Saving bones without risking brain—bisphosphonates and risk of stroke: matched case-control study
We investigated the association between bisphosphonate treatment and the risk of stroke using a large routine clinical dataset. We found no association between bisphosphonate treatment and risk of stroke, after adjusting for large number of clinical and demographic confounders.
There is conflicting evidence on the link between bisphosphonates and stroke with studies variously showing increased, decreased or unchanged risk. We investigated the association between bisphosphonate treatment and the risk of stroke using a large routine clinical dataset.
We used a matched nested case-control study design analysing routinely collected electronic data from patients registered at primary care practices in England participating in the Royal College of General Practitioners Research and Surveillance Centre. Cases were patients aged 18 years or over, either living or dead, recorded as having had a stroke in the period 1 January 2005 to 31 March 2016. Each case was matched to one control according to age, sex, general practice attended and calendar time. Data were analysed using Stata, version 14.2. and RStudio, version 1.1.463. Conditional logistic regression was used to determine odds ratios for stroke according to bisphosphonate treatment and duration in cases compared with controls. We adjusted for disease risk groups, cardiovascular risk factors, treatments, smoking status, alcohol consumption, ethnicity, bisphosphonate types, fracture and socioeconomic status using IMD (Index of Multiple Deprivation).
We included 31,414 cases of stroke with an equal number of matched controls. Overall, 83.2% of cases and controls were aged 65 years or older, and there were similar proportions of females (51.5%) and males (48.5%). Bisphosphonate treatment was not associated with stroke after adjusting for the wide range of confounders considered (OR 0.86, 95% CI 0.62–1.19).
We found no association between bisphosphonate treatment and risk of stroke, after adjusting for other confounders.
KeywordsBisphosphonates Electronic clinical-patient dataset Fracture Nested matched case-control study ONJ Stroke
The authors declare no competing financial interests.
Compliance with ethical standards
Conflict of interest
- 2.NICE (2017) Bisphosphonates for treating osteoporosis. National Institute for Health and Clinical Excellence, LondonGoogle Scholar
- 3.NICE (2012) Osteoporosis: Assessing the risk of fragility fracture. National Institute for Health and Clinical Excellence, LondonGoogle Scholar
- 4.Qaseem A, Forciea MA, McLean RM, Denberg TD, for the Clinical Guidelines Committee of the American College of Physicians (2017) Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med 166(11):818–839CrossRefPubMedGoogle Scholar
- 6.Kahwati LC, Weber RP, Pan H, Gourlay M, LeBlanc E, Coker-Schwimmer M, Viswanathan M (2018) Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: evidence report and systematic review for the US preventive services task force. JAMA 319(15):1600–1612CrossRefPubMedGoogle Scholar
- 17.de Lusignan S, Correa A, Pathirannehelage S, Byford R, Yonova I, Elliot AJ, Lamagni T, Amirthalingam G, Pebody R, Smith G, Jones S, Rafi I (2017) RCGP Research and Surveillance Centre annual report 2014-2015: disparities in presentations to primary care. Br J Gen Pract 67(654):e29–e40CrossRefPubMedGoogle Scholar
- 18.Hinton W, McGovern A, Coyle R, Han TS, Sharma P, Correa A, Ferreira F, de Lusignan S (2018) Incidence and prevalence of cardiovascular disease in English primary care: a cross-sectional and follow-up study of the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). BMJ Open 8(8):e020282CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Team, R (2018) RStudio: Integrated development for R. RStudio, B. Inc., MA URL, edGoogle Scholar
- 21.T, T (2015) A Package for Survival Analysis in S_ version 2:38Google Scholar
- 22.Fitzpatrick T et al How do neurologists diagnose transient ischemic attack: a systematic review. Int J Stroke. https://doi.org/10.1177/1747493018816430
- 24.Christensen DH, Horváth-Puhó E, Schmidt M, Christiansen CF, Pedersen L, Langdahl BL, Thomsen RW (2015) The impact of preadmission oral bisphosphonate use on 30-day mortality following stroke: a population-based cohort study of 100,043 patients. Clin Epidemiol 7:381–389CrossRefPubMedPubMedCentralGoogle Scholar