High-resolution Peripheral Quantitative Computed Tomography Research Articles

High-resolution peripheral quantitative computed tomography for the assessment of acro-osteolysis and calcinosis in patients with systemic sclerosis

ObjectiveTo assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc. MethodsHR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales. ResultsForty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66–99%) and 80% (95% CI: 59–93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47–90%) and 95% (95% CI: 76–99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1–3) versus 0 (IQR: 0–1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability. ConclusionHR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.

Bone microarchitecture and strength assessment in adults with osteogenesis imperfecta using HR-pQCT: normative comparison and challenges.

Data on bone microarchitecture in osteogenesis imperfecta (OI) are scarce. The aim of this cross-sectional study was to assess bone microarchitecture and strength in a large cohort of adults with OI using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to evaluate challenges of using HR-pQCT in this cohort. Second-generation HR-pQCT scans were obtained at the distal radius and tibia in 118 men and women with Sillence OI type I, III, or IV using an extremity-length-dependent scan protocol. In total, 102 radius and 105 tibia scans of sufficient quality could be obtained, of which 11 radius scans (11%) and 14 tibia scans (13%) had a deviated axial scan angle as compared with axial angle data of 13 young women. In the scans without a deviated axial angle and compared with normative HR-pQCT data, Z-scores at the radius for trabecular bone mineral density (BMD), number, and separation were -1.6 ± 1.3, -2.5 ± 1.4, and -2.7 (IQR: 2.7), respectively. They were -1.4 ± 1.5 and -1.1 ± 1.2 for stiffness and failure load and between ±1 for trabecular thickness and cortical bone parameters. Z-scores were significantly lower for total and trabecular BMD, stiffness, failure load, and cortical area and thickness at the tibia. Additionally, local microarchitectural inhomogeneities were observed, most pronounced being trabecular void volumes. In the scans with a deviated axial angle, the proportion of Z-scores <-4 or >4 was significantly higher for trabecular BMD and separation (radius) or most total and trabecular bone parameters (tibia). To conclude, especially trabecular bone microarchitecture and bone strength were impaired in adults with OI. HR-pQCT may be used without challenges in most adults with OI, but approximately 12% of the scans may have a deviated axial angle in OI due to bone deformities or scan positioning limitations. Furthermore, standard HR-pQCT parameters may not always be reliable due to microarchitectural inhomogeneities nor fully reflect all inhomogeneities.

Approaching virtual osteoid volume estimation and in-depth tissue characterization in patients with tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) poses a significant diagnostic challenge, leading to increased disease duration and patient burden also by missing clinical suspicion. Today, diagnosis of osteomalacia relies on invasive iliac crest biopsy, if needed. Therefore, a noninvasive method would be beneficial for patients with severe osteomalacia, such as TIO, to inform their clinical management and address specific needs, like estimating the regeneration capacity at high osteoid volumes (OVs) or the potential of a hungry bone syndrome after tumor removal. Furthermore, given the lack of comprehensive histological characterization of TIO, there is a need for additional tissue characterization. Therefore, our assessment encompassed iliac crest biopsies that were examined using quantitative electron backscattered microscopy, Raman spectroscopy, micro-computed tomography, and histology to analyze the biopsy tissue. Our clinical assessment encompassed DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) alongside with biochemical analyses and clinical evaluations. Combining imaging and clinical data, we established a model to predict the OV. We compared 9 TIO patients with 10 osteoporosis (OPO) patients and 10 healthy controls. Histological analyses confirmed a pronounced OV in TIO patients (OPO: 1.20% ± 1.23% vs TIO: 23.55% ± 12.23%, P < .0005), and spectroscopy revealed lower phosphate levels in TIO biopsies. By combining HR-pQCT and laboratory diagnostics, we developed a linear regression model to noninvasively predict the OV revealing significantly higher modeled OV/BVmodel values of 24.46% ± 14.22% for TIO compared to the control group (5.952% ± 3.44%, P ≤ .001). By combining laboratory diagnostics, namely, ALP and Tt.BMDRadius measured by HR-pQCT, we achieved the calculation of the virtual osteoid volume to bone volume ratio (OV/BVmodel) with a significant correlation to histology as well as reliable identification of TIO patients compared to OPO and control. This novel approach is potentially helpful for predicting OV by noninvasive techniques in diagnostic procedures and improving the clinical management of TIO.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

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

BackgroundObstructive 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.MethodsMale 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.ResultsNinety 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.ConclusionsIn 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.

