Alterations In Bone Microstructure Research Articles

Unveiling the hidden impact: Subclinical hypercortisolism and its subtle influence on bone health.

In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward-looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.

Low-Molecular-Weight Chondroitin Sulfates Alleviate Simulated Microgravity-Induced Oxidative Stress and Bone Loss in Mice

(1) Background: Many studies have shown that microgravity experienced by astronauts or long-term bedridden patients results in increased oxidative stress and bone loss. Low-molecular-weight chondroitin sulfates (LMWCSs) prepared from intact chondroitin sulfate (CS) have been demonstrated to possess good antioxidant and osteogenic activities in vitro. This study aimed to assess the antioxidant activity of the LMWCSs in vivo and evaluate their potential in preventing microgravity-induced bone loss. (2) Methods: we used hind limb suspension (HLS) mice to simulate microgravity in vivo. We investigated the effects of LMWCSs against oxidative stress damage and bone loss in HLS mice and compared the findings with those of CS and a non-treatment group. (3) Results: LMWCSs reduced the HLS-induced oxidative stress level, prevented HLS-induced alterations in bone microstructure and mechanical strength, and reversed changes in bone metabolism indicators in HLS mice. Additionally, LMWCSs downregulated the mRNA expression levels of antioxidant enzyme- and osteogenic-related genes in HLS mice. The results showed that overall effect of LMWCSs was better than that of CS. (4) Conclusions: LMWCSs protect against the bone loss caused by simulated microgravity, which may be related to their ability to reduce oxidative stress. LMWCSs can be envisaged as potential antioxidants and bone loss protective agents in microgravity.

Trabecular bone score, bone marrow fat and vertebral fractures in cushing syndrome.

Prediction of fragility fractures in Cushing syndrome (CS) is a challenge since dual energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD) does not capture all the alterations in bone microstructure induced by glucocorticoid excess. In this study we investigated the relationship between trabecular bone score (TBS), bone marrow fat (BMF) and vertebral fractures (VFs) in endogenous CS. Cross-sectional. Thirty subjects (7 M and 23 F, mean age 44.8 ± 13.4 yrs, range: 25-71) with active hypercortisolism were evaluated for VFs by quantitative morphometry, BMD and TBS by lumbar spine DXA and BMF by single-voxel magnetic resonance spectroscopy of vertebral body of L3. Subjects with VFs (17 cases; 56.7%) had higher BMF (P = 0.014) and lower BMD T-score (P = 0.012) and TBS (P = 0.004) as compared to those without VFs. Prevalence of VFs resulted to be significantly higher in individuals with impaired TBS as compared to those with normal TBS (77.8% vs. 25.0%; P = 0.008). Among patients with VFs, only 6 (35.3%) had either osteoporosis or "low BMD for age". In logistic regression analysis, impaired TBS maintained the significant association with VFs [odds ratio (OR) 6.60, 95% C.I. 1.07-40.61; P = 0.042] independently of BMF (OR 1.03, 95% C.I. 0.99-1.08; P = 0.152). TBS might be more accurate than BMF in identifying subjects with active CS and skeletal fragility at risk of VFs. Excess in glucocorticoids is associated with alterations in bone remodeling and metabolism, leading to fragility fractures regardless of bone mineral density, making more challenging for the clinician the identification of high-risk population and the definition of preventing strategies. In this context, instrumental parameters suggestive of bone quality alterations and predictive of increased fracture risk are needed. In this study, we found CS patients to have bone quality alterations as indicated by the decreased trabecular bone score and increased bone marrow fat, as measured by DEXA and MRI respectively. Both parameters were associated with high risk of VFs, and were inversely correlated, although TBS seems to be more accurate than BMF in fractures prediction in this clinical setting.

Bone Metabolism Parameters in Azerbaijani Pre and Postmenopausal Women with Diabetes.

