate 460 26,554 • Lung 1035 17,961 • Bladder 274 7,464 • Melanoma 241 4,998 • Ovary 204 3,427 • Pancreas 178 3,593 • Uterus 99 2,248 • Cervix 32 822 • Cases: exposed total • Breast 1324 25,444 • Prostate 376 23,176 • Lung 1114 19,059 • Bladder 280 7,084 • Melanoma 178 4,621 • Ovary 170 3,088 • Pancreas 196 3,485 • Uterus 96 2,149 • Cervix 35 739

  9. Any use of bisphosphonates and risk of cancer CPRD QResearch

  10. Any use of bisphosphonates and risk of cancer, combined analysis P-trend=0.2 P=0.004 P=0.003 P-trend=0.005 P=0.003 P-trend=0.02

  11. Prostate cancer: long-term use of bisphosphonates

  12. Prostate cancer: types of bisphosphonates CPRD QResearch P=0.004 Ptrend=0.009

  13. Summary of findings Use of bisphosphonates is not associated with increased risk of any of the most common cancers Decreased risk of breast, prostate and pancreatic cancers had no duration relationship in either database Decreased risk of prostate cancer associated with alendronate use only in QResearch

  14. Residual confounding as no information on stage of cancer on any cancer-related tests on bone density test Information on prescriptions only Missing data Limitations and Strengths • Large sample size and representative population • Data electronically collected – unlikely misclassification bias • Data collected before diagnosis – no recall bias • All cases used – no selection bias • Data in the last 6 months before the diagnosis was excluded as might be misleading • Based on the most recent data

  15. Thank you Questions?

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