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Context Poor diet quality and unhealthy dietary patterns have been linked to poor bone health, yet few studies have investigated the role of diet quality in bone health in pediatric populations. Objective This systematic review aims to assess the available evidence on the association between diet quality and bone health markers in children and adolescents. Data Sources The PubMed, Scopus, and Virtual Health Library databases were searched electronically from October to November 2022, without any restrictions on date or language. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist was used to assess the quality of the studies. Data Extraction Published observational studies in children and adolescents (ages 2 to 19 years) that investigated the association between diet quality and bone health were eligible for inclusion. Two researchers independently analyzed and selected all articles using the Rayyan app. Initially, 965 papers were identified. A total of 12 observational studies qualified, including 8 cross-sectional and 4 longitudinal studies. The sample comprised 7130 individuals aged 3 to 17.9 years, representing both sexes. Bone health was evaluated by measures of bone mineral density and bone mineral content. Data Analysis Seven studies (58.3%) showed significant associations between diet quality and bone health markers, all of which evaluated diet quality by identifying dietary patterns. Diet quality as evaluated by all dietary indexes was not associated with bone health markers. Conclusions Adherence to a healthy diet may benefit bone health in children and adolescents. These findings emphasize the importance of developing effective public health policies that encourage healthy eating habits from childhood to preserve bone health. Longitudinal research using a specific tool to assess diet quality in relation to bone health is warranted. Future studies should also measure bone-regulating hormones and markers of bone turnover. Systematic Review Registration PROSPERO registration no. CRD42022368610. [ABSTRACT FROM AUTHOR]

Former studies by Hoeschen and Buhr indicated a higher total noise in a thorn image than expected from technical noise, i.e. quantum and detector noise. This difference results from the overlay of many small anatomical structures along the X-ray beam, which leads to a noise-like appearance without distinguishable structures in the projected image. A method is proposed to quantitatively determine this 'anatomical noise' component, which is not to be confused with the anatomical background (eg. ribs). This specific anatomical noise pattern in a radiograph changes completely when the imaging geometry changes because different small anatomical structures contribute to the projected image. Therefore, two images are taken using slightly different exposure geometry, and a correlation analysis based on wavelet transforms allows to determining the uncorrelated noise components. Since the technical noise also differs from image to image, which makes it difficult to separate the anatomical noise, images of a Jung phantom were produced on a low-sensitive industrial X-ray film using high-exposure levels. From these results, the anatomical noise level in real clinical thorax radiographs using realistic exposure levels is predicted using the general dose dependence described in the paper text and compared with the quantum and detector noise level of an indirect flat-panel detector system. For consistency testing, the same lung phantom was imaged with the same digital flat-panel detector and the total Sage noise including anatomical noise is determined. The results show that the relative portion of anatomical noise may exceed the technical noise level. Anatomical noise is an important contributor to the total image noise and, therefore, impedes the recognition of anatomical structures. [ABSTRACT FROM AUTHOR]

Members of the genus Psilorhynchus are small benthic fishes, commonly referred to as torrent minnows, which inhabit the fast to swift flowing water bodies of the Indo-Burma region and the Western Ghats of Peninsular India. Despite being described scientifically in the mid 18th century, the morphology of Psilorhynchus remains poorly known and its phylogenetic placement within the order Cypriniformes is a matter of considerable debate. In this paper the osteology of Psilorhynchus sucatio is described and illustrated in detail. Notes and/or illustrations on the osteology of 12 other species of Psilorhynchus are also provided for the first time. A phylogenetic investigation of the position of Psilorhynchus within the order Cypriniformes is also conducted. Analysis of 127 morphological characters scored for 52 ingroup taxa (including 12 species of Psilorhynchus) and four outgroup taxa resulted in 14 equally parsimonious cladograms (287 steps long; consitency index, CI = 0.48; retention index, RI = 0.88). Psilorhynchus is recovered as the sister group to the family Cyprinidae, and is regarded as a member of the superfamily Cyprinoidea, which forms the sister group to the Cobitoidea (including all other cypriniform families). The sistergroup relationship between Psilorhynchus and Cyprinidae is supported by eight derived characters (five of which are homoplastic within the order Cypriniformes). The monophyly of Psilorhynchus is supported by 16 derived characters (eight of which are homoplastic within Cypriniformes). Three species groups of Psilorhynchus are proposed, the Psilorhynchus balitora group (including P. amplicephalus, P. balitora, P. breviminor, P. nepalensis, P. rahmani, P. pavimentatus, and P. brachyrhynchus), the Psilorhynchus gracilis group (including P. gracilis, P. melissa, P. robustus, and P. tenura), and the Psilorhynchus homaloptera group (including P. arunachalensis, P. homaloptera, P. microphthalmus, and P. pseudecheneis). The continued use of the family group name Psilorhynchidae is recommended. Comments on the interrelationships of the Cypriniformes are also provided. © 2011 The Linnean Society of London, Zoological Journal of the Linnean Society, 2011. [ABSTRACT FROM AUTHOR]

The in vivo measurement of the activity deposited in the skeleton is a very useful source of information on human internal contaminations with transuranic elements, e.g. americium 241, especially for long time periods after intake. Measurements are performed on the skull or the larger joints such as the knee or elbow. The paper deals with the construction of an anthropomorphic numerical phantom based on CT scans, its potential for calibration and the estimation of the uncertainties of the detection system. The density of bones, activity distribution and position of the detectors were changed in individual simulations in order to estimate their effects on the result of the measurement. The results from simulations with the numerical phantom were compared with the results of physical phantoms. [ABSTRACT FROM AUTHOR]

OBJECTIVES:: To determine the accuracy and reliability of radiographic methods for assessment of the marginal bone level around oral implants in human cadavers. METHODS:: In three human cadavers two implants were placed according to the Instruction Manual for the Brånemark System®. One implant was installed in the canine and one in the premolar region of the left mandible. For each implant, conventional and digital intra-oral paralleling radiography were performed. Digital images were printed with a Kodak 1200 Distributed Medical Imaging printer® on blue transparent film, glossy and plain paper. Furthermore, digital scanographic, panoramic and tomographic images were taken with the Cranex Tome® multimodal X-ray unit and printed on Agfa Drystar TM 1 B® transparent films. All images were evaluated by five dental specialists. Data were statistically compared with real measurements of the marginal bone level on the human cadavers, performed by the same group of observers. Intra- and inter-observer variability were determined. RESULTS:: Digital intra-oral images on glossy paper showed the smallest absolute difference between real and measured bone level, followed by digital intra-oral images on film and on plain paper, conventional intra-oral images on analogue film, panoramic, scanographic and tomographic images on film. The difference between real and radiographic measurements was not statistically significant (P>0.05) for all radiographic techniques. Intra- and inter-observer reproducibility was high for all techniques. CONCLUSIONS:: The selected imaging techniques showed an acceptable accuracy for peri-implant bone level measurements with an overall error of less than 0.5 mm. Intra-oral images showed the smallest absolute differences.Dentomaxillofacial Radiology (2002) 31, 176–181 DOI: 10.1038/sj/dmfr/4600694 [ABSTRACT FROM AUTHOR]

Context There is still controversy over the effect of vitamin D3 supplementation on bone health. Objective The effects of vitamin D3 supplementation on bone mineral density (BMD) and markers of bone turnover, as well as the dose-response relationship between vitamin D3 and bone health in adults, were evaluated. Data Sources The PubMed, Scopus, Cochrane, Web of Science, and AGRIS databases were searched for articles published through April 30, 2022. Thirty-nine of the 6409 records identified met the inclusion criteria Data Extraction Data were extracted from articles by 2 authors, and data extraction was cross-checked independently. A random-effects model was used to estimate the pooled effect size and the associated 95%CI for the effect of vitamin D3 for each outcome. A one-stage random-effects dose-response model was used to estimate the dose-response relationship between vitamin D3 supplementation and BMD. Data Analysis Results of meta-analysis showed a beneficial effect of vitamin D3 at the lumbar spine (standardized mean difference [SMD] = 0.06; 95%CI, 0.01–0.12) and femoral neck (SMD = 0.25; 95%CI, 0.09–0.41). Dose-response analysis revealed a linear relationship between vitamin D3 supplementation doses and BMD at the femoral neck, lumbar spine, and total hip sites. No significant effect of vitamin D3 supplementation on whole-body or total hip BMD was observed (P  >   0.05). Vitamin D3 supplementation significantly decreased BMD at both proximal and distal forearm (SMD = −0.16; 95%CI, −0.26 to −0.06). The variables of ethnicity, age, baseline 25-hydroxyvitamin D (25[OH]D), menopause status, vitamin D3 dosing frequency, and bone health status (P interaction = 0.02) altered the effect of vitamin D3 supplementation on BMD. Additionally, a nonlinear relationship between vitamin D3 supplement doses and markers of bone turnover was found. Conclusion A protective effect of vitamin D3 supplementation on BMD of the lumbar spine, femoral neck, and total hip is implicated. Systematic Review Registration PROSPERO registration number CRD42017054132. [ABSTRACT FROM AUTHOR]