This study aimed to determine the directionality of changes in serum bone remodeling markers and bone mineral density in the pre- and postmenopausal women with diabetes mellitus. This study was carried out during the years 2016-2017 on the basis of Azerbaijan Medical University and included 142 pre- and postmenopausal women with type 1 and 2 diabetes mellitus (DM 1and DM2) were compared with 43 age-matched non-diabetics. The groups evaluated Ca2+, PTH, CT, 25(OH)D levels, serum bone remodeling markers (ALP, P1NP, b-CTx), lumbar spine, proximal and femoral neck areas using DXA assessment. The results showed inconsistency observed between bone remodeling processes in women with diabetes. A negative correlation was observed between duration of diabetes and Lumbar T-scores (DM1: r = -0.568, P = 0.001; DM2: r = -0.267, P = 0.04). Lumbar T-scores was negatively correlated with b-CTx level (DM1: r = -0.452, P = 0.002; DM2: r = -0.357, P = 0.09). Postmenopausal groups with DM1 and DM2 were slightly higher b-CTx levels than premenopausal. The patients with DM2 compared to DM1 had higher average BMD at all measured areas. Bone fragility is the result not so much of a decrease in BMD, but alterations in bone microstructure, as indicated by the disregulation of bone remodeling markers. This suggests that patients with diabetes are at a higher risk of bone turnover disorders compared to individuals without diabetes, which does not necessarily correlate with differences in BMD.

Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome.

Klinefelter syndrome (KS) frequently causes skeletal fragility characterized by profound alterations in bone microstructure with increased risk of fractures. Increased body fat mass associated with decreased body lean mass are frequent features of KS with possible detrimental effects on skeletal health. In this cross-sectional study, we evaluated the associations between body composition parameters, vertebral fractures (VFs) and trabecular bone score (TBS) in adult subjects with KS. Seventy-one adult males (median age 41years, range 18-64) with 47, XXY KS were consecutively enrolled by two Endocrinology and Andrology Units (IRCCS Humanitas Research Hospital in Milan and ASST Spedali Civili in Brescia). Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density (BMD) at lumbar spine, femoral neck and total hip, TBS and body composition. Prevalence of VFs was assessed by quantitative morphometry on lateral spine X-rays. VFs were detected in 14 patients (19.7%), without significant association with low BMD (p = 0.912). In univariate logistic regression analysis, VFs were significantly associated with truncal/leg fat ratio (OR 2.32 per tertile; 95% CI 1.05-5.15; p = 0.038), whereas impaired TBS (detected in 23.4% of subjects) was associated with older age at study entry (p = 0.001) and at diagnosis of disease (p = 0.015), body mass index (BMI; p = 0.001),waist circumference (p= 0.007), fat mass index (FMI; p < 0.001), FMI/lean mass index (LMI) ratio (p = 0.001). Prevalence of VFs was not significantly different between subjects with impaired TBS as compared to those with normal TBS (26.7 vs. 18.4%; p = 0.485). Skeletal end-points were not significantly associated with duration of testosterone replacement therapy and serum testosterone and 25hydroxyvitamin D values. Body composition might influence bone quality and risk of VFs in subjects with KS.

Evaluation of Quality and Bone Microstructure Alterations in Patients with Type 2 Diabetes: A Narrative Review.

Bone fragility is a common complication in subjects with type 2 diabetes mellitus (T2DM). However, traditional techniques for the evaluation of bone fragility, such as dual-energy X-ray absorptiometry (DXA), do not perform well in this population. Moreover, the Fracture Risk Assessment Tool (FRAX) usually underestimates fracture risk in T2DM. Importantly, novel technologies for the assessment of one microarchitecture in patients with T2DM, such as the trabecular bone score (TBS), high-resolution peripheral quantitative computed tomography (HR-pQCT), and microindentation, are emerging. Furthermore, different serum and urine bone biomarkers may also be useful for the evaluation of bone quality in T2DM. Hence, in this article, we summarize the limitations of conventional tools for the evaluation of bone fragility and review the current evidence on novel approaches for the assessment of quality and bone microstructure alterations in patients with T2DM.

Skeletal disorders associated with the growth hormone-insulin-like growth factor 1 axis.

Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are important regulators of bone remodelling and metabolism and have an essential role in the achievement and maintenance of bone mass throughout life. Evidence from animal models and human diseases shows that both GH deficiency (GHD) and excess are associated with changes in bone remodelling and cause profound alterations in bone microstructure. The consequence is an increased risk of fractures in individuals with GHD or acromegaly, a condition of GH excess. In addition, functional perturbations of the GH-IGF1 axis, encountered in individuals with anorexia nervosa and during ageing, result in skeletal fragility and osteoporosis. The effect of interventions used to treat GHD and acromegaly on the skeleton is variable and dependent on the duration of the disease, the pre-existing skeletal state, coexistent hormone alterations (such as those occurring in hypogonadism) and length of therapy. This variability could also reflect the irreversibility of the skeletal structural defect occurring during alterations of the GH-IGF1 axis. Moreover, the effects of the treatment of GHD and acromegaly on locally produced IGF1 and IGF binding proteins are uncertain and in need of further study. This Review highlights the pathophysiological, clinical and therapeutic aspects of skeletal fragility associated with perturbations in the GH-IGF1 axis.

Hyperkyphosis is not dependent on bone mass and quality in the mouse model of Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant disease affecting cardiovascular, ocular and skeletal systems. It is caused by mutations in the fibrillin-1 (FBN1) gene, leading to structural defects of connective tissue and increased activation of TGF-β. Angiotensin II (ang-II) is involved in TGF-β activity and in bone mass regulation. Inhibition of TGF-β signaling by blockage of the ang-II receptor 1 (AT1R) via losartan administration leads to improvement of cardiovascular and pulmonary phenotypes, but has no effect on skeletal phenotype in the haploinsufficient mouse model of MFS mgR, suggesting a distinct mechanism of pathogenesis in the skeletal system. Here we characterized the skeletal phenotypes of the dominant-negative model for MFS mgΔlpn and tested the effect of inhibition of ang-II signaling in improving those phenotypes. As previously shown, heterozygous mice present hyperkyphosis, however we now show that only males also present osteopenia. Inhibition of ang-II production by ramipril minimized the kyphotic deformity, but had no effect on bone microstructure in male mutant animals. Histological analysis revealed increased thickness of the anterior longitudinal ligament (ALL) of the spine in mutant animals (25.8±6.3 vs. 29.7±7.7μm), coupled with a reduction in type I (164.1±8.7 vs. 139.0±4.4) and increase in type III (86.5±10.2 vs. 140.4±5.6) collagen in the extracellular matrix of this ligament. In addition, we identified in the MFS mice alterations in the erector spinae muscles which presented thinner muscle fibers (1035.0±420.6 vs. 655.6±239.5μm2) surrounded by increased area of connective tissue (58.17±6.52 vs. 105.0±44.54μm2). Interestingly, these phenotypes were ameliorated by ramipril treatment. Our results reveal a sex-dependency of bone phenotype in MFS, where females do not present alterations in bone microstructure. More importantly, they indicate that hyperkyphosis is not a result of osteopenia in the MFS mouse model, and suggest that incompetent spine ligaments and muscles are responsible for the development of that phenotype.

Bifidobacterium pseudocatenulatum CECT 7765 reverses the adverse effects of diet-induced obesity through the gut-bone axis.

Obesity and the associated chronic metabolic diseases (e.g., type-2 diabetes) adversely affect bone metabolism and health. Gut microbiota is considered to be involved in the pathophysiology of obesity and also represents a therapeutic target. This study has investigated the contribution of diet-induced obesity to alterations in bone health and metabolism and whether these could be restored by oral administration of Bifidobacterium pseudocatenulatum CECT 7765. To do so, adult male wild-type C57BL-6 mice were fed either a standard or high-fat diet (HFD), supplemented or not with B. pseudocatenulatum CECT 7765 (109 CFU/day) for 14 weeks. Effects on bone mass density (BMD), bone mineral content, bone remodeling, bone structure and gene expression were assessed. In HFD-fed mice, bone microstructural properties at the distal femur showed deteriorated trabecular architecture in bone volumetric fraction, trabecular number and trabecular pattern factor. Besides, the HFD reduced the volumetric bone mineral density in the trabecular bone, but not in the cortical bone. All these bone microstructural alterations found in obese mice were reversed by B. pseudocatenulatum CECT 7765. Administration of the bacterium increased (p < .05) the Wnt/β-catenin pathway gene expression, which could mediate effects on BMD. Bifidobacterium pseudocatenulatum CECT 7765 supplementation increased (p < .05) serum osteocalcin (OC, bone formation parameter), and decreased serum C-terminal telopeptide (CTX) (p < .01) and parathormone (PTH) (p < .05) (both bone resorption parameters). It also altered the microstructure of the femur. In summary, HFD interfered with the normal bone homeostasis leading to increased bone loss. In obese mice, B. pseudocatenulatum CECT 7765 lowered bone mass loss and enhanced BMD by decreasing bone resorption and increasing bone formation.

