The relationship between sarcopenia and fragility fracture-a systematic review.

Sarcopenia is a common geriatric syndrome characterized by progressive decrease of muscle mass and function leading to an increased risk of physical disability, poor quality of life, and mortality. Increasing evidence shows that sarcopenia is related with fragility fractures. This systematic review aimed to summarize the following: (1) the prevalence of sarcopenia in patients with fragility fracture and (2) the associated risk factors for fragility fracture in patients with sarcopenia. Literature search was conducted in PubMed and Cochrane databases. Studies with the prevalence of sarcopenia in elderly patients with fragility fracture and associated risk factors in patients with sarcopenia were included. A total of 15 papers were included, with 10 reporting sarcopenia prevalence, and 5 on fracture risk in patients with sarcopenia. The prevalence of sarcopenia after fracture ranged from 12.4 to 95% in males and 18.3 to 64% in females. The prevalence of sarcopenia in elderly patients with fragility fracture was high, especially in men. Two studies showed that sarcopenia was a risk factor for fragility fracture when associated with low bone mineral density (BMD) but only in men. Caution should be taken for male patients with sarcopenia and low BMD, which is related to significantly increased risk of fractures. There is a pressing need for further research on sarcopenia and its risk on fragility fracture to better understand the relationship, pathophysiology, and mechanisms, which may shed light on potential interventions to improve clinical outcomes.

Vibration treatment modulates macrophage polarisation and enhances early inflammatory response in oestrogen-deficient osteoporotic-fracture healing.

Fracture healing is a well-orchestrated and coordinated process and begins with the inflammatory stage involving the infiltration of immune cells and the release of cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Low-magnitude high-frequency vibration (LMHFV) stimulation is effective in promoting fracture healing. The study hypothesis was that the innate immune response was impaired in osteoporotic fracture and LMHFV could positively modulate it. 9-month-old ovariectomy (OVX)-induced osteoporotic rats were randomised into sham (SHAM), OVX control (OVX), OVX-vibration (OVX-VT) or OVX vibration plus administration of COX-2 specific non-steroid anti-inflammatory drugs (OVX-VT-NSAID). LMHFV (35 Hz, 0.3 g) was given 20 min/d and 5 d/week to the treatment groups. Healing and innate immune response were evaluated by weekly radiographs, endpoint micro-computed tomography (µCT), enzyme-linked immunosorbent assay (ELISA) and histomorphometry at weeks 1, 2, 4 and 8 post-treatment. Results showed that OVX slightly elevated systemic inflammation but impaired the innate immune response locally at the fracture site, with significantly lower expressions of TNF-α and IL-6 but higher IL-10 expression during the early stage of healing. LMHFV was effective in accelerating the delayed fracture healing in OVX bones by partly restoring the impaired innate immune response at the fracture site, accompanied by promoted progression of macrophage polarisation from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype. In conclusion, vibration treatment could positively modulate the impaired innate immune response and promote macrophage polarisation in osteoporotic-fracture healing.

A metaphyseal fracture rat model for mechanistic studies of osteoporotic bone healing.

Most osteoporotic fractures occur at metaphyseal regions of long bones. The present study proposed a clinically relevant animal model that satisfied: i) induction of osteoporosis, ii) unilateral complete osteotomy at metaphysis, iii) internal fixation. 6 months old female Sprague-Dawley rats (n = 64) were randomly divided into the ovariectomised-metaphyseal osteotomy (OVX, n = 32) and metaphyseal osteotomy (SHAM, n = 32) groups. The metaphyseal-osteotomy model was created with a plate-fixation of the osteotomy and assessed by X-ray, micro-computed tomography, histomorphometry and mechanical testing at weeks 1, 3 and 6. X-ray results showed complete healing of metaphyseal osteotomy at week 6. Histology showed 3 stages of metaphyseal healing. Stage 1 was characterised by fibrous tissue, consisting of disorganised orientation of collagen fibres, and infiltration of immune cells. At stage 2, a transitional zone consisting of maturing fibrous tissue and differentiating mesenchymal cells with early trabecular bone formation and disorganised woven bone were observed. During stage 3, cortical bone ends unified and woven bone underwent transformation to lamellar bone. OVX group healing was significantly delayed when compared to SHAM samples. The study demonstrated that healing of osteoporotic osteotomy at the metaphyseal region was delayed in terms of radiography, histomorphometry and mechanical strength. These quantitative evaluations, along with histological features, may provide key references for future studies. The animal model may provide additional clinical relevance as most osteoporotic fracture in humans occurs at metaphyseal regions.

