Higher rate of progesterone receptor positivity in skeletal metastases of breast cancer with a pathological fracture vs those without fracture.

Identifying risk factors for fracture occurrence in breast cancer (BC) skeletal metastases (SM) may guide the management of such bone deposits. There is sparse evidence regarding receptor status in SM and their relationship to fracture occurrence. Our study aimed to determine the relationship between estrogen (ER), progesterone (PR) and HER2 receptor status and Ki-67 index and fracture occurrence in SM of BC. Exactly 152 samples of SM of BC obtained from individual patients were evaluated. The status of the aforementioned receptors and Ki67 index were determined in SMs samples. Their expression was compared between SM that did and did not develop a fracture. Ninety-one cases sustained a pathological fracture at the SM site, and 61 did not. Patients who sustained a pathological fracture had a higher rate of PR positivity at their SMs as compared to those with no fracture. There was no significant difference between the two groups concerning ER, HER2+ or Ki67 status. SMs secondary to BC with a fracture are more likely to be PR positive than those with no fracture. Determining the receptor status in SMs may identify high-risk groups for fracture occurrence, and determining the PR status may also guide surgical and hormonal therapy.

Is the association of electrochemotherapy and bone fixation rational in patients with bone metastasis?

BACKGROUND: Bone metastases are frequent in patients with cancer. Electrochemotherapy (ECT) is a minimally invasive treatment based on a high-voltage electric pulse combined with an anticancer drug. Preclinical and clinical studies supported the use of ECT in patients with metastatic bone disease, demonstrating that it does not damage the mineral structure of the bone and its regenerative capacity, and that is feasible and efficient for the treatment of bone metastases. Year 2014 saw the start of a registry of patients with bone metastases treated with ECT, whose data are recorded in a shared database. QUESTIONS/PURPOSES: (1) Among patients who underwent ECT and internal fixation for bone metastasis, how many experienced a reduction of pain? (2) How many cases showed a radiological response? (3) How many patients presented local or systemic complication after ECT and fixation? PATIENTS AND METHODS: Patients were treated in Bologna at Rizzoli Orthopaedic Institute between March 2014 and February 2022 and recorded in the REINBONE registry (a shared database protected by security passwords): clinical and radiological information, ECT session, adverse events, response, quality of life indicators, and duration of follow-up were registered. We consider only cases treated with ECT and intramedullary nail during the same surgical session. Patients included in the analysis were 32: 15 males and 17 females, mean age 65 ± 13 years (median 66, range 38-88 years), mean time since diagnosis of primary tumor 6.2 ± 7.0 years (median 2.9, range 0-22 years). Nail was indicated in 13 cases for a pathological fracture in, 19 for an impending fracture. Follow-up was available for 29 patients, as 2 patients were lost to follow-up and 1 was unable to return to controls. Mean follow-up time was 7.7 ± 6.5 months (median 5, range 1-24), and 16 patients (50%) had a follow-up longer than 6 months. RESULTS: A significant decrease in pain intensity was observed at the mean Visual Numeric Scale after treatment. Bone recovery was observed in 13 patients. The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. Among all patients, bone recovery was observed in 13 patients: complete recovery in 1 patient (3%) and partial recovery in 12 patients (41%). The other 16 patients remained without changes, and one presented disease progression. One patient presented a fracture occurrence during the ECT procedure. However, healing was possible with normal fracture callus quality and healing time. No other local or systemic complications were observed. CONCLUSION: We found that pain levels decreased after treatment in 23 of the 29 cases for a pain relief rate of 79% at final follow-up. Pain is one of the most important indicators of quality of life in patients that undergo palliative treatments. Even if conventional external body radiotherapy is considered a noninvasive treatment, it presents a dose-dependent toxicity. ECT provides a chemical necrosis preserving osteogenic activity and structural integrity of bone trabeculae; this is a crucial difference with other local treatments and allows bone healing in case of pathological fracture. The risk of local progression in our patient population was small, and 44% experienced bone recovery while 53% of the cases remained unchanged. We observe intraoperative fracture in one case. This technique, in selected patients, improves outcome in bone metastatic patients combing both the efficacy of the ECT in the local control of the disease and the mechanical stability with the bone fixation to synergize their benefits. Moreover, the risk of complication is very low. Although encouraging data, comparative studies are required to quantify the real efficacy of the technique. Level of Evidence Level I, therapeutic study.

