High-resolution Peripheral Quantitative Computed Tomography Research Articles

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

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. 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 6months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. Eighteen women were included in the study (median age: 57years; range: 55-62years). At 6months 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. Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6months after chemotherapy.

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

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. To investigate the association between T2DM and HR-pQCT parameters in older men. 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. 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. 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.

Bone microarchitecture and strength assessed by HR-pQCT in individuals with type 2 diabetes and prediabetes: the Maastricht study

Abstract Type 2 Diabetes (T2D) is a prevalent disease and has been associated with an increased fracture risk despite normal or even higher areal bone mineral density (BMD). The aim of this study was to estimate the association between glucose metabolism status (GMS) and measurements of glycemic control with high-resolution peripheral quantitative computed tomography (HR-pQCT) parameters of bone microarchitecture and strength. Participants of The Maastricht Study who underwent a HR-pQCT scan at the distal radius and tibia were included. GMS was determined by use of an oral glucose tolerance test and grouped into a normal glucose metabolism (NGM), prediabetes or T2D. Linear regression models were used, stratified by sex with multiple adjustments. This study incorporated cross-sectional data from 1569 (885 (56.4%) NGM, 251 (16.0%) prediabetes and 433 (27.6%) T2D) men, and 1606 (1159 (72.2%) NGM, 231 (14.4%) prediabetes and 216 (13.4%) T2D) women. The mean age was 60.1 ± 8.6 and 57.8 ± 9.0 years for men and women, respectively. After adjustment, T2D was associated with a higher total BMD measured by HR-pQCT and cortical thickness, and a smaller total and trabecular area in men and women compared to NGM. In women, T2D was additionally associated with a higher stiffness and failure load at the radius. Results were more pronounced at the distal radius than at the distal tibia. To conclude, these findings suggest that in this cohort of Maastricht Study participants, total and trabecular bone area are smaller, but bone microarchitecture, density and bone strength assessed by HR-pQCT are not impaired in individuals with T2D.

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.

Skeletal effects of sleeve gastrectomy, by sex and menopausal status and in comparison to Roux-en-Y gastric bypass surgery.

Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. Data are lacking on the skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure. We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG. We compared the results to those previously reported after RYGB, hypothesizing lesser effects after SG than RYGB. Prospective observational cohort study of 54 adults with obesity undergoing SG at an academic center. Skeletal characterization with biochemical markers of bone turnover, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) was performed preoperatively and 6- and 12-months postoperatively. Over 12 months, mean percentage weight loss was 28.8%. Bone turnover marker levels increased, and total hip aBMD decreased -8.0% (95% CI -9.1%, -6.7%, p<0.01). Spinal aBMD and vBMD declines were larger in postmenopausal women than men. Tibial and radial trabecular and cortical microstructure worsened, as did tibial estimated strength, particularly in postmenopausal women. When compared to data from a RYGB cohort with identical design and measurements, some SG biochemical, vBMD, and radial microstructural parameters were smaller, while other changes were not. Bone mass, microstructure, and strength decrease after SG. Some skeletal parameters change less after SG than after RYGB, while for others, we find no evidence for smaller effects after SG. Postmenopausal women may be at highest risk of skeletal consequences after SG.

Distinguishing risk of curve progression in adolescent idiopathic scoliosis with bone microarchitecture phenotyping - a 6-year longitudinal study.

