Impact of Type 2 Diabetes Mellitus and Chronic Kidney Disease on Bone Mineral Density in Elderly Patients With Fragility Hip Fracture: A Cross‐Sectional Study

Canadian Society of Nephrology Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: Fragility hip fractures are a major public health burden and are considered a good measure of the quality of healthcare. However, contemporary trends in fragility hip fractures in women with low femoral neck bone mineral density (BMD) in the United States are not known. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 60 years with bone mineral density (BMD) T score ≤ -1 at the femur neck, which was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). Fragility fracture at the hip was defined as self-reported hip fracture resulting from a fall from standing height or less. Participants with missing BMD and fracture data were excluded. ANOVA was used for comparing means. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women aged ≥ 60 years with femoral neck T score ≤ -1, the average age of women of low BMD decreased from 71(±7.2) years to 69.6 (±6.7) years, whereas the mean T-score modestly worsened from – 1.96 (±0.62) to -2.04 (±0.77) from 2009-10 to 2017-18. Similarly, the prevalence of women with T score ≤ -2.5 increased from 18.1% to 21.3%. We also found no significant change in proportion of women who reported treatment for osteoporosis (2009-10: 19.8%, 2013-14: 18.5%, 2017-18: 19.7%; p trend = 0.052). However, proportion of women who experienced fragility hip fractures decreased significantly (2009-10: 2.4%, 2013-14: 1.5%, 2017-18: 1.2%; p trend = 0.001). The mean age of index fragility hip fracture was 70.6 years in 2009-10, 68.3 years in 2013-14 and 71.7 years in 2017-18 (p = 0.001). Age stratified analysis showed a decreasing trend in proportion of women ≥ 80 years who experienced their index fragility hip fracture (2009-10: 25.9%, 2013-14: 14.7%, 2017-18: 15%; p trend = 0.001) and 70-79 years (2009-10: 40.9%, 2013-14: 21.1%, 2017-18: 35.8%; p trend = 0.001), while an increasing trend was seen in women 60–69 years (2009-10: 33.2%, 2013-14: 64.2%, 2017-18: 49.2%; p trend = 0.001). Discussion In this nationally representative cohort of community-dwelling US women with a low femoral neck BMD, we found a 50% decrease in burden of fragility hip fractures over a 10-year period from 2009-10 to 2017-18. This trend was observed despite worsening mean femoral neck T-scores, T score ≤ -2.5, and similar rates of osteoporosis treatment. Interestingly, the proportion of women who experienced their index fragility hip fracture showed a declining trend among the 70-79 years and ≥ 80 years age-groups. This change may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education and environment modifications targeted towards the elderly population. Presentation: 6/2/2024

Disclosure: A. Atri: None. C. Anastasopoulou: None. Introduction: Fragility hip fractures are a major public health burden and are considered a good measure of the quality of healthcare. However, contemporary trends in fragility hip fractures in women with low femoral neck bone mineral density (BMD) in the United States are not known. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for the years 2009-10, 2013–14 and 2017–18 to include U.S. women aged ≥ 60 years with bone mineral density (BMD) T score ≤ -1 at the femur neck, which was measured by dual energy x-ray absorptiometry (DEXA) on Hologic Discovery Model A Densitometers (Hologic, Inc., Bedford, Massachusetts). Fragility fracture at the hip was defined as self-reported hip fracture resulting from a fall from standing height or less. Participants with missing BMD and fracture data were excluded. ANOVA was used for comparing means. The Cochran-Armitage test was utilized for trend analysis. Results: Overall, in women aged ≥ 60 years with femoral neck T score ≤ -1, the average age of women of low BMD decreased from 71(±7.2) years to 69.6 (±6.7) years, whereas the mean T-score modestly worsened from – 1.96 (±0.62) to -2.04 (±0.77) from 2009-10 to 2017-18. Similarly, the prevalence of women with T score ≤ -2.5 increased from 18.1% to 21.3%. We also found no significant change in proportion of women who reported treatment for osteoporosis (2009-10: 19.8%, 2013-14: 18.5%, 2017-18: 19.7%; p trend = 0.052). However, proportion of women who experienced fragility hip fractures decreased significantly (2009-10: 2.4%, 2013-14: 1.5%, 2017-18: 1.2%; p trend = 0.001). The mean age of index fragility hip fracture was 70.6 years in 2009-10, 68.3 years in 2013-14 and 71.7 years in 2017-18 (p = 0.001). Age stratified analysis showed a decreasing trend in proportion of women ≥ 80 years who experienced their index fragility hip fracture (2009-10: 25.9%, 2013-14: 14.7%, 2017-18: 15%; p trend = 0.001) and 70-79 years (2009-10: 40.9%, 2013-14: 21.1%, 2017-18: 35.8%; p trend = 0.001), while an increasing trend was seen in women 60–69 years (2009-10: 33.2%, 2013-14: 64.2%, 2017-18: 49.2%; p trend = 0.001). Discussion In this nationally representative cohort of community-dwelling US women with a low femoral neck BMD, we found a 50% decrease in burden of fragility hip fractures over a 10-year period from 2009-10 to 2017-18. This trend was observed despite worsening mean femoral neck T-scores, T score ≤ -2.5, and similar rates of osteoporosis treatment. Interestingly, the proportion of women who experienced their index fragility hip fracture showed a declining trend among the 70-79 years and ≥ 80 years age-groups. This change may be due to increasing awareness and utilization of measures to decrease falls such as exercise, nutrition, health education and environment modifications targeted towards the elderly population. Presentation: 6/2/2024