To choose the best anaesthetic approach through the retrospective review of different bone ablation procedures. We retrospectively evaluated 118 ablation procedures carried out in our institute over the last 30 months. Three different anaesthetic approaches were used: general anaesthesia, i.v. sedation/analgesia and loco-regional anaesthesia (brachial plexus block, spinal anaesthesia). The outcomes were evaluated based on three parameters: technical success, patient comfort (Scale 1–5) and operator comfort (Scale 1–5). The 118 interventional procedures were carried out on 62 benign and 56 malignant bone lesions. The overall procedural success rate was 100%. Three cases were treated under general anaesthesia: patient comfort was 5/5 in all cases; operator comfort was 5/5 in one case, and 4/5 in two cases. Twenty-one patients underwent sedation/analgesia: in three patients with benign bone lesions, patient comfort was 1/5 and operator comfort 3/5; in two patients with malignant bone lesions, patient comfort was 3/5 and operator comfort 4/5. Ninety-four patients underwent loco-regional anaesthesia: patient and operator comfort was 5/5 in all cases. Based on our experience, loco-regional anaesthesia is probably the best anaesthetic approach during bone ablation procedures. Benign bone lesions ablation are the more painful procedures. This is the first paper that systematically investigates about the best anaesthesiological support for IR procedures. [ABSTRACT FROM AUTHOR]

Ionising radiation-induced alterations affecting intercellular communication in the bone marrow (BM) contribute to the development of haematological pathologies. Extracellular vesicles (EVs), which are membrane-coated particles released by cells, have important roles in intercellular signalling in the BM. Our objective was to investigate the effects of ionising radiation on the phenotype of BM-derived EVs of total-body irradiated mice. CBA mice were irradiated with 0.1 Gy or 3 Gy X-rays. BM was isolated from the femur and tibia 24 h after irradiation. EVs were isolated from the BM supernatant. The phenotype of BM cells and EVs was analysed by flow cytometry. The mean size of BM-derived EVs was below 300 nm and was not altered by ionising radiation. Their phenotype was very heterogeneous with EVs carrying either CD29 or CD44 integrins representing the major fraction. High-dose ionising radiation induced a strong rearrangement in the pool of BM-derived EVs which were markedly different from BM cell pool changes. The proportion of CD29 and CD44 integrin-harbouring EVs significantly decreased and the relative proportion of EVs with haematopoietic stem cell or lymphoid progenitor markers increased. Low-dose irradiation had limited effect on EV secretion. Ionising radiation induced selective changes in the secretion of EVs by the different BM cell subpopulations. The novelty of the paper consists of performing a detailed phenotyping of BM-derived EVs after in vivo irradiation of mice. [ABSTRACT FROM AUTHOR]

This section presents abstracts of papers related to bones, muscles and rheumatology, presented at the Autumn Meeting of the British Geriatrics Society on October 5 to 7, 2006, including "Is Sarcopenia Associated With Health-Related Quality of Life?," "Bone Mineral Density (BMD): Correlation Between Total Hip and Femoral Neck Measurements" and "Intravenous Ibandronate Injection: 1-Year Results From Diva."

An introduction to the journal is presented in which the editor discusses two reports published within the issue such as a paper by Roman Romero-Ortuno and colleagues on a data offering insight into plasma 250HD levels in Irish community-dwelling older people and a paper from V. G. M. Chel and colleagues on the impact of ultraviolet B (UVB) exposure on vitamin D status in eight psycho-geriatric nursing home residents.

Objectives To investigate the reliability of the OMERACT US Task Force definition of US enthesitis in SpA. Methods In this web exercise, based on the evaluation of 101 images and 39 clips of the main entheses of the lower limbs, the elementary components included in the OMERACT definition of US enthesitis in SpA (hypoechoic areas, entheseal thickening, power Doppler signal at the enthesis, enthesophytes/calcifications, bone erosions) were assessed by 47 rheumatologists from 37 rheumatology centres in 15 countries. Inter- and intra-observer reliability of the US components of enthesitis was calculated using Light's kappa, Cohen's kappa, Prevalence And Bias Adjusted Kappa (PABAK) and their 95% CIs. Results Bone erosions and power Doppler signal at the enthesis showed the highest overall inter-reliability [Light's kappa: 0.77 (0.76–0.78), 0.72 (0.71–0.73), respectively; PABAK: 0.86 (0.86–0.87), 0.73 (0.73–0.74), respectively], followed by enthesophytes/calcifications [Light's kappa: 0.65 (0.64–0.65), PABAK: 0.67 (0.67–0.68)]. This was moderate for entheseal thickening [Light's kappa: 0.41 (0.41–0.42), PABAK: 0.41 (0.40–0.42)], and fair for hypoechoic areas [Light's kappa: 0.37 (0.36–0.38); PABAK: 0.37 (0.37–0.38)]. A similar trend was observed in the intra-reliability exercise, although this was characterized by an overall higher degree of reliability for all US elementary components compared with the inter-observer evaluation. Conclusions The results of this multicentre, international, web-based study show a good reliability of the OMERACT US definition of bone erosions, power Doppler signal at the enthesis and enthesophytes/calcifications. The low reliability of entheseal thickening and hypoechoic areas raises questions about the opportunity to revise the definition of these two major components for the US diagnosis of enthesitis. [ABSTRACT FROM AUTHOR]

The article discusses various reports within the issue including a study of data on the use of corticosteroids in the treatment of rheumatoid arthritis (RA), a paper on theoretical background to establish long-term low-dose glucocorticoid therapy, and research on the practical aspects of long-term inhibition of tumor necrosis factor (TNF).

Context: Increased bone fragility and reduced energy absorption to fracture associated with type 2 diabetes (T2D) cannot be explained by bone mineral density alone. This study, for the first time, reports on alterations in bone tissue's material properties obtained from individuals with diabetes and known fragility fracture status.Objective: To investigate the role of T2D in altering biomechanical, microstructural, and compositional properties of bone in individuals with fragility fracture.Methods: Femoral head bone tissue specimens were collected from patients who underwent replacement surgery for fragility hip fracture. Trabecular bone quality parameters were compared in samples of 2 groups, nondiabetic (n = 40) and diabetic (n = 30), with a mean duration of disease 7.5 ± 2.8 years.Results: No significant difference was observed in aBMD between the groups. Bone volume fraction (BV/TV) was lower in the diabetic group due to fewer and thinner trabeculae. The apparent-level toughness and postyield energy were lower in those with diabetes. Tissue-level (nanoindentation) modulus and hardness were lower in this group. Compositional differences in the diabetic group included lower mineral:matrix, wider mineral crystals, and bone collagen modifications-higher total fluorescent advanced glycation end-products (fAGEs), higher nonenzymatic cross-link ratio (NE-xLR), and altered secondary structure (amide bands). There was a strong inverse correlation between NE-xLR and postyield strain, fAGEs and postyield energy, and fAGEs and toughness.Conclusion: The current study is novel in examining bone tissue in T2D following first hip fragility fracture. Our findings provide evidence of hyperglycemia's detrimental effects on trabecular bone quality at multiple scales leading to lower energy absorption and toughness indicative of increased propensity to bone fragility. [ABSTRACT FROM AUTHOR]

Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine. JAK1 is involved in the signalling of 'γc' receptor cytokines (IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21), pro-inflammatory cytokines including IL-6, as well as IFN. The critical position of JAK1 downstream of these cytokines suggests that JAK1-selective inhibitors are comparable to non-selective ones, without the unwanted consequences of JAK2- or JAK3-blockade. JAK inhibition has led to a better understanding of the biology of synovial inflammation and bone homeostasis. Moreover, the efficacy of non-selective JAK inhibitors and novel JAK1-selective drugs in RA supports a role for JAK1 in its pathogenesis. JAK1-selective drugs are also showing promise in axial spondyloarthritis, suggesting that they may target additional regulatory pathways that impact cytokines such as TNF and IL-17A, which do not use JAKs. Additionally, evidence now supports a JAK1 predominance in the signalling of IL-6 and oncostatin M, and indirectly, of TNF in synovial fibroblasts, macrophages and endothelial cells. Notably, bone homeostasis is also dependent on cytokines relying on JAK1 signalling to promote receptor activator of NF-κB ligand expression in osteoblasts and T cells, contributing to osteoclastogenesis. Here, the contribution of JAK1 over other kinases is unclear. While beneficial effects of JAK inhibitors on bone erosion are supported by preclinical and clinical data, effects on new bone formation in axial spondyloarthritis requires additional study. [ABSTRACT FROM AUTHOR]

This paper is a review of the literature on the possible association between osteoporosis and oral bone loss, with an emphasis on radiological studies. Such an association was first suggested in 1960. Subsequent histomorphometric and microradiographic studies showed that after the age of 50 there was a marked increase in the cortical porosity of the mandible, with this increase being greater in the alveolar bone than the mandibular body; and that with this increase in porosity, there was a concomitant decrease in bone mass, which appeared to be more pronounced in females than in males, with the loss in bone mineral content estimated to be 1.5% per year in females and 0.9% in males. These studies also demonstrated a considerable amount of variation in the amounts of cortical and trabecular bone within and among individuals. Subsequent clinical studies reported associations between the bone densities of jaws and (1) metacarpals, (2) forearm bones, (3) vertebrae and (4) femurs. These studies indicated that women had lower mandibular bone mineral content (BMC) than men and that age-related loss of bone was more pronounced in women after the age of 50 years than in men of the same age, as was the case for the rest of the body. It was suggested that systemic factors responsible for osteoporotic bone loss may combine with local factors (periodontal diseases) to increase rates of periodontal alveolar bone loss. Although not all studies found associations between osteoporosis and oral bone loss, the conclusion of this review is that such an association exists; yet additional longitudinal investigations are needed to confirm this, and before the implications of this association could be fully utilized in clinical dentistry, inexpensive methods must be developed for sensitive and specific measures of oral bone loss. [ABSTRACT FROM AUTHOR]

The article presents information on the book "Mastocytosis and the Mast Cell," by Felix Sagher and Zvi Even-Paz. This beautifully illustrated book describes in a wealth of detail the various aspects of the mast cell and the diseases associated with it. There is a very long chapter on the cutaneous Mastocytosis, with all the photographs that one could hope to see. The different clinical varieties are described in full detail and the black and white photographs clearly illustrate various points made. In addition there are a few good colored photographs, not only of the clinical lesions but also of the histopathology of bone lesions.

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011. [ABSTRACT FROM PUBLISHER]

Objectives PsA prevalence among skin psoriasis is ∼30%. Nail psoriasis, especially onycholysis, is present in >70% of PsA and the risk of developing PsA is more than doubled in patients with nail involvement. We hypothesized that onycholysis may be associated with early bone erosions of the DIP joint without harbouring PsA symptoms. Methods We compared tendon thickness, assessed by US, and bone erosions, assessed by high-resolution peripheral quantitative CT, of the DIP joint in patients with psoriatic onycholysis without PsA (ONY) with those in patients with cutaneous psoriasis only (PSO). We used patients with PsA as reference (PsA group), and healthy age-matched controls (CTRL). Differences between groups were assessed by analysis of variance tests followed by post hoc analysis using the Scheffe method. Results Mean (s.e.m.) age of the 87 participants (61% males) was 45.2 (1.3) years. The mean extensor tendon thickness was significantly larger in ONY than in PSO patients. In the PsA group, 68% of patients exhibited erosions of three different shapes: V-, Omega- and U-shape. Association with erosions was greater in the ONY group than in the PSO group (frequency: 57 vs 14%; P  < 0.001; mean number of erosions: 1.10 (0.35) vs 0.03 (0.03); P  < 0.001). Conclusion Onycholysis was associated with significant enthesopathy and bone erosions in our cohort. These data support the pathogenic role of enthesopathy in PsA. Onycholysis may be considered as a surrogate marker of severity in psoriasis. Trial registration ClinicalTrails.gov, https://clinicaltrials.gov , NCT02813720 [ABSTRACT FROM AUTHOR]

Biomineralization is a fundamental process key to the development of the skeleton. The phosphatase orphan phosphatase 1 (PHOSPHO1), which likely functions within extracellular matrix vesicles, has emerged as a critical regulator of biomineralization. However, the biochemical pathways that generate intravesicular PHOSPHO1 substrates are currently unknown. We hypothesized that the enzyme ectonucleotide pyrophosphatase/phosphodiesterase 6 (ENPP6) is an upstream source of the PHOSPHO1 substrate. To test this, we characterized skeletal phenotypes of mice homozygous for a targeted deletion of Enpp6 (Enpp6−/−). Micro‐computed tomography of the trabecular compartment revealed transient hypomineralization in Enpp6−/− tibias (p < 0.05) that normalized by 12 weeks of age. Whole‐bone cortical analysis also revealed significantly hypomineralized proximal bone in 4‐ but not 12‐week‐old Enpp6−/− mice (p < 0.05) compared with WT animals. Back‐scattered SEM revealed a failure in 4‐week‐old trabecular bone of mineralization foci to propagate. Static histomorphometry revealed increased osteoid volume (p > 0.01) and osteoid surface (p < 0.05), which recovered by 12 weeks but was not accompanied by changes in osteoblast or osteoclast number. This study is the first to characterize the skeletal phenotype of Enpp6−/− mice, revealing transient hypomineralization in young animals compared with WT controls. These data suggest that ENPP6 is important for bone mineralization and may function upstream of PHOSPHO1 as a novel means of generating its substrates inside matrix vesicles. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

It has previously been stated that geckos are characterized by smooth cranial bones bearing no sculpturing; however, there are many exceptions. Here we systematically characterize variation in sculpturing in cranial bones across all seven gekkotan families and examine patterns of evolutionary transitions in these traits on a multigene molecular gekkotan phylogeny to elucidate trends in phenotypic diversification in bone sculpturing. Over 195 species were reviewed using specimens where smooth, grooved, pitted and rugose sculpturing patterns were found. Of the 26 cranial bones, only seven (premaxilla, maxilla, nasal, prefrontal, frontal, parietal and postorbitofrontal) were found to bear sculpturing across more than three species. Sculpturing was found to extend beyond these seven bones onto either the dentary, surangular and/or quadrate within five species. Phylogenetic analysis showed that sculpturing evolved recently and repeatedly in several distinct lineages. The remaining 19 skull bones were smooth, except in the five species above, supporting the suggestion that smooth skull bones were ancestral in gekkotans. There is no apparent relationship between body size and the presence of bone sculpturing. The functional significance, if any, of sculpturing requires further investigation. [ABSTRACT FROM AUTHOR]

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10–13, 2019. The conference was held as a follow‐up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The evaluation of bone complications in chronic kidney disease (CKD) often requires a bone biopsy, the analysis of which can refine the diagnosis of bone defects. Bone histomorphometry performed on sections of the iliac crest biopsy remains the reference procedure for the quantitative assessment of bone health in CKD patients, whereas immunohistochemistry and other molecular biology analyses are indispensable tools for studying the disrupted signaling pathways. Traditionally, the whole iliac crest biopsy was included in methyl‐methacrylate (MMA) and was exclusively used for bone histomorphometry to describe static, dynamic, and structural parameters. Therefore, further molecular analysis of the bone tissue or the need for tissue banking would require a second biopsy to be made, because inclusion in MMA prevents the extraction of good‐quality nucleic acids. In this work, we describe a simple approach to divide a single iliac crest bone biopsy into multiple parts. This allows for simultaneous assessments of histology, immunohistochemistry, biomolecular analysis, and tissue banking while preserving the same bone surface area for histomorphometry. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

