Search Results (73)

Background and Objectives: We wished to evaluate the effect of antiresorptive agents (ARAs) on peri-implant tissues and to examine the risk factors for peri-implant medication-related osteonecrosis of the jaw (MRONJ). Materials and Methods: The study cohort consisted of patients who underwent implant surgery or maintenance treatment between March 2012 and December 2024. The patients were divided into two groups: those in whom bisphosphonates (BPs) or denosumab (Dmab) was used to treat osteoporosis after implant treatment (the ARA group) and a control group. Peri-implant clinical parameters (implant probing depth (iPPD), implant bleeding on probing (iBoP), marginal bone loss (MBL), and mandibular cortical index (MCI)) measured at the baseline and at the final visit were statistically evaluated and compared in both groups. Risk factors were examined using a multivariate analysis of adjusted odds ratios (aORs). Results: A total of 192 implants in 61 patients (52 female, 9 male) were included in this study. The ARA group consisted of 89 implants (22 patients). A comparison of the clinical parameters showed that the ARA group had significantly higher variations in their maximum iPPD and iBoP values over time than those in the control group. Risk factors for peri-implantitis as objective variables were the use of ARAs (aOR: 3.91; 95% confidence interval [CI]: 1.29–11.9) and the change in the maximum iPPD over time (aOR: 1.86; 95% CI: 0.754–4.58). Conclusions: During long-term implant maintenance treatment, patients’ health and medication status change. Monitoring peri-implantitis, the presumed cause of peri-implant MRONJ, is essential, especially in patients who started ARA treatment after implant placement, and special attention should be paid to changes in implant pocket depth. Full article

Tanshinones are a class of lipophilic diterpenoid quinones extracted from Salvia miltiorrhiza (Dan shen), a widely used herb in traditional Chinese medicine. These compounds, particularly tanshinone IIA (T-IIA) and sodium tanshinone sulfonate (STS), have been acknowledged for their broad spectrum of biological activities, including anti-inflammatory, antioxidant, anti-tumor, antiresorptive, and antimicrobial effects. Recent studies have highlighted the potential of tanshinones in the treatment of osteolytic diseases, characterized by excessive bone resorption, such as osteoporosis, rheumatoid arthritis, and periodontitis. The therapeutic effects of tanshinones in these diseases are primarily attributed to their ability to inhibit osteoclast differentiation and activity, suppress inflammatory cytokine production (e.g., tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6), and modulate critical signaling pathways, including NF-kB, MAPK, PI3K/Akt, and the RANKL/RANK/OPG axis. Additionally, tanshinones promote osteoblast differentiation and mineralization by enhancing the expression of osteogenic markers such as Runx2, ALP, and OCN. Preclinical models have demonstrated that T-IIA and STS can significantly reduce bone destruction and inflammatory cell infiltration in arthritic joints and periodontal tissues while also enhancing bone microarchitecture in osteoporotic conditions. This review aims to provide a comprehensive overview of the pharmacological actions of tanshinones in osteolytic diseases, summarizing current experimental findings, elucidating underlying molecular mechanisms, and discussing the challenges and future directions for their clinical application as novel therapeutic agents in bone-related disorders, especially periodontitis. Despite promising in vitro and in vivo findings, clinical evidence remains limited, and further investigations are necessary to validate the efficacy, safety, and pharmacokinetics of tanshinones in human populations. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

Receptor activator of nuclear factor-κB ligand (RANKL) is essential for osteoclast formation and bone resorption, in osteolytic conditions such as osteoporosis and bone metastases. However, its role in metastasis progression remains incompletely understood. Herein, we examined whether the overexpression of human RANKL in transgenic mice (TgRANKL) affects their susceptibility to breast cancer bone metastasis compared to their wild-type (WT) littermates. Bone metastasis was induced by injecting EO771 mouse mammary adenocarcinoma cells into the caudal artery of syngeneic WT and TgRANKL mice. RANKL overexpression led to an earlier onset and increased burden of bone metastasis in EO771-bearing TgRANKL mice compared to WT mice. It also exacerbated the bone destruction caused by metastasis-associated osteolysis. The prophylactic inhibition of RANKL activity with denosumab, a monoclonal antibody targeting human RANKL, prevented osteolysis and significantly reduced the incidence and progression of bone metastases in TgRANKL mice. However, the therapeutic denosumab treatment had no effect on metastasis incidence or tumor burden, although it alleviated osteolysis. The treatment with zoledronic acid, an anti-resorptive agent inhibiting osteoclast activity, yielded results similar to those of denosumab. These findings emphasize the significance of initiating early treatment with anti-resorptive agents such as denosumab or zoledronic acid to reduce the risk of bone metastasis in patients at high risk. Full article

