High-resolution Peripheral Quantitative Computed Tomography Research Articles

Bone microarchitecture evaluated by HR-pQCT in Chinese adolescent and pediatric patients with X-linked hypophosphatemia.

X-linked hypophosphatemia (XLH) is the most common form of heritable hypophosphatemic rickets. Previous studies have found deteriorated bone microarchitecture in the XLH adults. Detailed studies on the skeletal microarchitecture of XLH adolescent and pediatric patients are still lacking. This study aimed to evaluate bone geometry, density, microarchitecture, stiffness in XLH adolescent and pediatric patients by using high-resolution peripheral quantitative computed tomography (HR-pQCT).Method: This study utilized HR-pQCT to assess bone geometry, density, microarchitecture, and stiffness in 106 Chinese adolescent and pediatric patients with XLH. Compared with the sex- and age-matched controls, XLH patients had significantly higher trabecular area (Tb.Ar), lower total volumetric bone mineral density (Tot.vBMD), lower cortical volumetric BMD (Ct.vBMD), and lower stiffness at both the distal radius and the tibia after adjusting for height and weight. Alkaline phosphatase Z score (ALP-Z), a marker to reflect the disease activity of rickets, was negatively correlated with Ct.vBMD and cortical thickness (Ct.Th) at the distal radius, and Ct.vBMD at the distal tibia, and positively correlated with cortical porosity (Ct.Po) at the distal tibia. We developed an online calculator to estimate Tb.Ar, Ct.vBMD, and stiffness of the distal tibia of XLH adolescent and pediatric patients based on clinical general characteristic and biochemical indicators. The bone microarchitecture of XLH adolescent and pediatric patients was deteriorated, and ALP-Z was negatively correlated with the skeletal quality of XLH adolescent and pediatric patients, especially in the cortical bone. HR-pQCT parameters can be estimated using clinical characteristics and biochemical indicators, which may assist physicians to monitor the disease progression in areas without HR-pQCT access.

Preferable effect of CTLA4-Ig on both bone erosion and bone microarchitecture in rheumatoid arthritis revealed by HR-pQCT.

This exploratory study aimed to examine the impact of abatacept treatment on bone structure in patients with rheumatoid arthritis (RA) using high-resolution peripheral quantitative computed tomography (HR-pQCT). RA patients initiating either abatacept or newly introduced csDMARDs were enrolled in this prospective, non-randomized, two-group study. Bone structure in the 2nd and 3rd metacarpal heads was assessed using HR-pQCT at 0, 6, and 12months after enrollment. Synovitis was evaluated using musculoskeletal ultrasound and MRI. The adjusted mean between-group differences (abatacept-csDMARDs group) were estimated using a mixed-effect model. Thirty-five patients (abatacept group: n = 15; csDMARDs group: n = 20) were analyzed. Changes in erosion volume, depth and width were numerically smaller in the abatacept group compared to the csDMARDs group (adjusted mean between-group differences: - 1.86 mm3, - 0.02mm, and - 0.09mm, respectively). Over a 12-month period, 5 erosions emerged in the csDMARDs group, while only 1 erosion appeared in the abatacept group. Compared to csDMARDs, abatacept better preserved bone microarchitecture; several components of bone microarchitecture were significantly worsened at 6months in the csDMARDs group, but were not deteriorated at 6months in the abatacept group. Changes in synovitis scores were similar between the two treatment groups. Our results indicate that abatacept prevented the progression of bone erosion including new occurrence, and also prevented worsening of bone strength independently with synovitis compared to csDMARDs including MTX. Thus, abatacept treatment may provide benefits not only in inhibiting the progress of bone erosion but also in preventing bone microarchitectural deterioration.

Aromatase inhibitors, bone microstructure, and estimated bone strength in postmenopausal women with breast cancer: a 5-year prospective study.

Aromatase inhibitors (AIs) are the standard treatment for early breast cancer (EBC) and are typical causative agents of cancer treatment-induced bone loss. However, the effects of long-term treatment with these drugs on bone microstructure remain unclear. This prospective, single-arm observational study included postmenopausal, non-osteoporotic women with hormone receptor-positive EBC. Patients who underwent dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type I N-terminal propeptide levels were compared at baseline and at 60months after commencing AI treatment. Fifteen women were included in the study, with a median age of 58years and a quartile range of 56.5-62.5years. At 60months, HR-pQCT revealed that the cortical area and thickness decreased with increased cortical porosity in the cortical bone. In addition, the number of trabeculae decreased and trabecular separation increased trabecular bones decreases, and trabecular bone separation opens, resulting in a decrease in the trabecular bone volume fraction. Total bone mineral density (BMD), trabecular volumetric BMD, and cortical volumetric BMD, and estimated bone strength significantly decreased. DXA BMD values significantly decreased in the total hip and femoral neck but not the lumbar spine. TRACP-5b values after 5years of AI treatment showed a significant negative correlation with the rate of change in the total volumetric BMD in the distal tibia. Postmenopausal women who received AIs for 5years for EBC experienced significant deterioration in the bone microstructure, BMD, and estimated bone strength.

