OBJECTIVE: This scoping review presents the preclinical and clinical data on the effects of high-dose radiation therapy (RT) on bone structure and function.
METHODS: An extensive PubMed search was performed for the relevant questions. The data were then synthesized into a comprehensive summary of the available relevant in-vitro, preclinical and clinical literature.
RESULTS: In-vitro studies of high-dose RT on cell cultures show considerable damage in the viability and functional capacity of the primary cells of the bones; the osteoclasts, the osteoblasts, and the osteocytes. In-vivo animal models show that high-dose RT induces significant morphological changes to the bone, inhibits the ability of bone to repair damage, and increases the fragility of the bone. Clinical data show that there is an increasing risk over time of damage to the bone, such as fractures, after high-dose RT.
CONCLUSIONS: These findings suggest that there may be a limit to the safe dose for single-fraction RT, and the long-term consequences of high-dose RT for the patients must be considered.

BACKGROUND: Menkes disease (MD) is a rare, inherited, multisystemic copper metabolism disorder. Classical Menkes disease is characterized by low serum copper and ceruloplasmin concentrations, leading to multiple abnormalities in the whole-body, especially in connective tissue and central nervous system. However, serum copper and ceruloplasmin levels are not reliable diagnostic biomarkers due to the low concentrations in healthy newborns either. The featured imaging manifestations play an important role in diagnosing Menkes disease. To our knowledge, there are few reports on the systemic imaging manifestations of Menkes disease.
METHODS: A 4-month-old male patient presented with recurrent seizures. He had cognitive, intellectual, growth, gross motor, precision movement, and language developmental lags. The patient\'s hemoglobin and serum ceruloplasmin level were low. On MRI, increased intracranial vascular tortuosity, cerebral and cerebellar atrophy, white matter changes, and basal ganglia abnormalities were observed. Plain radiograph revealed wormian bones, rib flaring, metaphyseal spurring, and periosteal reactions in the long bones of the limbs. A pathogenic variant in ATP7A gene was identified in the patient, so he was confirmed the diagnosis of Menkes disease. His symptoms did not improve despite symptomatic and supportive treatment during his hospitalization. Unfortunately, the infant died 3 months after leaving hospital.
CONCLUSIONS: A comprehensive and intuitive understanding of the disease\'s imaging manifestations can help clinicians to identify the disease and avoid delays in care.

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression with diverse roles in various biological processes. In recent years, research into circRNAs\' involvement in bone biology has gained significant attention, unveiling their potential as novel regulators and biomarkers in bone-related disorders and diseases. CircRNAs, characterized by their closed-loop structure, exhibit stability and resistance to degradation, underscoring their functional significance. In bone tissue, circRNAs are involved in critical processes such as osteogenic differentiation, osteoclastogenesis, and bone remodeling through intricate molecular mechanisms including microRNA regulation. Dysregulated circRNAs are associated with various bone disorders, suggesting their potential as diagnostic and prognostic biomarkers. The therapeutic targeting of these circRNAs holds promise for addressing bone-related conditions, offering new perspectives for precision medicine. Thus, circRNAs constitute integral components of bone regulatory networks, impacting both physiological bone homeostasis and pathological conditions. This review provides a comprehensive overview of circRNAs in bone biology, emphasizing their regulatory mechanisms, functional implications, and therapeutic potential.

Estrogens are involved in a number of physiological functions, including in the development of the brain, growth, reproduction and metabolism. The biological actions of estrogens are achieved by binding to estrogen receptors (ERs) in numerous types of tissues. ERα and ERβ belong to the nuclear receptor superfamily and the G‑protein coupled ER1 (GPER1) is a membrane receptor. The primary biologically active estrogen, 17β‑estradiol demonstrates a high affinity for ERs. Mechanistically, estrogens bind to the ERs in the nucleus, and the complex then dimerize and bind to estrogen response elements (EREs) located in the promoter regions of the target genes. This is referred to as the genomic mechanism of ERs\' function. Furthermore, ERs can also act through kinases and other molecular interactions leading to specific gene expression and functions, referred to as the non‑genomic mechanism. While ERα and ERβ exert their functions via both genomic and non‑genomic pathways, GPER1 exerts its function primarily via the non‑genomic pathways. Any aberrations in ER signaling can lead to one of a number of diseases such as disorders of growth and puberty, fertility and reproduction abnormalities, cancer, metabolic diseases or osteoporosis. In the present review, a focus is placed on three target tissues of estrogens, namely the bones, the breasts and the brain, as paradigms of the multiple facets of the ERs. The increasing prevalence of breast cancer, particularly hormone receptor‑positive breast cancer, is a challenge for the development of novel antihormonal therapies other than tamoxifen and aromatase inhibitors, to minimize toxicity from the long treatment regimens in patients with breast cancer. A complete understanding of the mechanism of action of ERs in bones may highlight options for novel targeted treatments for osteoporosis. Likewise, the aging of the brain and related diseases, such as dementia and depression, are associated with a lack of estrogen, particularly in women following menopause. Furthermore, gender dysphoria, a discordance between experienced gender and biological sex, is commonly hypothesized to emerge due to discrepancies in cerebral and genital sexual differentiation. The exact role of ERs in gender dysphoria requires further research.