Natural clinical course of progressive supranuclear palsy in Chinese patients in Hong Kong.

INTRODUCTION: Progressive supranuclear palsy (PSP) is a common type of atypical parkinsonism. To the best of our knowledge, there has been no study of its natural clinical course among Chinese patients. METHODS: This retrospective study included 21 patients with PSP who had radiological evidence of midbrain atrophy (confirmed by magnetic resonance imaging) from the geriatrics clinics of Queen Mary Hospital and Tuen Mun Hospital. Clinical information was retrieved from clinical records, including age at onset, age at presentation, age at death, duration of symptoms, level of education, sex, presenting scores on Cantonese version of Mini-Mental State Examination, clinical symptoms, and history of levodopa or dopamine agonist intake and response. Clinical symptoms were clustered into the following categories and the dates of development of these symptoms were determined: motor symptoms, bulbar symptoms, cognitive symptoms, and others. RESULTS: Motor symptoms developed early in the clinical course of disease. Cox proportional hazards modelling showed that the number of episodes of pneumonia, time to vertical gaze palsy, and presence of pneumonia were predictive of mortality. Apathy, dysphagia, pneumonia, caregiver stress, and pressure injuries were predictive of mortality when analysed as time-dependent covariates. There was a significant negative correlation between the age at presentation and time to mortality from presentation (Pearson correlation=-0.54, P=0.04). Approximately 40% of caregivers complained of stress during the clinical course of disease. CONCLUSION: Important clinical milestones, including the development of dysphagia, vertical gaze palsy, significant caregiver stress, pressure injuries, and pneumonia, may guide advanced care planning for patients with PSP.

The effect of whole body vibration on fracture healing - a systematic review.

This systematic review examines the efficacy and safety of whole body vibration (WBV) on fracture healing. A systematic literature search was conducted with relevant keywords in PubMed and Embase, independently, by two reviewers. Original animal and clinical studies about WBV effects on fracture healing with available full-text and written in English were included. Information was extracted from the included studies for review. In total, 19 articles about pre-clinical studies were selected. Various vibration regimes are reported; of those, the frequencies of 35 Hz and 50 Hz show better results than others. Most of the studies show positive effects on fracture healing after vibration treatment and the responses to vibration are better in ovariectomised (OVX) animals than non-OVX ones. However, several studies provide insufficient evidence to support an improvement of fracture healing after vibration and one study even reports disruption of fracture healing after vibration. In three studies, vibration results in positive effects on angiogenesis at the fracture site and surrounding muscles during fracture healing. No serious complications or side effects of vibration are found in these studies. WBV is suggested to be beneficial in improving fracture healing in animals without safety problem reported. In order to apply vibration on fractured patients, more well-designed randomised controlled clinical trials are needed to examine its efficacy, regimes and safety.

How well are we managing fragility hip fractures? A narrative report on the review with the attempt to setup a Fragility Fracture Registry in Hong Kong.

INTRODUCTION: In setting up a disease registry for fragility fractures in Hong Kong, we conducted a retrospective systematic study on the management of fragility hip fractures. Patient outcomes were compared with the standards from our orthopaedic working group and those from the British Orthopaedic Association that runs a mature fracture registry in the United Kingdom. METHODS: Clinical data on fragility hip fracture patients admitted to six acute major hospitals in Hong Kong in 2012 were captured. These included demographics, pre- and post-operative assessments, discharge details, complications, and 1-year follow-up information. Analysis was performed according to the local standards with reference to those from the British Orthopaedic Association. RESULTS: Overall, 91.0% of patients received orthopaedic care within 4 hours of admission and 60.5% received surgery within 48 hours. Preoperative geri-orthopaedic co-management was received by 3.5% of patients and was one of the reasons for the delayed surgery in 22% of patients. Only 22.9% were discharged with medication that would promote bone health. Institutionalisation on discharge significantly increased by 16.2% (P<0.001). Only 35.1% of patients attended out-patient follow-up 1 year following fracture, and mobility had deteriorated in 69.9% compared with the premorbid state. Death occurred in 17.3% of patients within a year of surgery compared with 1.6% mortality rate in a Hong Kong age-matched population. CONCLUSIONS: The efficiency and quality of acute care for fragility hip fracture patients was documented. Regular geri-orthopaedic co-management can enhance acute care. Much effort is needed to improve functional recovery, prescription of bone health medications, attendance for follow-up, and to decrease institutionalisation. A Fracture Liaison Service is vital to improve long-term care and prevent secondary fractures.

