Altered Bone Structure Research Articles

Skeletal Manifestations of Gender-Affirming Medical Interventions for Aiding in the Preliminary Identification of Trans Individuals

Because of systemic discrimination, transgender individuals are at greater risk of being the victims of violence and of homicide. Accurate post-mortem identification from skeletonized remains of transgender individuals must be incorporated into a new standard for forensic anthropological analyses. A critical component of any investigation is the assessment of skeletal remains for evidence of gender-affirming care. A systematic review of the current medical literature was conducted to compile in one document descriptions of changes that could be used by forensic anthropologists to recognize skeletal manifestations resulting from gender-affirming surgeries, including facial feminization surgery (FFS), shoulder width reduction surgery, and limb-lengthening procedures. These skeletal changes, when present bilaterally and without evidence of healed trauma, serve as key indicators of a person’s transgender identity postmortem. Recognizing common patterns in bone structure alterations due to gender-affirming interventions will assist in identifying transgender individuals and providing closure for families. By integrating markers from gender-affirming care practices into forensic investigations, this research contributes to more inclusive and rigorous forensic investigations.

Automatic Skeleton Segmentation in CT Images Based on U-Net

Bone metastasis, emerging oncological therapies, and osteoporosis represent some of the distinct clinical contexts which can result in morphological alterations in bone structure. The visual assessment of these changes through anatomical images is considered suboptimal, emphasizing the importance of precise skeletal segmentation as a valuable aid for its evaluation. In the present study, a neural network model for automatic skeleton segmentation from bidimensional computerized tomography (CT) slices is proposed. A total of 77 CT images and their semimanual skeleton segmentation from two acquisition protocols (whole-body and femur-to-head) are used to form a training group and a testing group. Preprocessing of the images includes four main steps: stretcher removal, thresholding, image clipping, and normalization (with two different techniques: interpatient and intrapatient). Subsequently, five different sets are created and arranged in a randomized order for the training phase. A neural network model based on U-Net architecture is implemented with different values of the number of channels in each feature map and number of epochs. The model with the best performance obtains a Jaccard index (IoU) of 0.959 and a Dice index of 0.979. The resultant model demonstrates the potential of deep learning applied in medical images and proving its utility in bone segmentation.

Modulatory interactions of T-2 and deoxynivalenol mycotoxins on murine femoral development and osteological integrity

In this study, we conducted a systematic assessment of the effectsof deoxynivalenol (DON) and T-2 mycotoxins (T-2) on the developmental processes and structural integrity of murine femurs, considering both the isolated and synergistic effects of these toxins. To this end, we divided 72 male mice into nine groups, each subjected to varying dosages of T-2, DON, or their combinations. Over a four-week experimental period, meticulous monitoring was undertaken regarding the mice's body weight, biochemical markers of bone formation and resorption, and the activity of relevant cells. To comprehensively evaluate alterations in bone structure, we employed biomechanical analysis, micro-computed tomography (micro-CT), and transmission electron microscopy.Our findings unveiled a significant revelation: the mice exhibited a dose-dependent decrease in body weight upon exposure to individual mycotoxins, while the combined use of these toxins manifested an atypical antagonistic effect. Furthermore, we observed variations in the levels of calcium, phosphorus, and vitamin D, as well as adjustments in the activities of osteoblasts and osteoclasts, all intricately linked to the dosage and ratio of the toxins. Alterations in biomechanical properties were also noted to correlate with the dosage and combination of toxins. Analyses via micro-CT and transmission electron microscopy further corroborated the substantial impact of toxin dosage and combinations on both cortical and trabecular bone structures.In summation, our research unequivocally demonstrates the dose- and ratio-dependent detrimental effects of DON and T-2 mycotoxins on the growth and structural integrity of murine femurs. These insights accentuate the importance of a profound understanding of the potential risks these toxins pose to bone health, offering pivotal guidance for future toxicological research and public health preventative strategies.

A Review of the Functional Characteristics and Applications of Aristotelia chilensis (Maqui Berry), in the Food Industry.

