Orthopaedic surgeons' ability to detect pathologic hip fractures: review of 1484 fractures reported to the Norwegian Hip Fracture Register.

BACKGROUND: The proximal femur is the most common location of metastases in the appendicular skeleton. Data on pathologic hip fractures, however, are sparse despite it is the most frequently operated pathologic fracture. The aim of this study was to investigate the ability of orthopaedic surgeons to identify pathologic hip fractures in an acute setting and secondly to validate the underlying cause of the pathologic fractures reported to Norwegian Hip Fracture Register (NHFR). METHODS: In the NHFR dataset between 2005 and 2019, we identified 1484 fractures reported to be pathologic possibly secondary to a malignancy. These fractures were thoroughly validated by reviewing X-rays, the patient journal, the operation description for date, side, why there had been suspicion of pathologic fracture, and implant choice. Pathology reports were reviewed once a biopsy had been performed. Based on this validation, information in the NHFR was corrected, whenever necessary. RESULTS: Of the 1484 fractures possible secondary to malignancy, 485 (32.7%) were not a pathologic fracture. When reviewing the 999 validated pathologic fractures, 15 patients had a pathologic fracture secondary to a benign lesion. The remaining 984 patients had a pathologic fracture secondary to malignancy. The underlying diagnosis reported was corrected in 442 of the 999 patients. The true rate of pathologic hip fractures secondary to malignancy in our material was 0.8%, and most patients had underlying prostate (30%), breast (20%), or lung (17%) cancer. CONCLUSION: Orthopaedic surgeons in Norway failed to report correct data on pathologic fractures and the corresponding cancer diagnosis in an acute setting in many patients. The corrected data on pathologic fractures in the NHFR from 2005 to 2019 can now be a valid resource for further studies on the subject.

Risk factors of fracture following curettage for bone giant cell tumors of the extremities.

BACKGROUND: Following curettage of giant cell tumor of bone (GCTB), it is common to fill the cavity with polymethylmethacrylate (PMMA) bone cement, bone allograft, or artificial bone to maintain bone strength; however, there is a 2-14% risk of postoperative fractures. We conducted this retrospective study to clarify the risk factors for fractures after curettage for GCTB of the extremities. METHODS: This study included 284 patients with GCTBs of the extremities who underwent curettage at our institutions between 1980 and 2018 after excluding patients whose cavities were not filled with anything or who had additional plate fixation. The tumor cavity was filled with PMMA bone cement alone (n = 124), PMMA bone cement and bone allograft (n = 81), bone allograft alone (n = 63), or hydroxyapatite graft alone (n = 16). RESULTS: Fractures after curettage occurred in 10 (3.5%) patients, and the median time from the curettage to fracture was 3.5 months (interquartile range [IQR], 1.8-8.3 months). The median postoperative follow-up period was 86.5 months (IQR, 50.3-118.8 months). On univariate analysis, patients who had GCTB of the proximal or distal femur (1-year fracture-free survival, 92.5%; 95% confidence interval [CI]: 85.8-96.2) presented a higher risk for postoperative fracture than those who had GCTB at another site (100%; p = 0.0005). Patients with a pathological fracture at presentation (1-year fracture-free survival, 88.2%; 95% CI: 63.2-97.0) presented a higher risk for postoperative fracture than those without a pathological fracture at presentation (97.8%; 95% CI: 95.1-99.0; p = 0.048). Patients who received bone grafting (1-year fracture-free survival, 99.4%; 95% CI: 95.7-99.9) had a lower risk of postoperative fracture than those who did not receive bone grafting (94.4%; 95% CI: 88.7-97.3; p = 0.003). CONCLUSIONS: For GCTBs of the femur, especially those with pathological fracture at presentation, bone grafting after curettage is recommended to reduce the risk of postoperative fracture. Additional plate fixation should be considered when curettage and cement filling without bone grafting are performed in patients with GCTB of the femur. This should be specially performed for those patients with a pathological fracture at presentation.

Fracture rate and time to fracture in dogs with appendicular osteosarcoma receiving finely fractionated compared to coarsely fractionated radiation therapy: A single institution study.

