Originally used as an indicator to assess nutritional status in the elderly, GNRI is calculated from albumin, weight and height and is a dual assessment of serum albumin and BMI that complements and improves the accuracy of diagnosis. Good nutritional status plays a good role in bone metabolism, Similarly, malnutrition increases the incidence of osteoporosis and fragility fractures [16]. In the present study we looked at the correlation between GNRI and osteoporosis in northern T2DM patients and showed that there is a positive correlation between GNRI and osteoporosis, the group with lower GNRI values had a higher prevalence of osteoporosis. Divided the participants into osteoporotic and non-osteoporotic groups, and low GNRI values in the osteoporotic group compared to those in the non-osteoporotic group, and the difference was statistically significant. Linear correlation analysis revealed that GNRI was positively correlated with lumbar BMD, femoral neck BMD and total hip BMD (P < 0.05). In the logistic regression analysis, Significant association of GNRI with osteoporosis. We evaluated the predictive effect of GNRI on osteoporosis using Roc curves. The analysis yielded a GNRI cut-off value of 99.56, similar to the findings of Liang Wang et al, they yielded cut-off value of 98.2 for predicting osteoporosis in men and 99.5 for predicting osteoporosis in women. Our results suggest a significant positive relationship between GNRI and osteoporosis and provide a theoretical basis for screening for osteoporosis in clinical practice.
The current mechanism of association between GNRI and osteoporosis is considered to be possibly related to the following. First, malnutrition affects calcium and vitamin D intake, which may increase bone mineral loss in patients, making it difficult to mineralize bone and leading to the development of osteoporosis. Secondly, hypoalbuminemia is a marker of both nutritional status and chronic inflammatory response; hypoalbuminemia activates osteoclasts and inhibits osteoblasts through NF-κB factors, other inflammatory cytokines [17]; hypoalbuminemia causes a decrease in insulin-like growth factor-1 synthesis, which also leads to a decrease in the number of osteoblasts and a decrease in cellular activity, increased osteoclast lifespan, increased bone resorption, and bone decreased remodeling [18]. Finally, hypoproteinemia leads to inadequate muscle synthesis and decreased skeletal muscle mass, resulting in decreased balance and gait capacity, which can cause falls as well as the occurrence of fractures [19, 20].
Our results yield that a high levels of GNRI have a protective effect on bone metabolism in patients. In contrast, no correlation between GNRI and 25(OH)D in the study by Liang Wang et al. Possible reasons for our different results are that in the south even though nutritional status leads to reduced vitamin intake, vitamin D levels can still be ensured with adequate sun exposure, while in the north insufficient sun exposure combined with nutritional barriers makes it more likely to cause vitamin D deficiency and deficiency. Studies show a close relationship between latitude sunlight deficiency, skin coverage and vitamin D. In China, there is a clear geographical division of vitamin D deficiency, with populations in northern, northeastern and northwestern China north of 35 degrees north latitude being more severely undernourished, while vitamin D levels are adequate in areas south of 25 degrees north latitude and in the middle of the country [21, 22].
Our study also found that GNRI was negative correlated with P1NP, are contrary to the findings of Liang Wang et al. Possible reasons for the negative correlation between GNRI and PINP are that PINP secreted by osteoblasts is known to be a marker of bone formation reflecting collagen formation and osteoblast activation, and that during bone turnover, bone formation and resorption are tightly coupled, with accelerated bone turnover predisposing to bone loss; therefore, high GNRI values are associated with low bone turnover and reduced bone loss. For the relationship between GNRI and PTH, the study found a positive correlation between serum PTH and BMI, fat mass, and Mehrotra indicated that reduced PTH is a risk factor for malnutrition [23, 24]. PTH can promote the inward flow of calcium ions into adipocytes and stimulate adipose synthesis, and accordingly, low levels of PTH inhibit adipose synthesis and cause protein depletion. In this study we yielded a higher GNRI value corresponding to a higher PTH. Among alkaline phosphatases, bone-specific alkaline phosphatase is closely related to normal bone growth and development, and is a marker of maturation and activity of osteoblasts. However, the specificity of our current assay is not good, and there is some crossover with liver-derived ALP, and we measure total ALP and not BALP; therefore, the relationship of ALP does not accurately reflect the level of bone metabolism.
In a logistic regression analysis, advanced age was an independent risk factor for osteoporosis, with bone density decreasing year by year with increasing age, and oxidative stress, which increases osteoclast activity and bone resorption, is a cause of age-related bone loss. The present study similarly concluded that the duration of diabetes is an influential factor in osteoporosis in T2DM. It has been shown that the relative risk (RR) of diabetes duration increases from 1. 40 (1. 08 ~ 1. 82) at less than 5 years to 2. 66 (2. 04 ~ 3. 47) at greater than 15 years [25]. The non-enzymatic glycosylation response of type 2 diabetes is known to contribute to the decline in bone mass. Hyperglycaemia leads to the accumulation of glycosylation end products (AGE) in the organic bone matrix, resulting in stiffening of type I collagen in the bone matrix, decreased bone strength, increased bone fragility and promotion of osteoblast apoptosis [26]. Our results suggest that suboptimal glycemic control is not an independent risk factor for the development of osteoporosis, possibly because measured glycemic parameters only reflect recent levels of glycemic control and that measured BMD in type 2 diabetic patients does not fully reflect the state of impaired bone mass in type 2 diabetic patients.
Furthermore, in our regression analysis of GNRI and osteoporosis, we concluded that uric acid was not associated with osteoporosis and was neither a protective nor a risk factor for osteoporosis. Several studies have concluded that higher UA levels are protective for osteoporosis [25–27]. Our difference with the results of these studies may be due to gender, region, ethnicity, study methodology and sample size. Finally, the association between serum UA and osteoporosis may be directly or indirectly confounded by the fact that many older adults suffer from two or more chronic diseases, such as obesity, diabetes mellitus, etc.
This study has some limitations, firstly, the retrospective nature of this study, it does not provide a mechanism-related explanation for the observed association; and the study is a cross-sectional study and doesn't indicate a causal relationship between GNRI and bone mineral density. Second, the serum data of the patients with the disease, of which only one was collected, and the BMD of each location was also collected once, thus leading to bias. Third, some relevant parameters affecting the study results may have been overlooked in this study, such as history of smoking, alcohol consumption, hormone levels, dietary habits, exercise situation, and history of previous fractures.
In summary, study results demonstrated that a lower GNRI is associated with increased osteoporosis and that GNRI is a convenient way to assess nutritional status and osteoporosis in patients with T2DM. Nutritional supplementation therapy may Reducing the incidence of osteoporosis in patients with T2DM.