For a long time, physicians believed all bones formed in the same way – through a universal process of ossification. However, this study, led by primary investigator Matthew Greenblatt, MD, PhD, associate professor of pathology and laboratory medicine at Weill Cornell Medicine and assistant scientist in the HSS research division, alongside clinical collaborator Sravisht Iyer MD, spine surgeon at HSS, illuminated that certain vertebral skeletal stem cells play a unique and formative role in the development and life cycle of spinal vertebrae. Specifically, the investigators identified a stem cell that is responsible for bone formation in the vertebrae. Their research was made possible by support from a Pershing Square Foundation Cancer Research Prize and a special program established by the Anna-Maria and Stephen Kellen Foundation and Marina Kellen French, Vice President of the Foundation and an HSS trustee, that provides support for clinicians pursuing research as a significant component of their careers.

This significant finding carries profound implications for the field of spine health, including spinal healing, degeneration, treatment approaches, comprehension of degenerative spine disorders – and the potential to lead to breakthroughs in the prevention and treatment of vertebral osteoporosis and cancer metastasis.

“Understanding how vertebrae develop will help us more effectively treat patients, screen them before surgical intervention, and will ultimately lead to more effective preventive care and optimized bone health,” said Dr. Iyer. “The identification of this unique stem cell in the spine has the potential to significantly enhance our patients' outcomes in spine fusion surgery–a procedure performed hundreds of thousands of times in the United States each year–because it may allow for us to screen for problems ahead of time,” he continued. “The findings may also advance care for people with osteoporosis and, specifically, the 30 to 50 percent of the global population who suffer a vertebral fracture at some point in their lives.”

By manipulating bone-like “organoids” made from vertebral stem cells, this study also explored the disparities in metastasis rates between spinal bones and long bones, which include bones of the thigh, leg, arm and forearm. "Traditionally, it was believed that cancer cells were attracted to the spine due to directed blood flow. However, our discovery of this vertebral stem cell provides a likely explanation of why some cancers most often spread to the spine,” stated Dr. Greenblatt. “We predict this discovery will lead to the targeting of these cells to disrupt the function and ultimately reduce the spread of cancer to the spine."

The research team for this study included Jun Sun, PhD, first author and a postdoctoral associate at Weill Cornell; Kyle Morse, MD, an orthopedic surgery resident at HSS; and Lingling Hu, PhD, researcher at HSS, and has implications extending far beyond the laboratory and has the potential to impact patient care worldwide. Armed with insights into spine development and evolution, physicians will be able to tailor treatments and surgical intervention with more precision, with hope for improved patient outcomes across the board.

Augmented reality refers to digital information that is superimposed on a user’s view of the physical environment, providing images that can’t be seen with the naked eye. AR navigation in spine surgery superimposes 3D images of a patient’s anatomy onto the surgeon’s view of the operative field. Critical elements include a preoperative CT scan of the patient’s spine, which is used to plan and perform the surgery, and an augmented reality headset worn during the procedure.

The system Dr. Cammisa uses consists of a near-eye-display headset and the elements of a traditional navigation system. During surgery, it accurately determines the position of surgical instruments in real time and superimposes them on the patient's CT data. It has been likened to giving surgeons “x-ray vision,” enabling them to see structures underneath the skin.

“The technology allows us to visualize the patient’s 3D spinal anatomy during surgery to accurately guide instruments and place surgical implants, such as pedicle screws, while looking directly at the patient rather than at a separate computer screen,” Dr. Cammisa explained. “Improved control and visualization of the patient’s anatomy and critical structures can lead to a more precise, efficient surgery and can enhance safety." 

He notes that the technology allows for a highly personalized surgery that can be used for most spinal procedures requiring the use of implants. People with degenerative disc disease, spinal stenosis and spinal deformities may be candidates.

Dr. Cammisa notes that as more surgeries are performed with the augmented reality system, patient follow-up and data collection will enable HSS researchers to compare AR to other technologies used in spine surgery to evaluate outcomes.

Spinal fusion is among the most commonly performed orthopedic surgeries in the United States, with more than 400,000 patients undergoing the procedure each year. Although most cases are successful, as many as 45 percent of patients experience complications after the operation, often resulting from the bone’s inability to tolerate the hardware surgeons use to support the skeleton. 

The most widely used technology to evaluate patients’ bones before spine fusion surgery is called dual x-ray absorptiometry, or DXA. DXA imaging gives physicians a rough sense of the strength of a person’s bone, but it is not foolproof. In some cases, surgeons find that patients whose DXA scans appear normal have bones that are so weak that the appliances they use during spinal fusion are at risk of failure. 

The HSS researchers hypothesized that a more sensitive measure of bone quality could identify abnormalities in the skeleton that DXA does not detect, and that these defects would be linked to postoperative complications. 