BACKGROUND: Radiation therapy (RT) is used for local pain alleviation in dogs with appendicular osteosarcoma (OS), especially among dogs that are poor surgical candidates for amputation. However, many historical reports of fractionated protocols lack time to fracture and fracture rates. OBJECTIVES: The primary objectives of this retrospective study were to determine fracture rate and time to fracture of dogs receiving RT (coarse or fine fractionated) for appendicular OS. Secondary objectives were to evaluate tolerability and disease outcome measures. METHODS: Fifty-one dogs that received RT as part of treatment for appendicular OS were available for evaluation. Forty-five received coarse fractionation (C-RT, 8 or 6 Gy per fraction protocols [C-RT8 or C-RT6]) while the remaining six received fine fractionation (F-RT). RESULTS: The overall pathologic fracture rate was 37%. Pathologic fracture rate was significantly higher for dogs that received F-RT (5/6, 83%) compared to dogs that received C-RT (12/40, 30%, p = 0.021). In the 17 dogs that fractured, the overall median time to fracture was 57 days. For all dogs, the median progression free interval (PFI) and median overall survival time (OST) were 90 and 140 days, respectively. In a very small cohort of dogs (n = 7) treated with zoledronate and RT, fracture rate was 0% and extended survival times were noted. CONCLUSIONS: In conclusion, C-RT is recommended over F-RT due to lower risk of pathologic fracture and similar PFI. Prospective evaluation of combined C-RT and zoledronate, especially for dogs with poor surgical candidacy, is warranted for the treatment of canine appendicular osteosarcoma.

Does surgical technique influence the burden of lung metastases in patients with pathologic long bone fractures?

BACKGROUND: The aims of this study are to (1) determine whether fixation of metastatic long bone fractures with an intramedullary nail (IMN) influences the incidence of lung metastasis in comparison to arthroplasty or ORIF (Arthro/ORIF); and (2) assess this relationship in primary tumor types; and (3) to assess survival implications of lung metastasis after surgery. METHODS: Retrospective cohort study investigating 184 patients (107 IMN, and 77 Arthro/ORIF) surgically treated for metastatic long bone fractures. Patients were required to have a single surgically treated impending or established pathologic fracture of a long bone, pre-operative lung imaging (lung radiograph or computed tomography) and post-operative lung imaging within 6 months of surgery. Primary cancer types included were breast (n = 70), lung (n = 43), prostate (n = 34), renal cell (n = 37). Statistical analyses were conducted using two-tailed Fisher's exact tests, and Kaplan-Meier survival analyses. RESULTS: Patients treated with IMN and Arthro/ORIF developed new or progressive lung metastases following surgery at an incidence of 34 and 26%, respectively. Surgical method did not significantly influence lung metastasis (p = 0.33). Furthermore, an analysis of primary cancer subgroups did not yield any differences between IMN vs Arthro/ORIF. Median survival for the entire cohort was 11 months and 1-year overall survival was 42.7% (95% CI: 35.4-49.8). Regardless of fixation method, the presence of new or progressive lung metastatic disease at follow up imaging study was found to have a negative impact on patient survival (p < 0.001). CONCLUSIONS: In this study, development or progression of metastatic lung disease was not affected by long bone stabilization strategy. IM manipulation of metastatic long bone fractures therefore may not result in a clinically relevant increase in metastatic lung burden. The results of this study also suggest that lung metastasis within 6 months of surgery for metastatic long bone lesions is negatively associated with patient survival. LEVEL OF EVIDENCE: III, therapeutic study.

Spine-specific skeletal related events and mortality in non-small cell lung cancer patients: a single-institution analysis.

OBJECTIVE: The population prevalence of non-small cell lung cancer (NSCLC) continues to increase; however, data are limited regarding the incidence rate of skeletal related events (SREs) (i.e., surgery to the spinal column, radiation to the spinal column, radiofrequency ablation, kyphoplasty/vertebroplasty, spinal cord compression, or pathological vertebral body fractures) and their impact on overall mortality. In this study, the authors sought to estimate the incidence rates of SREs in NSCLC patients and to quantify their impact on overall mortality. METHODS: This was a single-institution retrospective study of patients diagnosed with NSCLC between 2002 and 2014. The incidence rates for bone metastasis and subsequent SREs (per 1000 person-years) by time since lung cancer diagnosis were calculated and analyses were stratified separately for each histological type. Incidence rates for mortality at 1, 2, and 3 years from diagnosis stratified by the presence of SREs were also calculated. Kaplan-Meier survival curves were constructed to describe crude survival ratios in patients with spine metastasis and SREs and those with spine metastasis but without SREs. These curves were used to estimate the 1- and 2-year survival rates for each cohort. RESULTS: We identified 320 patients with incident NSCLC (median follow-up 9.5 months). The mean ± SD age was 60.65 ± 11.26 years; 94.48% of patients were smokers and 60.12% had a family history of cancer. The majority of first-time SREs were pathological vertebral body compression fractures (77.00%), followed by radiation (35%), surgery (14%), and spinal cord compression (13.04%). Mortality rates were highest in NSCLC patients with spine metastasis who had at least 1 SRE. Stratifying by histological subtype, the incidence rate of mortality in patients with SRE was highest in the large cell cohort, 7.42 per 1000 person-years (95% CI 3.09-17.84 per 1000 person-years); followed by the squamous cell cohort, 2.49 per 1000 person-years (95% CI 1.87-3.32 per 1000 person-years); and lowest in the adenocarcinoma cohort, 1.68 per 1000 person-years (95% CI 1.46-1.94 per 1000 person-years). Surgery for decompression of neural structures and stabilization of the spinal column was required in 6% of patients. CONCLUSIONS: SREs in NSCLC patients with bone metastasis are associated with an increased incidence rate of mortality.

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.

Vertebral multiple myeloma with pathological fracture: the most common etiology for emergency spine surgery in patients with no cancer diagnosis on admission.

OBJECTIVE: Vertebral compression fractures are common in multiple myeloma (MM). Modern treatment paradigms place emphasis on treatment with radiation, with surgery reserved for cases involving frank instability or severe neural compression. However, experience at the authors' institution has led them to suspect a more prominent role for surgical intervention in some settings. The authors undertook the present study to better understand the incidence of MM in undiagnosed patients who require urgent surgery for pathological vertebral fracture. METHODS: The authors reviewed a prospectively collected database of all patients who underwent surgery with the senior author at their main hospital between June 1, 1998, and June 30, 2020. Patients admitted from the emergency room or after transfer from another hospital who then underwent surgery for pathological fracture during the same admission were included in the final analysis. Patients scheduled for elective surgery and those with previous cancer diagnoses were excluded. RESULTS: Forty-three patients were identified as having undergone urgent surgical decompression and/or stabilization for pathological fracture. Histopathology confirmed diagnosis of MM in 22 (51%) patients, lung metastasis in 5 (12%) patients, and breast metastasis in 4 (9%) patients. Twelve (28%) patients were diagnosed with other types of metastatic carcinoma or undifferentiated disease. Sixteen of 29 (55%) men and 6 of 14 (42%) women were diagnosed with MM (p = 0.02). Seventeen of 34 (50%) patients who underwent surgery for neurological deficit, 5 of 6 (83%) patients who underwent surgery for spinal instability, and 0 (0%) patients who underwent surgery for pain with impending spinal cord injury were diagnosed with MM (p = 0.12). CONCLUSIONS: A majority of patients presenting to the authors' hospital with no history of malignancy who required urgent surgery for pathological compression fracture were found to have MM or plasmacytoma. This disease process may affect a significant portion of patients requiring decompressive or stabilizing surgery for compression fracture in academic medical centers.

The impact of pathological fractures on surgery, morbidity, functional and oncological outcomes in patients with primary bone sarcomas.

Background Although rare, pathological fractures may occur in primary bone sarcomas. There have been studies reporting that such patients have a poorer prognosis than those without a pathological fracture. This study investigates the impact of pathological fractures on surgery, morbidity, functional and oncological outcomes in patients with primary bone sarcomas. Patients and methods A retrospective analysis of 568 patients with primary bone sarcomas, treated between 2005 and 2019, was performed. The study included 41 patients with a pathological fracture and 51 control patients who did not have a pathological fracture. A multivariate Cox regression analysis was used to investigate the impact of pathological fractures and further independent variables on amount of intraoperative bleeding, duration of surgery, number of muscles and major neurovascular structures included in resection, tumor volume, surgical volume, Musculoskeletal Tumor Society (MSTS) functional score, postoperative complication rate, and local recurrence, distant metastasis, and survival rates. Results There were 36 (39%) female and 56 (61%) male patients. No statistically significant difference was noted in tumor volume, tumor/surgical volume percentage, number of major neurovascular structures included in resection, postoperative complication rate, and local recurrence, distant metastasis, and survival rates between the two groups (p > 0.05). A significantly higher amount of intraoperative bleeding and number of transfused blood components, a longer duration of surgery, and a higher amount surgical volume and number of resected muscles were detected in Group 1 compared to Group 2 (p=0.001, p=0.002, p=0.007, p=0.007, p < 0.001, respectively). The MSTS functional scores were lower in patients with a pathological fracture than in those without a pathological fracture (p=0.001). Conclusion We conclude that a pathological fracture through a primary bone sarcoma has no adverse effect on prognostic factors such as local recurrence, distant metastasis, and survival. However, pathological fractures increase the amount of intraoperative bleeding and surgical volume and result in a longer surgery, in addition to decreased functional outcomes.

Long-Term Safety and Efficacy of Subcutaneous Tanezumab Versus Nonsteroidal Antiinflammatory Drugs for Hip or Knee Osteoarthritis: A Randomized Trial.

OBJECTIVE: To assess the long-term safety and 16-week efficacy of subcutaneous tanezumab in patients with hip or knee osteoarthritis (OA). METHODS: This was a phase III randomized, double-blind, active treatment-controlled (using nonsteroidal antiinflammatory drugs [NSAIDs] as the active treatment control) safety trial of tanezumab (56-week treatment/24-week posttreatment follow-up) in adults who were receiving stable-dose NSAID therapy at the time of screening and who had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores of ≥5; patient global assessment (PtGA) of OA of fair, poor, or very poor; history of inadequate pain relief with standard analgesics; and no history or radiographic evidence of prespecified bone/joint conditions beyond OA. Patients received oral naproxen, celecoxib, or diclofenac twice daily (NSAID group; n = 996) or tanezumab 2.5 mg (n = 1,002) or 5 mg (n = 998) subcutaneously every 8 weeks. Coprimary efficacy end points at week 16 were changes in WOMAC pain and physical function scores and changes in PtGA. The primary joint safety end point over 80 weeks comprised adjudicated rapidly progressive OA type 1 or 2, primary osteonecrosis, subchondral insufficiency fracture, or pathologic fracture. Mean values, least squares mean values, and least squares mean differences between groups (with 95% confidence intervals [95% CIs]) were calculated. RESULTS: Of 3,021 randomized patients, 2,996 received ≥1 treatment dose. Adverse events (AEs) were similar between patients treated with tanezumab 2.5 mg and those treated with NSAIDs, and were more prevalent in those treated with tanezumab 5 mg. Composite joint safety events were significantly more prevalent with tanezumab 2.5 mg and tanezumab 5 mg than with NSAIDs (observation time-adjusted rate/1,000 patient-years 38.3 [95% CI 28.0, 52.5] and 71.5 [95% CI 56.7, 90.2], respectively, versus 14.8 [95% CI 8.9, 24.6]; P = 0.001 for tanezumab 2.5 mg versus NSAIDs; P < 0.001 for tanezumab 5 mg versus NSAIDs). Tanezumab 5 mg significantly improved pain and physical function but did not improve PtGA at week 16 when compared to NSAIDs; corresponding differences between the tanezumab 2.5 mg and NSAID groups were not statistically significant. CONCLUSION: In patients previously receiving a stable dose of NSAIDs, tanezumab administered subcutaneously resulted in more joint safety events than continued NSAIDs, with differences being dose dependent. Pain and physical function improved with both doses of tanezumab compared to NSAIDs, reaching statistical significance with tanezumab 5 mg at 16 weeks.

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.

The incidence and diagnostic relevance of pathological fracture in conventional central chondrosarcoma.

OBJECTIVE: To determine the incidence and diagnostic relevance of pathological fracture in patients with conventional central chondrosarcoma (CC-CS). MATERIALS AND METHODS: Retrospective review of patients with CC-CS diagnosed between January 2007 and December 2019. Data collected included age, sex, skeletal location and the presence of pathological fracture at presentation. Histological tumour grade based on surgical resection or needle biopsy was classified as atypical cartilaginous tumour (ACT)/grade 1 CS (ACT/Gd1 CS), high-grade CS (HG-CS) and dedifferentiated CS (DD-CS). The presence of pathological fracture was correlated with age, skeletal location and tumour grade. RESULTS: Three hundred seventeen patients were included (177 males and 140 females with mean age 55.8 years, range 9-91 years). Mean age of patients without pathological fracture was 54.4 years and those with pathological fracture 62.9 years (p = 0.002). The major long bones were involved in 171 cases, the flat bones in 112 cases, the mobile spine in 7 cases and the small bones of the hands and feet in 27 cases. There were 81 ACT/Gd 1 CS, 168 HGCS and 68 DD-CS. Pathological fracture was evident at presentation in 51 (16.1%) cases, the commonest bones involved being the femur (n = 21; 41.2%), humerus (n = 10; 19.6%) and acetabulum (n = 7; 13.7%). Pathological facture occurred in 7 cases of ACT/Gd 1 CS (13.7%), 23 cases of HGCS (45.1%) and 21 cases of DD-CS (41.2%) (p = 0.001). Following multivariate analysis, both older age and histological grade were independently significant factors. CONCLUSIONS: Pathological fracture was seen in 16.1% of patients with CC-CS. Pathological fractures in the femur, humerus and acetabulum very likely indicate higher tumour grade.

