OP is a prevalent condition among elderly patients, often leading to pain, swelling, joint deformity, limited mobility, and even fractures in advanced stages, severely impacting the quality of life39,40. Malnutrition, particularly protein-energy malnutrition, exacerbates the risk of OP and osteoporotic fractures in the elderly due to decreased bone mass and muscle strength41. Given the critical role of nutritional support in preventing and mitigating OP, understanding how to predict the progression and outcomes of malnutrition in elderly patients is of paramount importance. Common risk factors for OP include smoking, excessive alcohol consumption, and family history, with laboratory tests typically focusing on Ca, P, and SCr 42,43. In this study, we retrospectively analyzed clinical and laboratory data from 381 malnourished elderly patients and identified independent predictors of OP through statistical methods. The significant predictors included a history of hypertension, a history of T2DM, a low GNRI, low activity situation, high ALP, low Ca, high TC, high TG, low ALB, low overall hip joint BMD, and low overall lumbar spine BMD. Based on these findings, we developed a convenient and efficient nomogram, which was internally validated, demonstrating good predictive accuracy and clinical applicability. Research has established a link between malnutrition and poor bone health, with malnutrition-related OP significantly increasing the risk of fractures, worsening prognosis, and elevating mortality rates. BMD, measured by DXA, is the gold standard for OP diagnosis. However, BMD measurements can be influenced by equipment quality, measurement location, and patient morphology 44. Additionally, existing OP screening tools are limited and lack comprehensive validity and practicality. For instance, the OP Self-Assessment Tool for Asians (OSTA) is mainly applicable to postmenopausal women45 and has shown poor sensitivity and predictive power, the sensitivity was only 32.3% in subjects, and the AUR was only 61.8%46. Furthermore, studies exploring the relationship between malnutrition and OP in the elderly have predominantly focused on isolated clinical indicators or database-driven analyses21,47,48. The development of simple and practical early prediction tools is crucial for accurately identifying high-risk populations.
Our study identified history of hypertension, history of T2DM, low GNRI, low activity status, high ALP, low Ca, high TC, high TG, low ALB, low overall hip joint BMD, and low overall lumbar spine BMD as independent risk factors for OP in malnourished elderly patients. Hypertension and T2DM were found to be significant risk factors, with ALP, TC, TG, and Ca also contributing to OP risk, while GNRI, ALB, physical activity, overall hip joint BMD, and lumbar spine BMD were protective factors. Previous research suggests common risk factors and pathophysiological mechanisms between hypertension and OP, including secondary hyperparathyroidism, increased sympathetic activity, oxidative stress, and inhibition of matrix proteins dependent on vitamin K49–51. The renin-angiotensin system (RAS) plays a pivotal role in OP, with RAS activation promoting bone resorption and OP progression, whereas RAS inhibitors have been shown to reduce the incidence and complications of OP 52,53. T2DM and OP, both metabolic disorders, are often associated with systemic metabolic bone disease, increasing disability and mortality. Chen et al. found a significantly higher prevalence of low BMD in the T2DM group compared to nondiabetic controls, with increased risks of low BMD and fractures54. However, some studies report no association or even a protective effect of T2DM on OP. A meta-analysis of 33437 cases found that BMD in patients with T2DM was overall 25%-50% higher than in non-T2DM controls, regardless of the site of skeletal measurements, sex, or age55. Several Mendelian randomization studies have also identified a causal relationship between T2DM and OP, suggesting that T2DM may have a protective effect on OP. Therefore, there is a need for large, multicenter, randomized controlled trials to further clarify this relationship. Elevated levels of total alkaline phosphatase (T-ALP) typically indicate increased osteoblast activity and bone turnover. A cross-sectional study based on NHANES data found a negative correlation between T-ALP levels and lumbar spine BMD scores in young adults, suggesting that T-ALP may serve as a valid biomarker for the diagnosis and treatment of OP56. Another study demonstrated that T-ALP activity above 129 U/L could be used as an indicator of OP in men57. Additionally, treatment with alendronate has been shown to reduce T-ALP levels from 79.7 U/L to 64.8 U/L58. Therefore, ALP can be considered an important marker in the diagnosis and management of OP. Lipids as important metabolic indicators play a key role in assessing metabolic