As survival rates for lung cancer (LC) patients continue to rise, the adverse impacts of therapies become more relevant. Radiotherapy is known to negatively affect bone health. However, radiotherapy-induced vertebral fractures in lung cancer patients remain an exceedingly rare and underrecognized condition that could be mistaken for bone metastasis.

We identified three LC patients (all long-term survivors), aged 67 to 81, who developed thoracic vertebral fractures post-chest radiotherapy, within irradiated fields; two had advanced non-small cell lung cancer (NSCLC) and one had extensive small cell lung cancer (SCLC). Baseline imaging confirmed that the fractures occurred after therapy. The median time from radiotherapy to fracture onset was 19 months (range: 1-30 months), with a median follow-up time from the initial fracture of 39 months (range: 37-61 months). All observed fractures were compressive in nature. These patients shared common characteristics, including advanced age, a history of heavy smoking, and high radiation doses. Additionally, hypermetabolic activity at the fracture sites necessitated MRI to differentiate these fractures from bone metastases. Management involved interventional strategies such as vertebroplasty, kyphoplasty, and rhizotomy, along with general and pharmacological measures to prevent subsequent fractures.

Despite their low incidence, radiotherapy-induced vertebral fractures in LC patients are clinically significant and may resemble bone metastases on PET-CT imaging. MRI, alongside risk factors similar to those of osteoporosis, can facilitate prompt identification and differentiation. As survival rates in LC patients improve, the relevance of this adverse effect increases, underscoring the need for implementing bone protective strategies to further enhance patient outcomes and quality of life.

Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased bone turnover with spine fractures and hypercalcemia; evidence of the DMAb withdrawal effect in oncology is lacking.

This study aimed to identify the DMAb withdrawal effect amongst lung cancer patients treated with DMAb for bone metastases between January 2020 and December 2021. Patients who discontinued DMAb were included. Encounter notes, radiological and laboratory findings were comprehensively reviewed.

Thirty patients were included with a median follow-up of 21 months (interquartile range [IQR], 10-30) after DMAb discontinuation. Bisphosphonates were administered before starting DMAb in 7 patients (23.3%) and after DMAb withdrawal in 4 cases (13.3%). Three cases of DMAb withdrawal-related hypercalcemia and 3 cases of spine fractures following DMAb cessation were identified in 5 patients (16.7%), all of them were females and the median age was 65 years old (IQR, 65-70). No statistical difference in DMAb duration or number of injections was found in patients developing DMAb withdrawal-related spine fractures or hypercalcemia compared with others (binary logistic regression, p=0.688 and p=0.938, respectively).

Patients with bony-metastatic lung cancer, especially post-menopausal women, are at risk of fractures and calcium abnormalities after DMAb discontinuation, suggesting that DMAb withdrawal effect may also be present in the oncological setting. A close follow-up and careful monitoring during and after discontinuation of DMAb is necessary.

Bone metastasis is a common cause of death in patients with non-small cell lung cancer (NSCLC), with approximately 30-40% of NSCLC patients eventually developing bone metastases. Bone metastasis, especially the occurrence of skeletal-related events (SREs), significantly reduces overall survival (OS) and quality of life (QoL) in patients. Although bone-targeting agents (BTAs) have been shown to reduce SREs and improve QoL in NSCLC patients with bone metastases, the prognosis for these patients remains poor. Understanding the underlying molecular pathways of bone metastasis is crucial for the development of novel therapeutic approaches. Bone metastasis is a complex, multistep process that involves interactions between tumor cells and the bone microenvironment. The bone microenvironment provides a fertile soil for tumor cells, and crosstalk among various signaling pathways and secreted factors also plays a role in regulating the occurrence and progression of bone metastasis in NSCLC. In this article, we provide a comprehensive review of the process, regulatory mechanisms, and clinical treatment in NSCLC bone metastasis, with the hope of assisting with clinical treatment.

Osteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed.

A retrospective cohort study was performed.

87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 → 241.41 HU ± 22.58 (p < 0.001) and 82.45 ± 9.13 → 179.38 ± 47.83p = 0.026). There was a significant increase in absolute difference of BMD between the SM and reference vertebrae (p < 0.001). There was no significant difference between SBRT and cEBRT. There was no increase of BMD in renal lytic SM after radiation therapy (pre-treatment: 85.96 HU ± 19.07; 3 m 92.00 HU ± 21.86 (p = 0.882); 6 m 92.06 HU ± 23.94 (p = 0.902); 9 m 70.44 HU ± 7.45 (p = 0.213); 12 m 98.08 HU ± 11.24 (p = 0.740)). In all other primary tumors, a significant increase of BMD after radiation therapy was demonstrated (p < 0,05).