A large part of extant and past mammalian morphological diversity is related to variation in size through allometric effects. Previous studies suggested that craniofacial allometry is the dominant pattern underlying mammalian skull shape variation, but cranial allometries were rarely characterized within cranial units such as individual bones. Here, we used 3D geometric morphometric methods to study allometric patterns of the whole skull (global) and of cranial units (local) in a postnatal developmental series of nine-banded armadillos (Dasypus novemcinctus ssp.). Analyses were conducted at the ontogenetic and static levels, and for successive developmental stages. Our results support craniofacial allometry as the global pattern along with more local allometric trends, such as the relative posterior elongation of the infraorbital canal, the tooth row reduction on the maxillary, and the marked development of nuchal crests on the supraoccipital with increasing skull size. Our study also reports allometric proportions of shape variation varying substantially among cranial units and across ontogenetic stages. The multi-scale approach advocated here allowed unveiling previously unnoticed allometric variations, indicating an untapped complexity of cranial allometric patterns to further explain mammalian morphological evolution. [ABSTRACT FROM AUTHOR]

Despite well recognized improvements in obesity-related comorbidities, increasing evidence implicates bariatric surgery in the onset of adverse skeletal health outcomes. The p urpose of this review is to provide a focused update in three critical areas: (i) emergent data on sleeve gastrectom y and bone loss, (ii) evidence linking bariatric surgery to incident fracture, and (iii) intervention strategies designe d to mitigate surgical bone loss. Better understanding of these issues will inform our treatment of skeletal health for p atients planning bariatric surgery. [ABSTRACT FROM AUTHOR]

Anurans (frogs and toads) have a unique pelvic and hind limb skeleton among tetrapods. Although their distinct body plan is primarily associated with saltation, anuran species vary in their primary locomotor mode (e.g. walkers, hoppers, jumpers, and swimmers) and are found in a wide array of microhabitats (e.g. burrowing, terrestrial, arboreal, and aquatic) with varying functional demands. Given their largely conserved body plan, morphological adaptation to these diverse niches likely results from more fine-scale morphological change. Our study determines how shape differences in Anura's unique pelvic and hind limb skeletal structures vary with microhabitat, locomotor mode, and jumping ability. Using microCT scans of preserved specimens from museum collections, we added 3D landmarks to the pelvic and hind limb skeleton of 230 anuran species. In addition, we compiled microhabitat and locomotor data from the literature for these species that span 52 of the 55 families of frogs and ∼210 million years of anuran evolution. Using this robust dataset, we examine the relationship between pelvic and hind limb morphology and phylogenetic history, allometry, microhabitat, and locomotor mode. We find pelvic and hind limb changes associated with shifts in microhabitat ("ecomorphs") and locomotor mode ("locomorphs") and directly relate those morphological changes to the jumping ability of individual species. We also reveal how individual bones vary in evolutionary rate and their association with phylogeny, body size, microhabitat, and locomotor mode. Our findings uncover previously undocumented morphological variation related to anuran ecological and locomotor diversification and link that variation to differences in jumping ability among species. [ABSTRACT FROM AUTHOR]

Osteomas are benign osteogenic lesions with very slow growth, which may arise from proliferation of either cancellous or compact bone. In the jaw, these are uncommon lesions. Excluding the maxillary sinus, there are only eight cases of maxillary osteoma reported in the English-language literature. This paper reports an additional case of maxillary osteoma in a 40-year-old man. We discuss the clinical data from the previously described cases and the main differential diagnoses. [ABSTRACT FROM AUTHOR]

Context: Aromatase inhibitors have become a mainstay in the adjuvant treatment regimen in postmenopausal women with hormone receptor-positive breast cancer. While many of these patients have an excellent long-term prognosis, adverse effects on bone represent an emerging complication of aromatase inhibitor treatment, resulting in substantial bone loss and fragility fractures. Treatment approaches to prevent aromatase inhibitor-induced bone loss typically consist of an antiresorptive approach with bisphosphonates or the RANKL antibody denosumab. However, different guidelines vary with respect to treatment thresholds, duration, and dosing. The choice of antiresorptive regime is further complicated by comorbidities and potential disease-modifying effects of individual agents.Objective: This review summarizes the evidence of how aromatase inhibitors affect bone health and provides an update of clinical approaches to preserve bone strength in affected women. (J Clin Endocrinol Metab XX: 0-0, 2020). [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) adversely affects the normal functioning, intrinsic material properties, and structural integrity of many tissues, and bone fragility is one of them. To simulate human T2D and to investigate diabetic bone fragility, many rodent diabetic models have been developed. Still, an outbred genetically normal nonobese diabetic rat model is not available that can better simulate the disease characteristics of nonobese T2D patients, who have a high prevalence in Asia. In this study, we used a combination treatment of high‐fat diet (4 weeks, 58% kcal as fat) and low‐dose streptozotocin (STZ; 35 mg/kg i.p. at the end of the fourth week) to develop T2D in female Sprague‐Dawley (SD) rats. After 8 weeks of the establishment of the T2D model, the femoral bones were excised after euthanizing rats (animal age approximately 21 to 22 weeks; n = 10 with T2D, n = 10 without diabetes). The bone microstructure (μCT), mechanical, and material properties (three‐point bending, cyclic reference point indentation, nanoindentation), mean mineral crystallite size (XRD), bone composition (mineral‐to‐matrix ratio, nonenzymatic cross‐link ratio [NE‐xLR], Fourier transform‐infrared microspectroscopy), and total fluorescent advanced glycation end products were analyzed. We found that diabetic bone had reduced whole‐bone strength and compromised structural properties (μCT). The NE‐xLRs were elevated in the T2D group, and strongly and negatively correlated with postyield displacement, which suggests bone fragility was caused by a lack of glycation control. Along with that, the decreased mineral‐to‐matrix ratio and modulus, increased indentation distance increase, and wider mineral crystallite size in the T2D group were evidence that the diabetic bone composition and material properties had changed, and bone became weaker with a tendency to easily fracture. Altogether, this model simulates the natural history and metabolic characteristics of late‐stage T2D (insulin resistance and as disease progress develops, hypoinsulinemia) for nonobese young (and/or adolescent) T2D patients (Asians) and provides potential evidence of diabetic bone fragility at various organization levels. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Porous silicon carbide (SiC) has a specific biomorphous microstructure similar to the trabecular microstructure of human bone. Compared with that of bioactive ceramics, such as calcium phosphate, SiC does not induce spontaneous interface bonding to living bone. In this study, bioactive tantalum (Ta) metal deposited on porous SiC scaffolds by chemical vapour deposition was investigated to accelerate osseointegration and improve the bonding to bones. Scanning electron microscopy indicated that the Ta coating evenly covered the entire scaffold structure. Energy-dispersive spectroscopy and X-ray diffraction analysis showed that the coating consisted of Ta phases. The bonding strength between the Ta coating and the SiC substrate is 88.4 MPa. The yield strength of porous SiC with a Ta coating (pTa) was 45.8 ± 2.9 MPa, the compressive strength was 61.4 ± 3.2 MPa and the elastic modulus was ∼4.8 GPa. When MG-63 human osteoblasts were co-cultured with pTa, osteoblasts showed good adhesion and spreading on the surface of the pTa and its porous structure, which showed that it has excellent bioactivity and cyto-compatibility. To further study the osseointegration properties of pTa. PTa and porous titanium (pTi) were implanted into the femoral neck of goats for 12 weeks, respectively. The Van-Gieson staining of histological sections results that the pTa group had better osseointegration than the pTi group. These results indicate that coating bioactive Ta metal on porous SiC scaffolds could be a potential material for bone substitutes. [ABSTRACT FROM AUTHOR]

Prosymna is a specialized African snake genus lacking close relatives. The evolutionary relationships and history within Prosymna are poorly understood. Here we assembled a multi-gene data set including representatives for 11 of 16 species to investigate the phylogenetic relationships of this group. Our analyses support the monophyly of Prosymna and are congruent with species groups previously recognized on the basis of external morphology. Divergences among extant Prosymna began in the mid-Cenozoic, with the earliest divergence splitting northern from southern lineages. High-resolution computed tomography scans confirm that a specialized skull morphology is found across the genus and was probably present in the common ancestor of Prosymna. This specialization is exemplified by dentition featuring reduced anterior but greatly enlarged, blade-like posterior maxillary teeth and an unusually high degree of fusion of cranial bones. One species, P. visseri , has a hammer-like maxilla unlike that of any other known snake. Evidence for oophagy in Prosymna and the possible roles of morphological specializations in egg-slitting or egg-crushing feeding mechanisms are discussed. [ABSTRACT FROM AUTHOR]