Detecting New Erosions in Rheumatoid Arthritis over One Year - Radiography and High-Resolution Computed Tomography of Finger Joints.

To compare the number of new erosions in two metacarpophalangeal (MCP) joints over one year assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) and conventional radiography (CR). Furthermore, to estimate the diagnostic accuracy of erosive progression by CR with HR-pQCT as the reference standard. Paired sets of image data were available from patients with RA (n=310), who underwent HR-pQCT and CR, including the 2nd and 3rd MCP joints only of the dominant hand at baseline and at the one-year follow-up. Erosion number was determined using HR-pQCT and CR. Erosive volume was estimated from segmented HR-pQCT images, and erosion scores were obtained by the Sharp/van der Heijde method from CR. Erosive progression was defined as an increase in total erosion number or a study-specified increase in total erosive volume or total erosion score. At baseline, 250 erosions were identified by CR compared to 1864 erosions by HR-pQCT. After one year, 3 new erosions were detected by CR compared to 66 new erosions by HR-pQCT. Erosive progression was identified in 40 patients using HR-pQCT and in 3 patients using CR. With HR-pQCT as reference, CR had a sensitivity of 2.5% (95% CI: 0.1-13.2%) and a specificity of 99.3% (95% CI: 97.3-99.9%) for detecting erosive progression. HR-pQCT identified more than 20 times the number of new erosions, and more than 10 times as many patients with erosive progression than CR. HR-pQCT is a sensitive tool for monitoring new erosions and erosive progression over one year in RA.

Predictive Diagnostic Model for Early Osteoporosis Detection Using Deep Learning and Multimodal Imaging Data: A Systematic Review and Meta-Analysis

Osteoporosis is a common condition that weakens bones, making them more prone to fractures. Early detection is crucial for preventing fractures and improving patients’ quality of life. However, traditional methods, such as Dual-Energy X-ray Absorptiometry (DXA), often struggle to accurately predict fracture risk and may overlook minor changes in bone structure. This study focuses on developing a predictive model for early osteoporosis detection using deep learning algorithms combined with various imaging techniques, including MRI, CT, and High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT). A systematic review and meta-analysis of studies published between 2014 and 2024 were conducted, examining the use of deep learning models applied to multimodal imaging data. The meta-analysis highlighted differences in the accuracy and effectiveness of various models, and their performance was measured in terms of accuracy, sensitivity, and specificity, following PRISMA guidelines. The results showed that deep learning models outperformed traditional methods in early osteoporosis detection. The use of multiple imaging techniques provided a more detailed assessment of bone health, allowing the models to identify complex patterns that are difficult for human interpretation. These models demonstrated high accuracy and significant potential for improving clinical decision-making. By integrating deep learning with multimodal imaging, this approach offers a promising solution for enhancing the early detection of osteoporosis. The models tested in this study proved to be highly effective, yielding more accurate fracture risk predictions and enabling earlier interventions. This could lead to better patient outcomes and reduced healthcare costs.

Circulating Baseline CXCR3+Th2 and Th17 Cell Proportions Correlate With Trabecular Bone Loss After 48 Weeks of Biological Treatment in Early Rheumatoid Arthritis.

