Risk prediction of second hip fracture by bone and muscle density of the hip varies with time after first hip fracture: A prospective cohort study.

Purpose: Predictors of 'imminent' risk of second hip fracture are unknown. The aims of the study were to explore strength of hip areal bone mineral density (aBMD), and muscle area and density for predicting second hip fracture at different time intervals. Methods: Data of the Chinese Second Hip Fracture Evaluation were analyzed, a longitudinal study to evaluate the risk of second hip fracture (of the contralateral hip) by using CT images obtained immediately after first hip fracture. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur at the contralateral unfractured side. Patients were followed up for a median time of 4.5 years. Separate Cox models were used to predict second hip fracture risk at different time intervals after first event adjusted for age, sex, BMI and diabetes. Results: The mean age of subjects with imminent (within 1st or 2nd year) second hip fracture was 79.80 ± 5.16 and 81.56 ± 3.64 years. In the 1st year after the first hip fracture, femoral neck (FN) aBMD predicted second hip fracture (HR 5.88; 95 % CI, 1.32-26.09). In the remaining years of follow-up after 2nd year, muscle density predicted second hip fracture (G.MaxM HR 2.13; 95 % CI, 1.25-3.65,G.Med/MinM HR 2.10; 95 % CI, 1.32-3.34). Conclusions: Our results show that femoral neck aBMD is an important predictor for second hip fracture within the first year and therefore suggest supports the importance concept of early and rapid-acting bone-active drugs to increase hip BMD. In addition, the importance of muscle density predicting second hip fracture after the second year suggest post hip fracture rehabilitation and exercise programs could also be important to reduce muscle fatty infiltration.

Computational thermochemistry: extension of Benson group additivity approach to organoboron compounds and reliable predictions of their thermochemical properties.

High-level computational data for standard gas phase enthalpies of formation, entropies, and heat capacities are reported for 116 compounds of boron. A comparison of the results with extant experimental and computational benchmark values reveals important trends and clear outliers. Recommendations are made to revise some of the key quantities, such as the enthalpies of formation of orthoboric acid, trimethylthioborate, and triphenylborane, the last of which is found to be considerably in error. The uncertainties associated with the experimental values are found to exceed those of high-level calculations by a clear margin, prompting the redetermination of Benson group additivity contributions for boron-based groups on purely computational grounds. The applicability of the established group contribution values is demonstrated by estimating thermochemical data for large organoboron compounds that cannot be treated with high-level quantum chemical methods and comparing the results with existing experimental and computational values.

Bioactive glass granules versus standard autologous and allogeneic bone grafts: a randomized trial of 49 adult bone tumor patients with a 10-year follow-up.

BACKGROUND AND PURPOSE: As a synthetic bone void filler, bioactive glasses (BGs) may enhance angiogenesis and osteogenesis. In this randomized trial, we compared the clinical efficacy of BG granules and standard bone grafts in patients undergoing surgery for benign bone tumors. PATIENTS AND METHODS: 49 recruited patients were randomized to receive BG granules or undergo conventional bone grafting to fill defects following tumor removal. As the standard of care, small-sized defects were filled with autologous graft, and large-sized defects were filled with allogeneic graft. The primary endpoint was treatment success at 1 year, defined by no reoperation, no tumor recurrence, and no device-related adverse events. Secondary endpoints included patient-reported outcomes (Rand-36 and pain scores) and quantitative assessment of blood flow and metabolic activity by means of 18F-fluoride PET/CT imaging. As an off-trial group, 15 children and adolescents (age < 18 years) underwent tumor removal and BG-filling, without randomization. RESULTS: At 1-year, 21 of 25 BG-treated patients (risk estimate 0.84, 95% confidence interval [CI] 0.70-0.98) and 20 of 24 patients in the standard of care group (0.83, CI 0.68-0.98) met the criteria for treatment success. The groups had similar Rand-36 scores. In patients with small defects, BG filling was associated with shorter operative time and less postoperative pain at 1 month. In patients with large defects, blood flow was similar, but BG-filled defects showed higher metabolic activity than allograft-filled defects at 1-year. The survey of the postoperative period ≥10 years revealed no BG-related adverse events. INTERPRETATION: BG granules had similar overall rates of treatment success compared with autografts and allografts, but large-scale trials are needed for the confirmation of clinical equivalence. The extended metabolic activity confirms the expected cellular responses of osseointegrated BG granules.

High-Level Ab Initio Predictions of Thermochemical Properties of Organosilicon Species: Critical Evaluation of Experimental Data and a Reliable Benchmark Database for Extending Group Additivity Approaches.

A high-level composite quantum chemical method, W1X-1, is used herein to calculate the gas-phase standard enthalpy of formation, entropy, and heat capacity of 159 organosilicon compounds. The results set a new benchmark in the field that allows, for the first time, an in-depth assessment of existing experimental data on standard enthalpies of formation, enabling the identification of important trends and possible outliers. The calculated thermochemical data are used to determine Benson group additivity contributions for 60 Benson groups and group pairs involving silicon. These values allow fast and accurate estimation of thermochemical parameters of organosilicon compounds of varying complexity, and the data acquired are used to assess the reliability of experimental work of Voronkov et al. that has been repeatedly criticized by Becerra and Walsh. Recent results from other computational investigations in the field are also carefully discussed through the prism of reported advancements.

Denosumab in Cementless Total Hip Arthroplasty: Multivariate Reanalysis of 3D Femoral Stem Migration and the Influence on Outliers.

In cementless total hip arthroplasty, adequate implant stability is necessary for the success of osseointegration and rapid clinical recovery. Postoperative femoral stem migration, measured by radiostereometric analysis (RSA), defines the initial stability achieved during surgical implantation. In a recent trial of 65 postmenopausal women randomized 1:1 denosumab:placebo, denosumab failed to reduce the initial migration of a cementless femoral stem despite the successful prevention of periprosthetic bone loss. The trial applied the current RSA standard, which examined stem migration on an axis-by-axis basis and did not consider more complex three-dimensional (3D) migration. Therefore, we performed a reanalysis of the trial data using a multivariate hierarchical linear mixed model (LMM). As an additional limitation, the data included influential outliers. Women with normal bone mineral density exhibited significantly (p = 0.036) less stem subsidence compared with osteopenic and osteoporotic women. Denosumab significantly decreased the variance of stem migration in osteopenic and osteoporotic women. The mean magnitude of 3D stem migration did not differ between denosumab-treated and placebo-treated women (p = 0.820). After application of a common statistical definition for RSA outlier identification, there were eight (12%) outliers, six in the placebo group and two in the denosumab group (p = 0.149). After exclusion of the outliers, the repeated LMM analysis demonstrated a trending difference in 3D stem migration (p = 0.086), with a significant difference of z-axis rotation (valgus-varus tilt) of the femoral stem (p = 0.029). The observed effect size was small and without clinically important differences in postoperative recovery. Based on a Monte Carlo simulation with random-generated 3D migration data, multivariate LMM showed greater statistical power than univariate analyses. The application of hierarchical LMM facilitated the analysis of implant migration as a factual 3D event. The observed trend in the lower number of RSA outliers in denosumab-treated subjects warrants powered large-scale trials. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Volumetric Bone Mineral Density in Cementless Total Hip Arthroplasty in Postmenopausal Women: Effects on Primary Femoral Stem Stability and Clinical Recovery.

BACKGROUND: In cementless total hip arthroplasty, femoral stems should preferably not migrate at all postoperatively. This goal is difficult to achieve in postmenopausal women with impaired bone quality. Here, we explored the clinical importance of initial stem migration, measured by radiostereometric analysis (RSA), in women who underwent quantitative computed tomography (CT) of the involved hip preoperatively. METHODS: A prospective cohort of 65 postmenopausal women (mean age, 69 years) with hip osteoarthritis and Dorr type-A or B femoral anatomy underwent total hip arthroplasty with implantation of a tapered, single-wedge femoral stem. Volumetric bone mineral density (BMD) was measured using quantitative CT. Femoral stem translation and rotation were measured using model-based RSA within 3 days after the surgical procedure and were repeated at 3, 5, and 11 months. Postoperative recovery parameters included walking speed, walking activity, and patient-reported outcome measures. Subjects were categorized into 2 groups according to the magnitude of initial 5-month stem subsidence (<2 mm or ≥2 mm); RSA outliers (n = 7) were analyzed separately. RESULTS: Subjects with stem subsidence of ≥2 mm (mean, 3.09 mm [95% confidence interval (CI), 2.70 to 3.47 mm]) had lower intertrochanteric volumetric BMD (p = 0.008). Subjects with subsidence of <2 mm (mean, 0.80 mm [95% CI, 0.51 to 1.09 mm]) had faster improvement of patient-reported outcome measures and exhibited faster walking speed (p = 0.007) and greater walking activity (p = 0.010) at 11 months as well as better Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p = 0.002) and RAND 36-Item Health Survey mental component scores (p = 0.006) at 2 years. All cohort stems were osseointegrated at 2 years. CONCLUSIONS: Femoral stem stability and resistance to subsidence were sensitive to adequate intertrochanteric volumetric BMD. Low intertrochanteric volumetric BMD was associated with greater stem migration. With initial migration, clinical recovery was slower and patient-reported outcome measures were less satisfactory. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Contributing factors to the initial femoral stem migration in cementless total hip arthroplasty of postmenopausal women.

In cementless total hip arthroplasty (THA), femoral stems rely on the initial press-fit fixation against cortical bone to achieve osseointegration. Decreased bone mineral density (BMD) in postmenopausal women poses natural difficulties in achieving axial and rotational femoral stem stability. The present study examined contributing demographic, surgery-related and postoperative factors in determining the magnitude of early stem migration prior to osseointegration. A prospective cohort of 65 postmenopausal women with hip osteoarthritis (Dorr type A or B femur anatomy) underwent THA with implantation of an uncemented parallel-sided femoral component. Postoperative femoral stem translation and rotation were measured using model-based radiostereometric analysis. Based on analysis of covariance, which controlled for outliers and randomized antiresorptive treatment with denosumab or placebo, none of the analyzed demographics (including BMI) and surgery-related variables (including the stem-to-canal fil ratio) was associated with stem subsidence. Stem subsidence (mean 1.8 mm, 95% CI 1.2 to 2.4) occurred even in women with normal hip BMD. Total hip BMD and postoperative walking activity (measured three months after surgery) were significantly associated with stem rotation, and height acted as a confounding factor. The effect of walking activity on stem rotation was significant at 5 months (p = 0.0083) and at 11 months (p = 0.0117). This observation confirms the previous results of instrumented hip prostheses on torsional moments affecting stems during daily activities. High-resolution imaging modalities of local bone quality are needed to explore reasons for RSA-measurable stem subsidence even in women with normal hip BMD.

Discovery® elbow system arthroplasty: results of 10-year follow-up.

BACKGROUND: The semi-constrained Discovery® Elbow System (LimaCorporate, San Daniele del Friuli, Italy) allows varus-valgus laxity of 7° [8]. It has been reported to provide good pain relief and increased range of motion [5, 9] on mid-term follow-up. The aim of the study was to evaluate long-term outcomes of total elbow arthroplasty using the Discovery® Elbow System (LimaCorporate, San Daniele del Friuli, Italy). MATERIALS AND METHODS: The Mayo Elbow Performance Score (MEPS) and elbow range of motion (ROM) were assessed. Plain radiographs were obtained to assess radiolucency in the humerus and ulna. The data were extracted from electronic patient records. RESULTS: During the follow-up period of 105.4 (range 24.6-179.9) months, 132 patients (153 elbows) underwent surgery. The cause of surgery was rheumatoid arthritis in 105 (71%) cases, posttraumatic or primary arthritis in 17 (13%) and fracture in 10 (6%) patients. The total MEPS increased on average by 35.0 points. Elbow extension deteriorated by 5.0°. Respectively, flexion improved by 10.0° and pronation by 5.0°. The difference in supination was 0.0°. Pain severity improved by 2.5 points in motion and by 5.5 points at rest. During follow-up, 24 (16%) patients needed revision surgery. The most common cause for revision was periprosthetic fracture. Radiolucent lines were seen in all zones in both the ulna and the humerus. The Kaplan-Meier survival at 5 years was 88% and 79% at 10-14 years. CONCLUSION: The Discovery® Elbow System provides good results in ROM and pain relief of the elbow. The revision rate was relatively high (16% of patients). LEVEL OF EVIDENCE: IV.

Bone Mineral Density and Cortical-Bone Thickness of the Distal Radius Predict Femoral Stem Subsidence in Postmenopausal Women.

BACKGROUND: The distal radius is an optional site for evaluation of bone quality in postmenopausal women before cementless total hip arthroplasty. We hypothesized that dual-energy X-ray absorptiometry (DXA) and pulse-echo ultrasonometry of the distal radius may help discriminate subjects at high risk of femoral stem subsidence. METHODS: A prospective cohort of postmenopausal women with primary hip osteoarthritis underwent total hip arthroplasty with implantation of a parallel-sided femoral stem. Postoperative stem migration was measured using radiostereometric analysis. Preoperatively, subjects had multisite DXA measurement of bone mineral density (BMD) and pulse-echo ultrasonometry of the cortical-bone thickness. The diagnostic abilities of these methods to discriminate <2 mm and ≥2 mm femoral stem subsidence were tested. RESULTS: The accuracy of the distal radius BMD and cortical-bone thickness of the distal radius were moderate (area under the curve, 0.737 and 0.726, respectively) in discriminating between <2 mm and ≥2 mm stem subsidence. Women with low cortical-bone thickness of the radius were more likely (odds ratio = 6.7; P = .002) to develop stem subsidence ≥2 mm. These subjects had lower total hip BMD (P = .007) and reduced thickness of the medial cortex of the proximal femur (P = .048) with lower middle (P < .001) and distal (P = .004) stem-to-canal fill ratios. CONCLUSION: Femoral stem stability and resistance to subsidence are sensitive to adequate bone stock and unaltered anatomy. DXA and pulse-echo ultrasonometry of the distal radius may help discriminate postmenopausal women at high risk of stem subsidence.

Effect of Denosumab on Femoral Periprosthetic BMD and Early Femoral Stem Subsidence in Postmenopausal Women Undergoing Cementless Total Hip Arthroplasty.

Antiresorptive denosumab is known to improve the quality and strength of cortical bone in the proximal femurs of osteoporotic women, but its efficacy in preventing periprosthetic bone loss and reducing femoral stem migration has not been studied in women undergoing cementless total hip arthroplasty. We conducted a single-center, randomized, double-blinded, placebo-controlled trial of 65 postmenopausal women with primary hip osteoarthritis and Dorr type A or B proximal femur anatomy. The patients randomly received subcutaneous injections of denosumab 60 mg or placebo once every 6 months for 12 months, starting 1 month before surgery. The primary endpoint was the change in bone mineral density (BMD) of the proximal femur (Gruen zone 7) at week 48, and the secondary endpoint was stem subsidence measured by radiostereometric analysis (RSA) at week 48. Exploratory endpoints included changes in BMDs of the contralateral hip, lumbar spine and distal radius, serum levels of bone turnover markers, walking speed, walking activity, patient-reported outcome measures, and radiographic assessment of stem osseointegration. The participants underwent vertebral-fracture assessment in an extension safety study at 3 years. Denosumab significantly decreased bone loss in the medial femoral neck (zone 7) and increased periprosthetic BMD in the greater trochanteric region (zone 1) and lesser trochanteric region (zone 6). Denosumab did not reduce temporary femoral stem migration. The migration occurred mainly during the settling period (0 to 12 weeks) after implantation of the prosthesis. All of the stems osseointegrated, as evaluated by RSA and radiographs. There were no intergroup differences in functional recovery. Discontinuation of denosumab did not lead to any adverse events. In conclusion, denosumab increased periprosthetic BMD in the clinically relevant regions of the proximal femur, but the treatment response was not associated with any reduction of initial stem migration. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Right and Left Ventricles at Rest and During Exercise Using 15O-Labeled Compounds and PET.

Aims: Simultaneous measurement of right (RV) and left ventricle (LV) myocardial blood flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO2) non-invasively in humans would provide new possibilities to understand cardiac physiology and different patho-physiological states. Methods: We developed and tested an optimized novel method to measure MBF, OEF, and MVO2 simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at rest and during supine bicycle exercise. Results: Resting MBF was not significantly different between the three myocardial regions. Exercise increased MBF in the LVFW and septum, but MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was similar between the three different myocardial regions (~70%) and increased in response to exercise similarly in all regions. MVO2 increased approximately two to three times from rest to exercise in all myocardial regions, but was significantly lower in the RV during exercise as compared to septum LVFW. Conclusion: MBF, OEF, and MVO2 can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF between LV and RV myocardial regions in the resting myocardium, MVO2 per gram of myocardium appears to be lower the RV in the exercising healthy human heart due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO2 in hearts in different pathophysiological states.

The Effectiveness of Rehabilitation Interventions on the Employment and Functioning of People with Intellectual Disabilities: A Systematic Review.

Purpose This systematic review analyzed the effectiveness of rehabilitation interventions on the employment and functioning of people with intellectual disabilities (ID), as well as barriers and facilitators of employment. Methods This was a systematic review of quantitative, qualitative, and mixed methods studies. The outcomes were employment, transition to the open labor market and functioning. The review included qualitative studies of employment barriers and facilitators. The population comprised people with ID aged 16-68 years. Peer-reviewed articles published in English between January 1990 and February 2019 were obtained from the databases Cinahl, the Cochrane Library, Embase, Eric, Medic, Medline, OTseeker, Pedro, PsycInfo, PubMed, Socindex, and the Web of Science. We also searched Google Scholar and Base. The modified selection instrument (PIOS: participants, intervention, outcome, and study design) used in the selection of the articles depended on the selection criteria. Results Ten quantitative (one randomized controlled, one concurrently controlled, and eight cohort studies), six qualitative studies, one multimethod study, and 21 case studies met the inclusion criteria. The quantitative studies showed that secondary education increases employment among people with ID when it includes work experience and personal support services. Supported employment also increased employment in the open labor market, which sheltered work did not. The barriers to employment were the use of sheltered work, discrimination in vocational experience, the use of class teaching, and deficient work experience while still at school. The facilitators of employment were one's own activity, the support of one's family, job coaching, a well-designed work environment, appreciation of one's work, support form one's employer and work organization, knowledge and experience of employment during secondary education, and for entrepreneurs, the use of a support person. Conclusions The employment of people with ID can be improved through secondary education including proper teaching methods and personal support services, the use of supported work, workplace accommodations and support from one's family and employer. These results can be utilized in the development of rehabilitation, education, and the employment of people with ID, to allow them the opportunity to work in the open labor market and participate in society.

Decorin Expression in Human Vulva Carcinoma: Oncosuppressive Effect of Decorin cDNA Transduction on Carcinoma Cells.

The extracellular matrix proteoglycan decorin is well-known for its oncosuppressive activity. Here, decorin expression was examined in human vulva carcinoma tissue samples and in primary and commercial cell lines representing this malignant disease. Furthermore, the effect of adenovirus-mediated decorin cDNA (Ad-DCN) transduction on the viability, proliferation, and the expression and activity of the epidermal growth factor receptor (ErbB/HER) family members of the cell lines were investigated. Using in situ hybridization and immunohistochemistry for decorin, it was demonstrated that malignant cells in human vulva carcinoma tissues lack decorin expression. This result was true independently on tumor stage, grade or human papillomavirus status. RT-qPCR analyses showed that the human vulva carcinoma cell lines used in this study were also negative for decorin expression. Transduction of the cell lines with Ad-DCN caused a marked reduction in cell viability, while the proliferation of the cells was not affected. Experiments examining potential mechanisms behind the oncosuppressive effect of Ad-DCN transduction revealed that ErbB2/HER2 expression and activity in carcinoma cells were markedly downregulated. In conclusion, the results of this study showed that human vulva carcinoma cells lack decorin expression, and that Ad-DCN transduction of these cells induces oncosuppressive activity in part via downregulation of ErbB2/HER2.

Radiostereometric analysis of the initial stability of internally fixed femoral neck fractures under differential loading.

We examined the feasibility of radiostereometric analysis (RSA) in the assessment of the initial stability of internally fixed femoral neck fractures. The study included 16 patients (mean age 73 years). During surgery, multiple RSA-beads were inserted on both sides of the fracture. Radiographs for RSA were taken in the supine position within the first 3 days and 6, 12, 24, and 52 weeks after surgery. To detect any inducible motion at the fracture-site, radiographs for RSA were taken with the patient resting or applying a load through the fracture. Fracture loading was achieved by the patient pressing the ipsilateral foot as much as tolerated on a force plate while providing a counterforce through both hands. Micromotion exceeding the precision values of RSA (≥0.3 mm for the translation vector and/or ≥1.2 degrees for the rotation vector) was considered significant. Permanent three-dimensional fracture-site displacement was also recorded. Voluntary loading induced fracture-site micromotion, which exhibited a dichotomous distribution. In patients with uncomplicated fracture union, inducible micromotion was detectable only at baseline-if at all. Conversely, fractures that developed a nonunion were characterized by the continuation of inducible micromotion beyond baseline. Permanent fracture-site displacement was, on average, nearly an order of magnitude greater than the inducible micromotion. Fracture unions were characterized by the cessation of permanent fracture-site displacement by 12 weeks. Nonunions presented as outliers in permanent fracture-site displacement. Large-scale studies are warranted to evaluate whether the detection of inducible micromotion beyond baseline could serve as an indicator of insufficient fixation stability. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society.

Benson group additivity values of phosphines and phosphine oxides: Fast and accurate computational thermochemistry of organophosphorus species.

Composite quantum chemical methods W1X-1 and CBS-QB3 are used to calculate the gas phase standard enthalpy of formation, entropy, and heat capacity of 38 phosphines and phosphine oxides for which reliable experimental thermochemical information is limited or simply nonexistent. For alkyl phosphines and phosphine oxides, the W1X-1, and CBS-QB3 results are mutually consistent and in excellent agreement with available G3X values and empirical data. In the case of aryl-substituted species, different computational methods show more variation, with G3X enthalpies being furthest from experimental values. The calculated thermochemical data are subsequently used to determine Benson group additivity contributions for 24 Benson groups and group pairs involving phosphorus, thereby allowing fast and accurate estimations of thermochemical data of many organophosphorus compounds of any complexity. Such data are indispensable, for example, in chemical process design or estimating potential hazards of new chemical compounds. © 2018 Wiley Periodicals, Inc.