Factors associated with bone microstructural alterations assessed by HR-pQCT in long-term HIV-infected individuals.

In adults with long-term HIV infection, low bone density and increased fracture risk have emerged as significant comorbidities. Our aim was to assess the association of exercise, nutrition, and medications with bone quality in adults with long-term HIV infection. Forty-three adults with HIV infection were enrolled (median BMI 25.7, range 18.2-35.6kg/m2; median age 57, range 50-69years). Participants underwent ultradistal radius and tibia high-resolution peripheral quantitative CT (HR-pQCT). Questionnaires included the revised Community Healthy Activities Model Program for Seniors (CHAMPS), the Mini Nutritional Assessment (MNA) as well as medication assessments. Multivariable linear regression models were used to evaluate the association of exercise, nutritional status, tenofovir disoproxil fumarate (TDF) and protease inhibitor (PI) use with bone density and microstructure, adjusting for demographic risk factors. In regression models, higher nutrition scores were associated with higher tibia cortical thickness (R2=0.23; β=0.03; p=0.044) and higher radius cortical BMD (R2=0.43; β=8.4; p=0.026). Higher weekly frequency of all physical activities was significantly associated with higher radius trabecular BMD (R2=0.38; β=0.96; p=0.050), higher radius trabecular number (R2=0.31; β=0.01; p=0.026), lower tibia and radius trabecular separation (tibia: R2=0.30; β=-0.003; p=0.038; radius: R2=0.35; β=-0.003; p=0.021), and higher radius bone stiffness (R2=0.45; β=0.38; p=0.047). Higher frequency of bone loading physical activities was significantly associated with higher tibia trabecular density (R2=0.44; β=4.06; p=0.036), higher tibia bone stiffness (R2=0.46; β=3.06; p=0.050), and higher tibia estimated failure load (R2=0.46; β=0.17; p=0.049). TDF used in combination with a PI was associated with lower radius trabecular BMD (R2=0.39; β=-41.2; p=0.042), lower radius trabecular number (R2=0.34; β=-0.44; p=0.009) and greater radius trabecular separation (R2=0.42; β=0.16; p=0.002), while TDF use without a PI was not associated with reduced bone quality. In adults with HIV infection, malnutrition is associated with poor cortical bone quality, while reduced frequency of physical activities and specifically reduced frequency of mechanical loading activities are associated with deficient trabecular bone structure and reduced estimates of bone strength. TDF use in combination with a PI is associated with deleterious effects on trabecular bone structure.

Acromégalie : améliorer la prise en charge: Acromegaly: improving care

Acromegaly is characterized by increased release of growth hormone (GH) and, consequently, Insulin-Like Growth Factor I (IGF-I), most often by a pituitary adenoma. Prolonged exposure to excess hormone leads to progressive somatic disfigurement and a wide range of systemic manifestations that are associated with increased mortality. Transsphenoidal adenomectomy is the treatment of choice of GH-secreting pituitary tumors but surgical cure is not achieved in around 50% of patients, then adjuvant treatment is necessary. Mortality in acromegaly is normalized with biochemical control and has decreased in the last decade with the increased use of adjuvant therapy. Both GH and IGF-I are currently biomarkers for assessing disease activity in patients with acromegaly. However, discordance between GH and IGF-I results is encountered in a quarter of treated patients. The impacts of such a discrepancy over mortality and morbidity and the risk of biochemical and/or clinical recurrence are unclear. Moreover, despite a good biochemical control, some symptoms persist, leading to a decreased quality of life. Back pain due to vertebral fractures seem to be frequent in these patients and underdiagnosed. In patients with acromegaly, bone mineral density is not a reliable predictor of fracture risk. A more accurate evaluation of bone microstructural alterations associated with GH hypersecretion and vertebral fractures may be provided by new radiological devices analyzing alteration of trabecular microarchitecture, leading to a better prevention.© 2019 Published by Elsevier Masson SAS. All rights reserved.Cet article fait partie du numéro supplément Les Must de l’Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration

The aim of this study was to investigate how bone microstructure within bone marrow lesions (BMLs) relates to the bone and cartilage across the whole human tibial plateau. Thirty-two tibial plateaus from patients with osteoarthritis (OA) at total knee arthroplasty and eleven age-matched non-OA controls, were scanned exvivo by MRI to identify BMLs and by micro CT to quantitate the subchondral (plate and trabecular) bone microstructure. For cartilage evaluation, specimens were processed histologically. BMLs were detected in 75% of the OA samples (OA-BML), located predominantly in the anterior-medial (AM) region. In contrast to non-OA control and OA-no BML, in OA-BML differences in microstructure were significantly more evident between subregions. In OA-BML, the AM region contained the most prominent structural alterations. Between-group comparisons showed that the AM region of the OA-BML group had significantly higher histological degeneration (OARSI grade) (P<.0001, P<.05), thicker subchondral plate (P<.05, P<.05), trabeculae that are more anisotropic (P<.0001, P<.05), well connected (P<.05, P=n.s), and more plate-like (P<0.05, P<0.05), compared to controls and OA-no BML at this site. Compared to controls, OA-no BML had significantly higher OARSI grade (P<.0001), and lower trabecular number (P<.05). In established knee OA, both the extent of cartilage damage and microstructural degeneration of the subchondral bone were dependent on the presence of a BML. In OA-no BML, bone microstructural alterations are consistent with a bone attrition phase of the disease. Thus, the use of BMLs as MRI image-based biomarkers appear to inform on the degenerative state within the osteochondral unit.

Gender difference of CCAAT/enhancer binding protein homologous protein deficiency in susceptibility to osteopenia.

Expression of CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) is induced during endoplasmic reticulum (ER) stress, which is related to apoptosis in several cell types. CHOP null mice have been exhibited to decrease bone formation. However, a study of transgenic mice overexpressing CHOP in the bone microenvironment showed that CHOP overexpression impairs the osteoblastic function leading to osteopenia. The regulatory role of CHOP in bone formation is controversial and still remains to be clarified. Here, we investigated the alterations in bone microstructure of CHOP knockout (Chop-/- ) mice and tested the gender difference of CHOP deficiency in susceptibility to osteopenia. Adult female and male mice (WT) and Chop-/- mice were used. The microcomputed tomography (µCT) analysis in trabecular bone and cortical bone of tibia was determined. Trabecular bone volume fraction (BV/TV), trabecular number, and bone mineral density (BMD) in tibia are markedly decreased in both male and female Chop-/- mice compared to the control WT mice. Unexpectedly, the BMD and BV/TV in trabecular bone of tibia in female Chop-/- mice were significantly lower than in male Chop-/- mice. The similar results could also be observed in the cortical bone of tibia in Chop-/- mice. This gender difference was also observed in the decreased capacity of osteoblast differentiation of bone marrow cells isolated from Chop-/- mice. These results indicated that ER stress-related CHOP signaling might play an important role in the bone formation in a mouse model, especially in females. There is the gender difference of CHOP deficiency in susceptibility to osteopenia. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Bone microstructure is significantly altered in CRPS-affected distal tibiae as detected by HR-pQCT: a retrospective cross-sectional study.

In the course of complex regional pain syndrome (CRPS), local osteopenia in the subchondral/subcortical areas of the affected limb represents a central manifestation. Mechanistic aspects of CRPS-associated pathologies remain unclear, and knowledge about bone morphology in CRPS-affected areas is rare. The aim of this study was to assess trabecular and cortical bone microstructure in patients with CRPS of the distal tibiae. We retrospectively analysed 14 women diagnosed with unilateral CRPS type I of the lower limb whose affected and unaffected distal tibiae were examined by high-resolution peripheral quantitative computed tomography (HR-pQCT). Laboratory tests included serum levels of calcium, phosphate, 25-hydroxyvitamin D, bone alkaline phosphatase, parathyroid hormone, osteocalcin and urinary levels of deoxypyridinoline (DPD). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and both proximal femurs. Average urinary DPD levels, a biochemical marker of bone resorption, were elevated in the examined patient cohort (7.1 ± 1.9nmol/mmol, reference 3.0-7.0nmol/mmol). According to HR-pQCT, CRPS-affected distal tibiae showed significantly lower values of cortical BMD and cortical thickness compared to the unaffected contralateral side. Also, bone volume relative to total volume was significantly lower. Trabecular number and trabecular thickness tended to be lower in the affected tibiae. CRPS is associated with significant alterations in bone microstructure of the affected tibiae. Increased bone resorption seems to play a crucial role within a multifactorial process of CRPS-mediated bone atrophy. HR-pQCT could possibly serve as a diagnostic tool in specific CRPS therapy.