Am I big boned? Bone length scaled reference data for HRpQCT measures of the radial and tibial diaphysis in White adults

Cross-sectional size of a long bone shaft influences its mechanical properties. We recently used high-resolution peripheral quantitative computed tomography (HRpQCT) to create reference data for size measures of the radial and tibial diaphyses. However, data did not take into account the impact of bone length. Human bone exhibits relatively isometric allometry whereby cross-sectional area increases proportionally with bone length. The consequence is that taller than average individuals will generally have larger z-scores for bone size outcomes when length is not considered. The goal of the current work was to develop a means of determining whether an individual's cross-sectional bone size is suitable for their bone length. HRpQCT scans performed at 30 % of bone length proximal from the distal end of the radius and tibia were acquired from 1034 White females (age = 18.0 to 85.3 y) and 392 White males (age = 18.4 to 83.6 y). Positive relationships were confirmed between bone length and cross-sectional areas and estimated mechanical properties. Scaling factors were calculated and used to scale HRpQCT outcomes to bone length. Centile curves were generated for both raw and bone length scaled HRpQCT data using the LMS approach. Excel-based calculators are provided to facilitate calculation of z-scores for both raw and bone length scaled HRpQCT outcomes. The raw z-scores indicate the magnitude that an individual's HRpQCT outcomes differ relative to expected sex- and age-specific values, with the scaled z-scores also considering bone length. The latter enables it to be determined whether an individual or population of interest has normal sized bones for their length, which may have implications for injury risk. In addition to providing a means of expressing HRpQCT bone size outcomes relative to bone length, the current study also provides centile curves for outcomes previously without reference data, including tissue mineral density and moments of inertia.

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 82μm, HR-pQCT II at 60.7μm, and μCT at 37μm. 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.

The Application of Advanced Bone Imaging Technologies in Sports Medicine

Until recently, the evaluation of bone health and fracture risk through imaging has been limited to dual-energy X-ray absorptiometry (DXA) and plain radiographs, with a limited application in the athletic population. Several novel imaging technologies are now available for the clinical assessment of bone health, including bone injury risk and healing progression, with a potential for use in sports medicine. Among these imaging modalities is high-resolution peripheral quantitative computed tomography (HR-pQCT) which is a promising technology that has been developed to examine the bone microarchitecture in both cortical and trabecular bone at peripheral anatomical sites. Technologies that do not expose patients to ionizing radiation are optimal, particularly for athletes who may require frequent imaging. One such alternative is diagnostic ultrasound, which is preferable due to its low cost and lack of radiation exposure. Furthermore, ultrasound, which has not been a common imaging modality for monitoring fracture healing, has been shown to potentially demonstrate earlier signs of union compared to conventional radiographs, including callus mineralization and density at the healing site. Through the use of conventional magnetic resonance imaging (MRI), finite element analysis (FEA) can be used to simulate the structural and mechanical properties of bone. On the other hand, the ultrashort echo time (UTE) MRI can evaluate cortical bone quality by detecting water bound to the organic bone matrix and free water, providing important information about bone porosity. Several novel bone imaging techniques originally developed for osteoporosis assessment have great potential to be utilized to improve the standard of care in bone fracture risk assessment and healing in sports medicine with much greater precision and less adverse radiation exposure.

Diabetes Risk Factors and Bone Microarchitecture as Assessed by High-Resolution Peripheral Quantitative Computed Tomography in Adults With Long-standing Type 1 Diabetes.

To determine whether type 1 diabetes and its complications are associated with bone geometry and microarchitecture. This cross-sectional study was embedded in a long-term observational study. High-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the distal radius and distal and diaphyseal tibia were performed in a subset of 183 participants with type 1 diabetes from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study and 94 control participants without diabetes. HbA1c, skin advanced glycation end products (AGEs), and diabetes-related complications were assessed in EDIC participants with >30 years of follow-up. Compared with control participants (aged 60 ± 8 years, 65% female), EDIC participants (aged 60 ± 7 years, diabetes duration 38 ± 5 years, 51% female) had lower total bone mineral density (BMD) at the distal radius (-7.9% [95% CI -15.2%, -0.6%]; P = 0.030) and distal tibia (-11.3% [95% CI -18.5%, -4.2%]; P = 0.001); larger total area at all sites (distal radius 4.7% [95% CI 0.5%, 8.8%; P = 0.030]; distal tibia 5.9% [95% CI 2.1%, 9.8%; P = 0.003]; diaphyseal tibia 3.4% [95% CI 0.8%, 6.1%; P = 0.011]); and poorer radius trabecular and cortical microarchitecture. Estimated failure load was similar between the two groups. Among EDIC participants, higher HbA1c, AGE levels, and macroalbuminuria were associated with lower total BMD. Macroalbuminuria was associated with larger total area and lower cortical thickness at the distal radius. Higher HbA1c and AGE levels and lower glomerular filtration rate, peripheral neuropathy, and retinopathy were associated with deficits in trabecular microarchitecture. Type 1 diabetes is associated with lower BMD, larger bone area, and poorer trabecular microarchitecture. Among participants with type 1 diabetes, suboptimal glycemic control, AGE accumulation, and microvascular complications are associated with deficits in bone microarchitecture and lower BMD.

