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.

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.

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.

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 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.

The role of the sensory nerve response in ultrasound accelerated fracture repair.

This study was designed to test the hypothesis that the sensory innervation of bone might play an important role in sensing and responding to low-intensity pulsed ultrasound and explain its effect in promoting fracture healing. In 112 rats a standardised mid-shaft tibial fracture was created, supported with an intramedullary needle and divided into four groups of 28. These either had a sciatic neurectomy or a patellar tendon resection as control, and received the ultrasound or not as a sham treatment. Fracture union, callus mineralisation and remodelling were assessed using plain radiography, peripheral quantitative computed tomography and histomorphology. Daily ultrasound treatment significantly increased the rate of union and the volumetric bone mineral density in the fracture callus in the neurally intact rats (p = 0.025), but this stimulating effect was absent in the rats with sciatic neurectomy. Histomorphology demonstrated faster maturation of the callus in the group treated with ultrasound when compared with the control group. The results supported the hypothesis that intact innervation plays an important role in allowing low-intensity pulsed ultrasound to promote fracture healing.

Orthopaedic training in China: experiences from the promotion of orthopaedic specialist training in China.

There is no unified national training system for orthopaedic surgeons in China. With such rapid progress in many aspects of life in China, there is an imminent need for improvement in the training of orthopaedic specialists. Since 2003 the orthopaedic community in Hong Kong has been working in collaboration with their colleagues in mainland China to develop a training system for orthopaedic surgery. We adopted the system from the Royal College of Surgeons of Edinburgh (RCSEd), setting up a trial centre in the Beijing Jishuitan hospital in 2006, with trainers and trainees attaining the standards set by RCSEd and the Hong Kong College of Orthopaedic Surgeons (HKCOS). This trial is ongoing, with the success of two trainees who passed the exit examination in 2010 and became the first Chinese orthopaedic surgeons with a joint fellowship of both the RCSEd and the HKCOS. Following this inaugural success, we are confident that China will develop a training system for orthopaedic surgeons to a consistently high international standard.

Image-guided navigation in orthopaedic trauma.

Fluoronavigation is an image-guided technology which uses intra-operative fluoroscopic images taken under a real-time tracking system and registration to guide surgical procedures. With the skeleton and the instrument registered, guidance under an optical tracking system is possible, allowing fixation of the fracture and insertion of an implant. This technology helps to minimise exposure to x-rays, providing multiplanar views for monitoring and accurate positioning of implants. It allows real-time interactive quantitative data for decision-making and expands the application of minimally invasive surgery. In orthopaedic trauma its use can be further enhanced by combining newer imaging technologies such as intra-operative three-dimensional fluoroscopy and optical image guidance, new advances in software for fracture reduction, and new tracking mechanisms using electromagnetic technology. The major obstacles for general and wider applications are the inability to track individual fracture fragments, no navigated real-time fracture reduction, and the lack of an objective assessment method for cost-effectiveness. We believe that its application will go beyond the operating theatre and cover all aspects of patient management, from pre-operative planning to intra-operative guidance and postoperative rehabilitation.

Integration of CAD/CAM planning into computer assisted orthopaedic surgery.

Modern Computer Aided Design/Modeling (CAD/CAM) software allows complex surgical simulations, but it is often difficult to transfer and execute precisely the planned scenarios during actual operations. We describe a new method of integrating CAD/CAM surgical plans directly into a computer surgical navigation system, and demonstrate its use to guide three complex orthopaedic surgical procedures: a periacetabular osteotomy of a dysplastic hip, a corrective osteotomy of a post-traumatic tibial deformity, and a multi-planar resection of a distal femoral tumor followed by reconstruction with a CAD custom prosthesis.

Outcome of hematopoietic stem cell transplant as salvage therapy for Hodgkin's lymphoma in adolescents and young adults at a single institution.

