Lysosomes serve as catabolic centers and signaling hubs in cells, regulating a multitude of cellular processes such as intracellular environment homeostasis, macromolecule degradation, intracellular vesicle trafficking and autophagy. Alterations in lysosomal level and function are crucial for cellular adaptation to external stimuli, with lysosome dysfunction being implicated in the pathogenesis of numerous diseases. Osteoclasts (OCs), as multinucleated cells responsible for bone resorption and maintaining bone homeostasis, have a complex relationship with lysosomes that is not fully understood. Dysregulated function of OCs can disrupt bone homeostasis leading to the development of various bone disorders. The regulation of OC differentiation and bone resorption for the treatment of bone disease have received considerable attention in recent years, yet the role and regulation of lysosomes in OCs, as well as the potential therapeutic implications of intervening in lysosomal biologic behavior for the treatment of bone diseases, remain relatively understudied. This review aims to elucidate the mechanisms involved in lysosomal biogenesis and to discuss the functions of lysosomes in OCs, specifically in relation to differentiation, bone resorption, and autophagy. Finally, we explore the potential therapeutic implication of targeting lysosomes in the treatment of bone metabolic disorders.

OBJECTIVE: This systematic review aims to summarize and synthesize the evidence that investigates the secondary effects of the application of botulinum toxin (BT) into the masticatory muscles and its effects on bone density.
METHODS: Database searches were conducted until March 19th, 2024. The quality of the studies was assessed by the Cochrane tool risk of bias for the randomized controlled trials and the ROBINS-I tool for non-randomized studies. The Cochrane Grading of Recommendations Assessment Development and Evaluation (GRADE) was used to evaluate the confidence in the overall evidence.
RESULTS: Five studies looking at the effects of botulinum toxin on bone density and resorption when applied to masticatory muscles were found. No significant changes were observed in most of the studies when looking at the effects of botulinum toxin on mandibular condyle volume, density, mandibular angle thickness, and coronoid process volume. The only finding that was statistically and clinically relevant was the difference between patients who received a double application of BT when compared with patients who received a single application (SMD: -0.99 [95%CI: -1.94,-0.05]) on the volume of the mandibular angle.
CONCLUSIONS: There is no clear pattern on whether the application of botulinum toxin is associated with bone resorption or not. Although some studies show statistical significance of the findings, the magnitude of the changes in bone density and their clinical significance are not completely clear.
CONCLUSIONS: To understand the effectiveness of the use of botulinum toxin into the masticatory muscles and its possible secondary adverse effects on the density of the mandible.

OBJECTIVE: To assess the differential clinical response to step 2 of periodontal therapy and repeated subgingival instrumentation between teeth with suprabony and intrabony defects.
METHODS: Electronic and manual search were performed to identify studies reporting the differential clinical outcomes of non-surgical periodontal therapy (NSPT) in presence or absence of intrabony defects. The Cochrane Risk of Bias 2 and the Newcastle Ottawa scale were used to assess the risk of bias.
RESULTS: Two thousand three hundred forty-eight articles were initially screened, and a total of 5 articles were finally included. Regarding the primary outcome measure, two studies reported PPD reduction values at 6 months after step 2 of periodontal therapy, showing an opposite response of intrabony defects compared to suprabony defects (3.2 mm ± 1.9 versus 2.2 mm ± 1.7 and 0.48 mm ± 0.42 versus 0.72 mm ± 0.36, respectively), while one study reported no differences at 3 months. One study showed a negative association between the presence of intrabony defect and PPD reduction at 9 months after non-surgical step 3 (p < 0.05).
CONCLUSIONS: Due to the limited number of studies and heterogeneity of the data, conflicting evidence emerged for the differential response to NSPT of intrabony and suprabony defects.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures.
METHODS: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals.
CONCLUSIONS: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body\'s mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4\'s effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.