Is central sarcopenia a predictor of prognosis for patients with pathological fracture?

INTRODUCTION: We aimed to investigate the relationship between central sarcopenia and survival in patients with pathological fracture. METHODS: We reviewed records of patients who were treated for pathological fracture of axial and appendicular skeleton in our clinic between 2011 and 2020. We used the psoas: lumbar vertebral index (PLVI) on axial computer tomographic evaluation to assess for central sarcopenia. A multivariate Cox algorithm was applied to recognize these factors independently associated with one month, six months, one year, and overall survival. RESULTS: A total of 147 patients [61 (41.4%) male and 86 (58.6%) female] were included, with an average age of 62.4 years. During the study, 108 (73.4%) patients died, and 39 (26.6%) were alive. The survival rates at 1 month, 6 months, and 1 year after surgery were 94.6%, 68.7%, and 53.1%, respectively. PLVI values ranged from 0.21 to 1.20 with a mean of 0.536 and a median of 0.520. According to the median value of PLVI, 68 patients with sarcopenia had low PLVI and 79 patients without sarcopenia had high PLVI. For the first month, only the preoperative albumin level was identified as a prognostic factor. Eastern Cooperative Oncology Group Performance Status (ECOG), American Society of Anesthesia (ASA) scores and primary malignancy (rapid grade) were strong predictor of poor survival. The PLVI was independent significant predictor of first month (HR, 0.083 [95% CI, 0.011-0.649], p = 0.018) and overall survival (HR, 0.129 [95% CI, 0.034-0.492], p = 0.003). CONCLUSION: The PLVI was a strong predictor of first year, and overall survival in patients with pathological fracture.

Epidemiology of 936 humeral shaft fractures in a large Finnish trauma center.

BACKGROUND: Humeral shaft fractures are relatively common injuries and are classified according to location and fracture morphology. Epidemiological studies improve understanding of injury patterns and lay foundations for future research. There are only a few published larger epidemiological studies on humeral shaft fractures. METHODS: We retrospectively analyzed the medical records of adult patients having sustained a humeral shaft fracture treated in the Helsinki University Hospital between 2006 and 2016. We recorded patient and fracture characteristics, timing and mechanism of injury, associated injuries, and 1-year mortality. RESULTS: We identified 914 patients (489 females, median age = 61.4 years; 425 males, median age = 50.4 years) with 936 fractures. Over 60% of these fractures were sustained from simple falls. The patient age distribution was bimodal, with highest fracture rates in elderly females and young males. We divided the fractures into typical traumatic, periprosthetic, and pathological fractures. Of the 872 typical traumatic fractures, 3.0% were open. In addition, there were 24 (2.6%) periprosthetic and 40 (4.3%) pathological fractures. An associated injury was found in 24% of patients, with primary radial nerve palsy (PRNP) being the most common (10%). PRNPs were more common in distal shaft fractures and high energy injuries. The 1-year mortality was 9.2%. CONCLUSIONS: In this study, the most common injury mechanism was a simple fall. The most common associated injury was PRNP. The observed bimodal fracture distribution is consistent with previous literature.

Percutaneous balloon kyphoplasty for the vertebral compression osteoporotic and pathological fracture: one-year retrospective study of 112 patients.

AIM: The aim of the study was to look for the effectiveness of percutaneous balloon kyphoplasty in the management of vertebral compression osteoporotic and pathological fracture. METHODS: A retrospective analysis of 112 patients with 198 symptomatic wedge vertebral compression fractures who were treated by percutaneous balloon kyphoplasty was done. Visual Analogue pain (VAP) scale, Oswestry Disability index (ODI) and Short Form (SF-36) were used to look for the outcome. RESULTS: Pre-operative median VAS score was (8.0, IQR 2.0) which decreased to (4.0, IQR 3.0) at 12 months. Pre-operative median ODI score was (66, IQR 22) which at 12 months follow up decreased to (28, IQR 31). Short-form 36 showed improvement in all quality of life sub-domains. The physical component summary (PCS) improved from 33.0 ± 5.0 to 37.4 ± 6.1. The Mental component summary (MCS) improved from 17.1 ± 8.6 to 23.5 ± 18.9. The results were statistically significant (p < 0.001). CONCLUSION: Percutaneous balloon kyphoplasty alleviates pain and improves function, disability, and quality of life in osteoporotic and pathological fracture.

