Incidence and Risk Factors of Hypomagnesemia in Patients With Bone Metastasis From Solid Malignancies Treated With Denosumab: A Retrospective Chart Review.

BACKGROUND: Hypomagnesemia is associated with poor clinical outcomes in cancer patients. Patients with bone metastasis from solid malignancies receiving denosumab (Dmab) to prevent skeletal-related events often receive concurrent antineoplastic agents for cancer treatment. The incidence and risk factors of hypomagnesemia in patients receiving Dmab and the optimal frequency of monitoring serum magnesium (Mg) levels have not been studied in these patient populations. OBJECTIVE: The objective is to investigate the incidence and potential risk factors of hypomagnesemia and the optimal frequency of monitoring serum Mg levels. METHODS: A retrospective chart review identified patients with solid malignancies with bone metastases treated with Dmab at the Loma Linda University Cancer Center between January 2013 and February 2024. The incidence of hypomagnesemia was determined using the number of patients with hypomagnesemia and the total number of patients in the study. Univariate and multivariate logistic regression analyses identified risk factors for hypomagnesemia. RESULTS: Hypomagnesemia was observed in 19% (29/153) of patients, the majority of whom were on concurrent antineoplastic agents with ≥15% hypomagnesemia incidence (high-hypomagnesemic antineoplastics) or nonantineoplastic drugs with documented cases or incidence of hypomagnesemia (hypomagnesemic nonantineoplastics) in addition to high-hypomagnesemic antineoplastics. Multivariate analysis showed increased odds of developing hypomagnesemia with high-hypomagnesemic antineoplastics (odds ratio [OR]: 174.93, 95% confidence interval [CI]: 12.82 to 387.43, P < 0.001); hypomagnesemic nonantineoplastics plus high-hypomagnesemic antineoplastics (OR: 210.09, 95% CI: 11.80 to 3740.12, P < 0.001); and Mg level ≤ 0.85 prior to Dmab administration (OR: 16.79, 95% CI: 2.30 to 122.41, P = 0.005). CONCLUSION AND RELEVANCE: This study describes the incidence and potential risk factors for hypomagnesemia in patients with solid malignancies and metastatic bone disease treated with Dmab. This study's findings provide additional clinical insight into potential risk factors for hypomagnesemia and the need for more frequent serum Mg level monitoring of at-risk patients. Future prospective studies are needed to determine the exact frequencies most appropriate in monitoring serum Mg levels in this group of patients.

What Abductor Repair Technique Provides the Best Functional Outcomes After Proximal Femur Endoprosthetic Reconstruction for Oncologic Indications? A Systematic Review.

BACKGROUND: There is conflicting data regarding the optimal abductor mechanism (AM) repair technique after resection of proximal femur tumors. We sought to compare functional outcomes following tumor resection and reconstruction with proximal femoral replacement based on the AM repair technique utilized. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We established two study groups based on AM repair technique as follows: soft-tissue reattachment (STr) and greater trochanter preservation (GTp). In the STr group, the gluteus medius and minimus muscles were reattached to the endoprosthesis, whereas in the GTp group, the greater trochanter and gluteal tendons were preserved. The STr group was further subdivided into direct and indirect reattachments. Weighted means adjusting for sample size were calculated. RESULTS: A total of 658 patients from 12 articles were included. Patients who had STr displayed higher Musculoskeletal Tumor Society scores (75 versus 67.3%, P < 0.001), lower rates of Trendelenburg gait (33.9 versus 52.4%, P < 0.01), and ambulation with assistive devices (30.4 versus 54.9%, P < 0.001) compared to the GTp group. Within the STr group, indirect reattachment was associated with higher Musculoskeletal Tumor Society scores (87.2 versus 70.1%, P < 0.001) and lower rates of Trendelenburg gait (3.8 versus 36.3%, P < 0.001) and ambulation with assistive devices (0 versus 42.4%, P < 0.001) compared to direct reattachment. The reattachment hardware failure rate in GTp was 15%. CONCLUSION: A STr provided superior functional outcomes compared to GTp in tumor-related proximal femoral replacement. From a functional outcome perspective, the use of indirect STr was better compared to direct STr. LEVEL OF EVIDENCE: III.