This case report described the diagnosis and treatment of a patient with ectopic bone injury due to high-pressure electric shock. A 24-year-old male patient suffered from burns that covered 50% of TBSA, including on limbs and torso, after coming into contact with 10-kV high-voltage electricity. A repeated Meek micrografting technique (MEEK) was applied for wound healing; skin grafts were cut into micrografts and expanded at a ratio of 1:4 to cover large areas after burn trauma. After the injury, right elbow redness, fever, pains, and joint movement disorder were reported by the patient, which might be attributed to excessive exercises and acute scarring. However, these symptoms were not treated immediately. Six months after the injury, his right elbow joint showed 90° locking and a restricted 5° movement capacity. X-ray examination revealed a new bone formation at the inner tibia shin. In addition, 3D CT showed the formation of right tibia, the ruler bone, and the skull of the humming bridge. Under general anesthesia, the right elbow joint was released, the medial collateral ligament was repaired, and the hinge external fixator was fixed. A large number of hyperplastic bone masses were found at the right elbow joint during surgery, specifically in the foot bone hawk's beak nest. No complications after surgery were observed. X-ray examination in February showed disappearance of the bone bridge and normal relationship of the right elbow joint. This case study revealed that electric shock injury could lead to ectopic bone formation, and much attention should be paid on any changes that indicate aseptic inflammation, such as redness, swelling, fever, and pain during the treatment process. Finally, identification of the scar constriction phase could indicate surgical treatment in order to promote the limb rehabilitation process. [ABSTRACT FROM AUTHOR]

Sclerostin antibody (SclAb) therapy has been suggested as a novel therapeutic approach toward addressing the fragility phenotypic of osteogenesis imperfecta (OI). Observations of cellular and transcriptional responses to SclAb in OI have been limited to mouse models of the disorder, leaving a paucity of data on the human OI osteoblastic cellular response to the treatment. Here, we explore factors associated with response to SclAb therapy in vitro and in a novel xenograft model using OI bone tissue derived from pediatric patients. Bone isolates (approximately 2 mm3) from OI patients (OI type III, type III/IV, and type IV, n = 7; non‐OI control, n = 5) were collected to media, randomly assigned to an untreated (UN), low‐dose SclAb (TRL, 2.5 μg/mL), or high‐dose SclAb (TRH, 25 μg/mL) group, and maintained in vitro at 37°C. Treatment occurred on days 2 and 4 and was removed on day 5 for TaqMan qPCR analysis of genes related to the Wnt pathway. A subset of bone was implanted s.c. into an athymic mouse, representing our xenograft model, and treated (25 mg/kg s.c. 2×/week for 2/4 weeks). Implanted OI bone was evaluated using μCT and histomorphometry. Expression of Wnt/Wnt‐related targets varied among untreated OI bone isolates. When treated with SclAb, OI bone showed an upregulation in osteoblast and osteoblast progenitor markers, which was heterogeneous across tissue. Interestingly, the greatest magnitude of response generally corresponded to samples with low untreated expression of progenitor markers. Conversely, samples with high untreated expression of these markers showed a lower response to treatment. in vivo implanted OI bone showed a bone‐forming response to SclAb via μCT, which was corroborated by histomorphometry. SclAb induced downstream Wnt targets WISP1 and TWIST1, and elicited a compensatory response in Wnt inhibitors SOST and DKK1 in OI bone with the greatest magnitude from OI cortical bone. Understanding patients' genetic, cellular, and morphological bone phenotypes may play an important role in predicting treatment response. This information may aid in clinical decision‐making for pharmacological interventions designed to address fragility in OI. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Data from three experiments conducted to evaluate the effects of increasing available P in swine diets were used to compare two different bone processing methods. Our objective was to determine if the procedures influenced treatment differences and the ability to detect changes in the percentage bone ash. In each experiment, pigs (nursery pigs in experiments 1 and 2, and finishing pigs in experiment 3) were fed a wide range of available phosphorus levels provided from either increasing monocalcium P or added phytase. At the completion of each experiment, a subset of pigs was euthanized, and either fibulas (experiments 1 and 2) or metacarpals (experiment 3) were collected to determine the percentage bone ash. Bones were processed by cleaning away all soft tissues followed by ether extraction for 7 d (defatted), or no lipid extraction (non-defatted), and then ashed. In nursery and finishing pigs, defatted bones had increased (P < 0.001) percentage bone ash compared with non-defatted bones. No evidence of a method × treatment interaction or linear and quadratic interactions were observed in bone ash weight and percentage bone ash (P > 0.10) for nursery pigs; however, a linear interaction was detected (P < 0.05) in percentage bone ash for grow-finish pigs. This response was minimal and likely due to increased variation observed in grow-finish pigs when bones were not defatted. The processing method did not affect the ability to detect differences among treatments as a result of changing dietary P concentrations in the nursery or grow-finish pigs. In summary, either non-defatted or defatted bone processing methods can be used to determine bone ash weight and percentage bone ash as a way to assess bone mineralization and dietary treatment differences in nursery pigs; however, the increased variation observed in mature pigs suggests that defatted bone processing is the preferred method for grow-finish pigs. [ABSTRACT FROM AUTHOR]

Avifaunas derived from Lapita archaeological sites excavated between 2004 and 2014 from four sites in the Vava'u Group and two on Tongatapu, Kingdom of Tonga are described, revealing birds encountered by the first human arrivals. A total of 741 identifiable bones revealed 24 avian taxa, among which terrestrial birds, especially rails, pigeons and parrots, were the most abundant. At a minimum, eight taxa, or 50% of the original non-passerine land bird diversity in the sample, are globally extinct. These include two megapodes (Megapodius alimentum and a larger unnamed megapode), three pigeons (a large Caloenas sp. indet., Didunculus placopedetes and Ducula shutleri sp. nov.), two rails (Hypotaenidia vavauensis sp. nov. and an unnamed one) and the parrot Eclectus infectus. The rail H. vavauensis was restricted to Vava'u and was flightless, with reduced wings, and larger than Hypotaenidia woodfordi of the Solomons, the largest congener hitherto found in the Pacific. The pigeon Du. shutleri was volant, but was the largest species in its genus and was widespread in the Kingdom. The evolution of Tongan avifaunas is related to varying ages (Pliocene to Pleistocene) of the island groups, where geological youth apparently precluded true giantism in the fauna. [ABSTRACT FROM AUTHOR]

Amongst Mesozoic marine reptiles, metriorhynchid crocodylomorphs were unique in evolving into pelagically adapted forms with little-to-no posterodorsal retraction of the external nares. Narial retraction is a common adaptation seen in sustained swimmers, notably occurring during cetacean evolution. Mesosaurids and the basalmost known members of ichthyosauriforms, thalattosaurians, saurosphargids, sauropterygians, pleurosaurids and mosasauroids had the external nares divided by an ossified bar, bound by multiple cranial bones and were positioned back from the tip of the rostrum. However, metriorhynchids evolved from taxa with a single external naris bound solely by the premaxilla, and positioned near the tip of an elongate rostrum. We posit that metriorhynchids were uniquely disadvantaged in evolving into sustained swimmers. Herein we describe three Late Jurassic metriorhynchid cranial rostra that display differing degrees of narial retraction. In our new phylogenetic analyses, the backwards migration of the narial fossa posterior margin occurred independently at least four times in Metriorhynchidae, whereas the backwards migration of the anterior margin only occurred twice. Although Rhacheosaurini share the backwards migration of the anterior and posterior narial margins, posterodorsal retraction occurred differently along three lineages. This culminated in the Early Cretaceous, where a rhacheosaurin evolved nares bound by the premaxilla and maxilla, and significantly posterodorsally retracted. [ABSTRACT FROM AUTHOR]

