Search Results (507)

Fibrous dysplasia is an uncommon bone disorder affecting various parts of the skeleton, often affecting facial and cranial bones. In this case, a 10-year-old patient was diagnosed with fibrous dysplasia of the ethmoid sinus at an early age. The patient has experienced nasal congestion, snores, and worsening nasal patency since 2019. A CT scan revealed an expansive proliferative lesion, likely from the frontal or ethmoid bone, protruding into the nasal cavity, ethmoid sinus, and right orbit. The tumor causes bone defects in the area of the nasal bone, leading to fluid retention in the peripheral parts of the right maxillary sinus. The patient’s parents decided not to undergo surgery to remove the diseased tissue and reconstruct the area, as it would be very extensive, risky, and disfiguring. The patient is being treated conservatively with an MRI, with a contrast performed approximately every six months and infusions of bisphosphonates. Despite the lesion’s size, the patient does not experience pain characteristic of dysplasia, and functions typically. Fibrous dysplasia of bone is a rare condition that presents with the most visually apparent manifestations, often mistaken for other bone conditions. Advanced diagnostic tools, like CT and MRI, are used to identify conditions affecting the ethmoid sinus more frequently. However, diagnostic errors often occur in imaging studies, leading to confusion. The most common period for clinical manifestations and diagnosis is around 10 years of age. The preferred approach in managing fibrous dysplasia involves symptomatic treatment, which can alleviate airway obstruction, restore normal globe position and visual function, and address physical deformities. Surgical intervention is recommended only for patients with severe functional impairment, progressive deformities, or malignant transformation. Full article

Objectives: This work investigated the effect of bacterial nanocellulose (BNC) alone or with chemisorbed chlorhexidine or povidone-iodine on post-tooth extraction repair in rats undergoing bisphosphonate therapy. Methods: Forty Wistar rats were treated with zoledronic acid, subjected to tooth extractions and allocated into groups according to the material inserted in the post-extraction socket: (1) BNC (n = 10); (2) BNC/Iodine (n = 10); (3) BNC/Chlorhex (n = 10); (4) Control (n = 10). Maxillae were dissected and macro- and microscopically analyzed. Results: Oral lesion frequency on macroscopic examination did not differ between the groups, whereas it was larger in the BNC/Iodine group compared to the BNC/Chlorhex and Control. BNC/Chlorhex had significantly more connective tissue than did BNC but did not differ from the BNC/Iodine and Control. Epithelium, vital bone, non-vital bone, tooth fragment and inflammatory infiltrate did not significantly differ between the groups. BNC/Iodine showed greater CD31 immunostaining compared to BNC and the Control. Myeloperoxidase staining did not differ between the groups, and scanning electron microscopy analysis showed similar characteristics in all groups. Conclusions: BNC with chemisorbed povidone-iodine is associated with increased vascularization in post-extraction wounds of rats undergoing bisphosphonate therapy, whereas BNC with chemisorbed chlorhexidine improves connective tissue formation. BNC works as an effective carrier for the antiseptics tested. Full article

This study aimed to evaluate the incidence of total knee arthroplasty (TKA), a marker of severe knee osteoarthritis (OA), among older females with concurrent knee OA and osteoporosis (OP) who were treated with denosumab or bisphosphonates. By analyzing a large population-based cohort, we sought to clarify how these treatments influence the progression of knee OA to the point of requiring surgical intervention. We used data from the Taiwan National Health Insurance Research Database, including data from females aged ≥ 50 years diagnosed with knee OA and OP who initiated treatment between 2012 and 2019. Propensity score matching (1:1) resulted in the selection of 13,774 patients (6897 per group). The TKA incidence was analyzed using Cox proportional hazards models. Patients treated with denosumab had a lower TKA incidence than those treated with bisphosphonates (6.9 vs. 8.5 per 1000 person-years). The adjusted hazard ratio (aHR) for TKA in the denosumab group was 0.77 (95% CI: 0.62–0.97; p = 0.024), with the most pronounced effect observed in patients aged ≥ 80 years (aHR = 0.39, 95% CI: 0.20–0.77; p = 0.007). These findings suggest that denosumab reduces TKA risk more effectively than bisphosphonates and may serve as a superior treatment option for mitigating severe knee OA progression, especially in older adults. Full article