Contextualising the dead – Combining geoarchaeology and osteo-anthropology in a new multi-focus approach in bone histotaphonomy

Histotaphonomy has become an important area of research in funerary archaeology. It focuses on diagenetic alterations in bone microstructure and the reconstruction of post-mortem processes. Microbial bioerosion is the most common diagenetic change observed in archaeological bone, and its probable causes have been the subject of ongoing discussions.This paper presents a new integrative approach that combines methods from physical anthropology and geoarchaeology. The aim is to contextualise samples in regard to their sedimentary milieu (sediment type), the sedimentation processes they underwent, and the specific archaeological features they originate from. The analysis is based on 208 human and animal skeletal fragments from the Late La Tène site of Basel-Gasfabrik recovered from various feature types and embedded in different sediments. Both 80 μm and 30 μm thin sections were graded semi-quantitatively on a scale of 0 or 1 to 5 in regard to bacterial attack (BAI), Wedl tunnels (WTI), cyanobacterial attack (CAI), the formation of cracks (CRI), the collagen content (COI), and thermal alterations (HEI).Our results evinced no correlations between the intensity of bacterial attack and sediment types or sedimentation processes respectively. We therefore deduce that bacterial degradation of bone is mainly caused by endogenous gut bacteria. Wedl tunnels, on the other hand, are chiefly found in bones from exposed surfaces. Bone collagen content, as measured by birefringence, is dependent on a variety of factors, with thermal alteration being among the most important. Unlike the 80 μm sections used in anthropological investigations, the 30 μm thin sections typically utilized in geoarchaeological analyses permitted a reliable distinction of microbial bioerosion types. Our context-oriented histotaphonomic approach allows detailed conclusions on the causes of microbial bioerosion in bone. Moreover, it provides an important tool for reconstructing the post-mortem biographies of human and animal remains, especially in regard to (multi-stage) mortuary practices and the analysis of sedimentation processes. Thus, this novel approach generates a wealth of information from individual skeletal elements as well as from bone fragments embedded in soil samples.

Disease Duration and Stage Influence Bone Microstructure in Patients With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is known to be a major risk factor for osteoporosis reflected by a reduction of bone mineral density (BMD). However, both the extent of the macro- and microstructural alterations of bone as well as the causative factors are unknown. We have retrospectively analyzed a total of 96 patients with PBC and 53 healthy controls matched for age, sex, and body mass index. In addition to dual-energy X-ray absorptiometry (DXA) measurements at the lumbar spine and hip, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to assess the geometric, volumetric, and microstructural changes of bone at the distal radius and tibia. Furthermore, serum analyses and measures of disease duration and stage including transient elastography were performed. Total, cortical, and trabecular volumetric BMD as well as geometric parameters were significantly reduced in PBC patients. Microstructural analysis revealed a significantly lower cortical thickness (p < 0.001) and bone volume per tissue volume (p < 0.001) in the radius and tibia but unchanged trabecular number in patients with PBC (radius: p = 0.42; tibia: p = 0.12). Multivariate regression models pointed out that disease duration and stage are the primary factors that are independently associated with bone loss in PBC. A subgroup analysis of patients with additional autoimmune hepatitis (AIH) revealed no significant changes in bone structure compared with PBC only. Taken together, PBC patients demonstrate severe alterations in bone microstructure that are positively associated with disease duration and stage. By applying HR-pQCT in the distal radius and tibia, a combined bone loss syndrome expressed by a predominant decrease in BMD and cortical thickness could be detected. © 2018 American Society for Bone and Mineral Research.