We conclude that the BMD of lytic SM increases significantly after radiation therapy. Lytic SM of primary renal tumors are the exception; there is no significant remineralization of renal lytic SM after radiation therapy. There is no benefit of SBRT over cEBRT in this remineralization. These findings should be taken into account when deciding on surgery in the potentially unstable group defined by the spinal instability neoplastic score.

Lung cancer bone metastasis (LCBM) is a disease with a poor prognosis, high risk and large patient population. Although considerable scientific output has accumulated on LCBM, problems have emerged, such as confusing research structures.

To organize the research frontiers and body of knowledge of the studies on LCBM from the last 22 years according to their basic research and translation, clinical treatment, and clinical diagnosis to provide a reference for the development of new LCBM clinical and basic research.

We used tools, including R, VOSviewer and CiteSpace software, to measure and visualize the keywords and other metrics of 1903 articles from the Web of Science Core Collection. We also performed enrichment and protein-protein interaction analyses of gene expression datasets from LCBM cases worldwide.

Research on LCBM has received extensive attention from scholars worldwide over the last 20 years. Targeted therapies and immunotherapies have evolved into the mainstream basic and clinical research directions. The basic aspects of drug resistance mechanisms and parathyroid hormone-related protein may provide new ideas for mechanistic study and improvements in LCBM prognosis. The produced molecular map showed that ribosomes and focal adhesion are possible pathways that promote LCBM occurrence.

Novel therapies for LCBM face animal testing and drug resistance issues. Future focus should centre on advancing clinical therapies and researching drug resistance mechanisms and ribosome-related pathways.

Skeletal metastases make up 17% of all metastases from advanced-stage melanoma. Bone metastases are associated with increased morbidity and mortality and decreased quality of life due to their association with skeletal-related events (SREs), including pathological fracture, spinal cord compression, hypercalcemia, radiotherapy, and surgery. The study aimed to determine the incidence of bone metastases and SREs in melanoma, identify possible risk factors for the development of bone metastases and SREs, and investigate survival rates in this patient population.

A computer-based literature search was conducted using Pubmed, Embase, and Cochrane Central Register of Controlled Trials up to July 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was utilized for quality assessment. Study characteristics, patient information, risk factors for developing bone metastases and SREs, and characteristics for survival were recorded.

We included 29 studies. The average bone metastasis-free interval ranged from four to 72 months. Incidence of bone metastases varied from 2 % to 49 % across 14 studies. 69 % (20/29) of studies described the location of bone metastases, with 24 % (7/29) focusing solely on spinal metastases. In one study, 129 SREs were recorded in 71 % (59/83) of the patient cohort, with various manifestations. The use of bone-directed agents was independently associated with lower risk of SREs. Survival after detection of bone metastasis ranged from three to 13 months. Factors associated with survival included clinical, tumor-related, and treatment features.

This review highlights the notable prevalence and risk factors of developing bone metastases and subsequent SREs in patients with melanoma. The surge in bone metastases poses a challenge in complication management, given the high prevalence of SREs. While this study offers a comprehensive overview of the incidence, risk factors, and outcomes associated with bone metastases and SREs in melanoma patients that may guide patient and physician decision-making, a notable gap lies in the limited availability of high-quality data and the heterogeneous design of the existing literature. Future research should address predictive factors for bone metastases and SREs in melanoma to facilitate patient and physician decision-making and ultimately improve outcomes in this patient population.

Targeted therapy has greatly improved the outlook for patients with spinal metastatic cancers. Scoring systems like the Tokuhashi or Tomita scores are commonly used to predict prognosis and inform surgical decisions, but they are outdated and fail to consider recent advancements. We aimed to investigate the current state of the literature and treatment options pertaining to advancements in targeted therapy compared to other forms of medical management for metastatic spinal tumors. This study represents the first comprehensive systematic review that encompasses the most common primary cancers that metastasize to the spine and evaluates the median overall survival (mOS) across five different medical treatment modalities as well as surgical intervention. Additionally, our study analyzes the tumor receptor status in conjunction with these treatments. A PubMed search was conducted, and according to the PRISMA guidelines, 28 articles out of 1834 met the inclusion criteria. The pooled data analysis highlighted the superior efficacy of targeted therapy, evidenced by a significant improvement in the mOS and lower hazard ratios in patients with lung and breast cancers who received targeted therapy compared to those who did not. Our study provides valuable insights into the recent advancements in the medical management of metastatic spinal tumors. Future indications include incorporating this literature into personalized treatment approaches for metastatic spinal tumors.

