Safdar N. Khan, MD, Chief of the Division of Spine Surgery at The Ohio State University Wexner Medical Center, began researching cytokines when he was a resident.
At the time, his project had a completely novel view of fracture healing; he and his colleagues hypothesized that a cytokine produced in fat cells could modulate fracture healing and successfully tested this in a murine model of fracture. Now, Dr. Khan is researching how the same principles can be applied to spinal fusion.
"I was curious to determine if leptin has a role in spinal fusion. This worked stemmed from preliminary work done with Aaron Daluiski, MD, at The Hospital for Special Surgery in New York City," he says. "We are now in the process of starting a project with a rabbit model to examine whether it modulates spinal fusion. The exciting part of this is the idea is so novel. If we can show leptin plays a role in what we do, then we could have significant implications on the role adipose tissues have on spinal fusion healing."
In a 2013 Journal of Orthopedic Trauma article, Dr. Khan and his colleagues explored the complex role of leptin in fracture healing. Leptin is involved in a "direct stimulatory effect on bone growth, and/or an indirect suppressive effect on bone formation through the hypothalamus via the sympathetic nervous system. The local environment may provide bone cells with signals favoring proosteogenic behavior, whereas the central negative signal may exert a proosteoclastic effect that determines the density and length of long bones."
In the first arm of the study, leptin was seen to be expressed during normal fracture healing in normal mice. Subsequently, leptin-deficient mice were observed to have delayed fracture healing and interestingly this delay was reversed with local administration of leptin
In his new study, Dr. Khan is using a standard rabbit model to see if leptin is expressed during spinal fusion.
"If leptin is indeed expressed during spinal fusion, then this sheds new light on the role adipose tissue derived cytokines have during fusion biology," says Dr. Khan. "The corollary is we know fat cells produce leptin, so it is important to understand that what regional role purified leptin may have during spinal fusion. If successful, adipokines may be yet another source of pro-osteogenic factors to aid in spinal healing."
Patients with comorbidities such as high BMI sometimes aren't good candidates for spinal fusion currently because of their conditions; however, leptin could change that.
"Leptin is a quirky molecule," says Dr. Khan. "It has a primary role in the hypothalamus where it activates bone absorption and locally aids bone regeneration. I anticipate the in vitro data will be in by the end of the summer."
One of the exciting trends Dr. Khan sees for spinal fusion is the emergence of materials that aid in tissue regeneration and healing. Harvesting site-specific cytokines to promote healing could become part of the broader discussion. Currently, the most researched growth factors for spinal fusion are BMP-2 and BMP-7.
"Region-specific cytokines are very intriguing. At the very least, we will find if adipokines have a systematic role in spinal fusion and we should know that by the end of the year. This is all very exciting," says Dr Khan.
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