The Missing Link to a Missing Limb

Every year in the United States, 185,000 amputations are performed. The key to better prostheses may lie in understanding deer antlers

WHEN I LOOK INSIDE the heavy black trash bag, I find a leg, an entire human leg—hairy, male, cut off at the hip.

A parade of diseased organs crosses my desk in the surgical pathology lab every day: a uterus, knobby with fibroids; an appendix, swollen with pus and the stench of anaerobic infection; a shrunken gallbladder, packed with yellow-green stones, the last few drops of bile oozing out.

But a leg is something different.

A leg is a body part a person would miss.

Of course, we know that the two legs we humans walk around on might not remain perfect throughout the long stretch of our lives. We might break a bone or snap a ligament on a mid-winter ski trip. We might sacrifice a saphenous vein to bypass a clogged coronary artery or opt to strip out unsightly varicosities. Arthritis might settle in, signaling the need for a hip replacement, but, damaged or not, we all pretty much expect to make it through an entire lifetime with two legs.

Staring at the leg in the bag, I picture a man in a hospital bed, mid-thirties, with a full head of hair, and a wife and child, now short one very important part. Lying there, he can feel the lost limb, the phantom still connected to his brain. I wonder how this will change things for him. Will he have to take a desk job? Does he already have one? What will he have to give up as he adjusts to being a uniped versus a biped?

Later, I watch as the pathologist picks up the biggest knife on the tray and slices through the skin, fat, and muscle of the thigh in long, even strokes, as if cutting a loaf of artisanal bread. And then he finds it: the tumor buried inside the thigh, a big gelatinous ball, more than enough to kill a person.

Now new questions emerge that cloud all others: Has the cancer been removed in time? Will this man live?

I will never know the end of the story. This is just a summer job before I start medical school.

I will never know the stories of any of the body parts that pass through my hands, arriving with no “before” and leaving with no “after.” They move on and off the cutting board, into small plastic cassettes that become slides to be studied under the microscope, revealing the tea leaves of cellular anatomy.

For a whole summer, I log in samples. They all arrive neatly tucked into white plastic tubs. The leg is different, so heavy I have to pull it off the specimen cart and drag it to the grossing table. That is where I open the bag that holds a man’s future—the disease he hopes never comes back, wrapped inside a leg he will miss forever.

***

EVENTUALLY, I would know all too well the stories of the people whose legs, arms, fingers, and toes made their way to the pathology lab, because I would be the one wielding the reluctant scalpel that sent them there. There was the sixteen-year-old whose skidding motorcycle caught fire in a slick of gasoline. That night, he had bigger problems than a lower leg hanging by two burned bones and a twisted strand of muscle. We had to take his leg quickly and get him back to the intensive care unit because of the bigger threat to his life: shock and third-degree burns. When he finally woke up to find his leg missing, he sobbed for days. The loss had hit at the worst possible time, during the teenage years, when body image and invincibility loom large.

Not that there’s ever really a good time to lose a leg, as an elderly rancher found out after decades of diabetes and tobacco use narrowed his arteries and choked off the blood supply to his leg. “Just do what you gotta do,” he said, feigning a resolve that belied his overall condition. He was too frail to learn to walk with an artificial leg and never stood up again.

And there were times when even an amputation wasn’t enough, as in the case of a five-year-old who had been flown in from a Navajo reservation after an infected bug bite incited a lethal form of flesh-eating bacteria. We rushed her to the operating room in the middle of the night and amputated the leg as fast as we could, but it was too late. Despite our pouring in the strongest antibiotics available, her tiny body couldn’t fight back, and she died the next day.

Amputations were all too often tragic—sudden and unsettling for patient and surgeon alike—but as I had discovered long ago in that pathology lab, they, like most tragedies, were an unavoidable part of life.

***

IN 1993, Mark O’Leary, just an eighteen-year-old kid, veered too close to a car while riding his motorcycle in London, England. If he’d been able to swerve just six inches to the left, he would have avoided the accident altogether, but there was neither room nor time to make that move. Instead, he hit the front corner of the car, his leg dragging and banging along the side until it was mangled beyond repair. When doctors gave O’Leary the bad news, he lay on a stretcher in the emergency center, holding the consent to operate in his hands. Barely able to comprehend how his life could change so suddenly and severely, he signed it.
O’Leary had plenty of time to reflect on his change of circumstance during the two weeks he spent in intensive care, battling sepsis. He had just started college, with dreams of joining the Royal Air Force, but the accident forced him to come up with a new plan. Inspired by the medical care and equipment that kept him alive during his ordeal, he embarked on a new field of study and became a medical physicist, working in the radiology department of a hospital.

Before the accident, O’Leary was a member of rugby and soccer teams, but his real love was hiking and climbing mountains, being outside and soaking up nature. After his initial recovery, he described himself as a “relatively high-functioning above-knee amputee,” albeit one with new physical limitations.

The self-described “avid outdoorsman” had to set aside his plans to run any more marathons or scale mountains. He wasn’t lacking in energy or motivation, but his prosthetic leg thwarted his athletic drive. It was attached to his body with a hard plastic socket that slid over the stump of his leg, and after several hours of use, the socket would rub the skin of the stump, leaving it raw and sore. Even when simply walking long distances, he would have to stop, take off the prosthesis, and let his leg breathe, especially in warm weather, when his stump would sweat. He couldn’t wait to take the leg off as soon as he walked in the door at home. Getting around on one leg, he became “an accomplished hopper.”

***

THE PLIGHT of amputees has catapulted into the nation’s consciousness in recent years due to the wars in Iraq and Afghanistan and the Boston Marathon bombings. In the United States, Americans lose 30,000 arms, hands, fingers, toes, feet, and legs to trauma every year. They are lost in motorcycle or automobile crashes, industrial injuries, farm machinery mishaps, and run-ins with power equipment, such as electric saws and lawn mowers.

Additional limbs are lost to cancer, vascular disease, and flesh-eating bacteria, bringing the total number of amputations performed every year in the United States to approximately 185,000, roughly five hundred per day. There are currently an estimated 1.9 million amputees living in the United States, most of whom will need some kind of prosthesis to return to normal function.

All too often, an amputation is performed as an emergency, at a time when the patient’s life hangs in the balance because of shock from blood loss or infection and toxins accumulating in dead tissue. The surgeon races to get the limb off as quickly as possible—slicing through the skin, fat, and muscle, throwing silk sutures around blood vessels and nerves, and pulling back and forth on the Gigli saw while bone spicules fly through the air.

Once the leg is off, the cut edge of the bone is smoothed out with a rasp. And then it’s time to finish up with what the patient will walk around with for the rest of his life: the stump. The surgeon has to take whatever skin and soft tissue is left, and fashion the best possible closure, hoping there is enough healthy tissue remaining to provide a comfortable cushion for a prosthesis. Even with the best surgeon’s best efforts, the patient might still end up with a less than perfect stump.

The earliest iterations of prostheses, dating back to 600 BC and possibly even earlier, were little more than cosmetic stand-ins carved from wood. The current generation, focused on function over form, has improved so much that patients might even choose an amputation over the lengthy and painful reconstruction of a severely damaged extremity. Today, lightweight prosthetic legs are constructed of durable carbon fiber materials. Some come equipped with motorized battery-powered knees controlled by microprocessors. There are even limb prototypes that can be controlled by the wearer’s nerves and brain; we’re not too far from artificial limbs that will simulate touch and be able to relay data.

Prostheses offer tremendous hope, but they are still inherently problematic because they force the amputee to put a great deal of pressure on what is essentially a pad of soft tissue. The attachment point is usually a plastic or rubber cup molded to the user’s stump; if the fit isn’t right, not only is the wearer’s ability to walk stalled, but the stump can be damaged. Complicating the challenge, stumps can shrink and swell over a few hours, changing the fit of the prosthesis. A once secure fit becomes vulnerable to slippage and rubbing, leading to skin irritation, blisters, ulceration, and possibly infection. After an amputee like Mark O’Leary has been standing on a prosthesis all day, he feels it.

***

O’LEARY DIDN’T KNOW it, but while he was adapting to life as an amputee, researchers at a nearby university in London were five years into developing a new way to attach a leg to a person’s body. The core concept driving the research was osseointegration—that is to say, incorporating, directly into a patient’s bone, an implant or fixture to which a prosthesis could be attached. This idea had been bounced around since the 1960s, when a Swedish physician named Per-Ingvar Branemark developed dental implants that snapped into place via a fixture embedded in the mandible. Previously, patients in need of a set of false teeth, frequently the elderly, were stuck with a set of removable dentures, which tended to dislodge and limited the wearers to softer foods.

An implanted prosthesis could potentially be a huge upgrade for amputees because it would eliminate the stump-socket interface and the resulting wear and tear on the stump. And if the fixture was embedded into the wearer’s bone, the attached limb might actually feel and move more like a part of a person’s body.

But there was a reason osseointegration hadn’t caught on when it was first rolled out for limbs. The skin separates the sterile internal environment of the body from the external world and keeps out microorganisms that can cause infection. Implanted medical devices that breach the skin barrier, such as intravenous lines and feeding tubes, are highly susceptible to bacteria creeping in along the part of the device that extends outside the body. It was not surprising that early attempts to implant a prosthesis into the bone were defeated by stubborn bouts of recurring infection.

Implanting any foreign object into the stump of a bone presented the risk for a bone infection, a potentially costly complication that would take months to treat and would likely result in prolonged disability and, in worst-case scenarios, the loss of more of the leg. If surgeons were one day going to implant prostheses directly into bones, scientists would first have to find a way to seal off the body from external threats.

In 1998, at University College London, biomedical engineers Gordon Blunn and Catherine Pendegrass (at that time, a graduate student) took on the challenge of finding a way around the stump problem. The first step was to come up with the design that eluded earlier generations of osseointegration pioneers, one that would prevent the entry of bacteria into the body. Looking for a model to draw on, Pendegrass turned to the natural world and took note of the multitude of animals that sprout structures—tusks, hooves, and fingernails—through the skin without any apparent infection risk. On closer inspection, she discovered that each of these structures originates from a fold in the skin and does not actually penetrate it.

The only naturally occurring structures that truly penetrate the skin are deer antlers and the tusk of an Indonesian wild pig, the babirusa. Because babirusa are an endangered species, Pendegrass wisely chose to study the much more accessible antlers.
What made the deer antler such an appealing model was the obvious strength of the attachment to the skull. In addition to serving as a visual cue of health and virility to potential female mates, antlers are also used as weapons to fight and establish dominance over competing male deer. During sparring matches, antlers are subjected to tremendous axial forces. The typical deer antler can withstand six times the impact that the same animal’s femur bone—the largest in its body—can.

When Pendegrass started her research, no one knew exactly how the antler-skin interface of the deer kept bacteria out of the sterile environment of the skull. She not only needed to uncover nature’s secret but would also have to find a way to replicate it in a human.

***

OVER THE CENTURIES, deer have fed and clothed us, provided handles for kitchen utensils and pocketknives, and even hung on our walls. They have also been the source of tonics that can be traced back two thousand years to when deer antler extract was used in traditional Chinese medicine to treat a variety of ailments including uterine fibroids and mumps. The extract allegedly has antibacterial, antiviral, analgesic, and anti-inflammatory biologic properties.

Antlers, found predominantly in bucks, serve as a symbol of both social status and virility. The more mature the animal, the larger the antlers, but they must be regrown every year. Antlers are shed after the early spring mating season; a few weeks later, a surge in testosterone triggers regrowth and stimulates the development of a layer of hairy skin, deer antler velvet, which blankets and nourishes the nascent set of antlers in late spring and summer. By late summer, the antlers mineralize and harden, and the velvet sheds.

High in naturally occurring insulin-like growth factor (IgF-1, a substance that mediates levels of human growth hormone in the body), deer antler velvet has surged in popularity in recent years as a dietary supplement in powder or spray form. It is touted for its steroid-like properties; it is said to boost athletic performance, remedy erectile dysfunction, and relieve arthritis pain. It’s no wonder deer antler velvet made it to the World Anti-Doping Agency’s list of banned substances and almost resulted in the suspension of a National Football League star.

***

PENDEGRASS STARTED her investigation into the strength of the antler-skull bond with a scanning electron microscope capable of magnifying a structure by up to 20,000 times its size. And that is when she found the key. The portion of the antler that attaches to the skull is peppered with holes, hundreds of them. Skin grows directly into the microscopic holes of the antler base, plugging them and sealing off any route of entry for bacteria from the outside world. Right beneath the skin, the soft tissue overlying the deer’s skull likewise grows into the pores of the skull’s pedicle, creating another tight, impermeable interface.
Armed with this knowledge, Blunn and Pendegrass set out to design an implant that would reproduce the skull-antler interface. They started with a simple titanium alloy rod and coated the portion to be implanted inside the bone with hydroxyapatite, a mineral essential to bone formation, to promote adherence between rod and bone. They also created a porous subdermal titanium umbrella, which would be embedded at the junction of the interior segment of the rod and the hub that exits the skin. The skin and soft tissues would grow into the umbrella to seal off the interior section of the implant from the outside world. The titanium hub, sealed with a diamondlike coating that resists infection, also served as an external fixture to which a prosthesis could easily be snapped on and off, like a ski binding.

The design seemed straightforward on paper, but Pendegrass and Blunn would invest another decade of research developing the Intraosseous Transcutaneous Amputation Prosthesis (ITAP) before it could be implanted into a human leg for the first time.

***

O’LEARY HAD BEEN LIVING with a socket-attached prosthesis for fifteen years when the letter arrived notifying him of the first ITAP clinical trial and inviting him for evaluation in 2008. It was with a mixture of excitement and trepidation that he contemplated the possibility of an implant. An ITAP would mean shedding himself of the problematic stump-socket apparatus, but he would have to undergo an operation that would prevent him from wearing any prosthesis at all at first. For six months, he would be dependent on crutches while waiting for the titanium rod to bond completely to his femur and for his bone to get stronger. Plus, the process would require rigorous physical therapy.

There were also complications to consider—most seriously, the possibility of a postoperative infection in his stump, which could preclude wearing a prosthesis in the short-term or, possibly, ever. How does a guy who has gone through the terror of losing a leg and learned to walk again face the possibility of never walking again—the tremendous loss of that freedom?

There was also the fact that the ITAP technique was virtually unproven for leg amputees. It had been piloted in animals with some success, and an arm amputee had undergone a successful ITAP implant, but O’Leary was facing a vast unknown in joining the trial. But by this time, O’Leary was a trained physicist, a man of science himself. He examined the data and the ITAP design, performed his own “internal risk-benefit analysis,” and decided to go for it.

In December 2008, at Royal Orthopaedic Hospital in London, O’Leary became the second human to have an ITAP implanted into his femur. When he awoke from the anesthesia, he was unnerved by the sight of his stump, now swollen to three times its normal size and with a piece of metal sticking out of the end. But over the next few days, the stump shrank back to normal, the metal attachment sealed to his skin, and a reassured O’Leary went home to start the most crucial phase of recovery: an intensive physical therapy program.

First, he had to become accustomed to walking with crutches again and the inconvenience of not being able to carry anything. Then, once the incisions and the skin around the fixture healed, he was able to start physical therapy to strengthen his femur bone so it could tolerate heavier loads.

O’Leary used a training prosthesis, a short rod weighing about a pound, which attached to his implant and to which metal cylinders could be bolted. Once he was able to start adding weight, he added half-pound cylinders until he reached five pounds, enough to support the weight of his prosthesis. Then he started training exercises, including swinging the artificial leg and performing heel strikes. After he became accustomed to the weight of the leg, he was able to start walking around the house for minutes at a time.

The sensation of attaching the leg was “jarring” at first because his femur was not conditioned to absorb the direct impact of heel strikes on the floor, but almost immediately, O’Leary said, he could “sense the potential” of his new implant as he wore it while sitting or taking those first few hesitant steps without the stump soreness he had endured for half his life. After four months of postoperative rehabilitation, he was able to walk as far as he wanted without pain.

“Just knowing where my foot is—my ability to know where it is improved dramatically because you can feel it through the bone,” O’Leary later said of his life-transforming appendage. “A textured road crossing, I can feel that. You essentially had no sensation with a socket, and with ITAP, you can feel everything. It’s like they’ve given me my leg back.”

***

SINCE O’LEARY received his ITAP in 2008, another eighteen patients have undergone the procedure to complete the initial clinical trial. The device is not yet commercially available, and no results have been published, but it is likely they will be released soon.

While the ITAP trial has been ongoing over the last decade, the technique of osseointegration has taken off with centers in Sweden, Australia, and Germany, each developing unique devices that can be implanted into the femur for a prosthetic. In July of 2015, the U.S. Food and Drug Administration authorized the use of the first osseointegrated implant for above-the-knee amputations: the OPRA (Osseointegrated Prostheses for the Rehabilitation of Amputees) implant system, developed in Sweden. A clinical trial made up of ten war veteran amputees is now underway at the University of Utah.

Selection criteria for the procedure remain narrow. Participants in the first wave of clinical trials had to be otherwise healthy, with no prior bone radiation or chemotherapy and no other chronic diseases or history of recent infections. Attempting an integrated prosthesis in the wrong patient could compromise healing and expose the recipient to the life-threatening risk of infection.
Not everyone is on board with osseointegration as the technique of choice for prosthetic attachment. O’Leary himself has admitted that the ITAP procedure is steeped in controversy, largely because of the risk of infection. While successful in some recipients, the ITAP technique is still considered experimental at this stage. Even if osseointegration can help only a small sliver of the 185,000 people who become amputees every year, the technique is life-changing for those who are candidates.

***

IN SEPTEMBER 2010, less than two years after his ITAP was implanted, O’Leary was prepping to climb Mount Kilimanjaro by participating in a series of training climbs. In a 2012 photo commemorating the climb, he is wearing a headlamp, a green windbreaker, and a very wide smile. In almost eight years of living with the ITAP, he has climbed Kilimanjaro, walked ninety miles over six days, learned to trek in crampons so he could summit the snowy Atlas Mountains in Morocco, cycled up to sixty miles at a time, and rappelled down a building. He has also become the proud father of a little boy he carried around in a backpack on his walks.

At this juncture, O’Leary is one of the lucky ones. Not only has his implant been trouble-free, but because of it, he can finish endurance events that most people would never even dream of attempting on their own two legs.

O’Leary took a blind leap in the pursuit of his dream of returning to outdoor adventure, a risk that has paid off beyond what he could have imagined. Perhaps, in the near future, this groundbreaking technology will be extended to many more amputees like Mark O’Leary, a man who now stands on a leg as strong as an antler and, in its own way, just as magical.

About the Author

Catherine Musemeche

Catherine Musemeche is a pediatric surgeon and the author of Hurt: The Inspiring, Untold Story of Trauma Care, from which this essay is adapted. She lives in Austin, Texas.

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