Mechanical stimulation enhanced estrogen receptor expression and callus formation in diaphyseal long bone fracture healing in ovariectomy-induced osteoporotic rats.

UNLABELLED: Estrogen receptor (ER) in ovariectomy-induced osteoporotic fracture was reported to exhibit delayed expression. Mechanical stimulation enhanced ER-α expression in osteoporotic fracture callus at the tissue level. ER was also found to be required for the effectiveness of vibrational mechanical stimulation treatment in osteoporotic fracture healing. INTRODUCTION: Estrogen receptor(ER) is involved in mechanical signal transduction in bone metabolism. Its expression was reported to be delayed in osteoporotic fracture healing. The purpose of this study was to investigate the roles played by ER during osteoporotic fracture healing enhanced with mechanical stimulation. METHODS: Ovariectomy-induced osteoporotic SD rats that received closed femoral fractures were divided into five groups, (i) SHAM, (ii) SHAM-VT, (iii) OVX, (iv) OVX-VT, and (v) OVX-VT-ICI, where VT stands for whole-body vibration treatment and ICI for ER antagonization by ICI 182,780. Callus formation and gene expression were assessed at 2, 4, and 8 weeks postfracture. In vitro osteoblastic differentiation, mineralization, and ER-α expression were assessed. RESULTS: The delayed ER expression was found to be enhanced by vibration treatment. Callus formation enhancement was shown by callus morphometry and micro-CT analysis. Enhancement effects by vibration were partially abolished when ER was modulated by ICI 182,780, in terms of callus formation capacity at 2-4 weeks and ER gene and protein expression at all time points. In vitro, ER expression in osteoblasts was not enhanced by VT treatment, but osteoblastic differentiation and mineralization were enhanced under estrogen-deprived condition. When osteoblastic cells were modulated by ICI 182,780, enhancement effects of VT were eliminated. CONCLUSIONS: Vibration was able to enhance ER expression in ovariectomy-induced osteoporotic fracture healing. ER was essential in mechanical signal transduction and enhancement in callus formation effects during osteoporotic fracture healing enhanced by vibration. The enhancement of ER-α expression by mechanical stimulation was not likely to be related to the increased expression in osteoblastic cells but rather to the systemic enhancement in recruitment of ER-expressing progenitor cells through increased blood flow and neo-angiogenesis. This finding might explain the observed difference in mechanical sensitivity of osteoporotic fracture to mechanical stimulation.

Low-magnitude high-frequency vibration enhanced mesenchymal stem cell recruitment in osteoporotic fracture healing through the SDF-1/CXCR4 pathway.

Low-magnitude high-frequency vibration (LMHFV) has been proven to promote osteoporotic fracture healing. Mechanical stimulation was reported to enhance SDF-1/CXCR4 signalling in mesenchymal stem cells (MSCs). We hypothesised that LMHFV promoted osteoporotic fracture healing by enhancing MSC migration through the SDF-1/CXCR4 pathway. 152 ovariectomised SD-rats received closed femoral fracture in groups of vibration+MSC (VMG) (20 min/d, 5 d/week), vibration+MSC+AMD3100 (VMAG; AMD, a CXCR4 inhibitor) (1 mg/kg/d, intraperitoneal), MSC (MG) (1 × 106 MSC, intracardiac) or control (CG) for a treatment duration of 2, 4 or 8 weeks. MSC migration was evaluated by ex-vivo green fluorescent protein signal in the callus; and fracture healing was examined by weekly radiographs, endpoint computed-tomography and mechanical test. At week-2 and week-4, ex-vivo callus GFP intensity of VMG was significantly higher than other groups (p < 0.05). From week-2 to week-3, both callus width and callus area in VMG were significantly larger; and from week-7 to week-8, smaller than other groups (p < 0.05). At week-8, high-density bone volume fraction, bone volume fraction, bone mineral density and stiffness in VMG were significantly higher than other 3 groups (p < 0.05). This study demonstrated that LMHFV promoted MSC migration and fracture healing in osteoporotic rats. This effect was attenuated by CXCR4 inhibitor, providing strong evidence that SDF-1-mediated MSC migration was one of the important mechanisms through which LMHFV enhanced fracture healing.