The Aristotelia chilensis (Mol.) Stuntz, also known as Maqui, is an endemic berry native to southern Chile. It is a very popular berry for its nutritional attributes and health benefits, provided mainly by its polyphenols. This review aims to investigate the Maqui and its nutritional characteristics, its health benefits, and the application of Maqui in the food industry. This fruit provides 150 calories per 100 g of product and has a low protein content and a high fiber content. Its seeds contain monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs); however, its most outstanding feature is its high value of bioactive compounds, mainly anthocyanins, indole alkaloids and flavonoids, coumarins, caffeic and ferulic acids, and delphinidin 3-O-β-glucoside, the latter being the most representative, providing Maqui with high antioxidant activity. Maqui is considered a fruit of high interest as a nutraceutical product for the control and prevention of ongoing diseases, and among its benefits, we can highlight glycemic and metabolic control; the control and prevention of obesity, cancer, cognitive decline, and dementia; the prevention and treatment of bone structure alterations; prevention against oxidative stress, particularly in cigarette smoke-induced stress. In addition to its nutraceutical use, Maqui has been used in the food industry to improve the shelf life (by controlling lipid oxidation) and nutritional value of food products and as a substitute for synthetic additives. In addition, the inclusion of Maqui improves the organoleptic and sensory characteristics of foods. The incorporation of this fruit has been observed mainly in drinks, meat products, bakery products, and milk products. Evidence has shown that Maqui consumption, as well as products with Maqui added, have a good acceptability and exert benefits on people's health. Knowledge about the application of Maqui in food will allow us to create new nutraceutical and food products that improve their nutritional and functional value.

The direct impact of pegvisomant on osteoblast functions and bone development.

Acromegaly is a chronic disease characterized by growth hormone (GH) hypersecretion, usually caused by a pituitary adenoma, resulting in elevated circulating levels of insulin-like growth factor type I (IGF-I). Pegvisomant (PEG), the GH-receptor (GHR) antagonist, is used in treating acromegaly to normalize IGF-I hypersecretion. Exposure to increased levels of GH and IGF-I can cause profound alterations in bone structure that are not completely reverted by treatment of GH hypersecretion. Indeed, there is evidence that drugs used for the treatment of acromegaly might induce direct effects on skeletal health regardless of biochemical control of acromegaly. We investigated, for the first time, the effect of PEG on cell proliferation, differentiation, and mineralization in the osteoblast cell lines MC3T3-E1 and hFOB 1.19 and its potential impact on bone development in zebrafish larvae. We observed that PEG did not affect osteoblast proliferation, apoptosis, alkaline phosphatase (ALP) activity, and mineralization. After PEG treatment, the analysis of genes related to osteoblast differentiation showed no difference in Alp, Runx2, or Opg mRNA levels in MC3T3-E1 cells. GH significantly decreased cell apoptosis (-30 ± 11%, p < 0.001) and increased STAT3 phosphorylation; these effects were suppressed by the addition of PEG in MC3T3-E1 cells. GH and PEG did not affect Igf-I, Igfbp2, and Igfbp4 mRNA levels in MC3T3-E1 cells. Finally, PEG did not affect bone development in zebrafish larvae at 5days post-fertilization. This study provides a first evidence of the impact of PEG on osteoblast functions both in vitro and in vivo. These findings may have clinically relevant implications for the management of skeletal health in subjects with acromegaly.

High Levels of Vitamin A in Plant-Based Diets for Gilthead Seabream (Sparus aurata) Juveniles, Effects on Growth, Skeletal Anomalies, Bone Molecular Markers, and Histological Morphology.

