Prevalence and Risk Factors of Osteoporosis in Patients with Type 2 Diabetes Mellitus in Nanchang (China): A Retrospective Cohort Study

Introduction

Type 2 diabetes mellitus (T2DM) is a common metabolic disease and its prevalence has been increasing with the aging population. The current prevalence rate of T2DM in China is 11.2%.¹ Osteoporosis (OP) is also a commonly diagnosed metabolic disease in Chinese population over 50 years old, with a prevalence of 20.7% in females and 14.4% in males. The prevalence of OP is significantly increased in people over 60 years old, especially in females.² Many studies have shown that patients with T2DM have a higher risk of fracture than non-diabetic population and are more prone to OP.^3–9 Moreover, after fracture, diabetic patients with OP are prone to develop a series of complications such as pneumonia and bed sores, and even death. In the present study, we retrospectively reviewed the clinical data of T2DM patients hospitalized in Nanchang, China, aiming to summarize the prevalence of OP in T2DM patients in this area and analyze related influencing factors.

Materials and Methods

General Data

This study was approved by the Ethics Committee of the Nanchang First Hospital, China (Approval code: KY2021072). Patients with T2DM hospitalized at the Department of Endocrinology, Nanchang First Hospital, from June 2018 to September 2021 were selected as study subjects. The inclusion criteria were: 1. enrolled subjects met the diagnostic criteria for T2DM formulated by the World Health Organization (WHO) in 1999: (1) present with diabetes symptoms (ie polyuria, polydipsia, polyphagia, and unexplained weight loss caused by hyperglycemia) plus any one or more of the following criteria: (a) Random blood sugar ≥ 11.1 mmol/L or (b) fasting Blood glucose ≥ 7.0 mmol/L or (c) blood glucose ≥ 11.1 mmol/L 2 hours after glucose load; 2. aged > or equal to 18–75 years old. The exclusion criteria were patients: (1) with type 1 diabetes mellitus (T1DM) and other types of diabetes mellitus; (2) in critical condition or with abnormal mental conditions who could not cooperate with the medical history and relevant physical examinations; (3) patients that were bedridden, or with serious long-term infections, severe heart, lung, liver, and kidney diseases; (4) long-term administration of immunosuppressants or glucocorticoids; (3) bone tumors, hyper- or hypothyroidism, diseases of the adrenal glands, gonads, and other diseases affecting bone metabolism.

Research Methods

The subjects were retrospectively investigated, and the actual data (clinical and laboratory) of the subjects were obtained from electronic medical records. The following clinical data were collected on the subjects: gender, age, body mass index (BMI), duration of T2DM, glycated hemoglobin (HbA1c) (Huizhong MQ-2000PT), serum lipids, fundus photography, results of neurogram of both lower limbs, and so on.

According to the diagnostic criteria for OP issued by the WHO in 1994, bone mineral density (BMD) levels in premenopausal women and men under 50 years of age were represented by the Z-value. Normal bone mass was defined as a Z score of >–2.0, and osteopenia as a Z score of ≤–2.0. BMD levels in postmenopausal women and men over 50 years of age were expressed as T-values. Normal bone mass was defined as a T score of ≥–1.0, osteopenia as –2.5 < T score <–1.0, and OP as a T score of ≤–2.5.¹⁰ Fragility fracture was also included in the diagnosis of osteoporosis. In this study, both hip and lumbar were used for T/Z score measurements. The same DEXA machine (Hologic Explorer, USA) was used to measure BMD for all patients. Subjects were divided into the normal bone mass, osteopenia, and OP groups. The Research Ethics Committee of Nanchang First Hospital approved the present study.

Statistical Analysis

SPSS 22.0 software was used for statistical analysis. All continuous variables satisfying the normal distribution were expressed as mean ± standard deviation (X ± SD). The t-test was used to compare parameters between two groups, and analysis of variance was used to compare parameters among multiple groups. The categorical variables were compared by the chi-square test. Risk factors of abnormal bone mass were analyzed by logistic regression. P < 0.05 was considered statistically significant.

Results

General Clinical Data

A total of 1697 patients with T2DM were included this study. There were 733 females and 964 males, with an age range of 25–75 years. The prevalence of OP was 35.77%, the prevalence of osteopenia was 44.67%, and the prevalence of normal bone mass was 19.56%. There existed statistically significant differences in age, gender, BMI, waist-to-hip ratio (WHR), duration of T2DM, and educational backgrounds among the three groups (P < 0.05) (Table 1). There were statistically significant differences in age, BMI, and WHR among the three groups of female patients (P<0.05) (Table 2). There were statistically significant differences in age, BMI, course of disease, and education level among the three groups of male patients (P<0.05) (Table 3).