Outcomes of distal femoral replacement versus internal fixation for metastatic bone diseases of the distal femur.

Background: In clinical practice, internal fixation (IF) is a commonly utilized technique for metastatic bone disease (MBD) to the distal femur. Additionally, distal femoral reconstruction (DFR) has shown to be an effective surgical technique for primary tumors and MBD in the distal femur. The existing body of research comparing these methods has not focused on MBD or pathological fractures and thus does not guide surgical approach in the case of distal femoral MBD. Methods: A multi-institutional retrospective review of musculoskeletal oncology patients treated surgically with IF (n = 29) or DFR (n = 34) for distal femoral MBD between 2005 and 2023. Overall survival, revision risk, and functional status were assessed. Results: 5-year patient overall survival was 47.9 % (CI, 29.5-77.6 %) and 46.6 % (CI, 31.5-68.8 %), for DFR and IF, respectively (p = 0.91). After competing risk analysis, the 5-year risk of implant revision for DFR was 18 % (95 % CI: 5.1-37 %) and 11 % for IF (95 % CI: 2.4-28 %) (p = 0.3). DFR had longer operative times (p = 0.002), higher blood loss (p < 0.001), and greater postoperative (p = 0.006) complications than IF. In addition, patients undergoing DFR had more distal lesions than patients who received IF (p = 0.003). Conclusion: Despite similar overall survival and revision rates, IF may be preferable for patients due to its shorter operative time and lower rates of complication than DFR. However, specific anatomic location in the distal femur must be considered prior to deciding which procedure is optimal.

Comparing long and intermediate-length plates for metastatic bone disease of the proximal humerus: A retrospective analysis.

AIMS: Managing proximal humerus pathologic fractures requires strategic planning to ensure optimal patient outcomes. Traditionally, fixation of the humerus using long devices has been considered the standard of care, but emerging evidence has challenged this approach. This study aimed to compare long plates (LPs) and intermediate-length plates (IPs) in this clinical context. METHODS: Forty-four patients with proximal humerus metastatic bone disease were retrospectively studied from 2013 to 2019, with 11 (25%) receiving long plates (LPs) and 33 (75%) intermediate-length plates (IPs). Outcomes included tumor progression, reoperation rates, postoperative anemia, blood loss, operation time, and hospitalization duration. Tumor progression was classified into three categories, with Type III progression (new metastatic lesions in the distal humerus) theoretically benefiting most from whole bone stabilization. RESULTS: Tumor progression occurred in three patients (7%), all of them was in IPs. No revision surgery was needed to address these tumor progressions, including one type III progression which occurred 34 months postoperatively after IP surgery. IP were associated with a reduced operation time compared with LP (median, 1.5 h [IQR, 1.2-1.9] vs. 2.4 [IQR, 1.7-2.5]; p = 0.004). No differences were found for the other perioperative outcomes. CONCLUSIONS: Our findings reveal a low incidence of tumor progression and low reoperation rates in both groups. The shortened operative time associated with IP use suggests its particular suitability for patients with limited life expectancy. Further research is needed to elucidate the ideal prosthesis length that best balances the risks and benefits when addressing proximal humerus metastatic disease.

Deep Learning for Delineation of the Spinal Canal in Whole-Body Diffusion-Weighted Imaging: Normalising Inter- and Intra-Patient Intensity Signal in Multi-Centre Datasets.