Introduction: Bone health optimization is a key component of the preoperative management of spine surgery patients, as poor bone quality increases the odds of mechanical complications. The present study aimed to achieve the following: (1) compare the relative efficacy of current osteoporosis medications in improving bone quality; (2) identify factors influencing treatment response in preoperative spine surgery patients. Methods: Patients treated at a single, multisite institution who received osteoporosis treatment were identified. Data were gathered on pre- and post-treatment lumbar spine Hounsfield Unit (HU) measurements, patient demographics, frailty scores (modified Frailty Index/mFI, risk analysis index/RAI), and pharmacologic treatment details. The primary outcome was a ≥7 point improvement in lumbar HU, and baseline and logistic regression models were utilized to identify factors associated with this improvement. Medications were grouped as anabolic (teriparatide, romosozumab) and antiresorptive (denosumab, alendronate) therapies. Results: A total of 267 patients were included (median age: 74 years; IQR [66–81]; 67.3% female), with 127 (47.6%) improving by ≥7 HU. The treatment agents used were alendronate (95), denosumab (113), romosozumab (31), and teriparatide (28). Univariable comparisons revealed significant differences across medication groups in age (p < 0.001), sex (p < 0.001), mFI (p < 0.001), RAI (p = 0.004), BMI (p < 0.001), pre-treatment HU (p = 0.022), and treatment duration (p < 0.001). The highest HU improvement rates (ΔHU ≥ 7) were observed in patients receiving the anabolic medications romosozumab (67.7%) and teriparatide (60.7%). Univariable logistic regression identified male sex (OR 0.54, p = 0.019), higher pre-treatment HU (OR 0.99, p = 0.006), and longer treatment duration (OR 0.97, p = 0.003) as factors associated with lower odds of HU improvement. Only romosozumab was associated with significantly higher odds of HU improvement relative to alendronate (OR 3.02, p = 0.012). In our multivariable analysis, male sex (OR 0.53, p = 0.028) and higher pre-treatment HU (OR 0.99, p = 0.002) remained significant predictors of HU improvement. However, medication type was not significant in the multivariable analysis. Conclusions: Our study highlights that male sex and higher pre-treatment HU were independently associated with lower odds of HU improvement, while medication type was not a significant predictor. Additionally, anabolic agents offered superior improvement relative to antiresorptive therapies. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a multifactorial condition defined as an adverse drug reaction that results in progressive jawbone destruction and necrosis in individuals treated with certain medications, occurring without a history of prior radiotherapy. These drugs are mainly bisphosphonates, denosumab, and other bone-modifying agents, anti-angiogenic agents such as anti-endothelial growth factor, tyrosine kinase inhibitors, and proteins classified as mammalian targets of rapamycin. The diagnosis of MRONJ is based on clinical (exposed jawbone, fistula with pus, hyperplasia of the mucosa overlying the necrotic bone tissue) and radiological evaluation. We report four cases of clinical and radiological evidence of osteonecrosis of the jaw that are unrelated to the use of antiresorptive or anti-angiogenic agents. In two instances, histological and microbiological evidence was also found (high concentration of Actinomyces, the microbe most commonly found in oral sites affected by MRONJ). These atypical cases are reported to highlight the possibility that other, previously undocumented, drugs may also contribute to the development of ONJ Full article

The interaction between antiresorptive medication and dental implant procedures remains a subject of concern complicating the decision-making process for clinicians. The aim of the study is to conduct a literature review on the relationship between dental implant placement and the incidence of osteonecrosis of the jaw (ONJ) in patients receiving antiresorptive drugs. The systematic review relied on the PRISMA statement using the PICO tool. The literature search was performed using PubMed, EBSCOhost and Scopus for RCTs, controlled clinical trials and cohort studies. The choice of reference studies was made in a blind process with a 100% agreement rate. For all included studies, quality assessment was performed. The research led to the selection of 608 results. Only five studies were included in the review. Three of the included studies were judged as having a low risk of bias. Dental implants may not be linked to a higher risk of osteonecrosis of the jaw in patients taking low-dose bone-modifying agents. The long-term survival of implants in osteoporotic patients taking oral antiresorptive medication was similar to that in a healthy population and significantly higher than in untreated controls. Full article

