Causal relationships between height and weight with distal tibia microarchitecture and geometry in adult female twin pairs.

Higher stature and lower weight are associated with increased risk of fracture. However, the pathophysiology for the associations of height and weight with bone microarchitecture and geometry is unclear. We examined whether these associations were consistent with causation and/or with shared familial factors. In this cross-sectional study of 566 female twins aged 26-76 yr, a regression analysis for twin data, Inference about Causation by Examination of FAmilial CONfounding (ICE FALCON), was used for testing causation. The bone microarchitecture and geometry of the distal tibia was assessed using HR-pQCT and the StrAx1.0 software. Higher stature was associated with larger total bone cross-sectional area (CSA), lower total bone volumetric bone mineral density (vBMD), larger cortical CSA, thinner cortices, higher porosity of the total cortex, compact cortex, outer and inner transitional zone (TZ), lower cortical vBMD, and larger medullary CSA (regression coefficients (ß) ranging from -.37 to .60, all p<.05). Using ICE FALCON, the cross-pair cross-trait associations attenuated toward zero after adjusting for the within-individual association (absolute values of ß ranging from .05 to .31, all p<.001). Higher weight was associated with higher total bone vBMD, larger cortical CSA and thicker cortices, lower porosity of the total cortex and inner TZ, and higher cortical vBMD (ß ranging from -.23 to .34, all p<.001), and thinner trabeculae, higher trabecular number, lower trabecular separation, and higher trabecular vBMD (ß ranging from -.31 to .39, all p<.05). Only cortical CSA attenuated toward zero after adjusting for the within-individual association between weight and bone microarchitecture (ß = .042, p=.046). Higher stature was associated with a weaker cortical, not trabecular bone traits, whereas higher weight was associated with stronger cortical and trabecular bone traits. The results were consistent with height having a causal effect on weaker cortical bone structure, whereas weight had a casual effect on the larger cortical CSA.

A Randomized Controlled Trial on the Effect of Luseogliflozin on Bone Microarchitecture Evaluated Using HR-pQCT in Elderly Type 2 Diabetes.

INTRODUCTION: Bone fragility is a critical issue in the treatment of elderly people with type 2 diabetes (T2D). In the Canagliflozin Cardiovascular Assessment Study, the subjects with T2D who were treated with canagliflozin showed a significant increase in fracture events compared to a placebo group as early as 12 weeks post-initiation. In addition, it has been unclear whether sodium-glucose co-transporter 2 (SGLT2) inhibitors promote bone fragility. We used high-resolution peripheral quantitative computed tomography (HR-pQCT) to prospectively evaluate the short-term effect of the SGLT2 inhibitor luseogliflozin on bone strength and microarchitecture in elderly people with T2D. METHODS: This was a single-center, randomized, open-label, active-controlled pilot trial for ≥ 60-year-old Japanese individuals with T2D without osteoporosis. A total of 22 subjects (seven women and 15 men) were randomly assigned to a Lusefi group (added luseogliflozin 2.5 mg) or a control group (added metformin 500 mg) and treated for 48 weeks. We used the second-generation HR-pQCT (Xtreme CT II®, Scanco Medical, Brüttisellen, Switzerland) before and 48 weeks after the treatment to evaluate the subjects' bone microarchitecture and estimate their bone strength. RESULTS: Twenty subjects (Lusefi group, n = 9; control group, n = 11) completed the study, with no fracture events. As the primary outcome, the 48-week changes in the bone strength (stiffness and failure load) estimated by micro-finite element analysis were not significantly different between the groups. As the secondary outcome, the changes in all of the cortical/trabecular microarchitectural parameters at the radius and tibia from baseline to 48 weeks were not significantly different between the groups. CONCLUSIONS: In the pilot trial, we observed no negative effect of 48-week luseogliflozin treatment on bone microarchitecture or bone strength in elderly people with T2D. TRIAL REGISTRATION: UMIN-CTR no. 000036202 and jRCT 071180061.

Trabecular bone microstructure parameters as predictors for chronological age: a systematic review.