BACKGROUND: Whole-Body Diffusion-Weighted Imaging (WBDWI) is an established technique for staging and evaluating treatment response in patients with multiple myeloma (MM) and advanced prostate cancer (APC). However, WBDWI scans show inter- and intra-patient intensity signal variability. This variability poses challenges in accurately quantifying bone disease, tracking changes over follow-up scans, and developing automated tools for bone lesion delineation. Here, we propose a novel automated pipeline for inter-station, inter-scan image signal standardisation on WBDWI that utilizes robust segmentation of the spinal canal through deep learning. METHODS: We trained and validated a supervised 2D U-Net model to automatically delineate the spinal canal (both the spinal cord and surrounding cerebrospinal fluid, CSF) in an initial cohort of 40 patients who underwent WBDWI for treatment response evaluation (80 scans in total). Expert-validated contours were used as the target standard. The algorithm was further semi-quantitatively validated on four additional datasets (three internal, one external, 207 scans total) by comparing the distributions of average apparent diffusion coefficient (ADC) and volume of the spinal cord derived from a two-component Gaussian mixture model of segmented regions. Our pipeline subsequently standardises WBDWI signal intensity through two stages: (i) normalisation of signal between imaging stations within each patient through histogram equalisation of slices acquired on either side of the station gap, and (ii) inter-scan normalisation through histogram equalisation of the signal derived within segmented spinal canal regions. This approach was semi-quantitatively validated in all scans available to the study (N = 287). RESULTS: The test dice score, precision, and recall of the spinal canal segmentation model were all above 0.87 when compared to manual delineation. The average ADC for the spinal cord (1.7 × 10-3 mm2/s) showed no significant difference from the manual contours. Furthermore, no significant differences were found between the average ADC values of the spinal cord across the additional four datasets. The signal-normalised, high-b-value images were visualised using a fixed contrast window level and demonstrated qualitatively better signal homogeneity across scans than scans that were not signal-normalised. CONCLUSION: Our proposed intensity signal WBDWI normalisation pipeline successfully harmonises intensity values across multi-centre cohorts. The computational time required is less than 10 s, preserving contrast-to-noise and signal-to-noise ratios in axial diffusion-weighted images. Importantly, no changes to the clinical MRI protocol are expected, and there is no need for additional reference MRI data or follow-up scans.

Does Perioperative Radiation Affect Implant Survivorship of Primary Total Hip Arthroplasty in the Setting of Metastatic Bone Disease?

Background: Metastatic bone disease (MBD) commonly affects the hip and surgical intervention including total hip arthroplasty (THA) is often indicated to treat the joint and improve function. Patients with metastatic cancer often receive radiotherapy, and orthopaedic oncologists must consider surgical risks with operating on irradiated bone and soft tissue. We evaluated surgical outcomes and implant survival (IS) of titanium acetabular components and femoral components in patients treated for MBD in the setting of perioperative radiation. Methods: This was a retrospective review of patients who underwent THA for MBD at 3 institutions between 2017 and 2021. Outcomes included rates of reoperation, complications, IS, and overall survival. Results: Forty-six patients who received primary THA for MBD were included in the study. Twenty patients (43.5%) received perioperative radiation for MBD. Six postoperative complications including one superficial wound infection, 2 dislocations, 2 pathologic fractures, and one aseptic acetabular component loosening led to 5 reoperations. There were no significant differences in postoperative outcomes, reoperation after THA, and IS based on radiotherapy status. Conclusions: To our knowledge, this is the first paper evaluating primary THA outcomes and IS between patients who receive perioperative radiation for MBD to the hip and those who do not. As surgical management is a crucial part of the treatment in alleviating pain and disability in patients with MBD, we continue to recommend THA for patients who received radiation at the operative site.

[Acetabular metastatic defect reconstruction using the modular revision support cup MRS-C]. / Rekonstruktion von metastasenbedingten Defekten des Azetabulums mittels der MRS-C-Abstützschale.

OBJECTIVE: Stabilization of metastatic acetabular defects with a bone cement-augmented revision support cup for remobilization of oncological patients in advanced cancer stages. INDICATIONS: Metastatic acetabular defects (Metastatic Acetabular Classification, MAC 2-4) in patients with a prognostic medium or long-term survival. CONTRAINDICATIONS: Highly limited survival due to metastatic disease (< 6 weeks). Local bone or soft tissue infection. Primary bone tumor with curative treatment option. Advanced pelvic discontinuity. Recent wound compromising systemic therapy. SURGICAL TECHNIQUE: Standard hip approach. Curettage of the metastatic defect and careful reaming of the acetabulum before insertion of the cup. Predrilling of the dome und flange screws before application of the bone cement through the center hole of the implant and filling of the acetabular defect. Complete insertion of the screws for compound osteosynthesis. Implant of a modular inlay or dual mobility system. POSTOPERATIVE MANAGEMENT: Full weight bearing or mobilization with two crutches according to the level of pain. Adjuvant local radiation therapy after wound consolidation. Continuation of systemic therapy according to tumor board decision. RESULTS: Between 2012 and 2019, we treated 14 patients with metastatic acetabular defects using the modular revision support cup "MRS-TITAN® Comfort", MRS-C, Peter Brehm GmbH, Weisendorf, Germany) at our institution. Mean Harris Hip Score improvement was 23.2 with a mean patient's survival of 9.7 months due to the reduced cancer-related prognosis; 13 of the 14 implants endured the patient's prognosis. One implant had to be removed due soft tissue defect-related periprosthetic joint infection.

