Pain of artificial legs could be eased by real-time monitoring . . . When Ron Bailey lost his right leg below the knee 10 years ago after a head-on collision, he was fitted with a prosthetic leg and began learning to use it in his daily life as a real estate agent in Federal Way, Washington. For a couple of years after the amputation, Bailey, 66, said the remaining part of his leg shrank, which is common after the surgery. This caused him discomfort in the socket, the connection point of his limb to the prosthesis. To make it comfortable enough to wear, Bailey swapped out sockets of different sizes and used fabric pieces called socks to cushion the impact and adjust the fit. "In the end, the socket is the most important part," Bailey said. "You can have a great prosthetic foot, but if the socket isn't comfortable, you're not going to wear it." Many people who use prostheses experience pain on a daily basis where their skin meets the socket, particularly those who have diabetes or other diseases that affect their physiology. University of Washington (Seattle) engineers aim to ease this discomfort with research that could help build better sockets. They have developed a device that tracks how much a person's limb swells and shrinks when inside a prosthetic socket. The data could help doctors and patients predict how and when their limbs will swell, which could be used to build smarter sockets."This provides us a window into what's happening," said principal investigator Joan Sanders, a UW professor of bioengineering. "I'm really encouraged by what we have so far." This is the portable device that tracks fluid volume changes. The electrodes, at right, are fastened to a patient's leg and transmit data to the device Credit: Joan Sanders, U of Wash. Soft tissues in a prosthesis socket swell and shrink often during the day. This is a natural fluctuation that happens when we increase physical activity, sit or stand and even eat salty foods. But in a fixed socket, these fluid volume changes can be particularly painful, forcing people to seek relief by removing their artificial limb or adjusting the snugness of the fit by adding or removing fabric socks. If physicians can track when an individual typically experiences volume changes in his or her prosthesis socket, they can better fit patients with artificial limbs and reduce the amount of pain, said Kate Allyn, the team's lead research prosthetist who has worked for years making and fitting artificial limbs to patients.The device measures the percent increase or decrease of fluid volume in a patient's limb by receiving data from small electrodes placed in different spots on the leg. Instrument electronics can be worn in a fanny pack and include a circuit board that calculates the fluid volume change in the leg tissues, transmitting the data wirelessly to a computer or storing it on the device. Over the past two years, engineers tested a larger prototype on about 60 patients in their Seattle lab. Now they have a checkbook-sized portable version that they have brought to clinics in Seattle and San Francisco. Researchers are testing the device by asking patients to go through a routine that includes sitting, standing and walking as the device records fluid changes. In the UW lab, Bailey does a series of 90-second exercises while wearing the portable device. Data is transmitted wirelessly to a tablet that displays the changes in his limb size about 15 times a second. Longer term, researchers want to build a smaller device that patients could wear for a couple of weeks or longer to monitor changes in their limb size as they go about their daily routines. The hope is that prosthetic limb sockets will become more robust and flexible, accommodating natural changes in swelling without causing discomfort or inconvenience.

Fracture risk predicted by quality of bone as well as bone density . . . In a study carried out at the University of Eastern Finland, bone histomorphometry and infrared spectroscopy revealed abnormal bone properties in children with vertebral fractures and in children after solid organ transplantation. Bone compositional changes in children with vertebral fractures and after different types of organ transplantation have not been reported previously. Bone samples were investigated using bone histomorphometry, a microscopic method that provides information about bone metabolism and remodelling. In children with vertebral fractures, there were changes in bone composition, such as lower carbonate-to-phosphate-ratio and increased collagen maturity, which could explain the increased fracture risk. The results also suggest that in children who have undergone kidney, liver or heart transplantation, the various changes related to bone microarchitecture and turnover may be more important predictors of fracture risk than lowered bone mineral density alone. Early detection of such changes in bone quality could help prevent fractures. Osteoporosis is the most common metabolic bone disease characterized by abnormal bone formation and resorption which lead to increased risk of bone fractures. However, the present diagnostics based on the measurement of bone mineral density predict fractures only moderately. In addition to decreased bone mineral density, changes in bone quality could explain increased fragility related to osteoporosis. The present study confirmed that bone histomorphometry is needed in clinical practice to study remodelling balance in bone in certain patient groups. "Especially in clinically challenging scenarios where different treatment options are being considered, bone histomorphometry provides valuable information. An accurate diagnosis and choice of medication are especially important when treating paediatric patients," says Inari Tamminen, MD, whose doctoral thesis on the topic was published in June. The findings were originally published in the Journal of Bone and Mineral Research and the Journal of Bone and Mineral Metabolism. The histomorphometry laboratory at the University of Eastern Finland in Kuopio is one of the few in the world analyzing clinical bone biopsies. More than 70 patient samples are analyzed annually. Over 30 years of expertise in quantitative histomorphometry have formed a solid basis for high quality research. Recent projects focus on paediatric patients with osteoporosis, genetic disorders and insufficiency fractures.