The high prevalence of osteoporosis in rheumatoid arthritis (RA) is due to inflammation that stimulates differentiation of osteoclasts, a process involving circulating monocytes and T cell-derived factors. The aim of this study was to evaluate relations between circulating monocytes, T cell subsets, and changes in bone characteristics before and after treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in RA. Thirty patients with untreated early RA who met the American College of Rheumatology/EULAR 2010 criteria were included. Data were collected before and 48 weeks after treatment with methotrexate (MTX) together with one of three bDMARDs (abatacept, tocilizumab, or certolizumab pegol). Disease activity was measured using the Clinical Disease Activity Index, swollen or tender joint counts, C-reactive protein levels, and erythrocyte sedimentation rates. Proportions of monocyte and CD4+ T cell subsets in blood samples were analyzed by flow cytometry. Bone densitometry was performed using high-resolution peripheral quantitative computed tomography (HR-pQCT). HR-pQCT revealed an overall decrease in cortical (P = 0.009) and trabecular (P = 0.034) bone mineral density, although a subset of patients showed no bone loss after 48 weeks of treatment. The overall bone loss was not associated with age, body mass index, sex, intraarticular glucocorticoid injections, or baseline disease activity. Loss of trabecular bone volume fraction correlated with high proportions of circulating CXCR3+Th2 cells (r = -0.38, P = 0.04) and CXCR3+Th17 cells (r = -0.36, P = 0.05) at baseline. Similarly, no loss of trabecular bone volume fraction correlated with high proportions of regulatory T cells (r = 0.4, P = 0.03) at baseline. However, the associations were not significant when corrected for confounders and multiple testing. MTX together with bDMARDs efficiently reduce disease activity but only prevent bone loss in a subset of patients with RA after 48 weeks of treatment. The correlations of circulating baseline T helper cell and regulatory T cell populations with trabecular bone changes suggest a potential novel role for these cells in systemic bone homeostasis during early RA.

Patella Fractures are Associated with Bone Fragility - A Retrospective Study.

Patella fractures are not typically considered osteoporotic fractures. We compared bone mineral density (BMD) and microstructure in elderly women from a multiethnic population-based study in New York City with any history of a patella fracture (n = 27) to those without historical fracture (n = 384) and those with an adult fragility forearm fracture (n = 28) using dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HR-pQCT). Compared to those without fracture, women with patella fracture had 6.5% lower areal BMD (aBMD) by DXA only at the total hip (P=.007), while women with forearm fracture had lower aBMD at multiple sites and lower trabecular bone score (TBS), adjusted for age, body mass index (BMI), race and ethnicity (all P<.05). By HR-pQCT, adjusted radial total and trabecular (Tb) volumetric BMD (vBMD) and Tb number were 10-24% lower while Tb spacing was 12-23% higher (all P<.05) in the fracture groups versus women without fracture. Women with a forearm, but not a patella, fracture also had lower adjusted radial cortical (Ct) area and vBMD and 21.8% (P<.0001) lower stiffness vs. women without fracture. At the tibia, the fracture groups had 9.3-15.7% lower total and Tb vBMD (all P<.05) compared to the non-fracture group. Women with a forearm fracture also had 10.9, and 14.7% lower tibial Ct area and thickness versus those without fracture. Compared to women without fracture, tibial stiffness was 9.9 and 12% lower in the patella and forearm fracture groups, respectively (all P<.05). By HR-pQCT, the patella vs. forearm fracture group had 36% higher radial Tb heterogeneity (P<.05). In summary, women with patella fracture had Tb deterioration by HR-pQCT associated with lower tibial mechanical competence that was similar to those with fragility forearm fracture, a more universally accepted "osteoporotic" fracture. These data suggest patella fractures are associated with skeletal fragility and warrant skeletal evaluation.

Changes in bone density and microarchitecture in adolescents undergoing a first kidney transplantation: a prospective study

Purpose Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx), being due to pre-existing CKD-MBD, immunosuppressive therapies, and post-KTx hypophosphatemia. This study aimed to evaluate bone biomarkers and microarchitecture using high resolution peripheral quantitative computed tomography (HR-pQCT) at the time of KTx and 6 months thereafter and to compare these results with those of matched healthy controls (HC).Methods This study presented the single-center subgroup of patients aged between 10 and 18 years included in the prospective “Bone Microarchitecture in the Transplant Patient” study (TRANSOS-NCT02729142). Patients undergoing a first KTx were matched (1:2) with HC from the “Vitamin D, Bones, Nutritional and Cardiovascular Status” cohort (VITADOS) on sex, pubertal stage, and age.ResultsAt a median (interquartile range, IQR) age of 15 [13; 16] years, 19 patients (6 girls, 7 pre-emptive KTx, 7 steroid-sparing immunosuppressive strategies) underwent a first KTx, with a median [IQR] parathyroid hormone level of 1.9 [1.4; 2.9] the upper limit of normal (ULN). Higher total and trabecular bone densities, along with superior trabecular microarchitecture, were observed at KTx compared to HC. Six months post-KTx, patients had significantly impaired trabecular parameters at the radius, while results were not significantly different at the weight-bearing tibia, neither cortical parameters at both sites. Six months post-KTx, 6 (32%) patients still present with metabolic acidosis, 10 (53%) persistent hyperparathyroidism (always < 2 ULN), and 5 (26%) elevated FGF23 levels; 11 (58%) received phosphate supplementation.Conclusions: Bone density and microarchitecture at the time of KTx were superior compared to HC, but radial trabecular bone microarchitecture impairment observed 6 months post-KTx may reflect subtle albeit present post-KTx CKD-MBD.What is Known?• Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx) and is associated with morbidity. However, biochemical parameters and dual X-ray absorptiometry (DXA) are poor predictors of the underlying bone disease.What is new?• The present study on 19 adolescent KTx recipients with adequate CKD-MBD control at the time of KTx reveals no significant bone disease compared to matched healthy controls. Microarchitecture impairment observes 6 months post-KTx may reflect subtle, albeit present, post-KTx CKD-MBD.