Low bone mineral density and impaired bone qualities have been shown to be important prognostic factors for curve progression in Adolescent Idiopathic Scoliosis (AIS). There is no evidence-based integrative interpretation method to analyse high-resolution peripheral quantitative computed tomography (HR-pQCT) data in AIS. This study aimed to (a) utilize unsupervised machine learning to cluster bone microarchitecture phenotypes on HR-pQCT parameters in AIS girls, (b) assess the phenotypes' risk of curve progression and progression to surgical threshold at skeletal maturity (primary cohort), and (c) investigate risk of curve progression in a separate cohort of mild AIS girls whose curve severity did not reach bracing threshold at recruitment (secondary cohort). Patients were followed up prospectively for 6.22 ± 0.33years in the primary cohort (N = 101). Three bone microarchitecture phenotypes were clustered by Fuzzy C-Means at time of peripubertal peak height velocity (PHV). Phenotype-1 had normal bone characteristics. Phenotype-2 was characterized by low bone volume and high cortical bone density, and Phenotype-3 had low cortical and trabecular bone density and impaired trabecular microarchitecture. The difference in bone qualities amongst the phenotypes was significant at peripubertal PHV and continued to skeletal maturity. Phenotype-3 had significantly increased risk of curve progression to surgical threshold at skeletal maturity (Odd Ratios (OR) = 4.88; 95% Confidence Interval (CI): 1.03-28.63). In the secondary cohort (N = 106), both Phenotype-2 (adjusted OR = 5.39; 95%CI: 1.47-22.76) and Phenotype-3 (adjusted OR = 3.67; 95%CI: 1.05-14.29) had increased risk of curve progression ≥6° with mean follow-up of 3.03 ± 0.16years. In conclusion, three distinct bone microarchitecture phenotypes could be clustered by unsupervised machine learning on HR-pQCT generated bone parameters at peripubertal PHV in AIS. The bone qualities reflected by these phenotypes were found to have significant differentiating risk of curve progression and progression to surgical threshold at skeletal maturity in AIS.

Impaired bone mineral density and microarchitecture in female adolescents with IgE-mediated cow's milk allergy.

Persistent immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) may impair bone parameters and increase the risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) is a novel methodology that not only assesses trabecular and cortical bone compartments and volumetric density measurements, but also evaluates bone microarchitecture and estimates biomechanical properties through finite element analysis (FEA). Both HR-pQCT and bone strength parameters derived from FEA have shown a strong correlation with fracture risk. To assess the bone density, microarchitecture, and bone strength of adolescents with persistent IgE-mediated CMA (IgE-CMA). This was an observational, cross-sectional study with female adolescents with persistent IgE-CMA and healthy control participants matched by female sex and sexual maturation. Bone parameters were assessed by areal bone mineral density (aBMD) through dual-energy X-ray absorptiometry (DXA), bone microarchitecture by HR-pQCT at the radius and tibia, and laboratory markers related to bone metabolism. The median age of adolescents with persistent IgE-CMA (n = 26) was 13.0years (interquartile range (IQR) 11.4-14.7) and of healthy control participants (n = 28) was 13.6years (IQR 11.9-14.9). Adolescents with IgE-CMA ingested 27.4% less calcium (p = 0.012) and 28.8% less phosphorus (p = 0.009) than controls. Adolescents with IgE-CMA had lower bone mineral content (BMC) (38.83g vs. 44.50g) and aBMD (0.796g/cm2 vs. 0.872g/cm2) at lumbar spine, and lower BMC (1.11kg vs. 1.27kg) and aBMD (0.823g/cm2 vs. 0.877g/cm2) at total body less head (TBLH) (p < 0.05). However, Z-scores BMC and Z-scores aBMD at lumbar spine and TBLH, when adjusted for Z-score height/age, were not significantly different between the groups. Moreover, CMA adolescents had lower bone strength at the distal tibia (S 169 kN/mm vs. 194 kN/mm; F Load 8030 N vs. 9223 N) (p < 0.05). Pairing of groups by the presence of menarche showed compromised parameters at the tibia-lower total volumetric BMD (Tt.vBMD) (293.9mg HA/cm3 vs. 325.9mg HA/cm3) and trabecular vBMD (Tb.vBMD) (170.8mg HA/cm3 vs. 192.2mg HA/cm3), along with lower cortical thickness (Ct.th) (1.02mm vs. 1.16mm) and bone strength (S 174 kN vs. 210 kN; F Load 8301 N vs. 9950 N)-and at the radius (S 61 kN/mm vs. 71 kN/mm; F Load 2920 N vs. 3398 N) (p < 0.05) among adolescents with IgE-CMA. Adolescents with IgE-CMA on a total exclusion diet (n = 12) showed greater impairment of bone features than those on a partial exclusion diet (n = 14), with lower lumbar spine Z-score BMC (- 0.65 vs. 0.18; p = 0.013), lumbar spine trabecular bone score (TBS) (1.268 vs. 1.383; p = 0.005), Z-score TBS (0.03 vs. 1.14; p = 0.020), TBLH Z-score BMC (- 1.17 vs. - 0.35; p = 0.012), TBLH Z-score aBMD (- 1.13 vs. - 0.33; p = 0.027), Tt.vBMD at the tibia (259.0mg HA/cm3 vs. 298.7mg HA/cm3; p = 0.021), Ct.th at the tibia (0.77mm vs. 1.04mm; p = 0.015) and Ct.th at the radius (0.16mm vs. 0.56mm; p = 0.033). Adolescents with persistent IgE-CMA had lower aBMD and compromised microarchitecture (impaired trabecular microarchitecture and lower bone strength). Adolescents on a partial exclusion diet had better bone parameters than those on a total exclusion diet.

