By combining the tools of medicinal chemistry and zebrafish biology, a team of Vanderbilt investigators has identified compounds that may offer therapeutic leads for bone-related diseases and cancer. The findings, reported in ACS Chemical Biology, support using zebrafish as a novel platform for drug development. In 2007, Charles Hong, M.D., Ph.D., and colleagues described using fish embryos to screen for compounds that interfere with signaling pathways involved in early development - pathways known to play roles in a variety of disease processes. They discovered the compound "dorsomorphin" and demonstrated that it blocked BMP (bone morphogenetic protein) signaling, which has been implicated in anemia, inflammatory responses and bone-related disorders. But in examining dorsomorphin further, the investigators found that it had other "off-target" effects - it also blocked the VEGF (vascular endothelial growth factor) receptor and disrupted zebrafish blood vessel development, a process called angiogenesis.
Researchers at the National Institutes of Health and other institutions have discovered the third in a sequence of genes that accounts for previously unexplained forms of osteogenesis imperfecta (OI), a genetic condition that weakens bones, results in frequent fractures and is sometimes fatal. The newly identified gene contains the information needed to make the protein Cyclophilin B. This protein is part of a complex of three proteins that modifies collagen, folding it into a precise molecular configuration, before it is secreted from cells. Collagen functions as molecular scaffolding that holds together bone, tendons, skin and other tissues. Most types of osteogenesis imperfecta result from a dominant mutation in collagen itself, requiring only one copy of the mutated gene to bring about the disorder. osteogenesis imperfecta involving the Cyclophilin B gene is a recessive trait, requiring two defective copies of the gene to cause the disorder. "The discovery provides insight into a previously undescribed form of osteogenesis imperfecta, " said Alan E.
A team of anesthesiologists, nurses and orthopedic trauma surgeons from Hospital for Special Surgery in Manhattan headed for Haiti on Friday and have been performing surgery and tending to those impacted by the earthquake ever since. Led by David L. Helfet, M.D., and Dean G. Lorich, M.D., and including physicians from NewYork-Presbyterian Hospital, the team has been working round the clock at Hopital de la Communaute Haitienne in Port-au-Prince suburb of Petion-Ville and have already performed more than 50 surgical procedures. With air transport provided by global medical device company Synthes and surgical supplies donated by Synthes, Hospital for Special Surgery and NewYork-Presbyterian, the team is working under extremely rudimentary conditions with limited security. The medical team currently in Haiti will be relieved tomorrow evening when a new team from Hospital for Special Surgery will take their place. "This is an important humanitarian effort that requires our team to perform hands-on medicine on people who have been suffering since the earthquake last week, " said Dr.
The use of braces to correct excessive curvature of the spine, or scoliosis, in adolescents is still an area of controversy and is likely to remain that way until there is better evidence, concludes a new review of published research. Although some evidence points toward a benefit from using braces, research has failed to prove definitively that they work. Adolescent idiopathic scoliosis curvature of the spine in which the cause is unknown affects about 1 percent to 12 percent of the general population. Scoliosis is much more common in girls and is more likely to be severe in girls. About 10 percent of children and teenagers who have scoliosis will require treatment, based on the severity of the spinal curvature. Others can have monitoring without treatment to see if the spinal curve worsens. In severe scoliosis that remains untreated, lung, heart and spine damage might occur in adulthood. "Bracing is regarded as effective by some and as useless by others, " says Stefano Negrini, M.
Bones, muscles and tendons work together to provide the perfect balance between stability and movement in the skeleton. Now, Weizmann Institute scientists show that this partnership begins in the embryo, when the bones are still taking shape. The study, published in a recent issue of Developmental Cell, describes a previously unrecognized interaction between tendons and bones that drives the development of a strong skeletal system. 'Our skeleton, with its bones, joints and muscle connections serves us so well in our daily lives that we hardly pay attention to this extraordinary system, ' says Dr. Elazar Zelzer of the Weizmann Institute's Molecular Genetics Department. 'Although previous research has uncovered mechanisms that contribute to the development and growth of each component of this complex and wonderfully adaptable organ system, specific interactions between bones, muscles and tendons that drive the assembly of the musculoskeletal system are not fully understood.' Zelzer, research student Einat Blitz, Sergey Viukov and colleagues, were interested in uncovering the molecular mechanisms that regulate the formation of bone ridges - bony protuberances that provide a stable anchoring point for the tendons that connect muscles with bones.