Substitution of fish-based ingredients may alter the nutritional profile of the feeds, including the vitamin contents, ultimately leading to unbalanced vitamin supply. Vitamin A plays an essential role in epithelium preservation, cell differentiation, reproduction, and vision. It also intervenes in skeletogenesis through chondrocytes development. Therefore, low levels of vitamin A may cause poor growth and abnormal bone development among other symptoms. Besides, in gilthead seabream excess vitamin A altered bone structure and homeostasis, indicating that an upper level for vitamin A in feeds for this species must be defined. For this purpose, a practical plant-based diet (FM 10% and FO 6%) containing five increasing levels of vitamin A (24,000, 26,000, 27,000, 31,000, and 37,000 IU/kg) supplemented as retinyl acetate was formulated to identify the effects of high levels of vitamin A for gilthead seabream juveniles. The trial was conducted with 450 total fish distributed into 15 tanks, where each diet was tested in triplicates for 70 days. At the end of the trial, samples were taken for analyses of vitamin A-relevant markers. At the end of the trial the high levels of vitamin A supplementation did not cause a reduction in growth, whereas no significant effect was observed for the feed efficiency, specific growth rate, and feed convertion ratio. Although not significant, retinol content in liver showed a tendency to increase with the elevation of dietary vitamin A levels. Although minor, the highest level of vitamin A dietary content (37,000 IU/kg) caused a significant increase in caudal vertebrae partial fusion as well as caudal vertebrae malformations. Increasing dietary vitamin A was related to a reduction in the occurrence of microhemorrhages in the liver and a reduction in the presence of eosinophils associated to the pancreas. Overall, the results of the present study suggested that gilthead seabream juveniles fed a plant-based diet are able to tolerate very high levels of vitamin A supplementation when supplemented as retinyl acetate. Nevertheless, further supplementation should be avoided in order to reduce the prevalence of anomalies affecting the caudal vertebrae.

FRI079 Long-term Bone Consequences Of Roux-En-Y Gastric Bypass: A Cross-sectional And Case-Control Study Of Post-menopausal Women

Abstract Disclosure: G. Papadakis: None. E. Gonzalez Rodriguez: None. S. Mantziari: None. J. Pasquier: None. E. Shevroja: None. N. Vionnet: None. L. Favre: None. Bariatric surgery decreases bone mineral density (BMD) due to mechanical unloading (weight loss) and secondary hyperparathyroidism linked to nutrient deficiencies (calcium, vitamin D). Most studies on the bone impact of bariatric surgery have investigated premenopausal women after a follow up of less than 3 years. In the current study, we sought to determine the long-term bone impact of Roux-en-Y gastric bypass (RYGB) on post-menopausal women. A cross-sectional and a case-control study were performed in women for whom a Dual X-ray absorptiometry (DXA) at least 3 years after surgery was available. BMD was measured at lumbar spine (LS), total hip (TH) and femoral neck (FN). Trabecular bone score (TBS) at LS was analyzed after correction for soft tissue thickness. History of fractures was inquired and DXA images were reviewed for vertebral fractures. For patients on anti-osteoporotic drugs, the DXA scan before the onset of therapy was taken into account. One-hundred nineteen women were eligible at a mean 9.0 ± 5.6 years after RYGB. The fracture rate was 12% and 6% for major osteoporotic and vertebral fractures, respectively. As calcium/vitamin D supplements were administered to all patients, serum 25-hydroxyvitamin D levels exceeded the threshold of 75 nmol/l in 77% of participants with insufficient levels (less than 50 nmol/l) only in 3 patients. Serum PTH levels were within the normal range in 87% of participants. A multivariate regression model including BMI, age, time since RYGB, one-year weight loss and serum PTH highlighted higher BMI as the sole significant predictor for better BMD at LS and TH (p=0.001 and p=0.008, respectively). Time since RYGB was the only variable inversely associated with TBS. Plasma levels of bone turnover markers (β-crosslaps, P1NP) exhibited a strong inverse correlation with BMD at all sites. For the case-control substudy, 76 post-RYGB women were age- and BMI-matched to female participants of the OsteoLaus study, a population-based cohort in Lausanne. The patient group had significantly lower BMD at all sites: LS (p=0.03), TH (p=0.01), FN (p=0.007), as well as lower TBS (p=0.003) compared to controls. No statistical difference was observed for fractures, although more major osteoporotic fractures occurred in the post-RYGB group (8 vs 4 in the controls). Possibly contributing to the bone impairment, the post-bariatric cohort had more active smokers (21 vs 7 in the controls, p=0.006) and less hormonal replacement therapy users (2 vs 12 in the controls, p=0.009). In conclusion, post-bariatric BMI is the strongest determinant of long-term BMD levels. Despite satisfactory vitamin D/PTH levels, a history of RYGB several years ago was associated with lower BMD and altered bone structure in this postmenopausal cohort. Long-term bone health monitoring is warranted after RYGB especially in women who are smoking and achieved substantial weight loss. Presentation: Friday, June 16, 2023