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

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). 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. 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). 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.

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. 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. 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. 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.

Vascular function and skeletal fragility: A study of tonometry, brachial hemodynamics, and bone microarchitecture.

Osteoporosis and cardiovascular disease frequently occur together in older adults; however, a causal relationship between these two common conditions has not been established. By the time clinical cardiovascular disease develops, it is often too late to test whether vascular dysfunction developed before or after the onset of osteoporosis. Therefore, we assessed the association of vascular function, measured by tonometry and brachial hemodynamic testing, with bone density, microarchitecture, and strength, measured by high-resolution peripheral quantitative computed tomography (HR-pQCT), in 1391 individuals in the Framingham Heart Study. We hypothesized that decreased vascular function (pulse wave velocity, primary pressure wave, brachial pulse pressure, baseline flow amplitude and brachial flow velocity) contributes to deficits in bone density, microarchitecture and strength, particularly in cortical bone, which is less protected from excessive blood flow pulsatility than the trabecular compartment. We found that individuals with increased carotid-femoral pulse wave velocity had lower cortical volumetric bone mineral density (tibia: -0.21 [-0.26,-0.15] standardized beta [95% confidence interval], radius: -0.20 [-0.26,-0.15]), lower cortical thickness (tibia: -0.09 [-0.15,-0.04], radius: -0.07 [-0.12,-0.01]) and increased cortical porosity (tibia: 0.20 [0.15,0.25], radius: 0.21 [0.15,0.27]). However, these associations did not persist after adjustment for age, sex, height, and weight. These results suggest that vascular dysfunction with aging may not be an etiologic mechanism that contributes to the co-occurrence of osteoporosis and cardiovascular disease in older adults. Further study employing longitudinal measures of HR-pQCT parameters is needed to fully elucidate the link between vascular function and bone health.

Enhancing Osteoporosis Management: A Thorough Examination of Surgical Techniques and Their Effects on Patient Outcomes.

Managing osteoporotic fractures in older individuals is a difficult task in orthopedic surgery. It requires a careful approach that combines advanced diagnostic methods, customized surgical treatments, and comprehensive rehabilitation strategies. This article presents the results of an analysis carried out at the University Emergency Hospital, Bucharest. The analysis specifically examines the treatment of osteoporotic fractures using different osteosynthesis techniques. Although diagnostic tools like dual-energy X-ray absorptiometry (DXA) and Fracture Risk Assessment Tool (FRAX) have improved, a considerable number of fractures still happen in people who do not have obvious osteoporosis. This emphasizes the importance of using additional diagnostic measures such as high-resolution peripheral quantitative computed tomography (HR-pQCT) and quantitative computed tomography (QCT) to improve the accuracy of predictions. The study demonstrates the intricate nature of surgical decision-making and the significance of adjusting techniques to meet the specific needs of each patient. An instance of osteosynthesis failure resulting from the inappropriate choice of method highlighted the crucial significance of a thorough preoperative assessment. The discussion highlights the importance of early mobilization and rehabilitation in reducing the risks associated with prolonged immobilization and improving patient recovery. This paper strongly supports the use of evidence-based and patient-centered methods in the management of osteoporotic fractures. It emphasizes the importance of utilizing the most recent advancements in diagnostic and surgical technologies. Promising advancements in orthopedic medicine lie in the future, particularly in the integration of interdisciplinary research and personalized medicine. These advancements have the potential to enhance patient outcomes in this population that is at high risk.