Bone health is the result of a tightly regulated balance between bone modeling and bone remodeling, and alterations of these processes have been observed in several diseases both in adult and pediatric populations. The imbalance in bone remodeling can ultimately lead to osteoporosis, which is most often associated with aging, but contributing factors can already act during the developmental age, when over a third of bone mass is accumulated. The maintenance of an adequate bone mass is influenced by genetic and environmental factors, such as physical activity and diet, and particularly by an adequate intake of calcium and vitamin D. In addition, it has been claimed that the integration of specific nutraceuticals such as resveratrol, anthocyanins, isoflavones, lycopene, curcumin, lutein, and β-carotene and the intake of bioactive compounds from the diet such as honey, tea, dried plums, blueberry, and olive oil can be efficient strategies for bone loss prevention. Nutraceuticals and functional foods are largely used to provide medical or health benefits, but there is an urge to determine which products have adequate clinical evidence and a strong safety profile. The aim of this review is to explore the scientific and clinical evidence of the positive role of nutraceuticals and functional food in bone health, focusing both on molecular mechanisms and on real-world studies.

Ginsenosides, bioactive compounds from the genus Panax, have potential therapeutic effects on diverse ailments, including diabetes. Emerging evidence suggests their involvement in bone metabolism. The present review summarizes the current understanding of the effects of ginsenosides on osteoporosis, periodontal disease, and osteoarthritis. Their mechanisms of action include effects on osteoblasts, osteoclasts, periodontal ligament fibroblasts (PDLFs), and chondrocytes, which are pivotal in maintaining bone, periodontal tissue, and cartilage homeostasis. Ginsenosides may exert their beneficial effects by enhancing PDLF and osteoblast activity, suppressing osteoclast function, augmenting chondrocyte synthesis in the cartilage matrix, and mitigating connective tissue degradation. Moreover, they possess antioxidant, anti-inflammatory, antimicrobial, and anti-pyroptotic properties. Their efficacy in increasing bone density, ameliorating periodontitis, and alleviating osteoarthritis symptoms has been demonstrated in preclinical studies using animal models. In terms of their mechanism of action, ginsenosides modulate cellular differentiation, activity, and key signaling pathway molecules, such as mitogen-activated protein kinases (MAPKs), while also regulating various mediators. Furthermore, the symptomatic relief observed in animal models lends further credence to their therapeutic utility. However, to translate these preclinical findings into clinical practice, rigorous animal and clinical investigations are imperative to ascertain the safety, efficacy, and optimal dosing regimens in human subjects.

Bone tissue engineering (BTE) aims to develop implantable bone replacements for severe skeletal abnormalities that do not heal. In the field of BTE, chitosan (CS) has become a leading polysaccharide in the development of bone scaffolds. Although CS has several excellent properties, such as biodegradability, biocompatibility, and antibacterial properties, it has limitations for use in BTE because of its poor mechanical properties, increased degradation, and minimal bioactivity. To address these issues, researchers have explored other biomaterials, such as synthetic polymers, ceramics, and CS coatings on metals, to produce CS-based biocomposite scaffolds for BTE applications. These CS-based biocomposite scaffolds demonstrate superior properties, including mechanical characteristics, such as compressive strength, Young\'s modulus, and tensile strength. In addition, they are compatible with neighboring tissues, exhibit a controlled rate of degradation, and promote cell adhesion, proliferation, and osteoblast differentiation. This review provides a brief outline of the recent progress in making different CS-based biocomposite scaffolds and how to characterize them so that their mechanical properties can be tuned using crosslinkers for bone regeneration.

