Keeping you up-to-date on recent headlines in orthopedics.

Metallic glass for bone surgery ... It is possible that broken bones will in the near future be fixed using metallic glass. Materials researchers at ETH Zurich (Zurich, Switzerland) have developed an alloy that could herald a new generation of biodegradable bone implants. Their results have been published in the online edition of Nature Materials. When bones break, surgeons need screws and metal plates to fix the broken bones in place. These supports are usually made of stainless steel or titanium. Once the bones have healed, the metal parts have to be removed from the body via further surgery. In order to reduce the burden on patients, materials re-searchers have taken up the task of producing implants from bioabsorbable metals. These implants should stabilize the bones only for as long as they need to heal. The metal dissolves in the body over time, rendering removal surgery unnecessary. Implants made of magnesium-based alloys are proving particularly promising. Magnesium is mechanically stable and degrades completely by releasing ions which are tolerated by the body. However, all magnesium alloys have one major drawback: when they dissolve they produce hydrogen (H2), which can be harmful to the body. Around the magnesium implants gas bubbles develop which hinder bone growth and thus the healing process, and potentially cause infection. Materials researchers working with J rg L ffler, Professor of Metal Physics and Technology at ETH Zurich, have now eliminated these side-effects. They have succeeded in producing an innovative magnesium-zinc-calcium alloy in the form of a metallic glass which is biocompatible and shows significantly more favorable degradation behavior. Metallic glasses are produced by rapid cooling of the molten material. The speed of the cooling process prevents the atoms from adopting the crystal structure found in traditional metals. As a result, metallic glasses have an amorphous structure like that of window glass. Thanks to this procedure, the researchers can add much more zinc to the molten magnesium than is possible with conventional alloys. The glassy alloy developed by the ETH researchers contains up to 35% zinc and 5% calcium atoms, with the rest made up of magnesium. A crystalline magnesium-zinc alloy can contain a maximum of 2.4% zinc atoms. If the percentage is higher, an undesired crystalline phase precipitates in the magnesium matrix. The magnesium-zinc-calcium glass can be produced in a thickness of up to 5 mm. The major advantage of a high percentage of zinc is that it changes the corrosion behavior of the magnesium fundamentally. In fact, clinical tests with small platelets of the new magnesium-zinc-calcium alloy showed no hydrogen evolution! Thus this new alloy, in the form of a metallic glass, has considerable potential as a non-harmful bone implant material.

New brain pathway for regulating weight and bone mass identified ... Contrary to the prevailing view, the hormone leptin, which is critical for normal food intake and metabolism, appears to regulate bone mass and suppress appetite by acting mainly through serotonin pathways in the brain, according to a recent study published in Cell by Yale School of Medicine (New Haven, Connecticut) researchers and colleagues at Columbia University (New York). This new finding contradicts the view that leptin acts primarily in the hypothalamus. "Our study challenges the view that the hypothalamus is the critical brain site where leptin acts directly to alter neuronal circuit function to suppress appetite and bone metabolism," said Yale researcher and study co-author Tamas Horvath. "We've now found a novel explanation for how leptin can act on the brain." Horvath is chair and professor of comparative medicine and professor of neurobiology and obstetrics & gynecology at Yale School of Medicine. Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signal the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese. To determine whether leptin regulates bone mass through serotonin pathways, Horvath and his colleagues analyzed multiple lines of mice that were genetically altered to remove serotonin in the brain. "We found that when the serotonin pathway is turned off by leptin, the mice ate less, lost weight and their bones became weak. When the pathway is turned on, the mice ate more, gained weight and had more bone mass," said Horvath. "This might be why obese people tend to have much lower incidences of osteoporosis."

Bones weakened by diabetes ... Current research suggests that the inflammatory molecule TNF-a may contribute to delayed bone fracture healing in diabetics. The related report by Alblowi et al, "High Levels of TNF-a Contribute to Accelerated Loss of Cartilage in Diabetic Fracture Healing" appears in the October 2009 issue of the American Journal of Pathology. Diabetes, a condition where the body either does not produce enough, or respond to, insulin, affects at least 171 million people worldwide, a figure that is likely to double by 2030. Long-term complications of diabetes include cardiovascular disease, chronic renal failure, retinal damage that may lead to blindness, nerve damage, and blood vessel damage, which may cause erectile dysfunction and poor wound healing. Diabetic patients often experience low bone density, which is associated with increased risk of bone fractures and delayed fracture repair. To examine how diabetes affects bone, Dana Graves, MD, and colleagues of the University of Medicine and Dentistry of New Jersey (Newark) and the Boston University School of Medicine (Boston) explored bone repair in a mouse model of diabetes. They observed increased levels of inflammatory molecules, including TNF-a during fracture healing. The diabetic animals had rapid loss of cartilage in the healing bones, which was due to increased numbers of osteoclasts, cells that remove bone and cartilage. Factors that stimulate osteoclast formation were regulated by both TNF-a and a downstream mediator, FOXO1. These results suggest that diabetes-mediated increases in TNF-a and FOXO1 may underlie the impaired healing of diabetic fractures. Alblowi et al suggest that "TNF-a dysregulation plays a prominent role in the recently identified catabolic events associated with diabetic fracture healing." In future studies, Graves and colleagues plan to "examine the effect of FOXO1 on mineralized tissue to examine how it may regulate factors that control bone resorption and osteoclastogenesis, in addition to effects it may have on osteoblastic cells."

Study finds way to stop excessive bone growth following trauma or surgery ... A recent U.S. Army study found that excessive bone growth, also known as heterotopic ossificiation (HO), affects up to 70% of soldiers who are severely wounded during combat. A much smaller percentage of the civilian population also suffers from HO following trauma or invasive surgery. The excessive bone forms within muscles and other tissues causing severe pain, reduced mobility and even local paralysis if untreated. A new study by Thomas Jefferson University (Philadelphia) researchers found a way to prevent HO in animal models by shutting the process off in its early stages. The study, reported in September's Journal of Orthopaedic Research, is expected to lead to clinical trials and may hopefully provide a new, effective and safe treatment for HO. "This is a major breakthrough in HO research," said primary investigator Maurizio Pacifici, PhD, director of Orthopedic Research at Jefferson Medical College of Thomas Jefferson University. "We are able to largely prevent formation and progression of HO lesions. We presented our initial results at a recent U.S. Army Extremity War Injuries Symposium in Washington D.C. and they were very well-received and have elicited great hope on the part of military physicians to finally have a way to stop HO in troops wounded in war zones." In the ongoing study sponsored by the U.S. Army, Jefferson scientists were able to prevent HO by disrupting a series of cellular changes that are needed to produce HO. Following a trauma or invasive surgery, the condition begins when progenitor and stem cells are recruited to the injured site and give rise to cartilage tissue that then turns to bone. This multi-step process is regulated by several factors. One of these factors is a protein in the nucleus of the progenitor cells that is called the retinoid alpha receptor. This receptor must be turned off before the progenitor cells can form cartilage tissue. The Jefferson scientists, using a pharmacological agent, an alpha agonist, kept the receptors active, stifling the initiation of the disease in its tracks. Hopefully, if clinical trials are done and prove successful this treatment could be used as a cure for not only HO but for other HO-related diseases including Fibrodysplasia Ossificans Progressive, an inheritable and severe form of HO.

—Compiled by Holland Johnson, MDD