Long-term treatment with sodium warfarin results in decreased femoral bone strength and cancellous bone volume in rats

Simon, Ryan; Beaudin, Suzanne; Johnston, Marilyn; Walton, Kimberly J.; Shaughnessy, Stephen G.

doi:10.1016/s0049-3848(02)00035-x

Cited by 34 publications

(17 citation statements)

References 32 publications

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“…Oral anticoagulants such as sodium warfarin are widely used in patients with mechanical heart valves as prophylaxis of thrombosis. Although the most common side‐effect associated with the use of warfarin is bleeding, other non‐hemorrhagic side‐effects including skin necrosis and deleterious effects on bone are reported 16,17 …”

Section: Discussionmentioning

confidence: 99%

Reduced bone density in patients on long‐term warfarin

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Reduced bone density in patients on long‐term warfarin

et al. 2009

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“…Indeed the mean intake of our patients even with such a supplement, based on our dietary assessments in our Newcastle population, would still be lower than the mean intake of 245 μ g/d reported in Dutch adults aged 65 years and over (Schurgers et al , 1999). Although any subsequent increase in warfarin dose requirement following vitamin K supplementation offers the theoretical possibility of pathological effects on bone and the arterial system by greater inhibition of the gamma‐carboxylation systems in bone and the arterial wall (Howe & Webster, 2000; Simon et al , 2002), it is anticipated that the increase would be small and the revised dosing regimen well within the therapeutic warfarin dose range. An investigation of the effect of vitamin K supplementation with warfarin in patients whose control is, without apparent explanation, unstable is therefore warranted.…”

Section: Discussionmentioning

confidence: 99%

Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin

Khan¹,

Wynne²,

Wood³

et al. 2004

Br J Haematol

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SummaryThe relationship between dietary intake of vitamin K, fat, plasma vitamin K concentrations and anticoagulation response to warfarin within individuals, as well as the contribution of dietary vitamin K to differences in warfarin dose requirements between individuals were investigated in 53 patients on warfarin therapy who had stably controlled anticoagulation. Each patient completed a dietary record of all foods consumed on a daily basis for 4 weeks. Each week a blood sample was taken for measurement of the international normalized ratio (INR), plasma vitamin K, triglycerides and warfarin enantiomer concentrations. The patients' genotype for CYP2C9 was also determined. Regression analysis of the data showed that, for each increase of 100 lg in the daily dietary intake of vitamin K averaged over 4 d, the INR was reduced by 0AE2. There was no correlation between warfarin daily dose and average daily dietary vitamin K intake when calculated over 28 d. The regression model for warfarin dose showed that, while dietary vitamin K had no effect, CYP2C9 genotype (P ¼ 2%) and age (P < 1%) significantly contributed to inter-patient variability in warfarin dose requirements. A consistent intake of vitamin K could reduce intrapatient variability in anticoagulation response and thus improve the safety of warfarin therapy.

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“…Compared to individuals without AF, those with AF experience accelerated rates of cognitive decline and have a higher burden of covert brain infarctions and white matter abnormalities, which have been linked to impaired gait, and increased risk of falls and hip fractures [5-7]. In addition, warfarin, an anticoagulant used to prevent stroke, has been associated with reduced bone mineral density [8]. Warfarin use has been associated with a higher risk of fracture in some [9], but not all [10], observational studies.…”

Section: Introductionmentioning

confidence: 99%

Incident atrial fibrillation and the risk of fracture in the cardiovascular health study

et al. 2016

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In this prospective cohort of 4462 older adults, incident atrial fibrillation (AF) was not statistically significantly associated with subsequent risk of incident fracture. Purpose AF is associated with stroke, heart failure, dementia, and death, but its association with fracture is unknown. Therefore, we examined the association of incident AF with the risk of subsequent fracture in the Cardiovascular Health Study (CHS) cohort. Methods 4462 CHS participants aged ≥65 years were followed between 1991 and 2009, mean follow up 8.8 years. Incident AF was identified by annual study ECG, hospital discharge diagnosis codes, or Medicare claims. Fractures of the hip, distal forearm, humerus, or pelvis were identified using hospital discharge diagnosis codes or Medicare claims. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between incident AF (time-varying) and the risk of subsequent fracture. We also evaluated whether AF was associated with risk of sustaining a fall. Results Crude incident fracture rate was 22.9 per 1,000 person-years in participants with AF and 17.7 per 1,000 person-years in participants without AF. Individuals with incident AF were not at significantly higher risk of hip fracture (adjusted HR=1.09, 95% CI 0.83, 1.42) or fracture at any selected site (adjusted HR=0.97, 95% CI 0.77, 1.22) or risk of sustaining a fall (adjusted HR=1.00, 95% CI=0.87-1.16) compared with those without AF. Conclusion In this cohort of older, community-dwelling adults, incident AF was not shown to be associated with falls or hip or other fractures.

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Long-term treatment with sodium warfarin results in decreased femoral bone strength and cancellous bone volume in rats

Cited by 34 publications

References 32 publications

Reduced bone density in patients on long‐term warfarin

Reduced bone density in patients on long‐term warfarin

Dietary vitamin K influences intra‐individual variability in anticoagulant response to warfarin

Incident atrial fibrillation and the risk of fracture in the cardiovascular health study

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