Given that the biology of the recently extinct aepyornithids is poorly understood, we undertook a histological study of 29 skeletal elements of adult and juvenile specimens of Aepyornithidae, i.e. Aepyornis maximus , Aepyornis hildebrandti and Vorombe titan , in addition to a group of taxonomically unidentifiable juvenile Aepyornithiformes. Comparative analysis of the histology of the different skeletal elements showed that although the femur retained a good record of growth during early ontogeny, the tibiotarsus provided the best record of growth. Our data showed that, like other insular birds and their extant relative, the kiwi, Aepyornithidae experienced protracted growth. We also found that intracortical remodelling began early in ontogeny and continued throughout their lives, becoming more extensive throughout the compacta with age, albeit more restricted to the perimedullary region in the femora. We also deduced that the different skeletal elements experienced variable amounts of intracortical remodelling, which was most likely to be related to biomechanical constraints, size of the element and ontogenetic age. Additionally, we documented the occurrence of an unusual endosteal tissue within the large perimedullary erosional spaces of a femur of A. maximus. Overall, our study provided a lot of new information about the life history of these giant, recently extinct ratites. [ABSTRACT FROM AUTHOR]

Scelidosaurus fossils were first discovered during the commercial quarrying of the Liassic sea-cliffs between Charmouth and Lyme Regis in Dorset during the late 1850s. The original specimens included a well-preserved skull embedded in a block of argillaceous limestone (marlstone). Shortly after this skull was retrieved, a series of more-or-less contiguous marlstone slabs were recovered, containing most of the skeleton of the same animal (NHMUK R1111). After rudimentary (hammer and chisel) mechanical preparation, Owen published descriptions of this material (Owen, 1861, 1863). These two monographs have been the sole references pertaining to the anatomy of Scelidosaurus for >150 years. The skeleton of the lectotype of Scelidosaurus harrisonii (NHMUK R1111) has since been extracted from the surrounding matrix using an acid-immersion technique. Some additional specimens held in the collections of the Natural History Museum London, the Bristol City Museum and the Sedgwick Museum in Cambridge provide anatomical material that allows detailed description of this taxon, for which we have had, until now, a surprisingly poor understanding. Axial skeleton: The axial skeleton of Scelidosaurus comprises eight cervical, 16 dorsal, four sacral and > 40 caudal vertebrae. During ontogeny, the posterior centrum articular surface of the 16th dorsal vertebra develops a firm, ligament-bonded junction with the succeeding sacral centrum. Apart from the atlas rib, which is single headed, double-headed ribs are present throughout the presacral vertebral series, and none shows any indication of fusion to its associated vertebra. However, those ribs attached to cervical vertebrae 2–4 were evidently bound firmly by connective tissue to rugose diapophyses. The last two (presacral) dorsal ribs show merger of the capitulum and tuberculum, meaning that they are separated by only a step. The angulation and arching of the dorsal ribs suggest that these animals had a broad (barrel-like) torso. Intercostal uncinate plates were present, attached to the posterior margins of some of the largest dorsal ribs. Their attachment sites are clearly marked, and these plates might have been composed of calcified cartilage in larger individuals. The sacral vertebrae fuse progressively during ontogeny, in an anterior-to-posterior sequence. The sacral ribs are long and robust, and tilt the iliac blade outward dorsally. A sacricostal 'yoke' (created by the fusion of the distal ends of adjacent sacral ribs) never forms. The base of the tail has a unique ball-and-socket-style joint between the centra of caudal vertebrae 1 and 2 in only one skeleton. This might have permitted powerful, but controlled, movements of the tail as a defensive weapon (or increased flexibility at the base of the tail, which might have been necessary for reproduction). Caudal ribs are initially long, blade-shaped projections that gradually decrease in size and become stub-like remnants that persist as far back as the midtail (approximately caudal vertebra 25). Haemal arches (chevrons) disappear nearer to the distal end of the tail (approximately caudal vertebra 35). Ossified tendons are preserved as epaxial bundles that are clustered in the 'axillary' trough (between the neural spine and transverse processes on either side of the midline). Ossified tendons are restricted to the dorsal and sacral region. Flattened ossified tendons are fused to the sides of sacral neural spines. In life, the ossified tendons might have formed a low-angled trellis-like arrangement. Appendicular skeleton: The pectoral girdle comprises a long scapula, with a distally expanded blade. The proximal portion is expanded and supports an oblique promontory, forming an acromial process anteriorly and a thick, collar-like structure posteriorly above the glenoid. Between these two features is a shallow basin, bordered ventrally by a sutural edge for the coracoid. The scapula–coracoid suture remains unfused in large (5-m-long) individuals. The coracoid bears a discrete foramen and forms a subcircular dished plate, with the shallowest of embayments along its posterior edge. Clavicles are present as small fusiform bones attached to the acromial process of the scapulae and leading edge of each coracoid. A sternum was reported as 'some partially ossified element of the endoskeleton' Owen (1863 : 13), but subsequent preparation of the skeleton has removed all trace of this material. The humerus is relatively long and has a prominent rectangular and proximally positioned deltopectoral crest. The ulna is robust and tapers distally, but there is no evidence of an olecranon process. The radius is more rod-like and terminates distally in an enlarged, subcircular and convex articular surface for the carpus. The carpus is represented by an array of five discoid carpals. The manus is pentadactyl and asymmetrical, with short, divergent metacarpals and digits that terminate in small, arched and pointed unguals on digits 1–3 (only). The phalangeal formula of the manus is 2-3-4-3-2. The pelvis is dominated by a long ilium; the preacetabular process is arched, transversely broad, and curves laterally. In juveniles, this process is short and horizontal, but during ontogeny it increases considerably in length and becomes arched. The iliac blade is tilted laterally, meaning that its dorsal blade partly overhangs the femur. The acetabulum forms a partial cupola, and there is a curtain-like medial wall that reduces the acetabular fenestra to a comparatively low, triangular opening between the pubis and ischium. The postacetabular portion of the ilium is long and supports a brevis shelf. The ischium has a long, laterally compressed shaft that hangs almost vertically beneath the ilium, and there is no obturator process. The pubis has a long, narrow shaft and a relatively short, deep, laterally compressed prepubic process that twists laterally (its distal end lies almost perpendicular to the long axis of the ilium). The articular pad on the pubis for the femoral head faces posteriorly. The obturator foramen is not fully enclosed within the pubis, but its foramen is closed off posteriorly by the pubic peduncle of the ischium. The femur is stout and has a slightly medially offset femoral head, and the greater trochanter forms a sloping shoulder continuous with, and lateral to, the femoral head. The anterior (lesser) trochanter is prominent and forms a thick, thumb-shaped projection on the anterolateral corner of the femoral shaft. The fourth trochanter is pendent and positioned at midshaft. In larger individuals, it appears to become thickened and reinforced by becoming coated with metaplastic bone derived from the tendons attached to its surface. The distal end of the femoral shaft is slightly curved and expands to form condyles. There is a deep and broad posterior intercondylar groove, but the anterior intercondylar groove is barely discernible in juveniles and not much better developed in subadults. The tibia and fibula are shorter than the femur. The tibia is structurally dominant, and the shorter fibula is comparatively slender and bowed. The proximal tarsals are firmly bound by connective tissue to the distal ends of the tibia and fibula. The distal end of the tibia is stepped, which aids the firm interlock between the crus and proximal tarsals. There appear to be two roughly discoid tarsals (distal tarsals 3 and 4), and a rudiment of distal tarsal 5 appears to be sutured to the lateral margin of distal tarsal 4. Five metatarsals are preserved, but the fifth is a splint of bone attached to the proximal end of metatarsal 4. Metatarsals 2–4 are dominant, long and are syndesmotically interlocked proximally, but their shafts splay apart distally. Metatarsal 1 is much shorter than the other three, but it retains two functional phalanges (including a short, pointed ungual). The foot is anatomically tetradactyl but functionally tridactyl. The pedal digit formula is 2-3-4-5-0. The digits diverge, but each appears to curve medially along its length, creating the impression of asymmetry. This asymmetry is emphasized, because the three principal unguals are also twisted medially. The ungual of digit 2 is the largest and most robust of the three, whereas that of digit 4 is the smallest and least robust. The general girth of the torso and the displacement of the abdomen posteriorly (a consequence of the opisthopubic pelvic construction in this dinosaur) constrained the excursion of the hindlimb during the protraction phase of the locomotor cycle. The anterolateral displacement of the hindlimb during protraction is in accord with the freedom of motion that is evident at the acetabulum, the susceptibility of the hindlimb to torsion between and within its component parts, and the asymmetry of the foot. It is probable that thyreophorans (notably, ankylosaurs) used a similar oblique-parasagittal hindlimb excursion to accommodate their equally large and wide abdomens. This surmise accords with the structure of the pelves and hindlimbs of ankylosaurs. Derived stegosaurs might have obviated this 'problem', in part, because their hindlimbs were longer and their torsos and abdomens narrower and capable of being 'stretched' vertically to a greater extent. Nevertheless, the structure of their acetabula and hindlimbs indicates that the oblique-parasagittal style of hindlimb excursion remained a possibility and might be an evolutionary remnant of the locomotor style of basal, shorter-limbed stegosaurs. A reconstruction of the endoskeleton of Scelidosaurus is presented on the basis of this updated description. Although quadrupedal, this animal was only facultatively so, judged by its forelimb-to-hindlimb proportions and structure; it therefore betrays bipedality in its ancestry. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus‐ (HIV‐) infection and antiretroviral therapy (ART) exposure are associated with bone loss. African data are limited despite the region's HIV burden. Of 247 ART‐naïve, premenopausal, urban, black African women aged 33.9 ± 6.6 years from Soweto, South Africa, measured at baseline, 110 underwent anthropometry, DXA, and blood and urine collections at 12 and 24 months; 39 were HIV‐negative (Nref), 28 were people with HIV (PWH) not ART‐exposed for the duration of the study (ART‐N), and 43 were PWH who were ART‐exposed within the first 12 months (ART‐Y). At baseline, the ART‐Y group had lower BMI and fat mass than the Nref group. Within 12 months of ART initiation, areal bone mineral density (aBMD) had decreased at the lumbar spine and at the whole body less head, despite increased weight, and hip aBMD had not increased in line with the Nref group. There was no evidence of further bone changes between 12 and 24 months. By 24 months, the ART‐Y women had gained weight and fat mass, but remained lighter with less fat than the Nref women. ART initiation normalized the low serum albumin of the ART‐Y group at baseline, but was associated with elevated bone turnover markers at 12 and 24 months. Vitamin D status and renal phosphate handling were normal. ART‐N had similar aBMD and other characteristics to the Nref group throughout, except unlike the Nref group, weight and fat mass did not increase and serum albumin decreased. This study in African women of childbearing age demonstrated that the bone loss that had occurred in these PWH after ART initiation did not continue after 12 months and that bone loss did not occur in ART‐unexposed PWH over 2 years. At 24 months, despite gains in weight and fat mass, ART‐exposed women remained lighter, with lower aBMD, fat mass, and higher bone turnover than women without HIV. More studies are required to establish if the bone loss and fat gain reverse, stabilize, or continue with further ART exposure, particularly during and after menopause. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Epidemiological evidence links polychlorinated biphenyls (PCBs) to skeletal toxicity, however mechanisms whereby PCBs affect bone are poorly studied. In this study, coplanar PCB 126 (5 μmol/kg) or corn oil vehicle was administered to N  = 5 and 6 male and female, wild type (WT) or AhR −/− rats via intraperitoneal injection. Animals were sacrificed after 4 weeks. Bone length was measured; bone morphology was assessed by microcomputed tomography and dynamic histomorphometry. Reduced bone length was the only genotype-specific effect and only observed in males (p  < .05). WT rats exposed to PCB 126 had reduced serum calcium, and smaller bones with reduced tibial length, cortical area, and medullary area relative to vehicle controls (p  < .05). Reduced bone formation rate observed in dynamic histomorphometry was consistent with inhibition of endosteal and periosteal bone growth. The effects of PCB 126 were abolished in AhR −/− rats. Gene expression in bone marrow and shaft were assessed by RNA sequencing. Approximately 75% of the PCB-regulated genes appeared AhR dependent with 89 genes significantly (p  < .05) regulated by both PCB 126 and knockout of the AhR gene. Novel targets significantly induced by PCB 126 included Indian hedgehog (Ihh) and connective tissue growth factor (Ctgf/Ccn2), which regulate chondrocyte proliferation and differentiation in the bone growth plate and cell-matrix interactions. These data suggest the toxic effects of PCB 126 on bone are mediated by AhR, which has direct effects on the growth plate and indirect actions related to endocrine disruption. These studies clarify important mechanisms underlying skeletal toxicity of dioxin-like PCBs and highlight potential therapeutic targets. [ABSTRACT FROM AUTHOR]