The COVID-19 pandemic has significantly impacted healthcare systems worldwide, including dental care. This study aimed to investigate the effects of the pandemic on the management of medication-related osteonecrosis of the jaw (MRONJ). Abnormal blood glucose levels may contribute to the development of MRONJ and act as an important risk factor. This retrospective study included 217 patients with MRONJ. The patients were divided into two groups: the pre-COVID-19 group (16 March 2018 to 16 March 2020; 75 patients; 46 females and 29 males; average age, 74.5 years) and the post-COVID-19 group (1 June 2022 to 1 June 2024; 142 patients; 91 females and 51 males; average age, 69.6 years). Data pertaining to demographic characteristics, length of hospital stay, glucose levels, location of lesions, and underlying diseases were collected. The average length of hospital stays was 4 and 5 days in the pre- and post-COVID-19 groups, respectively. The average fasting glucose levels were 5.5 and 5.9 mmol/L in the pre- and post-COVID-19 groups, respectively. Localization patterns shifted, with a higher incidence in the maxilla in the post-COVID-19 group. These findings suggest a significant increase in MRONJ cases and changes in clinical outcomes due to the pandemic. The increase in the number of patients treated after the pandemic highlights the importance of ongoing vigilance and adaptation in preventing MRONJ, with a particular focus on risk factors. Full article

Background: Osteoporosis (OP) is a chronic inflammatory bone disease characterized by reduced bone structure and strength, leading to increased fracture risk. Effective therapies targeting both bone and cartilage are limited. This study compared the therapeutic effects of extracorporeal shockwave therapy (ESWT), bisphosphonate (Aclasta), and human Wharton jelly-derived mesenchymal stem cells (WJMSCs) in a rat model of OP. Methods: Female rats were assigned to four groups: Sham (no surgery or treatment), OP (bilateral ovariectomy, OVX), ESWT (OVX + ESWT on both tibias at 0.25 mJ/mm², 1500 impulses per tibia), Aclasta (OVX + zoledronic acid 0.1 mg/kg via tail vein injection), and WJMSC (OVX + 2 × 10⁶ WJMSCs). Pathological changes, bone microarchitecture (by micro-CT), serum cytokines (by ELISA), and tissue-specific molecular markers (by immunohistochemistry) were evaluated. Results: All treatments improved bone density, preserved cartilage, and modulated cytokines (IL31, IL33, VEGF, and BMP2), with Aclasta showing the greatest improvements in bone parameters and cartilage preservation. ESWT and WJMSC also demonstrated significant effects, with ESWT highlighting non-invasive chondroprotective potential. Conclusions: Aclasta provided the best overall therapeutic response, particularly in bone regeneration. However, ESWT and WJMSC also showed comparable chondroprotective effects. ESWT emerges as a promising non-invasive alternative for OP management when pharmacological or cell-based therapies are not feasible. Full article

Adult spinal deformity (ASD) commonly affects older adults, with up to 68% prevalence in those over 60, and is often complicated by osteoporosis, which reduces bone mineral density (BMD) and increases surgical risks. Osteoporotic patients undergoing ASD surgery face higher risks of complications like hardware failure, pseudoarthrosis, and proximal junctional kyphosis (PJK). Medical management with antiresorptive medications (e.g., bisphosphonates, SERMs, and denosumab) and anabolic agents (e.g., teriparatide, abaloparatide, and romosozumab) can improve BMD and reduce complications. While bisphosphonates reduce fracture risk, teriparatide and newer agents like romosozumab show promise in increasing bone density and improving fusion rates. Surgical adaptations such as consideration of age-adjusted alignment, fusion level selection, cement augmentation, and the use of expandable screws or tethers enhance surgical outcomes in osteoporotic patients. Specifically, expandable screws and cement augmentation have been shown to improve fixation stability. However, further research is needed to evaluate the effectiveness of these treatments, specifically in osteoporotic ASD patients. Full article