Background/Objectives: Bisphosphonates are effective in preventing osteoporotic fractures. However, the risk of atypical femur fractures (AFFs) increases with long-term bisphosphonate use. There are few existing publications on the analysis of clinical outcomes of atypical femur fracture cases in Chinese patients. Our objective was to review the clinical outcomes of AFF cases managed in a tertiary center in Hong Kong, China. Methods: Cases of AFF managed in the Prince of Wales Hospital from 2010 to 2024 were included. Data on demographics, type and duration of bisphosphonate use prior to AFF, fixation method, and mobility 1 year post-operation were retrospectively retrieved. One-way ANOVA was used to compare the duration of use prior to the development of AFF between different types of bisphosphonates. Results: Sixty-nine cases of AFF were included, with a mean age of 73.8 ± 9.7 years. A total of 95.6% of patients had a history of bisphosphonate use, with a mean duration of usage of 6.8 ± 5.6 years prior to the occurrence of AFF. The duration of bisphosphonate use prior to the development of AFF was comparable between alendronate, ibandronate, and a history of using more than one type of anti-resorptive agent. A non-union rate of 5.8% was observed in the current cohort, with 48.2% returning to pre-morbid mobility 1 year post-operation. Conclusions: AFF is more commonly seen in female patients with a history of bisphosphonate use. Considering the high success rate demonstrated in the current cohort, treating AFF with closed reduction followed by fixation with a long cephalomedullary device in dynamic locking together with immediate full-weight-bearing rehabilitation post-operation may be effective. 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

Medication-Related Osteonecrosis of the Jaw (MRONJ) is characterized by bone exposure in the oral and maxillofacial region for more than eight weeks in patients treated with anti-resorptive agents, immunosuppressants, or anti-angiogenic agents, without prior radiation therapy or metastatic disease to the jaws. Conservative treatments can control infection in mild cases, but surgical intervention is necessary for patients with severe symptoms. A 78-year-old female with a history of bisphosphonate treatment for osteoporosis presented with persistent pain, swelling, and malodor following implant placement in the upper right maxilla. SPECT/CT imaging revealed a high-risk hot spot in the right maxillary region. BIS-guided surgery using the Qray pen-C was performed, selectively removing red fluorescent bone tissue. The defect was grafted with HuBT incorporated with rhBMP-2. Postoperative follow-ups at 4, 7, and 14 months showed successful bone healing, transforming into a corticocancellous complex, and implant placement without MRONJ recurrence. Allogeneic demineralized dentin matrix (DDM) incorporated with rhBMP-2 demonstrates effective bone healing and implant placement following BIS-guided MRONJ surgery. This case supports the use of DDM/rhBMP-2 for tissue regeneration in MRONJ treatment, enabling successful prosthetic restoration without recurrence. Full article

Medication-related osteonecrosis of the jaw (MRONJ) is a debilitating adverse effect of bisphosphates, antiresorptive therapy or antiangiogenic agents that can potentially increase oxidative stress, leading to progressive osteonecrosis of the jaws. Despite the large number of published systematic reviews, there is a lack of potential MRONJ treatment protocols utilising photobiomodulation (PBM) as a single or adjunct therapy for preventive or therapeutic oncology or non-oncology cohort. Hence, this systematic review aimed to evaluate PBM laser efficacy and its dosimetry as a monotherapy or combined with the standard treatments for preventive or therapeutic approach in MRONJ management. The objectives of the review were as follows: (1) to establish PBM dosimetry and treatment protocols for preventive, therapeutic or combined approaches in MRONJ management; (2) to highlight and bridge the literature gaps in MRONJ diagnostics and management; and (3) to suggest rationalised consensus recommendations for future randomised controlled trials (RCTs) through the available evidence-based literature. This review was conducted according to the PRISMA guidelines, and the protocol was registered at PROSPERO under the ID CRD42021238175. A multi-database search was performed to identify articles of clinical studies published from their earliest records until 15 December 2023. The data were extracted from the relevant papers and analysed according to the outcomes selected in this review. In total, 12 out of 126 studies met the eligibility criteria. The striking inconsistent conclusions made by the various authors of the included studies were due to the heterogeneity in the methodology, diagnostic criteria and assessment tools, as well as in the reported outcomes, made it impossible to conduct a meta-analysis. PBM as a single or adjunct treatment modality is effective for MRONJ preventive or therapeutic management, but it was inconclusive to establish a standardised and replicable protocol due to the high risk of bias in a majority of the studies, but it was possible to extrapolate the PBM dosimetry of two studies that were close to the WALT recommended parameters. In conclusion, the authors established suggested rationalised consensus recommendations for future well-designed robust RCTs, utilising PBM as a monotherapy or an adjunct in preventive or therapeutic approach of MRONJ in an oncology and non-oncology cohort. This would pave the path for standardised PBM dosimetry and treatment protocols in MRONJ management. Full article

