The Impact of Diabetes and Diabetic Kidney Disease on Bone Mineral Density at the Lumbar Spine and Femoral Neck

Background:Type 2 diabetes mellitus (T2DM) and diabetic kidney disease are associated with metabolic disturbances that negatively affect bone health, increasing the risk of reduced bone mineral density (BMD), osteopenia, and osteoporosis. This study aimed to determine and compare the prevalence of osteopenia and osteoporosis among patients with T2DM with and without chronic kidney disease (CKD) and healthy non-diabetic controls. Materials and Methods:A total of 210 participants were enrolled and categorized into three groups: patients with T2DM and CKD, patients with T2DM without CKD, and healthy controls. BMD was measured at the lumbar spine and femoral neck using dual-energy X-ray absorptiometry (DEXA). Bone status was classified according to World Health Organization criteria: normal (T-score ≥ −1), osteopenia (T-score between −1 and −2.5), and osteoporosis (T-score < −2.5). Results:The prevalence of osteopenia and osteoporosis was significantly higher among diabetic patients compared to controls, with the highest rates observed in patients with diabetic kidney disease. Vertebral osteoporosis and osteopenia were present in 54% and 38% of patients with diabetic kidney disease, respectively. In patients with T2DM without CKD, osteoporosis and osteopenia were observed in 24% and 52% of cases, respectively. At the right femoral neck, osteoporosis prevalence was 24% in patients with diabetic kidney disease, 8% in patients with T2DM without CKD, and 4% in controls. Corresponding osteopenia rates were 38%, 42%, and 20%, respectively. Conclusion:Patients with T2DM, particularly those with concomitant CKD, exhibit a substantially higher prevalence of osteopenia and osteoporosis compared to non-diabetic individuals. These findings emphasize the need for routine bone health assessment and early osteoporosis screening in diabetic patients to reduce fracture risk and improve clinical outcomes. -------------------------------------------------------------------------------- Introduction Diabetes mellitus represents a major and escalating public health burden in India, with prevalence rates rising at an alarming pace. It is projected that the number of individuals affected by diabetes will increase from 40.6 million in 2006 to approximately 79.4 million by 2030 (1). This upward trend is likely to accelerate further as life expectancy increases and mortality from communicable diseases declines. Individuals with type 2 diabetes mellitus (T2DM) are predisposed to a broad spectrum of microvascular and macrovascular complications, the incidence and severity of which are largely determined by disease duration and the degree of glycemic control (2, 3, 4). Beyond the well-recognized complications such as ischemic heart disease, cerebrovascular events, and diabetic nephropathy, mounting evidence indicates that individuals with T2DM are at a substantially increased risk of fractures compared to their non-diabetic counterparts. This elevated fracture risk has traditionally been attributed to diabetes-related complications, including hypoglycemia induced by antidiabetic therapy, impaired muscle strength, visual impairment secondary to diabetic retinopathy, peripheral arterial disease, and diabetic neuropathy, all of which contribute to imbalance and an increased propensity for falls. However, recent studies have demonstrated that diabetes exerts direct effects on bone metabolism at the molecular level, resulting in altered bone remodeling dynamics, increased bone resorption, and compromised bone quality (5, 6, 7). Current evidence suggests a strong association between diabetes and reduced bone mineral density (BMD), manifesting as osteopenia and osteoporosis. This risk is further amplified in individuals with long-standing diabetes and those who develop chronic kidney disease (CKD), owing to disturbances in mineral metabolism, secondary hyperparathyroidism, and vitamin D deficiency (8, 9, 10). Despite the growing recognition of skeletal fragility in diabetes, data on the prevalence of osteopenia and osteoporosis among Indian patients with T2DM—particularly those with concomitant CKD—remain limited. In view of these considerations, the present study was undertaken to estimate and compare the prevalence of osteopenia and osteoporosis in patients with T2DM with and without CKD and to contrast these findings with those observed in non-diabetic healthy controls. Materials and Methods Study Design and Setting This hospital-based cross-sectional study was conducted between 2022 and 2023 through a collaborative effort between the Departments of Radiodiagnosis and Imaging and Medicine/Endocrinology at a tertiary care teaching hospital in the Kashmir Valley, India. Participants were recruited from the outpatient services of the Departments of Medicine and Endocrinology. Participants Eligible participants were adults aged ≥18 years attending the outpatient department who were