Subtrochanteric nonunion after intramedullary nailing due to pathological fracture: proximal femoral replacement as a salvage approach.

PURPOSE: To assess proximal femoral replacement as a treatment solution for nonunion of pathologic subtrochanteric fractures after cephalomedullary nailing in patients with pathological fracture and previously irradiated bone. METHODS: Retrospective review of five patients with pathological subtrochanteric femoral fractures that were treated with cephalomedullary nailing and developed a nonunion, which was revised with conversion to a proximal endoprosthetic replacement. RESULTS: All five patients had previously been treated with radiation. One patient had the latest follow-up at 2 months postoperatively. At that time, the patient was walking with a walker for assistance, with no evidence of hardware failure or loosening on imaging. The remaining four patients had the latest follow-up ranging from 9 to 20 months after surgery. At their latest follow-up, three of the four patients were ambulatory with no pain, using only a cane for assistance with longer distances. The other patient demonstrated pain in his affected thigh, utilizing a walker for assistance with ambulation at latest follow-up, but not requiring further surgical interventions. There were no hardware failures or implant loosening through the follow-up period. None of the patients required revision, and there were no postoperative complications observed at their last follow-up. CONCLUSIONS: In patients with pathological fractures in the subtrochanteric region that is treated with cephalomedullary nailing and developed a nonunion, treatment with conversion to a proximal femoral replacement with a mega prosthesis is a valuable treatment with good functional results and low risk for complications. LEVEL OF EVIDENCE: Therapeutic level IV.

Treatment of Epiphyseal Metastasis to the Proximal Humerus Secondary to Breast Carcinoma: A Case Report.

Metastasis to the bone is a known risk of breast cancer, with the humerus being the most common upper extremity site of metastases, with most lesions located at the humeral diaphysis. We present a unique case of proximal humeral metastasis involving the epiphysis secondary to primary invasive ductal carcinoma in a middle-aged Caucasian female. It is important to have a high degree of suspicion for metastasis when musculoskeletal pain occurs in breast cancer patients, as it may be masked by common, degenerative conditions about the shoulder girdle. When humeral metastases involve the epiphysis, treatment options are complicated by its location, which jeopardizes the integrity of articular cartilage and the function of the shoulder girdle. External beam irradiation provides pain control in a non-invasive manner, sans surgical risks. Surgical intervention will vary depending on the characteristics of the bony lesion, but the use of endoprosthetics has emerged as the most effective option for restoring range of motion and pain control with acceptable rates of implant survival.

Racial and Ethnic Disparities in Metabolic Bone Disease.

Racial and ethnic disparities exist in the prevalence and management of osteoporosis, metastatic cancer, and sickle cell disease. Despite being the most common metabolic bone disease, osteoporosis remains underscreened and undertreated among Black women. Skeletal-related events in metastatic cancer include bone pain, pathologic fractures, and spinal cord compression. Disparities in screening for and treating skeletal-related events disproportionately affect Black patients. Metabolic bone disease contributes significantly to morbidity in sickle cell disease; however, clinical guidelines for screening and treatment do not currently exist. Clinical care recommendations are provided to raise awareness, close health care gaps, and guide future research efforts.

Intramedullary brachytherapy for the treatment of long bone metastatic disease: A case report.

Case: A 56-year-old woman with metastatic melanoma and femoral lesions with impending pathologic fracture was indicated for intramedullary brachytherapy (IMBT) and intramedullary nail. Conclusions: IMBT + intramedullary nail is a new technique for the treatment of long bone metastases. IMBT maximizes radiation to the tumor and minimizes radiation to surrounding tissues. It allows the patient to resume systemic treatment expediently. Our cadaver model and patient were both treated for femoral metastases; however, this technique allows for the treatment of any long bone. This is a safe technique that minimizes treatment time compared with other standard radiation regimens.

