Persistent Mesodermal Differentiation Capability of Bone Marrow MSCs Isolated from Aging Patients with Low-Energy Traumatic Hip Fracture and Osteoporosis: A Clinical Evidence.

A low-energy hit, such as a slight fall from a bed, results in a bone fracture, especially in the hip, which is a life-threatening risk for the older adult and a heavy burden for the social economy. Patients with low-energy traumatic bone fractures usually suffer a higher level of bony catabolism accompanied by osteoporosis. Bone marrow-derived stem cells (BMSCs) are critical in osteogenesis, leading to metabolic homeostasis in the healthy bony microenvironment. However, whether the BMSCs derived from the patients who suffered osteoporosis and low-energy traumatic hip fractures preserve a sustained mesodermal differentiation capability, especially in osteogenesis, is yet to be explored in a clinical setting. Therefore, we aimed to collect BMSCs from clinical hip fracture patients with osteoporosis, followed by osteogenic differentiation comparison with BMSCs from healthy young donors. The CD markers identification, cytokines examination, and adipogenic differentiation were also evaluated. The data reveal that BMSCs collected from elderly osteoporotic patients secreted approximately 122.8 pg/mL interleukin 6 (IL-6) and 180.6 pg/mL vascular endothelial growth factor (VEGF), but no PDGF-BB, IL-1b, TGF-b1, IGF-1, or TNF-α secretion. The CD markers and osteogenic and adipogenic differentiation capability in BMSCs from these elderly osteoporotic patients and healthy young donors are equivalent and compliant with the standards defined by the International Society of Cell Therapy (ISCT). Collectively, our data suggest that the elderly osteoporotic patients-derived BMSCs hold equivalent differentiation and proliferation capability and intact surface markers identical to BMSCs collected from healthy youth and are available for clinical cell therapy.

Epidemiology of proximal femur fractures in the young population of Qatar.

PURPOSE: To review the epidemiological characteristics of proximal femur fractures in the young population (< 60 years) of Qatar between 2017 and 2019. METHODS: All patient treated for proximal femur fractures at Hamad General Hospital (HGH), a level one trauma center, were retrospectively reviewed between Jan 2017 and Dec 2019. All adults (18-60 years) with proximal femur fracture (femur head, femur neck, intertrochanteric and subtrochanteric fractures) were included with no restriction to the AO/OTA classification or fractures subtypes. Excluded cases were pathological fractures, cases with insufficient documentation or no radiographs. RESULTS: A total of 203 patients with a mean age of 40.07 ± 11.76 years were included, of who 89.9% were males. The incidence of proximal femur fracture was 3.12/100,000/year. Fall from height (48.1%) followed by road traffic accidents (26.9%) were common cause of injury. The most common fracture type was intertrochanteric fracture (36.1%) followed by femur neck fractures (33.7%). CONCLUSION: This study provides the initial insights into the proximal femur fractures in the young population of Qatar. This is the first study to investigate of the epidemiology of such fractures in this particular patient group. Contrary to the existing literature on older age groups, the majority of the injuries were observed in males. Falls from height followed by road traffic accidents were the primary mechanisms leading to these fractures. Improved understanding of the profile of these injuries can aid in their prevention by implementing more effective safety measures.

Patients with end-stage kidney disease have markedly abnormal cortical hip parameters by dual-energy X-ray absorptiometry.

BACKGROUND: Patients with end-stage kidney disease (ESKD) have higher fracture rates and post-fracture mortality than the general population, but bone mineral density by dual-energy X-ray absorptiometry (DXA) is less predictive of fracture in this patient group. Bone biopsy and high-resolution imaging indicate that cortical thickness (CT) is reduced and cortical porosity is increased in ESKD. The aim of this study was to assess cortical parameters using DXA in patients with ESKD. It was hypothesized that these parameters would show deterioration and be associated with fracture. METHODS: Using advanced hip analysis, normal age-related ranges were determined from 752 female and 861 male femur scans and were compared with scans of 226 patients with ESKD at the time of transplantation. RESULTS: Compared with controls, female patients had lower mean±SD CT (mms) at the femoral neck (FN) (2.59 ± 1.42 versus 5.23 ± 1.85), calcar (3.46 ± 1.07 versus 5.09 ± 1.30) and shaft (4.42 ± 1.21 versus 7.44 ± 2.07; P < 0.001 for each), and buckling ratios were higher (8.21 ± 4.6 versus 3.63 ± 1.42; P < 0.001), indicating greater FN instability. All findings were similar for men. Prevalent fracture was documented in 28.8% of patients; 12.4% vertebral only, 8.4% non-vertebral only and 8% vertebral plus non-vertebral. In adjusted models, each 1 SD reduction in FN CT and increase in the buckling ratio was associated with a respective 1.73 (1.22-2.46)- and 1.82 (1.49-2.86)-fold increase in the risk of prevalent vertebral fracture. CONCLUSIONS: In patients with ESKD, DXA-derived cortical parameters are markedly abnormal compared with age- and sex-matched controls. These parameters should be assessed for incident fracture prediction and targeting treatment.

