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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Quan H, Li B, Couris CM, Fushimi K, Graham P, Hider P, Januel JM, Sundararajan V (2011) Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 173(6):676–682
NICE (2017) Bisphosphonates for treating osteoporosis. National Institute for Health and Clinical Excellence, London
NICE (2012) Osteoporosis: Assessing the risk of fragility fracture. National Institute for Health and Clinical Excellence, London
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):818–839
Reid IR, Bolland MJ, Grey A (2014) Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 383(9912):146–155
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):1600–1612
Chung M, Tang AM, Fu Z, Wang DD, Newberry SJ (2016) Calcium intake and cardiovascular disease risk: an updated systematic review and meta-analysis. Ann Intern Med 165(12):856–866
Ford JA et al (2014) Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr 100(3):746–755
Vestergaard P, Schwartz K, Pinholt EM, Rejnmark L, Mosekilde L (2011) Stroke in relation to use of raloxifene and other drugs against osteoporosis. Osteoporos Int 22(4):1037–1045
Christensen S, Mehnert F, Chapurlat RD, Baron JA, Sørensen HT (2011) Oral bisphosphonates and risk of ischemic stroke: a case-control study. Osteoporos Int 22(6):1773–1779
Kang JH, Keller JJ, Lin HC (2012) A population-based 2-year follow-up study on the relationship between bisphosphonates and the risk of stroke. Osteoporos Int 23(10):2551–2557
Sharma A, Einstein AJ, Vallakati A, Arbab-Zadeh A, Walker MD, Mukherjee D, Homel P, Borer JS, Lichstein E (2014) Risk of atrial fibrillation with use of oral and intravenous bisphosphonates. Am J Cardiol 113(11):1815–1821
Sharma A, Chatterjee S, Arbab-Zadeh A, Goyal S, Lichstein E, Ghosh J, Aikat S (2013) Risk of serious atrial fibrillation and stroke with use of bisphosphonates: evidence from a meta-analysis. Chest 144(4):1311–1322
Kranenburg G, Bartstra JW, Weijmans M, de Jong PA, Mali WP, Verhaar HJ, Visseren FLJ, Spiering W (2016) Bisphosphonates for cardiovascular risk reduction: a systematic review and meta-analysis. Atherosclerosis 252:106–115
Kim DH, Rogers JR, Fulchino LA, Kim CA, Solomon DH, Kim SC (2015) Bisphosphonates and risk of cardiovascular events: a meta-analysis. PLoS One 10(4):e0122646
Correa A, Hinton W, McGovern A, van Vlymen J, Yonova I, Jones S, de Lusignan S (2016) Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) sentinel network: a cohort profile. BMJ Open 6(4):e011092
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–e40
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):e020282
Knol MJ, Vandenbroucke JP, Scott P, Egger M (2008) What do case-control studies estimate? Survey of methods and assumptions in published case-control research. Am J Epidemiol 168(9):1073–1081
Team, R (2018) RStudio: Integrated development for R. RStudio, B. Inc., MA URL, ed
T, T (2015) A Package for Survival Analysis in S_ version 2:38
Fitzpatrick T et al How do neurologists diagnose transient ischemic attack: a systematic review. Int J Stroke. https://doi.org/10.1177/1747493018816430
Caffarelli C, Montagnani A, Nuti R, Gonnelli S (2017) Bisphosphonates, atherosclerosis and vascular calcification: update and systematic review of clinical studies. Clin Interv Aging 12:1819–1828
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 7:381–389
Park J-H et al (2017) Compliance and persistence with oral bisphosphonates for the treatment of osteoporosis in female patients with rheumatoid arthritis. BMC Musculoskelet Disord 18(1):152
Paskins Z, Warburton L (2016) Bisphosphonates beyond five years. BMJ 352:i264
The authors declare no competing financial interests.
Conflict of interest
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Asghar, Z., Godoy Caballero, A., Pathirannehelage, S. et al. Saving bones without risking brain—bisphosphonates and risk of stroke: matched case-control study. Osteoporos Int 30, 1845–1854 (2019). https://doi.org/10.1007/s00198-019-05045-z
- Electronic clinical-patient dataset
- Nested matched case-control study