Failed Blood Supply Can Lead To Loose Chips In Joints

Osteochondrosis, or so-called "joint mice", is a very common illness of Norwegian horses, although its cause is as yet unknown. A recent Ph. D. degree by veterinary surgeon Kristin Olstad of the equine clinic of the Norwegian School of Veterinary Science concluded that failure of blood supply to the developing joint cartilage can lead to the development of the disease.


Osteochondrosis affects both people and a range of domestic animals including horses, cows, pigs and dogs. The disease is especially common among Norwegian horses, in particular warmblood, and can lead to the development of loose flakes within the joint. These loose pieces can cause irritation, causing the joint to swell and the horse to become lame.


The disease is usually treated by surgical removal of the loose pieces, a procedure that is associated with risk to the horse and expense for the owner. Osteochondrosis is heritable, and affected horses can be denied certification for breeding programs if the disease is discovered on x-ray.


It was established in the 1970's that osteochondrosis arises in the so-called growth cartilage. This is specialised tissue that is only found in the long bones of the skeleton before an animal attains its mature size.


For many years it was thought that cartilage is a non-vascular tissue, that is, without its own blood supply. Olstad and a research team from the equine clinic have now, however, discovered and described a rich blood supply running in so-called cartilage canals. This blood flow is, however, time-limited, and in the case of the hock joint, it disappears at around the age of two months. This explains to a large degree why the blood supply to the cartilage has been so poorly described previously.


Using a microscope, Olstad and the research group showed an association between the earliest stages of osteochondrosis and a failure of the blood flow to the growth cartilage.


The cartilage canals are repeatedly forced to cross the boundary between bone and cartilage. Studies have shown the blood vessels in these vascular channels failed at precisely the point where they crossed from solid bone over into the softer growth cartilage.


Olstad and the research team discovered that when the blood flow failed, the cartilage cells around the cartilage canals died, since they no longer received the oxygen and nourishment they depended on. Small areas of dead growth cartilage became isolated as weakened points under the joint surfaces. Upon loading, these areas could develop cracks and loosen, causing loose flakes within the joint.


Kristin Olstad B. V. Sc. , Cert. V.R,., M.R.C.V.S. defended her Philosophiae Doctor thesis with the title "Cartilage Canals in the Pathogenesis of Osteochondrosis in Horses", at the Norwegian School of Veterinary Science, on February 29, 2008.


NORWEGIAN SCHOOL OF VETERINARY SCIENCE

Ullevalsveien 72

veths.no

Smart Instrument For Tissue Damage Assessment Developed By QUT Researchers

A tool with the potential to determine the level of tissue damage in patients with osteo-arthritis, sports injuries and other conditions affecting bone and cartilage is being developed by QUT researchers



Professor Oloyede said that the device, which he calls a "smarthroscope", may be able to reduce the cost of surgery, eliminate unnecessary surgery, and could be useful in developing countries.



It aims to determine the degree and spread of damage to the tissue surrounding an area affected by illnesses such as osteo-arthritis, and other conditions which result in cartilage and bone damage.



The instrument would also help in joint research and for evaluating the effectiveness of established and new methods of joint treatment, acting as a "decision-maker" for surgeons assessing the damage of tissue surrounding focal cartilage damage, to decide how much cartilage needed to be operated on, and to what extent.



Professor Oloyede said at the moment surgeons depended on a subjective assessment of pictorial information obtained using arthroscopes when treating patients, which was not always accurate.



"What we are trying to do is give an accurate picture of what is going on inside the actual tissues," he said.



"We want to accurately assess the area of influence of a focal joint defect in a particular condition to determine the optimal amount of tissue to be removed for replacement surgery, and the area to be prepared for other forms of therapy such as those depending on cell-based procedures.



"If we were able to give an exact map of the cartilage and bone in a degenerating joint, they would then know how bad the condition is, and would be able to treat the right area in the right way."



He said he thought the instrument could also help in developing countries.



"Out there, they do not have as many surgeons who can carry out arthroscopy and make decisions about joint tissue treatment as we do, but this instrument would reduce the dependence on surgical experience and guide them in the process of managing conditions such as osteoarthritis, avascular necrosis and osteochondritis dessicans."



He said he hoped that a mock-up of the "smarthroscope", which is the subject of a QUT-owned patent, would be ready by mid-2009, and an optimised prototype may be possible in three years.







Source: Sharon Thompson


Queensland University of Technology

Biomedical Researchers Create Artificial Human Bone Marrow In A Test Tube

Artificial bone marrow that can continuously make red and white blood cells has been created in a University of Michigan lab.



This development could lead to simpler pharmaceutical drug testing, closer study of immune system defects and a continuous supply of blood for transfusions.



The substance grows on a 3-D scaffold that mimics the tissues supporting bone marrow in the body, said Nicholas Kotov, a professor in the U-M departments of Chemical Engineering; Materials Science and Engineering; and Biomedical Engineering.



The marrow is not made to be implanted in the body, like most 3-D biomedical scaffolds. It is designed to function in a test tube.



Kotov, principal investigator, is an author of a paper about the research currently published online in the journal Biomaterials. Joan Nichols, professor from the University of Texas Medical Branch, collaborated on many aspects of the project.



"This is the first successful artificial bone marrow," Kotov said. "It has two of the essential functions of bone marrow. It can replicate blood stem cells and produce B cells. The latter are the key immune cells producing antibodies that are important to fighting many diseases."



Blood stem cells give rise to blood as well as several other types of cells. B cells, a type of white blood cell, battle colds, bacterial infections, and other foreign or abnormal cells including some cancers.



Cancer-fighting chemotherapy drugs can strongly suppress bone marrow function, leaving the body more susceptible to infection. The new artificial marrow could allow researchers to test how a new drug at certain potencies would affect bone marrow function, Kotov said. This could assist in drug development and catch severe side effects before human drug trials.



Bone marrow is a complicated organ to replicate, Kotov said. Vital to the success of this new development is the three-dimensional scaffold on which the artificial marrow grows. This lattice had to have a high number of precisely-sized pores to stimulate cellular interaction.



The scaffolds are made out of a transparent polymer that nutrients can easily pass through. To create the scaffolds, scientists molded the polymer with tiny spheres ordered like billiard balls. Then, they dissolved the spheres to leave the perfect geometry of pores in the scaffold.



The scaffolds were then seeded with bone marrow stromal cells and osteoblasts, another type of bone marrow cell.



"The geometrical perfection of the polymer molded by spheres is very essential for reproducibility of the drug tests and evaluation of potential drug candidates," Kotov said. "The scaffold for this work had to be designed from scratch closely mimicking real bone marrow because there are no suitable commercially products.



"Certain stem cells that are essential for immunity and blood production are able to grow, divide and differentiate efficiently in these scaffolds due to the close similarity of the pores in the scaffold and the pores in actual bone marrow."



The researchers demonstrated that the artificial marrow gives a human-like response to an infectious New Caledonia/99/H1N1 flu virus. This is believed to be a first.



To determine whether the substance behaves like real bone marrow, the scientists implanted it in mice with immune deficiencies. The mice produced human immune cells and blood vessels grew through the substance.



Notes:



The paper is called "In vitro analog of human bone marrow from 3D scaffolds with Biomimetic inverted colloidal crystal geometry."



For more information:



Nicholas Kotov: engin.umich/dept/cheme/people/kotov.html



Michigan Engineering



The University of Michigan College of Engineering is ranked among the top engineering schools in the country. At more than $130 million annually, its engineering research budget is one of largest of any public university. Michigan Engineering is home to 11 academic departments and a National Science Foundation Engineering Research Center. The college plays a leading role in the Michigan Memorial Phoenix Energy Institute and hosts the world class Lurie Nanofabrication Facility. Michigan Engineering's premier scholarship, international scale and multidisciplinary scope combine to create The Michigan Difference. Find out more at engin.umich/.



Source:

Nicole Casal Moore

University of Michigan

Osteoporosis - Weighing In On Aging Bones: Excessive Weight Loss And Age-related Structural Change May Contribute To Fracture Risk

It is well established that post-menopausal women are at increased risk for developing osteoporosis, but could that be related to subtle pre-menopausal changes in bone structure? That may very well be, according to two new sets of data presented at the IOF World Congress on Osteoporosis this week. The findings were made possible by the use of a new sophisticated X-ray scanner that can measure tiny, three-dimensional changes in bone architecture.


In two additional presentations, researchers from Ireland and the U.S.A. reported a direct relationship between body weight and bone mineral density. Their studies emphasize the importance of maintaining adequate nutrition and suggest that simple weight cut-offs for men and women could be used to predict osteoporosis.


Bone Geometry and Architecture Change with Age


In any complex structure, geometry and architecture are important determinants of strength. Bone is no exception. That is why studies from IOF President Pierre Delmas and colleagues at the INSERM, Claude Bernard University of Lyon, France, may lead to better understanding of bone fragility. In separate presentations, lead authors Stephanie Boutroy and Elizabeth Sornay-Rendu report that gradual remodelling may change the overall architecture of bones as pre-menopausal women age (see conference Abstract No. OC16), while in post-menopausal women similar architectural changes correlate with fragility fractures (see conference Abstract No. OC6).


Changes in bone geometry and micro-architecture in young women have not been well studied to date, but the new findings indicate that there may be two distinct types of bone remodelling related to aging. Studying the tibia, the larger of the two calf bones, Boutroy and colleagues found that though older pre-menopausal women have an increase in bone size, there is no change in the thickness of the cortical layer, or tough envelope, that makes up the bone circumference. They also found that spongy tissue that makes up the bone core is less dense in older pre-menopausal women compared to their younger peers. Their findings suggest that minerals are slowly lost from the inside of the bone, while at the same time there is increased deposition of mineral in the cortical or outer envelope of the bone that increases the circumference but not the thickness.


To arrive at their conclusions, the researchers tested 251 pre-menopausal women aged between 19 and 50 years old. Each were scanned with a sophisticated quantitative computerized tomography (QCT) scanner (CAT scan) to develop a three-dimensional picture of the bone. They found that in older women, the sponge-like tissue, or trabecular bone, that makes up the bone core, is less dense and individual trabeculae are sparser and more widely separated. The researchers are now planning to follow individual volunteers to determine if age-related changes in bone mineral density are indeed due to this type of bone remodelling. Because bone mineral density is generally used as a surrogate for bone strength the research could have important implications for our understanding of bone fragility and osteoporosis.















In fact, in the second presentation, Sornay-Rendu reported that micro-architectural changes can be detected in post-menopausal women who have sustained a fragility fracture.


In this study the researchers compared post-menopausal women, average age 72 years, who had a fracture over the past 13 years with women who did not have a fracture over that period of time. The researchers found that there were significant differences in terms of bone architecture measured with this new high-resolution peripheral QCT scanner.


The scanner allows researchers to get a much more detailed picture of bone density than is allowed by traditionally dual X-ray absorption (DXA) scanners, which are routinely used worldwide to diagnose osteoporosis. "One interesting finding is that when you look at the differences between the fracture cases and the controls, if you adjust by their level of bone mineral density measured by DXA, the difference between the two groups is still significant. That means that, clearly, by this new technique we are measuring something that is different to what we measure using DXA. That difference is basically the architecture of the trabecular bone," said Delmas.


Sornay-Rendu and colleagues found that in the women who suffered a fragility fracture, the number of trabeculae and the thickness of the trabecular layer was reduced, as was the thickness of the cortical bone. These changes cannot be picked up by traditional DXA scanning.


Weight Loss may Put Bones at Risk


Bone remodelling is well known to be heavily influenced by the load placed upon it. Heavier people, for example, are more likely to have heavier bones. But how does weight loss impact bone density?


Laurie Milliken and colleagues at the University of Massachusetts, Boston, reported that changes in body weight account for a substantial change in bone density recorded in post-menopausal women (see conference Abstract No. P417MO).


"These findings demonstrate that in this population of postmenopausal women, changes in body composition are more important than the current public health messages regarding preserving bone may reflect," said Milliken.


For four years the researchers followed 167 post-menopausal women taking part in the Bone Estrogen Strength Training study. Correcting for other factors such as level of exercise, use of hormone replacement therapy and taking supplemental calcium, Milliken and colleagues found that 6%-32% of the change in bone mineral density (BMD) could be accounted for by change in body mass, with weight loss leading to lower BMD.


"These findings confirm the 'bone loading' role of body weight. However, it may add confusion for those who are trying to reduce the likelihood of developing osteoporosis, especially those who are also trying to prevent heart disease and Type II diabetes. The public health messages for heart disease and diabetes are to lose weight but that advice may be counterproductive for bone," said Milliken.


That sentiment was echoed by Dr. Bryan Whelan and colleagues at Cork University Hospital, Ireland (see conference Abstract No. P232SA). In a study of over 22,000 subjects, they found that there was a direct correlation between weight and bone mineral density at the hip, spine, and thigh bone.


"Our main finding was that setting a weight cut-off in postmenopausal women and men over 50 is a simple way of determining if they are likely to have osteoporosis or not," said Whelan.


Those cut-offs are 72kg for women 81 kg for men. The research suggests that people should be mindful of not dieting to a level where their weight falls below these limits. "In this age, when there is such an emphasis on being thin and losing weight, it must be said that a good balance-not too thin, not too heavy-is still best because there are drawbacks to being too light, said Whelan.


Osteoporosis, in which the bones become porous and break easily, is one of the world's most common and debilitating diseases. The result: pain, loss of movement, inability to perform daily chores, and in many cases, death. One out of three women over 50 will experience osteoporotic fractures, as will one out of five men 1, 2, 3. Unfortunately, screening for people at risk is far from being a standard practice. Osteoporosis can, to a certain extent, be prevented, it can be easily diagnosed and effective treatments are available.


The International Osteoporosis Foundation (IOF) is the only worldwide organization dedicated to the fight against osteoporosis. It brings together scientists, physicians, patient societies and corporate partners. Working with its 170 member societies in 84 locations, and other healthcare-related organizations around the world, IOF encourages awareness and prevention, early detection and improved treatment of osteoporosis.


1 Melton U, Chrischilles EA, Cooper C et al. How many women have osteoporosis? Journal of Bone Mineral Research, 1992; 7:1005-10

2 Kanis JA et al. Long-term risk of osteoporotic fracture in Malmo. Osteoporosis International, 2000; 11:669-674

3 Melton LJ, et al. Bone density and fracture risk in men. JBMR. 1998; 13:No 12:1915


IOF World Congress on Osteoporosis, held every two years, is the only global congress dedicated specifically to all aspects of osteoporosis. Besides the opportunity to learn about the latest science and developments in diagnosis, treatment and the most recent socio-economic studies, participants have the chance to meet and exchange ideas with other physicians from around the world. All aspects of osteoporosis will be covered during the Congress which will comprise lectures by invited speakers presenting cutting edge research in the field, and 35 oral presentations and more than 680 poster presentations selected from 720 submitted abstracts. More than 70 Meet the Expert Sessions covering many practical aspects of diagnosis and management of osteoporosis are also on the program.


For more information on osteoporosis and IOF please visit:
osteofound

Treatment Trends For Biceps Injuries

The following was released today by the American Academy of Orthopaedic Surgeons:


Synopsis:


A patient with a long head biceps (LHB) tendinopathy, which is a pain and/or tearing of the tendon, may also have a shoulder problem and/or a rotator cuff tear. LHB tendinopahy can be caused by injury, trauma, overuse, inflammation or degeneration. Because of the variety of the causes and the range of possible severity, a patient needs a thorough examination, including radiographic imaging to determine the diagnosis and treatment. Traditional treatments include both surgical and nonsurgical approaches.


"The surgeon's goal in treating any long head biceps tendinopathy is to address the pain in a way that also respects the patient's lifestyle. And, as we found, there is a variety of excellent surgical and nonsurgical options. In developing this review, we also discovered the need for more comparative research data on surgical versus nonsurgical treatment outcomes for this condition," said Shane Nho, MD, an orthopaedic surgeon who practices in Chicago and whose review appears in the November issue of the Journal of the American Academy of Orthopaedic Surgeons.


Statistics:



-- Recent studies reported no significant difference in function or patient satisfaction between the two primary surgical options, biceps tenotomy or tenodesis.



-- Each year, an average of 10 million people seek medical attention in a surgeon or physician's office or at the ER for a shoulder injury and an average of 4 million people come in with arm injuries.



-- Both surgical treatments for LHB tendinopathy are statistically successful, with a complication rate of less than 1 percent.


Trends noted:



-- Both surgical options -- biceps tenotomy and tenodesis (between which the article found no preference) now can be performed via arthroscopy.



-- The authors agree that nonsurgical treatment is the first and in many cases may be the only treatment necessary.



-- The authors of this review seem to agree that of the two surgical options, biceps tenodesis should be used in younger, active patients.



-- The first line of treatment for LHB tendinopathy is a variety of nonsurgical options, such as:



-- rest;



-- anti-inflammatory drugs;



-- activity modification; and



-- physical therapy.


If those treatments do not offer the patient relief, a course of corticosteroid injections may be attempted. The authors do, however, report a concern about intratendinous (within the tendinous portion of the muscle) corticosteroid injections, which may predispose the patient to tendon rupture. More research is needed to address this concern.


Symptoms:


See your doctor or orthopaedic surgeon if you experience any of these symptoms.



-- Sudden, sharp pain in the upper arm



-- Audible popping or snapping in the shoulder or elbow



-- Cramping of the biceps muscle with strenuous use of the arm



-- Bruising from the middle of the upper arm down toward the elbow



-- Pain or tenderness at the shoulder and the elbow



-- Weakness in the shoulder and the elbow



-- Difficulty turning the palm of the hand up or down



-- Because a torn tendon can no longer keep the biceps muscle tight, a bulge in the upper arm above the elbow ("Popeye Muscle") may appear, with a dent (signifying absence of muscle) closer to the shoulder.


Source: American Academy of Orthopaedic Surgeons

President's Council On Physical Fitness And Sports Names American Orthopaedic Society For Sports Medicine As A Science Partner

The President's Council on Physical Fitness and Sports (PCPFS) and the American Orthopaedic Society for Sports Medicine (AOSSM) are proud to announce that AOSSM will serve as a Science Partner to the PCPFS. The six other organizations already serving as Science Partners include the American Alliance for Health, Physical Education, Recreation and Dance, American College of Sports Medicine, American Physical Therapy Association, National Athletic Trainers' Association and the National Strength and Conditioning Association.


"As a world leader in sports medicine education, research, communication and fellowship, we are excited to work with PCPFS in promoting the distribution of action oriented educational materials and hope that our collaboration will enhance sports injury prevention and rehabilitation efforts nationwide," said AOSSM President, Bernard R. Bach, Jr., MD.