The aim of this 5-year longitudinal cohort study was to compare the risk of incident morphometric vertebral fracture (mVF) and longitudinal bone mineral density (BMD) change between individuals with early chronic kidney disease (CKD) and those without CKD. A total of 869 Chinese postmenopausal women were enrolled in the study. Serum creatinine levels were assessed using standard methods, and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident mVF was confirmed through lateral radiographs of the thoracolumbar spine. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absorptiometry. CKD was defined based on eGFR values: 60-89 mL/min/1.73m2 for stage 2 (n = 511) and 30-59 mL/min/1.73m2 for stage 3 (n = 92). The non-CKD group included individuals with an eGFR greater than or equal to 90 mL/min/1.73m2. The incidence of mVF was not statistically different between individuals with early CKD and those without CKD (4.1% in non-CKD, 6.3% in CKD stage 2, and 7.6% in CKD stage 3; p = 0.348). Neither eGFR nor CKD status was significantly associated with incident mVF in the multivariate logistic regression analysis. Baseline BMD T-scores were negatively associated with incident mVF (LS T-score, OR = 0.603, 95% CI = 0.468-0.777; FN T-score, OR = 0.511, 95% CI = 0.350-0.746). No evidence of interaction between BMD T-scores and CKD status were identified (p = 0.284-0.785) . The differences in longitudinal BMD changes between non-CKD and CKD groups were comparable (FN BMD: -6.31 ± 7.20% in non-CKD, -5.07 ± 8.20% in CKD stage 2, and -4.49 ± 8.40% in CKD stage 3, p = 0.556; LS BMD: -1.38 ± 8.18% in non-CKD, -0.32 ± 7.14% in CKD stage 2, and 1.5 ± 6.97% in CKD stage 3, p = 0.406). Individuals with a higher baseline FN BMD showed a greater longitudinal FN BMD loss (r = -0.185, p < 0.001) . Our study revealed that early CKD was not associated with an increased risk of incident mVF or greater longitudinal BMD loss. Moreover, CKD did not modify the association between BMD and the risk of incident mVF, suggesting that the management and prevention of fractures in early CKD should be approached similarly to those without CKD. Measurement of BMD appears to be crucial for predicting incident mVF risk and longitudinal bone loss in early CKD.