Estimating chronological age is crucial in forensic identification. The increased application of medical imaging in age analysis has facilitated the development of new quantitative methods for the macroscopic evaluation of bones. This study aimed to determine the association of age-related changes in the trabecular microstructure with chronological age for age estimation in forensic science through different non-invasive imaging techniques. This systematic review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. An electronic search was performed with PubMed/MEDLINE, Scopus, and Cochrane databases as well as with a Google Scholar search. Qualitative synthesis was performed using the Anatomical Quality Assessment tool. A detailed literature search yielded 3467 articles. A total of 14 articles were ultimately included in the study. A narrative approach was employed to synthesize the data. Microcomputed tomography, high-resolution peripheral quantitative computed tomography, and cone beam computed tomography have been used for the quantitative estimation of age. These imaging techniques aid in identifying the trabecular bone microarchitectural parameters for chronological age estimation. Age-related changes in trabecular bone included a decrease in the bone volume fraction, trabecular number, and connectivity density and an increase in trabecular separation. This study also revealed that morphometric indices vary with age and anatomical site. This study is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CDRD42023391873.

Chemotherapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer. MATERIALS AND METHODS: This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6 months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. RESULTS: Eighteen women were included in the study (median age: 57 years; range: 55-62 years). At 6 months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01; -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09; -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline. CONCLUSION: Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6 months after chemotherapy.

Risk Factors for Bone Microarchitecture Impairments in Older Men with Type 2 Diabetes - The MrOS Study.

CONTEXT: Impaired bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), may contribute to bone fragility in type 2 diabetes (T2DM) but data on men are lacking. OBJECTIVE: To investigate the association between T2DM and HR-pQCT parameters in older men. METHODS: HR-pQCT scans were acquired on 1794 participants in the Osteoporotic Fractures in Men (MrOS) study. T2DM was ascertained by self-report or medication use. Linear regression models, adjusted for age, race, BMI, limb length, clinic site, and oral corticosteroid use, were used to compare HR-pQCT parameters by diabetes status. RESULTS: Among 1777 men, 290 had T2DM (mean age 84.4 years). T2DM men had smaller total cross-sectional area (Tt.AR) at the distal tibia (p=0.028) and diaphyseal tibia (p=0.025), and smaller cortical area at the distal (p= 0.009) and diaphyseal tibia (p= 0.023). Trabecular indices and cortical porosity were similar between T2DM and non-T2DM. Among men with T2DM, in a model including HbA1c, diabetes duration, and insulin use, diabetes duration ≥ 10 years, compared with <10 years, was significantly associated with higher cortical porosity but with higher trabecular thickness at the distal radius. Insulin use was significantly associated with lower cortical area and thickness at the distal radius and diaphyseal tibia and lower failure load at all three scan sites. Lower cortical area, cortical thickness, total BMD, cortical BMD, and failure load of the distal sites were associated with increased risk of incident non-vertebral fracture in T2DM. CONCLUSIONS: Older men with T2DM have smaller bone size compared to non-T2DM, which may contribute to diabetic skeletal fragility. Longer diabetes duration was associated with higher cortical porosity and insulin use with cortical bone deficits and lower failure load.

High-Resolution Peripheral Quantitative Computed Tomography in Rheumatic Diseases: A New Option for Knee Osteoarthritis.

High-resolution peripheral quantitative computed tomography (HR-pQCT) provides a new opportunity for the noninvasive measurement of bone microarchitecture in patient research of rheumatic disease in joints of the extremities. Rheumatoid arthritis of the hand and osteoarthritis of the knee are highly prevalent and there are no cures, so an improved understanding of the etiology of these diseases, particularly when combining HR-pQCT with other imaging modalities, is important to develop new disease management strategies. Analysis of HR-pQCT data is challenging due to the large size of the datasets, but the field continues to rapidly develop, and there is excellent opportunity to integrate sophisticated analyses for this novel research tool.

Bone and muscle differences in children and adolescents with type 1 diabetes: The mediating role of physical activity.