5043 Skeletal Microstructure in Men with Celiac Disease

Abstract Disclosure: A. Rubenstein: None. A. Kondapalli: None. S. Agarwal: None. M. Bucovsky: None. I. Colon: None. N. Kil: None. S. Lewis: None. B. Lebwohl: None. P. Green: None. M. Walker: Advisory Board Member; Self; Alexion Pharmaceuticals, Inc.. The pathophysiology of osteoporosis related to celiac disease (CD) remains incompletely understood. High resolution peripheral quantitative computed tomography (HRpQCT) has revealed microarchitectural deficits in women with CD, but no data exist in men. We prospectively studied bone health using DXA and HRpQCT in 17 men with duodenal biopsy-confirmed CD (mean age 43±16 years; 82% white, 6% Asian, 12% other) and 5 male controls (mean age 40±12 years; 80% white, 20% Asian). Compared to controls, men with CD had lower self-rated health scores (p&amp;lt;0.05), but age, BMI, alcohol use, physical activity, acid blocker use, and vitamin D intake did not differ. Among patients with CD, 23.5% had other autoimmune diseases (type 1 diabetes, hypothyroidism, vitiligo, systemic sclerosis). At CD diagnosis, mean age was 34.3 ± 14.8. CD patients had a mean CD and gluten-free diet duration of 8 years. 29% of patients (n=5/17) were enrolled within 13 months of CD diagnosis. Mean tissue transglutaminase IgA, serum calcium, PTH, Vitamin D, and alkaline phosphatase were normal, but vitamin D levels were &amp;lt; 30 ng/mL in 36% (n=5/14) and PTH was elevated in 11% (n=1/9). T- (-0.5±1.5 vs. 0.8±0.8, p=0.03) and Z-scores (-0.1±1.4 vs. 1.1±0.9, p=0.05) by DXA were normal at all sites but tended to be lower at the 1/3-radius only in CD compared to controls. By HRpQCT, there were no differences. Compared to a larger control group including HRpQCT data from an additional 14 normative database controls (n=19), CD had lower radial cortical (-4.7%, p=0.02) and tibial trabecular (-13.3%, p=0.04) vBMD and a trend toward lower cortical volumetric BMD (vBMD; -3.5%, p=0.06) at the tibia. Within the CD group, longer CD duration was associated with worse tibial cortical vBMD at (r=-0.55, p=0.02). Higher PTH (n=9) correlated with lower lumbar spine areal BMD (r=-0.75, p=0.02), tibial trabecular thickness (Tb.Th; r=-0.77, p=0.02) as well as radial cortical vBMD (r=-0.81, p&amp;lt;0.01), trabecular Tb.Th (r=-0.78, p=0.01), and cortical thickness (r=-0.75, p=0.02). Those with greater dietary vitamin D intake had higher total vBMD (r=0.50, p=0.04) and trabecular thickness at the tibia (r=0.51, p=0.04). Similarly, higher 25-hydroxy vitamin D levels were associated with higher total hip aBMD (r=0.58, p=0.03). In summary, CD in men is associated with lower areal BMD at the 1/3-radius by DXA and lower vBMD at the radius and tibia by HRpQCT. Low vitamin D levels and secondary hyperparathyroidism may contribute. Further work is needed to understand the extent and pathophysiology of skeletal disease in men with CD. Presentation: 6/3/2024

7140 Assessing Bone Mineral Density and Cortical Geometry Using High-resolution Peripheral Quantitative Computed Tomography and Dual Energy X-ray Absorptiometry in Pediatric Survivors of High-risk Neuroblastoma with Growth Failure