For the new study, the team led by Emily Stein, MD, an endocrinologist and bone specialist, along with spine surgeons Han Jo Kim, MD, Matthew Cunningham MD, PhD, and Frank Schwab, MD, turned to a cutting-edge technique for assessing bone called high-resolution peripheral quantitative computed tomography (HR-pQCT). HR-pQCT can separately measure how much bone is in the outer (cortical) and inner (trabecular) compartments and measure on a microscopic level how the inner trabecular bone network is organized, including the number, thickness and spacing between the parts of that network called trabeculae. These measurements—known broadly as the microarchitecture—may provide a much more robust assessment of skeletal health than DXA, particularly in this population of patients who frequently have changes in the area of the fusion which undermine the utility of DXA. 

“DXA provides a two-dimensional measure of bone density, or the amount of bone present, whereas HR-pQCT provides a true three-dimensional measurement of the bone density,” Dr. Stein said. “This provides additional information about the structural features of bone that can be leading to weakness or fragility.”

The study included 54 men and women scheduled for spinal fusion at HSS between December 2017 and December 2019. Patients underwent conventional DXA scans, as well as HR-pQCT scans of the radius (forearm) and leg bone (tibia).

Of the 54 patients in the study, 14 experienced complications within the first six months of surgery, including broken rods, loosened bone screws, fractures and abnormal bending of the spine. Although the number of people in the study was small, the researchers found that those with abnormalities on HR-pQCT were significantly more likely to experience complications than those without such defects -- abnormalities that were not evident on DXA imaging. These abnormalities involved lower bone mineral density in the trabeculae (the spongy tissue in the center of bones), fewer and thinner trabeculae, as well as thinner cortices.

“We used HR-pQCT to show for the first time that abnormalities in the microscopic structure of bone are directly related to the development of complications after fusion. Our study identified several abnormalities in patients who had complications,” Dr. Stein said.

For the moment, HR-pQCT is a research tool that’s not widely available to surgeons. “I think that it does provide a lot of additional information that we’re not getting from DXA. On DXA, the spine is almost always going to look fine, which can be misleading,” noted Dr. Stein. 

Dr. Stein’s group is expanding their study to include more patients. “Spinal fusion surgeries are so invasive, the potential for complications is high,” she explained. “We want to have the most optimal strategies for lowering complications in our patients, and that begins with understanding who is at risk and why. In our future work with additional patients, we hope to be able to define which features, or group of features of the bone structure is most important in contributing to surgical success. This will help us to devise the most targeted treatment strategies for our patients.”

Dr. Stein's team published their findings in the journal Bone, and made available online first on November 4, 2020.

“I have always been a very active, outdoorsy nature lover, enjoying activities such as mountain climbing, biking, kayaking and rock-climbing all around the world with my family, as well as ballet dancing,” Ms. Hitchcock wrote on “Back in the Game,” the HSS patient blog. “By 2009 I was in constant pain and barely able to walk, much less dance or climb. Within a month of my total knee replacement I was back in the ballet studio doing my barre exercises and I climbed Mt Katahdin in Maine, crossing the ‘Knife’s Edge’ 11 months later. Dr. Westrich truly gave me back my life! With my new knee I was able to take a rock-climbing trip to Thailand in 2014 to celebrate our children’s’ PhDs! What fun!”

Over the years, Ms. Hitchcock has enjoyed numerous active vacations with her family. She has visited Zimbabwe, Botswana, Borneo and other exotic locales. In addition to climbing, she continues to go hiking, bicycling and has taken up snorkeling. She recently returned from an adventure vacation in New Zealand with her husband and daughter, which included mountain climbing and kayaking.

Ms. Hitchcock is among a growing number of baby boomers who refuse to slow down, despite joints worn out by years of activity, an injury or the passage of time. “I’m seeing more people in their 40’s and 50’s who refuse to be sedentary and, like Diane, will do what it takes to enjoy their active lives,” Dr. Westrich says. “Over the past few years, advances in joint implant design and surgical technique provide even more options for younger patients.” Robotic-assisted surgery and a newer cementless implant could lead to a longer-lasting knee replacement, he says.

Along with Dr. Westrich, Ms. Hitchcock credits two other highly specialized orthopedic surgeons at HSS with helping her maintain her active lifestyle. In addition to her knee replacement at age 56, she had a spinal fusion with Dr. Federico Girardi in 2017 and shoulder replacement surgery with Dr. Lawrence Gulotta in 2018.

She says each surgery has helped her enjoy life again. “Never once did any of my doctors at HSS express the notion that these goals were too extreme for someone my age,” she explains. Major surgery is never a walk in the park, but Ms. Hitchcock didn’t hesitate. She took each surgery and recovery very seriously, taking time off from work and vigorously adhering to her physical therapy regime after each procedure. She speaks very highly of all three of her HSS physicians, and says she had excellent outcomes after surgery.

 Her doctors applaud the motivation of Diane and others who wish to enjoy the physical and psychological benefits of exercise at every age. “Why give up years of an active lifestyle,” Dr. Westrich says, “when newer options are available to allow patients with arthritis or another orthopedic condition to live life to the fullest?”