Improvement in muscle performance after one-year cessation of low-magnitude high-frequency vibration in community elderly.

OBJECTIVES: To investigate the effects on muscle performance after one-year cessation of 18-month low-magnitude high-frequency vibration (LMHFV) intervention in the untrained community elderly. METHODS: This is a case-control study with 59 community elderly women (25 control without any treatment; 34 received 18-month LMHFV but discontinued for 1 year from our previous clinical study). Muscle strength, balancing ability, occurrence of fall/fracture, quality of life (QoL) were assessed 1-year after cessation of intervention. The 30-month results were compared with baseline and 18-month treatment endpoint data between groups. RESULTS: At 30 months (i.e. one year post-intervention), the muscle strengths of dominant and non-dominant legs relative to baseline in treatment group were significantly better than those of control. In balancing ability test, reaction time, movement velocity and maximum excursion of treatment group (relative to baseline) remained significantly better than the control group. The muscle strength, balancing ability and quality of life at 30 months relative to 18 months did not show significant differences between the two groups. CONCLUSION: The benefits of LMHFV for balancing ability, muscle strength and risk of falling in elderly were retained 1 year after cessation of LMHFV.

Acute carbon monoxide poisoning in a regional hospital in Hong Kong: historical cohort study.

OBJECTIVES: This study aimed to describe the clinical profiles of all patients with carbon monoxide poisoning admitted to a regional hospital in order to enhance the vigilance of health care professionals for delayed neurological sequelae associated with carbon monoxide poisoning and to identify the prognostic factors associated with their development. This study also aimed to assess the impact of hyperbaric oxygen therapy on the development of delayed neurological sequelae in these patients. METHODS: This was a historical cohort study in which all patients with a diagnosis of carbon monoxide poisoning managed in a regional hospital in Hong Kong from 12 February 2003 to 8 November 2013 were recruited. Main outcome measures included delayed neurological sequelae. RESULTS: Of the clinical profiles of 93 patients analysed, 24 patients received hyperbaric oxygen therapy and did not develop delayed neurological sequelae. Seven patients who did not receive hyperbaric oxygen therapy developed delayed neurological sequelae. Comparison of groups with and without delayed neurological sequelae (excluding hyperbaric oxygen therapy-treated patients) revealed that loss of consciousness (P=0.038), Glasgow Coma Scale score of 3 (P=0.012), elevated troponin level (P<0.001), higher creatine kinase level (P=0.008), and intubation requirement (P=0.007) were possible prognostic factors for the development of delayed neurological sequelae. CONCLUSION: Although not statistically significant, this study showed a 100% protective effect of hyperbaric oxygen therapy against development of severe delayed neurological sequelae in patients with severe carbon monoxide poisoning. Further study with better study design is warranted. Loss of consciousness, low Glasgow Coma Scale score, intubation requirement, elevated troponin and higher creatine kinase levels were possible prognostic factors for development of delayed neurological sequelae in patients with severe carbon monoxide poisoning. A well-defined treatment protocol, appropriate follow-up duration and neuropsychiatric tests together with a hospital-based hyperbaric chamber are recommended for management of patients with severe carbon monoxide poisoning.

Age-related differences in volumetric bone mineral density, microarchitecture, and bone strength of distal radius and tibia in Chinese women: a high-resolution pQCT reference database study.