Morbidity and mortality of surgically treated pathologic humerus fractures compared to native humerus fractures.

BACKGROUND: Despite an increasing prevalence of patients sustaining pathologic fractures of neoplastic origin, few studies have investigated 30-day postoperative complication profiles after surgical treatment of pathologic humerus fractures. The purposes of this study were to use a large nationally representative database to determine short-term complication profiles after surgical treatment of pathologic humerus fractures and assess how these complications compared with more commonly studied native humerus fractures. METHODS: Using the National Surgical Quality Improvement Program database, we identified 30,866 patients who underwent surgical treatment for either pathologic (n = 449) or native humerus fractures (n = 30,417) from 2007 to 2017. Thirty-day postoperative complication profiles were ascertained and compared between the 2 groups using χ2 analyses. Three logistic regression models were then performed to determine which complications were primarily attributable to the pathologic fracture itself vs. the increased comorbidity burden faced by these patients. RESULTS: Patients with pathologic humerus fractures experienced significantly higher rates of death (6.0% vs. 0.3%, P < .001), serious adverse events (12.2% vs. 3.7%, P < .001), minor complications (15.8% vs. 4.8%, P < .001), extended postoperative lengths of stay (42.3% vs. 21.3%, P < .001), discharge to facilities (22.3% vs. 13.5%, P < .001), and readmissions (14.8% vs. 3.4%, P < .001) compared with patients with native humerus fractures. With respect to specific complications, patients with pathologic fractures were at significantly higher risk of pulmonary complications (1.3% vs. 0.3%, P < .001), renal complications (0.7% vs. 0.2%, P = .007), thromboembolic complications (1.6% vs. 0.6%, P = .01), and transfusions (15.1% vs. 4.1%, P < .001). CONCLUSION: After surgical treatment, patients with pathologic humerus fractures had significantly higher complication rates compared with native humerus fractures, suggesting that guidelines and treatment algorithms for native humerus fractures may not be generalizable for those of pathologic origin. These findings have significant implications for preoperative patient counseling and may be used to negotiate higher reimbursement rates for these patients given a significantly higher morbidity and mortality than was previously described in literature. Postoperatively, orthopedic surgeons should closely monitor patients with pathologic humerus fractures for deep vein thrombosis, renal complications, and pulmonary complications, use blood-sparing techniques, and employ a multidisciplinary approach to help manage and prevent a more heterogeneous profile of postsurgical complications.

Association of Chemoradiotherapy With Thoracic Vertebral Fractures in Patients With Esophageal Cancer.

Importance: The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown. Objective: To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer. Design, Setting, and Participants: This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020. Exposures: Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group). Main Outcomes and Measures: The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated. Results: A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009). Conclusions and Relevance: This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.

High rate of fracture in long-bone metastasis: Proposal for an improved Mirels predictive score.