OBJECTIVE: To analyze the effectiveness of image-guided energy ablation techniques with and without concurrent therapies in providing palliative pain relief in patients with bone metastases.
METHODS: OVID Embase, OVID Medline, and Pubmed were searched from inception to April 14th, 2023 using search terms relating to bone lesions and MeSH terms regarding ablation therapy. English peer-reviewed primary articles were included that reported pain scores following image-guided energy-based ablation of bone metastases. Exclusion criteria included 1) non-palliative treatment, 2) pain scores associated with specific treatment modalities not reported, and 3) non-metastatic bone lesions. Mean percentage reduction in pain score was calculated.
RESULTS: 1396 studies were screened and 54 were included. All but one study demonstrated decreased pain scores at final follow-up. Mean reduction in pain scores at final follow-up were 49% for radiofrequency ablation (RFA), 58% for radiofrequency ablation and adjunct (RFA-A), 54% for cryoablation (CA), 72% for cryoablation and adjunct (CA-A), 48% for microwave ablation (MWA), 81% for microwave ablation and adjunct (MWA-A), and 64% for high-intensity focused ultrasound (HIFU). Post-procedural adverse event rates were 4.9% for RFA, 34.8% for RFA-A, 9.6% for CA, 12.0% for CA-A, 48.9% for MWA, 33.5% for MWA-A and 17.0% for HIFU.
CONCLUSIONS: Image-guided energy ablation demonstrated consistently strong reduction in pain across all modalities, with variable post-procedural adverse event rates. Due to heterogeneity of included studies, quantitative analysis was not appropriate. Future primary research should focus on creating consistent prospective studies with established statistical power, explicit documentation and comparison to other techniques.

UNASSIGNED: Bone defects arising from diverse causes, such as traffic accidents, contemporary weapon usage, and bone-related disorders, present significant challenges in clinical treatment. Prolonged treatment cycles for bone defects can result in complications, impacting patients\' overall quality of life. Efficient and timely repair of bone defects is thus a critical concern in clinical practice.
UNASSIGNED: This study aims to assess the scientific progress and achievements of magnesium phosphate bone cement (MPC) as an artificial bone substitute material. Additionally, the research seeks to explore the future development path and clinical potential of MPC bone cement in addressing challenges associated with bone defects.
UNASSIGNED: The study comprehensively reviews MPC\'s performance, encompassing e.g. mechanical properties, biocompatibility, porosity, adhesion and injectability. Various modifiers are also considered to broaden MPC\'s applications in bone tissue engineering, emphasizing drug-loading performance and antibacterial capabilities, which meet clinical diversification requirements.
UNASSIGNED: In comparison to alternatives such as autogenous bone transplantation, allograft, polymethyl methacrylate (PMMA), and calcium phosphate cement (CPC), MPC emerges as a promising solution for bone defects. It addresses limitations associated with these alternatives, such as immunological rejection and long-term harm to patients. MPC can control heat release during the curing process, exhibits superior mechanical strength, and has the capacity to stimulate new bone growth.
UNASSIGNED: MPC stands out as an artificial bone substitute with appropriate mechanical strength, rapid degradation, non-toxicity, and good biocompatibility, facilitating bone repair and regeneration. Modification agents can enhance its clinical versatility. Future research should delve into its mechanical properties and formulations, expanding clinical applications to create higher-performing and more medically valuable alternatives in bone defect repair.

Connective tissue attaches to bone across an insertion with spatial gradients in components, microstructure, and biomechanics. Due to regional stress concentrations between two mechanically dissimilar materials, the insertion is vulnerable to mechanical damage during joint movements and difficult to repair completely, which remains a significant clinical challenge. Despite interface stress concentrations, the native insertion physiologically functions as the effective load-transfer device between soft tissue and bone. This review summarizes tendon, ligament, and meniscus insertions cross-sectionally, which is novel in this field. Herein, the similarities and differences between the three kinds of insertions in terms of components, microstructure, and biomechanics are compared in great detail. This review begins with describing the basic components existing in the four zones (original soft tissue, uncalcified fibrocartilage, calcified fibrocartilage, and bone) of each kind of insertion, respectively. It then discusses the microstructure constructed from collagen, glycosaminoglycans (GAGs), minerals and others, which provides key support for the biomechanical properties and affects its physiological functions. Finally, the review continues by describing variations in mechanical properties at the millimeter, micrometer, and nanometer scale, which minimize stress concentrations and control stretch at the insertion. In summary, investigating the contrasts between the three has enlightening significance for future directions of repair strategies of insertion diseases and for bioinspired approaches to effective soft-hard interfaces and other tough and robust materials in medicine and engineering.