Early sclerostin expression explains bone formation inhibition before arthritis onset in the rat adjuvant-induced arthritis model

Periarticular bone loss in rheumatoid arthritis (RA) is considered to be mainly related to synovial inflammation. However, strong bone loss has also described at the time of arthritis onset. Recently, a paradoxical exacerbation of joint damage was described when blocking sclerostin in various arthritis models. Thus, we aimed to determine kinetics of bone loss and its mechanisms in the adjuvant induced arthritis (AIA) rat model of RA. AIA was induced (n = 35) or not (n = 35) at day 0. In addition to well-known arthritis at day 12, we showed with 3D-imaging and histomorphometry that bone microstructural alterations occurred early from day 8 post-induction, characterized by cortical porosity and trabecular bone loss. Active osteoclastic surfaces were increased from day 8 with RANKL upregulation. More surprisingly SOST and DKK1 were overexpressed from day 6 and followed by a dramatic decrease in bone formation from day 8. At the time of arthritis onset, SOST and DKK1 returned to control values, but frizzled related protein 1 (SFRP1), proinflammatory cytokines, and MMPs started to increase. Bone alterations before arthritis onset reinforce the hypothesis of an early bone involvement in arthritis. Kinetics of osteocyte markers expression should be considered to refine Wnt inhibitor treatment strategies.

HR-pQCT detects alterations in bone microstructure in men with CKD stages 3 and 4, which are influenced by hormonal changes and body composition .

Factors associated with osteodystrophy in predialysis patients are poorly understood. In the present study, we attempted to evaluate the impact of body composition and hormonal regulatory factors on the bone microstructure in a group of men with chronic kidney disease (CKD) stages 3 and 4. 46 men, aged 50-75 years, with previously unrecognized CKD were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT), and dual-energy X-ray absorptiometry (DXA). HR-pQCT parameters were correlated with estimated glomerular filtration rate (eGFR), age, body mass index (BMI), muscle mass index (MMI), and biochemistry. As compared to patients in stage 3 CKD, those with stage 4 CKD showed lower serum 25-hydroxyvitamin D (25(OH)D) and bicarbonate levels, and higher serum fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH) levels. They also exhibited lower total, trabecular, and cortical volumetric bone mineral density, lower trabecular bone volume/tissue volume, trabecular number, trabecular and cortical thickness, and increased heterogeneity of the trabecular network. In the whole cohort, cortical bone density and thickness were negatively associated with age, PTH, and FGF-23, and positively with BMI. Trabecular bone parameters were positively associated with MMI and 25(OH)D. After simultaneously adjusting for age and eGFR, BMI, and MMI remained significantly associated with bone microstructural variables. HR-pQCT showed significant differences in bone microstructure in stage 4 vs. stage 3 CKD patients. Increased BMI, probably due to increased muscle mass, may favorably affect bone architecture in predialysis CKD patients. .

Trabecular bone score (TBS) is associated with sub-clinical vertebral fractures in HIV-infected patients.

Fragility fractures risk is increased among HIV infected patients. Bone microstructure alterations, in addition to bone mineral density (BMD) reduction, might be responsible for the increased risk. The aim of this study was to determine the prevalence of vertebral fractures (VFs) and their association with trabecular bone score (TBS), an indirect index of bone microstructure, in a cohort of HIV-infected subjects. One-hundred and forty-one HIV-infected patients (87% males, median age 43years, 94% on stable antiretroviral therapy with undetectable viral load) underwent viro-immunological and bone metabolism biochemical screenings. Lumbar TBS and BMD at femoral neck, total hip, and lumbar spine, were measured with dual-energy X-ray absorptiometry (DXA). VFs were identified using the semiquantitative method and quantitative morphometric analysis from thoracic and lumbar spine X-ray images. VFs were observed in 19 patients (13.5%). BMD was below the expected range for age in 18 (12.8%) subjects. No significant differences were found stratifying VFs prevalence by BMD, whereas patients with lower TBS showed a higher prevalence of VFs (p=0.03). In multivariate analysis, TBS was the only factor significantly associated to VFs (OR=0.56; 95% CI=0.33-0.96; p=0.034), with increased fracture risk for lower TBS values. VFs are prevalent and associated with low TBS among HIV-positive patients, whereas no significant association was found with BMD.

Mice lacking periostin are resistant to bone microstructural alterations during lactation

Mice lacking periostin are resistant to bone microstructural alterations during lactation