Quantitative vs. Qualitative SPECT-CT Diagnostic Accuracy in Bone Lesion Evaluation-A Review of the Literature.

(1) Background: Considering the importance that quantitative molecular imaging has gained and the need for objective and reproducible image interpretation, the aim of the present review is to emphasize the benefits of performing a quantitative interpretation of single photon emission computed tomography-computed tomography (SPECT-CT) studies compared to qualitative interpretation methods in bone lesion evaluations while suggesting new directions for research on this topic. (2) Methods: By conducting comprehensive literature research, we performed an analysis of published data regarding the use of quantitative and qualitative SPECT-CT in the evaluation of bone metastases. (3) Results: Several studies have evaluated the diagnostic accuracy of quantitative and qualitative SPECT-CT in differentiating between benign and metastatic bone lesions. We collected the sensitivity and specificity for both quantitative and qualitative SPECT-CT; their values ranged between 74-92% and 81-93% for quantitative bone SPECT-CT and between 60-100% and 41-100% for qualitative bone SPECT-CT. (4) Conclusions: Both qualitative and quantitative SPECT-CT present an increased potential for better differentiating between benign and metastatic bone lesions, with the latter offering additional objective information, thus increasing diagnostic accuracy and enabling the possibility of performing treatment response evaluation through accurate measurements.

Thermal necrosis in orthopedic bone tumors: experimental research.

Introduction: The extent of surgical resection in orthopedic oncology differs according to tumor biology. While malignant bone tumors are operatively managed with wide resection, benign bone tumors and metastatic carcinomas are often treated through intralesional excision and adjuvant modalities, including the elimination of residual neoplastic cells through thermal necrosis. This study investigates in vitro temperature thresholds for thermal necrosis in common orthopedic bone tumors. Methodology: Eleven cell lines, including metastatic carcinomas to bone (A549, A498, FU-UR-1, PC3, MDA-MB-231, TT, MCF7, and K1), giant cell tumor of bone, osteosarcoma (HG-63), and control non-neoplastic cells (HEK293) were cultured. Cells were exposed to thermal stress at varying times and temperatures and evaluated for survival and viability with crystal violet and MTT assays. Results: Both the MTT and crystal violet assay demonstrated statistically superior rates of viability and survival for A549 (lung carcinoma), FU-UR-1 (renal carcinoma), K1 (thyroid carcinoma), and MG-63 (osteosarcoma) cell lines compared to control (HEK293 cells) at 60°C. Additionally, the MTT assay demonstrated superior viability for PC3 (prostate carcinoma), MCF7 (breast carcinoma), and A498 (renal carcinoma) compared to control. All cell lines demonstrated significantly decreased survival and viability in temperatures more than 90°C. Conclusion: This study demonstrated in vitro thresholds for thermal necrosis for cell lines of common orthopedic tumors of bone. The A549 (lung carcinoma), K1 (thyroid carcinoma), and FU-UR-1 (renal carcinoma) cell lines demonstrated greater resistance to heat stress compared to non-neoplastic control cells. Temperatures in excess of 90°C are necessary to reliably reduce cell survival and viability to less than 10%.

Functional outcomes after open reconstruction or nonoperative management of 81 pathologic acetabular fractures from metastatic bone disease.