diseases. A study conducted in Saudi Arabia found a significant increase in lipid levels and ALP in the OP group compared to the normal group59. Several studies have also demonstrated that higher levels of TC and TG are associated with a greater risk of OP60,61. The underlying mechanism may involve lipid metabolites activating the nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPAR γ), leading to increased PPAR γ activity62,which inhibits osteogenesis and accelerates bone loss. Furthermore, elevated oxidative stress levels can inhibit osteoblast differentiation while promoting adipocyte differentiation63. Ca, an essential nutrient stored in bones, is crucial for human growth and development64. The results of the present study found that the occurrence of OP was inversely related to Ca levels, consistent with clinical studies showing that Ca and vitamin D supplementation reduces bone loss and fracture risk in OP treatment regimens65,66. The negative correlation between Ca and OP is closely related to aging, which increases serum parathyroid hormone and ALP levels while decreasing Ca, P, and vitamin D metabolites67. Elderly patients are characterized by a complex and diverse disease profile, facing higher nutritional risks. The overall prevalence of malnutrition in the elderly ranges from 1–24.6%68. In this study, the GNRI, an indicator reflecting the nutritional status of the elderly, was included. The prevalence of OP was higher in the low GNRI group compared to the high GNRI group, which aligns with the findings of Huang-Wei et al21. High GNRI has also been identified as an independent protective factor against OP in elderly patients with T2DM, and it is a better predictor of OP in these patients compared to other nutritional scores such as COUNT and PNI2569. The GNRI assessment incorporates ALB levels and body weight, consistent with our findings that ALB is an independent protective factor in predicting OP. This may be related to hypoproteinemia, which activates osteoclasts and inhibits osteoblasts through inflammatory factors such as NF-κB70. A retrospective study also found that low ALB concentration was significantly and independently associated with the prevalence of OP71. A review also found that low ALB concentrations were significantly and independently associated with the prevalence of OP. Physical activity has been shown to have a positive effect on bone health in several studies72–74. A meta-analysis found that higher net training frequency in older adults had a better effect on BMD75. This aligns with our findings that increased activity levels help reduce OP risk in older adults. The mechanism may involve microRNAs (miRNAs) that regulate bone marrow stromal cell (BMSC) differentiation and physical activity-induced bone remodeling through different pathways76. BMD remains one of the most important diagnostic criteria for OP77. Studies have shown that, excluding physiological and mechanical factors, BMD decreases with age78,79. BMD is also associated with OP risk by gender, with gender differences leading to varying correlations between BMD and age. For example, lumbar spine and femoral neck BMD show significant negative correlations with age in males, while clavicle and femoral diaphysis BMD show significant negative correlations with age in females. Additionally, significant positive correlations were found between BMD loci in various combinations, such as between lumbar spine and femoral neck in males, and between clavicle and femoral stem in females80.These findings are consistent with our observation that BMD decreases with the onset of OP.
The aim of this study was to investigate the risk factors for OP in the elderly and to establish a nomogram for predicting its risk. 12 predictors were identified for inclusion in the nomogram, with a predictive power of 0.946 in the training group and 0.963 in the validation group. This study has three main strengths: First, the clinical data used to construct the prediction model are simple and objective; Second, the variables used are easy to obtain, enhancing the model's generalizability and facilitating its application in clinical practice; Third, we may be the first to develop a model for predicting OP based on elderly malnourished patients, which is crucial for early diagnosis and prevention. However, our study has limitations. First, it was a cross-sectional study with a limited sample size, which may introduce selection bias; Second, there are some limitations in the factors considered, as serum hormones, bone metabolism indices, and other relevant indicators were not included in this analysis; Moreover, this study only focused on elderly patients with OP, and further research is needed to determine whether the findings are applicable to other populations. Future studies should involve large-sample, multicenter, prospective studies to validate and refine the model.