Children with type 1 diabetes (T1D) experience an increased risk of fracture, which may be related to altered bone development. We aimed to assess differences in bone, muscle and physical activity (PA), and explore if better muscle and PA measures would mitigate bone differences between children and adolescents with T1D and typically developing peers (TDP). We matched 56 children and adolescents with T1D (mean age 11.9 yrs) and 56 TDP (11.5 yrs) by sex and maturity from 171 participants with T1D and 66 TDP (6-17 yrs). We assessed the distal radius and tibia with high-resolution peripheral quantitative computed tomography (HR-pQCT), and the radius and tibia shaft bone and muscle with pQCT. We also measured muscle function from force-related measures in neuromuscular performance tests (push-up, grip test, countermovement and long jump). We compared PA based on questionnaire scores and accelerometers between groups. Bone, muscle, and neuromuscular performance measures were compared using MANOVA. We used mediation to explore the role of PA and muscle in bone differences. Children and adolescents with T1D had 6-10 % lower trabecular density, bone volume fraction, thickness and number at both distal radius and tibia, and 11 % higher trabecular separation at the distal radius than TDP. They also had 3-16 % higher cortical and tissue mineral density, and cortical thickness at the distal radius, 5-7 % higher cortical density and 1-3 % higher muscle density at both shaft sites compared to TDP. PA mediated the between-group difference in trabecular number (indirect effect -0.04) at the distal radius. Children and adolescents with T1D had lower trabecular bone density and deficits in trabecular micro-architecture, but higher cortical bone density and thickness at the radius and tibia compared to TDP. They engaged in less PA but had comparable muscle measures to those of TDP. PA participation may assist in mitigating deficit in trabecular number observed in children and adolescents with T1D.

Erosive Progression by High-Resolution Peripheral Quantitative Computed Tomography and Conventional Radiography in Rheumatoid Arthritis.

OBJECTIVES: To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). METHODS: This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. RESULTS: In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). CONCLUSION: A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.

Evaluating high-resolution computed tomography derived 3-D joint space metrics of the metacarpophalangeal joints between rheumatoid arthritis and age- and sex-matched control participants.

Introduction: Rheumatoid arthritis (RA) is commonly characterized by joint space narrowing. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization and quantification of joint space in extremity joints commonly affected by RA, such as the 2nd and 3rd metacarpophalangeal joints. However, age, sex, and obesity can also influence joint space narrowing. Thus, this study aimed to determine whether HR-pQCT joint space metrics could distinguish between RA patients and controls, and determine the effects of age, sex and body mass index (BMI) on these joint space metrics. Methods: HR-pQCT joint space metrics (volume, width, standard deviation of width, maximum/minimum width, and asymmetry) were acquired from RA patients and age-and sex-matched healthy control participants 2nd and 3rd MCP joints. Joint health and functionality were assessed with ultrasound (i.e., effusion and inflammation), hand function tests, and questionnaires. Results: HR-pQCT-derived 3D joint space metrics were not significantly different between RA and control groups (p > 0.05), despite significant differences in inflammation and joint function (p < 0.05). Joint space volume, mean joint space width (JSW), maximum JSW, minimum JSW were larger in males than females (p < 0.05), while maximum JSW decreased with age. No significant association between joint space metrics and BMI were found. Conclusion: HR-pQCT did not detect group level differences between RA and age-and sex-matched controls. Further research is necessary to determine whether this is due to a true lack of group level differences due to well-controlled RA, or the inability of HR-pQCT to detect a difference.

Healing of tumor-induced osteomalacia as assessed by high-resolution peripheral quantitative computed tomography is not similar across the skeleton in the first years following complete tumor excision.