Increasing muscle contractility through low-frequency stimulation alters tibial bone geometry and reduces bone strength in mdx and dko dystrophic mice.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations or deletions in the dystrophin gene, for which there remains no cure. As DMD patients also develop bone fragility because of muscle weakness and immobilization, better understanding of the pathophysiological mechanisms of dystrophin deficiency will help develop therapies to improve musculoskeletal health. Since alterations in muscle phenotype can influence bone structure, we investigated whether modifying muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in mouse models of DMD. We tested the hypothesis that increasing muscle contractile activity could influence bone mass and structure in dystrophin-deficient (mdx) and dystrophin- and utrophin-deficient (dko) dystrophic mice. Tibial bone structure in dko mice was significantly different from that in mdx and wild-type (C57BL/10) control mice. Effects of LFS on bone architecture differed between dystrophic and healthy mice, with LFS thinning cortical bone in both dystrophic models. Bone mass was maintained in LFS-treated healthy mice, with a reduced proportion of high-density bone and concomitant increase in low-density bone. LFS-treated dko mice exhibited a net deficit in cortical thickness and reduced high-density bone but no equivalent increase in low-density bone. These alterations in bone structure and mineral density reduced mechanical strength in mdx and dko mice. The findings reveal that muscle activity can regulate bone mass, structure, mineral accrual, and strength, especially in the context of dystrophin and/or utrophin deficiency. The results provide unique insights into the development of bone fragility in DMD and for devising interventions to improve musculoskeletal health.NEW & NOTEWORTHY Patients with Duchenne muscular dystrophy (DMD) develop bone fragility because of muscle weakness and immobilization. We investigated whether increasing muscle contractile activity through low-frequency stimulation (LFS) could alter bone architecture in dystrophin-deficient (mdx) or dystrophin- and utrophin-deficient (dko) mouse models of DMD. Chronic LFS reduced tibial diaphysis cross sections in mdx and dko mice, without affecting bone shape in healthy mice. LFS affected the distribution of bone mineral density across all phenotypes, with the magnitude of effect being dependent on disease severity.

Typical X-ray Semiotic Signs of High-Density Inclusions of the Jaws According to Cone-Beam Computed Tomography

In the process of evaluating X-ray diagnostic images of the jaw bones of dental patients, foci of altered bone structure and atypical intraosseous inclusions of increased density are often found. The identified inclusions have different etiology, but at the same time a similar and in some cases implicit scialogical picture, which may cause an incorrect radiological conclusion. When analyzing the available literature, limited information was found about the typical radiosemiotic signs of dense intraosseous inclusions of the jaw bones found in everyday medical practice.

The Role of High-intensity and High-impact Exercises in Improving Bone Health in Postmenopausal Women: A Systematic Review.

Postmenopausal osteoporosis is a chronic condition with decreased bone mass and altered bone structure, leading to a greater risk of fractures among older women. Exercise has been proposed as a potentially effective non-pharmacological method to prevent this condition. In this systematic review, we investigate the effects and safety of high-impact and high-intensity exercises in improving bone density at popular sites of fragility fractures, namely, the hip and spine. This review also highlights the mechanism of these exercises in improving bone density and other aspects of bone health in postmenopausal women. This study is done adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After applying the eligibility criteria, we selected 10 articles from PubMed and Google Scholar to be included in our study. Based on the findings from the studies, we established that high-intensity and high-impact exercises are effective in improving, or at the very least maintaining, bone density in the lumbar spine and femur in postmenopausal women. An exercise protocol including high-intensity resistance exercises and high-impact training is shown to be most effective in improving bone density and other parameters of bone health. These exercises were found to be safe in older women, however, careful supervision is recommended. All limitations considered, high-intensity and high-impact exercises are an effective strategy to enhance bone density, and potentially reduce the burden of fragility as well as compression fractures in postmenopausal women.