UNLABELLED: In a cohort of 393 Chinese women, by using high-resolution peripheral quantitative computed tomography (HR-pQCT), we found that significant cortical bone loss occurred after midlife. Prominent increase in cortical porosity began at the fifth decade but reached a plateau before the sixth decade. Trabecular bone loss was already evident in young adulthood and continued throughout life. INTRODUCTION: This study aimed to investigate age-related differences in volumetric bone mineral density (vBMD), microarchitecture, and estimated bone strength at peripheral skeleton in Chinese female population. METHODS: In a cross-sectional cohort of 393 Chinese women aged 20-90 years, we obtained vBMD, microarchtecture, and micro-finite element-derived bone strength at distal radius and tibia using HR-pQCT. RESULTS: The largest predictive age-related difference was found for cortical porosity (Ct.Po) which showed over four-fold and two-fold differences at distal radius and tibia, respectively, over the adulthood. At both sites, cortical bone area, vBMD, and thickness showed significant quadratic association with age with significant decrease beginning after midlife. Change of Ct.Po became more prominent between age of 50 and 57 (0.26 %/year at distal radius, 0.54 %/year at distal tibia, both p ≤ 0.001) but thereafter, reached a plateau (0.015 and 0.028 %/year, both p > 0.05). In contrast, trabecular vBMD and microarchitecture showed linear association with age with significant deterioration observed throughout adulthood. Estimated age of peak was around age of 20 for trabecular vBMD and microarchitecture and Ct.Po and age of 40 for cortical vBMD and microarchitecture. Estimated stiffness and failure load peaked at mid-30s at the distal radius and at age 20 at distal tibia. CONCLUSIONS: Age-related differences in vBMD and microarchitecture in Chinese women differed by bone compartments. Significant cortical bone loss occurred after midlife. Prominent increase in Ct.Po began at the fifth decade but appeared to be arrested before the sixth decade. Loss of trabecular bone was already evident in young adulthood and continued throughout life.

Differential effects of low-magnitude high-frequency vibration on reloading hind-limb soleus and gastrocnemius medialis muscles in 28-day tail-suspended rats.

OBJECTIVES: Low-magnitude high-frequency vibration (LMHFV) was reported beneficial to muscle contractile functions in clinical and preclinical studies. This study aims to investigate the effects of LMHFV on myofibers, myogenic cells and functional properties of disused soleus (Sol) and gastrocnemius medialis (GM) during reloading. METHODS: Sprague Dawley rats were hind-limb unloaded for 28 days and assigned to reloading control (Ctrl) or LMHFV group (Vib). Sol and GM of both groups were harvested for fiber typing, proliferating myogenic cell counting and in vitro functional assessment. RESULTS: Myogenic cells proliferation was promoted by LMHFV in both Sol and GM (p<0.001 and p<0.05 respectively). Force generating capacity was not much affected (Vib=Ctrl, p>0.05) but fast-fiber favorable changes in fiber type switching (more type IIA but lower type I in Vib; p<0.05 and 0.01 respectively) and fiber hypertrophy (type I, Vib

Effect of daily short-duration weight-bearing on disuse-induced deterioration of musculoskeletal system.

OBJECTIVES: To investigate deterioration of musculoskeletal system due to prolonged disuse and the potential of daily short-duration weight-bearing as countermeasures. METHODS: Twenty-four adult male Sprague-Dawley rats were divided into Control Group (CG, no intervention), Tail-suspension Group (TG, tail-suspension without treatment), and Weight-Bearing Group (WBG, tail-suspension with 20 min/day, 5 days/week body weight loading). After four weeks of treatment, femur and tibia, soleus and extensor digitorum longus were evaluated for bone and muscle quality respectively. Tensile properties of bone-tendon insertion (BTI) were evaluated using patella-patellar tendon complex. RESULTS: Disuse induced deterioration on bone, muscle, and BTI after four weeks. Compared with CG, TG and WBG showed significant decrease in bone mineral density (BMD) of trabecular bone in distal femur (4.3-15.2%), muscle mass (31.3-52.3%), muscle cross-sectional area (29.1-35%), and failure strength of BTI (23.9-29.4%). Tensile test showed that the failure mode was avulsion of bone at the BTI. No significant difference was detected between TG and WBG for all assessments on bone, muscle, and BTI. CONCLUSIONS: Disuse caused deterioration of bone, muscle, and BTI while daily short-duration of weight-bearing did not prevent this deterioration. Mechanical stimulation with higher intensity and longer duration may be necessary to prevent musculoskeletal deterioration resulted from prolonged disuse.

Low magnitude high frequency vibration accelerated cartilage degeneration but improved epiphyseal bone formation in anterior cruciate ligament transect induced osteoarthritis rat model.