Patients with end-stage kidney disease (ESKD) caused by type 1 diabetes mellitus (T1DM) have a heightened fracture risk. Bone mineral density (BMD) may predict fracture less accurately in ESKD than in patients with chronic kidney disease (CKD) stages 1-3b or the general population. Alternate, readily available imaging modalities are needed to improve ESKD fracture risk assessment. This study aimed to assess dual-energy X-ray absorptiometry (DXA)-derived BMD, the trabecular bone score (TBS) and advanced hip analysis parameters in patients with ESKD due to T1DM and to compare their results with those of patients with ESKD from other causes. We compared the DXA-derived TBS, hip cortical thickness (CT) and femoral neck (FN) buckling ratio (BR), an index of FN stability, of patients with T1DM and ESKD undergoing simultaneous pancreas kidney transplantation, patients with ESKD from other causes receiving kidney transplants and population reference ranges. Of 227 patients with ESKD, 28% had T1DM and 65% were male. Compared with other ESKD patients, patients with T1DM were younger (42 ± 7.7 vs 51 ± 13.8 years), had shorter dialysis duration (24.4 ± 21 vs 42.6 ± 40 months), had higher HbA1c (7.9 ± 1.57% vs 5.4 ± 0.95%) and had lower BMI (25 ± 6 vs 27 ± 5 kg/m2). They had lower spine, hip and UD radius BMD Z-scores (all P ≤ 0.001), TBS (1.33 ± 0.12 vs 1.36 ± 0.12; P = 0.05), CT at the FN (P = 0.03), calcar (P = 0.006) and shaft (P < 0.001) and higher BR (10.1±7.1 vs 7.7±4; P = 0.006). All ESKD parameters were lower than population-based reference ranges (P < 0.001). Adjusting for age, sex, dialysis vintage and weight, prevalent vertebral fractures in patients with T1DM and ESKD were associated with higher BR (odds ratio (OR): 3.27 (95% CI: 1.19-8.92), P = 0.002) and lower FN CT (OR: 3.70 (95% CI: 1.13-12.50)). Patients with ESKD and T1DM have reduced TBS, reduced CT and increased BR compared with other ESKD patients. Prospective study of these parameters is warranted to determine their utility in fracture risk prediction and management. Patients with ESKD and T1DM have an elevated fracture risk due to decreased bone strength. As an adjunct to BMD, evaluating dual-energy X-ray absorptiometry parameters that incorporate structural change may have greater value in patients with ESKD and T1DM than in the general population. In this study, patients with ESKD due to T1DM had lower BMD, lower trabecular bone scores, more severe loss of CT and higher BR than other patients with ESKD and people from the general population. Both lower CT and higher BR were associated with prevalent vertebral fractures in patients with T1DM and ESKD. Changes to these parameters should be evaluated for incident fracture prediction.

Low Bone Mineral Density and Fractures in Long-Term Hemodialysis Patients: A Meta-Analysis

Low bone mineral density (BMD) is a strong risk factor for low trauma fractures in the postmenopausal population without known chronic kidney disease (CKD). In stage 1–3 CKD, low BMD can also be used to predict fracture risk with the gradient of risk similar to patients without CKD even though patients with stage 3 CKD have an approximate doubling of risk compared with age-matched patients without CKD. This greater risk of fracture in stage 3 CKD is not calculated in the current FRAX model. In stage 4–5 CKD, BMD by dual-energy x-ray absorptiometry (DXA) is a poor predictor of fracture risk probably related to the severe derangements in bone metabolism in severe CKD, which alter bone quality and strength not measured by DXA. Serial BMD by DXA, however, may be useful in all stages of CKD to monitor for potential loss of BMD or effect of pharmacological agents to improve BMD. Newer radiological technologies, particularly high-resolution peripheral quantitative computerized tomography (HRpQcT) of the radius and tibia show promise to define the microstructural changes in bone that explain the greater risk of fracture observed in patients with CKD versus patients without CKD. BMD by DXA may still be of value across the spectrum of CKD, but physicians should realize its limitations and understand the greater risk of fracture in patients in all stages of CKD as compared to age-matched and BMD-matched patients without CKD.

BACKGROUND AND OBJECTIVES:The effects of vitamin D on bone mass remain to be understood. This study was conducted with the objective of evaluating the influence of 25-hydroxyvitamin D (25OHD) levels on bone mineral density (BMD) among Saudi nationals.DESIGN AND SETTING:Cross-sectional study carried out at university hospital from 1 February 2008 to 31 May 2008.SUBJECTS AND METHODS:Healthy Saudi men and women in the peak bone mass (PBM) age group and those aged ≥50 years were recruited from the outpatient department of King Fahd University Hospital, Al Khobar, Saudi Arabia, between February 1, 2008, and May 31, 2008. Patient age and sex were documented, and body mass index was calculated. Hematological, biochemical, and serum 25OHD tests were performed. BMD was determined by dual-energy x-ray absorptiometry of the upper femur and lumbar spine. Patients were divided into three groups, based on their 25OHD level.RESULTS:Data from 400 patients were analyzed. Among individuals with a normal 25OHD level, 50% of women and 7% of men in the PBM age group and 26.4% of women and 49.2% of men aged ≥50 years had low bone mass. In patients with 25OHD insufficiency, 84.2% of women and 88.9% of men in the PBM age group and 83.3% of women and 80% of men aged ≥50 years had low bone mass. Results for patients with 25OHD deficiency revealed that none of the men and women in the PBM age group or ≥50 years old had normal BMD. Significant positive correlations between 25OHD level and BMD and significant negative correlations with parathyroid hormone were shown in most of the groups.CONCLUSIONS:This study showed that the vitamin D level significantly influences BMD reading among Saudi individuals. Evaluation and treatment of hypovitaminosis D should be considered during management of low bone mass.

