25-hydroxycholecalciferol (25-OHD3 ) formed via hepatic hydroxylation from vitamin D, cholecalciferol, represents the precursor of the biologically active vitamin D hormone, 1,25-dihydroxyvitamin D. Due to a higher absorption rate and the omission of one hydroxylation, dietary supplementation of 25-OHD3 instead of vitamin D3 is considered to be more efficient as plasma concentrations of 25-OHD3 are increased more pronounced. The present review summarises studies investigating potential beneficial effects on mineral homeostasis, bone metabolism, health status and performance in sows, piglets and fattening pigs. Results are inconsistent. While most studies could not demonstrate any or only a slight impact of partial or total replacement of vitamin D3 by 25-OHD3 , some experiments indicated that 25-OHD3 might alter physiological processes when animals are challenged, for example, by a restricted mineral supply.

BACKGROUND: The intestinal flora is involved in the bone development of children through a variety of mechanisms, but it remains unclear whether intervention of the intestinal flora can enhance children\'s bone development.
METHODS: Six databases (PubMed, Web of Science, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health, and China National Knowledge Infrastructure) were searched for all English and Chinese studies published up to August 2021. Stata version 16.0 (StataCorp, College Station, TX, USA) was used. Bone mass density and biochemical markers related to bone metabolism were reported as the primary outcome, and the secondary outcomes were anthropometric parameters such as height, height Z score for age, and height velocity. Intergroup differences were determined by standardized mean differences (SMDs) and 95% confidence intervals (CIs).
RESULTS: A total of 3245 participants from 20 RCTs and 370 participants from 8 crossover trials were included in the study. Significant differences were found in bone mineral density (SMD 0.47; 95% CI, 0.28 to 0.66; p < 0.001; I2 = 0.00%) and total serum calcium (SMD 1.07; 95% CI, 0.39 to 1.74; p < 0.001; I2 = 61.9%), as well as in height Z score for age (SMD = 0.11; 95% CI, 0.00 to 0.22; P = 0.044; I2 = 0%). The overall quality of evidence ranged from moderate to very low.
CONCLUSIONS: This systematic review and meta-analysis suggested that intestinal flora intervention was an effective method of improving bone mineral density, serum calcium, and height in infants, children, and adolescents. Future studies with a larger sample size and longer intervention period are needed. The protocol of this systematic review was registered in PROSPERO and the registered number was CRD42021282606.

During endochondral bone development, a complex process that leads to the formation of the majority of skeletal elements, mesenchymal cells condense, differentiating into chondrocytes and producing the foetal growth plate. Chondrocytes progressively hypertrophy, induce angiogenesis and are then gradually replaced by bone. Epidermal Growth Factor (EGF), one of many growth factors, is the prototype of the EGF-ligand family, which comprises several proteins involved in cell proliferation, migration and survival. In bone, EGF pathway signalling finely tunes the first steps of chondrogenesis by maintaining mesenchymal cells in an undifferentiated stage, and by promoting hypertrophic cartilage replacement. Moreover, EGF signalling modulates bone homeostasis by stimulating osteoblast and osteoclast proliferation, and by regulating osteoblast differentiation under specific spatial and temporal conditions. This evidence-based narrative review describes the EGF pathway in bone metabolism and endochondral bone development. This comprehensive description may be useful in light of possible clinical applications in orthopaedic practice. A deeper knowledge of the role of EGF in bone may be useful in musculoskeletal conditions which may benefit from the modulation of this signalling pathway.Key messagesThe EGF pathway is involved in bone metabolism.EGF signalling is essential in the very early stages of limb development by maintaining cells in an undifferentiated stage.EGF pathway positively regulates chondrocyte proliferation, negatively modulates hypertrophy, and favours cartilage replacement by bone.EGF and EGF-like proteins finely tune the proliferation and differentiation of bone tissue cells, and they also regulate the initial phases of endochondral ossification.