Evaluation of Bone Health Using High Resolution Peripheral Quantitative Computed Tomography in Survivors of Paediatric Acute Lymphoblastic Leukemia

Bone mass accrual, bone architecture, and strength may be impaired in children with a history of acute lymphoblastic leukemia (ALL) resulting in low bone mineral density (BMD) and fractures. The Children's Oncology Group recommends evaluating ALL survivors' bone health with dual-energy X-ray absorptiometry (DXA) testing. However, DXA testing may not accurately measure bone health in survivors due to low bone area for height, short stature, growth delays or decreased lean muscle mass. Further, it does not differentiate between trabecular and cortical bone, nor does it provide insights into bone microarchitecture and strength. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional non-invasive imaging modality that provides a comprehensive assessment bone microarchitecture, volumetric BMD (vBMD) of both cortical and trabecular bone, and bone strength. In adult patients, HR-pQCT parameters have been shown to predict incident fractures. In this pilot study we utilized HR-pQCT to evaluate bone microarchitecture, vBMD, bone geometry and bone strength of peri-pubertal and pubertal survivors of ALL compared to healthy controls. Methods: We prospectively recruited ALL survivors (&amp;gt;1 year off therapy) with a DXA BMD Z-score between -2.0 to 0 within the proceeding six months, who were in early-late puberty (pre-pubertal patients excluded), and aged 11 to 18 years, along with healthy controls in the same age range at a single academic pediatric center in Canada. While a BMD Z-score of -2.0 to 0 has historically been considered normal, many children with Z-scores in this range have skeletal fragility and an increased fracture risk. Patients were excluded if they had comorbidity that impacts bone microarchitecture (ex. chronic kidney disease), were on a medication that impacts bone health (ex. corticosteroids) or had a genetic syndrome that increased their sensitivity to radiation (ex. Ataxia Telangiectasia). HR-pQCT of the distal radius and tibia was performed using the a standardized protocol. Bone mass was compared using total, trabecular and cortical vBMD, bone architecture was compared using cortical porosity and bone strength was compared using failure load. HR-pQCT derived variables were compared between ALL and control groups following stratification by sex. HR-pQCT values were summarized using medians and interquartile ranges and medians were compared using the Wilcoxon signed-rank test. Demographic and clinical characteristics were compared using the chi-square test. All tests were two tailed and p&amp;lt;0.05 was considered significant. Results: A total of 59 subjects were recruited (34 ALL survivors, 25 healthy controls). The sex of participants was male for 56.0% (n=14) of controls and 61.7% (n=21) of ALL survivors and female for 44.0% (n=11) of controls and 38.3% (n=13) of survivors. All survivors had received corticosteroids and methotrexate, and five (15%) had received cranial radiation. ALL survivors were not more likely than controls to report a history of a fracture (32.4%, n=11 vs. 16%, n=4). Additional data regarding the participants demographics is presented in Table 1. Male survivors had a lower radial trabecular vBMD, tibial total vBMD, and tibial trabecular vBMD, and a higher tibial failure load compared to healthy male controls. Female survivors had a lower radial total vBMD, radial trabecular vBMD, tibial total vBMD, and tibial trabecular vBMD. Female ALL survivors also had higher radial and tibial failure loads compared to healthy female controls. No differences in cortical porosity or cortical vBMD were identified between survivors and healthy controls. Complete HR-pQCT data is presented in Table 2. Conclusions: We demonstrated differences in the HR-pQCT parameters of peripubertal and pubertal ALL survivors compared to healthy controls. Survivors had reductions in key HR-pQCT parameters and an increased tibial failure load compared to healthy controls. In future studies HR-pQCT should be performed at a uniform time point post ALL therapy and used to predict future adverse bone health outcome such as fractures. Using this HR-pQCT guided approach ALL survivors at greatest risk of an adverse bone health outcome can be offered early interventions to prevent these outcomes.