For patients with relapsed Hodgkin's lymphoma (HL), high dose chemotherapy with stem cell rescue (HDCT-SCT) may improve survival over chemotherapy alone. We assessed the outcomes of HDCT-SCT in 37 consecutive adolescent and young adult patients with relapsed HL whose malignancy was categorized based on sensitivity to chemotherapy. We determined whether current outcomes supported the use of HDCT-SCT in all of our patients or just those patients with lower-risk characteristics such as chemosensitivity. With a median follow-up of 6.5 years, the 2-year overall survival (OS) was 89% (95% CI: 62-97%) for the chemosensitive patients (n = 21), whereas for patients with resistant disease (n = 16), OS was 53% (95% CI: 25-74%). Both autologous and allogeneic transplants were well tolerated, with 100-day treatment-related mortality under 10%. Our data show encouraging outcomes for patients with chemosensitive relapsed HL who receive hematopoietic stem cell transplant (HSCT) and support the value of the procedure even when the disease is chemoresistant.

[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.

Precision tumour resection and reconstruction using image-guided computer navigation.

The use of a navigation system in musculoskeletal tumour surgery enables the integration of pre-operative CT and MRI images to generate a precise three-dimensional anatomical model of the site and the extent of the tumour. We carried out six consecutive resections of musculoskeletal tumour in five patients using an existing commercial computer navigation system. There were three women and two men with a mean age of 41 years (24 to 47). Reconstruction was performed using a tumour prosthesis in three lesions and a vascularised fibular graft in one. No reconstruction was needed in two cases. The mean follow-up was 6.9 months (3.5 to 10). The mean duration of surgery was 28 minutes (13 to 50). Examination of the resected specimens showed clear margins in all the tumour lesions and a resection that was exactly as planned.

Multiple bioimaging modalities in evaluation of an experimental osteonecrosis induced by a combination of lipopolysaccharide and methylprednisolone.

AIMS: The present study employed both static and dynamic imaging modalities to study both intra- and extravascular events attributing to steroid-associated osteonecrosis (ON) using an experimental protocol with a single low-dose lipopolysaccharide (LPS) injection and subsequently three injections of high-dose methylprednisolone (MPS). METHODS: Fourteen 28-week-old male New Zealand white rabbits received one intravenous injection of LPS (10 microg/kg). 24 h later, three injections of 20 mg/kg of MPS were given intramuscularly at a time interval of 24 h. Additional 6 rabbits were used as controls. Dynamic MRI was performed on bilateral femora for local intraosseous perfusion before and after LPS injection. Blood samples were collected for hematological examinations before and after LPS injection. Bilateral femora were dissected and decalcified for microCT-based microangiography. ON lesion, intravascular thrombus and extravascular marrow fat cell size were examined histopathologically. RESULTS: Intravascular thrombus was observed in all ON rabbits. Extravascular marrow fat cell size was significantly increased in ON rabbits than that of the controls (P<0.05). Compared to baseline, a significant decrease in ratio of tissue-type plasminogen activator/plasminogen activator inhibitor 1, activated partial thromboplatin time and a significant increase in ratio of low-density lipoprotein/high-density lipoprotein were only found in ON rabbits (P<0.05). Dynamic MRI showed a significant decrease in the perfusion index 'maximum enhancement' in the ON rabbits (P<0.05), and microCT-based microangiography showed blocked stem vessels in ON samples. Overall, 93% of the rabbits (13/14) developed ON, and no rabbits died throughout the experiment period. CONCLUSION: Both intra- and extravascular events were found attributing to the steroid-associated ON based on our experimental protocol with a single low-dose LPS injection and subsequent three injections of high-dose MPS. Both high ON incidence and no mortality in rabbits treated with this inductive protocol suggested its effectiveness for future studies on evaluation of therapeutic efficacy of interventions developed for prevention of steroid-associated ON.

Danshen prevents the occurrence of oxidative stress in the eye and aorta of diabetic rats without affecting the hyperglycemic state.

