SURELY the most common symbol of mortality is the grinning human skull, perched atop our strangely athletic-looking skeleton with its long bones and delicate fingers and feet. No matter how a lady may look in the flesh during her lifetime, as Shakespeare’s Hamlet said while exclaiming over the skull of poor Yorick: “To this favour she must come.”
And so must we all. The thought that our life hangs on a bony frame seldom occurs to any of us — until you slip and fall, and feel your bone crack. