Intravenous tranexamic acid reduces complications following surgical treatment of pathologic fractures of the lower extremity.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the postoperative complications associated with administering intravenous (IV) tranexamic acid (TXA) in patients undergoing surgical fixation for neoplastic pathologic fractures of the lower extremities. METHODS: Patients ≥18 years old who underwent surgical intervention for neoplastic pathologic lower extremity fractures from 2015 to 2021 were identified using the Premier Healthcare Database. This cohort was divided by TXA receipt on the index surgery day. Patient demographics, hospital factors, patient comorbidities, and 90-day complications were assessed and compared between the cohorts. RESULTS: From 2015 to 2021, 4497 patients met inclusion criteria (769 TXA[+] and 3728 TXA[-]). Following propensity score matching, patients who received TXA had a significantly shorter length of stay than those who did not (7.6 ± 7.3 days vs. 9.0 ± 15.2, p = 0.036). Between the two cohorts, there were no significant differences in comorbidities. Regarding differences in postoperative complications, TXA(+) patients had significantly decreased odds of deep vein thrombosis (DVT) (1.87% vs. 5.46%; odds ratio [OR]:0.33; 95% confidence interval: 0.17-0.62; p = 0.001). CONCLUSION: Administration of IV TXA may be associated with a decreased risk of postoperative DVT without an increased risk of other complications. Orthopedic surgeons should consider the utilization of IV TXA in patients treated surgically for neoplastic pathologic fractures of the lower extremity.

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.

An easy way to determine bone mineral density and predict pelvic insufficiency fractures in patients treated with radiotherapy for cervical cancer.

PURPOSE: The aim of this study was to investigate whether bone mineral density (BMD) as measured in planning computed tomographies (CTs) by a new method is a risk factor for pelvic insufficiency fractures (PIF) after radio(chemo)therapy (R(C)T) for cervical cancer. METHODS: 62 patients with cervical cancer who received definitive or adjuvant radio(chemo)therapy between 2013 and 2017 were reviewed. The PIF were detected on follow-up magntic resonance imaging (MRI). The MRI of the PIF patients was registered to the planning CT and the PIF contoured. On the contralateral side of the fracture, a mirrored structure of the fracture was generated (mPIF). For the whole sacral bone, three lumbar vertebrae, the first and second sacral vertebrae, and the PIF, we analyzed the BMD (mg/cm3), V50Gy, Dmean, and Dmax. RESULTS: Out of 62 patients, 6 (9.7%) had a fracture. Two out of the 6 patients had a bilateral fracture with only one of them being symptomatic. PIF patients showed a significantly lower BMD in the sacral and the lumbar vertebrae (p < 0.05). The BMD of the contoured PIF, however, when comparing to the mPIF, did not reach significance (p < 0.49). The difference of the V50Gy of the sacrum in the PIF group compared to the other (OTH) patients, i.e. those without PIF, did not reach significance. CONCLUSION: The dose does not seem to have a relevant impact on the incidence of PIF in our patients. One of the predisposing factors for developing PIF after radiotherapy seems to be the low BMD. We presented an easy method to assess the BMD in planning CTs.

Bisphosphonate use in children with cerebral palsy.

BACKGROUND: Cerebral palsy (CP) is a heterogeneous group of non-progressive disorders of posture or movement, caused by a lesion of the developing brain. Osteoporosis is common in children with cerebral palsy, particularly in children with reduced gross motor function, and leads to an increased risk of fractures. Gross motor function in children with CP can be categorised using a tool called the Gross Motor Function Classification System (GMFCS). Bisphosphonate increases bone mineral density (BMD) and reduces fracture rates. Bisphosphonate is used widely in the treatment of adult osteoporosis. However, the use of bisphosphonate in children with CP remains controversial, due to a paucity of evidence and a lack of recent trials examining the efficacy and safety of bisphosphonate use in this population. OBJECTIVES: To examine the efficacy and safety of bisphosphonate therapy in the treatment of low BMD or secondary osteoporosis (or both) in children with cerebral palsy (GMFCS Levels III to V) who are under 18 years of age. SEARCH METHODS: In September 2020, we searched CENTRAL, MEDLINE, Embase, six other databases, and two trial registers for relevant studies. We also searched the reference lists of relevant systematic reviews, trials, and case studies identified by the search, and contacted the authors of relevant studies in an attempt to identify unpublished literature. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs), and quasi-RCTs, comparing at least one bisphosphonate (given at any dose, orally or intravenously) with placebo or no drug, for the treatment of low BMD or osteoporosis in children up to 18 years old, with cerebral palsy (GMFCS Levels III to V). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We were unable to conduct any meta-analyses due to insufficient data, and therefore provide a narrative assessment of the results. MAIN RESULTS: We found two relevant RCTs (34 participants). Both studies included participants with non-ambulatory CP or CP and osteoporosis. Participants in both studies were similar in severity of CP, age distribution, and sex distribution. The two trials used different bisphosphonate medications and different intervention durations, but further comparison of the interventions was not possible due to a lack of published data from one trial. One trial received funding and support from research, academic, and hospital foundations, with pharmaceutical companies providing components of the calcium and vitamin supplement; the other trial did not report sources of funding. We judged one study at an overall high risk of bias; the other as overall unclear risk of bias. PRIMARY OUTCOME: Compared to placebo or no treatment, both studies provided very low certainty evidence of improved BMD at least four months post-intervention in children treated with bisphosphonate. Only one study (12 participants) provided sufficient detail to assess a measure of the effect, and reported an improvement at six months post-intervention in lumbar spine z-score (mean difference (MD) 18%, 95% confidence interval (CI) 6.57 to 29.43; very low certainty evidence). SECONDARY OUTCOMES: Very low certainty evidence from one study found that bisphosphonate reduced serum N-telopeptides (NTX) more than placebo; the other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced NTX, but did not compare groups. One study reported inconclusive results between groups for serum bone-specific alkaline phosphatase (BAP). The other study reported that both bisphosphonate plus alfacalcidol and alfacalcidol alone reduced BAP, but did not compare groups. Neither study reported data for the effect of bisphosphonate treatment on changes in volumetric BMD in the distal radius or tibia, changes in fracture frequency, bone pain, or quality of life. One study reported that two participants had febrile events noted during their first dosing schedule, but no further adverse events were reported in either relevant study. AUTHORS' CONCLUSIONS: Based on the available evidence, there is very low certainty evidence that bisphosphonate treatment may improve bone health in children with cerebral palsy. We could only include one study with 14 participants in the assessment of the effect size; therefore, the precision of the effect estimate is low. We could only evaluate one planned primary outcome, as there was insufficient detail reported in the relevant studies. Further research from RCTs on the effect and safety of bisphosphonate to improve bone health in children with cerebral palsy is required. These studies should clarify the optimal standard treatment regarding weight-bearing exercises, vitamin D and calcium supplementation, and should include fracture frequency as a primary outcome.

Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism. OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence). AUTHORS' CONCLUSIONS: Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.

A retrospective study of end-stage kidney disease patients on maintenance hemodialysis with renal osteodystrophy-associated fragility fractures.

BACKGROUND: Nephropathy associated metabolic disorder induces high incidence of fragility fracture in end-stage renal disease (ESRD) patients. As the risk factors and prognosis of fragility fracture in ESRD patients are unclear, more research is needed. This study aimed to evaluate various risk factors for ESRD-related fragility fractures, explore factors affecting the prognosis of patients with such fractures, and provide information for prevention and treatment of renal osteopathy to improve the prognosis of patients. METHODS: In this retrospective case-control study, the case notes of 521 ESRD patients who received maintenance dialysis for at least 3 months were examined. Finally, 44 patients diagnosed with fragility fractures were assigned to the fragility fracture (FF) group and 192 patients were included in the control group (CG). Demographic information, underlying diseases, nutritional, bone metabolism, and renal function parameters, along with the number and causes of any deaths, were recorded for multiple statistical analysis. RESULTS: The FF group had increased incidences of essential hypertension and diabetes mellitus and higher serum calcium, corrected calcium, alkaline phosphatase, and hemoglobin levels. Immunoreactive parathyroid hormone (iPTH), total cholesterol (TC), and low density lipoprotein (LDL) levels were higher in the CG. Multivariate Cox regression analysis revealed that fragility fracture was an independent risk factor for all-cause mortality in ESRD patients (P < .001, RR: 4.877, 95% CI: 2.367-10.013). CONCLUSIONS: Essential hypertension and diabetes, high serum calcium and alkaline phosphatase levels, and reduced iPTH levels were risk factors for fragility fracture in ESRD patients. Maintaining iPTH and serum TC levels may protect against fragility fractures in them. Fragility fractures may yield poor prognosis and shorter lifespan. The presence of fragility fracture was an independent predictor of all-cause death in ESRD patients.

Prevention and Treatment of Pathologic Femur Fractures: Evidence as of 2019.

This chapter is largely drawn from the recently published (2019) clinical practice guideline on the treatment of metastatic carcinoma and myeloma of the femur jointly produced by the Musculoskeletal Tumor Society, American Society for Radiation Oncology, and American Society of Clinical Oncology. Previous clinical practice guidelines on this topic broadly addressed the potential benefits of bone-targeted agents (eg, diphosphonates) on skeletal-related events, a broad term that encompasses pathologic fractures of any bone, need for surgery or radiation, and hypercalcemia. Guidelines on the use of palliative radiation therapy primarily focused on short-term pain control and long-term radiation-induced adverse effects. The starting goals of this guideline were twofold-focus on the femur, as fractures of the femur almost always require surgery and, when about the hip, dramatically alter patients' quality of life and, potentially, survival; and to address this topic in a multidisciplinary fashion that includes the insights of orthopaedic surgeons, along with radiation oncologists and medical oncologists. For many important clinical topics, there is a dearth of evidence, which will hopefully prompt researchers and funding agencies to help fill these evidentiary gaps.

Synthetic Bone Graft Substitute for Treatment of Unicameral Bone Cysts.

BACKGROUND: Treatments for unicameral bone cysts (UBCs) have high documented failure rates (27% to 63%) because of recurrence or persistence of the cyst, similar to nonoperative management. Recent evidence suggests that filling of the defect with a synthetic bone graft substitute (SBGS) supports the weakened cortex and promotes new bone growth. A calcium sulfate, brushite, calcium phosphate, composite graft material (PRODENSE, Wright Medical, Memphis, TN) has been evaluated as a substitute for autogenous or allogenous graft in animal and human studies. The purpose of this study was to compare the rates of revision surgery in patients treated for UBCs with an SBGS compared with historical treatments with allograft or autologous bone marrow aspirate. METHODS: The authors reviewed 27 of 33 patients (age, 6 months to 21 years) an average of 121 months (range, 32 to 228) after filling of a UBC with an injection of SBGS (n=18) versus allograft or autologous bone marrow aspirate (n=9) between June 2008 and December 2017. Six patients with no follow-up were excluded. Groups did not differ in age at surgery, sex (19/27 male), history of pathologic fracture (22/27), or previous treatments (11/27). The primary outcome was the rate of revision surgery. Secondary outcomes included revision surgery-free survival as evaluated by the log-rank test, rate of postoperative fracture, persistent cysts, continued pain, and/or growth disturbance at the final follow-up. RESULTS: Seven of 9 patients treated with allograft or autograft underwent revision surgery for postoperative pathologic fracture (n=2) or resorption of the graft (n=5) compared with 2 of 18 patients injected with the SBGS, both treated for graft resorption. The use of SBGS was associated with a decreased need for revision surgery over all time periods (hazard ratio, 0.14; 95% confidence interval, 0.03-0.05). There was no significant difference between postoperative fracture (2/18 vs. 2/9), persistent cyst (7/18 vs. 5/9), pain (0/18 vs. 2/9), or growth disturbance (1/18 vs. 3/9). CONCLUSIONS: Treatment of UBCs with SBGS may decrease reoperation rates. Initial radiographic appearance after SBGS treatment shows solid structural support, followed by new bone formation. This appearance may lead to a less aggressive approach in considering revision surgery. LEVEL OF EVIDENCE: Level III-retrospective comparative study investigating the results of treatment.

Preventing hip fractures with multidisciplinary teams: a Canadian perspective.

Fragility fractures (FFs) are low-energy trauma fractures that occur at or below standing height. Among FFs, hip fractures are associated with the greatest morbidity, mortality and cost to Canadian health care systems. This review highlights the current state of medical care for hip fractures in Canada, with specific focus on the role of the multidisciplinary team. Gaps in care exist, as FFs represent a unique challenge requiring both acute and chronic management. Furthermore, there is a lack of ownership of FFs by a medical specialty. These gaps can be addressed through the use of multidisciplinary teams, which have been shown to be efficacious and cost-effective. This model of care also addresses numerous patient-identified barriers to treatment, including inadequate patient counselling. However, there is still room for improvement in both the identification of patients at risk for hip fracture and patient adherence to therapy.

Les fractures de fragilisation (FF) sont des fractures qui surviennent lors d'un traumatisme léger se produisant depuis la position debout ou d'une hauteur moindre. Les fractures de la hanche sont les FF associées aux plus grands taux de morbidité et de mortalité et aux plus grands coûts pour les systèmes de santé au Canada. La présente revue s'intéresse à l'état actuel des soins médicaux pour une fracture de la hanche au pays et porte une attention spéciale au rôle de l'équipe multidisciplinaire. Des lacunes dans les soins existent et sont mises en évidence par les FF, qui posent un défi bien particulier en nécessitant une prise en charge à la fois aiguë et chronique. De plus, cette prise en charge ne relève d'aucune spécialité médicale. La correction de ces lacunes peut passer par le recours aux équipes multidisciplinaires, dont l'efficacité et la rentabilité ont été démontrées. Ce modèle de soins élimine également de nombreux obstacles au traitement signalés par les patients, y compris le counseling inadéquat. Des améliorations sont néanmoins encore nécessaires dans l'identification des patients à risque de fracture de la hanche et dans l'observance du traitement.