Do patients with type 2 diabetes have impaired hip bone microstructure? A study using 3D modeling of hip dual-energy X-ray absorptiometry.

Patients with type 2 diabetes (T2DM) have more risk of bone fractures. However, areal bone mineral density (aBMD) by conventional dual-energy x-ray absorptiometry (DXA) is not useful for identifying this risk. This study aims to evaluate 3D-DXA parameters determining the cortical and trabecular compartments in patients with T2DM compared to non-diabetic subjects and to identify their determinants. Case-control study in 111 T2DM patients (65.4 ± 7.6 years old) and 134 non-diabetic controls (64.7 ± 8.6-year-old). DXA, 3D-DXA modelling via 3D-Shaper software and trabecular bone score (TBS) were used to obtain aBMD, cortical and trabecular parameters, and lumbar spine microarchitecture, respectively. In addition, biochemical markers as 25-hydroxyvitamin d, type I procollagen N-terminal propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), and glycated haemoglobin (HbA1c) were analysed. Mean-adjusted values showed higher aBMD (5.4%-7.7%, ES: 0.33-0.53) and 3D-DXA parameters (4.1%-10.3%, ES: 0.42-0.68) in the T2DM group compared with the control group. However, TBS was lower in the T2DM group compared to the control group (-14.7%, ES: 1.18). In addition, sex (β = 0.272 to 0.316) and body mass index (BMI) (β = 0.236 to 0.455) were the most consistent and positive predictors of aBMD (p ≤ 0.01). BMI and P1NP were negative predictors of TBS (β = -0.530 and -0.254, respectively, p ≤ 0.01), while CTX was a positive one (β = 0.226, p=0.02). Finally, BMI was consistently the strongest positive predictor of 3D-DXA parameters (β = 0.240 to 0.442, p<0.05). Patients with T2DM present higher bone mass measured both by conventional DXA and 3D-DXA, suggesting that 3D-DXA technology is not capable of identifying alterations in bone structure in this population. Moreover, BMI was the most consistent determinant in all bone outcomes.

Abstract 273: Prostate cancer metastasis induces irregular bone formation associated to specific androgen dependent phenotypes