Influence of demographic factors on the occurrence of motion artefacts in HR-pQCT

SummaryThe study shows a high incidence of motion artefacts in a central European population and a significant increase of those artefacts with higher age. These findings may impact on the design and conduct of future in vivo HR-pQCT studies or at least help to estimate the potential number of drop outs due to unusable image quality.PurposeMotion artefacts in high-resolution peripheral quantitative computed tomography (HR-pQCT) are challenging, as they introduce error into the resulting measurement data. The aim of this study was to assess the general occurrence of motion artefacts in healthy distal radius and to evaluate the influence of demographic factors.MethodsThe retrospective study is based on 525 distal radius second-generation HR-pQCT scans of 95 patients. All stacks were evaluated by two experienced observers and graded according to the visual grading scale recommended by the manufacturer, ranging from grade 1 (no visible motion artefacts) to grade 5 (severe motion artefacts). Correlations between demographic factors and image quality were evaluated using a linear mixed effects model analysis.ResultsThe average visual grading was 2.7 (SD ± 0.7). Age and severity of motion artefacts significantly correlated (p = 0.026). Patients aged 65 years or above had an average image quality between grades 1 and 3 in 72.7% of cases, while patients younger than 65 had an average image quality between grades 1 and 3 in 91.9% of cases. Gender, smoking behaviour, and handedness had no significant influence on motion artefacts.ConclusionThis study showed a high incidence of motion artefacts in a representative central European population, but also a significant increase of motion artefacts with higher age. This could impact further study designs by planning for a sufficiently large and if possible a more selective study population to gain a representative amount of high-quality image data.

Predicting Bone Adaptation in Astronauts during and after Spaceflight.

A method was previously developed to identify participant-specific parameters in a model of trabecular bone adaptation from longitudinal computed tomography (CT) imaging. In this study, we use these numerical methods to estimate changes in astronaut bone health during the distinct phases of spaceflight and recovery on Earth. Astronauts (N = 16) received high-resolution peripheral quantitative CT (HR-pQCT) scans of their distal tibia prior to launch (L), upon their return from an approximately six-month stay on the international space station (R+0), and after six (R+6) and 12 (R+12) months of recovery. To model trabecular bone adaptation, we determined participant-specific parameters at each time interval and estimated their bone structure at R+0, R+6, and R+12. To assess the fit of our model to this population, we compared static and dynamic bone morphometry as well as the Dice coefficient and symmetric distance at each measurement. In general, modeled and observed static morphometry were highly correlated (R2> 0.94) and statistically different (p < 0.0001) but with errors close to HR-pQCT precision limits. Dynamic morphometry, which captures rates of bone adaptation, was poorly estimated by our model (p < 0.0001). The Dice coefficient and symmetric distance indicated a reasonable local fit between observed and predicted bone volumes. This work applies a general and versatile computational framework to test bone adaptation models. Future work can explore and test increasingly sophisticated models (e.g., those including load or physiological factors) on a participant-specific basis.

Indices of sarcopenic obesity are important predictors of finite element analysis-derived bone strength in older adults with obesity.

The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT). One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement. Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2=0.301 to 0.448, HGS: R 2=0.346 to 0.472, FM%: R 2=0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05). These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

A multi-stack registration technique to improve measurement accuracy and precision across longitudinal HR-pQCT scans.

