Renal Osteodystrophy: Multimodality Imaging

The trabecular bone score: Relationships with trabecular and cortical microarchitecture measured by HR-pQCT and histomorphometry in patients with chronic kidney disease.

This study evaluates TBS for estimating bone microarchitecture in ESRD patients using HR-pQCT as the reference technique. TBS correlates significantly with vBMD and bone microarchitecture, unlike aBMD. TBS may complement bone health assessment in ESRD patients by offering additional information alongside aBMD. Given the high fracture risk, non-invasive techniques for assessing bone fragility in chronic kidney disease (CKD) remain important. Trabecular bone score (TBS) may provide additional information that could help guide treatment and follow-up decisions. The aim of this study is to investigate whether TBS reflects bone microarchitecture in end-stage renal disease (ESRD) patients, using high-resolution peripheral quantitative computed tomography (HR-pQCT) as the reference technique. Additionally, we aim to identify parameters associated with a low TBS. Seventy-five ESRD patients were included at the time of kidney transplantation (KTx). Areal bone mineral density (aBMD) was analyzed using dual-energy X-ray absorptiometry (DXA). TBS was assessed from the L1-L4 area during DXA. Volumetric BMD (vBMD) and bone microarchitecture at tibia and radius sites were analyzed using HR-pQCT. In ESRD patients, those with TBS < 1.370 were older and had a higher body mass index (BMI). In contrast to T-score-based classification (≤ -2.5 or > -2.5), low TBS was linked to significantly lower trabecular and cortical vBMD, reduced trabecular bone volume fraction (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). In multivariate analysis, older age, higher BMI, and lower Tb.N remained independently associated with low TBS, while no HR-pQCT parameters were linked to low aBMD (T-score ≤ -2.5). TBS correlates with both trabecular and cortical parameters measured by HR-pQCT, potentially offering a complementary perspective on bone microstructure compared to aBMD. At the time of KTx, a low TBS appears to better discriminate patients with significantly lower vBMD than aBMD alone.

To evaluate whether bone assessment by radiofrequency echographic multi-spectrometry (REMS) is influenced by trabecular bone integrity by comparing it to dual-energy X-ray absorptiometry (DXA) and the trabecular bone score (TBS). Additionally, the study aims to determine if comparing fracture risk using FRAX and the National Osteoporosis Guideline Group (NOGG) using the T-score from each method would lead to differences in a Brazilian female population. A sample of women aged 30-80 underwent REMS and DXA scans of axial sites at the Hospital São Paulo, Brazil. Subsequently, TBS was applied to DXA exams. Clinical data were obtained from hospital records and phone interviews to calculate fracture risk. Among the 343 participants enrolled, 213 had comparable lumbar spine exams by REMS, DXA, and TBS, and 166 had comparable hip exams by REMS and DXA. The correlation between lumbar spine bone mineral density (BMD) by REMS and the TBS was low (r = 0.27, p < 0.001), as was the correlation between DXA and TBS (r = 0.39, p < 0.001). No statistically significant difference was found between the TBS classifications of osteoporotic lumbar spine by REMS and DXA (p = 0.178). Fracture risk data by FRAX were obtained from 119 participants, with 92% receiving concordant NOGG classifications for major osteoporotic fracture risk from REMS and DXA (κ = 0.71 CI95% (0.54 to 0.89), p < 0.001), and 87% for hip fracture risk (κ = 0.58 CI95% (0.38 to 0.77), p < 0.001). REMS performed similarly to DXA in assessing trabecular integrity using TBS. Additionally, no statistically significant difference was observed in fracture risk assessment by FRAX based on NOGG recommendations.

Bone Health in Chronic Kidney Disease–Mineral and Bone Disease

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n=113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L1 to L4 aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and β-isomerized C-terminal telopeptide of type I collagen (β-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).

In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. This was a cross-sectional study conducted in a referral center. Participants were 22 postmenopausal women with PHPT. Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT.