Tumor-induced osteomalacia is caused by excessive fibroblast growth factor 23 production mainly from phosphaturic mesenchymal tumors. Surgical excision or tumor ablation are the preferred treatment. Information on bone microarchitecture parameters assessed by high-resolution peripheral quantitative computed tomography is limited. We report a woman with hypophosphatemic osteomalacia with generalized pain, weakness and recurrent fractures, and a large thoracic vertebral mass extending to the posterior mediastinum. Detailed radiologic and histopathologic evaluation revealed a phosphaturic mesenchymal tumor. Two surgeries were necessary for complete removal of the mass. Clinical symptoms improved after attaining normophosphatemia. Four-year post-surgical HR-pQCT parameters, compared to baseline, showed in the left distal radius, stable trabecular and cortical volumetric bone mineral density although below reference range. There was stability of trabecular number and thickness. Both stiffness and failure load decreased. A shift in cortical parameters was noted in year 2. In the left distal tibia, trabecular volumetric bone mineral density decreased whereas cortical volumetric bone mineral density markedly increased, as did cortical area. There was stability in the trabecular number and thickness. Both stiffness and failure load improved. Findings from HR-pQCT measurements in this patient disclosed that the healing of osteomalacia is not similar across the peripheral skeletal sites in the first years following tumor removal. Results contrasted low but stable volumetric bone mineral density in the distal radius with increase in the distal tibia at the expense of cortical bone. Our report helps further delineate the pattern of bone healing after treatment of this rare bone disorder.

Peripheral quantitative computed tomography is a valid imaging technique for tracking changes in skeletal muscle cross-sectional area.

Peripheral quantitative computed tomography (pQCT) has recently expanded to quantifying skeletal muscle, however its validity to determine muscle cross-sectional area (mCSA) compared to magnetic resonance imaging (MRI) is unknown. Eleven male participants (age: 22 ± 3 y) underwent pQCT and MRI dual-leg mid-thigh imaging before (PRE) and after (POST) 6 weeks of resistance training for quantification of mid-thigh mCSA and change in mCSA. mCSA agreement at both time points and absolute change in mCSA across time was assessed using Bland-Altman plots for mean bias and 95% limits of agreement (LOA), as well as Lin's concordance correlation coefficients (CCC). Both pQCT and MRI mCSA increased following 6 weeks of resistance training (∆mCSApQCT: 6.7 ± 5.4 cm2, p < 0.001; ∆mCSAMRI: 6.0 ± 6.4 cm2, p < 0.001). Importantly, the change in mCSA was not different between methods (p = 0.39). Bland-Altman analysis revealed a small mean bias (1.10 cm2, LOA: -6.09, 8.29 cm2) where pQCT tended to overestimate mCSA relative to MRI when comparing images at a single time point. Concordance between pQCT and MRI mCSA at PRE and POST was excellent yielding a CCC of 0.982. For detecting changes in mCSA, Bland-Altman analysis revealed excellent agreement between pQCT and MRI (mean bias: -0.73 cm2, LOA: -8.37, 6.91 cm2). Finally, there was excellent concordance between pQCT and MRI mCSA change scores (CCC = 0.779). Relative to MRI, pQCT imaging is a valid technique for measuring both mid-thigh mCSA at a single time point and mCSA changes following a resistance training intervention.

Precision Errors and Monitoring Time Interval in Pediatric Muscle Imaging and Neuromuscular Performance Assessment.

OBJECTIVES: To determine precision errors and monitoring time intervals in imaged muscle properties and neuromuscular performance, and to explore growth-related factors associated with precision errors in children. METHODS: We included 35 children (mean age 10.5yrs) in the precision study cohort and 40 children (10.7yrs) in the follow-up study cohort. We assessed forearm and lower leg muscle properties (area, density) with peripheral quantitative computed tomography. We measured neuromuscular performance via maximal pushup, grip force, countermovement and standing long jump force, power, and impulse along with long jump length. We calculated precision errors (root-mean-squared coefficient of variation) from the precision cohort and monitoring time intervals using annual changes from the follow-up cohort. We explored associations between precision errors (coefficient of variation) and maturity, time interval (between repeated measures), and anthropometric changes using Spearman's rank correlation (p<0.05). RESULTS: Muscle measures exhibited precision errors of 1.3-14%. Monitoring time intervals were 1-2.6yrs, except muscle density (>43yrs). We identified only one association between precision errors and maturity (maximal pushup force: rho=-0.349; p=0.046). CONCLUSIONS: Imaging muscle properties and neuromuscular performance measures had precision errors of 1-14% and appeared suitable for follow-up on ~2yr scales (except muscle density). Maximal pushup force appeared more repeatable in mature children.

