A two-sample MR study was conducted utilizing the publicly available GWAS summary dataset to investigate the reciprocal causal relationship between the frailty index and low back pain. The MR analysis revealed a bidirectional causal relationship, where frailty increased the risk of developing low back pain, and low back pain, in turn, contributed to an increase in the frailty index. This study is the first to assess the causal relationship between frailty and low back pain using MR methodology. These findings provide a theoretical basis for the development of management strategies targeting frailty and low back pain in elderly patients.
Frailty and low back pain are common issues in older adults that can severely impact their quality of life and overall health. Numerous epidemiological studies have examined the association between these two conditions. For instance, a 12-month longitudinal study involving 165 older adults suffering from low back pain revealed that over two-thirds of the participants were classified as being either pre-frail or frail. Furthermore, the researchers observed that frailty was significantly linked with increased disability in older adults affected by low back pain [23]. A longitudinal observational study of older adults in Brazil revealed a significant correlation between the degree of low back pain and frailty [24]. Additionally, a prospective cohort study involving 602 individuals revealed that physical frailty was associated with increased pain intensity, lower scores in both physical and psychological aspects of quality of life, and higher disability scores among individuals with low back pain [12]. It is important to acknowledge that prior research has been limited in its ability to determine causation of the relationship between debility and low back pain due to the susceptibility of observational studies to reverse causation and confounding variables. Our current study provides additional support of a reciprocal causal effect between debility and low back pain, using a MR approach which is less susceptible to confounding bias than traditional observational designs.
Several potential factors may explain the bidirectional causal relationship between frailty and low back pain. First, frailty may lead to undesirable consequences such as falls, reduced endurance and altered morphology of the lumbar paravertebral muscles, and ultimately low back pain [25, 26]. Additionally, frailty can lead to factors such as inadequate nutrition, sleep and mood disorders, increased healthcare expenses, and reduced social interaction, which may also contribute significantly to the development of low back pain [27–29]. Conversely, mood and sleep disorders related to low back pain may also increase the risk of frailty [30]. Low back pain has also been linked to cognitive impairment, which may further contribute to the development of frailty [31, 32]. Moreover, treatments that are effective for debilitation and low back pain can have synergistic benefits. For instance, physical activity not only enhances physical function in older and vulnerable populations, but also reduces pain and disability while improving quality of life in individuals with low back pain [33, 34]. Therefore, the bidirectional relationship between debilitation and low back pain is not a random occurrence, and all of these findings provide support for this hypothesis. The current etiological model of the bidirectional causal relationship between frailty and low back pain is too intricate to attribute to one or a few factors. Hence, additional research is imperative to investigate the specific mechanisms that underlie the bidirectional causality between frailty and low back pain.
The discovery of this bidirectional mutual relationship has significant implications for public health and clinical practice. Debility and low back pain are reversible disorders with numerous modifiable factors. A bidirectional causal relationship between debility and low back pain implies that frailty and low back pain in older adults can result in physical health issues and a cascade of adverse outcomes, establishing a vicious cycle. Hence, continuous early screening for frailty and low back pain in older adults is necessary, along with the development of interventions that address shared risk factors to prevent these conditions, mitigate associated adverse outcomes, and enhance the quality of life for older adults.
The present study aimed to elucidate the bidirectional causal relationship between debilitation and low back pain, and it highlights the following key aspects. Firstly, this study is the first of its kind to investigate the causal relationship between debilitation and low back pain utilizing a comprehensive GWAS pooled dataset. Secondly, our study employed multiple sensitivity analyses to test the hypotheses, thus enhancing the reliability of our results to a certain extent. Lastly, we employed MR analysis methods to minimize the impact of confounding factors, resulting in more accurate estimates in this study. There are limitations associated with our findings. Specifically, our analysis exclusively focused on a European population, which limits the generalizability of our results to other populations. Furthermore, our utilization of summary datasets impeded our ability to stratify the data by gender, age, or other relevant factors.