Trabecular Bone Score Is Associated With Volumetric Bone Density and Microarchitecture as Assessed by Central QCT and HRpQCT in Chinese American and White Women

Background/Objectives: A significantly higher fracture risk characterizes Type 2 diabetes mellitus (T2DM) patients when compared to the non-diabetic population, even though their average bone mineral density (BMD) tends to be normal or high. This elevated risk is primarily driven by defective bone quality. The trabecular bone score (TBS) and radiofrequency echographic multispectrometry (REMS) have recently been proposed to improve the assessment of bone quality in T2DM individuals. This study aimed to evaluate whether TBS and REMS can improve the identification of osteoporosis and fracture risk in these patients. Methods: BMD was measured in 223 consecutive T2DM patients (126 women and 97 man) and 102 controls. BMD values for the lumbar spine (LS), femoral neck (FN), and total hip (TH) were obtained via both dual-energy X-ray absorptiometry (DXA) and radiofrequency echographic multi-spectrometry (REMS). In all patients, TBS and Fragility Score (FS) by REMS were measured and prior major osteoporotic fractures (MOF) were assessed. Results: All BMD T-scores measured by REMS were significantly lower than those obtained by DXA at both lumbar and femoral sites. T2DM patients with previous MOF exhibited lower T-scores for both BMD-LS and BMD-TH, as assessed by DXA and REMS, compared with patients without fractures. However, these differences reached statistical significance for BMD-TH with both techniques and for BMD-LS with REMS, but not for BMD-LS with DXA. Moreover, patients with a history of MOF had significantly lower TBS values (p < 0.05) and significantly higher FS values at both lumbar (p < 0.05) and femoral (p < 0.01) sites compared with those without fractures. Conclusions: The results of this study suggest that the parameters obtained using REMS technology (BMD and FS) may be valuable tools for improving the diagnosis of osteoporosis and assessing fracture risk in patients with T2DM.

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)

Patients with acromegaly are at increased risk of fractures, regardless of areal bone mineral density (BMD). This study aimed to identify whether vertebral fractures (VFs) are related to decreases in bone volumetric density and microstructure via high-resolution peripheral quantitative computed tomography (HR-pQCT) and the trabecular bone score (TBS). VF was evaluated in 49 patients with acromegaly (22 men and 27 women) via spine X-ray. Areal BMD, volumetric BMD, and bone microstructure were analyzed via dual-energy X-ray absorptiometry (DXA) and HR-pQCT. Lumbar spine trabecular quality was assessed via TBS. Morphometric VFs were identified in 22 patients (11 men and 11 women), accounting for 44.9% of the cohort. Hypogonadism was more common in patients with VFs (59.1% vs. 22.2%; p = 0.017). BMD measured by DXA or HR-pQCT did not differ between patients with and without VFs. The proportion of patients classified as having partially degraded or degraded bone microstructure according to a TBS < 1.310 was 26% (with VF) vs. 32% (without VF; p = 0.749). There was no difference in bone geometry (trabecular and cortical area, cortical perimeter) or microstructure (number, thickness, separation, and trabecular heterogeneity, as well as cortical thickness), except for a trend toward greater cortical porosity at the distal radius in patients with VFs (p = 0.067). VFs were identified in 44.9% of patients with acromegaly, and hypogonadism was more common among those with VFs. There were no significant differences in bone density or microstructure measured by DXA, TBS, or HR-pQCT in patients with or without VFs.

Imaging in osteogenesis imperfecta: Where we are and where we are going

Background Areal bone mineral density is predictive for fracture risk. Microstructural bone parameters evaluated at the appendicular skeleton by high-resolution peripheral quantitative computed tomography (HR-pQCT) display differences between healthy patients and fracture patients. With the simple geometry of the cortex at the distal tibial diaphysis, a cortical index of the tibia combining material and mechanical properties correlated highly with bone strength ex vivo. The trabecular bone score derived from the scan of the lumbar spine by dual-energy X-ray absorptiometry (DXA) correlated ex vivo with the micro architectural parameters. It is unknown if these microstructural correlations could be made in healthy premenopausal women.Methods Randomly selected women between 20–40 years of age were examined by DXA and HR-pQCT at the standard regions of interest and at customized sub regions to focus on cortical and trabecular parameters of strength separately. For cortical strength, at the distal tibia the volumetric cortical index was calculated directly from HR-pQCT and the areal cortical index was derived from the DXA scan using a Canny threshold-based tool. For trabecular strength, the trabecular bone score was calculated based on the DXA scan of the lumbar spine and was compared with the corresponding parameters derived from the HR-pQCT measurements at radius and tibia.Results Seventy-two healthy women were included (average age 33.8 years, average BMI 23.2 kg/m2). The areal cortical index correlated highly with the volumetric cortical index at the distal tibia (R = 0.798). The trabecular bone score correlated moderately with the microstructural parameters of the trabecular bone.Conclusion This study in randomly selected premenopausal women demonstrated that microstructural parameters of the bone evaluated by HR-pQCT correlated with the DXA derived parameters of skeletal regions containing predominantly cortical or cancellous bone. Whether these indexes are suitable for better predictions of the fracture risk deserves further investigation.