Oxidative stress has been implicated in the pathogenesis of diabetic complications. We have previously demonstrated the occurrence of oxidative stress in the eye and aorta but not in the kidney of diabetic rats. In the present study we have investigated the effects of danshen, a herb used in traditional Chinese medicine to treat ailments related to diabetic complications, on the onset of oxidative stress in the above tissues. Diabetic rats were treated with 3 g/kg of danshen via oral intubation for 7 weeks. Afterwards, the tissue levels of glutathione (GSH), the primary endogenous antioxidant, and malondialdehyde (MDA), a marker of oxidative stress, were measured. Our results showed that danshen treatment did not alter the hyperglycemic status of the diabetic animals. However, the GSH levels were normalized in both the eye and aorta of the diabetic rats when these rats were administered with danshen. Administration with danshen also restored the level of MDA in the eye and aorta of the diabetic rats to that found in the control rats. These changes, however, were not observed in the kidney where oxidative stress did not occur. These results suggested that oral administration of danshen can effectively prevent the occurrence of oxidative stress in the eye and aorta of the diabetic rats. Furthermore, danshen treatment did not affect the blood glucose concentration of the animals irrespective of their diabetic state. These data therefore provide important information on mode of action of danshen, thereby establishing a basis for this herb to be used as a supportive treatment regime to ameliorate the severity of diabetic complications.

A study of trabecular bones in ovariectomized goats with micro-computed tomography and peripheral quantitative computed tomography.

Osteoporotic fractures occur most frequently in trabeculae-rich skeletal sites. The purpose of this study was to use a high-resolution micro-computed tomography (micro-CT) to investigate the changes in trabecular bone microarchitecture and to use a peripheral quantitative computed tomography (pQCT) to study changes in volumetric bone mineral density (BMD) in a large animal model resulted from ovariectomy (OVX). Ten adult goats were used for this study. The first iliac crest biopsy was harvested before OVX and served as baseline; the second biopsy was collected 6 months later from the opposite side for both pQCT and micro-CT measurements. Results showed that after 6 months of OVX, the BMD of the iliac crest biopsies decreased significantly by 16.3% (P < 0.05). The bone volume density (BV/TV), trabecular number (Tb.N), and connectivity density (Conn.D) measured with micro-CT decrease significantly after OVX, with an average decrease of 8.34%, 8.51%, and 18.52% (P < 0.05 each), respectively. The trabecular plate separation (Tb.Sp) was 8.26% (P < 0.05) greater than baseline after OVX. Significant correlations were found between the reduction of BMD and the decreases of BV/TV and Tb.N (r = 0.839 and 0.719, respectively; P< 0.001 both), as well as the increase of Tb.Sp (r = -0.758, P< 0.001) and SMI (r = -0.697, P< 0.001). In conclusion, this was the first experimental study in goat model to show that OVX-induced bone loss in goats was attributed by deterioration of trabecular microarchitecture.

TGF-beta1 is the factor secreted by proliferative chondrocytes to inhibit neo-angiogenesis.

Growth plate is an avascular tissue, which has been reported to be capable of retarding tumor spread. It is believed that angiogenic inhibitor(s) exist to inhibit the neo-vascularization of tumor, thus impeding the tumor growth. In this study, growth plate chondrocyte-derived TGFbeta1 was identified to be anti-angiogenic. It was found that growth plate chondrocytes (GPC) secreted TGFbeta1 mostly in latent form as demonstrated by gel filtration and immunoblotting. Enzyme-linked immunosorbent assay (ELISA) was followed to quantify TGFbeta1 in GPC conditioned medium (CM), in which 866 pg/ml of TGFbeta1 was found. Besides, the angiogenesis inhibitory effect of GPC CM was abolished by the addition of anti-TGFbeta1 antibody in the in vitro culture system and the in vivo chick chorioallantoic membrane (CAM) assay. This confirmed the anti-angiogenic properties of chondrocyte-derived TGFbeta1. TGFbeta1 was expressed predominantly in the proliferative zone of porcine growth plate. This explains the low incidence of tumor invasion across the entire growth plate. Also, this helps to explain the observation that tumor invasion across the physis increases with age as the proliferative zone gradually disappears. J. Cell. Biochem. Suppl. 36: 79-88, 2001.