Recent applications of high-resolution peripheral quantitative computed tomography (HR-pQCT) have demonstrated that changes in local bone remodelling can be quantified in vivo using longitudinal three-dimensional image registration. However, certain emerging applications, such as fracture healing and joint analysis, require larger multi-stack scan regions that can result in stack shift image artifacts. These artifacts can be detrimental to the accurate alignment of the bone structure across multiple timepoints. The purpose of this study was to establish a multi-stack registration protocol for evaluating longitudinal HR-pQCT images and to assess the accuracy and precision error in comparison with measures obtained using previously established three-dimensional longitudinal registration. Three same day multi-stack HR-pQCT scans of the radius (2 stacks in length) and tibia (3 stacks in length) were obtained from 39 healthy individuals who participated in a previous reproducibility study. A fully automated multi-stack registration algorithm was developed to re-align stacks within a scan by leveraging slight offsets between longitudinal scans. Stack shift severity before and after registration was quantified using a newly proposed stack-shift severity score. The false discovery rate for bone remodelling events and precision error of bone morphology and micro-finite element analysis parameters were compared between longitudinally registered scans with and without the addition of multi-stack registration. Most scans (82%) improved in stack alignment or maintained the lowest stack shift severity score when multi-stack registration was implemented. The false discovery rate of bone remodelling events significantly decreased after multi-stack registration, resulting in median false detection of bone formation and resorption fractions between 3.2 to 7.5% at the radius and 3.4 to 5.3% at the tibia. Further, precision error was significantly reduced or remained unchanged in all standard bone morphology and micro-finite element analysis parameters, except for total and trabecular cross-sectional areas. Multi-stack registration is an effective strategy for accurately aligning multi-stack HR-pQCT scans without modification of the image acquisition protocol. The algorithm presented here is a viable approach for performing accurate morphological analysis on multi-stack HR-pQCT scans, particularly for advanced application investigating local bone remodelling in vivo.

Comparison of Motion Grading in 1,000 Patients by First- and Second-Generation HR-pQCT: A Propensity Score Matched Cohort Study

In-vivo bone microstructure measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) is gaining importance in research and clinical practice. Second-generation HR-pQCT (XCT2) shows improved image quality and shorter measurement duration compared to the first generation (XCT1). Predicting and understanding the occurrence of motion artifacts is crucial for clinical practice. We retrospectively analyzed data from HR-pQCT measurements at the distal radius and tibia of 1,000 patients (aged 20 to 89) evenly distributed between both generations of HR-pQCT. Motion artifacts were graded between 1 (no motion) and 5 (severe motion), with grades greater 3 considered unusable. Additionally, baseline characteristics and patients’ muscle performance and balance were measured. Various group comparisons between the two generations of HR-pQCT and regression analyses between patient characteristics and motion grading were performed. The study groups of XCT1 and XCT2 did not differ by age (XCT1: 64.9 vs. XCT2: 63.8 years, p = 0.136), sex (both 74.5% females, p > 0.999), or BMI (both 24.2 kg/m2, p = 0.911) after propensity score matching. XCT2 scans exhibited significantly lower motion grading in both extremities compared to XCT1 (Radius: p < 0.001; Tibia: p = 0.002). In XCT2 motion-corrupted scans were more than halved at the radius (XCT1: 35.3% vs. XCT2: 15.5%, p < 0.001), and at the tibia the frequency of best image quality scans was increased (XCT1: 50.2% vs. XCT2: 63.7%, p < 0.001). The strongest independent predictor for motion-corrupted images is the occurrence of high motion grading at the other scanning site during the same consultation. The association between high motion grading in one scan and a corresponding high motion grading in another scan within the same session suggests a non-resting patient. Additionally, aged, female, and patients with smaller stature tend towards higher motion grading, requiring special attention to a correct extremity fixation.

Deteriorated bone microarchitecture caused by sympathetic overstimulation in pheochromocytoma and paraganglioma.

Despite the potentially destructive effect of sympathetic activity on bone metabolism, its impact on bone microarchitecture, a key determinant of bone quality, has not been thoroughly investigated. This study aims to evaluate the impact of sympathetic activity on bone microarchitecture and bone strength in patients with pheochromocytoma and paraganglioma (PPGL). A cross-sectional study was conducted in 38 PPGL patients (15 males and 23 females). Bone turnover markers serum procollagen type 1 N-terminal propeptide (P1NP) and β-carboxy-terminal crosslinked telopeptide of type 1 collagen (β-CTX) were measured. 24-h urinary adrenaline (24hUE) and 24-h urinary norepinephrine levels (24hUNE) were measured to indicate sympathetic activity. High-resolution peripheral quantitative computed tomography (HR-pQCT) was conducted to evaluate bone microarchitecture in PPGL patients and 76 age-, sex-matched healthy controls (30 males and 46 females). Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (DXA) simultaneously. PPGL patients had a higher level of β-CTX. HR-pQCT assessment revealed that PPGL patients had notably thinner and more sparse trabecular bone (decreased trabecular number and thickness with increased trabecular separation), significantly decreased volume BMD (vBMD), and bone strength at both the radius and tibia compared with healthy controls. The deterioration of Tt.vBMD, Tb.Sp, and Tb.1/N.SD was more pronounced in postmenopausal patients compared with the premenopausal subjects. Moreover, subjects in the highest 24hUNE quartile (Q4) showed markedly lower Tb.N and higher Tb.Sp and Tb.1/N.SD at the tibia than those in the lowest quartile (Q1). Age-related bone loss was also exacerbated in PPGL patients to a certain extent. PPGL patients had significantly deteriorated bone microarchitecture and strength, especially in the trabecular bone, with an increased bone resorption rate. Our findings provide clinical evidence that sympathetic overstimulation may serve as a secondary cause of osteoporosis, especially in subjects with increased sympathetic activity.