DCES-PA: Deformation-controllable elastic shape model for 3D bone proliferation analysis using hand HR-pQCT images

Bone proliferation is an important pathological feature of inflammatory rheumatic diseases. Although recent advance in high-resolution peripheral quantitative computed tomography (HR-pQCT) enables physicians to study microarchitectures, physicians’ annotation of proliferation suffers from slice inconsistency and subjective variations. Also, there are only few effective automatic or semi-automatic tools for proliferation detection. In this study, by integrating pathological knowledge of proliferation formation with the advancement of statistical shape analysis theory, we present an unsupervised method, named Deformation-Controllable Elastic Shape model, for 3D bone Proliferation Analysis (DCES-PA). Unlike previous shape analysis methods that directly regularize the smoothness of the displacement field, DCES-PA regularizes the first and second-order derivative of the displacement field and decomposes these vector fields according to different deformations. For the first-order elastic metric, DCES-PA orthogonally decomposes the first-order derivative of the displacement field by shearing, scaling and bending deformation, and then penalize deformations triggering proliferation formation. For the second-order elastic metric, DCES-PA encodes both intrinsic and extrinsic surface curvatures into the second-order derivative of the displacement field to control the generation of high-curvature regions. By integrating the elastic shape metric with the varifold distances, DCES-PA achieves correspondence-free shape analysis. Extensive experiments on both simulated and real clinical datasets demonstrate that DCES-PA not only shows an improved accuracy than other state-of-the-art shape-based methods applied to proliferation analysis but also produces highly sensitive proliferation annotations to assist physicians in proliferation analysis.

TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = -0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

The Effectiveness of a Lactobacilli-Based Probiotic Food Supplement on Bone Mineral Density and Bone Metabolism in Australian Early Postmenopausal Women: Protocol for a Double-Blind Randomized Placebo-Controlled Trial.

Osteoporosis affects one in three women over the age of 50 and results in fragility fractures. Oestrogen deficiency during and after menopause exacerbates bone loss, accounting for higher prevalence of fragility fractures in women. The gut microbiota (GM) has been proposed as a key regulator of bone health, as it performs vital functions such as immune regulation and biosynthesis of vitamins. Therefore, GM modulation via probiotic supplementation has been proposed as a target for potential therapeutic intervention to reduce bone loss. While promising results have been observed in mouse model studies, translation into human trials is limited. Here, we present the study protocol for a double-blind randomized controlled trial that aims to examine the effectiveness of three lactobacilli strains on volumetric bone mineral density (vBMD), trabecular, and cortical microstructure, as measured using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT). The trial will randomize 124 healthy early postmenopausal women (up to 8 years from menopause) to receive either probiotic or placebo administered once daily for 12 months. Secondary outcomes will investigate the probiotics' effects on areal BMD and specific mechanistic biomarkers, including bone metabolism and inflammatory markers. The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12621000810819).

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT.

Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment with the GH receptor antagonist pegvisomant on bone microstructure were unknown. We studied 25 patients with acromegaly (15 men, 10 women). In 20, we evaluated areal bone mineral density (BMD) by dual-energy X-ray absorptiometry and bone turnover markers (BTMs) longitudinally, before and during pegvisomant treatment. After long-term pegvisomant in 17, we cross-sectionally assessed volumetric BMD, microarchitecture, stiffness, and failure load of the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HRpQCT) and compared these results to those of healthy controls and 2 comparison groups of nonpegvisomant-treated acromegaly patients, remission, and active disease, matched for other therapies and characteristics. In the longitudinal study, areal BMD improved at the lumbar spine but decreased at the hip in men after a median ∼7 years of pegvisomant. In the cross-sectional study, patients on a median ∼9 years of pegvisomant had significantly larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to healthy controls. Microstructure was similar in the pegvisomant and acromegaly comparison groups. BTMs were lowered, then stable over time. In this, the first study to examine bone microstructure in pegvisomant-treated acromegaly, we found deficits in volumetric BMD and microarchitecture of the peripheral skeleton. BTM levels remained stable with long-term therapy. Deficits in bone quality identified by HRpQCT may play a role in the pathogenesis of fragility in treated acromegaly.

Differences in dietary intake in early postmenopausal women with different levels of areal and volumetric bone mineral density: a cross-sectional analysis of baseline data from an intervention study

Osteoporosis is a degenerative disease of the bone. The rate of bone loss is accelerated during the first postmenopausal years in women which results in their disproportionate prevalence of osteoporosis(2). Some of the factors contributing to the development and maintenance of bone mineral density (BMD) relate to diet, particularly the intake of protein, calcium and other micronutrients that play a crucial role in bone composition(3). The most common method of measuring BMD is dual-energy X-ray absorptiometry (DXA) which generates a two-dimensional image of the scan site (typically spine, hip and/or forearm) to determine areal BMD (aBMD). However, new methods have recently emerged, including High Resolution peripheral Quantitative Computed Tomography (HRpQCT), that offer more accurate three-dimensional measurements of volumetric BMD (vBMD) and microstructure of distal tibia and radius(4). The aim of this study was to examine the differences in the dietary intake of nutrients that represent organic or inorganic components of the bone, in early postmenopausal women with different spine aBMD and tibia and radius vBMD levels. One hundred and fourteen healthy early postmenopausal women with a lumbar spine or total hip BMD T score &gt; −2.5 (measured by DXA) were recruited as part of a larger interventional study. Dietary intake was recorded using a 297-point self-reported validated food frequency questionnaire(5) for assessing the intake of energy, macro and micronutrients. Physical activity was self-reported using the validated Active Australia Questionnaire. Years since menopause were self-reported. DXA and HRpQCT scans measured L1-L4 spine, proximal femur aBMD, and distal tibia and radius vBMD respectively. Non-parametric statistical tests examined differences in dietary intake and physical activity levels between women at different levels of aBMD and vBMD. Data reported as median and interquartile ranges. There were no significant differences observed in the total sample between tertiles of aBMD and vBMD, regarding nutrient intake. However, for women with less than 3 years since menopause (i.e., the time-period of accelerated bone loss), lower dietary intakes of energy [8,658(3,324) vs 10,068(3,688) kJ/day; p = 0.047], protein [94(29) vs 103(32) g/day; (p = 0.044)], sodium [1,927(992) vs 2,625(2,185) mg/d; (p = 0.044)], potassium [4,064(1,373) vs 5,121(2,377) mg/d; (p = 0.041)], calcium [969(325) vs 1,214(652) mg/d; (p = 0.028)] and zinc [10(3) vs 12(4) mg/d; (p = 0.005)] were observed for women with osteopenia (−1&lt; L1-L4 aBMD T-score &lt;2.5) compared to those with normal L1-L4 aBMD (i.e., T-score &gt; −1). No significant differences were observed for women with more than 3 years since menopause, with the only exception of alcohol intake (p = 0.033), which was found to be lower in women with osteopenia compared to those with normal aBMD. These findings highlight the importance of targeting osteopenic women within the first 3 years following menopause as candidates for tailored dietary intervention programs for preventing osteoporosis.