PCPFS is an advisory committee of volunteer citizens who advise the President through the Secretary of Health and Human Services about physical activity, fitness and sports in America. The President's Council on Physical Fitness and Sports, is an office within the U.S. Department of Health and Human Services. Through its programs and partnerships with the public, private and nonprofit sectors, the Office of the PCPFS serves as a catalyst to promote health, physical activity, fitness and enjoyment for people of all ages, backgrounds and abilities through participation in physical activity and sports.


"AOSSM has a long history of dynamic educational materials and programs and we are looking forward to working together to promote wellness through physical activity," said Melissa Johnson, MS, executive director of the President's Council.


AOSSM will be working with PCPFS to distribute and create patient education materials for both the public and professional communities via product distribution and web site initiatives. For more information on either AOSSM or PCPFS please visit sportsmed or fitness.


The American Orthopaedic Society for Sports Medicine (AOSSM) is a world leader in sports medicine education, research, communication and fellowship, and includes national and international orthopaedic sports medicine leaders. The Society works closely with many other sports medicine specialists, including athletic trainers, physical therapists, family physicians, and others to improve the identification, prevention, treatment, and rehabilitation of sports injuries.

American Orthopaedic Society for Sports Medicine

UK Charity Tackles Health Risk For Children - Engaging Website Launches To Educate Children At A Crucial Age In Bone Development

Research from the National Osteoporosis Society has revealed that almost half (49%)* of young people do not know that there are steps they can take to keep their bones healthy. This knowledge gap puts them at risk of osteoporosis and fractures in later life.


In response to this research, the charity has developed an exciting online project that will educate UK children about bone health and provide inspiring resources for school teachers and parents. Bones4life gives vital health messages to young people while their bone strength is still being built. Through knowledge enhancing, creativity developing activity, the new website will help to prevent children risking their future health.


Lesley Millard, Education Officer for the National Osteoporosis Society, has over 30 years experience working with children. Her experience as a Head Teacher has provided inspiration for the resources.


"Our YouGov research highlighted massive shortfalls in knowledge around bone health in young people," she said. "Children don't realise the damage that unhealthy lifestyles can have on their bones in later life. The majority were unaware that exercise can help reduce the risk of osteoporosis and one in three did not know about the positive role diet can play. Bones4life is launching at a time when electronic and interactive resources could not be more valuable to the curriculum. We want to make sure children take care of their bones for the future so we've involved young people and teachers throughout the development of Bones4life to help us achieve this."


The website is tailored to the requirements of the national curriculum for 7-10 year olds and is particularly relevant for information technology and health and fitness. It teaches children about the importance of building healthy bones from a young age, to protect this living tissue.


Divided in to two sections, the children's part of the website includes a flash game, fun educational quizzes and a gallery where their work can be posted. The adult section hosts a variety of resources including lesson plans, PowerPoint presentations, film clips, photos, resource lists and music. There will also be a link to the charity's main web site for forum discussions.


Illustrating the site are three characters that children can interact with, developed by the charity to represent the three main elements required to look after your bones. 'Sneakers', the exercise lover, knows that weight-bearing exercise is important for general health and strengthening bones; 'Munch' loves healthy eating and calcium rich foods; 'Blaze' gets power from sunlight, which enables the body to produce bone-healthy vitamin D.


Simon Brown, a teacher at Christchurch Primary School in Wiltshire, welcomes the new website: "It is great to find a resource that both educates and entertains. The children love the fun characters and games that help them learn all about their bones. I'm keen to incorporate Bones4life into my lesson plans."


Christchurch Primary School helped to test-drive the site and provided valuable feedback for its development.


Sophie, year 5 said, "The website is really fun - especially the game which is challenging. I really like the characters as well."


Osteoporosis is one of the most common diseases in the UK, and more than a thousand people per month die as a result of hip fracture. 70,000 hip fractures occur every year, costing the UK healthcare system and government ВЈ2.3 billion - approximately ВЈ6 million a day. Younger people need to 'bank' strong bone before they reach 30 in order to reduce the risks of osteoporosis and poor bone health. Often called the 'silent disease' osteoporosis has no specific symptoms and can go undetected until the time of a first broken bone.


Source
The National Osteoporosis Society

Proprio Foot™ Stands And Delivers For Amputees

Ossur North America, a trusted and global developer of more scientifically advanced prosthetic innovations than any other company in the field, is pleased to introduce the PROPRIO FOOT TM. It is the latest addition from Bionic Technology by Ossur, the company's brand for a pioneering category of prosthetic devices. The world's first motor-powered and artificially intelligent prosthesis for transtibial amputees, the foot operates as closely as you can get today to natural, anatomical functioning. Developed by Ossur's R&D department, the foot's motion analysis capabilities are facilitated by real-time sensor technology from Dynastream Innovations of Canada.



While the foot will commence a controlled launch in September, the Department of Defense and the VA are both actively using the foot to benefit servicemen returning from the Iraq and Afghanistan conflicts, as well as veterans of past wars. Like Ossur's POWER KNEE TM, the PROPRIO FOOT replaces muscle function that was lost with the amputation. The foot enables amputees to perform activites in a normal and functional pattern by:



* Sensing. Knowing where their foot is in space is a huge safety issue for amputees. Sophisticated sensor technology mimics the body's own neural receptors that are sensitive to mechanical change, providing artificial proprioception (that sense of where the limb is in space). Hence the name PROPRIO FOOT.



* Thinking. Patented artificial intelligence (AI) processes information from the sensors and activates the most appropriate response for the next step.



* Acting. The AI transmits a constant stream of signals which instruct high-precision actuator technology to act and deliver optimal function.



Canadian company Dynastream's expertise in real-time motion analysis enables the PROPRIO FOOT to detect and adapt to changes making for easier locomotion and an improved quality of life for the user. "Dynastream's real-time detection algorithms, high accuracy, and overall reliability are particularly critical for this innovative prosthetic application, and further solidifies our position as a provider of platform technology for all markets and applications wanting to digitize motion," said Kip Fyfe, Dynastream's president and CEO. A motor and battery generate appropriate prosthetic function to the PROPRIO FOOT, providing the precise amount of power necessary. This addition of power motion represents a significant step in human energy conservation, and the ability to deliver the required response.



PROPRIO FOOT Stands and Delivers for Amputees This merging of new technologies and artificial intelligence makes it possible for the PROPRIO FOOT to offer unmatched benefits for amputees:



* The foot can identify slopes and stairs after the first step, and instruct the ankle to flex appropriately. Users place their foot on a step when climbing or descending stairs and it automatically adapts its ankle position to enable the next step.
















* This active ankle motion also allows wearers to more easily sit down or rise from a chair: actions once taken for granted only by the able-bodied. Just try standing up from a seated position on one foot to get an idea of the impact of the PROPRIO FOOT.



* The foot's anatomically correct response creates a more symmetrical and balanced gait, reducing the need both to "hip hike" and to load the entire body weight on the sound limb. "This reduces the energy that patients spend in reacting consciously to the environment," said Hilmar B. Janusson, Ph.D., Ossur's vice president of research and development. "And it gives them more confidence and puts less strain on the sound limb and the hips, back and knees."



* Despite its sophisticated technology, the PROPRIO FOOT is user-friendly and is easy to set up and operate. During a simple calibration process, in 15 steps the device evaluates and memorizes the wearer's unique way of walking.







After the limited launch of the PROPRIO FOOT and the nationwide debut of the POWER KNEE on September 27, 2006 at the American Orthotic and Prosthetic Association's (AOPA) annual National Assembly in Hollywood, Florida, the world of prosthetics will have entered a new era: the age of advanced bionic technology.



To purchase a PROPRIO FOOT, prosthetists and amputees will receive training from Ossur's Proprio Foot specialists to guarantee a successful outcome for each user. For more information about the PROPRIO FOOT, or any products under the Bionic Technology by Ossur umbrella, please visit ossur/bionics or call one of Ossur's knowledgeable Customer Service Representatives at (800) 233-6263.



OSSUR

Ossur (Icelandic Stock Exchange: OSSR) is as much about helping people to live a life without limitations as it is about its orthopaedic products. A trusted and global leader in the development, manufacturing, distribution, sales and marketing of bracing and support products and prosthetics, Ossur pioneers award-winning designs - including its bionic technologies - and partners with the health practitioners who use them to deliver successful clinical and business outcomes. Headquartered in Reykjavik, Iceland, the company has operations and a distribution network throughout the world. The company allocates an industry record of 6-8 percent of its revenue on research and development to conceive and harness the most advanced technologies for incorporation in its product designs, and provides extensive education programs through the Ossur Academy. Ossur is a 2006 World Economic Forum Technology Pioneer. Website: ossur/



DYNASTREAM

Dynastream Innovations is a privately owned company with world-leading expertise in the research and development of wireless and inertial technology for consumer, commercial, medical and industrial markets. Dynastream is headquartered in Cochrane, Alberta, Canada. Website: dynastream/



Contact:



Ossur North America

Tabi King

Marketing

tkingossur



Ossur Public Relations



Beverly Millson

Missing Sock Public Relations

Beverlymissingsock



Dynastream Innovations, Inc.