Background: Pathologic acetabular fracture secondary to skeletal metastasis may result in debilitating pain, inability to ambulate, and impaired quality of life, which may mark the first period of dependent care in cancer patients. Acetabular reconstruction may involve morbid procedures with increased complication rates. This study aimed to evaluate the evolution of pain, performance status, and ambulation following nonoperative management or open reconstruction of pathologic acetabular fractures. Methods: A retrospective cohort of 2630 adult patients with osseous metastatic disease treated at a high-volume cancer center between 2005 and 2021 was screened for pathologic fractures of the acetabulum. The study outcomes were pain, performance status, and the ability to ambulate. We identified 78 patients (median age, 60 years; 37 female patients [46%]) with 81 fractures. Of these, treatment consisted of open reconstruction (n = 34) or nonoperative management alone (n = 47). The mean follow-up in surviving patients was 3.4 years. Results: Open reconstruction was performed more frequently for displaced fractures (P < 0.01), Harrington class III or IV acetabula (P < 0.01), and patients with a performance status ≥3 at hospitalization (P = 0.00). Open reconstruction was associated with clinically meaningful improvements in pain (adjusted odds ratio [aOR], 8.3; 95% CI, 1.4-50.6; P = 0.02) and performance status (aOR, 10.9; 95% CI, 1.7-71.0; P = 0.01) at discharge and a restoration of ambulation (aOR, 7.5; 95% CI, 1.9-29.8; P < 0.01) at final follow-up. Conclusions: In patients with pathologic acetabular fracture due to osseous metastatic disease, functional improvements in pain, performance status, and ambulation were observed following open acetabular reconstruction in carefully selected patients, with no impact on survival, while noninferior improvements were observed in patients receiving nonoperative management when considering their larger clinical context. Level of evidence: Level III, therapeutic study.

Computer-aided diagnosis of skeletal metastases in multi-parametric whole-body MRI.

The confident detection of metastatic bone disease is essential to improve patients' comfort and increase life expectancy. Multi-parametric magnetic resonance imaging (MRI) has been successfully used for monitoring of metastatic bone disease, allowing for comprehensive and holistic evaluation of the total tumour volume and treatment response assessment. The major challenges of radiological reading of whole-body MRI come from the amount of data to be reviewed and the scattered distribution of metastases, often of complex shapes. This makes bone lesion detection and quantification demanding for a radiologist and prone to error. Additionally, whole-body MRI are often corrupted with multiple spatial and intensity distortions, which further degrade the performance of image reading and image processing algorithms. In this work we propose a fully automated computer-aided diagnosis system for the detection and segmentation of metastatic bone disease using whole-body multi-parametric MRI. The system consists of an extensive image preprocessing pipeline aiming at enhancing the image quality, followed by a deep learning framework for detection and segmentation of metastatic bone disease. The system outperformed state-of-the-art methodologies, achieving a detection sensitivity of 63% with a mean of 6.44 false positives per image, and an average lesion Dice coefficient of 0.53. A provided ablation study performed to investigate the relative importance of image preprocessing shows that introduction of region of interest mask and spatial registration have a significant impact on detection and segmentation performance in whole-body MRI. The proposed computer-aided diagnosis system allows for automatic quantification of disease infiltration and could provide a valuable tool during radiological examination of whole-body MRI.

Minimally invasive stabilization of pelvic metastatic bone disease: A review of an emerging technique.

Percutaneous pelvic stabilization is an emerging technique that provides mechanical stability to pathologic fractures of the pelvic ring and acetabulum. Variability exists in procedural technique among institutions; however, early case series consistently demonstrate an acceptable complication profile and significant improvement in patients' pain and function. This minimally invasive approach is less morbid than traditional, open acetabular and pelvic reconstructions. Therefore, this procedure is an encouraging palliative intervention for a growing patient population in need.

Metastatic sarcomatoid carcinoma to bone.

BACKGROUND AND OBJECTIVES: Distinguishing sarcomatoid carcinoma from primary sarcoma is clinically important. We sought to characterize metastatic sarcomatoid bone disease and its management. METHODS: We analyzed the characteristics of all cases of sarcomatoid carcinoma to bone at a single institution from 2001 to 2021, excluding patients with nonosseous metastases. Survival was evaluated using the Kaplan-Meier method. RESULTS: We identified 15 cases of metastatic sarcomatoid carcinoma to bone. In seven cases the primary cancer was unknown at presentation. Renal cell carcinoma was suspected or confirmed in nine cases. Nine patients presented with pathologic fracture and two with concomitant visceral metastases. All patients underwent image-guided core needle or open biopsy. Ten required surgery for discrete osseous metastases; in four cases definitive surgery was delayed (median delay, 19 days) due to inability to rule out sarcoma with frozen section. No patients required reoperation or had construct failure. Thirteen died of disease; median survival was 17.5 months (interquartile range, 6.2-25.1). CONCLUSIONS: Metastatic sarcomatoid carcinoma is a clinically challenging entity. Multidisciplinary input and communication are key to identifying the primary carcinoma, locating osseous metastases, and defining an operative fixation that will survive the remainder of the patient's life.