OBJECTIVES: To evaluate the effects of low-magnitude high-frequency vibration (LMHFV) on degenerated articular cartilage and subchondral bone in anterior cruciate ligament transection (ACLT) induced osteoarthritis (OA) rat model. METHODS: 6 months old female Sprague-Dawley rats received ACLT on right knee and randomly divided into treatment and control groups. OA developed 12 weeks after surgery. LMHFV (35 Hz, 0.3 g) treatment was given 20 min/day and 5 days/week. After 6, 12 and 18 weeks, six rats of each group were sacrificed at each time point and the right knees were harvested. OA grading score, distal femur cartilage volume (CV), subchondral bone morphology, elastic modulus of cartilage and functional changes between groups were analyzed. RESULTS: Increased cartilage degradation (higher OA grading score) and worse functional results (lower duty cycle, regular index and higher limb idleness index) were observed after LMHFV treatment (P = 0.011, 0.020, 0.012 and 0.005, respectively). CV increased after LMHFV treatment (P = 0.019). Subchondral bone density increased with OA progress (P < 0.01). Increased BV/TV, Tb.N and decreased Tb.Sp were observed in distal femur epiphysis in LMHFV treatment group (P = 0.006, 0.018 and 0.011, respectively). CONCLUSION: LMHFV accelerated cartilage degeneration and caused further functional deterioration of OA affected limb in ACLT-induced OA rat model. In contrast, LMHFV promoted bone formation in OA affected distal femur epiphysis, but did not reverse OA progression.

Effects of 18-month low-magnitude high-frequency vibration on fall rate and fracture risks in 710 community elderly--a cluster-randomized controlled trial.

UNLABELLED: This study is a prospective cluster-randomized controlled clinical trial involving 710 elderly subjects to investigate the long-term effects of low-magnitude high-frequency vibration (LMHFV) on fall and fracture rates, muscle performance, and bone quality. The results confirmed that LMHFV is effective in reducing fall incidence and enhancing muscle performance in the elderly. INTRODUCTION: Falls are direct causes of fragility fracture in the elderly. LMHFV has been shown to improve muscle function and bone quality. This study is to investigate the efficacy of LMHFV in preventing fall and fractures among the elderly in the community. METHODS: A cluster-randomized controlled trial was conducted with 710 postmenopausal females over 60 years. A total of 364 participants received daily 20 min LMHFV (35 Hz, 0.3 g), 5 days/week for 18 months; 346 participants served as control. Fall or fracture rate was taken as the primary outcome. Also, quadriceps muscle strength, balancing abilities, bone mineral density (BMD), and quality of life (QoL) assessments were done at 0, 9, and 18 months. RESULTS: With an average of 66.0% compliance in the vibration group, 18.6% of 334 vibration group subjects reported fall or fracture incidences compared with 28.7% of 327 in the control (adjusted HR = 0.56, p = 0.001). The fracture rate of vibration and control groups were 1.1 and 2.3 % respectively (p = 0.171). Significant improvements were found in reaction time, movement velocity, and maximum excursion of balancing ability assessment, and also the quadriceps muscle strength (p < 0.001). No significant differences were found in the overall change of BMD. Minimal adverse effects were documented. CONCLUSION: LMHFV is effective in fall prevention with improved muscle strength and balancing ability in the elderly. We recommend its use in the community as an effective fall prevention program and to decrease related injuries.

Resistive vibration exercise retards bone loss in weight-bearing skeletons during 60 days bed rest.

UNLABELLED: Countermeasures are desirable to retard bone loss during long-term space flight. We evaluated the effect of an intervention protocol on bed rest-induced bone loss. INTRODUCTION: We developed a resistive vibration exercise (RVE) platform to test if an intervention RVE protocol would be effective to protect bed rest-induced bone loss. METHODS: Fourteen male subjects were assigned randomly to either the RVE group (n = 7) that performed daily supervised resistive vibration exercise or to the no any exercise control (CON) group (n = 7). Both dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to monitor changes in bone mineral density. RESULTS: RVE significantly prevented bone loss at multiple skeletal sites, including calcaneus, distal tibia, hip, and lumbar spine (L2-L4). The ratio of urinary calcium and creatinine was found higher after starting bed rest in CON group while no significant changes were observed in RVE group. No significant temporal change was found for osteocalcin-N during and after bed rest in CON group. However, a significant increase was shown after bed rest in RVE group. In both groups, the urinary concentration of bone resorption markers, such as C-telopeptide of type I collagen (CTX-I) and deoxypyridinoline (DPD), were significantly elevated after bed rest. In the CON group, no significant temporal effect was found for hydroxyproline (HOP), CTX-I, and DPD during bed rest and the serum concentration of HOP and TGF-ß significantly increased about 52.04% and 24.03%, respectively only after bed rest. However, all these markers tended to decrease in the RVE group. CONCLUSIONS: Our results might imply that the intervention of RVE retarded bone loss induced by simulated microgravity in humans that was mainly attributed to its anabolic effects.

The impact of particulate matter air pollution (PM2.5) on atherosclerosis in modernizing China: a report from the CATHAY study.

BACKGROUND: Air pollution has been associated with an increase in cardiovascular diseases incidence. To evaluate whether air pollution can accelerate atherogenic processes, we assessed the effects of air pollution on important surrogate markers of atherosclerosis [brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT)]. METHODS: A total of 1656 Han Chinese (mean age 46.0 + 11.2 years; male 47%) in Hong Kong, Macau, Pun Yu, Yu County and the 3-Gorges Territories (Yangtze River) were studied between 1996 and 2007 [Chinese Atherosclerosis in the Aged and Young Project (the CATHAY Study)]. Cardiovascular risk profiles were evaluated. Particulate matter with an aerodynamic diameter <2.5 µm (PM2.5) parameters were computed from satellite sensors. Brachial FMD and carotid IMT were measured by ultrasound. RESULTS: Health parameters [age, gender, body mass index, waist : hip ratio (WHR) and glucose)] were similar in lowest and highest PM2.5 exposure tertiles, systolic and diastolic blood pressures and triglycerides were higher (P < 0.001) and low-density cholesterol (LDL-C) was lower in the top PM2.5 tertile (P < 0.001). Brachial FMD [7.84 ± 1.77, 95% confidence interval (CI) 7.59-8.10%, vs 8.50 ± 2.52, 95% CI 8.23-8.77%, P < 0.0001) was significantly lower and carotid IMT (0.68 ± 0.13 mm, 95% CI 0.67-0.69 mm vs 0.63 mm ± 0.15 mm 95% CI 0.62-0.64 mm; P < 0.0001) was significantly thicker in the top PM2.5 tertile compared with the lowest tertile. On multiple regression, FMD was inversely related to PM2.5 (beta = 0.134, P = 0.015) independent of gender, age and blood pressure (model R2 = 0.156, F-value = 7.6, P < 0.0001). Carotid IMT was significantly correlated with PM2.5 exposure (beta = 0.381, P < 0.0001) independent of age, location, gender, WHR, blood pressure and LDL-C (model R2 = 0.408, F-value = 51.4, P-value <0.0001). CONCLUSIONS: Air pollution is strongly associated with markers of early atherosclerosis, suggesting a potential target for preventive intervention.

A delayed bone-tendon junction healing model established for potential treatment of related sports injuries.

BACKGROUND: Animal models for the study of tendinopathy and bone-tendon (B-T) junction repair have been established in the past for sports medicine research. As healing at the B-T junction is difficult and sometimes delayed, establishing a delayed B-T healing experimental model is therefore essential to study the efficacy of potential biophysical and biological interventions for treatment of B-T junction healing. OBJECTIVE: To test the hypothesis that a delay in B-T healing could be modelled by shielding the B-T healing interface for the initial few weeks. METHODS: Using an established partial patellectomy model in rabbits, the B-T healing interface was shielded with a latex slice for the first 4 postoperative weeks in mature female rabbits. The characteristics of delay in B-T repair (n = 10) compared with controls (n = 10) were evaluated at 8 and 12 postoperative weeks. RESULTS: Radiology showed consistent delay in osteogenesis at the healing interface in all samples in the delayed healing group; growth of new bone was only 25.8% and 50.1% of that in the control group at weeks 8 and 12, respectively. Bone mineral density was 56.0% lower in the delayed healing group at week 8, but this difference diminished at week 12. The quality of B-T healing was poor in the delayed healing group, with 22.9% and 24.2% lower failure load than the control group at weeks 8 and 12, respectively. The healing quality was also reflected by histological findings. CONCLUSIONS: A delayed B-T healing experimental model was established for the first time for future sports medicine research.