Comparison of the clinical outcomes of intramedullary nailing between impending and completed pathological fractures caused by metastatic femoral tumors from solid cancers.

BACKGROUND: We examined the treatment outcomes following intramedullary nailing in patients with metastatic femoral tumors, excluding those from hematological malignancies. METHODS: We retrospectively evaluated treatment outcomes following intramedullary nailing between patients who underwent preventative surgery compared with those who had surgery following pathological fracture. Patients who underwent preventative surgery (Mirels' score ≥8) were allocated to the impending fracture group (n = 11) and those who underwent surgery after pathological fracture were allocated to the completed fracture group (n = 20). RESULTS: Duration of surgery was significantly shorter in the impending fracture group than in the completed fracture group. Median blood loss was significantly less, and the median duration of hospital stay was significantly shorter in the impending fracture group than in the completed fracture group. Among patients who died following surgery, the median postoperative survival duration was significantly longer in the impending fracture group than in the completed fracture group. Significantly more patients regained walking function in the impending fracture group than in the completed fracture group. Regarding complications, infection occurred in one patient in the completed fracture group. No implant damage was observed in either group. CONCLUSIONS: Patients with metastatic femoral tumors who underwent intramedullary nailing in the impending fracture group had better postoperative survival and gait function, less blood loss, and shorter durations of surgery and hospital stay than those in the completed fracture group. These findings indicate the importance of early diagnosis and treatment and value of treatment prior to fracture occurrence.

Pathological fracture of a solitary bone cyst in the calcaneus: a case series and literature review.

INTRODUCTION: Solitary bone cysts in the calcaneus (calcaneal bone cysts) are often asymptomatic. Pathological fractures are rare, and few reports are available concerning its risk assessment. Therefore, the indication for operative interventions remains debatable, and further discussion on the treatment of symptomatic cysts and pathological fractures in calcaneal bone cysts is necessary. MATERIALS AND METHODS: Clinical data of 21 patients with calcaneal bone cysts (16 men and five women) was retrospectively reviewed. The average age was 13.3 (range, 7-23) years. Clinical data, such as concerning symptoms, radiological findings, pathological findings and outcomes, were investigated, and the pathogenesis of symptomatic cysts was studied. RESULTS: Thirteen cysts were symptomatic, and eight were incidentally discovered. Computed tomography revealed no fracture in 12 cases, microfracture in eight and complete fracture in one. The areas under the curves of the receiver operating characteristic curves calculated to establish an association between cyst size and symptoms and cyst size and pathological fractures (microfracture and complete fracture) were 0.78 and 0.71, respectively. Symptomatic cysts and pathological fractures were associated with the cyst ratio (cyst size/calcaneus ≥ 0.20). On magnetic resonance imaging (MRI), fluid levels were observed in 11 of 21 (52%) patients. At the time of surgery, blood from the haemorrhage was aspirated from 15 of 21 (71%) cysts. CONCLUSIONS: Orthopaedic surgeons should be aware that the cyst ratio is associated with clinical symptoms and pathological fractures. MRI and gross findings revealed haemorrhage in the cystic fluid. In calcaneal bone cysts, repeated microfractures and spontaneous healing might occur.

The role of routine transpedicular biopsies during kyphoplasty or vertebroplasty for vertebral compression fractures in the detection of malignant diseases: a systematic review.