A recently proposed model for the incorporation of xenobiotics of forensic interest into the human skeleton suggests nerve agent metabolites may incorporate into bone at relatively elevated concentrations based on their unique chemical properties. To test the hypothesis that nerve agent metabolites interact with bone, methods for the extraction, isolation and semi-quantitative detection of nerve agent metabolites (MPA, EMPA, IMPA, iBuMPA, CMPA and PMPA, corresponding to the nerve agents VX, Russian VX, sarin, cyclosarin and soman, respectively) from osseous tissue were developed using liquid chromatography–mass spectrometry with both quadrupole time-of-flight and triple quadrupole (QqQ) instruments. The optimized methods were validated on the QqQ instrument. Despite high ion suppression, the achieved limits of detection (5–20 pg/g for four analytes; 350 pg/g for the fifth analyte) were lower than many of those published for the same analytes in other biomatrices, including serum and urine. These methods were tested on the skeletal remains of minipigs exposed to the chemical weapon VX in vivo. The VX metabolite was detected in multiple minipig bone samples; to the authors' knowledge, this is the first time in vivo nerve agent exposure has been detected from bone. Further, detected concentrations and diaphyseal-to-epiphyseal area count ratios reflect animal exposure history. Although the results are limited, they are promising, indicating that nerve agent metabolites may interact with bone as a pharmacokinetic compartment and can be extracted from bone postmortem. Additional studies, assessing the effects of different agents, exposure pathways and taphonomic variables, are needed; however, these results suggest the method may be used with human bone to detect use of chemical weapons from postmortem biomatrices even well after a suspected attack. More general implications for both nerve agent toxicology and skeletal toxicology are also discussed. [ABSTRACT FROM AUTHOR]

Tail morphology and function vary considerably across mammals. While studies of the mammalian tail have paid increasing attention to the caudal vertebrae, the chevron bones, ventrally positioned elements that articulate with the caudal vertebrae of most species and that serve to protect blood vessels and provide attachment sites for tail flexor musculature, have largely been ignored. Here, morphological variation in chevron bones is documented systematically among mammals possessing different tail locomotor functions, including prehensility, terrestrial propulsion (use for pentapedal locomotion), and postural prop, during which chevron bones are presumably under different mechanical stresses or serve different mechanical roles. Several chevron bone morphotypes were identified along the tail, varying both within and between tail regions. While some morphotypes were present across many or all clades surveyed, other morphotypes were clade-specific. Chevron bone dorsoventral height was examined at key vertebral levels among closely related species with different tail locomotor functions to assess whether variation followed any functional patterns. Dorsoventral height of chevron bones differed between prehensile- and nonprehensile-tailed, prop-tailed and nonprop-tailed, and pentapedal and nonpentapedal mammals. However, small sample sizes precluded rigorous statistical analyses. Distinctions were also qualified among species (not grouped by tail locomotor function), and the utility of metrics for quantifying specific aspects of chevron bone anatomy is discussed. This study offers information about the functional morphology of mammalian tails and has implications for reconstructing tail function in the fossil record. [ABSTRACT FROM AUTHOR]

The integrity of the skeleton is maintained by the coordinated and balanced activities of the bone cells. Osteoclasts resorb bone, osteoblasts form bone, and osteocytes orchestrate the activities of osteoclasts and osteoblasts. A variety of in vitro approaches has been used in an attempt to reproduce the complex in vivo interactions among bone cells under physiological as well as pathological conditions and to test new therapies. Most cell culture systems lack the proper extracellular matrix, cellular diversity, and native spatial distribution of the components of the bone microenvironment. In contrast, ex vivo cultures of fragments of intact bone preserve key cell–cell and cell–matrix interactions and allow the study of bone cells in their natural 3D environment. Further, bone organ cultures predict the in vivo responses to genetic and pharmacologic interventions saving precious time and resources. Moreover, organ cultures using human bone reproduce human conditions and are a useful tool to test patient responses to therapeutic agents. Thus, these ex vivo approaches provide a platform to perform research in bone physiology and pathophysiology. In this review, we describe protocols optimized in our laboratories to establish ex vivo bone organ cultures and provide technical hints and suggestions. In addition, we present examples on how this technical approach can be employed to study osteocyte biology, drug responses in bone, cancer‐induced bone disease, and cross‐talk between bone and other organs © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Forensic anthropology casework frequently encounters evidence of animal scavenging associated with fragmentation and loss of skeletal material. Published research demonstrates that patterns of destruction in bone can suggest the size and type of animal involved. This study analyzes 107 cases reported on by the first author at the Smithsonian Institution to investigate patterns of scavenging in forensic anthropology casework. This investigation reveals that the extent of scavenger impact varies across the body, but primarily is concentrated in the central body area. Although extensive animal scavenging can limit analysis, some evidence of foul play can be preserved. [ABSTRACT FROM AUTHOR]