Homogenized finite element analysis of distal tibia sections: Achievements and limitations

High-resolution peripheral quantitative computed tomography (HR-pQCT) based micro-finite element (μFE) analysis allows accurate prediction of stiffness and ultimate load of standardised (∼1 cm) distal radius and tibia sections. An alternative homogenized finite element method (hFE) was recently validated to compute the ultimate load of larger (∼2 cm) distal radius sections that include Colles' fracture sites. Since the mechanical integrity of the weight-bearing distal tibia is gaining clinical interest, it has been shown that the same properties can be used to predict the strength of both distal segments of the radius and the tibia. Despite the capacity of hFE to predict structural properties of distal segments of the radius and the tibia, the limitations of such homogenization scheme remain unclear. Therefore, the objective of this study is to build a complete mechanical data set of the compressive behavior of distal segments of the tibia and to compare quantitatively the structural properties with the hFE predictions. As a further aim, it is intended to verify whether hFE is also able to capture the post-yield strain localisation or fracture zones in such a bone section, despite the absence of strain softening in the constitutive model.Twenty-five fresh-frozen distal parts of tibias of human donors were used in this study. Sections were cut corresponding to an in-house triple-stack protocol HR-pQCT scan, lapped, and scanned using micro computed tomography (μCT). The sections were tested in compression until failure, unloaded and scanned again in μCT. Volumetric bone mineral density (vBMD) and bone mineral content (BMC) were correlated to compression test results. hFE analysis was performed in order to compare computational predictions (stiffness, yield load and plastic deformation field pattern) with the compressive experiment. Namely, strain localization was assessed based on digital volume correlation (DVC) results and qualitatively compared to hFE predictions by comparing mid-slices patterns.Bone mineral content (BMC) showed a good correlation with stiffness (R2 = 0.92) and yield (R2 = 0.88). Structural parameters also showed good agreement between the experiment and hFE for both stiffness (R2 = 0.96, slope = 1.05 with 95 % CI [0.97, 1.14]) and yield (R2 = 0.95, slope = 1.04 [0.94, 1.13]). The qualitative comparison between hFE and DVC strain localization patterns allowed the classification of the samples into 3 categories: bad (15 sections), semi (8), and good agreement (2).The good correlations between BMC or hFE and experiment for structural parameters were similar to those obtained previously for the distal part of the radius. The failure zones determined by hFE corresponded to registration only in 8 % of the cases. We attribute these discrepancies to local elastic/plastic buckling effects that are not captured by the continuum-based FE approach exempt from strain softening. A way to improve strain localization hFE prediction would be to use longer distal segments with intact cortical shells, as done for the radius. To conclude, the used hFE scheme captures the elastic and yield response of the tibia sections reliably but not the subsequent failure process.

Deep Convolutional Neural Networks Provide Motion Grading for High-Resolution Peripheral Quantitative Computed Tomography of the Scaphoid.

In vivo high-resolution peripheral quantitative computed tomography (HR-pQCT) studies on bone characteristics are limited, partly due to the lack of standardized and objective techniques to describe motion artifacts responsible for lower-quality images. This study investigates the ability of such deep-learning techniques to assess image quality in HR-pQCT datasets of human scaphoids. In total, 1451 stacks of 482 scaphoid images from 53 patients, each with up to six follow-ups within one year, and each with one non-displaced fractured and one contralateral intact scaphoid, were independently graded by three observers using a visual grading scale for motion artifacts. A 3D-CNN was used to assess image quality. The accuracy of the 3D-CNN to assess the image quality compared to the mean results of three skilled operators was between 92% and 96%. The 3D-CNN classifier reached an ROC-AUC score of 0.94. The average assessment time for one scaphoid was 2.5 s. This study demonstrates that a deep-learning approach for rating radiological image quality provides objective assessments of motion grading for the scaphoid with a high accuracy and a short assessment time. In the future, such a 3D-CNN approach can be used as a resource-saving and cost-effective tool to classify the image quality of HR-pQCT datasets in a reliable, reproducible and objective way.

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

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. 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. 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). 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.

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 8years 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 48.3months, 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.