Bone mineral density progression following long-term simultaneous pancreas-kidney transplantation in type-1 diabetes

The utility of bone mineral density (BMD) testing in chronic kidney disease (CKD) is not known. We performed a meta-analysis of studies reporting on BMD and fracture in CKD. All but one study was cross-sectional. BMD was lower in those with CKD and fractures compared to those without fractures. CKD is associated with an increased risk of fracture. The utility of dual energy X-ray absorptiometry (DXA) to assess fracture risk in CKD is unknown. We performed an updated meta-analysis and systematic review of published studies that reported on the association between DXA and fracture (morphometric spine or clinical nonspine) in predialysis and dialysis CKD. We identified 2,894 potential publications, retrieved 292 for detailed review, and included 13. All but one study was cross-sectional and three reported on the ability of DXA to discriminate fracture status in predialysis CKD. Results were pooled using a random effects model and statistical heterogeneity was assessed using the I2 statistic. BMD was statistically significantly lower at the femoral neck, lumbar spine, the 1/3 and ultradistal radius in subjects with fractures compared to those without regardless of dialysis status. For example, femoral neck BMD was 0.06 g/cm2 lower in dialysis subjects and 0.102 g/cm2 lower in predialysis subjects with fractures compared to those without. Lumbar spine BMD was 0.05 g/cm2 lower in dialysis subjects and 0.108 g/cm2 lower in predialysis subjects with fractures compared to those without. Our meta-analysis was limited to studies with small numbers of subjects and even smaller numbers of fractures. All of the studies were observational and only one was prospective. There was statistical heterogeneity at the lumbar spine, 1/3 and ultradistal radius. Our findings suggest that BMD can discriminate fracture status in predialysis and dialysis CKD. Larger, prospective studies are needed.

Both the presence of peripheral arterial disease and chronic kidney disease has been reported to be independent risk factors associating with poor prognosis. However, the impact of combination of peripheral arterial disease and chronic kidney disease remains unknown. The long-term outcome in 715 consecutive patients who had undergone coronary angiogram for the evaluation of chest pain was analyzed. Patients on haemodialysis were excluded from this analysis. Cohort patients were divided into four groups according to the Ankle Brachial Index (ABI <0.9) and glomerular filtration rate (GFR <60 mL/min per m(2)): group A (n= 498; ABI >0.9, GFR >60); B (n = 65, ABI <0.9, GFR >60); C (n = 99; ABI >0.9, GFR <60); and D (n = 53; ABI <0.9, GFR <60). The mean follow-up period was 620 +/- 270 days and evaluated the major cardiac adverse events included survival, stroke, acute coronary syndrome and heart failure. The mean follow-up period was 620 +/- 270 days. Total long-term event was present in 89 patients (groups A-D were 9.4%, 18.5%, 15.2% and 28.3%, respectively). Long-term event rate was 28.3% for patients with the presence of peripheral arterial disease and chronic kidney disease, compared to 9.4% for those without peripheral arterial disease and chronic kidney disease (P < 0.0001). Kaplan-Meier event-free survival curves also showed that the combination of peripheral arterial disease and chronic kidney disease predicted long-term event rate. The combination of chronic kidney disease and ABI of less than 0.9 undergoing coronary angiogram is strongly associated with long-term event rate.

When and how should bone mineral density be measured?

Decreased lean body mass or muscle mass is associated with decreased bone mineral density in individuals with preserved renal function. However, the association between muscle mass and bone mineral density in chronic kidney disease (CKD) patients is not well known. The aim of this study was to assess the relationship between muscle mass estimated from urine creatinine (UCr) and bone mineral density in Korean CKD patients. This cross-sectional study analyzed 1872 participants from the Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) cohort. Participants underwent UCr (g/day) and bone mineral density measurements, which were measured at the lumbar spine, total hip, and femoral neck by dual-energy X-ray absorptiometry. Patients were divided into three groups according to the tertiles of 24h UCr (T1-T3). The mean values for 24h urine creatinine of T1, T2, and T3 were 0.83 ± 0.23g, 1.18 ± 0.24g, and 1.55 ± 0.38g, respectively. A total of 172 patients were diagnosed withosteoporosis. The number of patients in each group was 92 (14.4%) in T1, 45 (7.3%) in T2, and 35 (5.7%) in T3. The odds ratio (95% confidence interval) for osteoporosis was 0.37 (0.20-0.69) for 1g/day increase of UCr. Compared with T1, the odds ratios (95% confidence interval) for osteoporosis were 0.58 (0.39-0.87) for T2 and 0.51 (0.32-0.80) for T3. Low 24-h UCr was associated with low bone mineral density. Low 24h UCr was significantly and independently associated with osteoporosis in Korean pre-dialysis CKD patients. Further research is warranted to verify the influence of muscle mass on bone health in CKD.

