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.

A Multi-Institutional Randomized Controlled Trial to Investigate Whether Zoledronate Prevents Bone Loss After Discontinuation of Denosumab: The Study Protocol of Denosumab Sequential Therapy (DST) Trial.

Background: Though denosumab is an effective treatment for osteoporosis, the rebound effect after discontinuation has drawn investigators' attention. It includes a dramatic loss of gained bone mineral density (BMD) and an increased risk of vertebral fractures. This prospective multi-institutional randomized controlled trial aims to investigate whether zoledronate prevents loss of BMD after discontinuation of denosumab. The trial was registered as Denosumab Sequential Therapy (DST) trial in March 2019 at clinicaltrials.gov, with the identifier NCT03868033. Methods: The study is conducted at National Taiwan University Hospital and its branches. Patients who have continuously received denosumab treatment for two or more years are surveyed for eligibility. Baseline characteristics and questionnaires of life quality are recorded after recruitment. BMD, circulating levels of bone turnover markers (BTMs), including serum N-terminal propeptide of type 1 collagen (P1NP) and C-terminal telopeptide (CTX), are checked before the stratified randomization to 4 groups. Biological sex and the T-scores are used to create 4 strata. The participants in group 1 adhere to regular denosumab therapy for another 2 years. All the other patients receive on-time zoledronate treatment in the first year. The participants in group 2, 3, and 4 have on-time denosumab, on-time zoledronate and drug holiday in the second year, respectively. BMDs are checked annually. Pre-scheduled checkpoints of BTMs are also arranged. For patient safety, rescue treatment with another injection of zoledronate will be applied to the patients on drug holiday if the CTX levels raise above the pre-specified threshold, 0.573 ng/mL for women and 0.584 ng/mL for men. The primary outcomes are the percentage changes of BMDs in lumbar spine, total hip and femoral neck. The secondary outcomes include the changes of serum level of the BTMs, new osteoporotic fractures, extra zoledronate injections needed in group 4 and the differences of quality of life. Discussion: We aim to provide evidence whether zoledronate prevents bone loss after denosumab cessation. To our knowledge, the study has the largest sample size. No other randomized controlled study included all the three different treatment strategies and a positive control. It is also the first associated randomized controlled trial outside Europe.

Complications of clavicle fracture surgery in patients with concomitant chest wall injury: a retrospective study.

BACKGROUND: The impact of associated chest wall injuries (CWI) on the complications of clavicle fracture repair is unclear to date. This study aimed to investigate the complications after surgical clavicle fracture fixation in patients with and without different degrees of associated CWI. METHODS: A retrospective review over a four-year period of patients who underwent clavicle fracture repair was conducted. A CWI and no-CWI group were distinguished, and the CWI group was subdivided into the minor-CWI (three or fewer rib fractures without flail chest) and complex-CWI (flail chest, four or more rib fractures) subgroup. Demographic data, classification of the clavicle fracture, number of rib fractures, and associated injuries were recorded. Overall complications included surgery-related complications and unplanned hospital readmissions. Univariate analysis and stepwise backward multivariate logistic regression were used to identify potential risk factors for complications. RESULTS: A total of 314 patients undergoing 316 clavicle fracture operations were studied; 28.7% of patients (90/314) occurred with associated CWI. Patients with associated CWI showed a significantly higher age, body mass index, and number of rib fractures. The overall and surgical-related complication rate were similar between groups. Unplanned 30-day hospital readmission rates were significantly higher in the complex-CWI group (p = 0.02). Complex CWI and number of rib fractures were both independent factor for 30-day unplanned hospital readmission (OR 1.59, 95% CI: 1.00-2.54 and OR 1.33, 95% CI: 1.06-1.68, respectively). CONCLUSION: CWI did not affect surgery-related complications after clavicle fracture repair. However, complex-CWI may increase 30-day unplanned hospital readmission rates.

Functional workspace and patient-reported outcomes improve after reverse and total shoulder arthroplasty.

BACKGROUND: Low-cost motion analysis systems (LCMASs) have emerged as easy and practical methods to measure the functional workspace (FWS). Thus, we ventured to apply an LCMAS, the Kinect2 gaming camera, to evaluate the FWS in patients with shoulder osteoarthritis (OA) and patients who underwent total shoulder arthroplasty (TSA) or reverse total shoulder arthroplasty (RTSA). METHODS: A cross-sectional study of participants with OA (n = 53), TSA (n = 70), and RTSA (n = 34) was performed. The FWS as measured by an LCMAS, the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form score, and the Patient-Reported Outcomes Measurement Information System (PROMIS) score were collected. For participants who underwent TSA or RTSA, the FWS was evaluated at 6, 12, and 24 months postoperatively. The correlation of the FWS with the ASES score and PROMIS score was determined. Significance was set at P < .05. RESULTS: Patients who underwent TSA or RTSA had a significantly higher FWS than patients with shoulder OA at almost all time points. Patients who underwent TSA had a significantly higher FWS than patients who underwent RTSA at 24 months after surgery. PROMIS and ASES scores showed strong correlations with the FWS in patients who underwent TSA (R = 0.75 [P < .001] and R = 0.83 [P < .001], respectively) and RTSA (R = 0.84 [P < .001] and R = 0.73 [P < .001], respectively). CONCLUSION: The FWS measured by an LCMAS is an easy and low-cost method to quantify the reachable space of the hand in patients and shows strong correlations with patient-reported outcome measures. This may be a useful tool to assess upper-extremity range of motion before and after shoulder arthroplasty.