There is growing evidence that bone health may be programmed in the first years of life. Factors during the prenatal period, especially maternal nutrition, may have an influence on offspring\'s skeletal development and thus the risk of osteoporosis in further life, which is an increasing societal, health and economic burden. However, it is still inconclusive which early life factors are the most important and to what extent they may affect bone health. We searched through three databases (PubMed, Google Scholar, Cochrane Library) and after eligibility criteria were met, the results of 49 articles were analyzed. This narrative review is an overall summary of up-to-date studies on maternal diet, nutritional status, and birth-related factors that may affect offspring bone development, particularly bone mineral density (BMD). Maternal vitamin D status and diet in pregnancy, anthropometry and birth weight seem to influence BMD, however other factors such as subsequent growth may mediate these associations. Due to the ambiguity of the results in the analyzed studies, future, well-designed studies are needed to address the limitations of the present study.

Intermuscular bones (IBs) are slender linear bones embedded in muscle, which ossify from tendons through a process of intramembranous ossification, and only exist in basal teleosts. IBs are essential for fish swimming, but they present a choking risk during human consumption, especially in children, which can lead to commercial risks that have a negative impact on the aquaculture of these fish. In this review, we discuss the morphogenesis and functions of IBs, including their underlying molecular mechanisms, as well as the advantages and disadvantages of different methods for IB studies and techniques for breeding and generating IB-free fish lines. This review reveals that the many key genes involved in tendon development, osteoblast differentiation, and bone formation, e.g., scxa, msxC, sost, twist, bmps, and osterix, also play roles in IB development. Thus, this paper provides useful information for the breeding of new fish strains without IBs via genome editing and artificial selection.
肌间刺（intermuscular bones，IBs）是仅存在于低等硬骨鱼类肌肉中的细长的线形骨骼， 由肌腱组织通过膜内骨化形成。虽然肌间刺在鱼类游泳过程中发挥重要作用，但是在人类食用过程中会导致潜在的卡喉咙的风险，尤其不方便儿童的食用，这也进一步影响了水产业的经济效益。该文综合阐述了肌间刺的形态发生和功能、相关发育分子机制、肌间刺不同研究方法，以及用于培育无肌间刺鱼类品系的相关技术。该综述揭示了许多与肌间刺发育相关的关键基因，它们主要参与肌腱发育、成骨细胞分化和骨形成发育，如scxa、msxC、sost、twist、bmps和osterix基因。因此，该文对如何利用基因组编辑和人工选育等办法培育无肌间刺的鱼类品系提供了有价值的信息。.

Macro-scale changes in longitudinal bone growth resulting from mechanical loading were shown in Part 1 of this review to depend on load magnitude, anatomical location, and species. While no significant effect on longitudinal growth was observed by varying frequency and amplitude of cyclic loading, such variations, in addition to loading duration and species, were shown to affect the morphology, viability, and gene and protein expression within the growth plate. Intermittent compression regimens were shown to preserve or increase growth plate height while stimulating increased chondrocyte presence in the hypertrophic zone relative to persistent and static loading regimens. Gene and protein expressions related to matrix synthesis and degradation, as well as regulation of chondrocyte apoptosis were shown to exhibit magnitude-, frequency-, and duration-dependent responses to loading regimen. Chondrocyte viability was shown to be largely preserved within physiological bounds of magnitude, frequency, amplitude, and duration. Persistent static loading was shown to be associated with overall growth plate height in tension only, reducing it in compression, while affecting growth plate zone heights differently across species and encouraging mineralization relative to intermittent cyclic loading. Lateral loading of the growth plate, as well as microfluidic approaches are relatively understudied, and age, anatomical location, and species effects within these approaches are undefined. Understanding the micro-scale effects of varied loading regimes can assist in the development of growth modulation methods and device designs optimized for growth plate viability preservation or mineralization stimulation based on patient age and anatomical location.

The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a \"poor\" quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.