Risk factors for skeletal-related events in patients with bone metastasis from breast cancer undergoing treatment with zoledronate.

BACKGROUND: Skeletal-related events (SREs) are significant contributors to the morbidity and mortality in patients with bone metastasis from breast cancer. Thus, bone-modifying agents (BMAs) are recommended in this population. However, the baseline risk factors of SREs in patients with bone metastasis from breast cancer receiving BMAs are not well understood. METHODS: We analyzed the patient-level data from a controlled arm of a clinical trial comparing denosumab with zoledronate in patients with bone metastases from breast cancer (ClinicalTrial.gov ID: NCT00321464) available at Project Data Sphere, a broad-access research platform that collects and curates patient-level data from completed, phase III cancer trials. The primary endpoint was the first SRE after the inclusion to the trial. The time to the first on study SRE was analyzed using Cox proportional hazards model based on patients' baseline characteristics including age, race, ECOG performance status (PS), histology and immunohistochemistry of breast cancer, and urine and serum laboratory data. RESULTS: Among 756 patients in the zoledronate arm of the trial, we excluded 64 patients with a documented history of osteopenia or osteoporosis. The median age of the patients was 56 years old, the median follow-up was 553 days, and 249 patients (36%) had SREs. The univariate analysis showed that black or African American heritage, ECOG PS > 0, human epidermal growth factor receptor 2 (HER2) positivity, high urine N-telopeptide cross-links / creatinine ratio (NTx/Cre), and elevated serum alkaline phosphatase (ALP) are significant baseline risk factors for SREs. Patients with the characteristics of ECOG PS > 0, HER2 positivity, and elevated ALP also showed a significantly higher hazard ratio of SREs in multivariate analysis. CONCLUSIONS: We determined risk factors for SREs in patients with bone metastasis from breast cancer.

Image-guided Percutaneous Fixation with Internal Cemented Screws of Impending Femoral Neck Pathologic Fractures in Patients with Metastatic Cancer: Safety, Efficacy, and Durability.

Background Prophylactic image-guided procedures performed by interventional radiologists for impending pathologic fractures are becoming more pertinent, as patients with metastatic cancer have extended overall survival because of advanced therapies. Purpose To evaluate the efficacy, safety, and palliative durability of collimated-beam CT-guided percutaneous fixation with internal cemented screws (FICS) for impending pathologic fractures of the femoral neck. Materials and Methods This single-institute retrospective study examined all patients with metastatic cancer treated between February 2010 and October 2019 with collimated-beam CT-guided percutaneous FICS procedures for preventive consolidation of impending femoral neck pathologic fractures. The short-term palliative efficacy was assessed through comparison of visual analog scale (VAS) scores before and 1 month after FICS. A review of cross-section imaging and clinic reports identified any procedural complications. Long-term consolidation efficacy was defined as the absence of any screw dislodgement or development of a pathologic fracture at completion of the study. The Wilcoxon test was used for the mean comparison of paired nonparametric variables. Results Sixty-one consecutive patients (mean age, 59 years ± 11 [standard deviation]; 35 women) underwent preventive FICS for consolidation of impending pathologic femoral neck fracture with a mean follow-up of 533 days ± 689. Two patients died of cancer within the first month. Complications were limited to three self-resolving hematomas. The mean VAS score decreased 1 month after FICS from 4.2 ± 3.2 to 1.8 ± 2.0 (P < .001). The long-term consolidation efficacy was 92% (54 of 59 patients), with three of 59 patients (5%) subsequently developing fractures despite FICS and an additional two of 59 patients (3%) with durable FICS undergoing definitive total hip arthroplasty surgery because of local tumor progression. Conclusion Percutaneous fixation with internal cemented screws as performed by the interventional radiologist is a safe nonsurgical treatment that provides an effective palliative result and durable prevention for impending pathologic fractures of the femoral neck. © RSNA, 2020 Online supplemental material is available for this article.

Is There an Association Between Prophylactic Femur Stabilization and Survival in Patients with Metastatic Bone Disease?

BACKGROUND: The femur is the most common site of metastasis in the appendicular skeleton, and metastatic bone disease negatively influences quality of life. Orthopaedic surgeons are often faced with deciding whether to prophylactically stabilize an impending fracture, and it is unclear if prophylactic fixation increases the likelihood of survival. QUESTIONS/PURPOSES: Is prophylactic femur stabilization in patients with metastatic disease associated with different overall survival than fixation of a complete pathologic fracture? METHODS: We performed a retrospective, comparative study using the national Veterans Administration database. All patient records from September 30, 2010 to October 1, 2015 were queried. Only nonarthroplasty procedures were included. The final study sample included 950 patients (94% males); 362 (38%) received prophylactic stabilization of a femoral lesion, and 588 patients (62%) underwent fixation of a pathologic femur fracture. Mean followup duration was 2 years (range, 0-7 years). We created prophylactic stabilization and pathologic fracture fixation groups for comparison using Common Procedural Terminology and ICD-9 codes. The primary endpoint of the analysis was overall survival. Univariate survival was estimated using the Kaplan-Meier method; between-group differences were compared using the log-rank test. Covariate data were used to create a multivariate Cox proportional hazards model for survival to adjust for confounders in the two groups, including Gagne comorbidity score and cancer type. RESULTS: After adjusting for comorbidities and cancer type, we found that patients treated with prophylactic stabilization had a lower risk of death than did patients treated for pathologic femur fracture (hazard ratio = 0.75, 95% CI, 0.62-0.89; p = 0.002). CONCLUSIONS: In the national Veterans Administration database, we found greater overall survival between patients undergoing prophylactic stabilization of metastatic femoral lesions and those with fixation of complete pathologic fractures. We could not determine the cause of this association, and it is possible, if not likely, that patients treated for fracture had more aggressive disease causing the fracture than did those undergoing prophylactic stabilization. Currently, most orthopaedic surgeons who treat pathological fractures stabilize the fracture prophylactically when reasonable to do so. We may be improving survival in addition to preventing a pathological fracture; further study is needed to determine whether the association is cause-and-effect and whether additional efforts to identify and treat at-risk lesions improves patient outcomes. LEVEL OF EVIDENCE: Level III, therapeutic study.

Proceedings of the 2018 Santa Fe Bone Symposium: Advances in the Management of Osteoporosis.

The Santa Fe Bone Symposium is an annual meeting devoted to clinical applications of recent advances in skeletal research. The 19th Santa Fe Bone Symposium convened August 3-4, 2018, in Santa Fe, New Mexico, USA. Attendees included physicians of many specialties, fellows in training, advanced practice providers, clinical researchers, and bone density technologists. The format consisted of lectures, case presentations by endocrinology fellows, and panel discussions, with all involving extensive interactive discussions. Topics were diverse, including an evolutionary history of calcium homeostasis, osteoporosis treatment in the very old, optimizing outcomes with orthopedic surgery, microbiome and bone, new strategies for combination and sequential therapy of osteoporosis, exercise as medicine, manifestations of parathyroid hormone excess and deficiency, parathyroid hormone as a therapeutic agent, cell senescence and bone health, and managing patients outside clinical practice guidelines. The National Bone Health Alliance conducted a premeeting on development of fracture liaison services. A workshop was devoted to Bone Health TeleECHO (Bone Health Extension for Community Healthcare Outcomes), a strategy of ongoing medical education for healthcare professions to expand capacity to deliver best practice skeletal healthcare in underserved communities and reduce the osteoporosis treatment gap.

Retrospective analysis of 51 intralesionally treated cases with progressed giant cell tumor of the bone: local adjuvant use of hydrogen peroxide reduces the risk for tumor recurrence.

BACKGROUND: Giant cell tumor of the bone (GCT) has high local recurrence rates and the prognosis is hard to predict. We therefore retrospectively analyzed clinical outcome and recurrences of 51 GCT cases focusing on the effects of adjuvant local use of hydrogen peroxide. METHODS: The series enclosed 51 advanced GCT cases of the upper and lower extremities (n = 27 Campanacci grade III; n = 24 grade II; n = 39 surgery at our institution, n = 12 elsewhere). Mean follow-up was 88.3 (± 62.0) months. Surgical details, histology, metastases, recurrences, and interview-based data on satisfaction and function including the Musculoskeletal Tumor Society (MSTS) score were evaluated. It was investigated whether hydrogen peroxide was additionally used or not to clean the tumor cavity after curettage as we hypothesized influence on recurrences. To analyze the underlying mechanisms, GCT-derived stromal cell lines were cultured in vitro and tested for cell viability and apoptosis after treatment with hydrogen peroxide. Statistical analysis was performed with Student's t tests, analysis of variance (ANOVA) with post hoc testing, Mann-Whitney U tests, chi-square tests, Kaplan-Meier analysis, and multivariate Cox regression analysis. RESULTS: The whole series had 21 recurrences (41%). Eleven recurrences were found (28%) after surgery at our institution. Kaplan-Meier analysis of cumulative recurrence-free survival revealed at 2 years follow-up 69% (72%, only our institution) and at 10 years follow-up 54% (68%, only our institution). Intralesional resection was performed by vigorous curettage, burring, and defect filling with either polymethylmethacrylate bone cement (n = 45) or cancellous bone from the iliac crest (n = 6). Univariate chi-square analysis showed significantly lower recurrence rate after bone cement filling (2.3-fold, p = 0.024). Cleaning of the lesion cavity with hydrogen peroxide significantly reduced recurrence rate (whole collective 2.9-fold, p = 0.004; our institution 2.8-fold, p = 0.04) and significantly increased cumulative recurrence-free survival rate (whole collective at 10 years follow-up 74% versus 31%, p = 0.002; our institution 79% versus 48%, p = 0.02) compared to cases without hydrogen peroxide treatment. In multivariate analysis, significant risk factors for recurrence were pathological fracture (hazard ratio 3.7; p = 0.04), high mitosis rate (hazard ratio 15.6; p = 0.01), and lack of hydrogen peroxide use (hazard ratio 6.0; p = 0.02). In vitro cell culture analyses found apoptotic nature of hydrogen peroxide induced GCT cell death. CONCLUSIONS: The present series proved for the first time that additional cleaning of the tumor cavity with hydrogen peroxide before defect filling significantly reduced recurrence rate and significantly increased recurrence-free survival in advanced but intralesionally treated GCT cases.