Osteoporosis, a metabolic bone disorder characterized by decreased bone mass per unit volume, poses a significant global health burden due to its association with heightened fracture risk and adverse impacts on patients’ quality of life. This review synthesizes the current understanding of the pathophysiological mechanisms underlying osteoporosis, with a focus on key regulatory pathways governing osteoblast and osteoclast activities. These pathways include RANK/RANKL/OPG, Wingless-int (Wnt)/β-catenin, and Jagged1/Notch1 signaling, alongside the involvement of parathyroid hormone (PTH) signaling, cytokine networks, and kynurenine in bone remodeling. Pharmacotherapeutic interventions targeting these pathways play a pivotal role in osteoporosis management. Anti-resorptive agents, such as bisphosphonates, estrogen replacement therapy/hormone replacement therapy (ERT/HRT), selective estrogen receptor modulators (SERMs), calcitonin, anti-RANKL antibodies, and cathepsin K inhibitors, aim to mitigate bone resorption. Conversely, anabolic agents, including PTH and anti-sclerostin drugs, stimulate bone formation. In addition to pharmacotherapy, nutritional supplementation with calcium, vitamin D, and vitamin K2 holds promise for osteoporosis prevention. However, despite the availability of therapeutic options, a substantial proportion of osteoporotic patients remain untreated, highlighting the need for improved clinical management strategies. This comprehensive review aims to provide clinicians and researchers with a mechanistic understanding of osteoporosis pathogenesis and the therapeutic mechanisms of existing medications. By elucidating these insights, this review seeks to inform evidence-based decision-making and optimize therapeutic outcomes for patients with osteoporosis. Full article

New gelatin methacryloyl (GelMA)—strontium-doped nanosize hydroxyapatite (SrHA) composite hydrogel scaffolds were developed using UV photo-crosslinking and 3D printing for bone tissue regeneration, with the controlled delivery capacity of strontium (Sr). While Sr is an effective anti-osteoporotic agent with both anti-resorptive and anabolic properties, it has several important side effects when systemic administration is applied. Multi-layer composite scaffolds for bone tissue regeneration were developed based on the digital light processing (DLP) 3D printing technique through the photopolymerization of GelMA. The chemical, morphological, and biocompatibility properties of these scaffolds were investigated. The composite gels were shown to be suitable for 3D printing. In vitro cell culture showed that osteoblasts can adhere and proliferate on the surface of the hydrogel, indicating that the GelMA-SrHA hydrogel has good cell viability and biocompatibility. The GelMA-SrHA composites are promising 3D-printed scaffolds for bone repair. Full article

A challenge in tissue engineering and the pharmaceutical sector is the development of controlled local release of drugs that raise issues when systemic administration is applied. Strontium is an example of an effective anti-osteoporotic agent, used in treating osteoporosis due to both anti-resorptive and anabolic mechanisms of action. Designing bone scaffolds with a higher capability of promoting bone regeneration is a topical research subject. In this study, we developed composite multi-layer three-dimensional (3D) scaffolds for bone tissue engineering based on nano-hydroxyapatite (HA), Sr-containing nano-hydroxyapatite (SrHA), and poly-ε-caprolactone (PCL) through the material extrusion fabrication technique. Previously obtained HA and SrHA with various Sr content were used for the composite material. The chemical, morphological, and biocompatibility properties of the 3D-printed scaffolds obtained using HA/SrHA and PCL were investigated. The 3D composite scaffolds showed good cytocompatibility and osteogenic potential, which is specifically recommended in applications when faster mineralization is needed, such as osteoporosis treatment. Full article

Development of efficient controlled local release of drugs that prevent systemic side effects is a challenge for anti-osteoporotic treatments. Research for new bone-regeneration materials is of high importance. Strontium (Sr) is known as an anti-resorptive and anabolic agent useful in treating osteoporosis. In this study, we compared two different types of synthesis used for obtaining nano hydroxyapatite (HA) and Sr-containing nano hydroxyapatite (SrHA) for bone tissue engineering. Synthesis of HA and SrHA was performed using co-precipitation and hydrothermal methods. Regardless of the synthesis route for the SrHA, the intended content of Sr was 1, 5, 10, 20, and 30 molar %. The chemical, morphological, and biocompatibility properties of HA and SrHA were investigated. Based on our results, it was shown that HA and SrHA exhibited low cytotoxicity and demonstrated toxic behavior only at higher Sr concentrations. Full article