McMaster researchers find home of best stem cells for bone marrow transplants . . . McMaster University (Hamilton, Ontario) researchers have revealed the location of human blood stem cells that may improve bone marrow transplants. The best stem cells are at the ends of the bone. It is hoped this discovery will lead to lowering the amount of bone marrow needed for a donation while increasing regeneration and lessening rejection in the recipient patients, says principal investigator Mick Bhatia, professor and scientific director of the McMaster Stem Cell and Cancer Research Institute. In a paper published online by the journal Cell Stem Cell, his team reports that human stem cells (HSC) residing in the end (trabecular region) of the bones display the highest regenerative ability of the blood and immune system. "Like the best professional hockey players, our findings indicate blood stem cells are not all equal," said Bhatia. "We now reveal the reason why - it's not the players themselves, but the effect the arena has on them that makes them the highest scorers." Bone marrow transplants have been done for more than 50 years and are routine in most hospitals, providing a life saving treatment for cancer and other diseases including leukemia, anemia, and immune disorders.

Study links vitamin D deficiency to accelerated aging of bones . . . Everyone knows that as we grow older our bones become more fragile. Now a team of U.S. and German scientists led by researchers with the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California Berkeley has shown that this bone-aging process can be significantly accelerated through deficiency of vitamin D – the sunshine vitamin. Vitamin D deficiency is a widespread medical condition that has been linked to the health and fracture risk of human bone on the basis of low calcium intake and reduced bone density. However, working at Berkeley Lab's Advanced Light ALS), a DOE national user facility, the international team demonstrated that vitamin D deficiency also reduces bone quality. "The assumption has been that the main problem with vitamin D deficiency is reduced mineralization for the creation of new bone mass, but we've shown that low levels of vitamin D also induces premature aging of existing bone," says Robert Ritchie, who led the U.S. portion of this collaboration. Ritchie holds joint appointments with Berkeley Lab's Materials Sciences Division and the University of California (UC) Berkeley's Materials Science and Engineering Department. "Unraveling the complexity of human bone structure may provide some insight into more effective ways to prevent or treat fractures in patients with vitamin D deficiency," says Björn Busse, of the Department of Osteology and Biomechanics at the University Medical Center in Hamburg, Germany, who led the German portion of the team. Ritchie and Busse have reported their findings in the journal Science Translational Medicine. The paper is titled "We hypothesized that restoring the normal level of vitamin D not only corrects the imbalance of mineralized and non-mineralized bone quantities, but also initiates simultaneous multiscale alterations in bone structure that affects both the intrinsic and extrinsic fracture mechanisms," Ritchie says. To test this hypothesis, Busse and his German team collected samples of iliac crest bone cores from 30 participants, half of whom were deficient in vitamin D and showed early signs of osteomalacia. For this study, a normal vitamin D level was defined as a serum concentration of 20 micrograms per liter or higher. For the vitamin D deficiency group the mean serum concentration was 10 micrograms per liter. The bone samples were sent to Ritchie and his team for analysis at the ALS using Fourier Transform Infrared (FTIR) spectroscopy and X-ray computed microtomography. The FTIR spectroscopy capabilities of ALS beamlines 1.4.3 and 5.4.1 provide molecular-level chemical information, and ALS Beamline 8.3.2 provides non-destructive 3-D imaging at a resolution of approximately one micron. Ritchie and his team found that while vitamin D-deficient subjects had less overall mineralization due to a reduction of mineralized bone, underneath the new non-mineralized surfaces, the existing bone was actually more heavily mineralized, and displayed the structural characteristics – mature collagen molecules and mineral crystals – of older and more brittle bone.

— Compiled by Holland Johnson, MDD Executive Editor

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