Bone metastases are a prevalent complication in advanced cancers, particularly in breast, prostate, and lung cancers, and are associated with severe skeletal-related events (SREs), including fractures, spinal cord compression, and debilitating pain. Conventional bone-targeted treatments like bisphosphonates and RANKL inhibitors (denosumab) reduce osteoclast-mediated bone resorption but do not directly impact tumor progression within the bone. This review focuses on examining the growing potential of immunotherapy in targeting the unique challenges posed by bone metastases. Even though immune checkpoint inhibitors (ICIs) have significantly changed cancer treatment, their impact on bone metastases appears limited because of the bone microenvironment’s immunosuppressive traits, which include high levels of transforming growth factor-beta (TGFβ) and the immune-suppressing cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). This review underscores the investigation of combined therapeutic approaches that might ease these difficulties, such as the synergy of immune checkpoint inhibitors with agents aimed at bones (denosumab, bisphosphonates), chemotherapy, and radiotherapy, as well as the combination of immune checkpoint inhibitors with different immunotherapeutic methods, including CAR T-cell therapy. This review provides a comprehensive analysis of preclinical studies and clinical trials that show the synergistic potential of these combination approaches, which aim to both enhance immune responses and mitigate bone destruction. By offering an in-depth exploration of how these strategies can be tailored to the bone microenvironment, this review underscores the need for personalized treatment approaches. The findings emphasize the urgent need for further research into overcoming immune evasion in bone metastases, with the goal of improving patient survival and quality of life. Full article

This study aimed to identify whether there is an ideal concentration for applying ozonized oil (OZ) in the post-exodontic alveoli of senescent rats treated with zoledronate (ZOL). Thirty-five female rats, aged 18 months, were divided into five groups: ZOL; ZOL+OZ500; ZOL+OZ600; ZOL+OZ700; and SAL. The groups treated with ZOL, and other concentrations of OZ received applications at a dose of 100 μg/kg, while the SAL group received saline. After three weeks of ZOL application, the animals underwent extraction of the lower first molar. Subsequently, local therapies were initiated: group ZOL+OZ500 at 500 mEq/kg; ZOL+Z600 at 600 mEq/kg; and ZOL+OZ700 at 700 mEq/kg at baseline, and on days 2 and 4 post-operation. Euthanasia was performed on day 28. The microtomographic parameter of bone volume and histometric data on the area of neoformed bone (NFBT) showed the highest values for the ZOL+OZ600 group (p < 0.05). All OZ groups had smaller areas of non-vital bone than the ZOL group (p < 0.05). The clinical appearance of the operated region showed the alveoli covered with soft tissue, particularly in the OZ groups. All the tested concentrations of OZ were able to prevent and modulate MRONJ. As it presents a greater amount of NFBT, the concentration of 600 mEq/kg seems to be ideal. Full article

Long-term treatment with bisphosphonates is accompanied by an increased risk of medication-related osteonecrosis of the jaw (MRONJ). Currently, no clinically useful biomarkers for the predictive diagnosis of MRONJ are available. To investigate the potential key proteins involved in the pathogenesis of MRONJ, a proteomic LC-MS/MS analysis of saliva was performed. Differentially expressed proteins (DEPs) were analyzed using BiNGO, ClueGO, cytoHubba, MCODE, KEGG, and ReactomeFI software packages using Cytoscape platforms. In total, 1545 DEPs were identified, including 43 up- and 11 down-regulated with a 1.5-fold cut-off value and adj. p-value < 0.05. The analysis provided a panel of hub genes, including APOA2, APOB, APOC2, APOC3, APOE, APOM, C4B, C4BPA, C9, FGG, GC, HP, HRG, LPA, SAA2-SAA4, and SERPIND1. The most prevalent terms in GO of the biological process were macromolecular complex remodeling, protein–lipid complex remodeling, and plasma lipoprotein particle remodeling. DEPs were mainly involved in signaling pathways associated with lipoproteins, the innate immune system, complement, and coagulation cascades. The current investigation advanced our knowledge of the molecular mechanisms underlying MRONJ. In particular, the research identified the principal salivary proteins that are implicated in the onset and progression of this condition. Full article