UNASSIGNED: Mechanical forces applied during an orthodontic tooth movement (OTM) propel several biochemical and molecular responses in the periodontal ligament and alveolar bone. Here, we compile the existing clinical and preclinical evidence on these biological changes, aiming to provide a comprehensive discussion on the influence of the mechanical parameters of the OTM in the biological profile of the periodontium.
UNASSIGNED: This systematic integrative review was conducted according to PICOS strategy and PRISMA guidelines. A bibliographic search was performed in three electronic databases (PubMed, Scopus, and Web of Science) to find research articles published until 2023 and written in English. This search resulted in a total of 2279 publications, which were independently assessed by two evaluators using appropriate tools.
UNASSIGNED: Forty-six studies were selected for this review. These revealed that compression, and stretching of the periodontal ligament fibers and cells are observed in the initial phase of the OTM. Specifically, on the tension side, high levels of IL-1β, OPG, and TIMPs are identified. On the compression side, an increase of RANKL, RANK, and MMPs levels predominate.
UNASSIGNED: This paper describes the release profile of common biomarkers according to the orthodontic protocol, suggesting the most appropriate parameters to keep the teeth and their supporting structures healthy. Overall, this manuscript provides a better understanding of the OTM-associated biological phenomena, also highlighting the importance of early evaluation of oral health, and thus it contributes as a fundamental basis for the development of more effective and safe orthodontic treatments with conventional appliances and aligners.

OBJECTIVE: Cervical total disc replacement (cTDR) has been established as an alternative treatment for degenerative cervical radiculopathy and myelopathy. While the rate of complications for cTDR is reasonably low, recent studies have focused on bone loss after cTDR. The purpose of this work is to develop a clinical management plan for cTDR patients with evidence of bone loss. To guide our recommendations, we undertook a review of the literature and aimed to determine: (1) how bone loss was identified/imaged, (2) whether pre- or intraoperative assessments of infection or histology were performed, and (3) what decision-making and revision strategies were employed.
METHODS: We performed a search of the literature according to PRISMA guidelines. Included studies reported the clinical performance of cTDR and identified instances of cervical bone loss.
RESULTS: Eleven case studies and 20 cohort studies were reviewed, representing 2073 patients with 821 reported cases of bone loss. Bone loss was typically identified on radiographs during routine follow-up or by computed tomography (CT) for patients presenting with symptoms. Assessments of infection as well as histological and/or explant assessment were sporadically reported. Across all reviewed studies, multiple mechanisms of bone loss were suspected, and severity and progression varied greatly. Many patients were reportedly asymptomatic, but others experienced symptoms like progressive pain and paresthesia.
CONCLUSIONS: Our findings demonstrate a critical gap in the literature regarding the optimal management of patients with bone loss following cTDR, and treatment recommendations based on our review are impractical given the limited amount and quality evidence available. However, based on the authors\' extensive clinical experience, close follow-up of specific radiographic observations and serial radiographs to assess the progression/severity of bone loss and implant changes are recommended. CT findings can be used for clinical decision-making and further follow-up care. The pattern and rate of progression of bone loss, in concert with patient symptomatology, should determine whether non-operative or surgical intervention is indicated. Future studies involving implant retrieval, histopathological, and microbiological analysis for patients undergoing cTDR revision for bone loss are needed.

BACKGROUND: Preclinical and animal studies have suggested that excess catecholamines can lead to bone mineral loss. However, to date, no systematic review is available that has analyzed the impact of catecholamine excess in the context of pheochromocytoma/paraganglioma (PPGL) on bone metabolism. We conducted this meta-analysis to address this knowledge gap.
METHODS: Electronic databases were searched for studies evaluating bone metabolism, including assessments of bone mineral density (BMD), quantitative computed tomography (qCT), trabecular bone score (TBS), or bone turnover markers in patients with PPGL. These markers included those of bone resorption, such as tartrate-resistant acid phosphatase 5b (TRACP-5b) and cross-linked C-telopeptide of type I collagen (CTx), as well as markers of bone formation, such as bone-specific alkaline phosphatase (BS ALP).
RESULTS: Out of the initially screened 1614 articles, data from six studies published in four different patient cohorts with PPGL that met all criteria were analysed. Individuals with PPGL had significantly lower TBS [Mean Difference (MD) -0.04 (95% CI: -0.05--0.03); p < 0.00001; I2 = 0%], higher serum CTx [MD 0.13 ng/ml (95% CI: 0.08-0.17); p < 0.00001; I2 = 0%], and higher BS-ALP [MD 1.47 U/L (95% CI: 0.30-2.64); p = 0.01; I2 = 1%]. TBS at 4-7 months post-surgery was significantly higher compared to baseline [MD 0.05 (95% CI: 0.02-0.07); p < 0.0001]. A decrease in CTx has been documented post-surgery.
CONCLUSIONS: Bone health deterioration is a major concern in patients with PPGL. In addition to providing a definitive cure for catecholamine excess, monitoring and treating osteoporosis is essential for individuals with secondary osteoporosis due to PPGL. Long-term studies on bone health outcomes in PPGL are warranted.