Fracture risk based on high-resolution peripheral quantitative computed tomography measures does not vary with age in older adults-the bone microarchitecture international consortium prospective cohort study.

Fracture risk increases with lower areal bone mineral density (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) dual energy X-ray absorptiometry (DXA) which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8 years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3 months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures.

Individual trabecula segmentation validation in first- and second-generation high-resolution peripheral computed tomography compared to micro-computed tomography in the distal radius and tibia.

High-resolution peripheral quantitative computed tomography (HR-pQCT) has been used for in vivo 3D visualization of trabecular microstructure. Second-generation HR-pQCT (HR-pQCT II) has been shown to have good agreement with first generation HR-pQCT (HR-pQCT I). Advanced Individual Trabecula Segmentation (ITS) decomposes the trabecula network into individual plates and rods. ITS based on HR-pQCT I showed a strong correlation to ITS based on micro-computed tomography (µCT) and identified trabecular changes in metabolic bone diseases. ITS based on HR-pQCT II has new potential because of the enhanced resolution but has yet to be validated. The objective of this study was to assess the agreement between ITS based on HR-pQCT I, HR-pQCT II, and µCT to assess the capability of ITS on HR-pQCT images as a tool for studying bone structure. Freshly frozen tibia and radius bones were scanned in the distal region using HR-pQCT I at 82 µm, HR-pQCT II at 60.7 µm, and µCT at 37 µm. Images were registered, binarized, and ITS analysis was performed. Bone volume fraction (pBV/TV, rBV/TV), number density (pTb.N, rTb.N), thickness (pTb.Th, rTb.Th), and plate-to-rod (PR) ratio (pBV/rBV) of trabecular plates and rods were obtained. Paired Student's t-tests with post hoc Bonferroni analysis were used to examine the differences. Linear regression was used to determine the correlation coefficient. The HR-pQCT I parameters were different from the µCT measurements. The HR-pQCT II parameters were different from the µCT measurements except for rTb.N, and the HR-pQCT I parameters were different from the HR-pQCT II measurements except for pTb.Th. The strong correlation between HR-pQCT II and µCT microstructural analysis (R2 = 0.55-0.94) suggests that HR-pQCT II can be used to assess changes in plate and rod microstructure and that values from HR-pQCT I can be corrected.

Bone remodeling and responsiveness to mechanical stimuli in individuals with type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) has been linked to increased osteocyte apoptosis, local accumulation of mineralized lacunar spaces, and microdamage suggesting an impairment of the mechanoregulation network in affected individuals. Diabetic neuropathy might exacerbate this dysfunction through direct effects on bone turnover, and indirect effects on balance, muscle strength, and gait. However, the in vivo effects of impaired bone mechanoregulation on bone remodeling in humans remain underexplored. This longitudinal cohort study assessed consenting participants with T1DM and varying degree of distal symmetric sensorimotor polyneuropathy (T1DM, n = 20, median age 46.5 yr, eight female) and controls (CTRL; n = 9, median age 59.0 yr, four female) at baseline and 4-yr follow-up. Nerve conduction in participants with T1DM was tested using DPNCheck and bone remodeling was quantified with longitudinal high-resolution peripheral quantitative-computed tomography (HR-pQCT, 82 µm) at the standard distal sites. Local trabecular bone formation (Tb.F) and resorption (Tb.R) sites were captured by implementing 3D rigid image registration of HR-pQCT images, and the mechanical environment across the bone microarchitecture at these sites was simulated using micro-finite element analysis. We calculated odds ratios to determine the likelihood of bone formation (ORF) and resorption (ORR) with increasing/decreasing strain in percent as markers for mechanoregulation. At the distal radius, Tb.F was 47% lower and Tb.R was 59% lower in T1DM participants compared with CTRL (P < .05). Tb.F correlated positively with nerve conduction amplitude (R = 0.69, P < .05) in participants with T1DM and negatively with glycated hemoglobin (HbA1c) (R = -0.45, P < .05). Additionally, ORF was 34% lower and ORR was 18% lower in T1DM compared with CTRL (P < .05). Our findings represent in vivo evidence suggesting that bone remodeling in individuals with T1DM is in a state of low responsiveness to mechanical stimuli, resulting in impaired bone formation and resorption rates; these correlate to the degree of neuropathy and level of diabetes control.