Atypical tibial fracture in breast cancer patient with bone metastasis receiving denosumab therapy: a case report and review of the literature.

BACKGROUND: Denosumab therapy is often used to reduce skeletal-related events in metastatic bone disease. On the other hand, there have been some instances of atypical femoral fracture in patients with metastatic bone disease treated with denosumab. In this case report, we describe a patient with metastatic bone disease due to breast cancer who had been using denosumab for 4 years to prevent skeletal-related events and suffered an atypical tibial fracture. CASE PRESENTATION: We report here the case of an 82-year-old Japanese woman who had received yearly intravenous denosumab for 4 years and presented with a fracture fulfilling the criteria for an atypical fracture, except for being located at the tibial diaphysis. She was found to have stage 4 breast cancer with multiple bone metastases 4 years prior. She had difficulty walking due to her tibial pain and underwent surgical treatment. Four months after surgery, the tibial fracture site exhibited bone fusion. CONCLUSION: In patients with long-term use of denosumab to prevent skeletal-related events in metastatic bone disease, it is important to be aware of shin and thigh pain and to examine for signs of atypical tibial fractures to pay attention to atypical femoral fractures.

Increased Number of Medical Comorbidities Associated With Increased Risk of Presenting With Pathological Femur Fracture in Metastatic Bone Disease.

Background: Many cancers metastasize to bone and may lead to pathologic fracture or impending pathologic fracture. Prophylactically stabilizing bones before fracture has been shown to be more cost-effective with improved outcomes. Many studies have examined risk factors for pathological fracture, with radiographic and functional pain data serving as predominant indicators for surgery. Conditions associated with poor bone health and increased risk of fracture in the non-oncologic population, including diabetes mellitus, chronic obstructive pulmonary disease (COPD), cardiovascular disease, renal disease, smoking, corticosteroid use, and osteoporosis, have not been studied in the context of metastatic disease. Characterization of these factors could help providers identify candidates for prophylactic stabilization thereby reducing the number of completed pathological fractures. Methods: 298 patients over the age of 40 with metastatic bone disease of the femur treated between 2010-2021 were retrospectively identified. Patients without complete medical documentation or with non-metastatic diagnoses were excluded. 186 patients met inclusion and exclusion criteria, including 74 patients who presented with pathological femur fracture and 112 patients who presented for prophylactic stabilization. Patient demographics and comorbidities including diabetes mellitus, COPD, cardiovascular disease, renal disease, osteoporosis, active tobacco or corticosteroid use, and use of anti-resorptive therapy were collected. Descriptive statistics were compiled, with univariable analysis by Mann-Whitney or chisquared testing. Multiple logistic regression was then performed to identify the most significant patient variables for presenting with completed fracture. Results: On univariable analysis, patients with COPD were more likely to present with pathologic fracture (19/32 [59%] compared to 55/154 [36%], p = 0.02). A trend emerged for patients with an increasing number of comorbidities (28/55 [51%] for 2+ comorbidities compared to 18/61 [29%] with zero comorbidities, p = 0.06). On multivariable analysis, patients with two or more comorbidities (OR: 2.49; p=0.02) were more likely to present with a femur fracture. Conclusion: This analysis suggests that those with an increasing number of comorbidities may be at increased risk for pathologic fracture. This study raises the possibility that patient factors and/ or comorbidities alter bone strength and/or pain experiences and may guide orthopaedic oncologists weighing prophylactic stabilization of femur lesions. Level of Evidence: III.

The dynamic microenvironment associated with metastatic bone disease: Current concepts.

Patients with bone metastases may experience debilitating pain, neurological conditions, increased risk of pathological fractures, and death. A deeper understanding of the bone microenvironment, the molecular biology of cancer types prone to metastasis, and how bone physiology promotes cancer growth, may help to uncover targeted treatment options. The purpose of this paper is to outline the current concepts relevant to topics including bone remodeling, angiogenesis, and immunomodulation as it relates to metastatic bone disease.