INTRODUCTION: Pathologic fracture is the most feared complication in long-bone metastasis. Various radiographic tools are available for identifying at-risk patients and guide preventive treatment. The Mirels score is the most frequently studied and widely used, but has been criticized, many patients not being operated on until the actual fracture stage. We therefore conducted a French national multicenter prospective study: (1) to determine the proportion of patients operated on at fracture stage versus preventively; (2) to compare Mirels score between the two; and (3) to identify factors for operation at fracture stage according to Mirels score and other epidemiological, clinical and biological criteria. HYPOTHESIS: Simple discriminatory items can be identified to as to complete the Mirels score and enhance its predictive capacity. MATERIAL AND METHODS: A non-controlled multicenter prospective study included 245 patients operated on for non-revelatory long-bone metastasis, comparing patients operated on for fracture versus preventively according to body-mass index (BMI), ASA score, Katagiri score items and the 4 Mirels items. RESULTS: One hundred and twenty-six patients (51.4%) were operated on at fracture stage: 106 (84.1%) showed high risk on Mirels score (score>8), and 15 (11.9%) moderate risk (score=8). On multivariate analysis, 4 independent factors emerged: in increasing order, advanced age (OR=1.03; 95%CI 1.01-1.06), VAS pain score>6 (OR=1.47; 95%CI 1.02-2.11), WHO grade>2 (OR=2.74; 95%CI 1.22-6.15), and upper-limb location (OR=5.26; 95%CI 2.13-12.84). DISCUSSION: The present study confirmed that more than half of patients with long-bone metastasis are operated on at actual fracture stage, in agreement with the literature. Several studies highlighted the weakness of the Mirels score as a predictive instrument. Comparison between preventive and fracture-stage surgery showed that upper-limb location, intense pain, advanced age and impaired functional status were associated with fracture-stage surgery, and should be taken into account alongside the original Mirels criteria. This improved scoring instrument remains to be validated in a prospective study. LEVEL OF EVIDENCE: IV, prospective cohort study without control group.

Nationwide Patterns of Pathologic Fractures Among Patients Hospitalized With Bone Metastases.

OBJECTIVES: Pathologic fractures from bone metastases can significantly affect quality-of-life, although it is unclear which patients may be at high risk of this outcome. We aim to determine risk factors for pathologic fracture among patients admitted with bone metastases and to evaluate the association of pathologic fracture with clinical and economic outcomes. METHODS: The Healthcare Cost and Utilization Project National Inpatient Sample was queried for all patients hospitalized with bone metastases in 2016. Baseline differences between patients with and without pathologic fractures were assessed by χ and analysis of variance testing. Multivariable logistic regression was used to identify factors associated with fractures. RESULTS: In 2016, 272,275 hospital admissions were associated with a diagnosis of bone metastases, of which 11,960 (4.4%) had a primary diagnosis of pathologic fracture. Patients with pathologic fractures had a longer length-of-hospital-stay (mean 7.5 vs. 6.4 d; P<0.001) and higher cost-of-hospital-stay (mean $23,611 vs. $15,942; P<0.001) compared to patients without pathologic fractures. Primary cancers associated with increased likelihood of pathologic fracture included liver and intrahepatic bile duct (odds ratio [OR] 2.34; 95% confidence interval [CI], 1.65-3.32), multiple myeloma (OR 1.94; 95% CI, 1.31-2.86), and kidney and renal pelvis cancer (OR 1.89; 95% CI, 1.50-2.37). CONCLUSIONS: Nearly 5% of hospitalizations with bone metastases presented with a concomitant pathologic fracture, which was associated with longer inpatient stay and higher cost. Patients with hepatobiliary, renal cell carcinoma, or multiple myeloma, had a higher likelihood of pathologic fracture. These groups may benefit from increased outpatient monitoring, prophylactic stabilization, or early irradiation.

Bone fracture among people living with HIV: A systematic review and meta-regression of prevalence, incidence, and risk factors.

INTRODUCTION: People living with HIV (PLWH) had a higher prevalence and incidence rate of bone fracture compared to general population. Although several studies have explored this phenomenon, the prevalence and incidence rate of fracture were varied. OBJECTIVE: The aim of the study is to determine and analyze the pooled prevalence, incidence rate of fracture and fracture risk factors among people living with HIV (PLWH). METHODS: PubMed, Cochrane Library, CINAHL with full Text, and Medline databases for studies published up to August 2019 were searched. Studies reporting the prevalence or incidence of fracture among PLWH were included. Study quality was assessed using the Joanna Briggs Institute (JBI) appraisal tool. A meta-analysis with random-effects model was performed to determine pooled estimates of prevalence and incidence rates of fracture. A meta-regression was performed to determine the source of heterogeneity. RESULTS: The pooled estimated prevalence of fracture among PLWH was 6.6% (95% CI: 3.8-11.1) with pooled odds ratio of 1.9 (95%CI: 1.1-3.2) compared to the general population. The pooled estimates of fracture incidence were 11.3 per 1000 person-years (95% CI: 7.9-14.5) with incidence rate ratio (IRR) of 1.5 (95% CI: 1.3-1.8) compared to the general population. Risk factors for fracture incidence were older age (aHR 1.4, 95% CI: 1.3-1.6), smoking (aHR 1.3, 95% CI: 1.1-1.5), HIV/HCV co-infection (aHR 1.6, 95% CI: 1.3-1.9), and osteoporosis (aHR 3.3, 95% CI: 2.2-5.1). CONCLUSIONS: Our finding highlights a higher risk of fracture among PLWH compared to the general population. Osteoporosis, smoking and HIV/HCV coinfection as the significant modifiable risk factors should be prioritized by the HIV health providers when care for PLWH.