In a healthy adult, the body's skeleton self-repairs­or remodels­itself to maintain its strength. At the microscopic level, this process is orchestrated by cells, called osteocytes, which can sense and respond to local mechanical forces. Recent studies have suggested that type 1 diabetes mellitus (T1DM), a metabolic bone disease, may negatively impact this mechanically regulated process and reduce bone strength. To investigate this further, we utilized novel methods to monitor local changes in bone microstructure over time using high­resolution peripheral quantitative­computed tomography, allowing us to study the results of cellular behavior on bone remodeling in participants over time. Our study found that bone formation was 47% lower and bone resorption was 59% lower in participants with T1DM compared with controls (CTRL). Bone formation correlated positively with peripheral nerve function and negatively with glycaemic control in participants with T1DM. Furthermore, the links between mechanical forces acting on bone remodeling were 34% weaker for formation and 18% weaker for resorption compared with CTRL. Our findings show that bone remodeling in people with T1DM is in a state of low responsiveness to mechanical stimuli, resulting in impaired bone formation and resorption rates, and ultimately, impaired self-repair.

Transferability of bone phenotyping and fracture risk assessment by µFRAC from first-generation high-resolution peripheral quantitative computed tomography to second-generation scan data.

INTRODUCTION: The continued development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has led to a second-generation scanner with higher resolution and longer scan region. However, large multicenter prospective cohorts were collected with first-generation HR-pQCT and have been used to develop bone phenotyping and fracture risk prediction (µFRAC) models. This study establishes whether there is sufficient universality of these first-generation trained models for use with second-generation scan data. METHODS: HR-pQCT data were collected for a cohort of 60 individuals, who had been scanned on both first- and second-generation scanners on the same day to establish the universality of the HR-pQCT models. These data were each used as input to first-generation trained bone microarchitecture models for bone phenotyping and fracture risk prediction, and their outputs were compared for each study participant. Reproducibility of the models were assessed using same-day repeat scans obtained from first-generation (n = 37) and second-generation (n = 74) scanners. RESULTS: Across scanner generations, the bone phenotyping model performed with an accuracy of 93.1%. Similarly, the 5-year fracture risk assessment by µFRAC was well correlated with a Pearson's (r) correlation coefficient of r > 0.83 for the three variations of µFRAC (varying inclusion of clinical risk factors, finite element analysis, and dual X-ray absorptiometry). The first-generation reproducibility cohort performed with an accuracy for categorical assignment of 100% (bone phenotyping) and a correlation coefficient of 0.99 (µFRAC), whereas the second-generation reproducibility cohort performed with an accuracy of 96.4% (bone phenotyping) and a correlation coefficient of 0.99 (µFRAC). CONCLUSION: We demonstrated that bone microarchitecture models trained using first-generation scan data generalize well to second-generation scans, performing with a high level of accuracy and reproducibility. Less than 4% of individuals' estimated fracture risk led to a change in treatment threshold, and in general, these dissimilar outcomes using second-generation data tended to be more conservative.

Establishing the universality of first-generation-trained HR-pQCT prediction models on second-generation scan data is important to move the bone microarchitecture field forward. We found that despite the difference in resolutions between the two HR-pQCT generations, models developed with first-generation data generalized well to second-generation systems. This avoids unnecessarily repeating complex studies.

A comprehensive set of ultrashort echo time magnetic resonance imaging biomarkers to assess cortical bone health: A feasibility study at clinical field strength.