In subjects with chronic kidney disease (CKD) who suffer a minimal trauma fracture, the problem is to differentiate between osteoporosis and the various forms of renal bone disease associated with CKD-mineral and bone disorder. This problem is exacerbated by the fact that renal osteodystrophy may coexist with osteoporosis. The World Health Organization's bone mineral density (BMD) criteria for osteopenia ( -2.5<T-score<-1.0) and osteoporosis (a T-score≤-2.5) may be used in patients with CKD stages 1-3. In CKD stages 4-5, BMD by dual-energy X-ray absorptiometry (DXA) is less predictive and may underestimate fracture risk. The development of absolute fracture risk (AFR) algorithms, such as FRAX® and the Garvan absolute fracture risk calculator, to predict risk of fracture over a given time (usually 10years) aims to incorporate non-BMD risk factors into the clinical assessment. FRAX® has been shown to be useful to assess fracture risk in CKD but may underestimate fracture risk in advanced CKD. The trabecular bone score is a measure of grey scale homogeneity obtained from spine DXA, which correlates to trabecular microarchitecture and is an independent risk factor for fracture. Recent data demonstrate the potential utility of the trabecular bone score adjustment of AFR through the FRAX® algorithm in subjects with CKD. Parameters of bone microarchitecture using peripheral quantitative computed tomography (pQCT) or high-resolution pQCT are also able to discriminate fracture status in subjects with CKD. However, there are at present no convincing data that the addition of pQCT or high-resolution pQCT parameters to DXA BMD improves fracture discrimination. More advanced estimates of bone strength derived from measurements of micro-architecture, by QCT-derived finite element analysis may be incorporated into AFR algorithms in the future.

Bone microstructure evaluated by TBS and HR-pQCT in Chinese adults with X-linked hypophosphatemia

Bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT) was assessed in adult patients with mild, moderate, and severe osteogenesis imperfecta (OI). The trabecular bone score (TBS), bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA), and dual X-ray and laser (DXL) at the calcaneus were likewise assessed in patients with OI. Trabecular microstructure and BMD in particular were severely altered in patients with OI. OI is characterized by high fracture risk but not necessarily by low BMD. The main purpose of this study was to assess bone microarchitecture and BMD at different skeletal sites in different types of OI. HR-pQCT was performed in 30 patients with OI (mild OI-I, n = 18 (41.8 [34.7, 55.7] years) and moderate to severe OI-III-IV, n = 12 (47.6 [35.3, 58.4] years)) and 30 healthy age-matched controls. TBS, BMD by DXA at the lumbar spine and hip, as well as BMD by DXL at the calcaneus were likewise assessed in patients with OI only. At the radius, significantly lower trabecular parameters including BV/TV (p = 0.01 and p < 0.0001, respectively) and trabecular number (p < 0.0001 and p < 0.0001, respectively) as well as an increased inhomogeneity of the trabecular network (p < 0.0001 and p < 0.0001, respectively) were observed in OI-I and OI-III-IV in comparison to the control group. Similar results for trabecular parameters were found at the tibia. Microstructural parameters were worse in OI-III-IV than in OI-I. No significant differences were found in cortical thickness and cortical porosity between the three subgroups at the radius. The cortical thickness of the tibia was thinner in OI-I (p < 0.001), but not OI-III-IV, when compared to controls. Trabecular BMD and trabecular bone microstructure in particular are severely altered in patients with clinical OI-I and OI-III-IV. Low TBS and DXL and their significant associations to HR-pQCT parameters of trabecular bone support this conclusion.