Growth plate chondrocytes inhibit neo-angiogenesis -- a possible mechanism for tumor control.

Clinically, tumors seldom grow across the articular cartilage and physeal plate. It is believed that avascular cartilage may inhibit the neo-vascularization of tumor spread. The conditioned medium of growth plate chondrocytes resisted the migration of ECV304 by approximately 41% in invasion assay. Growth plate chondrocytes were shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to have an insignificant effect on the viability of human endothelial cells and fibroblasts. However, the proliferation of human endothelial cells was significantly inhibited by growth plate chondrocytes. The inhibitory activity was up to 35% and specific to endothelial cells. Inhibition of blood vessel formation was also demonstrated in the chick chorioallantoic membrane (CAM) assay. These findings demonstrated that growth plate chondrocytes secrete anti-angiogenesis factor(s) which specifically inhibit both the migration and proliferation of endothelial cells.

Goats as an osteopenic animal model.

A large osteopenic animal model that resembles human osteoporotic changes is essential for osteoporosis research. This study aimed at establishing a large osteopenic animal model in goats. Twenty-five Chinese mountain goats were used in which they were either ovariectomized (OVX) and fed with a low-calcium diet (n = 16) or sham-operated (SHAM; n = 9). Monthly photodensitometric analysis on proximal tibial metaphysis and calcaneus was performed. Two iliac crest biopsy specimens obtained before and 6 months after OVX were used for bone mineral density (BMD) measurement with peripheral quantitative computed tomography (pQCT). Lumbar vertebrae (L2 and L7), humeral heads, and calcanei were collected for BMD measurement after euthanasia. The humeral heads and calcanei were used in biomechanical indentation test. BMD measurement showed a significant 25.0% (p = 0.006) decrease in BMD of the iliac crest biopsy specimens 6 months after OVX. It also was statistically significant when compared with the SHAM (p = 0.028). BMD at L2, L7, calcaneus, and humeral head reduced by 24-33% (p ranged from 0.001 to 0.011) when compared with the SHAM. Photodensitometry showed a continuous decrease in bone density after OVX. There were significant decreases of 18.9% in proximal tibial metaphysis (p = 0.003) and 21.8% in calcaneus (p = 0.023) in the OVX group 6 months postoperatively. Indentation test on the humeral head and calcaneus showed a significant decrease 52% (p = 0.006) and 54% (p = 0.001), respectively, in energy required for displacement of 3 mm in the OVX group compared with the SHAM group. The decreases correlated significantly to the decrease in BMD of the corresponding specimens (r2 = 0.439 and 0.581; p < 0.001 for both). In conclusion, this study showed that OVX plus a low-calcium diet could induce significant osteopenia and deterioration of mechanical properties of the cancellous bone in goats.

Partial patellectomy induces a decrease in the proteoglycan content in the remaining patellar articular cartilage. An experimental study in rabbits.

We studied the alterations and distribution of the proteoglycan (PG) content of the remaining patellar articular cartilage after unilateral partial patellectomy in 13 rabbits. Sagittal sections of the patella were prepared and stained with Safranin O for quantification of changes in the PG content of the patellar articular cartilage using a commercially available imaging analysis system. Our findings suggest that partial patellectomy results in a decreased PG content in the remaining patellar articular cartilage. In addition, the postoperative development of metaplasia in the scar tissue next to the healing interface may represent a compensatory response, which could prevent a further reduction in the PG content and hence the development of osteoarthritis in the remaining patellar articular cartilage.