Abstract Bone metastases (BM) occur in ~80% of advanced prostate cancer (PC) patients, and are a major cause of morbidity. PCBMs are predominantly osteoblastic with mixed, and lytic regions; all of which compromise bone strength. How PCs alter bone structure is unresolved. Prolonged use of modern androgen receptor (AR) targeting agents has increased development of AR pathway-independent PC phenotypes. We hypothesize that defining the structural changes, cellular composition, and PC classification of PCBM-affected bone will help reveal mechanisms of PCBM pathology, and identify potential therapeutic opportunities. We analyze the 3D structure of 14 cadaveric PCBM lumbar vertebrae using micro-computed tomography (microCT). We performed scanning electron microscopy quantitative backscattering electron (qBSE), and energy-dispersive X-ray spectroscopy (EDX) to determine mineral morphology and composition. We analyzed sequential decalcified sections for collagen structure, fibril orientation, and extracellular matrix composition using bright field and polarized light microscopy. We determined lesion structure and cell distribution from two PCBM vertebral specimens resected during decompression surgery using histology and immunohistochemistry, and characterized PCBM cell populations using single cell RNA sequencing (sc RNA Seq) on one vertebral specimen. MicroCT imaging revealed three distinct dysmorphic bone patterns: 1) osteolytic, defined by thinned broken trabecula of well-organized mineral and collagen structures; 2) osteoblastic, with disorganized matrix deposited on pre-existing trabecula; and 3) osteoblastic, with little, if any, residual trabecula, and dominated by accumulation of disorganized mineralized matrix. qBSE and EDX revealed heterogeneous mineral composition, with higher variability in mineral content. Disorganized matrix had a higher voids or “lacunae” density, poorly organized collagen fiber alignment, and higher decorin and pan-proteoglycan content. Sc RNA Seq revealed a PCBM tumor microenvironment composed of a variety of immune cells, hematopoietic progenitors, and bone resident cells. Importantly, we identified AR-high, AR-low, and double-negative PC cells in the same lesion, with minimum neuroendocrine component. Simultaneous presence of these PC phenotypes was confirmed by immunohistochemistry. Morphologically, AR-positive cells adopt two configurations in PCBM, i) clusters within bone cavities in which cells maintain secretory polarization and resemble prostate acini, and ii) diffuse cells in intimate contact with bone-resident cells that lack polarization. PCBM lesions have abnormal bone structures lacking collagen organization, and with mineral heterogeneity consistent with bone weakness. PC cells interact with bone cells, but how distinct PC phenotypes affect bone turnover and structure need further analysis. Citation Format: Felipe Eltit, Qiong Wang, Raphaële Charest-Morin, Colm Morrissey, Eva Corey, Rizhi Wang, Michael E. Cox. Prostate cancer metastasis induces irregular bone formation associated to specific androgen dependent phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 273.

Study of the Mandibular Bone Microstructure and Blood Minerals Bioavailability in Rainbow Trout (Oncorhynchus mykiss, Walbaum 1792) from Freshwater.

Simple SummaryBone deformities in the axial skeleton represent a frequent bone pathology in farmed salmonids, affecting the quality of life and even increasing mortality. Bone deformation can affect the formation, repair, and regeneration of inorganic-bone components and is associated with diet, culture conditions, and genetics. If diet and culture conditions are factors in the development of bone deformity, wild fish lack them and present fewer deformations than farmed fish. Hence, we studied mandibular bone microstructure using variable pressure scanning electron microscope (VP-SEM) coupled to EDS detector. Two groups of smolt rainbow trout were analyzed: Group 1, farmed fish with a control diet, and Group 2, wild fish without a control diet. We observed that serum protein levels remained within normal ranges. However, the calcium and phosphorus ratio was not the same in blood as in bone; phosphorus deficiency was more critical because it forms other structural molecules such as nucleic acid, phosphoproteins, phospholipids, and high-energy phosphates. Consequently, the microstructure in wild fish showed a more significant number of pores and microfractures per area, which was detrimental to the biomechanical properties of the bone.Farmed salmonids show alterations in bone structure that result in skeletal deformities during formation, repair, and regeneration processes, with loss of mineralization at the level of the axial skeleton, mainly the head and spine, affecting their quality of life and even causing death. Despite improving factors, such as farming conditions, diets, and genetics, bone alterations appear more frequently in farmed fish than in wild fish. Thus, we used SEM-EDX, and TGA-DSC to study bone mineralization in farmed and wild rainbow trouts. As expected, we found significant differences in the nutritional parameters of farmed and wild fish (p < 0.05). Microstructural analyses indicated that farmed fish have a more robust mineral structure (p < 0.05), confirming the differences in mineralization and microstructure between both groups. However, the mechanisms regulating absorption and distribution in the organism and their effect on bone mineralization remain to be known. In our study, the combined use of techniques such as SEM-EDX and TGA-DSC allows a clearer assessment and detailed characterization beneficial to understanding the relationship between diet control and bone microstructure.

Investigation of the effects of eugenol and quercetin on bone loss in STZ-NA induced diabetic rats utilizing micro CT.