INTRODUCTION: Procedures like kyphoplasty or vertebroplasty have become an established treatment option for vertebral compression fractures (VCF). The transpedicular approach used during these procedures allows to take biopsies from the affected vertebral body. The aim of this study was to systematically summarize the existing knowledge on the value of routine transpedicular biopsies during kyphoplasty or vertebroplasty for vertebral compression fractures. METHODS: A systematic review of the literature using PubMed/Medline databases with the goal of finding all articles describing the value trans-pedicular biopsies for detecting primary bone tumors, metastases, bone diseases, or spondylitis in patients with vertebral compression fractures was performed. Search terms were (*biopsy/ OR biops*.ti,ab.) AND (vertebral compression fracture*.ti,ab.). RESULTS: Sixteen articles met the inclusion criteria, among these were six prospective and ten retrospective case series. Publication dates ranged from 2005 to 2020. A total of 3083 patients with 3667 transpedicular biopsies performed were included. Most biopsies confirmed osteoporosis as the dominant underlying pathology of VCFs. Transpedicular biopsies revealed an unexpected malignant diagnosis in 0.4-6% of the cases. CONCLUSION: Routine transpedicular biopsies during kyphoplasty or vertebroplasty detect unexpected malignant lesions in 0.4-6% of the patients, even though the definition of "unexpected" varies among the analyzed studies. The evidence to support a routine biopsy is inconsistent. Nevertheless, routine biopsies can be considered, especially when sufficient preoperatvie imaging is not available or radiological findings are unclear.

Do cancer patients undergoing surgery for a non-neoplastic related fragility hip fracture have worse outcomes? A retrospective study.

INTRODUCTION: An increasing number of patients sustaining a fragility hip fracture (FHF) have either an active diagnosis or a history of cancer. However, little is known about the outcomes of non-malignant related FHF in this group of patients. We aimed to evaluate the mortality and complications rates during hospitalization, as well as at 1-year follow-up within this population. METHODS: A retrospective cohort study of patients 65 years of age and above, who underwent surgery for the treatment of proximal femoral fractures between January 2012 and June 2016 was conducted. Patients diagnosed with malignancies, both solid (Carcinomas) and a hematological neoplasias (Lymphomas, Multiple Myeloma) were included, along with consecutive controls without a diagnosis of cancer in the 5 years prior to the study period. Demographic, clinical and radiographic parameters were recorded and analyzed. RESULTS: Seven hundred and fifty-two patients with FHF were included, of whom 51 had a malignancy diagnosis within the 5-year period preceding the fracture (18% metastatic disease). The mean time from malignancy diagnosis to FHF was 4.3 ± 4.8 years. Time to surgery did not differ between groups, and the vast majority of patients from both groups (over 87%) were operated within the desirable 48 h from admission. Patients with malignancy had a higher probability of being admitted to an internal medicine department both pre and post-surgically (p < 0.001), and were more susceptible to pre-operative anemia (p = 0.034). In-hospital mortality did not differ between groups, yet 1-year mortality was higher for the malignancy group (41.2% vs 19.5%, p < 0.001). At 1-year post-operatively, orthopedic complications were similar between groups. CONCLUSION: Patients with a history of malignancy in the 5-years prior to a non-neoplastic FHF, showed similar mortality and complications rates during admission but increased 1 year mortality rate when compared to patients without cancer undergoing surgical treatment of a non-neoplastic proximal femoral fracture.

CLINICAL FEATURES OF CONNECTIVE TISSUE DYSPLASIA, OSGOOD-SCHLATTER DISEASE AND MULTIPLE CORTICAL DISORDERS IN A CHILD.

OBJECTIVE: The aim: To analyze scientific data on the problems of disorders of bone morphogenesis in children, in particular, non-ossifying fibroma. To analyze modern methods of diagnosis and treatment of this disease in the context of the latest scientific achievements. PATIENTS AND METHODS: Materials and methods: The latest data of scientists from the world's leading clinics describing various forms of fibrous skeletal lesions in children of differ¬ent ages were analyzed. We examined a boy with fibrous lesions of the cortical layer of the knee joint bones and a girl with a large fibrous focus of the distal femoral metaphysis, which resulted in a closed pathological bone fracture. Surgical treatment, osteosynthesis, marginal resection of the tumor, bone grafting and histological examination were conducted. CONCLUSION: Conclusions: Despite numerous studies of this disease, the etiopathogenesis of this disease has not been studied. There are no early symptoms of fibrous bone lesions in children. Diagnosis is possible only when a pathological fracture of the affected bone occurs due to extensive growth of fibrous tissue and a significant decrease in the mechanical strength of the bone. Most cases of recognition of such a disease occur accidentally when performing X-ray examinations for other reasons - bruises, sprains, arthralgias, osteochondropathy, infectious diseases, etc. It is known that boys are more mobile and require more frequent X-ray examinations for limb injuries than girls, so the likelihood of accidental detection of such changes increases significantly. Thus, long-term observations of children with fibrous bone lesions have shown that after 40 years, patients rarely developed malignant tumors - osteogenic sarcoma, fibrosarcoma, malignant fibroma of tubular bones, pelvic bones. There are no early symptoms of fibrous bone lesions in children. Recognition of such a disease occurs by chance when X-ray examinations are performed for other reasons.