Vascular calcification (VC) and arterial stiffness are major contributors to cardiovascular (CV) disease in chronic kidney disease (CKD). Both are independent predictors of CV mortality and are inversely correlated with bone mineral density (BMD). Few studies have addressed the extent of VC in the pre-dialysis CKD population, with associated measurements of BMD and arterial compliance. We report cross-sectional data on 48 patients with CKD (GFR 17-55 ml/min) assessing the prevalence of VC and its associations. All patients had computed tomography (CT) scans through abdominal aorta and superficial femoral arteries (SFAs) to determine VC, pulse wave velocity (PWV) using SphygmoCor device (AtCor PWV Inc., Westmead, Australia) measuring arterial stiffness, and dual-energy X-ray absorptiometry (DEXA) scans to determine BMD, as well as serum markers of renal function and mineral metabolism. Patients, 71% male, 54% diabetic, had a median age 64.5 years. Mean estimated GFR was 35.1 +/- 10 ml/min. Mean PWV was 10.0 +/- 4.5 m/s and mean aortic VC score was 421.5 +/- 244 Hounsfield units, with 90% of subjects having some aortic VC present. In univariate linear regression analysis, aortic VC correlated positively with age (r 0.50, P < 0.001), triglycerides (r 0.47, P = 0.002) and PWV (r 0.33, P = 0.03). There was also greater VC with declining renal function (r -0.28, P = 0.05). There was no significant association between VC and serum markers of mineral metabolism, however phosphate and Ca x P correlated positively with PWV (r 0.35, P = 0.02, r 0.36, P = 0.02, respectively). There was also a positive association between PWV and triglycerides (P = 0.008), and a trend towards greater PWV with increasing age (P = 0.09). In multivariate regression analysis only increasing age and triglyceride levels were significantly associated with aortic VC and PWV. Mean spine and femoral T-scores on DEXA were 0.48 and -1.31 respectively, with 13% of subjects having femoral T-score <-2.5 (osteoporotic range). SFA VC inversely correlated with femoral T-scores (r -0.43, P = 0.004); however, there was a positive (likely false) association between spine T-scores and aortic VC (r 0.37, P = 0.01), related to the limitation of vertebral DEXA in CKD. There is a high prevalence of VC in pre-dialysis CKD patients, worse with increasing age, triglycerides and reducing renal function. Correlation exists between VC and PWV and determination of one or both may be useful for CKD patient CV risk assessment. Femoral BMD is inversely associated with SFA VC, but measurement of vertebral BMD by DEXA is unreliable in CKD patients with aortic VC.

Introduction: Chronic kidney disease (CKD) and osteoporosis are important health problems. There is an interrelationship between osteoporosis and CKD. Bone densitometry is the “gold” standard in the diagnosis of osteoporosis. Unfortunately, there are some problems with the interpretation of bone densitometry in CKD patients. The goal of this study was to determine bone mineral density (BMD) in CKD patients, to assess the difference between genders and different sites of bone densitometry correlation between BMD and laboratory parameters, and to assess the most optimal measuring site. Methods: We studied 134 hemodialysis (HD) patients (62 females, 72 males). The mean age was 56.4 ± 12.4 years and the mean duration of HD was 54.4 ± 60 months. BMD of the lumbar spine (posterior–anterior projection and lateral projection), hip (femoral neck, trochanter, intertrochanter, total femur, the Ward's Triangle), and forearm (ultradistal (UD), middistal (MID), distal third portion, and total forearm) was measured using dual X-ray absorptiometry (DXA) (Hologic Delphi apparatus). Values were expressed as BMD, T-score, and Z-score. Results: Females had lower values of BMD in all measurement points. There were no significant differences in T- and Z-scores of forearm between males and females. Age was in a positive correlation with lumbar spine BMD in males and females. There was a negative correlation with neck and forearm BMD in both groups. Serum parathyroid hormone (PTH) was also in negative correlation with hip and forearm BMD in both groups. The best correlation of BMD in different sites was between forearm and neck. Conclusion: BMD data in CKD patients should be interpreted with caution and appendicular skeletal sites should be included in the evaluation.