Annette McLeod - Marketing Manager

Cochrane, Canada

annette.mcleoddynastream



Contact: Beverly Millson

Ossur

Leaders In Minimally Invasive Spinal Surgery Acquire Non Surgical Spine Therapy Pioneer

After helping thousands of patients get their lives back through minimally invasive endoscopic spinal surgery at facilities in Tampa and Scottsdale and soon Philadelphia, the Laser Spine Institute (LSI) announces their acquisition of Aspen Back & Body, LLC (ABB), extending LSI's patient care capabilities into non-surgical areas for the first time. Founded and led by visionary entrepreneur Clint Phillips, CSCS, ABB is a nationally branded destination provider of highly innovative therapies, blending spine fitness and wellness to prevent and relieve back and neck pain. Situated in the distinguished St. Regis Hotel in Aspen, Colo., ABB offers clients extraordinary one- to three-week "spine fitness" programs encompassing three to four hours a day of personalized therapy. All sessions are overseen by a Doctor of physical therapy with the goal of improving spine-related muscle strength, flexibility, alignment and general wellness. These programs include strength training, Gyrotonic flexibility sessions, vibration training, water therapy and Pilates, as well as education sessions, signature massage and healthy meals.


"With this acquisition, LSI can now provide patients a full range of highly effective, non-surgical treatments, complementary with existing surgical services," said LSI chief development officer Trey Traviesa.


"This will allow LSI to care for our patients across the cycle of spinal care whether patients seek maximum pre-surgical relief or continued support for post-surgical results," said LSI founder and chief surgeon Dr. James St. Louis.


LSI was able to make the purchase possible due to the great success of its minimally invasive endoscopic procedures utilizing cutting-edge lasers and a five-day process from evaluation to recovery. With an incision measuring less than one inch, LSI's expert surgeons can treat a variety of back and neck ailments from degenerative disc disease and spinal stenosis, to herniated discs and spinal arthritis. The company performs more procedures than any spine surgery provider in the world.


Over the last three years, ABB has treated more than 2,000 clients (90 percent of which travel more than 500 miles) from Jane Seymour to George Hamilton, with exemplary results and exceptional service satisfaction.


"The team at ABB is thrilled to be aligned with the world leader in spine surgery outcomes and patient satisfaction. Now, no matter who walks through our door, we can provide world-class care regardless of their condition," explains Phillips. "What I witnessed at LSI is so much more than surgery. It's a comprehensive patient experience utilizing specialized techniques to achieve surgical results better than I have ever seen, while sparing the patient from the muscle cutting, scar tissue, hardware implants, bed rest and general anesthetic characteristic of traditional spine surgery."


About Laser Spine Institute: Laser Spine Institute offers a successful alternative to traditional open back and neck surgeries. The orthopedic surgeons at LSI can treat painful ailments with endoscopic outpatient procedures. Chronic pain that stems from pinched nerves, herniated discs, bulging discs, degenerative disc disease, spinal stenosis, foraminal stenosis, spinal arthritis, bone spurs, scar tissue and failed open back or neck surgery can be alleviated with Laser Spine Institute's minimally invasive approach.


Source: Laser Spine Institute

Heel To Heal: New Stretch Relieves Pain From Plantar Fasciitis

A new stretch is proving quite effective to help treat and potentially cure plantar fasciitis, a condition that affects nearly 2.5 million Americans each year. In a study recently published in Journal of Bone and Joint Surgery, researchers found that patients suffering from the painful heel spur syndrome had a 75 percent chance of having no pain and returning to full activity within three to six months of performing the stretch. In addition, patients have about a 75 percent chance of needing no further treatment.



The study is a two-year follow-up on 82 patients with plantar fasciitis, all of whom were part of an original clinical trial of 101 patients in 2003. The patients were taught a new stretch, specifically targeting the plantar fascia, that was developed by Benedict DiGiovanni, M.D., associate professor of orthopaedic surgery at the University of Rochester and author of the study, and Deborah Nawoczenski, P.T., Ph.D., professor of physical therapy at Ithaca College.



The stretch requires patients to sit with one leg crossed over the other, and stretch the arch of the foot by taking one hand and pulling the toes back toward the shin for a count of 10. The exercise must be repeated 10 times, and performed at least three times a day, including before taking the first step in the morning and before standing after a prolonged period of sitting. More than 90 percent of the patients were totally satisfied or satisfied with minor reservations, and noted distinct decrease in pain and activity limitations. The most common cause of heel pain, plantar fasciitis occurs when the plantar fascia, the flat band of tissue that connects your heel bone to your toes, is strained, causing weakness, inflammation and irritation. Common in middle-aged people as well as younger people who are on their feet a lot, like athletes or soldiers, people with plantar fasciitis experience extreme pain when they stand or walk. Plantar fasciitis can be a frustrating experience, as the chronic cycle of reinjury and pain can last for up to one year. DiGiovanni likens it to pulling a hamstring, and continuing to run without proper stretching. "Walking without stretching those foot tissues is just re-injuring yourself," he said.



Most physicians will recommend a non-surgical approach to treating plantar fasciitis, advising a regimen of anti-inflammatory medications, foot inserts, and stretches. Surgery occurs in about 5 percent of all cases, and has a 50 percent success rate of eliminating pain and allowing for full activity.



"Plantar fasciitis is everywhere, but we really haven't had a good handle on it," said DiGiovanni. "The condition often causes chronic symptoms and typically takes about nine to 10 months to burn itself out, and for people experiencing this pain, that's way too long to suffer through it."



DiGiovanni should know. He's experienced plantar fasciitis first-hand. Deciding to get some extra exercise on a golf outing one recent afternoon, he carried his clubs around all 18 holes instead of taking an easy-going ride in a golf cart. The next morning, he woke up with severe heel pain, which brought the topic of his study close to home.



"We need to further optimize non-operative treatments prior to considering surgical options," DiGiovanni said. "If you look at the results of the study, I think we've succeeded."






Contact: Germaine Reinhardt


University of Rochester Medical Center

Rotator Cuff Tears: Are They All In The Family?

People with relatives who have experienced rotator cuff tears are at increased risk of similar tendon tears themselves, according to a study published in the May 2009 issue of The Journal of Bone and Joint Surgery (JBJS). "This strongly suggests genetic predisposition as a possible cause for rotator cuff disease," said Robert Z. Tashjian, MD, associate professor of orthopaedic surgery, University of Utah School of Medicine Orthopaedic Center in Salt Lake City.


By using the Utah Population Database combined with the University of Utah Health Sciences Data Warehouse numbers, researchers found an increased risk for these tears in family members of patients with rotator cuff tears. The risk extends out and beyond third-cousin relationships (Third cousins are the great-great-grandchildren of one's great-great-grandparents.)


"While we have not determined the exact genetic component," said Dr. Tashjian, "Our family history data supports that heredity plays a role in the development of rotator cuff tearing."


This problem usually affects people in their 50s and 60s. It is believed to have both mechanical and environmental influences; however, scientists unclear as to exactly why it occurs, have several theories including:



-- Decreased blood flow leading to tendon dysfunction and tearing



-- Bumping (impingement) of the rotator cuff on the undersurface of the shoulder cap (acromion) when moving the arm



-- This may lead to a slow development of tears due to repetitive micro-trauma over time



-- Age-related degeneration


The potential impact of this research is that it is a springboard for attempting to identify an exact genetic component for this injury. Dr. Tashjian and his colleagues are currently collecting blood samples for DNA analysis of patients with rotator cuff tears, which will be used later for various genetic analyses to determine the exact genetic component.


The results of this research have potential long term implications, including:



-- Prevention



-- Knowing about a family history of rotator cuff disease can alert patients to take some precautionary measures to protect against their own injuries



-- Orthopaedic surgeons can initiate a shoulder stretching and strengthening program for patients to help limit the effects of possible future rotator cuff problems


While an exercise program would not completely prevent development of rotator cuff disease, it may limit the negative impact on shoulder function.


The research results can also lead to future treatment options. "Rotator cuff healing is often incomplete and identifying a possible genetic link to the disease may provide targets for biologic treatments to improve the healing rates," noted Dr. Tashjian.


More Information: The Utah Population Database is a multigenerational database including, birth, death and family history data on over 10 million individuals. The University of Utah Health Sciences Data Warehouse includes all medical record information on more than two million individuals evaluated and treated at the University of Utah. The combined database allows a hereditary analysis of any piece of the medical record of these individuals stored in the Data Warehouse.


Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the National Institutes of Health-National Library of Medicine (NLM R01 LM009331). Partial support less than $10,000 for all datasets within the Utah Population Database was provided by the University of Utah Huntsman Cancer Institute. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.


Source: The Journal of Bone and Joint Surgery

Bone Regeneration Could Be Triggered By A Gene-Activated Matrix

Gene-activated matrix combined with a bone transcriptional factor, Cbfa1 that induce bone formation may be a key advancement in treating bone loss due to periodontal diseases, trauma, or congenital disorders, researchers say.


These results were recently published in Wound Repair and Regeneration, Volume 15, June 2007.


Millions of Americans are afflicted with periodontal diseases that cause destruction of supporting structures of teeth: periodontal ligament (PDL), alveolar bone, and cementum. The process can lead to the loss of attachment, with destruction of the connective tissue matrix and cells. Loosening and eventual loss of teeth may follow. However, despite considerable research efforts in this area, regeneration of the periodontium remains an elusive goal of periodontal therapy. Now good news is that bones that refuse to heal in periodontal diseases may one day be set straight by a gene-activated matrix (GAM) method that enhances bone wound healing according to the new research from a team led by Dr. Qisheng Tu in Chen lab at Tufts University, Boston.


As bone biology researchers already know, Cbfa1, or core-binding factor 1 (Cbfa1), a runt domain transcription factor and its cognate enhancer, also referred to as runt-related transcription factor 2 (Runx2), is identified as a "master gene" required for osteoblastic differentiation and bone formation. Scientists are studying whether Cbfa1 can affect bone regeneration in Cbfa1 deficiency mice. "Compared with wild-type normal mice, bone wound healing was dramatically delayed in Cbfa1 heterozygous mice that miss one copy of cbfa1 gene, characterized by the presence of a small amount of bone formation near the base of the wounds.", said Dr. Qisheng Tu, a scientist of oral biology at Tufts University.