Antibiotic prophylaxis in dentistry has been recommended for different groups of patients, such as patients with impaired immunologic function, patients at risk of developing infective endocarditis or prosthetic joint infection, patients previously exposed to high-dose irradiation of the head and neck regions, and patients receiving intravenous bisphosphonate and antiangiogenic treatment. The guidelines have been changed over the years, and the list of medical conditions requiring antibiotic prophylaxis has been shortened considerably in the context of antibiotic resistance and unnecessary antibiotic prescription. Full article

Bisphophonates (BPs) are widely used in Osteogenesis imperfecta (OI). Cone Beam Computed Tomography (CBCT) shows clinical usefulness in evaluating impacted teeth and adjacent structure relationships, extraction socket healing, bone mineral density (BMD) and BP-related jaw osteonecrosis (BRONJ). The aim of the study was to compare alveolar sockets and the adjacent bone area before and after third molar extraction in OI type I (OI-I) adolescents treated with BPs and age-matched healthy subjects (HSs) by CBCT. Methods: Five adolescents with genetically proven OI-I treated with BPs (three males and two females, mean age: 15.2 ± 1.78 years) and four age-matched healthy subjects (two males and two females, mean age: 15.5 ± 1.29 years) were included in this study. Eight Regions of Interest (ROIs) were evaluated: between 3.7 and 3.8 (ROI-1) and 4.7 and 4.8 (ROI-2); after 3.8 (ROI-3) and 4.8 (ROI-4); alveolar sockets 3.8 (ROI-5) and 4.8 (ROI-6); left (ROI-7) and right (ROI-8) cortical bone. Results: ROIs were evaluated on both sides of the mandible for all the subjects except one OI patient in which CBCTs were performed pre- and-post third molar extraction only on the right side. CBCT was performed 12.8 ± 4.60 and 11.5 ± 2.51 days before and 8.0 ± 1.41 and 7.7 ± 0.5 months after extraction in OI-I and HSs, respectively. BPs were discontinued 62.0 ± 36.5 months before extraction. None of the OI-I adolescents developed BRONJ. Statistically significant greater values were observed in OI-I for ROI-1 and -2 (p = 0.0464), ROI-3 and -4 (p = 0.0037) and ROI-7 and -8 (p = 0.0079) after extraction. Conclusions: This descriptive study confirms that, in OI-I adolescents treated with BPs, third molar extraction is safe, and socket healing occurs properly. In addition, it demonstrates that, if the same device and imaging conditions are used and comparisons to predetermined standard values are avoided, CBCT can be used to monitor BMD changes. The significant greater BMD observed for different ROIs in OI-I could reflect the increased secondary mineralization related to the BP-dependent reduction in bone turnover. Full article

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption through a rise in pro-inflammatory cytokines (IL-1, IL-6, TNF-α) and RANKL, which promote osteoclastogenesis. In the classic genomic pathway, estrogen binds to estrogen receptors in the cytoplasm, forming a complex that migrates to the nucleus and binds to estrogen response elements on DNA, regulating gene transcription. Androgens can be defined as high-affinity ligands for the androgen receptor; their combination can serve as a ligand-inducible transcription factor. Hormone replacement therapy has shown promise but comes with associated risks and side effects. In contrast, the non-genomic pathway involves rapid signaling cascades initiated at the cell membrane, influencing cellular functions without directly altering gene expression. Therefore, the ligand-independent actions and rapid signaling pathways of estrogen and androgen receptors can be harnessed to develop new drugs that provide bone protection without the side effects of traditional hormone therapies. To manage primary osteoporosis, other pharmacological treatments (bisphosphonates, teriparatide, RANKL inhibitors, sclerostin inhibitors, SERMs, and calcitonin salmon) can ameliorate osteoporosis and improve BMD via actions on different pathways. Non-pharmacological treatments include nutritional support and exercise, as well as the dietary intake of antioxidants and natural products. The current study reviews the processes of bone remodeling, hormone actions, hormone receptor status, and therapeutic targets of primary osteoporosis. However, many detailed cellular and molecular mechanisms underlying primary osteoporosis seem complicated and unexplored and warrant further investigation. Full article