Population-based Analysis for Risk of Suicide Death in Elderly Patients after Osteoporotic Fracture: a Nested Case-Control Study.

BACKGROUND: The purpose of study was to investigate the incidence rate of suicide in elderly patients with osteoporotic fractures in a nested case-control model and to analyze the change in the risk of suicide death over time after each osteoporotic fracture. METHODS: We used the National Health Insurance Service-Senior cohort of South Korea. Suicide cases and controls were matched based on sex and age at the index date. Controls were randomly selected at a 1:5 ratio from the set of individuals who were at risk of becoming a case at the time when suicide cases were selected. Conditional logistic regression analysis was performed to evaluate the association between each type of osteoporotic fracture and the risk of suicide death. RESULTS: Three thousand seventy suicide cases and 15,350 controls were identified. Patients with hip fracture showed an increased risk of suicide death within 1 year of fracture (adjusted odds ratio [aOR] = 2.64; 95% confidence interval [CI], 1.57-4.46; P < 0.001) compared to controls. However, the increased risk of suicide death in patients with hip fracture lasted up to 2 years (aOR = 1.59; 95% CI, 1.04-2.41; P = 0.031). Spine fracture increased the risk of suicide deaths for all observation periods. There was no evidence that humerus fracture increased the risk of suicide death during the observational period. Radius fracture increased only the risk of suicide death within 2 years of fracture (aOR = 1.43; 95% CI, 0.74-2.77; P = 0.282). CONCLUSION: There were noticeable differences in both degree and duration of increased suicide risks depending on the type of osteoporotic fracture. Mental stress and suicide risk in elderly patients after osteoporotic fracture should be assessed differently depending on the types of fracture.

TAFA2 Induces Skeletal (Stromal) Stem Cell Migration Through Activation of Rac1-p38 Signaling.

Understanding the mechanisms regulating recruitment of human skeletal (stromal or mesenchymal) stem cells (hMSC) to sites of tissue injury is a prerequisite for their successful use in cell replacement therapy. Chemokine-like protein TAFA2 is a recently discovered neurokine involved in neuronal cell migration and neurite outgrowth. Here, we demonstrate a possible role for TAFA2 in regulating recruitment of hMSC to bone fracture sites. TAFA2 increased the in vitro trans-well migration and motility of hMSC in a dose-dependent fashion and induced significant morphological changes including formation of lamellipodia as revealed by high-content-image analysis at single-cell level. Mechanistic studies revealed that TAFA2 enhanced hMSC migration through activation of the Rac1-p38 pathway. In addition, TAFA2 enhanced hMSC proliferation, whereas differentiation of hMSC toward osteoblast and adipocyte lineages was not altered. in vivo studies demonstrated transient upregulation of TAFA2 gene expression during the inflammatory phase of fracture healing in a closed femoral fracture model in mice, and a similar pattern was observed in serum levels of TAFA2 in patients after hip fracture. Finally, interleukin-1ß was found as an upstream regulator of TAFA2 expression. Our findings demonstrate that TAFA2 enhances hMSC migration and recruitment and thus is relevant for regenerative medicine applications. Stem Cells 2019;37:407-416.

Three-Dimensional Microstructural Basis for Differential Occurrence of Subcapital versus Basicervical Hip Fractures in Men.