Outcomes of revision arthroplasty for shoulder periprosthetic joint infection: a three-stage revision protocol.

BACKGROUND: This study evaluated outcomes after treatment of shoulder periprosthetic joint infection (PJI) with a 3-stage revision protocol consisting of (1) débridement, explantation, and cement spacer placement, followed by parenteral antibiotics; (2) open biopsy and débridement; and (3) reimplantation if cultures were negative. We hypothesized this protocol would eradicate persistent infection while producing excellent functional and subjective outcomes, and there would be no difference in these parameters for patients with shoulder PJI compared with patients with revision for aseptic indications. METHODS: We retrospectively analyzed a prospectively collected revision shoulder arthroplasty cohort to identify shoulder PJI patients treated with a 3-stage protocol. Demographics, culture data, range of motion, and patient-reported outcomes were collected. Outcomes for patients with shoulder PJI and revision to RTSA were compared with patients revised to RTSA for noninfectious indications. Significance was defined as P < .05. RESULTS: There were 28 cases of shoulder PJI in 27 patients (age, 66.4 ± 11.2 years,); of these, 21 shoulders were revised to RTSA, and 7 shoulders were revised to hemiarthroplasty. There was no recurrent infection at a mean 32-month follow-up. One year after surgery, mean forward flexion was 110° ± 41° and abduction was 106° ± 42°. Mean final American Shoulder and Elbow Surgeons subjective score was 66.5 ± 23.3. The 21 shoulders with PJI revised to RTSA had no differences for functional and subjective outcomes compared with revised patients without shoulder PJI. CONCLUSIONS: A 3-stage revision protocol for shoulder PJI reliably eradicated infection. Patients with PJI revised to RTSA can have similar outcomes as patients with noninfectious revision to RTSA.

Treatment of osteoarthritis with collagen-based scaffold: A porcine animal model with xenograft mesenchymal stem cells.

OBJECTIVE: With the goal to explore a new approach to treat the early degenerative lesions of hyaline cartilage, we implanted in a porcine OA model a collagen-based scaffold containing chondroprogenitor cells derived from human bone marrow mesenchymal stem cells (hBM-MSCs). EXPERIMENTAL DESIGN: Porcine knee joints were subjected to anterior cruciate ligament (ACL) transection to surgically induce OA. After 4 months, the time necessary for the development of cartilage surface damage, animals were treated either with trephination bone plug wrapped with the chondroprogenic hBM-MSCs-embedded collagen scaffold or microfractures alone. Histological and histomorphometric evaluations were performed at 5 months after surgery. RESULTS: All animals subjected to ACL transection showed osteoarthritic changes including mild lateral femoral condyle or moderate medial femoral condyle ulcerations. After 14 days' chondrogenic induction, hBM-MSCs seeded onto the scaffold showed expression of chondroprogenitor markers such as SOX9 and COMP. At 5 months after the implantation, significant differences in the quality of the regenerated tissue were found between the hBM-MSCs-embedded scaffold group and the control group. Newly generated tissue was only observed at the site of implantation with the hBM-MSCs-embedded scaffolds. Furthermore, histological examination of the generated tissue revealed evidence of cartilage-like tissue with lacuna formation. In contrast, fibrous layers or fissures were formed on the surface of the control knee joint. CONCLUSIONS: This study shows that xenogenic hBM-MSC derived chondroprogenitor scaffolds can generate new cartilage tissue in porcine articular cartilage and have the potential as a useful treatment option for osteoarthritis.

Notch sensitivity jeopardizes titanium locking plate fatigue strength.

INTRODUCTION: Notch sensitivity may compromise titanium-alloy plate fatigue strength. However, no studies providing head-to-head comparisons of stainless-steel or titanium-alloy locking plates exist. MATERIALS AND METHODS: Custom-designed identically structured locking plates were made from stainless steel (F138 and F1314) or titanium alloy. Three screw-hole designs were compared: threaded screw-holes with angle edges (type I); threaded screw-holes with chamfered edges (type II); and non-threaded screw-holes with chamfered edges (type III). The plates' bending stiffness, bending strength, and fatigue life, were investigated. The stress concentration at the screw threads was assessed using finite element analyses (FEA). RESULTS: The titanium plates had higher bending strength than the F1314 and F138 plates (2.95:1.56:1) in static loading tests. For all metals, the type-III plate fatigue life was highest, followed by type-II and type-I. The type-III titanium plates had longer fatigue lives than their F138 counterparts, but the type-I and type-II titanium plates had significantly shorter fatigue lives. All F1314 plate types had longer fatigue lives than the type-III titanium plates. The FEA showed minimal stress difference (0.4%) between types II and III, but the stress for types II and III was lower (11.9% and 12.4%) than that for type I. CONCLUSIONS: The screw threads did not cause stress concentration in the locking plates in FEA, but may have jeopardized the fatigue strength, especially in the notch-sensitive titanium plates. Improvement to the locking plate design is necessary.

