A recent study found that abnormal vitamin B12 levels, including both deficiencies and high levels, were associated with a higher risk of fractures in adults over 50. The research, published in the journal Scientific Reports, analyzed data from over 1.8 million patients with normal vitamin B12 levels and 115,735 patients with vitamin B12 deficiency.
The study’s findings suggest that vitamin B12 may play a role in bone health and fracture risk, but the relationship is complex and not fully understood. Vitamin B12 is essential for cell division and neurological function, and deficiency may contribute to skeletal fragility and increase susceptibility to falls.
Vitamin B12 and Fracture Risk
Researchers used electronic health records to compare the vitamin B12 levels of patients with fractures to those without fractures. They found that patients with vitamin B12 deficiency had a 33% higher risk of fractures compared to patients with normal vitamin B12 levels. Additionally, patients with borderline and high vitamin B12 levels also had an increased risk of fractures, although the associations were weaker.
The study’s results are biologically plausible, as vitamin B12 is involved in homocysteine metabolism, which is associated with bone health. However, the observational design of the study means that it cannot establish causality between vitamin B12 deficiency and fractures. The authors note that unmeasured factors may still have influenced the association, and that vitamin B12 status was only measured at baseline and not updated during follow-up.
The study’s population was limited to patients who had undergone clinically indicated vitamin B12 testing, which may not be representative of the wider population. They also note that bone mineral density measurements were unavailable, and that potentially important factors such as vitamin D and calcium levels, muscle strength, and physical activity could not be fully accounted for.
Despite these limitations, the study’s findings suggest that vitamin B12 deficiency may be a potential marker for fracture risk in adults over 50. The researchers found that the association between vitamin B12 deficiency and fracture risk was consistent across different sensitivity analyses and subgroup analyses. However, further prospective studies are needed to establish causality and determine whether vitamin B12 supplementation can reduce the risk of fractures.
The study’s results also highlight the importance of considering the complex relationships between vitamin B12, bone health, and fracture risk. The authors note that the association between vitamin B12 deficiency and fracture risk may be influenced by a range of factors, including underlying health conditions, medications, and lifestyle factors. As the population ages, understanding these relationships will become increasingly important for preventing and treating fractures.
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In the study, the researchers used a propensity score-matched cohort to compare the outcomes of patients with vitamin B12 deficiency to those with normal vitamin B12 levels. The cohort was matched according to a range of demographic and clinical characteristics, including age, sex, and comorbidities. The researchers found that the matched cohort had similar baseline characteristics, but that the follow-up period was shorter in the vitamin B12-deficient group.
Study Methodology
The study used data from the TriNetX Global Collaborative Network, which includes electronic health records from multiple healthcare organizations. The researchers applied initial eligibility criteria to select patients who had undergone vitamin B12 testing between 2016 and 2023 and had at least one healthcare visit during the previous five years. Patients were then grouped according to their vitamin B12 concentrations, with deficiency defined as 199 pg/mL or less.
They used a one-year landmark design to reduce the possibility that an existing or imminent fracture influenced vitamin B12 testing. Participants had to be alive and free of fracture, osteoporosis, and repeated falls when outcome follow-up began. The researchers tracked incident fractures across multiple parts of the body as the primary outcome, and also analyzed secondary outcomes including lower-limb and osteoporotic fractures, osteoporosis without fracture, all-cause falls, and repeated falls.
The adjusted analysis found that the fracture hazard was 33% higher among patients who remained alive and under observation in the deficiency group.
Further analysis of the study’s results revealed that the association between vitamin B12 deficiency and fracture risk was strongest among patients aged 50–65 years. The researchers found that this age group had a higher hazard of fractures compared to those above 65. However, the association was not significant in other subgroups, including sex, obesity, or proton pump/metformin use.
Limitations and Future Directions
The study was published in the journal Scientific Reports, with the DOI: https://doi.org/10.1038/s41598-026-74010-8, and is available online at https://www.nature.com/articles/s41598-026-74010-8. The researchers concluded that their findings add to the existing knowledge on the relationship between vitamin B12 and fracture risk, but that further research is needed to fully understand this complex relationship. The study ended with 115,735 patients in each of the B12-deficient and normal-B12 groups.