Prevention of Pathological Fracture of the Proximal Femur: A Systematic Review of Surgical and Percutaneous Image-Guided Techniques Used in Interventional Oncology.

Background and objectives: Patients suffering from bone metastasis are at high risk for pathological fractures and especially hip fractures. Osteolytic metastases can induce a high morbidity rate (i.e., pain, facture risk, mobility impairment), and operation on them can be difficult in this frail population having a reduced life expectancy. Several medical devices have been investigated for the prevention of these pathological hip fractures. Materials and Methods: To investigate these solutions, a literature review and a meta-analysis of primary studies was performed. Data sources included electronic databases (PubMed, CENTRAL and ClinicalTrials.gov) from 1990 until 1 January 2019. Titles, abstracts and full-text articles were reviewed in order to select only studies evaluating the performance of the studied solution to prevent osteoporotic and/or pathological hip fracture. The main outcomes were the occurrence of hip fracture, pain evaluation (VAS score) and adverse events occurrence (including severe adverse events and deaths). All randomised controlled trials (RCTs) and cohort studies were considered. A Bayesian cumulative meta-analysis was undertaken on the primary studies conducted in patients with bone metastasis. Results: A total of 12 primary studies were identified, all were cohort studies without a control group, and one compared two devices, and were thereafter considered separately. In those 12 samples, 255 patients were included, mean age 61.7 years. After implantation, the cumulative risk of fracture was 5.5% (95% confidence interval, 3.0% to 8.6%), and adverse event occurrence was 17.4% (95%CI, 12.6 to 22.8%), with a median follow-up of 10 months. The posterior probability of a fracture rate below 5% was 40.3%. Conclusions: The literature about medical devices evaluation for preventing hip fractures in metastatic patients is poor and mostly based on studies with a limited level of evidence. However, this systematic review shows promising results in terms of efficacy and tolerance of these devices in patients with bone metastases. This treatment strategy requires further investigations.

Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study.

BACKGROUND: Multiple myeloma is characterised by monoclonal paraprotein production and osteolytic lesions, commonly leading to skeletal-related events (spinal cord compression, pathological fracture, or surgery or radiotherapy to affected bone). Denosumab, a monoclonal antibody targeting RANKL, reduces skeletal-related events associated with bone lesions or metastases in patients with advanced solid tumours. This study aimed to assess the efficacy and safety of denosumab compared with zoledronic acid for the prevention of skeletal-related events in patients with newly diagnosed multiple myeloma. METHODS: In this international, double-blind, double-dummy, randomised, active-controlled, phase 3 study, patients in 259 centres and 29 countries aged 18 years or older with symptomatic newly diagnosed multiple myeloma who had at least one documented lytic bone lesion were randomly assigned (1:1; centrally, by interactive voice response system using a fixed stratified permuted block randomisation list with a block size of four) to subcutaneous denosumab 120 mg plus intravenous placebo every 4 weeks or intravenous zoledronic acid 4 mg plus subcutaneous placebo every 4 weeks (both groups also received investigators' choice of first-line antimyeloma therapy). Stratification was by intent to undergo autologous transplantation, antimyeloma therapy, International Staging System stage, previous skeletal-related events, and region. The clinical study team and patients were masked to treatment assignments. The primary endpoint was non-inferiority of denosumab to zoledronic acid with respect to time to first skeletal-related event in the full analysis set (all randomly assigned patients). All safety endpoints were analysed in the safety analysis set, which includes all randomly assigned patients who received at least one dose of active study drug. This study is registered with ClinicalTrials.gov, number NCT01345019. FINDINGS: From May 17, 2012, to March 29, 2016, we enrolled 1718 patients and randomly assigned 859 to each treatment group. The study met the primary endpoint; denosumab was non-inferior to zoledronic acid for time to first skeletal-related event (hazard ratio 0·98, 95% CI 0·85-1·14; pnon-inferiority=0·010). 1702 patients received at least one dose of the investigational drug and were included in the safety analysis (850 patients receiving denosumab and 852 receiving zoledronic acid). The most common grade 3 or worse treatment-emergent adverse events for denosumab and zoledronic acid were neutropenia (126 [15%] vs 125 [15%]), thrombocytopenia (120 [14%] vs 103 [12%]), anaemia (100 [12%] vs 85 [10%]), febrile neutropenia (96 [11%] vs 87 [10%]), and pneumonia (65 [8%] vs 70 [8%]). Renal toxicity was reported in 85 (10%) patients in the denosumab group versus 146 (17%) in the zoledronic acid group; hypocalcaemia adverse events were reported in 144 (17%) versus 106 (12%). Incidence of osteonecrosis of the jaw was not significantly different between the denosumab and zoledronic acid groups (35 [4%] vs 24 [3%]; p=0·147). The most common serious adverse event for both treatment groups was pneumonia (71 [8%] vs 69 [8%]). One patient in the zoledronic acid group died of cardiac arrest that was deemed treatment-related. INTERPRETATION: In patients with newly diagnosed multiple myeloma, denosumab was non-inferior to zoledronic acid for time to skeletal-related events. The results from this study suggest denosumab could be an additional option for the standard of care for patients with multiple myeloma with bone disease. FUNDING: Amgen.

