IN this study, we explored the relationship between RBP and the outcomes of hip fractures. As shown in the results, RBP might be a protective factor for the rehabilitation of patients who underwent hip surgeries due to hip fractures: patients with increasing RBP may face a low risk of mortality and favorable walking ability. Moreover, we also determined a cutoff point of RBP (20.95 mg/L) and the patients with high levels of RBP (> 20.95 mg/L) may also face a better prognosis.
We set relatively strict inclusion criteria. As we know, RBP is synthesized by the liver, so liver diseases may influence the levels of RBP, and then the RBP might be sensitive to liver status, instead of bone metabolism and nutrition. That is why we excluded the patients with severe liver disease. To better show the difference in RBP in patients with different outcomes, the PSM was carried out to reduce the impact caused by co-factors, and the ROC curve and the identification of cutoff points were also performed based on the matched populations. We believe that we can minimize the bias in this way. Similarly, the outcomes compared directly in groups of low and high levels of RBP may also face the impact of co-variables. Therefore, the logistic analysis was used to provide stronger evidence. As shown in Tables 3 and 4, the predictive value of high levels of RBP is not significant in the logistics models for 6-month walking ability and 1-year walking ability while in the univariate analysis, the 6-months and 1-year walking ability are significantly high in the high RBP group, which means the covariable may affect the waking ability. Therefore, we finally concluded that the low RBP group may have poor mortality at 3 months, 6 months, and 1 year, and free walking ability at 3 months.
Recent studies had reported the relationship between RBP and bone: RBP may associate with BMD and osteoporosis via multiple pathways. Li G and their team explored the impact of RBP1 on bone regeneration: they found that the RBP1 may promote osteogenic differentiation of bone marrow-derived mesenchymal stem cells through inhibiting RXRα-induced β-catenin degradation and then affect the process of bone regeneration . Moreover, the pathway between PTH and RBP was also reported: PTH, PTH-related peptide, and (Bu)2cAMP increased the RBP mRNA level in chondrocyte cultures, and the PTH may regulate the bone metabolism by modulating RBP . Otherwise, RBP may also impact bone metabolism through fat mass. It is reported that the rats with knockout RBP faced a decreased level of non-esterified fatty acids , and many studies also proved that the high RBP was associated with adipose tissue . The expression of signal factors in adipose tissue, such as adiponectin, visfatin, and leptin, may affect BMD [20, 21]. It was also reported that the RBP as one of the adipokines, may interact with other adipokines including fibroblast growth factor 21 (FGF21), bone morphogenetic protein (BMP)-4, BMP-7, and so on, and these signaling factors were key factors in pathways involved in bone metabolism .
Population study also showed consistent results: a study enrolled 355 patients grouped by different levels of BMD showed that the RBP, as well as alkaline phosphatize, was positively correlated with BMD at the lumbar spine, femoral neck, and hip . Moreover, a study comparing the predictive efficiency of various bone parameters reported that RBP, after alkaline phosphatase and age, was the strongest predictor for BMD in treated postmenopausal osteoporosis . Similarly, many studies also suggested that RBP may relate to vitamin D by influencing nutrition status [24, 25]. As for the relation between RBP and fractures, a study that enrolled the patients with osteoporotic fractures and age-matched control subjects showed that the patients with osteoporotic hip fractures have lower RBP than their controls .
RBP plays an important role in metabolism, especially in adipose tissue . The liver synthesizes the majority of RBP, but almost 20% of retinol was stored in adipose tissue . The levels of RBP fluctuate rapidly and sensitively when the body faces different nutrition statuses: the RBP may increase facing malnutrition . It was reported that the glucose transporter (GLUT4), a marker in adipocytes, was positively related to RBP . A study enrolled the individuals who underwent gastric bypass surgery found that the patients with decreased body fat may have a significant reduction in RBP than those with unchanged body fat . In a study about diet, the RBP decreased in the situation of a calorie diet while RBP in turn increased in the period of normal food . In our study, the levels of RBP at the first time of hospital admission were selected to analyze, because RBP could sensitively indicate the nutrition status. Moreover, BMI and albumin as indicators of nutrition status were also analyzed in PSM, Cox models, and logistics models to control the bias caused by malnutrition.
There are some limitations to this study. First, our study is a retrospective single-center study based on relatively small samples, the missing data from follow-up and RBP may increase the bias. Moreover, the values of RBP are fluctuant. We cannot control the time from injury to admission. Though we select the data at the first laboratory test, the time may also affect the values. Thirdly, we failed to include some potential covariable, such as the diagnosis of osteoporosis and the use of anti-osteoporosis drugs. Lastly, walking ability as a functional outcome may be influenced by many factors, including the occurrence of complications and mechanical failure, fracture patterns, and so on. These factors not included in our study may cause bias in outcomes.
RBP as an indicator associated with bone metabolism and nutrition status could predict the outcomes of hip fracture. We could serve our patients better by noting the RBP and trying our best to improve their nutrition status, which may provide a better prognosis for patients. Moreover, due to the role played by RBP in many pathways, we may also notice the bone metabolism status of patients, and provide potential treatment. We hope experimental studies with a high level of evidence could prove the relation between RBP and outcomes of hip fracture.