Abstract Disclosure: S. Gera: None. M. Guo: None. N. Pollock: None. I. Hampton: None. M. Song: None. D. Weber: None. M. Denburg: None. S. Mostoufi-Moab: None. Introduction: Survival of children with high-risk neuroblastoma (HR-NBL) has increased with multimodal therapy. Cis-retinoic acid (cis-RA), cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure, posing a threat to skeletal structure. HR-NBL survivors demonstrate profound growth failure. DXA measures areal bone mineral density (aBMD). DXA is confounded by short stature and fails to distinguish between trabecular and cortical bone. We previously reported no significant difference in height-per-age adjusted aBMD-Z in HR-NBL survivors compared to healthy controls[1]. However, aBMD-Z in severe short stature may attenuate bone density deficits. High-resolution peripheral quantitative computed tomography (HRpQCT) yields 3D measures of volumetric BMD and bone architecture. Objectives: Assess volumetric BMD (vBMD) and cortical structure using distal tibia HRpQCT and leg lean mass by DXA in HR-NBL survivors compared to healthy controls in a cross-sectional study. Methods: We prospectively enrolled 20 HR-NBL survivors (median age 12.2 yrs, range 9.5 to 15.8, 7 female) treated with cis-RA (median age 2.6 yrs at start of therapy, range 0.3-9.1), and 20 age-, sex-, and race-matched healthy controls. We assessed leg lean mass adjusted for leg length by DXA. For HRpQCT, we compared tibia length (cm), cortical and trabecular vBMD (mg HA/cm3), geometry parameters (cortical and trabecular area [mm2]), and structural parameters (cortical thickness [μm] and porosity, trabecular number [mm-[1]] and separation [μm]). Outcomes were compared using Student’s t-test or Mann-Whitney U test. Linear regression models assessed difference in outcomes of bone microarchitecture and leg lean mass between both groups. Results: Compared to controls, tibia length was significantly shorter in HR-NBL survivors (32.3 ± 0.8 vs. 35.7 ± 0.6, P&amp;lt;0.005). HR-NBL survivors demonstrated lower cortical area (187.6 ± 43.8 vs. 218.7 ± 42.3, P&amp;lt;0.05), cortical perimeter (62.4 ± 7.71 vs. 69.5 ± 8.1, P&amp;lt;0.01), and leg lean mass Z-score (-1.47 ± 1.34 vs. -0.20 ± 0.84, P&amp;lt;0.001) compared to controls. Cortical geometry deficits were explained by muscle deficits (P&amp;lt;0.001). Trabecular area, BMC, areal and volumetric BMD, and measures of bone structure were not significantly different in HR-NBL survivors compared to controls. IGF-1 and 25-OH D levels had no significant effects on DXA or HRpQCT parameters. Conclusion: Bone density is not severely impacted in HR-NBL survivors. Muscle deficits persist years after treatment and explain cortical geometry deficits. HRpQCT substantiates prior DXA evaluation in HR-NBL survivors with significant short stature, demonstrating preserved bone density and structure. 1.Guo et al. Sarcopenia and preserved bone mineral density in pediatric survivors of high-risk neuroblastoma with growth failure. J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):1024-1033. Presentation: 6/3/2024

8136 Using High-Resolution Peripheral Quantitative Computed Tomography to Assess Bone Microarchitecture and Guide Osteoporosis Treatment

Abstract Disclosure: S.V. Rupani: None. J. Sfeir: None. L. Graeff-Armas: None. Bone microarchitecture is an important factor that impacts bone strength. Unlike other factors that affect bone strength, such as bone mineral density and bone turnover, assessment of bone microarchitecture is not yet widely accessible in clinical practice. Computed tomography is the primary method of non-invasively assessing bone microarchitecture. High-resolution peripheral quantitative CT (HR-pQCT) is an emerging imaging modality that provides a three-dimensional assessment of bone densitometry, morphometry, and microarchitecture with a low effective radiation dose. It provides a quantitative and qualitative assessment of cortical and trabecular structural and mechanical properties. We present two similar cases of osteoporosis in males, where knowledge of bone microarchitecture through HR-pQCT helped formulate two distinct and targeted therapeutic approaches. The first case is of a 46-year-old male with a history of idiopathic osteoporosis with multiple nontraumatic vertebral fractures. Given his presentation and age, anabolic therapy such as teriparatide was being considered. He underwent HR-pQCT scanning, which showed average radial trabecular parameters, but his cortical porosity was significantly above average, with similar findings in his tibial parameters. Since teriparatide has been shown to increase cortical porosity, this would not be the best option for our patient, given the risk of further weakening of the microarchitecture of his cortical bone. Therefore, denosumab, which has been shown to decrease cortical porosity, was chosen. Our second patient is a 52-year-old male with idiopathic osteoporosis with multiple nontraumatic vertebral fractures, whose HR-pQCT showed average cortical parameters at both the radius and tibia but low trabecular number and increased trabecular separation at both sites. Since teriparatide increases trabecular thickness and mass, we could confidently choose teriparatide for this patient, with less concern for significant deleterious effects on his cortical bone parameters. These case reports highlight the impact that the assessment of qualitative properties of bone, such as microarchitecture, can have in the management of osteoporosis. Currently, the lack of sufficient validated normative data for HR-pQCT limits its widespread use in the diagnosis of osteoporosis and fracture prediction. However, given that HR-pQCT can characterize the properties of trabecular and cortical bone, it may have a role in helping guide osteoporosis treatment, especially in challenging and atypical cases. Presentation: 6/3/2024