We analyzed the bone microarchitecture of the subcapital and basicervical subregions of the femoral neck in men, to determine whether microarchitectural differences of cortical or trabecular bone can explain differential frequency of subcapital vs. basicervical fractures, especially in aged persons. The study sample encompassed twenty male proximal femora obtained during autopsy. They were divided in two age groups: young (< 40 years, n = 10) and aged (> 60 years, n = 10). Micro-computed tomography was used to evaluate cortical and trabecular microarchitecture of the subcapital and basicervical regions of the superolateral femoral neck-typical fracture initiation site. Basicervical region showed significantly thicker and less porous cortex than subcapital region (p = 0.02, p < 0.001, respectively), along with increased distance between cortical pores (p = 0.004) and smaller pore diameters (p = 0.069). Higher trabecular number (Tb.N: p = 0.042), lower trabecular thickness (Tb.Th: p < 0.001), and lower trabecular separation (p = 0.003) were also hallmarks of the basicervical compared to subcapital region, although BV/TV was similar in both regions (p = 0.133). Age-related deterioration was mostly visible in trabecular bone (for BV/TV, Tb.Th, Tb.N and fractal dimension: p = 0.026, p = 0.049, p = 0.059, p = 0.009, respectively). Moreover, there were tendencies to age-specific patterns of trabecular separation (more pronounced inter-site differences in aged) and cortical thickness (more pronounced inter-site differences in young). Trabecular microarchitecture corresponded to cortical characteristics of each region. Our study revealed the microarchitectural basis for higher incidence of subcapital than basicervical fractures of the femoral neck. This is essential for better understanding of the fracture risk, as well as for future strategies to prevent hip fractures and their complications.

Fractures and their sequelae in non-dialysis-dependent chronic kidney disease: the Stockholm CREAtinine Measurement project.

INTRODUCTION: People undergoing maintenance dialysis are at high risk for fractures, but less is known about fracture incidence and associated outcomes in earlier stages of chronic kidney disease (CKD). METHODS: We conducted an observational analysis from the Stockholm Creatinine Measurement project, a Swedish health care utilization cohort during 2006-11. We identified all adults with confirmed CKD Stages 3-5 and no documented history of fractures and extracted information on comorbid history, ongoing medication, cardiovascular events and death. We studied incidence rates of fractures (overall and by location), with the estimated glomerular filtration rate (eGFR) as time-dependent exposure. We then studied hazard ratios [HRs and 95% confidence intervals (CIs)] for the events of death and major adverse cardiac events (MACE) using Cox regression with fracture as time-varying exposure. RESULTS: We identified 68 764 individuals with confirmed CKD (mean age 79 years, 56% women). During a median follow-up of 2.7 years, 9219 fractures occurred, of which 3105 were hip fractures. A more severe CKD stage was associated with a higher risk of fractures, particularly hip fractures: compared with CKD Stage 3a, the adjusted HR was 1.10 (95% CI 1.02-1.19), 1.32 (1.17-1.49) and 2.47 (1.94-3.15) for CKD Stage 3b, 4 and 5, respectively. Spline curves suggested a linear association with fracture risk with an eGFR <30 mL/min/1.73 m2. Compared with non-fracture periods, incident fracture was associated with a 4-fold increased mortality within 90 days [HR 4.21 (95% CI 3.95-4.49)]. The risk remained elevated beyond 90 days [HR 1.47 (95% CI 1.40-1.54)] and was stronger after hip fractures. Post-fracture MACE risk was also highest in the first 90 days [HR 4.02 (95% CI 3.73-4.33)], particularly after hip fractures, and persisted beyond 90 days [HR 1.20 (95% CI 1.10-1.30)]. CONCLUSION: Our findings highlight the commonness of fractures and the increased risk for subsequent adverse outcomes in CKD patients. These results may inform clinical decisions regarding post-fracture clinical surveillance and fracture prevention strategies.

Distribution of Femoral Head Subchondral Fracture Site Relates to Contact Pressures, Age, and Acetabular Structure.

