Warfarin use and fracture risk: an evidence-based mechanistic insight

An evidence-based perspective on warfarin and the growing skeleton

“…Of note, osteoblast-specific GGCX-deficient mice have higher bone mass compared to their controls [15]. This is consistent with higher bone mass in osteocalcindeficient mice because warfarin decreases osteocalcin content in bone, as described previously [6]. Indeed, warfarin use could impair mineral-related bone quality but the mild reduction of bone material stiffness can be compensated by skeletal adaptation to mechanical loading [16], which might explain a small, but statistically significant increase in areal bone mineral density (BMD) in the lumbar spine among warfarin users [17].…”

“…There is also debate on the potential adverse effect of warfarin on the skeleton in adults [4], but it has been recently suggested that warfarin use does not cause fragility fractures, especially in the hip [5][6][7]. This suggestion would be supported by the latest meta-analysis [8], although further research could be required [9,10]; in longitudinal studies, use of vitamin K antagonists was associated with the increased incidence of total and hip fractures (risk ratio 1.09, 95 % confidence interval 1.01 to 1.18 and 1.17, 1.05 to 1.31, respectively), but this association was not confirmed in those used variables for matching between vitamin K antagonist and control groups (1.03, 0.90 to 1.18 and 1.13, 0.96 to 1.34) [8].…”

Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation

“…First, although mechanism for any deleterious effect of dabigatran on bone has not been identified, 24 the mechanism of action of warfarin may interfere with processes that contribute to bone formation. 1 Warfarin antagonizes vitamin K-dependent processes including the γ-carboxylation of osteocalcin and other bone matrix proteins that are required in bone mineralization. 1 Previous studies have demonstrated an increased level of undercarboxylated osteocalcin in warfarin users 3 and its association with reduced bone mineral density and increased fracture risk.…”

“…1 Warfarin antagonizes vitamin K-dependent processes including the γ-carboxylation of osteocalcin and other bone matrix proteins that are required in bone mineralization. 1 Previous studies have demonstrated an increased level of undercarboxylated osteocalcin in warfarin users 3 and its association with reduced bone mineral density and increased fracture risk. 25 In contrast, the mechanism of dabigatran is independent of vitamin K and theoretically does not interfere with bone metabolism.…”

Oral anticoagulation and hip fracture risk: a common misconception?

“…Considering results in the above-mentioned study [2] that the percentage of the patients with osteoporosis was lower in VKA resumption (18.2%) than in NOAC resumption (26.2%), there might have been a common misconception that use of VKAs such as warfarin increases the risk of hip fracture. However, it is important to note that accumulating evidence consistently indicates that warfarin use does not result in an increased risk of hip fracture [3][4][5][6]. Although data regarding NOACs are limited, the first metaanalysis of 12 randomized controlled trials including 44 816 patients receiving NOACs and 44 733 patients receiving warfarin [7] found that relative risks (RRs) of NOACs versus warfarin about hip fracture and femoral neck fracture were 0.99 (95% CI 0.72-1.34) and 1.00 (95% CI 0.66-1.51), respectively, suggesting that use of NOACs as well as VKAs does not influence the risk of hip fracture.…”