Background: Bisphosphonates used for the treatment of osteoporosis, hypercalcemia, or heterotopic calcifications can cause serious adverse dental events such as osteonecrosis of the maxillary and mandibular bones. However, the effects in childhood remain scarcely explored. Case Presentations: We encountered two children who had started bisphosphonate therapy before completion of the primary dentition. No systemic disease causing congenital delayed tooth eruption was diagnosed. Although the children’s height and weight increased with age, their tooth eruption was significantly delayed compared with the mean. The primary teeth gradually erupted in the follow-up period; however, some teeth did not completely erupt and needed to be extracted to allow for permanent tooth eruption. Conclusions: We report a case of children with early use of bisphosphonates and eruption disturbance, highlighting the need for further investigation into the relationship between these factors. Full article

Background and Objectives: Osteoporosis is becoming more prevalent with the rise in the aging population, leading to the increased use of bisphosphonates for treatment. While these medications are effective in preventing osteoporotic fractures, long-term use has been associated with atypical insufficiency fractures, primarily in the femur. However, atypical fractures in other weight-bearing bones, such as the tibia, have rarely been reported. This study aims to present a case of an atypical insufficiency fracture of the tibia in an elderly female who has been on long-term bisphosphonate therapy and to review treatment outcomes within the context of the current literature. Patient concerns: A 76-year-old female presented with pain in the proximal right tibia, developing two months prior without trauma. She had been receiving long-term bisphosphonate therapy for osteoporosis, initially taking sodium risedronate orally for 4 years, followed by intravenous ibandronate for 10 years. Physical examination revealed localized tenderness, and radiographs showed cortical thickening and a horizontal fracture line in the proximal right tibia. MRI confirmed these findings, along with surrounding edema. The laboratory results were mostly normal, but the bone formation marker osteocalcin was significantly reduced. The patient had a history of insufficiency fractures in the ipsilateral tibia and contralateral femur, previously treated conservatively with teriparatide. A similar conservative approach was attempted but failed, leading to surgical intervention with intramedullary nailing and supplementary plating. At the 8-month follow-up, the patient showed successful fracture union and resolution of symptoms. Conclusion: Long-term use of bisphosphonates, though effective for osteoporosis, can lead to atypical insufficiency fractures, primarily in the femur but also occasionally in the tibia. Clinicians should consider this possibility when patients present with pain in weight-bearing bones without a history of trauma. Prompt diagnosis through thorough history-taking, physical examination, and appropriate imaging is essential to ensure timely management. Full article

Background: Osteoporosis and vertebral fractures (VFs) are frequently observed in males living with HIV (MLWH). While bisphosphonates seem effective on bone mineral density (BMD) in MLWH, data on VFs are lacking. In this real-life longitudinal study performed on 118 MLWH (median age 53) who were followed-up for a median of 7 years, we aimed to evaluate the long-term efficacy of oral bisphosphonates on VFs in MLWH. Methods: The inclusion criteria were age >18, stable HIV infection, bisphosphonate-naïve, blood samples from the same laboratory, and three densitometries and morphometries performed with the same densitometer. Results: At baseline, VFs were detected in 29/118 patients (24.6%). Patients with VFs were older (p. 0.042), had longer HIV infection duration (p. 0.046) and antiretroviral exposure (p. 0.025), and demonstrated higher luteinizing hormone levels (LH, p. 0.044). Of the 29 patients with VFs at inclusion, 11 developed new VFs, of which 8 were under oral bisphosphonates (p. 0.018). Among the 89 without basal VFs, 11 developed VFs, of which 2 were under oral bisphosphonates. Patients with a worsened bone condition (regarding BMD and/or new VFs, n. 32) had more frequently high LH levels (>9.4 mIU/mL, p. 0.046) and higher HCV co-infection compared to patients with a stable bone condition (p. 0.045). It should be noted that 38.6% of patients discontinued oral bisphosphonates due to medical indication or personal choice, and 14.0% never started them. Conclusions: In conclusion, we found that oral bisphosphonates were not completely effective in preventing VFs, especially in patients with VFs at baseline; this is probably due to the multifactorial pathogenesis of fragility fractures in this population. A poor adherence to treatment and attention to gonadal function are also important issues in this population. Full article