Diabetes Mellitus (DM) is a systemic disease that can effect tissues and their physiological functions at molecular and biochemical levels. Diabetic osteoporosis is one of the chronic diseases of bone metabolism effected by and characterized by augmented risk of osteoporotic fractures and destroying of bone microarchitecture. It was aimed to investigate the alterations in femoral bone structure that may take place as a complication of DM by using the antioxidant properties of eugenol and quercetin, which are phenolic compounds, in streptozotocin nicotinamide (STZ-NA) induced rats as an experimental type 2 DM (T2 DM) model. The antioxidant effect of eugenol and quercetin in case of DMdevelopment was determined by GSH ELISA kit. The effect of DM on alterations in bone structure was analyzed by micro CT. BMD, Tb.Bv/Tb.Tv, Tb.N, Tb.Th, Ct.Th, Tb.Sp and SMI data were calculated with the software CTAn. Serum GSH levels, Tb.Th and Tb.Bv/Tb.Tv values statistically decreased, and SMI values statistically increased in diabetic group compared with controls. Serum GSH levels in eugenol group were higher than diabetic group, and Tb.Bv/Tb.Tv values in eugenol group were lower than controls. Quercetin group had higher serum GSH levels and Tb.Th values compared with diabetic group, while SMI values were lower in quercetin group compared with diabetic group. Eugenol and quercetin were revealed to have antioxidant, antidiabetic and osteoprotective effects on the repair of bone structure in experimental STZ-NA T2 DM model.

Effects of testosterone and exercise training on bone microstructure of rats.

Background and Aim:Male hypogonadism results from failure to produce physiological levels of testosterone. Testosterone in men is essential in masculine development, sperm production, and adult man’s health. Osteoporosis is one of the consequences of hypogonadism. Regular physical exercise and exogenous testosterone administration are frequently used to prevent or treat this condition. This study aimed to understand the effects of lifelong exercise training and testosterone levels (isolated and together) in the main bone structure parameters.Materials and Methods:A total of 24 rats were used and randomly divided into four groups: Control group (CG; n=6), exercised group (EG, n=6), testosterone group (TG, n=6), and testosterone EG (TEG, n=6). A micro-computed tomography equipment was used to evaluate 15 bone parameters.Results:Both factors (exercise training and testosterone) seem to improve the bone resistance and microstructure, although in different bone characteristics. Testosterone influenced trabecular structure parameters, namely, connectivity density, trabecular number, and trabecular space. The exercise promoted alterations in bone structure as well, although, in most cases, in different bone structure parameters as bone mineral density and medullar mineral density.Conclusion:Overall, exercise and testosterone therapy seems to have a synergistic contribution to the general bone structure and resistance. Further studies are warranted, comparing different individual factors, as gender, lifestyle, or testosterone protocols, to constantly improve the medical management of hypogonadism (and osteoporosis).

Tibial metaphyseal sleeves in primary total knee arthroplasty following high tibial osteotomy and tibial plateau fracture; preliminary mid-term survival and outcome

BackgroundPrevious high tibial osteotomy (HTO), and tibial plateau fractures (TPF) may cause problems in subsequent total knee arthroplasty (TKA) due to altered metaphyseal bone structure. Higher rates of loosening of the tibial component have been described.In post-HTO and TPF cases, a more durable fixation could be achieved by tibial sleeves. This study investigates the preliminary short-to-midterm clinical and radiographic results in a cohort of these cases. MethodsA cohort of 28 patients was selected, 11 following HTO, and 17 following TPF. Standard clinical and radiologic follow-up was performed at 6 weeks, and one and two years. Revision with removal of primary prosthesis for any reason was the primary outcome. Patient reported pre- and postoperative pain, satisfaction and general health scores were collected at one and two years. Postoperative radiographs were analyzed for radiolucent lines. ResultsThere were no cases of aseptic loosening. Survival for all reasons was 96.4% (CI 77.2%–99.5%). One progressive radiolucent line was seen. Numerical rating scale (NRS) for pain with and without weightbearing at 2-year follow-up improved from 8 to 3 and from 5 to 2 points respectively. Overall general health scores improved with a median of 70 at ≥ 2 years, compared to 63 pre-operatively. ConclusionWith no revision for aseptic loosening the use of tibial sleeves in primary TKA seems a safe and reliable method for fixation of the tibial component in metaphyseal bone with altered bone structure at short and mid-term follow-up.Level of evidence: Level IV, cohort study.