approached consecutively and provided with detailed information regarding the study objectives and procedures. Written informed consent was obtained from all participants prior to enrollment. Patients diagnosed with T2DM, with or without diabetic kidney disease, were included. Healthy controls were selected from attendants of patients admitted for elective surgical procedures and were screened to ensure the absence of diabetes or other systemic illnesses affecting bone metabolism. Case Definitions Participants were categorized into three groups of 70 individuals each: T2DM with CKD, T2DM without CKD, and non-diabetic controls. The control group was age- and sex-matched and recruited from the same hospital setting to provide representative reference BMD values. T2DM was defined by one or more of the following criteria: fasting plasma glucose ≥126 mg/dL, postprandial plasma glucose ≥200 mg/dL, glycated hemoglobin (HbA1c) ≥6.5%, or a prior diagnosis of diabetes with ongoing antidiabetic therapy. Diabetic kidney disease was defined as urinary albumin excretion >15 µg, 24-hour urinary albuminuria >300 mg/day, or serum creatinine >120 µmol/L in a patient with diabetes. Study Procedures Following informed consent, all participants underwent a comprehensive baseline clinical evaluation and laboratory assessment. Sociodemographic and clinical data—including medical and surgical history, smoking and alcohol consumption, medication use, physical activity levels, and other factors influencing bone metabolism—were collected using a standardized questionnaire. Laboratory investigations included fasting and postprandial plasma glucose, HbA1c, renal function tests, 24-hour urinary protein estimation, serum 25-hydroxyvitamin D, calcium, phosphorus, albumin, alkaline phosphatase, and thyroid-stimulating hormone levels. Bone mineral density of the lumbar spine and right femoral neck was assessed using dual-energy X-ray absorptiometry (DEXA). Variables and Definitions Bone mineral density was classified according to World Health Organization criteria: normal BMD (T-score ≥ −1), osteopenia (T-score between −1 and −2.5), and osteoporosis (T-score < −2.5). Body mass index (BMI) was calculated using standard formulas. Sample Size Sample size estimation was based on previous studies reporting the prevalence of osteoporosis in patients with T2DM. Assuming a power of 80% and a two-sided alpha of 0.05, a minimum sample size of 70 participants per group was calculated to detect statistically significant differences in BMD between patients with T2DM with and without CKD. Statistical Analysis Categorical variables were expressed as frequencies and percentages. The distribution of continuous variables was assessed using histograms, probability plots, and the Kolmogorov–Smirnov and Shapiro–Wilk tests. Normally distributed variables were summarized as mean ± standard deviation, while non-normally distributed variables were expressed as median with interquartile range. Comparisons between categorical variables were performed using Pearson’s χ² test or Fisher’s exact test, as appropriate. The Mann–Whitney U test was used for comparisons between two groups, and the Kruskal–Wallis test was applied for comparisons involving more than two groups. Statistical analyses were performed using Stata version 15. Ethical Considerations The study protocol was approved by the Institutional Ethics Committee. Written informed consent was obtained from all participants. Individuals younger than 18 years and those with cognitive impairment affecting decision-making capacity were excluded. Results Demographic and Clinical Characteristics A total of 210 participants were included: 70 patients with T2DM and CKD (Group 1), 70 patients with T2DM without CKD (Group 2), and 70 healthy controls (Group 3). The three groups were comparable with respect to age and sex distribution. The mean age was 60.16 ± 10.32 years in Group 1, 58.26 ± 9.93 years in Group 2, and 59.60 ± 4.92 years in Group 3. Male participants constituted 62.86%, 62.86%, and 60% of Groups 1, 2, and 3, respectively. Body mass index did not differ significantly among the groups. Serum electrolytes, calcium, phosphorus, and albumin levels were comparable across groups. However, fasting and postprandial glucose levels and HbA1c values were significantly higher in Group 1 compared to Group 2, with both groups exhibiting higher values than controls. Serum urea and creatinine levels were significantly elevated in patients with diabetic kidney disease. Bone Mineral Density Mean vertebral T-scores were −2.49 ± 0.88, −1.69 ± 1.25, and −0.75 ± 1.02 for Groups 1, 2, and 3, respectively, with corresponding Z-scores of −1.62 ± 1.02, −0.76 ± 0.95, and −0.62 ± 1.22. These differences were statistically significant. At the right femoral neck, mean T-scores were −1.29 ± 1.06, −0.84 ± 1.13, and −0.40 ± 0.90 for Groups 1, 2, and 3, respectively, with corresponding Z-scores of −0.42 ± 1.24, −0.25 ± 1.03, and −0.26 ± 1.12. The differences in T-scores were statistica