High short-term and long-term excess mortality in geriatric patients after hip fracture: a prospective cohort study in Taiwan.

BACKGROUND: Hip fracture has a high mortality rate, but the actual level of long-term excess mortality and its impact on population-wide mortality remains controversial. The present prospective study investigated short- and long-term excess mortality after hip fractures with adjustment of other risk factors. We calculated the population attributable risk proportion (PARP) to assess the impact of each risk factor on excess mortality. METHODS: We recruited 217 elders with hip fractures and 215 age- and sex-matched patients without fractures from the geriatric department of the same hospital. The mean follow-up time was 46.1 months (range: 35 to 57 months). We recorded data on 55 covariates, including baseline details about health, function, and bone mineral density. We used the multivariate Cox proportional hazards model to analyze hazard ratios (HRs) of short-term (<12 months follow-up) and long-term (≧ 2 months follow-up) excess mortality for each covariate and calculated their PARP. RESULTS: Patients with hip fractures had a higher short-term mortality than non-fractured patients, and the long-term excess mortality associated with hip fracture remained high. The significant risk factors for short-term mortality were hip fracture, comorbidities, and lower (below cutoff) Mini Mental State Examination score with HRs of 2.4, 2.3, and 2.3, respectively. Their PARPs were 44.7%, 38.1%, and 34.3%, respectively. The significant risk factors for long-term mortality were hip fracture (HR: 2.7; PARP: 48.0%), lower T-score (HR: 3.3; PARP: 36.2%), lower body mass index (HR: 2.5; PARP: 42.8%), comorbidities (HR: 2.1; PARP: 34.8%), difficulty in activities of daily living (HR: 1.9; PARP: 31.8%), and smoking (HR: 2.5; PARP: 19.2%). CONCLUSIONS: After comprehensive adjustment, hip fracture was a significant risk factor and contributed the most to long-term as well as short-term excess mortality. Its adequate prevention and treatment should be targeted.

Hip fracture risk assessment: artificial neural network outperforms conditional logistic regression in an age- and sex-matched case control study.

BACKGROUND: Osteoporotic hip fractures with a significant morbidity and excess mortality among the elderly have imposed huge health and economic burdens on societies worldwide. In this age- and sex-matched case control study, we examined the risk factors of hip fractures and assessed the fracture risk by conditional logistic regression (CLR) and ensemble artificial neural network (ANN). The performances of these two classifiers were compared. METHODS: The study population consisted of 217 pairs (149 women and 68 men) of fractures and controls with an age older than 60 years. All the participants were interviewed with the same standardized questionnaire including questions on 66 risk factors in 12 categories. Univariate CLR analysis was initially conducted to examine the unadjusted odds ratio of all potential risk factors. The significant risk factors were then tested by multivariate analyses. For fracture risk assessment, the participants were randomly divided into modeling and testing datasets for 10-fold cross validation analyses. The predicting models built by CLR and ANN in modeling datasets were applied to testing datasets for generalization study. The performances, including discrimination and calibration, were compared with non-parametric Wilcoxon tests. RESULTS: In univariate CLR analyses, 16 variables achieved significant level, and six of them remained significant in multivariate analyses, including low T score, low BMI, low MMSE score, milk intake, walking difficulty, and significant fall at home. For discrimination, ANN outperformed CLR in both 16- and 6-variable analyses in modeling and testing datasets (p?

Time orientation and visual construction subdomains of the MMSE as independent risk factors for hip fractures.

Hip fractures may result in severe morbidity and mortality among elderly patients. Many risk factors for hip fracture have been identified, including cognitive impairment. The authors used the Mini-Mental State Examination (MMSE), a screen test for cognitive impairment, as the study material for their hip fracture survey. The authors hypothesized that certain subdomains would have a strong association with hip fractures. A total of 217 individuals with hip fracture and 215 individuals without hip fractures matched by age and sex were recruited for the study. A standardized questionnaire was used to register their MMSE performance and demographic data. Scores for these subdomains were analyzed using conditional logistic regression with adjustment of 5 clinically important risk factors for hip fractures, including educational level, difficulty with activities of daily living, physical activities, body mass index, and bone mineral density. In univariate analyses, those subdomains with lower scores had significantly higher hip fracture risks. In multivariate analyses, only the subdomains time orientation and visual construction remained significant. Further receiver operating characteristic curve analysis revealed that these 2 subdomains could differentiate hip fractures from nonfractures better than total MMSE. Time orientation and visual construction subdomains are strong predictors for hip fractures and can be used effectively in the hospital to screen patients at high risk of hip fractures. Prospective cohort studies are warranted to further validate this finding.