Skeletal growth rates reconstructed from bone histology in extinct insular hippopotamids, elephants, bovids and sauropods have been used to infer dwarfism as a response to island conditions. Limited published records of osteocyte lacunae densities (Ot.Dn), a proxy for living osteocyte proliferation, have suggested a slower rate of bone metabolism in giant mammals. Here, we test whether insularity might have affected bone metabolism in a series of small to giant murine rodents from Timor. Ten adult femora were selected from a fossil assemblage dated to the Late Quaternary (~5000–18 000 years old). Femur morphometric data were used in computing phylogenetically informed body mass regressions, although the phylogenetic signal was very low (Pagel's λ = 0.03). Estimates of body weight calculated from these femora ranged from 75 to 1188 g. Osteocyte lacunae densities from histological sections of the midshaft femur were evaluated against bone size and estimated body weight. Statistically significant (P  < 0.05) and strongly negative relationships between Ot.Dn, femur size and estimated weight were found. Larger specimens were characterized by lower Ot.Dn, indicating that giant murines from Timor might have had a relatively slow pace of bone metabolic activity, consistent with predictions made by the island rule. [ABSTRACT FROM AUTHOR]

We report the first example of ossified pelvic vestiges in an anomalepidid snake, Liotyplophs beui , and provide a review of the diversity of limb and pelvic elements within Serpentes. We trace the evolution, homology and reduction of the pelvic elements and hindlimbs from the oldest known snakes through to living forms. Evolutionary analysis of the pelvic and limb data shows that the most recent common ancestor of all living snakes (Serpentes) most probably retained all three pelvic elements and rudimentary hindlimbs (femoral spurs). Subsequently, there have been multiple losses of ossified pelvic and hindlimb elements and regaining of ossified pelvic elements. Reduction of the pelvis has followed different routes in the two primary groups of living snakes (scolecophidians and alethinophidians). The single remaining rod-like element in some scolecophidians is the ischium, whereas the single remaining rod-like element in many basal alethinophidians is the pubis. Notably, many basal alethinophidians share a distinctive configuration of cloacal spur (claw), femur and a sizeable pubis, which is likely to be related functionally to the widespread use of the hindlimbs in mating and courtship, rather than the usual representation of the bones as non-functional vestiges. [ABSTRACT FROM AUTHOR]

Multiple myeloma is characterized by accumulation of malignant plasma cells in the bone marrow. Most patients suffer from an osteolytic bone disease, caused by increased bone degradation and reduced bone formation. Bone morphogenetic protein 4 (BMP4) is important for both pre‐ and postnatal bone formation and induces growth arrest and apoptosis of myeloma cells. BMP4‐treatment of myeloma patients could have the potential to reduce tumor growth and restore bone formation. We therefore explored BMP4 gene therapy in a human‐mouse model of multiple myeloma where humanized bone scaffolds were implanted subcutaneously in RAG2−/− γC−/−mice. Mice were treated with adeno‐associated virus serotype 8 BMP4 vectors (AAV8‐BMP4) to express BMP4 in the liver. When mature BMP4 was detectable in the circulation, myeloma cells were injected into the scaffolds and tumor growth was examined by weekly imaging. Strikingly, the tumor burden was reduced in AAV8‐BMP4 mice compared with the AAV8‐CTRL mice, suggesting that increased circulating BMP4 reduced tumor growth. BMP4‐treatment also prevented bone loss in the scaffolds, most likely due to reduced tumor load. To delineate the effects of BMP4 overexpression on bone per se, without direct influence from cancer cells, we examined the unaffected, non‐myeloma femurs by μCT. Surprisingly, the AAV8‐BMP4 mice had significantly reduced trabecular bone volume, trabecular numbers, as well as significantly increased trabecular separation compared with the AAV8‐CTRL mice. There was no difference in cortical bone parameters between the two groups. Taken together, BMP4 gene therapy inhibited myeloma tumor growth, but also reduced the amount of trabecular bone in mice. Our data suggest that care should be taken when considering using BMP4 as a therapeutic agent. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

Hypoparathyroidism patients suffer a variety of complaints often leading to reduced quality of life. Currently, no specific standard instrument exists to measure corresponding disease manifestations. We therefore aimed to develop a disease‐characteristic questionnaire for hypoparathyroid patients. We used an analytical‐empirical approach for questionnaire construction based on retrospective analysis of four well‐established but non‐disease‐specific questionnaires (Symptom Checklist 90, revised [SCL‐90‐R]; Giessen Complaint List [GBB]; Short‐Form‐36 Health Survey [SF‐36]; von Zerssen Symptom List [B‐L Zerssen]) and two additional unpublished or local questionnaires (SHGdQ and GPQ) in a German hypoparathyroidism self‐help group (n = 60). Retrospective data were compared with corresponding general population norms. The new questionnaire was administered prospectively over 1 year to patients with postoperative hypoparathyroidism and two control groups to validate specificity. Exploratory factor analysis (EFA) and reliability testing were applied to identify relevant scales and reduce overlapping items. In the self‐help group, SCL‐90‐R revealed elevated symptom load in four complaint areas (p = 0.003 to p < 0.001). The SF‐36 mental summary score (p < 0.001) and further scales were lowered. In the GBB, four of five scales (p = 0.009 to p < 0.001) were elevated. In the B‐L Zerssen, 6 of 24 items revealed complaint areas. Based on these findings, the new 40‐item "Hypoparathyroid Patient Questionnaire" (HPQ 40) was developed, tested prospectively, and further analyzed. EFA revealed five scales (pain and cramps, gastrointestinal symptoms, depression and anxiety, neurovegetative symptoms, loss of vitality), all with Cronbach's alpha >0.7. The questionnaire was revised accordingly and shortened to 28 questions to avoid redundancy. We present a new disease‐characteristic questionnaire for hypoparathyroidism patients. Prospective testing revealed five major complaint areas and promising psychometric properties. This questionnaire can be tested for usefulness in further clinical trials. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

ESR (electron spin resonance) can date sites that span the whole Paleolithic, but requires accurate sedimentary dose rates, especially in caves where the internal and cosmic dose rates can approach 0 mGy/yr. This study examines the sedimentary radioactivity in the upper layers at Golema Pešt, North Macedonia. Reaching > 5.5 m deep, > 21 flatly lying, silty-sandy matrix-supported gravel layers with éboulis clasts fill the cave. In Sondage 2, Layers 0–5 contained many hearths and yielded thousands of bones and teeth, many from ungulates. In Layers 2-5a sat thousands of lithics and small tools, many made on tiny quartz crystals. Layers 2c-6 have Mousterian assemblages with denticulates, notched tools, Levallois cores and flakes. To measure the volumetrically averaged sedimentary dose rates for ungulate teeth dated by ESR from Sondage 2, 66 sediment samples were analyzed by NAA. Adding éboulis , calcined bone, and charcoal associated with the hearths lowered the sedimentary dose rates or left them unchanged. In Layer 2 at 198 cm below the cave datum, the Campanian Ignimbrite (CI) cryptotephra occurred, where it caused abnormally high sedimentary U, Th, and K concentrations and dose rates. Since the CI tephra lay 28–30 cm above AT77, a tooth dated from Layer 3, using time- and volumetrically averaging increased AT77's sedimentary dose rate by 32%, and dropped its calculated age by 25%. Analyzing the sedimentary compositions at every 2 cm in Layers 0–2 yielded a highly detailed stratigraphy that reduced the uncertainty in the sedimentary dose rates and the ESR ages, but more detailed geochemical analyses must be completed within the lower layers in Sondage 2. [ABSTRACT FROM AUTHOR]