Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Purulent flexor tenosynovitis: Factors influencing the functional outcome

This retrospective study aimed to evaluate the factors that influence the final outcome of treatment of purulent flexor tenosynovitis, viz. delay in treatment, severity of the condition, the infecting pathogen and the method of treatment. Of 41 patients with this condition treated by drainage and irrigation through two small incisions (16) and wide incision (25), 16 were treated after a delay. Continuous postoperative irrigation was applied in 26 patients. Re-operation was necessary in 11 patients. In most cases, Staphylococcus aureus was detected. The results were excellent in 32 cases and the mean Disabilities of the Arm, Shoulder and Hand score was 8.1. Irrigation through small incisions and continuous postoperative irrigation decreased the probability of an unfavourable outcome. Delayed treatment and infections with specific pathogens led to a worse outcome. Early diagnosis of purulent flexor tenosynovitis followed by drainage through small incisions and continuous postoperative irrigation appear, from this retrospective review, to lead to the best functional outcome

Ancient Schwannoma of the Hand

Ancient schwannoma is a schwannoma subtype, characterized by extensive degeneration and diffuse hypocellular areas. These changes are believed to occur because it takes a long time for ancient schwannomas to develop. Schwannomas with these degenerative changes can be misdiagnosed as sarcomas or other soft-tissue neoplasms. We present a case of a slowly enlarging ancient schwannoma of the thenar area in a 67-year-old woman. The differential diagnosis included atypical soft tissue sarcomas and tumors of neural origin. The combination of ultrasound and magnetic resonance imaging findings provided features that narrowed the differential diagnosis, and histology confirmed the presence of an encapsulated schwannoma with extensive myxomatous degeneration and multiple vessel thrombosis. The clinical, radiological, and histological features and the diagnostic approach of this rare entity are described. (J Hand Surg 2011;36A:2030-2033. Copyright (C) 2011 by the American Society for Surgery of the Hand. All rights reserved.

Vascularized periosteal flaps of distal forearm and hand

Background: Vascularized periosteal flaps (VPFs) are flexible osteogenic flaps, suitable for the reconstruction of small skeletal defects. Pedicled VPFs, harvested near the recipient site, minimize donor-site morbidity and procedure duration. The donor sites and the potential recipient sites for pedicled VPFs of the distal forearm-hand were identified in this study. Methods: In 16 fresh cadaver upper extremities, the dimensions and arcs of rotation of the VPF pedicle(s) were studied. Results: Pedicled VPFs with mean dimensions ranging between 0.5 x 3 cm and 2.5 x 4 cm could cover, after adequate mobilization, the distal half of the forearm, wrist, and hand to the proximal interphalangeal joints. Conclusion: The VPFs identified in this study can be used for the reconstruction of small skeletal defects and for the treatment of osteonecrotic lesions and nonunions of the distal forearm, wrist, and hand. The choice of the most suitable VPF will be based on the anatomic location and the dimensions of the recipient site

Autologous (non-vascularised) fibular grafting with recombinant bone morphogenetic protein-7 for the treatment of femoral head osteonecrosis

This preliminary study evaluates a combination of bone morphogenetic protein (BMP)-7 and non-vascularised autologous fibular grafting (AFG) for the treatment of osteonecrosis of the femoral head. BMP-7/AFG combination was applied in seven pre-collapse femoral heads (five Steinberg stage II, two stage III) in six patients. Pre- and post-operative evaluation included clinical (Harris hip score (HHS), visual analogue scale (VAS) for pain) and radiological assessment (radiographs, quantitative CT) at a mean follow-up of 4 years (2 to 5.5). A marked improvement of function (mean HHS increase of 49.2) and decrease of pain level (mean VAS decrease of 5) as well as retention of the sphericity of the femoral head was noted in five hips at the latest follow-up, while signs of consolidation were apparent from the third post-operative month. One patient (two hips) required bilateral total hip replacement at one year post-operatively. In the series as a whole, quantitative-CT evaluation revealed similar densities between affected and normal bone. Heterotopic ossification was observed in four hips, without compromise of the clinical outcome. In this limited series AFG/BMP-7 combination proved a safe and effective method for the treatment of femoral head osteonecrosis, leading to early consolidation of the AFG and preventing collapse in five of seven hips, while the operative time and post-operative rehabilitation period were much shorter compared with free vascularised fibular grafts

Beware of the ulno-palmar distal radial fragment

Five patients sustained isolated fractures of the ulnopalmar rim of the distal radius. In three cases the fragment was small and was classed as an avulsion fracture of the short radiolunate ligament. Palmar wrist subluxation occurred in all cases, four during treatment in a cast or splint. The ulnopalmar rim of the distal radius contributes to the stability of the radiocarpal joint and fractures in this region merit particular attention