Radiotherapy combined with zoledronate can reduce skeletal-related events in renal cell carcinoma patients with bone metastasis.

BACKGROUND: Skeletal-related events (SRE) are common in patients with renal cell carcinoma (RCC) that includes bone metastasis. The purpose of this study was to clarify the effectiveness of zoledronate with and without sunitinib, combined with radiotherapy, for the treatment of bone metastasis from RCC. METHODS: We retrospectively analyzed 62 RCC patients with bone metastasis, who had been treated with radiotherapy at our institution. We divided the study cohort into two groups: patients treated with radiotherapy alone (RT; n = 27) and those treated with radiotherapy combined with zoledronate (RT + Z; n = 35). We investigated the overall survival and post-irradiation (PI)-SRE-free rate for each group, as well as the effect of sunitinib in the RT + Z treatment group. In addition, we determined treatment effectiveness by imaging assessments and relative response rates. RESULTS: There was no significant difference in the survival rates between the RT and RT + Z treatment groups (p = 0.11). However, the PI-SRE-free rate in the RT + Z group was significantly higher than that in the RT group (p = 0.02). The PI-SRE-free rate was significantly higher in patients who were treated with sunitinib after radiotherapy than in those who were treated without sunitinib (p = 0.03). However, there was no significant difference in the relative response rates, as assessed by imaging, in each group. CONCLUSION: Radiotherapy combined with zoledronate is an effective treatment for RCC with bone metastasis to prevent PI-SRE. Sunitinib may reduce PI-SRE if used after radiotherapy and combined with zoledronate.

Not All Patients Undergoing Stabilization of Impending Pathologic Fractures for Renal Cell Carcinoma Metastases to the Femur Need Preoperative Embolization.

BACKGROUND: Preoperative transarterial embolization has been utilized in the surgical treatment of metastatic renal cell carcinoma of the femur to decrease perioperative blood loss. However, few studies have documented its efficacy in decreasing the proportion of patients receiving transfusions in the setting of prophylactic treatment of impending pathologic femur fractures. QUESTIONS/PURPOSES: In a population of patients with metastatic renal cell carcinoma of the femur who underwent prophylactic fixation, the purpose of this study was to quantify and compare the proportion of patients who received at least one transfused unit of blood between a group treated with preoperative embolization and a group without preoperative embolization. METHODS: A retrospective study was performed using a Medicare claims-based database. International Classification of Diseases, 9 Revision and Current Procedural Terminology codes were used to identify 1285 patients with metastatic renal cell carcinoma of the femur who underwent prophylactic fixation. The proportion of patients who received one or more blood transfusions was compared between 135 patients who underwent preoperative embolization and a group of 1150 concurrent control patients who did not undergo preoperative embolization. The control group was older than the embolization group, with 44% of these patients > 75 years old and 33% of the embolization group > 75 years. There was no difference in the female:male ratio between groups. Statistical comparisons of outcomes related to transfusion percentages were performed using Pearson chi square analysis with p < 0.05 considered significant. With the numbers available, we had 80% power to detect a difference in the percentage of patients transfused of 11% between the study groups at α = 0.05. RESULTS: No difference in transfusion percentage was observed between preoperative transarterial embolization (41 of 135 [30%]) and the control group (359 of 1150 [31%]; relative risk, 0.973; 95% confidence interval, 0.743-1.274; p = 0.84). The percentage of all patients who received a transfusion was 31% (400 of 1285). CONCLUSIONS: Preoperative embolization may not be mandatory in the prophylactic treatment of metastatic renal cell carcinoma of the femur, as demonstrated by the 69% of patients who received zero units of blood despite not receiving embolization. However, assessment of the efficacy of embolization in decreasing blood loss in the current study is limited as a result of biases associated with the database design of the study; the decision of whether to send a patient for embolization should be made on a case-by-case basis. The current study does not identify specific risk factors that should factor into this decision and underscores the need for further research in this regard. A plausible future research design to account for the low numbers and selection bias that limited the current study as well as the existing studies might be a multicenter, retrospective case-control study. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Is the Adverse Event Profile After Prophylactic Treatment of Femoral Shaft or Distal Femur Metastases?