Considering the key role of Cbfa1 in osteoblast differentiation, it can be deduced that Cbfa1 may also play an important role in bone regeneration and may induce an embryonic (regenerative) environment in the injured adult tissues.


To test Cbfa1 as a possible treatment, Dr. Tu and his colleagues worked with 22 mice with periodontal window wounds and femoral defects that were being treated with pain-relieving drugs. The mice were divided into two groups randomly. In group I, bone defects were filled with Cbfa1-GAM with a dose of 1.2 mg plasmid Cbfa1 DNA per wound. Control sponges in group II were comprised of biodegradable, biocompatible collagen without plasmid DNA. Animals were euthanized at 7 and 14 days after the transplantation. Histological analysis and immunohistochemical staining demonstrated that compared with controls, there was increased new bone formation that almost filled the wound defects 14 days after surgery in the Cbfa1-GAM group.


"Our results indicate that the application of Cbfa1-GAM could increase the relative volume of new bone matrix in the defects more than two-fold," said Dr. Qisheng Tu, "Consistently, the data demonstrated that the Cbfa1-GAM significantly up-regulated the expression of Cbfa1 in submandibular defects as early as day 7, and remained at a high level until 14 days after surgery," he added.















However, unique to this study is that the researchers use the GAM method to deliver reagents, which offers an alternative and safer approach to virus-based tissue-engineering applications routinely used before. This method was designed specifically to provide an ideal environment for tissue regeneration and engineering, with which therapeutical genes can be delivered, in a polymer gel matrix, directly to actually injured bone, muscle, and ligament. The GAM could serve as a platform technology for local gene delivery in various tissues and organs. The carrier serves as a scaffold that holds exogenous genes in situ until endogenous wound-healing cells arrive. Up to 50% of available healing repair cells will get gene transfer. Then the cells in the matrix carrier act as local in vivo bioreactors, producing new gene-coding proteins that augment tissue repair and regeneration. GAM implantation at sites of bone injury is associated with retention and expression of the gene of interest for at least 6 weeks. "At day 7, we observed that the GAM porous architecture provided scaffolding to promote cell ingrowth. The local granulation tissue fibroblasts, along with capillaries, migrated into the GAM. The osteogenic progenitor cells within the tissue uptook the local plasmid DNA and transiently expressed the gene. This leads to a significant augment in periodontal bony tissue regeneration," Dr. Tu said.



Although more research is necessary, Cbfa1-GAM treatment could help to give a happy ending to the tragic stories of patients who suffer from bone loss due to periodontal diseases, trauma, or congenital disorders. In addition to studying Cbfa1's role in bone healing, Chen lab is examining the effects of too little or too much Cbfa1 on skeletal development. In the end, they may not need to use much protein to make the GAM effective. Those are things they're looking at now. Clinical trials will be the next step goal in the future.


tufts

Patent for New Glenoid Component for Shoulder Prosthesis Design

The US Patent Office has awarded a patent to the Hospital for Special Surgery for a new type of shoulder joint prosthesis
design for the glenoid component aimed at improving stability while maintaining fixation. The new design, the subject of US
Patent 6,875,234, issued on April 5, 2005, is designed to reduce the risk of future dislocation or artificial shoulder
component loosening, two common problems with existing products. However, clinical research still needs to be conducted to
show the complete benefits of this new patented design.


"Approximately 20,000 total shoulder replacement surgeries are performed annually in the U.S. with the volume growing at 5% a
year due to the increasingly active lives led by aging members of America's post World War II baby boom generation," said
Joseph Lipman, managing director of HSS Ventures, an affiliate of the Hospital for Special Surgery focused on product
development, technology licensing and venture investing in orthopedics and rheumatology. Mr. Lipman is the director of joint
development at Hospital for Special Surgery. [hssventures]


Shoulder joint replacements are composed of two parts, humeral and glenoid, which function in a ball-in-socket manner like
other joints in the body. Finding the right design to optimize movement and minimize wear over time has been a challenge in
the past. Prior designs sometimes have been associated with instability and component loosening over time, the leading
complication of total shoulder arthroplasty (replacement), according to a Journal of Bone and Joint Surgery paper, entitled
"Complications of Total Shoulder Replacement Arthroplasty,' written by Michael Wirth and Charles Rockwood in 1996.


The HSS-patented design involves the glenoid component and features two radii of curvature, decreasing the likelihood of
dislocation, a problem seen in current designs on the market. The design can be used with the various materials used in
replacement shoulders, including metal or polyethylene.
v
About Hospital for Special Surgery


Founded in 1863, Hospital for Special Surgery is a world leader in orthopedics, rheumatology and rehabilitation. Top ranked
in the Northeast in its specialties by U.S. News & World Report, HSS was awarded Magnet Recognition for Excellence in Nursing
Service from the American Nurses Credentialing Center. A member of the NewYork-Presbyterian Healthcare System and an
affiliate of Weill Medical College of Cornell University, HSS provides orthopedic and rheumatologic patient care at
NewYork-Presbyterian Hospital at NewYork Weill Cornell Medical Center. All HSS medical staff are on the faculty of Weill
Medical College of Cornell University. Its Research Division is internationally recognized as a leader in the investigation
of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City, hss


Hospital for Special Surgery

535 E. 70th St.

New York, NY 10021

USA

hss

Roche Announces Positive Results In Solid Tumors Using Human Monoclonal Antibody Against IGF-1R (R1507)

Roche announced positive
results from a Phase I trial of R1507, a human monoclonal antibody to
target IGF-1R (insulin-like growth factor receptor), in patients with solid
tumors. IGF-1 is one of the most potent natural activators of the AKT and
MAPK signaling pathways, which promote cell growth and cell survival. The
IGF-1R pathway has also been shown to have an important role in mediating
the resistance to cytotoxic drugs and EGFR/HER2-targeted agents. The
results were reported during the AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics, held in San Francisco.


Study Results



In the Phase I study, R1507 was administered by intravenous infusion.
Nine of 34 adult patients with advanced solid tumors experienced disease
stabilization. Four of the seven heavily pretreated patients with Ewing's
sarcoma demonstrated clinical benefit with two of these patients achieving
durable, objective partial responses.



Once a week administration of R1507 was well tolerated with very few
side effects. Treatment with R1507 was not associated with the typical
side-effects normally observed with cancer therapy (e.g., low blood counts,
infection, hair loss, severe nausea and vomiting). The most frequent side
effects observed were fatigue, anorexia and weight loss, symptoms that are
commonly observed in patients with advanced cancer.



"We are very encouraged by these early results with R1507 in patients
with refractory Ewing's sarcoma," said Kapil Dhingra, MD, Head, Oncology
Disease Biology Area at Roche. "As a result, we have given this program a
very high priority as we believe this molecule has the potential to be very
beneficial in treating patients with sarcoma as well as a variety of other
solid tumors."



The antibody (R1507) was initially developed under Roche's broad
antibody development collaboration with Genmab, which began in 2001.



The Phase I study is being conducted at four sites in the U.S.,
including the University of Colorado Cancer Center (Aurora, CO), The
University of Texas M.D. Anderson Cancer Center (Houston, TX), Cancer
Institute of New Jersey (New Brunswick, NJ) and The Institute for Drug
Development (San Antonio, TX). R1507 has also been investigated in 26
patients on a three week schedule in the Phase I study. This treatment
schedule was also generally well tolerated with a side effect profile
similar to the weekly schedule.



"This drug attacks the IGF pathway and may provide a new class of drugs
to treat a variety of cancers, including breast, prostate, colon, melanoma,
myeloma and a variety of sarcomas, which could greatly add to the way that
we currently treat these patients," says Stephen Leong, M.D., assistant
professor of Medical Oncology at the University of Colorado Cancer Center
and lead author of the abstract.
















Razelle Kurzrock, MD, investigator at the M.D. Anderson Cancer Center
and the senior author of the abstract, noted that some of the responses
were very impressive. For instance, one 28 year-old Ewing's sarcoma patient
with large tumors unresponsive to many other treatments showed dramatic
tumor shrinkage within six weeks, without side effects. "This is one of the
best responses I've seen in over 20 years of oncology experience," stated
Dr. Kurzrock.



Based on these initial results with R1507, Roche plans to conduct
additional trials and work with a global consortium of sarcoma experts,
including the Sarcoma Alliance for Research through Collaboration (SARC).
"We are very excited about our collaboration with SARC, which represents a
new approach to sarcoma clinical trials, and we look forward to combining
our expertise with that our colleagues at SARC to expedite new sarcoma
treatments," added Dhingra.



"We are excited to be partnering with Roche on the development of a new
treatment against an important target, which could result in a potential
breakthrough treatment for sarcoma as well as other cancers," said Laurence
Baker, DO, professor of Medicine and Pharmacology at the University of
Michigan and the Executive Director, SARC. "With Roche's considerable
expertise in oncology and SARC's vast network of physicians and
institutions, we look forward to determining the potential of R1507 in this
important disease area."