Intramedullary nailing versus cemented plate for treating metastatic pathological fracture of the proximal humerus: a comparison study and literature review.

BACKGROUND: Pathological fracture of the humerus causes severe pain, limited use of the hand, and decreased quality of life. This study aimed to compare the outcomes of intramedullary nailing and locking plate in treating metastatic pathological fractures of the proximal humerus. METHODS: This retrospective comparison study included 45 patients (22 male, 23 female) with proximal humerus metastatic pathological fractures who underwent surgical treatment between 2011 and 2022. All data were collected from medical records and were analyzed retrospectively. Seventeen cases underwent intramedullary nailing plus cement augmentation, and 28 cases underwent locking plate plus cement augmentation. The main outcomes were pain relief, function scores, and complications. RESULTS: Among 45 patients with mean age 61.7 ± 9.7 years, 23 (51.1%) had multiple bone metastases, and 28 (62.2%) were diagnosed with impending fractures. The nailing group had significantly lower blood loss [100 (60-200) versus 500 (350-600) ml, p < 0.001] and shorter hospital stay (8.4 ± 2.6 versus 12.3 ± 4.3 days, p < 0.001) than the plating group. Average follow-up time of the nailing group was 12 months and 16.5 months for the plating group. The nailing group had higher visual analog scale (VAS) scores than the plating group, indicating greater pain relief with nailing [7 (6-8) versus 6 (5-7), p = 0.01]. Musculoskeletal Tumor Society functional scores [28 (27-29) versus 27 (26.5-28.5), p = 0.23] were comparable between groups. No complications, local recurrence, or revision surgery were reported until the last follow-up in either group. However, one case in the plating group had a humeral head collapse and fragmentation without needing revision surgery. CONCLUSIONS: Intramedullary nailing with cement augmentation is a viable option for treating proximal humerus metastatic pathological fracture, providing rigid fixation and better pain relief resulting in earlier mobility to optimize functional outcomes. Less invasive procedure with less blood loss and shorter hospital stay also benefits patients. Level of evidence Level II. Trial registration statement Not applicable.

Risk assessment of femoral pathological fracture in prostate cancer patients by computed tomography analysis.

INTRODUCTION: Prostate cancer often forms osteoblastic lesions that appear as a high-dense shadow upon X-ray. Although the lesions may seem to increase bone strength, pathological fracture occurs in one in four patients with prostate cancer. The aim of this study is to elucidate the factors that may increase the risk of pathological fracture in patients with prostate cancer metastases in the proximal femur by analyzing computed tomography data. MATERIALS AND METHODS: Computed tomography data of the femur of 62 prostate cancer patients were retrospectively analyzed. The patients were divided into three groups based on the presence or absence of femoral metastatic lesions and pathological fracture. Surgical specimens of the proximal femur collected from patients who had a pathological fracture were histologically analyzed. RESULTS: Bone density in the marrow area was increased in all cases with metastases compared with those with no metastases. Contrarily, the cortical bone density at the medial trochanter region was significantly lower in patients who had pathological fractures in the proximal femur than those who did not. Accordingly, histological analysis of the surgical specimens revealed that the affected cortical bone was osteopenic without any apparent new bone formation. CONCLUSION: These results indicate that prostate cancer is less effective in inducing bone formation in the cortex than in the marrow and that the decrease in the cortical bone density at the medial trochanter region leads to an increased risk of pathological fracture. Therefore, a previously undocumented risk factor for pathological fracture in prostate cancer patients is presented.

Preoperative coagulation biomarkers associate with survival and pulmonary embolism after surgical treatment of non-spinal skeletal metastases.