BACKGROUND: Prophylactic surgical treatment of the femur is commonly offered to patients with metastatic disease who have a high risk of impending pathologic fracture. Prophylactic fixation is associated with improved functional outcomes in appropriate patients selected based on established criteria, but the perioperative complication profile has received little attention. Given the substantial comorbidity in this population, it is important to characterize surgical risks for surgeons and patients to improve treatment decisions. QUESTIONS/PURPOSES: (1) What is the incidence of postoperative adverse events after prophylactic surgical stabilization of metastatic lesions of the femoral shaft or distal femur? (2) How does this complication profile compare with stabilization of pathologic fractures adjusted for differences in patient demographics and comorbidity? METHODS: We performed a retrospective study using the National Surgical Quality Improvement Program (NSQIP) database. We identified patients undergoing prophylactic treatment of the femoral shaft or distal femur by Current Procedural Terminology (CPT) codes. Patients undergoing treatment of a pathologic fracture were identified by CPT code for femur fracture fixation as well as an International Classification of Diseases code indicating neoplasm or pathologic fracture. We tracked adverse events, operative time, blood transfusion, hospital length of stay, and discharge to a facility within 30 days postoperatively. There were 332 patients included in the prophylactic treatment group and 288 patients in the pathologic fracture group. Patients in the prophylactic treatment group presented with greater body mass index (BMI), whereas the pathologic fracture group presented with a greater incidence of disseminated cancer. The odds of experiencing adverse events were initially compared between the two groups using bivariate logistic regression and then using multivariate regression controlling for age, sex, BMI, and American Society of Anesthesiologists (ASA) class and disseminated cancer causing marked physiological compromise per NSQIP guidelines. RESULTS: With multivariate analysis controlling for age, sex, BMI, and ASA class, patients with pathologic fracture were more likely to experience any adverse event (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03-2.29; p = 0.036), major adverse events (OR, 1.61; 95% CI, 1.01-2.55; p = 0.043), death (OR, 1.90; 95% CI, 1.07-3.38; p = 0.030), blood transfusion (OR, 1.57; 95% CI, 1.08-2.27; p = 0.017), and hospital stay ≥ 9 days (OR, 1.51; 95% CI, 1.05-2.19; p = 0.028) compared with patients undergoing prophylactic treatment. However, when additionally controlling for disseminated cancer, the only difference was that patients with pathologic fractures were more likely to receive a blood transfusion than were patients undergoing prophylactic fixation (OR, 1.61; 95% CI, 1.12-2.36; p = 0.011). CONCLUSIONS: After controlling for differences in patient characteristics, prophylactic treatment of femoral metastases was associated with a decreased likelihood of blood transfusion and no differences in terms of the frequency of other adverse events. In the context of prior studies supporting the mechanical and functional outcomes of prophylactic treatment, the findings of this cohort suggest that the current guidelines have achieved a reasonable balance of morbidity in patients with femoral lesions and further support the current role of prophylactic treatment of impending femur fractures in appropriately selected patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Beyond Mirels: Factors Influencing Surgical Outcome of Metastasis to the Extremities in the Modern Era.

Mirels scoring system for determining prophylactic stabilization need of skeletal metastases includes a limited number of variables and does not differentiate between procedure types. This study sought to identify additional variables associated with surgical failure, radiographic disease progression, and patient survival. A retrospective review was performed of patients from January 2004 to 2014 who underwent surgical treatment of skeletal metastases of the extremities, were >18 years of age, and had adequate radiographic surveillance. Eighty-nine metastatic bone lesions in 77 patients were included. Mirels score >8 (p = .015) and tumor origin (p = .008) were associated with surgical failure, which was 16.8%. Male gender (p < .001) and use of bone cement (p = .019) were associated with radiographic progression, 43.8% overall. Antiresorptive medications usage (p = .02) was associated with survival. The study concluded that tumor origin may be highly important when considering surgical treatment for metastatic bone disease and antiresorptive medications should be used postoperatively, given an association with survival. (Journal of Surgical Orthopaedic Advances 27(3):178-186, 2018).