A new research program at The Methodist Hospital in Houston is the nation's first dedicated solely to advancing nanotechnology in orthopedics and spine surgery. Dr. Bradley Weiner, chief of spinal surgery at Methodist, is the director of the Spine Advanced Technology Laboratory (SATL). Methodist Drs. Harvey Smith and Christopher Loo are co-directors. "Nanotechology has the ability to affect things at a molecular level, " Weiner said. "The use of nanotechnologies to treat disease or repair damaged tissues---such as bone, cartilage, muscle or nerve---might allow physicians to intervene more efficiently and safely than currently possible." Researchers in the lab---working on-site and with collaborators within the Texas Medical Center and beyond---will be looking at various ways nanotechnology can improve the treatment of musculoskeletal disease. "Using nanotechnology, we hope to be able to deliver drugs directly to the affected area thereby limiting exposure to other tissues. In the future, we hope to give an injection into the vein and, with sophisticated mapping, send it directly to specific musculoskeletal tissues, including the spine, and release the medication exactly where it is needed, " Weiner said.
More and more Americans with chronic pain not caused by cancer are taking medically prescribed opioids like Oxycontin ( oxycodone ) and Vicodin (hydrocodone). The January 19 Annals of Internal Medicine features the first study to explore the risk of overdose in patients prescribed opioids for chronic noncancer pain in general health care. The study links risk of fatal and nonfatal opioid overdose to prescription use - strongly associating the risk with the prescribed dose. A team led by Michael Von Korff, ScD, a senior investigator at Group Health Research Institute, studied nearly 10, 000 patients who received multiple opioid prescriptions for common chronic pain conditions like back pain and osteoarthritis. Patients who received higher opioid doses were 9 times more likely to overdose than were those receiving low doses. Still, most of the overdoses occurred among patients receiving low to medium doses, because prescriptions at those levels were much more common. More than 8 million U.
Register now for the most important osteoporosis conference of 2010. The IOF WCO-ECCEO10 is expected to attract some 5000 researchers and clinicians from all continents, including Key Opinion Leaders in the field. Stimulating plenary lectures on varied 'hot' topics will be enhanced by focused Meet-the-Expert Sessions and numerous special sessions and satellite symposia will give in-depth coverage of specific clinical topics. Online registration at http://www.iofwco-ecceo10.org/registration/ Submit your abstract by February 4th! Abstracts will be published in the field's leading journal, Osteoporosis International., with opportunity for poster presentation. Authors of the top abstracts selected for oral presentation are invited to present their work to a large and important audience. Visit http://www.iofwco-ecceo10.org/abstracts/ We hope to welcome you to Florence this spring! The congress center is located in the heart of this beautiful city and near many of the world's most renowned cultural sites.
Endocrinologists at the University of Pittsburgh School of Medicine and UPMC are launching a human trial of a new drug that their research indicates holds great promise for building bones weakened by osteoporosis. For the study, 105 participants will be randomly assigned to receive either teriparitide ( Forteo ® ), a drug that already is FDA-approved for osteoporosis treatment, or an experimental agent called parathyroid hormone-related protein (PTHrP), explained principal investigator Mara J. Horwitz, M.D., an assistant Professor of Medicine in the Division of Endocrinology and Metabolism, Pitt School of Medicine, and a practicing metabolic bone specialist at UPMC. "We are very eager to find out how this new drug compares to a therapy that is currently available, " Dr. Horwitz said. "Our previous studies suggest that it may increase bone density more dramatically with fewer side effects, but this is the first head-to-head comparison." On the cellular level, bone is constantly being broken down, a process known as resorption, and then rebuilt.
Bone loss around dental implants is far more common than previously realised, reveals a thesis from the Sahlgrenska Academy at the University of Gothenburg, Sweden. Around a quarter of patients loose some degree of supporting bone around their implants. The study analysed X-rays of over 600 patients. The more implants a patient had in the jaw, the more common it was to find loss of supporting bone. Just over a quarter 28 per cent of patients had lost some degree of supporting bone around their implants. "Contrary to what we had previously assumed, the bone loss in these patients was not linear, but instead accelerated with time, " says consultant dental surgeon Christer Fransson, who wrote the thesis. "This is a new discovery that shows just how important it is to detect and treat bone loss around implants at an early stage." Smoking is one of several factors that increase the risk of bone loss. In the study smokers had more implants with bone loss than non-smokers. The thesis also shows that the soft tissues surrounding an implant with bone loss is often inflamed.