About Ewing's Sarcoma



The Ewing's family of tumors (EFT) includes primary tumors of bone
(classic Ewing's sarcoma, primitive neuroectodermal tumor, and Askin tumor)
and extraosseous primary tumors {National Cancer Institute}. Studies using
immunohistochemical markers, cytogenetics, molecular genetics, and tissue
culture indicate that these tumors are all derived from the same primordial
stem cell. EFTs account for 4 percent of childhood and adolescent
malignancies. The estimated incidence (US) is approximately 300 new cases
per year. The median age for patients with EFT is 15 years and more than 50
percent of patients are adolescents. There is a slight male predominance
and the lower limbs are affected in 40 percent of the patients.



Approximately 20 to 30 percent of the patients with ETB have overt
metastases at the time of diagnosis. However, outcomes for patients with
metastatic disease have improved little during the last 20 years.
Approximately 25-30 percent survival could be achieved with current
therapies for patients who present with metastatic disease at initial
diagnosis.



About Roche



Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world's leading
research-oriented healthcare groups with core businesses in pharmaceuticals
and diagnostics. For more than 100 years in the U.S., Roche has been
committed to developing innovative products and services that address
prevention, diagnosis and treatment of diseases, thus enhancing people's
health and quality of life. An employer of choice, in 2007 Roche was named
Top Company of the Year by Med Ad News and one of the Top 20 Employers
(Science magazine). In 2006, Roche was ranked the No. 1 Company to Sell For
(Selling Power), and one of AARP's Top Companies for Older Workers, and in
2005, Roche was named one of Fortune magazine's Best Companies to Work For
in America. For additional information about the U.S. pharmaceuticals
business, visit our websites: rocheusa or roche.us.



About SARC



The purpose of the Sarcoma Alliance for Research through Collaboration
(SARC) is to engage all appropriate and necessary resources to cure and
prevent sarcoma. SARC brings together expert sarcoma researchers and
clinicians from 29 centers of excellence in the United States. SARC by the
charter, promotes international collaboration in sarcoma clinical trials
through is association with European sarcoma experts. SARC is unique as a
clinical trial organization in that its trials at the inception include
pediatric and medical patients with sarcoma, because sarcomas affect people
of all ages. SARC is a 501c3, non-profit organization that is headquartered
in Ann Arbor, Michigan.


Hoffmann-La Roche Inc.

roche.us

Daily Use Of Antidepressants And Increased Risk Of Fracture In Older Adults Linked

Daily use of the antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) by adults 50 years and older is associated with a doubled risk of some fractures, according to a report in the January 22, 2007 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.



Depression affects about 10 percent of primary care patients in the United States, according to background information in the article. The use of SSRIs for the treatment of depressive symptoms is widespread due to the medication's presumed favorable adverse effect profile. Past studies have found the use of these antidepressants to be associated with an increased risk of clinical fragility fracture (fractures due to falling from bed, chair or standing height), but did not reliably examine such factors as falls and bone mineral density, the authors note.



J. Brent Richards, M.D., of McGill University, Montreal, Quebec, and colleagues evaluated 5,008 community-dwelling adults 50 years and older who were followed up for over five years for incident fractures. Researchers examined the relationships between SSRI use, bone mineral density (BMD) and falls. Participants who used the medication at the beginning of the study and at year five were considered to be recurrent users. BMD of the lower spine and hip were measured at the beginning of the study. Patients were then sent a yearly questionnaire to determine if they had experienced clinical fragility fractures and all reported fractures were confirmed radiographically. Other factors such as demographic information, history of falls and medication use were all assessed.



Daily use of SSRIs was reported by 137 participants with an average age of 65.1 years. The researchers found that "daily SSRI use remained associated with a two-fold increased risk of incident clinical fragility fracture even after adjustment for many potential confounding variables." These fractures occurred at the forearm (40 percent), ankle and foot (21 percent), hip (13 percent), rib (13 percent) femur (9 percent) and back (4 percent). Participants who used SSRIs at the beginning of the study had similar increased risks of fracture to those who used them at follow-up.



During the initial interview, the daily use of SSRIs was associated with an increased risk of falling. The effect was dose-dependent; doubling the daily dose of SSRIs increased the odds of falling 1.5-fold during the previous month. Daily use of SSRIs was also associated with a 4 percent decreased BMD at the total hip and a 2.4 percent decrease at the lumbar spine.



"Our results suggest that BMD and falls may be affected adversely by daily SSRI use but that fracture rates remain elevated despite adjustment for these two risk factors, indicating that other pathways, such as impaired bone quality leading to reduced bone strength, may be of particular relevance," the authors conclude. "In light of the high rate of SSRI use among the general population, and among elderly persons in particular, further studies that include controlled prospective trials are needed to confirm our findings."






(Arch Intern Med. 2007;167:188-194.)


The Canadian Multicentre Osteoporosis Study was funded by the Canadian Institutes of Health Research, Merck Frosst Canada, Ltd., Eli Lilly Canada Inc., Novartis Pharmaceuticals Inc., The Alliance for Better Bone Health (Sanofi-Aventis and Proctor & Gamble Pharmaceuticals Canada Inc.), The Dairy Farmers of Canada and The Arthritis Society. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.



Contact: CГ©line Poissant

JAMA and Archives Journals

Study Recommends Best Care For Neck Pain

A seven-year, international study just published finds that some alternative therapies such as acupuncture, neck manipulation and massage are better choices for managing most common neck pain than many current practices. Also included in the short-list of best options for relief are exercises, education, neck mobilization, low level laser therapy and pain relievers.



Therapies such as neck collars and ultrasound are not recommended. The study found that corticosteroid injections and surgery should only be considered if there is associated pain, weakness or numbness in the arm, fracture or serious disease.



The Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders 236 page review of the current research on neck pain is published in the journal Spine. The multi-national and inter-disciplinary study team included Canadian, American, South American, Australasian and European researchers. The Task Force was created to help neck pain sufferers and health professionals use the best research evidence to prevent, diagnose and manage neck pain.



"Neck pain is not a trivial condition for many people," says Task Force president Dr. Scott Haldeman, clinical professor, department of neurology at the University of California, Irvine; and adjunct professor, department of epidemiology University of California Los Angeles. "It can be associated with headaches, arm and upper back pain and depression. Whether it arises from sports injuries, car collisions, workplace issues or stress, it can be incapacitating. Understanding the best way to diagnose and manage this problem is of high importance for those who are suffering and for those who manage and pay for its care."



The study found that neck pain is a widespread experience that is a persistent and recurrent condition for the majority of sufferers. It is disabling for approximately two out of every 20 people who experience neck pain and affects their ability to carry on with daily activities says the Task Force.



A key recommendation of the Task Force is that neck pain, including whiplash-related pain, be classified and treated in a common system of 4 grades:



Grade 1: neck pain with little or no interference with daily activities


Grade 2: neck pain that limits daily activities


Grade 3: neck pain accompanied by radiculopathy ("pinched nerve" -- pain weakness and/or numbness in the arm)


Grade 4: neck pain with serious pathology, such as tumor, fracture, infection, or systemic disease.



"The majority of neck pain falls into Grades 1 or 2," says Task Force member, Dr. Linda Carroll, Associate Professor, School of Public Health at the University of Alberta, and Associated Scientist, Alberta Centre for Injury Control and Research (ACICR). "Many sufferers manage to carry on with their daily activities. Others find their pain interferes with their ability to carry out daily chores, participate in favorite activities or be effective at work. For these people, the evidence shows there are a relatively small number of therapies that provide some relief for a while, but there is no one best option for everyone."
















In addition to its comprehensive review of the existing body of research on neck pain, the Task Force also initiated a new study into the association between chiropractic care of the neck and stroke. This innovative piece of research found that patients who visit a chiropractor are no more likely to experience a stroke than are patients who visit their family physician. The study concludes that this type of stroke commonly begins with neck pain and/or headache which causes the patient to seek care from their chiropractor or family physician before the stroke fully develops.



"This type of stroke is extremely rare and has been known to occur spontaneously or after ordinary neck movements such as looking up at the sky or shoulder-checking when backing up a car," noted the study's lead author, Dr. David Cassidy, professor of epidemiology at the University of Toronto and senior scientist at the University Health Network at Toronto Western Hospital.



For the minority of neck pain sufferers who experience Grade 3 neck pain -- that is neck pain accompanied by pain, weakness and/or numbness in the arm, also referred to as a "pinched nerve", corticosteroid injections may provide temporary relief says the study. Surgery is a last resort according to the findings and should only be considered if accompanying arm pain is persistent or if the person is experiencing Grade 4 pain due to serious injury or systemic disease.



Top findings for neck pain suffers:



* Stay as active as you can, exercise and reduce mental stress.



* Don't expect to find a single "cause" for your neck pain.



* Be cautious of treatments that make "big" claims for relief of neck pain.



* Trying a variety of therapies or combinations of therapies may be needed to find relief -- see the therapies for which the Task Force found evidence of benefits.



* Once you have experienced neck pain, it may come back or remain persistent.



* Lengthy treatment is not associated with greater improvements; you should see improvement after 2-4 weeks, if the treatment is the right one for you.



* There is relatively little research on what does or does not prevent neck pain; ergonomics, cervical pillows, postural improvements etc. may or may not help.



"This is an important body of research that will help to improve the quality of patient care by incorporating the best evidence into practice and patient education," says Dr. Carroll. "Neck pain can be a stubborn problem -- we hope this comprehensive analysis of the evidence will help both sufferers and health care providers better manage this widespread complaint."







Source: Angela Kargus

American Chiropractic Association

Early Menopause No Predictor Of Hip Fracture

Women who have an early menopause are unlikely to have a long term increased risk of hip fractures associated with menopausal bone density weakening, according to a new study from The Australian National University.