OBJECTIVE. Nontraumatic subchondral fracture of the femoral head (FH) is often seen in elderly patients with osteoporosis and acetabular dysplasia. Although this injury can also occur in young people, even those without osteoporosis, it remains unclear who is at risk. We examined the acetabular structure and sites of subchondral fracture of the FH in young patients compared with those in middle-aged and older patients. MATERIALS AND METHODS. Forty-eight hips with nontraumatic subchondral fracture of the FH were divided into two groups according to patient age: young (< 40 years) and middle-aged and older (≥ 40 years). Dysplasia and retroversion were defined as a lateral center-edge angle of < 20° and crossover sign on anterosuperior radiographs, respectively. Locations and extents of fracture were evaluated by measuring the edge location of low-signal-intensity bands on coronal T1-weighted MR images. Stress distribution on subchondral bone in young patients was evaluated in contralateral unaffected hips with the same acetabular structure using finite element modeling based on CT. RESULTS. Twelve hips were in young patients and 36 were in middle-aged and older patients. Hips in young patients showed retroversion in 41.7%, whereas those in middle-aged and older patients had dysplasia in 38.9%. Young patients had larger mediolateral fractures; fractures in middle-aged and older patients were laterally located. Anterosuperior fractures were seen in both groups. Contact stress in patients with retroversion was mainly distributed on the mediolateral and superior sides but was concentrated laterally and superiorly in one patient with dysplasia. CONCLUSION. Mediolateral and anterosuperior fractures and stress distribution by retroversion were commonly observed in young patients, suggesting partial involvement of retroversion in the mechanism of injury of nontraumatic subchondral fractures of the FH in young patients.

Evaluation of Hip Geometry Parameters in Patients With a Distal Radius Fracture.

BACKGROUND: Patients with a distal radius fracture (DRF) have an increased risk of subsequent fractures including hip fractures. The purpose of this study was to evaluate whether women with a DRF have certain hip geometry parameters known to indicate susceptibility to hip fractures. METHODS: We compared bone mineral density (BMD) and hip geometry parameters (hip axis length, neck shaft angle, mean cortical thickness, femur neck width, cross-sectional area [CSA], cross-sectional moment of inertia, section modulus, and buckling ratio) in 181 women with a DRF (DRF group) and 362 propensity score-matched women without a fracture (control group). We evaluated the associations between DRF and hip geometry parameters using logistic regression analysis. RESULTS: The DRF group had lower hip BMD; lower cortical thickness, CSA, and section modulus; and higher buckling ratio than the control group (all p < 0.05). The occurrence of a DRF was significantly associated with decreases in neck shaft angle (odds ratio [OR], 1.047; 95% confidence interval [CI], 1.008-1.088) and CSA (OR, 3.114; 95% CI, 1.820-5.326) after adjusting for age, BMI, and total hip BMD. CONCLUSIONS: In this study, women with a DRF were more likely than women without a DRF to have hip geometry parameters known to indicate susceptibility to hip fractures. Our results suggest that not only low hip BMD but also a decreased CSA could account for the increased risk of subsequent hip fracture in patients with a DRF.

Blood Transfusion for Elderly Patients with Hip Fracture: a Nationwide Cohort Study.

BACKGROUND: This nationwide study aimed to investigate the blood transfusion status of elderly hip fracture patients and to examine the effect of packed red blood cell transfusion on all-cause mortality. METHODS: From the Korean National Health Insurance Service-Senior cohort consisting of 588,147 participants aged over 60 years in 2002, a total of 14,744 new-onset hip fracture patients aged 65-99 years were followed up for 11 years. The adjusted hazard ratios (aHRs), risk ratios, and their 95% confidence intervals were estimated by the Cox proportional hazard model and Poisson regression model. RESULTS: There were 10,973 patients (74.42%) in the transfusion group and 3,771 (25.58%) patients in the non-transfusion group. The mean volume of blood transfusion was 1,164.51 mL (± 865.25; median, 800 mL; interquartile range, 640-1,440). In the multivariable-adjusted Cox proportional hazard model, the transfusion group had 1.34-fold more risk of all-cause mortality than the non-transfusion group (aHR, 1.34; 95% confidence interval [CI], 1.26-1.42). In the multivariate-adjusted Poisson regression model, hip fracture patients in the transfusion group were 1.43 (adjusted risk ratio [aRR], 1.43; 95% CI, 1.09-1.87; P = 0.009) folds more likely to die within 30 days than those in the non-transfusion group. The mortality risk was highest at 90 days (aRR, 1.64; 95% CI, 1.40-1.93; P < 0.001) and slightly decreased at 180 days (aRR, 1.58; 95% CI, 1.40-1.79; P < 0.001) and 1 year (aRR, 1.43; 95% CI, 1.31-1.58; P < 0.001). CONCLUSION: In this nationwide representative cohort study, blood transfusion was performed in 75% of hip fracture patients. Even after adjusting for comorbidity and anticoagulant use, the postoperative results (hospitalization, mortality) of the transfusion group did not show significantly worse results than the non-transfusion group. Therefore, adequate patient blood management can only improve the patient's outcome after hip fracture surgery.

The Influence of Renal Dialysis on All-Cause Mortality in Older Patients with Hip Fracture: a Korean Nationwide Cohort Study.

BACKGROUND: The purpose of this study was to analyze the all-cause mortality rate over time after elderly hip fracture in end-stage renal disease (ESRD) patients with dialysis, using a Korean nationwide claims database. METHODS: This retrospective nationwide study identified subjects from the Korean National Health Insurance Service-Senior cohort (NHIS-Senior). The NHIS-Senior (total of 588,147 participants) was constructed by 10% random sampling and was designed to represent the elderly living in Korea. Subjects were patients aged 65-99 years who underwent surgical treatment for femoral neck fractures or intertrochanteric fractures. A generalized estimating equation model with Poisson distribution and logarithmic link function was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) to measure associations between renal dialysis and cumulative mortality in various time frames. RESULTS: The total number of patients included in this study was 16,818. These patients were divided into two groups: 116 (0.69%) in the dialysis group and 16,702 (99.31%) in the no-dialysis group. The mean length of hospital stay was 43.87 ± 48.45 days in the dialysis group and 36.29 ± 37.49 days in the no-dialysis group (P = 0.095). The effect of renal dialysis on all-cause mortality was 2.29-fold (aRR; 95% CI, 1.29-4.06; P = 0.005) within 30 days and 1.72-fold (aRR; 95% CI, 1.34-2.21; P < 0.001) within 1-year after hip fracture compared to the no-dialysis group. And, the effect of renal dialysis of in-hospital mortality was 2.72-fold (aRR; 95% CI, 1.71-4.33; P < 0.001) compared to the no-dialysis group. CONCLUSION: Elderly patients who underwent dialysis have very high mortality rates after hip fracture. Therefore, it is considered that postoperative care through multidisciplinary management and understanding of pathophysiology for the ESRD patients is necessary.

Effect of Pneumonia on All-cause Mortality after Elderly Hip Fracture: a Korean Nationwide Cohort Study.

BACKGROUND: The purposes of this study were 1) to investigate the incidence of pneumonia during hospitalization in elderly hip fracture patients, 2) to evaluate the effect of pneumonia on 30 day to 1 year mortality and 3) to analyze the impact of age and gender on the mortality rate in the pneumonia patients using a nationwide cohort of Korea. METHODS: The Korean National Health Insurance Service (NHIS) database included approximately 5.5 million Korean enrollees > 60 years of age. A total of 588,147 participants were randomly selected for senior cohort using 10% simple random sampling. We identified senile (> 65 years old) patients who underwent hip fracture surgery from January 2005 to December 2014 and those who developed pneumonia during hospitalization from the NHIS-Senior cohort. The index date of hip fracture occurrence was defined as the date of admission to the acute care hospital. The last date of follow-up was defined as the date of death or 31 December 2015, whichever came first. A multivariable-adjusted Cox proportional hazards model was used to investigate the effects of pneumonia on all-cause mortality. RESULTS: During the enrollment period, a total of 14,736 patients, who were older than 65 years, underwent hip fracture surgeries. Among them, 1,629 patients (11.05%) developed pneumonia during the hospitalization. The pneumonia incidence was 16.39% (601/3,666) in men patients and 9.29% (1,028/10,042) in women patients. Compared to 13,107 non-pneumonia patients, adjusted relative risk (aRR) of death in pneumonia patients was 2.69 (95% confidence interval [CI], 2.14-3.38; P < 0.001) within postoperative 30-day, 3.40 (95% CI, 3.01-3.83; P < 0.001) within postoperative 90-day, 2.86 (95% CI, 2.61-3.15; P < 0.001) within postoperative 180-day and 2.31 (95% CI, 2.14-2.50; P < 0.001) within postoperative 1-year. According to patient's age, the aRR of death in pneumonia patients was 5.75 (95% CI, 2.89-11.43) in adults aged < 70 years, 5.14 (95% CI, 4.08-6.46) in those aged 70-79 years, 3.29 (95% CI, 2.81-3.86) in those aged 80-89 years and 2.02 (95% CI, 1.52-2.69) in those aged ≥ 90 years. The aRR was 3.63 (95% CI, 3.01-4.38) in men pneumonia patients, and 3.27 (95% CI, 2.80-3.83) in women pneumonia patients. CONCLUSION: The prevalence of pneumonia in elderly hip fracture patients was 11.05%. Men had higher incidence (16.39%) than women (9.29%). Compared to non-pneumonia patients, the pneumonia patients had higher 30-day to 1-year mortalities with aRR of 2.31 to 3.40. They had increased mortality in all age groups older than 65 years with aRR of 1.52 to 4.08. Both genders of pneumonia patients had higher risk of mortality (aRR, 3.63 in men and 3.27 in women) compared to non-pneumonia patients.

Lesser Trochanteric Fragments in Unstable Pertrochanteric Hip Fractures: A Morphological Study Using Three-Dimensional Computed Tomography (3-D CT) Reconstruction.

BACKGROUND The lesser trochanter (LT) posterior cortical extension (LTPE) fragment is important for joint stability during reconstruction in unstable pertrochanteric hip fractures. This study aimed to investigate the morphological characteristics of the LT fragments using three-dimensional computed tomography (3-D CT) reconstruction and to compare clinical outcomes in different subgroups of 31A2 fractures. MATERIAL AND METHODS A retrospective study included CT images of 58 cases of 31A2 type unstable pertrochanteric fractures, using the Arbeitsgemeinschaft für Osteosynthesefragen and Orthopedic Trauma Association (AO/OTA) classification. After 3-D CT reconstruction, all the displaced fragments were reduced and the morphologic parameters of the LT fragments were measured. RESULTS At the mid-level of the LT, the mean cortical extension of the LT fragment was 33.5 mm in the posterior wall (83%), 19.0 mm in the medial wall (53%). The mean distal cortical extension from the lower edge of the LT was 13.0 mm. The LT fragment occupied 38% of the whole cortical circumference. Comparison of the subgroups showed that the LT fragment of A2.3 had a larger cortical extension in the posterior, medial, and distal cortex. The mean fracture collapse was 4.7 mm in A2.2 fractures and 5.4 mm in A2.3 fractures (p=0.311). Despite the increased size of the LT fragment in subtype A2.3 fracture compared with subtype A2.2 fracture, this did not influence the clinical outcome. CONCLUSIONS The 3-D morphology of the LT fragment from CT imaging provided a better understanding of the characteristics of subgroups of unstable pertrochanteric fractures, which may improve and guide implant choice.

Clinical utility of virtual noncalcium dual-energy CT in imaging of the pelvis and hip.

Dual-energy virtual noncalcium images are increasingly used to identify marrow edema which accompanies bony pelvic injuries and marrow pathology obscured by cancellous bone. We present a clinical perspective of our experience using virtual noncalcium images in the work up of pelvic osseous pathology.

Lower risk of hip fractures among Swedish women with large hips?

In women, a large hip circumference (HC) related to lower hip fracture risk, independent of age and regardless if HC was measured long before or closer to the fracture. In older women, body mass index (BMI) explained the protection. INTRODUCTION: In postmenopausal women, HC has been suggested to inversely associate with hip fracture while this has not been investigated in middle-aged women. We examined the association between HC, measured at two different time points, and hip fracture in a Swedish female population-based sample monitored for incident hip fractures over many years. METHODS: Baseline HC, measured in 1968 or 1974 (n = 1451, mean age 47.6 years), or the HC measures that were the most proximal before event or censoring (n = 1325, mean age 71.7 years), were used to assess the effects of HC on hip fracture risk in women participating in the Prospective Population Study of Women in Gothenburg. HC was parameterized as quintiles with the lowest quintile (Q1) as reference. Incident hip fractures over 45 years of follow-up (n = 257) were identified through hospital registers. RESULTS: Higher quintiles of HC at both baseline and proximal to event were inversely associated with hip fracture risk in age-adjusted models, but only baseline HC predicted hip fractures independently of BMI and other covariates (HR (95% CI) Q2, 0.85 (0.56-1.27); Q3, 0.59 (0.36-0.96); Q4, 0.57 (0.34-0.96); Q5, 0.58 (0.31-1.10)). CONCLUSIONS: A large HC is protective against hip fracture in midlife and in advanced age, but the association between proximal HC and hip fracture was explained by concurrent BMI suggesting that padding was not the main mechanism for the association. The independent protection seen in middle-aged women points to other mechanisms influencing bone strength.

What Factors Are Associated With Early Mortality in Patients Undergoing Femur Surgery for Metastatic Lung Cancer?

BACKGROUND: Pathologic fractures of the femur resulting from metastasis severely increase mortality in patients with nonsmall cell lung cancer (NSCLC). However, factors associated with early mortality after surgery have not been elucidated. QUESTIONS/PURPOSES: The purpose of this study was to identify clinical and laboratory factors available to surgeons before surgery for a metastatic femur in patients with metastatic lung cancer that might be associated with mortality at 1 and 3 months. METHODS: Between 2010 and 2014 we treated 126 patients for pathologic fracture of the femur caused by NSCLC. Of those, complete data sets for the parameters of interest (including clinical factors, laboratory factors, and survivorship) were available in 105 (83%). The factors we considered included sex, age, fracture location, surgical procedure, postoperative complications, blood cell counts, serum biomarkers, genetic alterations of primary cancer, chemotherapeutic agents, preoperative radiation therapy, pleural effusion, bone and internal organ metastasis, performance scores, and medical center where the treatment was performed. Multivariate logistic regression was performed to identify factors associated with mortality at 1 and 3 months. RESULTS: Intertrochanteric location was associated with a higher risk of death (odds ratio [OR], 17.0; 95% confidence interval [CI], 2.65-109.5), lower serum albumin level was associated with an increased risk of death (OR, 0.13; 95% CI, 0.028-0.60), and availability of a suitable chemotherapeutic target agent was associated with a lower risk of death (OR, 0.28; 95% CI, 0.08-0.91) within 3 months of surgery. Undergoing reconstruction with an endoprosthesis was associated with a higher risk of death (OR, 48.3; 95% CI, 1.7-1329) and elevated serum leukocyte count (OR, 1.2; 95% CI, 1.0-1.4) and elevated alanine aminotransferase (ALT) were associated with a higher risk of death (OR, 1.1; 95% CI, 1.0-1.2) within 1 month of surgery. CONCLUSIONS: Although the risk factors for early mortality need to be validated by prospective studies, surgical options need to be reconsidered in patients with femoral metastases from NSCLS showing high ALT or leukocytosis on the preoperative blood test. LEVEL OF EVIDENCE: Level III, prognostic study.

The depth of the low-intensity band on the T1-weighted MR image is useful for distinguishing subchondral insufficiency fracture from osteonecrosis of the collapsed femoral head.

PURPOSE: To verify the hypothesis that depth of the low-intensity band on T1-weighted MR image is useful for distinguishing subchondral insufficiency fracture (SIF) from osteonecrosis of the collapsed femoral head (ON). PATIENTS AND METHODS: We reviewed 35 consecutive hips in 35 patients with radiological evidence of subchondral collapse of the femoral head and available MR images and histology between May 2013 and January 2016. Both clinical and radiological appearances were investigated. The ratios of distance from articular surface of the femoral head to the T1 low-intensity band to femoral head diameter (band depth ratio: BDR) on (1) mid-coronal slice of MR images and that on (2) coronal slice of MR images in which the highest BDR was observed, were calculated. RESULTS: The mean age in SIF group was significantly higher than that in ON group (SIF: 68 years, ON: 49 years, P = 0.0017). The rates of history of steroid intake or alcohol consumption in SIF group were significantly lower than those in ON group (P = 0.0022 and P = 0.0408, respectively). The mean BDRs in SIF group were (1) 0.16 and (2) 0.23, which were significantly lower than those in ON group [(1) 0.42 and (2) 0.59] (P < 0.0001 for both). The cut-off BDR values to differentiate SIF from ON were (1) 0.22 and (2) 0.38, respectively. CONCLUSION: The results of the study suggest that depth of the low-intensity band on T1-weighted MR image is useful for distinguishing SIF from ON in cases with collapsed femoral heads.

No difference in flexion power despite iliopsoas fatty degeneration in healed hip fractures with large lesser trochanter displacement.

