Obesity and osteoporosis are genetically linked . . . When it comes to body shape, diet and exercise can only take us so far. Our body shape and geometry are largely determined by genetic factors. Genetics also have an impact on our body composition – including soft fat tissue and hard bone tissue – and can lead to excess fat or osteoporosis. Now Prof. Gregory Livshits of Tel Aviv University's Department of Anatomy and Anthropology at the Sackler Faculty of Medicine, working alongside Dr. Michael Korostishevsky, has uncovered a clear genetic link between fat and bone mass. These factors, which contribute to bone metabolism, also affect body mass index (BMI), which often serves as an indicator of overall health. Reported in the journal Bone, this finding is a step towards understanding how these tissues are inter-related on a biological level, and will help doctors develop better treatment plans for patients dealing with fat or bone related pathologies. “When a patient is prescribed a medication, it is always important to know the potential side effects,“ says Prof. Livshits. As a result of this genetic connection, “a medication that is prescribed to treat obesity might have a negative impact on skeletal health,“ he says. Previous studies revealed that osteocalcin, a protein produced by bone cells, has an impact not only on bone but also on fat tissue metabolism. The protein's function is associated with bone formation and bone mineralization. But recent data suggest that osteocalcin is also involved in the regulation of glucose and fat metabolism and that osteocalcin levels are lower in obese and overweight individuals. Livshits and Korostishevsky set out to determine the underlying mechanism of this osteocalcin link - whether it was purely environmental or had a genetic basis. The researchers conducted their study on a European population called the Chuvasha - descendants of Bulgarian tribes that have lived along the Volga River for more than a thousand years. As a relatively isolated and ethnically homogeneous population, they are highly appropriate for the study of genetic effects. 1,112 participants over the age of 20 hailing from a total of 230 families were tested for variants in the osteocalcin gene. Genetic information was analyzed in connection with measurements that reflect body mass, including BMI, thickness of skin folds, reflecting the amount of fat beneath the skin and others. “We discovered a statistically significant association between osteocalcin gene variants and measures of body mass, suggesting the involvement of this gene in body mass regulation,“ said Livshits. To check the reliability of their findings, they asked researchers at Tulane University in Louisiana to test the same association between genetic variants of the osteocalcin gene and body mass measurements in an extensive sample of 2,244 Americans of European background. The results revealed a very similar pattern. Because the connection between fat and bone mass has been shown to be genetic rather than environmental, related issues can't be addressed separately, Livshits said. Bisphosphonates, for example, are effective agents for the treatment of bone mineral density loss and are therefore commonly used to treat osteoporosis. However, it is also important to know how this therapy impacts fat tissue. “After a few years of treatment that improves the bones, we don't want to discover that we have harmed the fat tissue in the process,“ he adds.

X-ray imaging sheds new light on bone damage by illuminating fractures . . . From athletes to individuals suffering from osteoporosis, bone fractures are usually the result of tiny cracks accumulating over time – invisible rivulets of damage that, when coalesced, lead to that painful break. Using cutting-edge X-ray techniques, Cornell University (Ithaca, New York) researchers have uncovered cellular-level detail of what happens when bone bears repetitive stress over time, visualizing damage at smaller scales than previously observed. Their work could offer clues into how bone fractures could be prevented. Marjolein van der Meulen, professor of biomedical engineering, led the study published online March 5 in PLOS One using transmission X-ray microscopy at the Stanford Synchrotron Radiation Lightsource, part of the SLAC National Accelerator Laboratory. Using the high-energy hard X-rays at SLAC's synchrotron, the researchers produced images of damage in sheep bone at a resolution of 30 nanometers – several times better than standard imaging via X-ray microcomputed tomography, which is at best 2-4 microns in resolution. (A nanometer is one-billionth of a meter. For comparison, the width of a human hair is about 70 microns, or 70,000 nanometers.) “In skeletal research, people have been trying to understand the role of damage,“ said van der Meulen, whose research is called mechanobiology – how mechanics intersects with biological processes. “One of the things people have hypothesized is that damage is one of the stimuli that cells are sensing.“ The inability of cells to repair microdamage over time ultimately contributes to the failure and breaking of bone, van der Meulen said. Until now, visualization techniques of microdamage were limited to lower resolution images. More detailed bone features, such as the small spaces called lacunae, where cells reside, and the microscopic canals between them, called caniliculi, were not visible. The imaging involved special preparation of sheep bone samples led by graduate student and first author Garry Brock. First they cut 2 mm square matchstick-like samples. The matchsticks were “damaged“ in the lab at various levels: Some received 20,000 cycles of “loading“ in bending; others received a single dose of loading; and others were notched before loading. All samples were treated with a lead-uranyl acetate X-ray negative stain that seeps into porosity caused by damage in the bone tissue. Then sections from the loaded segment were polished to 50-micron thicknesses. A greater amount of stain was seen in sections subjected to repetitive stress. But instead of seeing new surfaces formed by damage, or cracks, as was expected, the researchers observed damage in the cellular structures. The X-rays picked up the dye within existing, intact structures, like the lacunae where the cells sit, and in the caniliculi. “The tissue is not breaking, but rather, there is staining within the cells,“ Brock said. Added van der Meulen: “We were surprised by how cell-based the staining was, as opposed to forming lots of new surfaces in the material.“ In osteoporotic individuals, including many postmenopausal women, fractures usually occur in the forearm, spine and hip. van der Meulen's team is trying to understand why these fractures occur by studying nano- and microscale changes in bone tissue. They are also exploring the possibility of studying whether a class of osteoporosis drugs called bisphosphonates, which reduce the overall rate of hip fractures but can lead to “atypical femoral fractures,“ affect nanoscale damage processes. These unusual fractures occur at sites that normally do not fracture with osteoporosis such as in the middle of the bone shaft. The new damage visualization method could lend new insights in future studies.

Alphatec Spine receives FDA 510(K) market clearance for Solus system . . . Alphatec Spine (Carlsbad, California) reported that it has received clearance from the FDA to market and sell its patented Alphatec Solus internal fixation anterior lumbar interbody fusion (ALIF) device. The device's 510(k) application was filed with the FDA during the fourth quarter of 2012. The Alphatec Solus ALIF device features two counter-rotating titanium blades, which deploy into adjacent vertebrae on a zero-degree axis, locking the device in place. This provides four points of fixation delivered in what the company believes is an industry leading single step. The patented device is designed to provide enhanced segmental stability with a simplified surgical technique, while providing substantial spacing to insert bone graft to help promote rapid fusion at the site. Alphatec Solus is designed to provide fast, easy and effective stabilization for a surgeon's ALIF procedures. “We are extremely pleased to announce that the Alphatec Solus ALIF system will soon be available for commercial release within the United States,“ said Les Cross, chairman and CEO of Alphatec. “We launched Alphatec Solus in Europe in January this year and thus far it has been a success. Our product development programs will remain a collaborative effort between spine surgeons and our internal development group to ensure that the latest product innovations keep advancing improved patient care in the operating room.“ According to Millennium Research Group, the market for internal fixation ALIF spacer devices is estimated to be approximately $129 million in 2013, representing approximately half of the total market for the ALIF spacer devices.

— Compiled by Holland Johnson, MDD Executive Editor