For decades medical practitioners have understood a link between menopause and a decrease in bone density. This has translated into clinicians advising women who had an early menopause that they are at particularly high risk of hip fracture - a common complaint amongst the elderly.



The study, led by Associate Professor Emily Banks of the National Centre for Epidemiology and Population Health at ANU, has found that age is the main determinant of hip fracture and that among the elderly their age at menopause has little, if any, effect on hip fracture risk. Hence, doctors should base their advice on the age of patients alone.



The researchers used data from the UK's Million Women Study to reach their findings. The Million Women Study recruited 1.3 million women aged 50-64 years who attended breast cancer screening clinics between 1996 and 2001 to investigate how reproductive and lifestyle factors affect women's health.



"The findings show that among post-menopausal women, age is the major determinant of hip fracture risk and that for women of a given age, their age at menopause has little effect on hip fracture risk," said Dr Banks.



"The results suggest that clinicians advising women about hip fracture prevention should probably base their advice on the woman's age and on age-related factors such as frailty, rather than on factors related to menopause. Clinicians can also now reassure elderly women who had early menopause that their risk of hip fracture is unlikely to be higher than that of similar women who had a later menopause," she said.



Hip fractures are a serious problem for elderly people, especially women. As people age, their bones gradually lose minerals and become less dense, which makes them more susceptible to fracture. Because women lose bone density faster than men as they age and because women constitute the majority of the elderly, three-quarters of hip fractures occur in women.



"Although surgical repair of a broken hip only requires a hospital stay of about a week, a quarter of elderly people who were living independently before their fracture have to stay in a nursing home for at least a year after their injury, and a fifth of elderly people who break a hip die within a year," said Dr Banks.



The study has been published today in Public Library of Science Medicine.



Source
Australian National University

Results Of Phase 3 Clinical Trial Of Chrysalin(R) (TP508) In Fracture Repair

OrthoLogic Corp. (Nasdaq: OLGC) today announced results of an analysis of topline data from its
Phase 3 clinical trial of the novel synthetic peptide Chrysalin(R) (TP508) in
unstable, displaced distal radius (wrist) fractures. Treatment with 10ug
Chrysalin did not demonstrate a statistically significant benefit compared to
placebo in the primary efficacy endpoint of time to removal of immobilization.


A secondary endpoint, radiographic evidence of time to radial cortical
bridging, showed a statistically significant benefit for Chrysalin-treated
subjects (p = 0.049). This benefit mirrored findings from the Phase 1/2
clinical trial that provided part of the foundation for the Phase 3 study. No
difference was observed between Chrysalin treatment and placebo in the other
secondary endpoints.


The trial met the pre-specified safety endpoint by demonstrating no
significant difference in adverse event rates between the Chrysalin and
placebo groups.


"We will be conducting a full examination of these results in order to
guide our program going forward, including a planned interim analysis of
results from the ongoing Phase 2b dose ranging trial of Chrysalin in distal
radius fractures, which includes a 30ug dose," commented James M. Pusey, MD,
President and CEO of OrthoLogic.


The Company expects to communicate results of its interim analysis during
the third quarter of 2006.


Study Description


The study was a prospective, double-blind, randomized, placebo-controlled
Phase 3 clinical trial designed to evaluate the safety of Chrysalin and its
efficacy regarding the rate of healing in adult subjects with unstable and/or
displaced distal radius fractures. Subjects were randomized to receive a
single 1mL percutaneous injection of Chrysalin at 10 ug or placebo
administered into the fracture site under fluoroscopic guidance. Five hundred
three subjects were enrolled at 27 active centers in the United States.


Subjects were evaluated post-surgery at weeks 1-8, 10, 12, 26 and 52. The
primary efficacy endpoint was time to removal of all immobilization, defined
as the elapsed time between the date of fracture surgery and the first study
visit at which the investigator, based on clinical and radiographic
assessments of healing, removed all rigid immobilization hardware used to
stabilize the fracture.


Secondary efficacy endpoints included:


* Time to clinical and radiographic bone healing


* Assessment of the fractured wrist range of motion and grip strength
relative to the contralateral limb


* Clinical outcomes as measured by the Patient Rated Wrist Evaluation
questionnaire


Safety was measured as the proportion of subjects with treatment-emergent
adverse events.


About OrthoLogic


OrthoLogic is a biotechnology company focused on the development and
commercialization of the novel synthetic peptide Chrysalin(R) (TP508) in two
lead indications, both of which represent areas of significant unmet medical
need -- fracture repair and diabetic foot ulcer healing. Based on the
Company's pioneering scientific research of the natural healing cascade,
OrthoLogic has become a leading company focused on tissue and bone repair.
The Company owns exclusive worldwide rights for Chrysalin.















OrthoLogic is committed to developing a pipeline of novel peptides and
other molecules aimed at helping patients with equally under-served
conditions. The Company has an exclusive worldwide license to the novel
pre-clinical 24-amino acid peptide AZX100, the first of a new class of
compounds in the field of smooth muscle relaxation called Intracellular Actin
Relaxing Molecules, or ICARMs(TM). AZX100 is currently being investigated for
medically and commercially significant applications, such as the treatment of
vasospasm associated with subarachnoid hemorrhage, the prevention of keloid
scarring and the treatment of asthma.


OrthoLogic's corporate headquarters are in Tempe, Arizona. For more
information, please visit the Company's Web site: orthologic.


Statements in this press release or otherwise attributable to OrthoLogic
regarding our business that are not historical facts are made pursuant to the
safe harbor provisions of the Private Securities Litigation Reform Act of
1995. These forward-looking statements, which include the timing and
acceptability of FDA filings and the efficacy and marketability of potential
products, involve risks and uncertainties that could cause actual results to
differ materially from predicted results. These risks include: delays in
obtaining or inability to obtain FDA, institutional review board or other
regulatory approvals of preclinical or clinical testing; unfavorable outcomes
in our preclinical and clinical testing; the development by others of
competing technologies and therapeutics that may have greater efficacy or
lower cost; delays in obtaining or inability to obtain FDA or other necessary
regulatory approval of our products; our inability to successfully and cost
effectively develop or outsource manufacturing and marketing of any products
we are able to bring to market; changes in FDA or other regulations that
affect our ability to obtain regulatory approval of our products, increase our
manufacturing costs or limit our ability to market our products; our possible
need for additional capital in the future to fund the continued development of
our product candidates; and other factors discussed in our Form 10-K for the
fiscal year ended December 31, 2005, and other documents we file with the
Securities and Exchange Commission.


OrthoLogic Corp.

orthologic

Why Metal-On-Metal Resurfacings Go Wrong - Journal Of Bone And Joint Surgery

An article has been published in The Journal of Bone and Joint Surgery -British Volume surveying patients who had their metal-on-metal resurfacing procedures revised. A first of its kind, the paper looks to explore possible reasons for failure of these resurfacings including malpositioning of the components.


Although the sample size was small, over 60% of patients studied suffered from malpositioning and this was also associated with 'metallosis and a high level of serum ions'. Metallosis is a complication of joint replacement caused by abrasion of metal components. Typically, it involves the accumulation of metal ions in the areas surrounding the joint and can cause the formation of giant cells and fibrosis.


The authors conclusion was that in the group studied 'malpositioning of the acetabular component was the main cause of revision' and that therefore 'accurate positioning of the implant is of paramount importance to ensure a low wear rate of metal-on-metal bearings'. This will impact procedure and hopefully result in less revisions in the future.


Read the research article.


- The Journal of Bone and Joint Surgery - British Volume is a world leading orthopaedics journal with an Impact Factor of 1.868


- JBJS-Br publishes twelve issues a year of high-quality, peer-reviewed research, overseen by an international editorial board led by Editor James Scott


- The Journal was first published in 1948 by The British Editorial Society of Bone and Joint Surgery, a registered charity (No. 209299), with the object of the advancement and improvement of education in orthopaedic surgery and allied branches of surgery and the diffusion of knowledge of new and improved methods of teaching and practicing orthopaedic surgery in all its branches


- You can find out more about The Journal at jbjs.uk.

The Journal of Bone and Joint Surgery - British Volume

NICE Issues Guidance On The Prevention Of Venous Thromboembolism, UK

The National Institute for Health and Clinical Excellence (NICE) has published final guidance on the use of dabigatran etexilate for the prevention of venous thromboembolic events after elective total hip or elective total knee replacement surgery in adults.


NICE produced the guidance as part of its rapid single technology appraisal (STA) work programme. The guidance states:


Dabigatran etexilate, within its marketing authorisation, is recommended as an option for the primary prevention of venous thromboembolic events in adults who have undergone elective total hip replacement surgery or elective total knee replacement surgery.


Deep vein thrombosis (DVT) occurs in over 20% of surgical patients and over 40% of patients undergoing major orthopaedic surgery. The blood clot itself is not life threatening, and more often than not does not cause any symptoms. However, if it comes loose it can be carried in the blood to another part of the body where it can cause problems - this is called a venous thromboembolism.


Dabigatran etexilate (also known as Pradaxa) is an oral anticoagulant medicine that helps to prevent blood from clotting. It does this by interfering with a substance in the body (thrombin) that is involved in the development of blood clots. Dabigatran etexilate should be given shortly after surgery to help prevent venous thromboembolism.