INTRODUCTION: Conventional bone imaging methods primarily use X-ray techniques to assess bone mineral density (BMD), focusing exclusively on the mineral phase. This approach lacks information about the organic phase and bone water content, resulting in an incomplete evaluation of bone health. Recent research highlights the potential of ultrashort echo time magnetic resonance imaging (UTE MRI) to measure cortical porosity and estimate BMD based on signal intensity. UTE MRI also provides insights into bone water distribution and matrix organization, enabling a comprehensive bone assessment with a single imaging technique. Our study aimed to establish quantifiable UTE MRI-based biomarkers at clinical field strength to estimate BMD and microarchitecture while quantifying bound water content and matrix organization. METHODS: Femoral bones from 11 cadaveric specimens (n = 4 males 67-92 yrs of age, n = 7 females 70-95 yrs of age) underwent dual-echo UTE MRI (3.0 T, 0.45 mm resolution) with different echo times and high resolution peripheral quantitative computed tomography (HR-pQCT) imaging (60.7 µm voxel size). Following registration, a 4.5 mm HR-pQCT region of interest was divided into four quadrants and used across the multi-modal images. Statistical analysis involved Pearson correlation between UTE MRI porosity index and a signal-intensity technique used to estimate BMD with corresponding HR-pQCT measures. UTE MRI was used to calculate T1 relaxation time and a novel bound water index (BWI), compared across subregions using repeated measures ANOVA. RESULTS: The UTE MRI-derived porosity index and signal-intensity-based estimated BMD correlated with the HR-pQCT variables (porosity: r = 0.73, p = 0.006; BMD: r = 0.79, p = 0.002). However, these correlations varied in strength when we examined each of the four quadrants (subregions, r = 0.11-0.71). T1 relaxometry and the BWI exhibited variations across the four subregions, though these differences were not statistically significant. Notably, we observed a strong negative correlation between T1 relaxation time and the BWI (r = -0.87, p = 0.0006). CONCLUSION: UTE MRI shows promise for being an innocuous method for estimating cortical porosity and BMD parameters while also giving insight into bone hydration and matrix organization. This method offers the potential to equip clinicians with a more comprehensive array of imaging biomarkers to assess bone health without the need for invasive or ionizing procedures.

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

Osteogenesis imperfecta (OI) is a rare phenotypically and genetically heterogeneous group of inherited skeletal dysplasias. The hallmark features of OI include bone fragility and susceptibility to fractures, bone deformity, and diminished growth, along with a plethora of associated secondary features (both skeletal and extraskeletal). The diagnosis of OI is currently made on clinical grounds and may be confirmed by genetic testing. However, imaging remains pivotal in the evaluation of this disease. The aim of this article is to review the current role played by the various radiologic techniques in the diagnosis and monitoring of OI in the postnatal setting as well as to discuss recent advances and future perspectives in OI imaging. Conventional Radiography and Dual-energy X-ray Absorptiometry (DXA) are currently the two most used imaging modalities in OI. The cardinal radiographic features of OI include generalized osteopenia/osteoporosis, bone deformities, and fractures. DXA is currently the most available technique to assess Bone Mineral Density (BMD), specifically areal BMD (aBMD). However, DXA has important limitations and cannot fully characterize bone fragility in OI based on aBMD. Novel DXA-derived parameters, such as Trabecular Bone Score (TBS), may provide further insight into skeletal changes induced by OI, but evidence is still limited. Techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) can be useful as problem-solvers or in specific settings, including the evaluation of cranio-cervical abnormalities. Recent evidence supports the use of High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT) as a promising tool to improve the characterization of bone fragility in OI. However, HR-pQCT remains a primarily research technique at present. Quantitative Computed Tomography (QCT) is an alternative to DXA for the determination of BMD at central sites, with distinct advantages but considerably higher radiation exposure. Quantitative Ultrasound (QUS) is a portable, inexpensive, and radiation-free modality that may complement DXA evaluation, providing information on bone quality. However, evidence of usefulness of QUS in OI is poor. Radiofrequency Echographic Multi Spectrometry (REMS) is an emerging non-ionizing imaging method that holds promise for the diagnosis of low BMD and for the prediction of fracture risk, but so far only one published study has investigated its role in OI. To conclude, several different radiologic techniques have proven to be effective in the diagnosis and monitoring of OI, each with their own specificities and peculiarities. Clinicians should be aware of the strategic role of the various modalities in the different phases of the patient care process. In this scenario, the development of international guidelines including recommendations on the role of imaging in the diagnosis and monitoring of OI, accompanied by continuous active research in the field, could significantly improve the standardization of patient care.