7892 Longitudinal Changes in Bone Microarchitecture and Strength in Girls with Type 1 Diabetes

Abstract Disclosure: R. Dhaliwal: None. R.K. Saunders: None. M. Misra: None. M.L. Bouxsein: None. D.M. Mitchell: None. Introduction: Type 1 diabetes (T1D) confers an increased fracture risk, only partly explained by low areal bone mineral density (aBMD). We have previously shown in a cross-sectional study that bone microarchitecture is altered early in the course of T1D. The goal of this study is to evaluate how T1D influences longitudinal changes in volumetric BMD (vBMD) and microarchitecture. Methods: This is a 2-year prospective study of girls ages 10-16 years (62 with T1D and 59 controls). We used dual-energy x-ray absorptiometry (DXA) to measure aBMD, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius (7% site) and tibia (8% site) to measure vBMD and microarchitecture. We used linear mixed models to assess the effects of T1D on change in bone parameters over time, adjusting for bone age as an index of skeletal maturity, height, lean mass index (LMI), and fat mass index (FMI). Results: At baseline, mean duration of disease in T1D was 4.8 ± 3.2 years, and mean HbA1c was 8.6 ± 1.4%. The groups did not differ by age, bone age, and height, while T1D participants had higher LMI (p&amp;lt;0.001) and borderline higher FMI (p=0.107). Linear growth, weight gain, and changes in body composition over time did not differ between groups. Growth-mediated aBMD gains were observed in both groups at the subtotal body, total hip, femoral neck, and spine. While adjusted aBMD as well as trabecular bone score were lower in T1D, we did not observe between-group differences in changes in these endpoints over time. In both groups, at the distal radius, we observed significant increases over time in total and cortical vBMD, cortical thickness, trabecular (Tb) thickness, and estimated failure load, while cortical porosity decreased. While several microarchitectural parameters were altered in T1D participants, we did not observe significant between-group differences in changes in these measures over time. Of note, trabecular development was subtly altered, with T1D participants demonstrating a borderline significant decrease in Tb vBMD (-14.3 ± 9.0 mg HA/cm3, p=0.112) and Tb number (-0.14 ± 0.07 mm-[1], p=0.057), while control participants had no change in Tb vBMD or number, but a significant increase in Tb thickness (5.8 ± 2.5 µm, p=0.018). At the distal tibia, we observed similar overall detrimental effects of T1D at baseline. However, we did not observe between-group differences in microarchitectural change over time. Glycemic control as measured by HbA1c was not associated with changes in skeletal parameters among T1D participants. Conclusions: T1D leads to substantially altered areal and volumetric BMD as well as microarchitectural parameters in girls. While our data suggest that much of this deficit appears to occur early in the course of disease as prospective change is similar in T1D and controls, subtle changes in trabecular bone development at the radius may indicate ongoing impairment of bone accrual. Presentation: 6/3/2024

Association between bone microarchitecture and sarcopenia in postmenopausal women with type 2 diabetes.