Dr Gillian Leng, NICE Deputy Chief Executive and Executive Lead for the appraisal, said: "People having surgery to replace their hip or knee joint are at risk of venous thromboembolism because they are inactive during and after their operation and because of the damage caused during surgery. If a clot travels to the lungs it can be fatal and even if a blood clot does not come loose, it can still cause long-term damage to the veins leading to pain and swelling. The independent Committee carefully considered the evidence and concluded that dabigatran is as a cost effective option for preventing DVT, alongside other effective treatments already recommended by NICE. "


About the guidance


1. The dabigatran etexilate guidance is available at: nice.uk/TA157


2. A deep vein thrombosis (DVT) occurs when a blood clot forms in a vein. The DVT usually forms in a deep leg vein, and can cause immobility (lack of movement). Deep leg veins are the larger veins that run through the muscles of the calf or thigh. A DVT can form across all, or part, of the width of the vein, which can block blood flow either completely or partially.


3. In April 2007, NICE published a clinical guideline on reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in inpatients undergoing surgery. The clinical guideline is available at nice.uk/Guidance/CG46


About NICE


The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.


NICE produces guidance in three areas of health:


public health - guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector

health technologies - guidance on the use of new and existing medicines, treatments and procedures within the NHS

clinical practice - guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.


NICE

AAOS Responds To FDA's Public Health Communication On Metal-On-Metal Hips

The U.S. Food and Drug Administration (FDA) today posted a public health communication about metal-on-metal hip components used in total hip arthroplasty (THA). The American Academy of Orthopaedic Surgeons (AAOS) appreciates this thorough and well-considered look at the concerns surrounding the use of these implants. The FDA's communication also keeps each of the key stakeholders in mind: patients, potential patients, orthopaedic surgeons and other medical practitioners.


With the patient's safety, health, and quality of life always in mind, the members of the AAOS will continue to work with device makers and agencies such as the FDA to share knowledge and communicate any potential concerns.


"The FDA is a partner in patient safety and education. We believe that a significant majority of metal-on-metal hip replacement implants have successfully relieved pain and improved function without any problems for the patients who have received them but there have been some concerning exceptions. We are working together to investigate and report these concerns and will continue to communicate with our 36,000 members, the medical community and the public," stated AAOS President John J. Callaghan, MD.


According to the AAOS patients have several options for hip replacement implants, each with its own advantages and potential drawbacks. For the vast majority of patients, hip replacements - no matter what type of bearing surface is used - dramatically improve overall quality of life. Metal-on-metal hip implants are made of a cobalt-chromium alloy.


What did the statement say? The FDA's public health communication included an overview of the concerns and effectiveness of metal-on-metal hip implants, as well as information for orthopaedic surgeons, healthcare professionals, and patients who have these implants or are considering them.


What has the AAOS done to educate its members and help communicate the concerns raised in the FDA's message? The AAOS has notified all members about the possible side effects of the metal-on-metal devices. We also have included this in our Headline News Now e-blast to all members. We have updated our existing patient-education page on metal-on-metal hip implants to include the FDA's comments at orthoinfo and will send an e-mail to more than a dozen national medical specialty societies, asking primary and specialty care physicians to work with us to identify patients who may have adverse reaction to the metal implants. We also are working closely with the Hip Society and the American Association of Hip and Knee Surgeons, whose members are specialists in joint replacement surgery.


Why would an orthopaedic surgeon suggest a metal-on-metal implant? In general, metal-on-metal hip implants have been known to generate less wear debris, which can reduce the risk of osteolysis (loosening of the implant and weakening of the bone.) They also use a larger ball/socket component, which can reduce the risk of a dislocated hip. MoM hip implants typically have been used in younger patients to treat osteoarthritis and pain in the joint.















To whom does this public health communication apply?


- Patients who have had or are considering a metal-on-metal hip implant: According to data from the Nationwide Implant Sample database, in a one-year period from 2005-2006, approximately 39,200 MoM hip replacements were performed.


- Orthopaedic surgeons


- The general medical community.


What should a patient do if he or she has had a metal-on-metal hip replacement? Most patients have not had any problems with metal-on-metal implants. If the patient does not have any medical or health changes, and the hip is not painful, there is no reason to believe a problem exists. Periodic follow up with their orthopaedic surgeon is recommended. If, however, the patient notices new pains or medical concerns, he or she should talk to a doctor and orthopaedic surgeon. An open dialogue with a physician is the best way for patients to protect their own health.


The members of the AAOS strongly feel that a patient understands his or her own body best. A patient who notices any changes to his or her medical status, has any new symptoms develop or has pain that is new or gradually increasing, since the joint replacement surgery, must speak to an orthopaedic surgeon as any new symptom may be a symptom of an adverse reaction to an implant.


"We recommend all patients tell their physicians about their metal-on-metal implants, because if they are experiencing new symptoms or new pain, that can indicate a complication," stated Joshua Jacobs, MD, spokesperson for the AAOS and an orthopaedic surgeon and researcher in Chicago.


Total hip arthoplasty is one of the most successful surgeries of the past several decades. This procedure has relieved pain and restored movement to hundreds of thousands of people. The decision to have hip replacement surgery should only be made after discussion between the patient and his or her orthopaedic surgeon. As with any surgery, joint replacement surgery has some risks, but is successful in more than nine out of ten people. If complications occur, most can be successfully treated.


As a way of identifying early problems that may arise from any joint replacement procedure, the Academy has helped to establish the American Joint Replacement Registry (AJRR). The AJRR will track data on outcomes and devices, just as joint registries in other countries do. This national database will serve as an early alert system for continued or new device problems. The data collection process has just begun and will allow orthopaedic surgeons to track the success and failures of any implant used nationwide.


Source:

American Academy of Orthopaedic Surgeons

Octogenarians: Not Too Old For Joint Replacement

Knee replacement (orthoinfo.aaos/topic.cfm?topic=A00389) surgery can improve the quality of life even for very elderly patients, according to a study presented at the 2009 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS) (aaos/). The study found that patients in their 80s can benefit both physically and socially from knee replacement surgery, also called total knee arthroplasty (TKA), once thought too risky for the very elderly.


"As patients are living longer, there is an upward trend in the demand for quality of life among the elderly population," said Edsel Arandia, M.D., lead author of the study and an orthopaedic surgeon at Philippine Orthopaedic Center and a Fellow at Singapore General Hospital. "As patients age, debilitating diseases like arthritis of the knee (orthoinfo.aaos/topic.cfm?topic=A00228) begin to develop. We conducted this study to determine the viability of TKA in octogenarians and to learn whether their quality of life improves after TKA."


Dr. Arandia and his team reviewed data from 128 patients older than 80 years of age who underwent knee replacement surgeries at Singapore General Hospital between October 1998 and December 2006.


The results were measured using two quality-of-life scales, the SF-36 and the Oxford Knee Score, which assign scores to elements of physical and emotional health, such as:



-- physical pain



-- social functioning



-- vitality



-- physical functioning


When researchers compared the patients' preoperative scores to their postoperative scores up to 2 years following surgery, they found the patients' quality of life scores had risen significantly during the postoperative period.


"The improvement in pain and function of elderly patients was remarkable as early as 6 months and showed long-lasting improvement at the 2-year follow-up," Dr. Arandia noted. "Overall, total knee arthroplasty in elderly patients resulted in significant gains in their quality of life, which was reflected in both health- and social-related quality of life score dimensions."


"In our institution, many surgeons are still skeptical to perform TKA in the very elderly since few data or studies pertaining to the gains of TKA versus the complications and risks that can occur with surgery in elderly patients exist," Dr. Arandia said. "This study shows that with the advent of new technology and techniques in both orthopaedics and geriatric medicine, total knee arthroplasty in the very elderly population is very safe and offers significant gains in their quality of life."


American Academy of Orthopaedic Surgeons

aaos

Exploration Of 'Garbage Disposal' Role Of VCP And Implications For Degenerative Disease

It's important to finish what you start, say Jeong-Sun Ju and researchers from Washington University School of Medicine, St. Louis. In the December 14, 2009 issue of the Journal of Cell Biology, Ju et al. reveal how a mutant ATPase blocks autophagy partway through to cause a multi-tissue degenerative disease.



Mutations in VCP, a member of the AAA ATPase family, cause inclusion body myopathy, Paget's disease of the bone, and frontotemporal dementia (IBMPFD), a rare disorder that mainly affects skeletal muscle, brain, and bone. Patient muscle contains aggregates of membrane and proteins called rimmed vacuoles, which accumulate and disrupt cellular architecture. This pileup of membranous trash is inconsistent with VCP's known involvement in proteasome-mediated protein degradation. Ju et al. thus wondered whether the ATPase might also be involved in garbage disposal via the autophagy pathway.



Knocking down or expressing mutated VCP in cells increased levels of the autophagy markers p62 and LC3. Microscopy revealed that although autophagosomes containing these two proteins formed, they failed to mature into autolysosomes capable of degradation. VCP mutant mice and IBMPFD patients also accumulated p62 and LC3 in their muscle, and the two proteins localized to rimmed vacuoles, suggesting that the membrane-protein aggregates arise from frustrated autophagosomes. Indeed, injecting wild-type mice with a drug that blocks autophagosome maturation also produced rimmed vacuoles, as well as inducing other markers of IBMPFD myopathy.



The researchers now want to determine the mechanism by which VCP promotes the final stages of autophagy and how this is perturbed in IBMPFD patients. However, senior author Chris Weihl points out that many therapies being developed to treat degenerative diseases attempt to rescue cells by stimulating autophagy. In the case of IBMPFD, this could make matters worse, as autophagy has no problem initiating - it's the failure to finish that causes the problem.



Source: Rita Sullivan


Rockefeller University Press