Growth modulation is an emerging method for treatment of angular skeletal deformities such as adolescent idiopathic scoliosis (AIS). The Hueter-Volkmann law, by which growth is stimulated in tension and inhibited in compression, is widely understood, and applied in current growth-modulating interventions such as anterior vertebral body tethering (AVBT) for AIS. However, without quantification of the growth rate effects of tension or compression, the possibility of under- or over- correction exists. A definitive mechanical growth modulation relationship relating to treatment of such skeletal deformities is yet to exist, and the mechanisms by which growth rate is regulated and altered are not fully defined. Review of current literature demonstrates that longitudinal (i.e., lengthwise) growth rate in multiple animal models depend on load magnitude, anatomical location, and species. Additionally, alterations in growth plate morphology and viability vary by loading parameters such as magnitude, frequency, and whether the load was applied persistently or intermittently. The aggregate findings of the reviewed studies will assist in work towards increasingly precise and clinically successful growth modulation methods. Part 1 of this review focuses on the effects of mechanical loading, species, age, and anatomical location on the macro-scale alterations in longitudinal bone growth, as well as factors that affect growth plate material properties. Part 2 considers the effects on micro-scale alterations in growth plate morphology such as zone heights and proportions, chondrocyte viability, and related gene and protein expression.

The assessment of bone age and skeletal maturity and its comparison to chronological age is an important task in the medical environment for the diagnosis of pediatric endocrinology, orthodontics and orthopedic disorders, and legal environment in what concerns if an individual is a minor or not when there is a lack of documents. Being a time-consuming activity that can be prone to inter- and intra-rater variability, the use of methods which can automate it, like Machine Learning techniques, is of value.
The goal of this paper is to present the state of the art evidence, trends and gaps in the research related to bone age assessment studies that make use of Machine Learning techniques.
A systematic literature review was carried out, starting with the writing of the protocol, followed by searches on three databases: Pubmed, Scopus and Web of Science to identify the relevant evidence related to bone age assessment using Machine Learning techniques. One round of backward snowballing was performed to find additional studies. A quality assessment was performed on the selected studies to check for bias and low quality studies, which were removed. Data was extracted from the included studies to build summary tables. Lastly, a meta-analysis was performed on the performances of the selected studies.
26 studies constituted the final set of included studies. Most of them proposed automatic systems for bone age assessment and investigated methods for bone age assessment based on hand and wrist radiographs. The samples used in the studies were mostly comprehensive or bordered the age of 18, and the data origin was in most of cases from United States and West Europe. Few studies explored ethnic differences.
There is a clear focus of the research on bone age assessment methods based on radiographs whilst other types of medical imaging without radiation exposure (e.g. magnetic resonance imaging) are not much explored in the literature. Also, socioeconomic and other aspects that could influence in bone age were not addressed in the literature. Finally, studies that make use of more than one region of interest for bone age assessment are scarce.

High rates of anterior cruciate ligament (ACL) injury and surgical reconstruction in both skeletally immature and mature populations have led to many studies investigating the size and shape of the healthy ligament. The purposes of the present study were to compile existing quantitative measurements of the geometry of the ACL, its bundles, and its insertion sites and to describe effects of common covariates such as sex and age.
A search of the Web of Science was conducted for studies published from January 1, 1900, to April 11, 2018, describing length, cross-sectional area, volume, orientation, and insertion sites of the ACL. Two reviewers independently screened and reviewed the articles to collect quantitative data for each parameter.
Quantitative data were collected from 92 articles in this systematic review. In studies of adults, reports of average ACL length, cross-sectional area, and volume ranged from 26 to 38 mm, 30 to 53 mm, and 854 to 1,858 mm, respectively. Reported values were commonly found to vary according to sex and skeletal maturity as well as measurement technique.
Although the geometry of the ACL has been described widely in the literature, quantitative measurements can depend on sex, age, and measurement modality, contributing to variability between studies. As such, care must be taken to account for these factors. The present study condenses measurements describing the geometry of the ACL, its individual bundles, and its insertion sites, accounting for common covariates when possible, to provide a resource to the clinical and scientific communities.
Quantitative measures of ACL geometry are informative for developing clinical treatments such as ACL reconstruction. Age and sex can impact these parameters.