BACKGROUND: Thrombotic complications are synergistic and associated with orthopedic procedures, trauma, and malignancy. Because cancer enhances coagulation activity and vice versa, we assessed preoperative biomarkers for survival and complications after treatment of pathologic fractures in non-spinal skeletal metastases. PATIENTS/METHODS: Our study population comprised 113 actual or impending pathologic fractures in 100 patients admitted to two referral centers. Laboratory variables were collected retrospectively from patient records and analyzed related to incidence of pulmonary embolism (PE) and mortality (Kaplan-Meier and Cox regression analyses and biomarker quartiles). RESULTS: Preoperative coagulation variables were high without exceptions. PE occurred in 12 patients at 36 post-operative days at incidence of 11% in the lower and 13% in the upper extremity fractures. Patients with fibrinogen exceeding 5 g/l (log-rank 0.022) developed PE earlier (5 to 15 days postoperatively) than others. Also, mean patient survival with normal fibrinogen range (2-4 g/l) was 34 months, whereas it halved upon elevated fibrinogen (log-rank p = 0.009). Survival in patients with FVIII levels under 326 IU/dl (Q3) was 22 months, but only 7 months if FVIII exceeded 326 IU/dl (log-rank p = 0.002). Combined elevated fibrinogen and FVIII predicted survival: for patients with levels below threshold limits was 22 months versus only 7 months when both variables exceeded the ranges (log-rank p < 0.001). Multivariate analysis to control confounders supported an independent role of fibrinogen and FVIII for survival. CONCLUSIONS: Our study has established fibrinogen and FVIII as potential preoperative contributors of survival and complications after treatment of metastatic fractures. These results highlight the need for novel anticoagulation and thromboprophylaxis strategies among these patients.

Liposarcoma of Probable Medullary Bone Origin in a Lovebird (Agapornis roseicollis).

A 15-year-old female peach-faced lovebird (Agapornis roseicollis) was presented to the hospital for a possible left wing injury and an inability to fly after falling in its cage. On physical examination the left elbow was swollen and painful. Radiographic images revealed left wing soft tissue swelling surrounding the elbow and lysis of the distal humerus with extensive cortical thinning. Subsequent high-definition volumetric-imaging 3-dimensional computed tomography (HDVI 3D CT) revealed a pathological fracture, cortical lysis, periosteal reaction, and abnormal intraosseous soft tissue of the left humerus with associated soft tissue swelling, suggestive of neoplasia. No evidence of metastatic disease was identified. Surgical amputation of the left wing was elected. A liposarcoma and pathologic fracture of the humerus were diagnosed histologically and by oil red O staining for lipids in the neoplastic cells. The morphologic features of the tumor suggested that it developed within the adipocyte component of the medullary bone. The incision at the amputation site healed without complication. A follow-up HDVI 3D CT performed 4 months postsurgery showed no evidence of metastatic disease. To the authors' knowledge, this is the first report of a primary liposarcoma of medullary bone origin in an avian species.

Primary intraosseous solitary fibrous tumor: an extremely rare case report and brief review of the literature.

Solitary fibrous tumor (SFT), a rare mesenchymal neoplasm of fibroblastic origin, was initially discovered in the mediastinal pleura and then described in many extra-pleural sites.The reports of primary solitary fibrous tumor of bone are extremely rare and only a few cases have been previously mentioned in the literature, most of which in flat and short bones.Here we present the case of a 53-year-old female, who was referred to the emergency department of a peripheral hospital after an accidental fall. Imaging studies revealed an intertrochanteric fracture with an underlying intramedullary lytic lesion. A biopsy was performed and a diagnosis of Ewing sarcoma was initially suggested. She arrived at our hospital where we reevaluated the case. The biopsy was reviewed and a diagnosis of intraosseous SFT was proposed. She underwent en-block resection of the proximal right femur.Primary SFTs of the bone are, like in our case, easily misdiagnosed due to the low specificity of the imaging studies and the extreme rarity of the localization. An accurate diagnosis and early resection are very important and with careful long-term follow-up is essential, particularly in those who with malignant behavior, for the early detection of possible recurrence or metastasis.

Exosomal tumor necrosis factor-α from hepatocellular cancer cells (Huh-7) promote osteoclast differentiation.