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.

Prevalence and complications of nonsurgical hypoparathyroidism in Korea: A nationwide cohort study.

OBJECTIVE: The risk of complications of nonsurgical hypoparathyroidism in Asia is unclear. We estimated the prevalence and risk of complications in patients with nonsurgical hypoparathyroidism. METHODS: We performed a retrospective cohort study using a nationwide claims database from 2005 to 2016. Among the entire Korean population, we identified 897 patients diagnosed with nonsurgical hypoparathyroidism during 2005-2015. We selected 210 patients with nonsurgical hypoparathyroidism during 2005-2008 who had no complications at baseline and followed them to 2016. Control subjects (n = 2075) were matched using propensity scores based on age, sex, and comorbid disease with a 1:10 ratio and monitored until 2016. RESULTS: The age-standardized prevalence of nonsurgical hypoparathyroidism was 0.2 cases per 100,000 persons in 2005. During a mean follow-up period of 9.5 years, patients with nonsurgical hypoparathyroidism had a higher risk of cardiovascular disease, especially arrhythmia (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.11-3.70) and heart failure (HR, 2.43; 95% CI, 1.22-4.83). The risk of vertebral fracture was higher in patients than in controls (HR, 2.27; 95% CI, 1.09-4.72). Patients had a significantly increased risk of renal disease (HR, 2.57; 95% CI, 1.56-4.21), seizure (HR, 5.74; 95% CI, 3.34-9.86), depression and bipolar disease (HR, 1.82; 95% CI, 1.30-2.56), and cataract (HR, 1.90; 95% CI, 1.30-2.79) compared with controls. CONCLUSIONS: The prevalence of nonsurgical hypoparathyroidism was very low in Korea but was associated with a higher risk of incident cardiovascular disease and vertebral fracture as well as known complications including renal disease, seizure, and cataract.

Assessment of Risk Factors for Fractures in Patients with Type 2 Diabetes over 60 Years Old: A Cross-Sectional Study from Northeast China.

AIMS: Previous evidence has demonstrated an increased fracture risk among the population with type 2 diabetes mellitus (T2DM). This study investigated the prevalence of bone fractures in elderly subjects (with and without type 2 diabetes) and identified any fracture risk factors, especially the risk factors for common known fractures in particular diabetic populations. METHODS: This cross-sectional study was conducted with community-dwelling people over 60 years old in nine communities from the city of Shenyang, which is the capital of Northeast China's Liaoning Province. A total of 3430 elderly adults (2201 females, mean ± standard deviation age 68.16 ± 6.1 years; 1229 males, 69.16 ± 6.7 years) were included. Our study measured the heel bone mineral density (BMD) and used the timed "up and go" (TUG) test and other indicators. In addition, we performed logistic regression analysis to explore the risk factors for fractures in the general population and the diabetic population and to analyze the differences. RESULTS: The results revealed that a total of 201 elderly persons (5.8%), with an average age of 70.05 ± 6.54 years, suffered from a history of fragility fractures, which affected more females (74.6%) than males (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (p = 0.001). The prevalence of fractures in the T2DM population was 7.3%, which was much higher than the 5.2% in non-T2DM population (T-score≤-2.5 (OR 1.750) were independent risk factors for fragility fractures in the non-T2DM population, but they were not risk factors in the T2DM population. CONCLUSIONS: This study found that low BMD and slow TUG time were independent risk factors for fractures in non-T2DM patients, while no associations were found in the T2DM population. Patients with T2DM have a higher risk for fractures even when they have sufficient BMD and a short TUG time. TUG and BMD underestimated the risk for fractures in the T2DM population.

Mineral bone disorder and osteoporosis in hemodialysis patients.

BACKGROUND: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. METHODS: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. RESULTS: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. CONCLUSIONS: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.