OBJECTIVE: To evaluate iliopsoas atrophy and loss of function after displaced lesser trochanter fracture of the hip. DESIGN: Cohort study. SETTING: District hospital. PATIENTS: Twenty consecutive patients with pertrochanteric fracture and displacement of the lesser trochanter of > 20 mm. INTERVENTION: Fracture fixation with either an intramedullary nail or a plate. OUTCOME MEASUREMENTS: Clinical scores (Harris hip, WOMAC), hip flexion strength measurements, and magnetic resonance imaging findings. RESULTS: Compared with the contralateral non-operated side, the affected side showed no difference in hip flexion force in the supine upright neutral position and at 30° of flexion (205.4 N vs 221.7 N and 178.9 N vs. 192.1 N at 0° and 30° flexion, respectively). However, the affected side showed a significantly greater degree of fatty infiltration compared with the contralateral side (global fatty degeneration index 1.085 vs 0.784), predominantly within the psoas and iliacus muscles. CONCLUSION: Severe displacement of the lesser trochanter (> 20 mm) in pertrochanteric fractures did not reduce hip flexion strength compared with the contralateral side. Displacement of the lesser trochanter in such cases can lead to fatty infiltration of the iliopsoas muscle unit. The amount of displacement of the lesser trochanter did not affect the degree of fatty infiltration. LEVEL OF EVIDENCE: II.

Increased cortical porosity in women with hip fracture.

BACKGROUND: Hip fractures cause increased mortality and disability and consume enormous healthcare resources. Only 46% of hip fracture patients have osteoporosis at the total hip according to dual-energy X-ray absorptiometry (DXA) measurement. Cortical porosity increases with ageing and is believed to be important for bone strength. OBJECTIVE: To investigate whether older women with hip fracture have higher cortical porosity than controls, and if so whether this difference is independent of clinical risk factors and areal bone mineral density (aBMD). METHODS: From an ongoing population-based study, we identified 46 women with a prevalent X-ray-verified hip fracture and 361 control subjects without any fractures. aBMD was measured with DXA. High-resolution peripheral quantitative computed tomography was used to measure bone microstructure at the standard (ultradistal) site and at 14% (distal) of the tibial length. RESULTS: Women with a previous hip fracture had lower aBMD at the femoral neck (-11.8%) and total hip (-14.6%) as well as higher cortical porosity at the ultradistal (32.1%) and distal (29.3%) tibia compared with controls. In multivariable logistic regression analysis, with adjustment for covariates (age, height, weight, smoking, calcium intake, physical activity, walk time, oral glucocorticoids, parental hip fracture, rheumatoid arthritis, previous fall, current bisphosphonate treatment and femoral neck aBMD), cortical porosity at the ultradistal [odds ratio per standard deviation increase (95% confidence interval) 2.61 (1.77-3.85)] and distal [1.57 (1.12-2.20)] sites was associated with prevalent hip fracture. CONCLUSION: Cortical porosity was associated with prevalent hip fracture in older women independently of femoral neck aBMD and clinical risk factors.

Porotic paradox: distribution of cortical bone pore sizes at nano- and micro-levels in healthy vs. fragile human bone.

Bone is a remarkable biological nanocomposite material showing peculiar hierarchical organization from smaller (nano, micro) to larger (macro) length scales. Increased material porosity is considered as the main feature of fragile bone at larger length-scales. However, there is a shortage of quantitative information on bone porosity at smaller length-scales, as well as on the distribution of pore sizes in healthy vs. fragile bone. Therefore, here we investigated how healthy and fragile bones differ in pore volume and pore size distribution patterns, considering a wide range of mostly neglected pore sizes from nano to micron-length scales (7.5 to 15000 nm). Cortical bone specimens from four young healthy women (age: 35 ± 6 years) and five women with bone fracture (age: 82 ± 5 years) were analyzed by mercury porosimetry. Our findings showed that, surprisingly, fragile bone demonstrated lower pore volume at the measured scales. Furtnermore, pore size distribution showed differential patterns between healthy and fragile bones, where healthy bone showed especially high proportion of pores between 200 and 15000 nm. Therefore, although fragile bones are known for increased porosity at macroscopic level and level of tens or hundreds of microns as firmly established in the literature, our study with a unique assessment range of nano-to micron-sized pores reveal that osteoporosis does not imply increased porosity at all length scales. Our thorough assessment of bone porosity reveals a specific distribution of porosities at smaller length-scales and contributes to proper understanding of bone structure which is important for designing new biomimetic bone substitute materials.