Background/Objective: Surgical treatment of aneurysmal bone cysts (ABCs) can be challenging, especially in the spine. Non-surgical treatments such as with denosumab have shown promising results in different osteolytic pathologies. This retrospective observational study aimed to evaluate the long-term clinical and radiologic response of patients with ABCs of the mobile spine treated with denosumab and propose an updated treatment algorithm. Methods: Six patients with relapsed and symptomatic ABCs of the mobile spine were treated with denosumab (120 mg subcutaneously on days 1, 8, 15, 29, and every 4 weeks thereafter) between 2012 and 2023. Disease assessments were conducted using CT and MRI at 3, 6, 9, and 12 months post-treatment. Clinical data, including pain levels, symptoms, and adverse events, were documented from patients\' charts. Results: Patients underwent an initial phase of treatment with denosumab, receiving a mean of 22 administrations (range 13-42) over a median follow-up period of 41 months (range 15-98 months). Clinical improvement was observed in all patients after 4 weeks of treatment, and all patients demonstrated a radiological response after 12-24 weeks on denosumab. Three patients were progression-free after discontinuing denosumab following 13, 15, and 42 administrations, respectively. At the last follow-up, after 38, 43, and 98 months, these patients remained stable without relapse of the disease. Three patients had a relapse of disease after denosumab; two of them underwent denosumab re-challenge, while one patient received one mesenchymal stem cells (MSCs) injection. All patients showed clinical and radiological improvement and were resulted to be disease-free at the last follow-up. Conclusions: This study demonstrates the long-term efficacy and safety of denosumab in treating ABCs of the mobile spine, as well as the potential of re-challenge in managing recurrence. A treatment algorithm is proposed, positioning denosumab as a viable therapeutic option after other local treatments. Careful patient selection, monitoring, and further research are necessary to optimize denosumab use for ABCs.

Primary intraosseous malignant peripheral nerve sheath tumors (MPNSTs) are rare yet highly aggressive neoplasms originating from peripheral nerves. Typically manifesting as soft tissue masses accompanied by pain or functional impairment, these tumors pose significant challenges in management. Surgical intervention remains the cornerstone of treatment for patients with MPNST lacking distant metastasis, with generally modest success rates. In cases of recurrence and metastasis, the pursuit of effective systemic therapies has been a focus of clinical investigation. Herein, we present a case study involving an elderly female patient with refractory MPNST. In light of surgical limitations, a multimodal therapeutic approach combining chemotherapy, denosumab, and subsequent administration of anlotinib was pursued following collaborative consultation. This regimen yielded noteworthy clinical benefits, exemplifying a promising avenue in the management of challenging MPNST cases.

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OBJECTIVE: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS raises awareness to the prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with breast cancer treated with adjuvant bone-modifying agents (BMA).
METHODS: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care.
RESULTS: In patients treated with adjuvant BMA, dento-alveolar surgery poses a moderate risk for MRONJ that ranges between the high risk for MRONJ in patients with metastatic breast cancer and the low risk for MRONJ in patients with osteoporosis. Existing MRONJ guidelines serve as a starting point for adjuvant BMA use. Urgent procedures should be delivered without delay using the accepted precautions to prevent MRONJ. If elective surgery is considered, the individual risk for MRONJ following surgery should be assessed according to common risk factors.
CONCLUSIONS: Prevention of MRONJ in primary breast cancer patients treated with adjuvant BMA requires risk-benefit assessment; collaboration between the medical team, dental professional, and patient; and patient-specific tailored dental treatment planning. The patient should be informed about this risk. Additional research is needed to define optimal MRONJ care for this population.

Medication-Related Osteonecrosis of the Jaw (MRONJ) is a challenging and evolving aspect of Oral and Maxillofacial Surgery. In recent years, several medications apart from those traditionally associated with MRONJ such as bisphosphates (BPs) and Denosumab (DMB) have been implicated in bony necrosis of the jaw. This aim of this report is to demonstrate a significant case of bone necrosis following dental extractions on a patient being treated with infliximab therapy for Crohn\'s disease. Several cases in literature have reported MRONJ associated with infliximab but very few patients have developed as significant a form of the disease as seen in this report. Previous investigators have proposed pathophysiological pathways via which TNF-α inhibitors such as infliximab have a causative mechanism for MRONJ. When osteoclastic activity is restricted via these pathways, bone healing is impaired and MRONJ can occur. However, it remains a diagnostic challenge to differentiate between antiresorptive MRONJ and chronic osteomyelitis with bone necrosis in patients with acquired immunodeficiency. This case aims to illustrate why the antiresorptive effects of TNF-α inhibitors need to be considered as a possible primary driver of bone necrosis in such patients.

Purpose Medication-related osteonecrosis of the jaw (MRONJ) is a serious side effect of antiresorptive agents such as bisphosphonates (BPs) and denosumab (DMB). We investigated whether a difference exists between BP- and DMB-related osteonecrosis of the jaw (ONJ). Patients and methods Histological images of 30 patients with BP-related ONJ and 13 patients with DMB-related ONJ were observed using hematoxylin-eosin and cathepsin K staining. Moreover, bone metabolism markers in the blood and bone mineral density were measured in 18 patients with BP-related ONJ and five patients with DMB-related ONJ. Furthermore, we conducted a quantitative analysis of local bone metabolism-related genes using surgical specimens through real-time reverse transcription polymerase chain reaction. Additionally, a retrospective study of 298 patients with MRONJ examined the differences in the characteristics of BP- and DMB-related ONJ and the factors associated with treatment outcomes. Results Histological examination revealed that patients treated with DMB had more severe osteoclast suppression than those treated with BP. No significant difference was observed in blood-bone metabolism markers between the two drugs; however, the suppression of local bone metabolism-related genes was stronger in patients treated with DMB. Clinical studies indicate that DMB-related ONJ is more frequently observed without osteolysis. Conclusion BP-associated ONJ and DMB-associated ONJ were shown to differ slightly. Clinical studies indicate that osteolysis is often unclear in DMB-related ONJ, and methods of bone resection during surgery need to be established.

Bone is a dynamic tissue. It remodels, preserving serum calcium, repairing microdamage, and maintaining strength. Osteoporosis is caused by a decrease in bone strength, which manifests clinically as low-energy vertebral and non-vertebral fractures. Osteoporosis poses a significant public health challenge. While it\'s often portrayed as primarily impacting postmenopausal women, there\'s been growing recognition among researchers and clinicians regarding its prevalence in men. Major fracture in men has higher mortality rates than in women. Denosumab is a fully human monoclonal immunoglobulin G2 (IgG2) antibody that binds to RANKL, the principal regulator of osteoclastic bone resorption. Multiple studies suggest that denosumab is both effective and safe, exhibiting higher adherence rates and greater patient satisfaction. In this narrative review, we highlighted the effects of denosumab in men with osteoporosis, subsequent changes in bone mineral density, and bone turnover markers outlining the literature and guideline support.

UNASSIGNED: There are challenges for the treatment of osteoporosis in patients with kidney failure and monoclonal antibodies (MAb) might be a suitable therapy. However, the efficacy and safety of MAb among patients with osteoporosis and renal insufficiency remains unclear.
UNASSIGNED: We systematically searched PubMed, Embase, and Cochrane Central for studies evaluating the efficacy and safety of the use of MAb in patients with osteoporosis and renal insufficiency. We pooled risk ratios (RR) and 95% confidence intervals (CI) for binary outcomes. Mean difference (MD) was used for continuous outcomes.
UNASSIGNED: We included 5 studies with 33,550 patients. MAb therapy decreased the risk of vertebral fractures (RR 0.32; 95% CI 0.26-0.40; P < 0.01) when compared to placebo and no statistical difference was found when comparing to bisphosphonate (RR 0.71; 95% CI 0.49-1.03; P = 0.07). MAb therapy also decreased the risk of nonvertebral fractures (RR 0.79; 95% CI 0.69-0.91; P = 0.0009). Lumbar spine bone mineral density (BMD) was higher in the MAb therapy when compared to both placebo (MD 10.90; 95% CI 8.00-13.80; P < 0.01) and bisphosphonate (MD 7.66; 95% CI 6.19-9.14; P < 0.01). There was no statistically significant difference in the change of estimated glomerular filtration rate and in the incidence of hypocalcemia and serious adverse events between groups.
UNASSIGNED: There were reductions in both vertebral and nonvertebral fracture risks, alongside improvements in BMD among patients with renal insufficiency treated with MAb.

OBJECTIVE: To analyze osteoporosis medication prescribing trends across specialties in the context of a Bone Health Clinic.
BACKGROUND: Osteoporosis affects over 10 million adults in the US, taking a significant toll on patients and the healthcare system. Although screening methods and treatments are improving, the disease remains underdiagnosed and undertreated. This study aims to evaluate the prescribing trends of osteoporosis medication among department specialties to delineate the benefits of a bone health clinic.
METHODS: Retrospective data collection identified and analyzed patients within the Penn State Health system prescribed one of the following osteoporosis medications: Bisphosphonate, denosumab, romosozumab, teriparatide, abaloparatide, or raloxifene. Date range: 4/18/2016 to 4/14/2021. Data collection identified the specialty origin of prescriptions for osteoporosis medications across various medical specialties (e.g., orthopaedics, family medicine, and internal medicine).
RESULTS: 10,736 prescription orders were issued to patients with an average age of 68 years. Non-Hispanic Caucasian patients received 88.6% of prescriptions, followed by Asian (3.4%) and African American (2.2%). Female patients accounted for 87.8% of all prescriptions. The Bone Health Clinic under two orthopaedic providers wrote 3,619 prescriptions, averaging 361.9 prescriptions per provider per year-marking the highest rate among specialties. The clinic prescriptions constituted 33.7% of all prescriptions across specialties. Orthopaedic surgery prescribed the most denosumab, romosozumab, teriparatide, and abaloparatide prescriptions, and had the highest number of male osteoporosis patients compared to other specialties (15.6%), consequently prescribing the most male prescriptions (578).
CONCLUSIONS: Establishing a bone health clinic dedicated to osteoporosis management leads to significantly higher prescription rates per provider, increased utilization of anabolic therapies compared to other specialties, and more male patients being treated-an often-neglected population in osteoporosis.

BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness.
METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness.
RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients\' LRFS and OS.
CONCLUSIONS: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.