Type 2 diabetes (T2D) increases the risk of sarcopenia, which independently contributes to bone fragility. We aimed to explore the association between sarcopenia/sarcopenic obesity and bone quality using second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) in T2D. We analyzed the baseline participant characteristics of an ongoing randomized clinical pilot trial (CTRI/2022/02/039978). Postmenopausal women (≥ 50years) with T2D and high risk of fragility fractures were included. Areal BMD (aBMD), trabecular bone score (TBS), and body composition were measured using DXA. Bone microarchitecture was assessed at distal radius/distal tibia using HR-pQCT. Muscle strength was estimated using dominant handgrip strength (HGS). Sarcopenia was defined as low HGS (< 18.0kg) and low appendicular skeletal muscle index (ASMI) (< 4.61kg/m2). Probable sarcopenia was defined as low HGS with normal ASMI. Sarcopenic obesity was classified as co-existence of sarcopenia and obesity (BMI ≥ 25.0kg/m2). We recruited 129 postmenopausal women (mean age 64.2 ± 6.7years). Participants were categorized into four mutually exclusive groups: group A (normal HGS and ASMI, n = 17), group B (probable sarcopenia, n = 77), group C (non-obese sarcopenia, n = 18), and group D (obesesarcopenia, n = 18). The four groups did not differ significantly with regard to baseline characteristics, fracture prevalence, HbA1c, aBMD, and TBS. However, HR-pQCT-derived volumetric BMD and cortical/trabecular microarchitecture were significantly poorer in group C/group D than in group A/group B. Bone quality rather than bone density (quantity) is adversely affected in T2D postmenopausal women with sarcopenia/sarcopenic obesity, which could increase the fracture risk in this patient sub-population.

Two Decades of High-Resolution Peripheral Quantitative Computed Tomography: Present and Future Clinical Perspectives.

Twenty years have passed since the introduction of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess human bone microarchitecture. During that time, the technique has emerged as an important research tool used by clinicians and scientists to learn about the pathophysiology of bone adaptation in the context of osteoporosis and many other bone-affected conditions. Its rich three-dimensional data is well suited for precise longitudinal monitoring of bone microarchitecture and associated patient-specific estimated bone strength.However, uptake of HR-pQCT as a clinical diagnostic tool has been limited, in part due to challenges such as availability, regulatory approvals, and demonstrated cost effectiveness. New research suggests fracture risk assessment using HR-pQCT is comparable with current standards based on traditional bone densitometry, but its contribution to clinical care is best suited to two areas: (1) leveraging microarchitectural information to assist in treatment decisions for the large subset of patients who lie in the so-called gray zone by current fracture risk assessment, and (2) longitudinal monitoring that establishes highly refined trajectories of bone adaptation and can inform decisions to initiate treatment, monitor treatment effects, and inform cessation.

Reliability of Time-Lapse High-Resolution Peripheral Quantitative CT (HR-pQCT) in Determining Bone Remodeling in Patients with ESKD

Reliability of Time-Lapse High-Resolution Peripheral Quantitative CT (HR-pQCT) in Determining Bone Remodeling in Patients with ESKD

Psoas muscle cross sectional area relates to bone density and microarchitecture in candidates for spine fusion surgery

Prior studies demonstrate that muscle and bone health are integrally related, and both independently impact orthopedic surgery outcomes. However, relationships between bone density, in vivo microarchitecture, and muscle area have not been previously investigated in orthopedic surgery patients. This study assessed associations between psoas cross sectional area (CSA), bone mineral density (BMD), and microstructure in a cohort undergoing spine fusion. Pre-operatively, bilateral psoas CSA was measured on axial lumbar spine CT in the L3-L4 disc space. To adjust for body size, Psoas Muscle Index (PMI) was calculated (CSA divided by the square of patient height). High resolution peripheral quantitative CT (HR-pQCT, XtremeCT2) assessed volumetric BMD (vBMD), cortical (Ct) and trabecular (Tb) microarchitecture at the distal radius and tibia. Areal BMD (aBMD) was measured by DXA at the lumbar spine (LS), total hip (TH), femoral neck (FN), and the 1/3 radius (1/3R). Pearson correlations related psoas CSA and bone imaging parameters before and after correcting for height and weight. Among 88 patients included, mean age was 63 ± 12 years, BMI was 28 ± 7 kg/m2, 47 (53 %) were female. Larger psoas CSA was associated with higher vBMD, greater Ct thickness and better Tb microarchitecture (higher Tb number and lower Tb separation) at the tibia and radius. Larger psoas CSA was also associated with greater aBMD at TH and FN bilaterally and 1/3R (r 0.33 to 0.61; p < 0.002 for all comparisons). Psoas CSA was not associated with aBMD at the LS. Similar results were observed when relating PMI, and adjusting for age, height and weight to HR-pQCT and DXA measurements. Investigation of subgroups by sex demonstrated that relationships were similar magnitude among women but not the men. Patients who underwent primary compared to revision spine surgery had similar associations. Our results demonstrate a link between psoas muscle size and peripheral bone microarchitecture among patients undergoing posterior lumbar spinal fusion. Given the importance of both muscle and skeletal integrity to the success of spine surgery, further study regarding the associations between measurements of psoas muscle, bone microarchitecture, and surgical outcomes is warranted.