Bone is the common extra-hepatic site for cancer metastasis. Hepatic cancer is associated with a higher incidence of pathological fracture. However, this important regulatory mechanism remains unexplored. Thus, exosome-mediated cell-cell communication between hepatocellular cancer and bone might be key to osteolytic bone destruction. Huh-7 exosomes were characterized for size and exosome marker expressions (CD63, Alix). Exosome mediated osteoclast differentiation in the RAW 264.7 cells was monitored from day 1 to 6 and multinucleated osteoclast formation and bone resorption activity were analyzed. The osteoclastogenic factor expressions in the exosomes and osteoclast differentiation markers such as tumor necrosis factor receptor 6 (TRAF6), nuclear factor κB (NF-κB), nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), and cathepsin K (CTSK) were analyzed using western blot. Exosomes released by liver cancer cells (Huh-7) promoted osteoclast differentiation in RAW 264.7 cells. Analysis of osteoclastogenic factors in the exosomes showed that exosomes were specifically enriched with tumor necrosis factor α (TNF-α). Huh-7 exosomes promoted osteoclast differentiation by significantly increasing the number of TRAP-positive multi nucleated osteoclasts and resorption pits. Importantly, exosomes upregulated osteoclast markers TRAF6, NF-κB, and CTSK expressions. Further, neutralizing exosomal TNF-α reverted exosome-mediated osteoclast differentiation in RAW 264.7 cells. Collectively, our findings show that cellular communication of exosomal TNF-α from hepatocellular cancer cells (Huh-7) regulates osteoclast differentiation through NF-κB/CTSK/TRAP expressions. Thus, exosomal TNF-α might act as an important therapeutic target to prevent hepatocellular cancer mediated pathological bone disease.

Clinicopathologic characteristics, metastasis-free survival, and skeletal-related events in 628 patients with skeletal metastases in a tertiary orthopedic and trauma center.

BACKGROUND: Skeletal-related events (SREs) due to bone metastases (BM) significantly impact the morbidity and mortality of cancer patients. The present study sought to investigate clinicopathological characteristics, metastasis-free survival (MFS), and SREs in patients referred to a tertiary orthopedic and trauma center. METHODS: Data were retrieved from electronic health records (n=628). Survival curves were estimated utilizing the Kaplan-Meier method. The Cox regression model was used to determine factors influencing MFS based on estimated hazard ratios (HRs). RESULTS: Breast (55.8%) and lung (18.2%), and lung (32.9%) and prostate (16.8%) cancer were the most common cancer types in our cohort in women and men, respectively. Fifteen percent of patients presented with BM as the first manifestation of tumor disease, 23% had metastasis diagnosis on the same day of primary tumor diagnosis or within 3 months, and 62% developed BM at least 3 months after primary tumor diagnosis. Osteolytic BM were predominant (72.3%) and most commonly affecting the spine (23%). Overall median MFS was 45 months (32 (men) vs. 53 (women) months). MFS was shortest in the lung (median 15 months, 95% CI 8.05-19) and longest in breast cancer (median 82 months, 95% CI 65.29-94). Age (≥ 60 vs. < 60 years) and primary cancer grading of ≥2 vs. 1 revealed prognostic relevance. CONCLUSION: Women with breast or lung cancer, men with lung or prostate cancer, age ≥60 years, male sex, and primary cancer grading ≥2 are associated with increased risk for MBD. Intensified follow-up programs may reduce the risk of SREs and associated morbidity and mortality.

Osteitis Fibrosa Cystica and pathological fractures-the classic but neglected skeletal manifestation of primary hyperparathyroidism: a case report.

BACKGROUND: Osteitis fibrosa cystica is the classic manifestation of primary hyperparathyroidism (PHPT), occurs after prolonged exposure of bone to high serum parathyroid hormone (PTH) level. It has become increasingly rare due to early detection of PHPT. CASE PRESENTATION: A 37-year-old woman was referred to our institution for fixation of multiple fractures of upper and lower extremities that had been reoccurring in the past 5 years. Her medical history showed right-shoulder, left-elbow, and right-femur fractures after a fall 5 years previously. One month ago, she sustained fractures of the right distal humerus, left tibia, and left femur without history of trauma. Upon arrival to our hospital, a thorough review of her plain radiographs demonstrated brown tumors at multiple sites, along with a salt-and-pepper appearance of the skull and a rugger-jersey spine, compatible with osteitis fibrosa cystica. Patient was diagnosed with PHPT, confirmed by high-corrected serum calcium (13.6 [8.6-10.0] mg/dl), low serum phosphate (2.2 [2.5-4.5] mg/dL), high serum alkaline phosphatase (1482 [35-105] U/L), and significantly elevated parathyroid hormone (PTH 3850 [15-65] pg/mL). A histologically confirmed, 2.5-cm parathyroid adenoma was removed by parathyroidectomy. Ten days later, closed reduction and internal fixation of the left proximal femoral shaft was performed. Pain and ambulation were significantly improved 6 months postoperatively. At the 1.5-year follow-up, fracture unions and complete mineralization of brown tumors were noted; the patient could ambulate with neither pain nor an assistive device. CONCLUSIONS: PHPT has become more asymptomatic in countries where routine calcium screening is performed. Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture.

