Aims

Osteoporosis (OP) is a metabolic bone disease, characterized by a decrease in bone mineral density (BMD). However, the research of regulatory variants has been limited for BMD. In this study, we aimed to explore novel regulatory genetic variants associated with BMD.

Aims

The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA).

Aims

Despite the interest in the association of gut microbiota with bone health, limited population-based studies of gut microbiota and bone mineral density (BMD) have been made. Our aim is to explore the possible association between gut microbiota and BMD.

Osteosarcoma (OSA) is a rare, but disproportionately lethal cancer that predominantly affects children. Sadly, discovery of new therapies for OSA has largely been unsuccessful in the past 30 years; there is an urgent need to identify new treatments for OSA. Pet dogs with naturally-occurring OSA represent a unique comparative “model” to discover new treatments for OSA. Unlike humans, in which fewer than 1,000 cases of OSA occur each year, there are nearly 50,000 new cases each year of OSA in dogs. In addition, dogs have an intact immune system, a shared environment with humans, and more rapid progression of disease. Together these factors make dogs an important comparative model for new therapies for OSA. The purpose of this study was: 1) to validate this mouse-dog-human pipeline for drug discovery and 2) to validate CRM1 as a novel target for ostesoarcoma treatment.

We developed patient-derived cell lines and xenografts of OSA from both dogs and humans and applied these models to identify new therapies for OSA using high-throughput drug screens in vitro followed by in vivo validation. Whole exome sequencing was performed on the patient-derived models and original tumors to identify potential driver mutations.

A high-throughput screen in both dog and human OSA identified CRM1 inhibitors as effective at killing dog and human OSA patient-derived cell lines in vitro. In vivo, CRM1 inhibition led to significant tumor growth inhibition in patient-derived xenografts from dogs and humans. Western blotting demonstrated increased levels of CRM1 protein expression across nine different dog and human OSA cell lines compared to non-transformed human osteoblasts. CRM1 upregulation in OSA cells was further verified by immunofluorescence staining. Increased CRM1 expression was prognostic for poorer metastasis-free survival and poorer overall survival.

Our cross-species personalized medicine pipeline identified CRM1 as a potential therapeutic target to treat OSA in both dogs and humans. Future studies are focused on testing CRM1 inhibitors in canine clinical trials.

Aims

Kashin-Beck disease (KBD) is a kind of chronic osteochondropathy, thought to be caused by environmental risk factors such as T-2 toxin. However, the exact aetiology of KBD remains unclear. In this study, we explored the functional relevance and biological mechanism of cartilage oligosaccharide matrix protein (COMP) in the articular cartilage damage of KBD.

Aims

Osteoarthritis (OA) is the most prevalent joint disease. However, the specific and definitive genetic mechanisms of OA are still unclear.

Objective

Shoulder instability is a common cause of morbidity amongst Professional Rugby Union players. This study explores whether the risk of shoulder dislocation is associated with innate shoulder laxity.

Shoulder instability is a common cause of morbidity amongst Professional Rugby Union players. This study explores whether the risk of shoulder dislocation is associated with innate shoulder laxity. A prospective, randomised controlled study was completed in which all the Premiership Rugby Clubs in England were visited. 169 professional rugby players with no history of instability in either shoulder and 46 players with one shoulder with clinical instability symptoms were assessed. Shoulder laxity was measured by clinical evaluation, questionnaires and ultrasound. Anterior, posterior and inferior translation was measured in both shoulders for healthy players and the uninjured shoulder only for injured players. The results showed there was no significant difference between the left (anterior: mean 2.92 +/− 1.15 mm; posterior: mean 5.10 +/− 1.75 mm; inferior: mean 3.08 +/− 1.00 mm) and right (anterior: mean 3.07 +/− 1.14 mm; posterior: mean 4.87 +/− 1.61 mm; inferior: mean 2.91 +/− 0.99 mm) shoulders in healthy players (P > 0.05). The comparison between healthy shoulders (anterior: mean 3.00 +/− 1.15 mm; posterior: mean 4.99 +/− 1.68 mm; inferior: mean 3.00 +/− 1.00 mm) from healthy players and the uninjured shoulder (anterior: mean 4.16 +/− 1.70 mm; posterior: mean 6.16 +/− 3.04 mm; inferior: mean 3.42 +/− 1.18 mm) from injured players identified that players with unstable shoulders have a significantly higher shoulder translation in their normal shoulder than healthy players (P < 0.05). This is the first study looking at laxity and the risk of shoulder dislocations in sportsmen involved in a high contact sport. These results support the hypothesis that rugby players with “lax” shoulders are more likely to sustain a dislocation or subluxation injury to one of these lax shoulders in their sport.

Background: Reconstruction nail had developed since 1985. General indications reviewed from literatures are 1. Ipsilateral femoral neck-shaft fracture (nondisplaced), 2. Russell-Type IB subtrochanteric fracturtes (intact piriformis fossa, fractured less trochanter). Many authors did not recommend that application of reconstruction nail in displaced ipsilateral femoral neck-shaft fractures. The reason is that unpredictable femoral neck-shaft reduction and over-distraction of shaft fracture. We developed one new method for overcoming such technical puzzle to achieve one-step reduction for displaced ipsilateral femoral neck-shaft fractures.

Material: There are 24 consecutive cases were treated by reconstruction nail by the same operator in Chi-Mei Foundation Hospital from February, 1999 to June, 2000. Five of them were diagnosed as displaced ipsilateral femoral neck-shaft fractures and treating new surgical technique in reconstruction nailing. Initial radiographic assessment revealed displaced neck fracture can be classified as Garden III, the fracture morphology is vertical (Pauwell III). Average age of these five patients is 37.6 y/o. The sex distribution is M:F=3:2

Method: Provisional proximal fixation of femur is mandatory. First, we use two 5.0mm drillpit transfixed trochanter region after assure of femoral anteversion. Second, release of traction and distal locking for reduction and fixation of shaft fracture part. Third, remove application handle and use Internal rotation or other remote maneuver for restoration of neck-shaft angle. Finally, complete drilling through neck and sequent proximal cephalomedullary locking was performed by free-hand method.

Result: Initial reduction result was acceptable. There was no significant coxa-varus or coxa-brevis. Two of them had removed of implants and clinical result was satisfied. No avascular necrosis was noted in our following up.

Discussion: How to treat displaced ipsilateral femoral neck-shaft fractures in one-step was obstacle in our orthopedic practice. Abandonment of reconstruction nail just due to technique demanding purpose is very pity. We developed such technique to make patient with displaced ipsilateral femoral neck-shaft fractures treat by closed and one-step method and gained more satisfaction.