Utility of HR-pQCT in detecting training-induced changes in healthy adult bone morphology and microstructure.

Healthy bone adjusts its traits in an exceptionally coordinated, compensatory process. Recent advancements in skeletal imaging via High-Resolution Peripheral Quantitative Computed Tomography (HR-pQCT) allows for the in vivo 3-dimensional and longitudinal quantification of bone density, microarchitecture, geometry, and parameters of mechanical strength in response to varying strain stimuli including those resulting from exercise or military training. Further, the voxel size of 61 microns has the potential to capture subtle changes in human bone in as little as 8 weeks. Given the typical time course of bone remodeling, short-term detection of skeletal changes in bone microstructure and morphology is indicative of adaptive bone formation, the deposition of new bone formation, uncoupled from prior resorption, that can occur at mechanistically advantageous regions. This review aims to synthesize existing training-induced HR-pQCT data in three distinct populations of healthy adults excluding disease states, pharmacological intervention and nutritional supplementation. Those included are: 1) military basic or officer training 2) general population and 3) non-osteoporotic aging. This review aims to further identify similarities and contrasts with prior modalities and cumulatively interpret results within the scope of bone functional adaptation.

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.

Erosion Identification in Metacarpophalangeal Joints in Rheumatoid Arthritis using High-Resolution Peripheral Quantitative Computed Tomography.

Bone erosions are a pathological feature of several forms of inflammatory arthritis including rheumatoid arthritis (RA). The increased presence and size of erosions are associated with poor outcomes, joint function, and disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides unparalleled in vivo visualization of bone erosions. However, at this resolution, discontinuities in the cortical shell (cortical breaks) that are associated with normal physiological processes and pathology are also visible. The Study grouP for xtrEme Computed Tomography in Rheumatoid Arthritis previously used a consensus process to develop a definition of pathological erosion in HR-pQCT: a cortical break detected in at least two consecutive slices, in at least two perpendicular planes, non-linear in shape, with underlying trabecular bone loss. However, despite the availability of a consensus definition, erosion identification is a demanding task with challenges in inter-rater variability. The purpose of this work is to introduce a training tool to provide users with guidance on identifying pathological cortical breaks on HR-pQCT images for erosion analysis. The protocol presented here uses a custom-built module (Bone Analysis Module (BAM) - Training), implemented as an extension to an open-source image processing software (3D Slicer). Using this module, users can practice identifying erosions and compare their results to erosions annotated by expert rheumatologists.

The Vitamin D Metabolite Ratio Is Associated With Volumetric Bone Density in Older Men.

Serum 25-hydroxyvitamin D (25(OH)D) is the current marker of vitamin D adequacy, but its relationship with bone health has been inconsistent. The ratio of 24,25-dihydroxyvitamin D3 to 25(OH)D3 (vitamin D metabolite ratio or VMR) is a marker of vitamin D that has been associated with longitudinal changes in bone mineral density (BMD) and fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides information on bone health beyond standard dual-energy x-ray absorptiometry, in that it measures volumetric BMD (vBMD) as well bone strength. The relationship of the VMR with vBMD and bone strength remains unknown. We evaluated the associations of the VMR and 25(OH)D3 with vBMD and bone strength in the distal radius and tibia, assessed by HR-pQCT in 545 older men participating in the Osteoporotic Fractures in Men (MrOS) Study. Primary outcomes were vBMD and estimated failure load (EFL, a marker of bone strength) at the distal radius and tibia. The mean age was 84 ± 4 years, 88.3% were White, and 32% had an estimated glomerular filtration rate <60 mL/min/1.73 m2. In adjusted models, each twofold higher VMR was associated with a 9% (3%, 16%) higher total vBMD and a 13% (5%, 21%) higher EFL at the distal radius. Results were similar at the distal tibia. 25(OH)D3 concentrations were not associated with any of the studied outcomes. Among older men, a higher VMR was associated with greater vBMD and bone strength while 25(OH)D3 was not. The VMR may serve as a valuable marker of skeletal health in older men.