Single-center outcomes for percutaneous pedicle screw fixation in metastatic spinal lesions: can spontaneous facet fusion occur?

OBJECTIVE: Survival of cancer patients continues to improve with systemic treatment advancements, leading to an increase in cancer-related complications such as pathological spinal fractures. In this study, the authors aimed to evaluate the outcome of percutaneous stabilization with cement augmentation of the pedicle screws in the management of patients with metastatic cancer to the spine. METHODS: The authors reviewed a retrospective case series of 74 patients with symptomatic pathological spine fractures treated with cement-augmented pedicle screws implanted with a percutaneous technique. The mean imaging follow-up was 11.3 months. Data on demographics, clinical outcomes, and complications were collected. Cement extravasation, spinal hardware integrity, and fusion rates were assessed on CT scans. RESULTS: Among 50 patients with follow-up imaging, 23 patients (46%) showed facet joint fusion. The length of segmental stabilization was not a significant predictor of the occurrence of fusion. Pre- or postoperative radiation therapy, postoperative chemotherapy, and the location of spinal lesions did not have a statistically significant effect on the occurrence of fusion. Patients older than 60 years of age were more likely to have fusion across facet joints compared with younger patients. There was a significant difference in the mean visual analog scale pain score, with 6.28 preoperatively and 3.41 postoperatively, regardless of fusion status (p < 0.001). Cement extravasation was seen in 51% of the cohort, but in all instances, patients remained asymptomatic. Most importantly, the incidence of hardware failure was low (4%). CONCLUSIONS: Percutaneous fixation with cement-augmented pedicle screws in patients with pathological spine fractures provides an improvement in mechanical back pain, with a low incidence of failure, and in some patients, spontaneous facet fusion was observed. Further research is necessary with regard to both short-term benefits and long-term outcomes.

Risks and Complications After Arthroplasty for Pathological or Impending Pathological Fracture of the Hip.

BACKGROUND: Treatment options for metastatic osseous lesions of the proximal femur include hemiarthroplasty (HA) or total hip arthroplasty (THA) depending on lesion characteristics and patient demographics. Studies assessing short-term outcomes after HA/THA in this patient population are limited. Therefore, the purpose of this present study was to identify short-term rates of morbidity and mortality after HA/THA for pathological proximal femur fractures, as well as readmission and reoperation rates and reasons. METHODS: This study utilized a large, prospectively collected registry to identify patients who underwent HA/THA between 2011 and 2018. Patients were stratified by indication for surgery, including pathological fracture, nonpathological fracture, and osteoarthritis. Baseline patient characteristics and postoperative complications were compared using bivariate and/or multivariate analysis. RESULTS: In total, 883 patients undergoing HA/THA for a pathological fracture were identified. Relative to an osteoarthritis cohort, these patients tended to be older, had a lower body mass index, and had significantly more preoperative comorbidities. These patients had high rates of total complications (13.93%), including thirty-day mortality (3.29%), unplanned return to the operating room (4.98%), and pulmonary complications (3.85%). Patients with pathological fracture had a longer operative duration relative to osteoarthritis and nonpathological cohorts (+27 and +25 minutes, respectively), despite having high rates of HAs performed. CONCLUSION: Patients undergoing hip arthroplasty for pathologic proximal femur fracture have increased morbidity and mortality relative to an osteoarthritis cohort. However, patients with a pathological fracture have similar rates of morbidity and mortality when compared with a nonpathological fracture cohort, but did experience higher rates of perioperative blood transfusion and unplanned readmissions. LEVEL OF EVIDENCE: III.