Accuracy of photon-counting computed tomography for the measurement of bone quality in the knee.

Visualization and quantification of bone microarchitecture in the human knee allows gaining insight into normal bone structure, and into the structural changes occurring in the onset and progression of bone diseases such as osteoporosis and osteoarthritis. However, current imaging modalities have limitations in capturing the intricacies of bone microarchitecture. Photon counting computed tomography (PCCT) is a promising imaging modality that presents high-resolution three-dimensional visualization of bone with a large field of view. However, the potential of PCCT in assessing trabecular microstructure has not been investigated yet. Therefore, this study aimed to evaluate the accuracy of PCCT in quantifying bone microstructure and bone mechanics in the knee. Five human cadaveric knees were scanned ex vivo using a PCCT scanner (Naetom alpha, Siemens, Germany) with an in-plane resolution of 146.5 µm and slice thickness of 100 µm. To assess accuracy, the specimens were also scanned with a high-resolution peripheral quantitative computed tomography (HR-pQCT; XtremeCT II, Scanco Medical, Switzerland) with a nominal isotropic voxel size of 60.7 µm as well as with micro-computed tomography (micro-CT; TESCAN UniTOM XL, Czech Republic) with a nominal isotropic voxel size of 25 µm which can be considered gold standards for in vivo and ex vivo scanning, respectively. The thickness and porosity of the subchondral bone and the microstructure of the underlying trabecular bone were assessed in the load bearing regions of the proximal tibia and distal femur. The apparent Young's modulus was determined by micro-finite element (µFE) analysis of subchondral trabecular bone (STB) in the load bearing regions of the proximal tibia using PCCT, HR-pQCT and micro-CT images. The correlation between PCCT measurements and micro-CT and HR-pQCT, respectively, was calculated. The coefficients of determination (R2) between PCCT and micro-CT based parameters, ranged from 0.69 to 0.87. The coefficients of determination between PCCT and HR-pQCT were slightly higher and ranged from 0.71 to 0.91. Apparent Young's modulus, assessed by µFE analysis of PCCT images, correlated well with that of micro-CT (R2 = 0.80, mean relative difference = 19 %). However, PCCT overestimated the apparent Young's modulus by 47 %, but the correlation (R2 = 0.84) remained strong when compared to HR-pQCT. The results of this study suggest that PCCT can be used to quantify bone microstructure in the knee.

Early bone loss in patients with obstructive sleep apnea: a cross-sectional study.

BACKGROUND: Obstructive sleep apnea (OSA) and osteoporosis are both prevalent diseases with shared pathophysiological mechanisms and risk factors. However, the association between the two diseases is seldom studied. This study aimed to identify the link between OSA and bone metabolism. METHODS: Male participants aged 30-59-years who visited the sleep clinic were continuously recruited. Polysomnography was used to evaluate sleep and respiratory conditions. Blood samples were collected to detect metabolic, inflammatory and bone turnover indicators. High-resolution peripheral quantitative computer tomography was used to measure the non-dominant lateral radius and tibia. RESULTS: Ninety subjects were recruited. The cortical area (Ct.Ar) of tibia of the severe OSA group was significantly higher than that of the mild and moderate OSA groups (P = 0.06 and P = 0.048). There were significant differences between the four groups in terms of total volumetric bone mineral density (vBMD) (F = 2.990, P = 0.035), meta trabecular vBMD (F = 3.696, P = 0.015), trabecular thickness (Tb.Th) (F = 7.060, P = 0.000) and cortical thickness (Ct.Th) (F = 4.959, P = 0.003). The mean values of the OSA groups were lower than control group. Hypopnea index and percentage of total sleep time with SpO2 < 90% were both positively correlated with alkaline phosphatase (R = 0.213, P = 0.044; R = 0.212, P = 0.045). Sleep efficiency was correlated with multiple indicators of the radius. CONCLUSIONS: In non-elderly male populations, OSA patients tended to have lower vBMD, Tb.Th and Ct.Th than non-OSA patients. The negative effect of OSA may mainly affect the osteogenesis process, and is presumed to be related to sleep-related hypoxemia and sleep efficiency.