During the course of lung cancer progression, bone metastases occur in about 40% of patients. Common complications associated with bone metastases in lung cancer patients include musculoskeletal pain, pathologic fractures, spinal cord compression, and hypercalcemia. We discuss the efficacy of bone-modifying agents (BMAs) in reducing skeletal-related events (SREs) and improving cancer-related outcomes, particularly in patients with stage IV non-small-cell lung cancer with bone metastases. In addition, the combined effects of BMAs with radiotherapy or immunotherapy in reducing SREs in patients with lung cancer and bone metastases are explored.

We investigated the incidence/trend of osteonecrosis of the jaw by antiresorptive agent dose over a 5-year period in Kure city, Japan. The incidence was 24 times higher among osteoporosis patients with low-dose agents and 421 times higher among cancer patients with high-dose agents than in the population without agents.

We launched the registry system of osteonecrosis of the jaw (ONJ) cases in 2015 to investigate the trend in ONJ incidence. The purpose of our study was to estimate the ONJ incidence among patients with antiresorptive agent use by dosage and people without antiresorptive agent use in Kure and its trend from 2016 to 2020.

From 2016 to 2021, 98 eligible ONJ patients were enrolled. Medication-related ONJ (MRONJ) was diagnosed based on the American Association of Oral and Maxillofacial Surgeons criteria. The annual number of those with and without antiresorptive agents was obtained from the claims database. Antiresorptive agents used for cancer and osteoporosis patients were defined as high- and low-dose medications, respectively.

The annual incidence of high-dose MRONJ was 2305.8 per 100,000 and that of low-dose MRONJ was 132.5 per 100,000, while the ONJ incidence among people without antiresorptive agents was 5.1 per 100,000. The incidence ratio was 23.6 (p < 0.001, 95% confidence interval (CI) 13.3-41.8) among osteoporosis patients who used low-dose antiresorptive agents and 420.6 (p < 0.001, 95% CI 220.8-801.4) among cancer patients who used high-dose agents compared with people who did not use these agents. MRONJ incidence increased from 2016 to 2020, but the incidence of high-dose MRONJ decreased, although this was nonsignificant.

We demonstrated the incidence and trend of ONJ by antiresorptive agent dose over a 5-year period in Kure after launching the multiprofession study. This collaborative study for the early detection and prevention of ONJ will continue.

Bone metastasis is frequently common in advanced lung cancer with the major issue of a pathological fracture. Previous studies suggested that Astragalus membranaceus (Qi) and Ampelopsis japonica (Lian), which are used as folk medicine in China, have potential effects on inhibiting tumor growth and protecting bones, respectively. In this study, an experiment on the inhibitory effect of the Qilian formula (AAF) in vivo was designed to examine tumor growth in bone and osteoclast formation.

The bone metastasis xenograft models were established by implanting NCI-H460-luc2 lung cancer cells into the right tibiae bones of mice. After confirming the model's viability through optical imaging 7 days post-implantation, 2 groups, namely the AAF group and the control group, were administered 0.3 mL of AAF extract (9 g/kg/day) or normal saline via intragastric delivery for a duration of 4 weeks. Throughout the study, we longitudinally assessed tumor burden, bone destruction, and weight-bearing capacity in vivo using reporter gene bioluminescence imaging (BLI), micro-CT, and dynamic weight-bearing (DWB) tests. Mechanistic insights were gained through Hematoxylin-eosin (H&E) staining, immunohistochemical (IHC) analysis, western blotting, and flow cytometry.

Qilian formula produced significant inhibition to the progress of bone destruction and tumor burden in the right tibiae bone in the treatment group. It was further evidenced by molecular imaging in vivo via small animal micro-CT and BLI with parametric quantification, characterizing significantly lower uptake of BLI signal in the treated tumor lesions and improving the pathological changes in the microstructure of bone. Furthermore, DWB tests revealed that Qilian formula treatment significantly maintained the weight-bearing capacity. According to immunohistochemical analysis, the effect of the Qilian formula appeared to involve the suppression of osteoclast formation by lower expression of the tartrate-resistant acid phosphatase. Cell apoptosis and death induction were evidenced by a higher percentage of Bal2、BAX and caspase 3 expressions of Qilian formula-treated tumor tissues.

Our study demonstrated a significant inhibitory effect of the Qilian formula on the progression of osteolytic invasion in vivo by suppressing osteoclastogenesis and promoting apoptotic cell death.