Table 1 Comparison of Clinical Data Among All Patients

Table 2 Comparison of Clinical Data Among Female Patients

Table 3 Comparison of Clinical Data Among Male Patients

Glucose and Lipid Metabolism in Patients with Different Bone Mass

There were no significant differences in HbA1c, total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) among patients with different bone mass (P > 0.05). The differences in the levels of high-density lipoprotein cholesterol (HDL-C) were statistically significant among the three groups (P < 0.05) (Table 4). There was a statistically significant difference in high-density lipoprotein cholesterol (HDL-C) among the three groups in male patients (P<0.05) (Table 5), but not in female patients (Table 6).

Table 4 Comparison of Glucose and Lipid Metabolism Among All Patients

Table 5 Comparison of Glucose and Lipid Metabolism Among Male Patients

Table 6 Comparison of Glucose and Lipid Metabolism Among Female Patients

Diabetic Complications in Patients with Different Bone Mass

The comparison of diabetic complications among patients with different bone mass groups showed that the prevalence of diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN) were statistically different among the three groups of all patients (P < 0.05) (Table 7), male patients (P < 0.05) (Table 8), and female patients (P < 0.05) (Table 9).

Table 7 Comparison of Diabetic Complications Among All Patients

Table 8 Comparison of Diabetic Complications Among Male Patients

Table 9 Comparison of Diabetic Complications Among Female Patients

Factors Influencing Bone Mineral Density in Patients with T2DM

Age, gender, education, duration of T2DM, BMI, HDL-C, the prevalence of DR and DPN were taken as variables and introduced into the multiple regression equation. In all patients, compared with those in the normal bone mass group, age, educational background, BMI, duration of T2DM, levels of HDL-C, and prevalence of DR were the influencing factors of osteopenia. Compared with those in the normal bone mass group, gender, age, BMI, duration of T2DM, levels of HDL-C, and prevalence of DR and DPN were the influencing factors of OP (Table 10).

Table 10 Influencing Factors of Abnormal Bone Mass in All Patients with T2DM

In male patients, compared with those in the normal bone mass group, educational background (below high school), age, BMI, HDL-C, and diabetic retinopathy were the influencing factors of osteopenia in male patients. Compared with those in the normal bone mass group, age, BMI, HDL-C, diabetic retinopathy, and diabetic peripheral neuropathy were the influencing factors of OP (Table 11). In female patients, compared with in the normal bone mass group, age and BMI are the influencing factors of osteopenia. Compared with those in the normal bone mass group, age, BMI, and the presence of diabetic retinopathy were the influencing factors of OP (Table 12).

Table 11 Influencing Factors of Abnormal Bone Mass in Male Patients with T2DM

Table 12 Influencing Factors of Abnormal Bone Mass in Female Patients with T2DM

In patients younger than 45 years, compared with those in normal bone mass group, age, BMI, TG, gender are the influencing factors of osteopenia (Table 13). In patients between 45 and 60 years, compared with those in the normal bone mass group, age, BMI, HDL-C, educational background (below high school), and diabetic peripheral neuropathy were the influencing factors of osteopenia. Compared with those in the normal bone mass group, age, BMI, male gender, diabetic retinopathy, and diabetic peripheral neuropathy were the influencing factors of OP (Table 14). In patients above 60 years, compared with the normal bone mass group, BMI, duration of T2DM, gender (male), HDL-C, and diabetic retinopathy were the influencing factors of osteopenia. Compared with the normal bone mass group, duration of T2DM, gender (male), and diabetic retinopathy were the influencing factors of OP (Table 15).