Differentiated activities of decorin and biglycan in the progression of post-traumatic osteoarthritis

To delineate the activities of decorin and biglycan in the progression of post-traumatic osteoarthritis (PTOA). Three-month-old inducible biglycan (BgniKO) and decorin/biglycan compound (Dcn/BgniKO) knockout mice were subjected to the destabilization of the medial meniscus (DMM) surgery to induce PTOA. The OA phenotype was evaluated by assessing joint structure and sulfated glycosaminoglycan (sGAG) staining via histology, surface collagen fibril nanostructure and calcium content via scanning electron microscopy, tissue modulus via atomic force microscopy-nanoindentation, as well as subchondral bone structure and meniscus ossification via micro-computed tomography. Outcomes were compared with previous findings in the inducible decorin (DcniKO) knockout mice. In the DMM model, BgniKO mice developed similar degree of OA as the control (0.44 [-0.18 1.05] difference in modified Mankin score), different from the more severe OA phenotype observed in DcniKO mice (1.38 [0.91 1.85] difference). Dcn/BgniKO mice exhibited similar histological OA phenotype as DcniKO mice (1.51 [0.97 2.04] difference vs control), including aggravated loss of sGAGs, salient surface fibrillation and formation of osteophyte. Meanwhile, Dcn/BgniKO mice showed further cartilage thinning than DcniKO mice, resulting in the exposure of underlying calcified tissues and aberrantly high surface modulus. BgniKO and Dcn/BgniKO mice developed altered subchondral trabecular bone structure in both Sham and DMM groups, while DcniKO and control mice did not. In PTOA, decorin plays a more crucial role than biglycan in regulating cartilage degeneration, while biglycan is more important in regulating subchondral bone structure. The two have distinct activities and modest synergy in the pathogenesis of PTOA.

Cigarette smoke-associated inflammation impairs bone remodeling through NF\u03baB activation

BackgroundCigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation.MethodsWe developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated.ResultsSmoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression.ConclusionsOur findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a “smoke sensor” for bone remodeling.

Integrative multiomics analysis of Premolis semirufa caterpillar venom in the search for molecules leading to a joint disease

The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases.

Single-sided NMR to estimate morphological parameters of the trabecular bone structure.

Single-sided 1 H-NMR is proposed for the estimation of morphological parameters of trabecular bone, and potentially the detection of pathophysiological alterations of bone structure. In this study, a new methodology was used to estimate such parameters without using an external reference signal, and to study intratrabecular and intertrabecular porosities, with a view to eventually scanning patients. Animal trabecular bone samples were analyzed by a single-sided device. The Carr-Purcell-Meiboom-Gill sequence of 1 H nuclei of fluids, including marrow, confined inside the bone, was analyzed by quasi-continuous T2 distributions and separated into two 1 H pools: short and long T2 components. The NMR parameters were estimated using models of trabecular bone structure, and compared with the corresponding micro-CT. Without any further assumptions, the internal reference parameter (short T2 signal intensity fraction) enabled prediction of the micro-CT parameters BV/TV (volume of the trabeculae/total sample volume) and BS/TV (external surface of the trabeculae/total sample volume) with linear correlation coefficient >0.80. The assignment of the two pools to intratrabecular and intertrabecular components yielded an estimate of average intratrabecular porosity (33±5)%. Using the proposed models, the NMR-estimated BV/TV and BS/TV were found to be linearly related to the corresponding micro-CT values with high correlation (>0.90 for BV/TV; >0.80 for BS/TV) and agreement coefficients. Low-field, low-cost portable devices that rely on intrinsic magnetic field gradients and do not use ionizing radiation are viable tools for in vitro preclinical studies of pathophysiological structural alterations of trabecular bone.