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

The Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial design and methods

BackgroundAmong older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research. The main objective of the Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial (NCT05764733) is to compare the independent and combined effects of a 12-month intervention of resistance training (RT) plus bone-loading exercises and bisphosphonate use on dietary WL-associated bone loss among 308 older (≥60 years) adults living with an indication for WL and bisphosphonate use. MethodsAll participants will receive the same group-mediated dietary intervention targeting 8–10 % WL and be randomized to one of four groups: no RT and placebo capsules (NoRT+PL); progressive RT plus bone-loading exercises and placebo capsules (RT++PL); no RT and oral bisphosphonate (70 mg weekly oral alendronate; NoRT+BIS); or progressive RT plus bone-loading exercises and oral bisphosphonate (RT++BIS). Total hip areal (a)BMD measured via dual-energy x-ray absorptiometry (DXA) is the primary, powered study outcome. Secondary skeletal outcome measures include femoral neck and lumbar spine aBMD, high resolution peripheral quantitative computed tomography (HRpQCT) bone assessments of the radius and tibia, and biomarkers of bone turnover. DiscussionBEACON will address an understudied, yet important, clinical research question by studying the independent and combined effects of two scalable intervention strategies aimed at optimizing skeletal integrity in older adults undergoing WL.Clinical Trials Registration: NCT05764733

Intermittent fasting for systemic triglyceride metabolic reprogramming (IFAST): Design and methods of a prospective, randomized, controlled trial

BackgroundCaloric restriction prolongs lifespan in model organisms and improves metrics of aging-related diseases in humans, but daily compliance is challenging. Intermittent fasting improves metrics of lipid and glucose metabolism in the setting of weight loss but whether these metrics are improved independent of weight loss is not known. MethodsWe seek to address this gap with IFAST, a single-center, three-arm, prospective, randomized, controlled clinical trial. Eligible study participants are adults with no chronic medical conditions beyond prediabetes or overweight but who are at high risk for type 2 diabetes mellitus (T2D), defined as having a history of gestational diabetes or a first-degree relative with T2D. Participants will be randomized in a 1:2:2 schema to either a control group, a fasting group, or a fasting/weight maintenance group. The fasting groups will complete a 24-h fast one day per week for 12 weeks. The key mechanistic endpoint is change in triglyceride composition (defined by carbon content and degree of saturation) as measured by longitudinal metabolomics. The key safety endpoint is percent change from baseline in bone volume fraction (BV/TV; high-resolution peripheral quantitative CT) at the radius in the fasting group. Secondary endpoints include measures of insulin sensitivity (hyperinsulinemic-euglycemic clamp), clinical lipid profiling, systemic inflammation markers, hunger assessment, bone density, and bone microarchitecture with high-resolution peripheral quantitative CT. ConclusionIFAST will investigate intrinsic metabolic benefits of intermittent fasting beyond weight loss. Trial registrationClinicalTrials.gov ID NCT05722873.

Microarchitectural analysis of the metacarpophalangeal joint using HR-pQCT in patients with rheumatoid arthritis: A comparison with healthy controls

ObjectiveTo investigate which joint microarchitectural parameters measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) serve as imaging markers for rheumatoid arthritis (RA). MethodsThe second and third metacarpophalangeal (MCP) joints of 50 patients with RA and 50 healthy controls (HCs) (aged 50–79 years, all females) were scanned using a HR-pQCT. Joint space, trabecular bone microarchitecture, and erosion were measured and compared between RA patients and HCs. ResultsThere were no differences in joint space parameters between RA patients and HCs.For bone microarchitecture, RA patients had lower trabecular bone mineral density (127 vs. 167 mg/cm3), thinner trabecular thickness (0.20 vs. 0.21 mm), fewer trabecular number (1.49 vs. 1.55 /mm), more rod-like structure (1.68 vs. 1.23), and poorer trabecular connectivity (4.51 vs. 5.72 /mm3) than HCs.Regarding erosion, RA patients had a higher number of erosions per joint (36/100 vs. 18/100), larger volume (4.62 vs. 1.89 mm3), and longer width (2.40 vs. 1.82 mm) and longer length (2.34 vs. 1.64 mm) than HCs.Most of the erosions in HCs were <5 mm3 in volume (95 %) and located on the radial side (85 %). When erosions <5 mm3 were compared between RA patients and HCs, there were no differences in their location or morphology. ConclusionsDeterioration of bone microarchitecture and existences of erosions >5 mm3 in the MCP joints are sensitive imaging markers of RA. Erosions <5 mm3 in RA patients may include not only early pathological erosion but also physiological erosion because even HCs can have erosions <5 mm3.