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Bone fractures are a risk to be considered when choosing the oral anticoagulant for a patient with non-valvular atrial fibrillation (Afib), a study suggested.

The risk of poor osteoporotic outcomes was significantly lower with direct oral anticoagulant (DOAC) compared with vitamin K antagonist (VKA) therapy, as follows:

• Any fracture: 3.09% vs 3.77% (adjusted HR 0.85, 95% CI 0.74-0.97)

• Major osteoporotic fractures: 2.29% vs 2.82% (adjusted HR 0.85, 95% CI 0.72-0.99)

• Initiation of osteoporosis medication: 2.44% vs 3.14% (adjusted HR 0.82, 95% CI 0.71-0.95)

• Any fracture or starting osteoporosis medication: 5.21% vs 6.43% (adjusted HR 0.84, 95% CI 0.76-0.93)

"Because of a more favorable skeletal health profile, DOAC treatment could be preferred to VKA in patients with Afib with strong risk factors for osteoporotic fractures," said Casper Binding, BMedSc, of Copenhagen University Hospital Herlev and Gentofte in Denmark, and colleagues.

As the team noted in the study online in the , VKAs like warfarin (Coumadin) have been widely used for stroke prophylaxis for decades. The newer DOACs have been shown to have efficacy similar to that of warfarin in preventing stroke in Afib and do not require international normalized ratio (INR) monitoring, Binding and colleagues explained.

Using data from the Danish National Patient Register, the investigators identified 37,350 people with non-valvular Afib as having had no prior use of osteoporosis medication and having undergone 180 days of oral anticoagulation with a VKA or a DOAC, including dabigatran, rivaroxaban, apixaban, or edoxaban.

Two-thirds of the cohort received DOAC rather than VKA treatment. The DOAC group was significantly older; included more women; and were more often on hormone-replacement therapy and to have had previous fractures, stroke, or a diagnosis of alcohol abuse.

"Studies suggest a link between warfarin and undercarboxylated osteocalcin, which is associated with low bone mineral density," the researchers wrote. "These results correlate with findings that propose a connection between warfarin and an increased risk of osteoporotic fractures."

Then there is the theory that dietary restrictions around VKA treatment could lead to low folic acid intake and a resulting risk of hyperhomocysteinemia, which can reduce bone strength, the researchers continued, adding that in the end, the main results are in line with those of a of Chinese patients.

"The results of our study not only support what other studies have suggested, but also more importantly they show that the risk reductions apply to nationwide data from a Western society and persist when all DOACs are analyzed and compared with VKA," the investigators said.

They noted that their analysis may be subject to residual confounding from unmeasured variables such as INR, body mass index (BMI), hemoglobin, and renal function.

Writing in an , Brian Gage, MD, MSc, of Washington University in St. Louis, Missouri, said: "Because patients with low creatinine clearance or low BMI are both more likely to have an osteoporotic fracture and to be prescribed a VKA rather than a DOAC, residual confounding could have exaggerated the association between VKA and fracture."

"Thus, at least for patients who have Afib and no prior osteoporotic fracture (the population studied), the decision to prescribe a VKA or a DOAC should depend on the risks of ischemic stroke, hemorrhage, need for monitoring, and affordability rather than on the risk of osteoporotic fracture," Gage argued.

In summary, he said, the researchers "had a strong biochemical basis to search for a link between VKAs and osteoporotic fracture. Their well-done observational study provides additional evidence of this link, but residual confounding may have exaggerated the association."