UNASSIGNED: Leptin has a great effect on bone through direct or indirect involvement in bone remodeling. Considering the ambiguities that exist regarding the effect of leptin on bone and bone-related diseases including osteoporosis, in this study, we aimed to conduct a systematic review of various studies on the effect of leptin on osteoporosis, which may find an answer to the existing ambiguities.
UNASSIGNED: The search was performed to review studies on the effects of leptin on osteoporosis by using several databases including Scopus, PubMed, Web of Science, and Google Scholar. Electronic searches were conducted on 5 Jan 2023. There was no limit on the publication date of the articles. The risk of bias for the animal study was assessed with the CAMARADES checklist, and the study quality assessment was also assessed based on the guidelines for in vivo experiments (ARRIVE). In this study, the risk of bias (quality) of human studies was assessed using the quality assessment checklists by NHLBI.
UNASSIGNED: Overall, 34 articles were included for data extraction and quality assessment. Overall, 27 human studies and seven animal studies were included in the article. The results of most of the studies conducted in this study showed that leptin has a physiological role in maintaining bone mass and better bone quality and reduces bone marrow adipogenesis and increases bone mineral density (BMD). As plasma leptin levels increased, BMD values or bone formation biomarkers increased.
UNASSIGNED: Leptin has an inhibitory role against bone resorption and increasing osteoprotegerin (OPG) levels, which, as a result, maintains bone density and reduces osteoclast activity, and has a positive relationship with increasing osteocalcin.

OBJECTIVE: Idiopathic condylar resorption (ICR), also known as progressive condylar resorption, is poorly understood, particularly in adolescent patients. Therefore, this scoping review aims to summarize the available literature on the prevalence, aetiology, pathogenesis, diagnostic process, treatment and/or any outcome regarding ICR in adolescent individuals.
METHODS: This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and its extension for scoping reviews (PRISMA-ScR), as well as Joanna Briggs Institute studies. The search strategy was defined adopting a core search structure for each source, and the search was performed on MEDLINE, EMBASE, Cochrane Library, Web of Science, Scopus and Google Scholar. After duplicate removal, two independent reviewers screened abstracts, followed by complete articles, to achieve the definition of included studies. Data collection was performed, and the extracted data were organized in tabular form, along with a narrative summary of main findings that aligns with the objective of this review.
RESULTS: Six observational studies were included in this review. Three studies focused on signs and symptoms, one on prevalence and signs and symptoms, one on treatment and one on disease pathogenesis.
CONCLUSIONS: This scoping review revealed inadequate published research regarding prevalence, aetiology, early diagnosis, pathogenesis and treatment of ICR in adolescents.

Glycogen synthase kinase 3-beta (GSK3β) is a highly conserved protein kinase originally involved in glucose metabolism, insulin activity, and energy homeostasis. Recent scientific evidence demonstrated the significant role of GSK3β in regulating bone remodelling through involvement in multiple signalling networks. Specifically, the inhibition of GSK3β enhances the conversion of osteoclast progenitors into mature osteoclasts. GSK3β is recognised as a pivotal regulator for the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG), phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT), nuclear factor-kappa B (NF-κB), nuclear factor-erythroid 2-related factor 2 (NRF2)/Kelch-like ECH-associated protein 1 (KEAP1), canonical Wnt/beta (β)-catenin, and protein kinase C (PKC) signalling pathways during osteoclastogenesis. Conversely, the inhibition of GSK3β has been shown to prevent bone loss in animal models with complex physiology, suggesting that the role of GSK3β may be more significant in bone formation than bone resorption. Divergent findings have been reported regarding the efficacy of GSK3β inhibitors as bone-protecting agents. Some studies demonstrated that GSK3β inhibitors reduced osteoclast formation, while one study indicated an increase in osteoclast formation in RANKL-stimulated bone marrow macrophages (BMMs). Given the discrepancies observed in the accumulated evidence, further research is warranted, particularly regarding the use of GSK3β silencing or overexpression models. Such efforts will provide valuable insights into the direct impact of GSK3β on osteoclastogenesis and bone resorption.