Table 13 Influencing Factors of Abnormal Bone Mass in T2DM Patients Younger Than 45 Years

Table 14 Influencing Factors of Abnormal Bone Mass in T2DM Patients Between 45 and 60 Years

Table 15 Influencing Factors of Abnormal Bone Mass in T2DM Patients Above 60 Years

Discussion

T2DM and OP are the most common metabolic diseases in middle-aged and older adults, and the prevalence of OP in patients with T2DM is significantly higher than in those without T2DM.¹¹ In the present study, the prevalence of OP in patients with T2DM was 35.77%, which was slightly lower than 37.8% in the meta-analysis by Si.¹²

Age and gender were risk factors for OP, which was consistent with previous studies.^13–17 This might be due to the decreased physical activity with age, decreased calcium absorption in the gut, and decreased synthesis of 1.25-(OH)2D3 in the kidneys.¹⁸ The relative and secondary increase in parathyroid hormones may result in a decreased bone turnover rate. Meanwhile, bone absorption will be affected due to the depletion of ovarian follicles in postmenopausal women and the decline in levels of sex hormones. Increased microRNA-151a-3p levels in postmenopausal women promote osteoclast differentiation and affect BMD through targeting SOCS5 and activating the JAK2/STAT3 signaling pathways.^19,20

With a longer duration of T2DM, patients are at an increased risk of developing bone mass abnormalities. In patients with T2DM, insulin function gradually declines with prolonged disease duration, and long-term insulin deficiency can lead to continuous hyperglycemia and decreased bone turnover, affecting osteoclast activity and promoting bone resorption.^21,22

It was suggested in the present study that BMI might be a protective factor of bone tissue. Several studies²³ suggest that bone mineral density increases with increased BMI, which correlates with fracture risk reduction.²⁴ On the one hand, when BMI increases, it can increase the bearing capacity of bone, increase the mechanical stress on bones, and promote bone formation. On the other hand, people with high BMI have higher body fat content, which may be converted into fat-related hormones, such as vitamin D, estrogen, androgen, etc. through the secretion of adipokines, such as leptin, adiponectin, and Tumor Necrosis Factor (TNF), and affect bone metabolism by inflammatory factors that increase bone resorption.^13,23

High HDL-C levels are correlated with abnormal bone mass. Ahmed et al²⁵ found that low HDL-C levels had a protective effect on bone mass. A meta-analysis of 12,395 subjects²⁶ also showed that HDL-C could be used as an indicator to predict osteopenia, OP, and even fractures. With the increase of HDL-C, the risk of OP also increases. A study on the differentiation of mesenchymal stem cells showed²⁷ that specific hydroxyl sterols could stimulate the osteogenic differentiation of mesenchymal stem cells, while HDL-C could clear the hydroxyl sterols from peripheral tissues, suggesting that high HDL-C levels might not be conducive to osteogenic differentiation, but the specific mechanism is still unclear.

At present, many studies consider diabetic microangiopathy as a risk factor for OP.^28,29 Diabetic microangiopathy (ie diabetic retinopathy and diabetic peripheral neuropathy) is also considered a risk factor for abnormal bone mass. Chronic hyperglycemia and oxidative stress in diabetic patients lead to the accumulation of advanced glycation end products (AGEs), stimulation of the production of inflammatory factors, changes of the vascular endothelial growth factor signal transduction, and affect bone metabolism.^30,31 It has been reported that the peripheral nervous system in patients with T2DM regulates bone metabolism through the influence of local neurotransmitters on bone cells and neuromodulation supplied by bone vessels.³² Since DPN may result in loss of coordination, balance, and walking problems,³³ low physical activity or lack of activity is common in patients with DPN, especially in those with painful DPN,³⁴ which ultimately leads to decreased bone mass and bone mineral density.

In this study, we presented the analysis results of related risk factors for male and female patients, respectively, and for patients at different ages, respectively. This is the strengths of the present study. However, there were still some limitations in this study. First, we did not analyze the correlations between various metabolic indicators and bone mass in these patients. Future investigations are needed to explore the potential relationships between these parameters. Secondly, no further analysis considering post-menopausal status as a confounding factor was performed when analyzing the gender difference among different groups. Thirdly, as this was a retrospective study, other T2DM- and OP-related parameters (ie fasting blood glucose levels, insulin levels, insulin sensitivity, glucose tolerance, and vitamin D), socioeconomic data (ie calcium consumption status, exercise habits, smoking status, and daily alcohol consumption), and complications (ie diabetic nephropathy, diabetic foot, and diabetic peripheral vascular disease) were not available for all patients. Lastly, all patients included in this study were hospitalized T2dM patients and most of them were admitted due to poor blood sugar control. It might explain why there was no significant difference in the HbA1c levels among groups with different bone mass.

In conclusion, the prevalence of OP in T2DM was high. Risk factors for abnormal bone mass in T2DM were females, advanced age, long duration of T2DM, low BMI, high levels of HDL-C, and diabetic microangiopathy. Therefore, in the clinical treatment of patients with the above risk factors, it might be necessary to strengthen BMD screening, with early bone mass screening and intervention.