A complete genomic analysis of hepatitis B virus genotypes and mutations in HBeAg-negative chronic hepatitis B in China.

We aimed to study the distribution of hepatitis B virus (HBV) genotypes/subgenotypes in different parts of China and their clinical impact on the severity of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Residual serum samples from a cohort of HBeAg-negative chronic hepatitis B patients in Hong Kong, Shanghai and Beijing were studied. Complete HBV genomic sequencing was performed for phylogenetic tree analysis and determination of HBV mutations was carried out. Mutations associated with severe liver fibrosis (Ishak score 4 or more) were selected by computerized information gain criteria. Genotype B (all subgenotype Ba) HBV was present in 19 of 45 (42%), 12 of 31 (39%) and 5 of 25 (20%) patients in Hong Kong, Shanghai and Beijing, respectively (P = 0.16). Ninety-seven per cent of genotype C HBV in Shanghai and Beijing belonged to subgenotype Ce whereas 69% of genotype C patients in Hong Kong belonged to subgenotype Cs (P < 0.001). Patients infected by subgenotype Cs had the lowest serum albumin and highest alanine aminotransferase levels compared with subgenotype Ce and Ba. Patients infected by subgenotype Cs also had more severe histological necroinflammation than subgenotype Ce. Two HBV mutations were identified to associate with severe liver fibrosis (G2858C and C2289A) and one mutation was protective against severe liver fibrosis (T2201C). The T2201C mutation was found exclusively among patients (21 of 46 patients, 45%) infected by HBV subgenotype Ce. The clinical differences in HBeAg-negative chronic hepatitis B in China may be influenced by different distribution of subgenotype C HBV.

[Percutaneous screw fixation in treatment of fractures of acetabular columns using computer-assisted imaging navigation system: experiment with cadaver model].

OBJECTIVE: To establish a new imaging protocol to acquire the most appropriate fluoro-images for fluoro-navigated percutaneous fixation of acetabular fracture and to evaluate the safety and efficiency of the procedures. METHODS: Guide needles were inserted into the bilateral anterior and posterior columns of the acetabula of 4 dry human cadaver pelvic skeletons and 4 plastic pelvic models. Then the pelvis skeletons were fixed to imaging guided surgery mimic operation modules. Dynamic fluoroscopy was conducted with C-arm X-ray machine vertically on the 4 virtual planes of the acetabulum, inner, outer, anterior, and posterior from multiple angles. The fluoroscopic images clearly showing the guide needles, anterior and posterior columns, and acetabulum were selected as registration images, and the relative space positions between the C-arm X-ray fluoroscope and pelvis and operation table. Guided by the navigation system, totally 16 titanium hollow screws were inserted into bilateral anterior and posterior columns of acetabula of the 4 pelvis skeletons. The screw positions were estimated by visual method. The time needed to position the C-arm so as to obtain the standard registration image, time needed for fluoroscopy, and operation time, including establishment of navigation system, software interface operation, and screw insertion, were recorded. RESULTS: All the screws were inserted to the satisfying positions: placed within the desired bony corridor of the column and none of then were inserted into the joint. While inserting the screw into the anterior column fluoroscopy should be conducted with obturated oblique view, obturated inlet view, obturated oblique outlet view, or pelvic AP view. While inserting the screw into the posterior column fluoroscopy should be conducted with iliac-oblique view, obturated oblique view, pelvic inlet view, or obturated oblique outlet view. The total surgical time required for screw insertion was 11.7 min for anterior column, and was 9.2 min for posterior column. 9.5 and 7.3 minutes were needed to position the C-arm X-ray machine so as to obtain the images of the anterior and posterior columns respectively. 2.9 and 1.7 seconds were needed for the actual fluoroscopy during insertion of the screws into the anterior and posterior columns respectively. CONCLUSION: The standard registered fluoro-images are different from the conventional standard Judet-Letournel oblique views. How to get appropriate fluoro-images is the key point for fluoro-navigated percutaneous fixation of acetabular fractures.