Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin 

SLR - April 2023 - Terry Ng 

Title: Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin 

Reference: Nalevaiko JZ, Marques JVO, Oliveira MF, Raetsch AWP, Marques GL, Petterle RR, Moreira CA, Borba VZC. Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin. Bone. 2021 Sep;150:116000. doi: 10.1016/j.bone.2021.116000. Epub 2021 May 8. PMID: 33971316. 

Level of Evidence: Level III 

Scientific Literature Review 

Reviewed By: Terry Ng 

Residency Program: Mercy Health – St. Rita’s Medical Center 

Podiatric Relevance: Anticoagulation is frequently seen in podiatric surgical patients. This article compares commonly used anticoagulants in terms of their effect on bone healing and fracture risk. 

Methods: Cross-sectional observational study was performed in 150 patients aged 35-70 years . Fifthy patients were on warfarin over 1 year, 50 patients on DOACs over 1 year, and 50 patients in the control group. Primary outcome measures were assessed using DXA scan to measure bone mineral density and trabecular bone score at the spine, hip, and femoral neck. 

Results: Low bone mass was found in 42%, 50%, and 66% of patients in the control, DOAC, and warfarin groups respectively. The difference between groups was significant with a p-value of 0.012. Mean trabecular bone score was found to be 1.328, 1.264, and 1.203 in the control, DOAC, and warfarin groups, respectively, with a p-value of <0.001. In the DOAC and warfarin groups, TBS was negatively correlated with BMI. No correlation was observed between bone quality and prior duration of anticoagulant use.  

Conclusions: The authors of this paper found that prolonged use of oral anticoagulants was associated with worse bone mineral density and trabecular bone score, which was worse with patients on warfarin compared to those on DOACs. They attribute this difference to the negative effects of vitamin K inhibition on bone metabolism. The authors did not find any significant association of classic risk factors for low bone mass such as sex, race, and age with measured bone mineral density in this study. BMI, however, was found to have a protective effect on bone density. Although previous literature has correlated an increased risk of fracture with warfarin use, this is the first study to quantify these effects in terms of bone density and trabecular bone score. The authors state that this paper reinforces the presence of harmful effects of warfarin on bone metabolism while also showing that these effects are reduced with DOACs. 

In the context of podiatric medicine, the main conclusion to be taken from this paper is that oral anticoagulation, be it DOACs or warfarin, can have a negative effect on bone healing and fracture risk. Knowledge of this fact is relevant due to the large patient population on long term anticoagulation for various comorbidities,as well as the prevalent use of anticoagulation perioperatively. Knowing that these patients are at increased risk of fracture, podiatric physicians can better account for this effect and take precautions if needed.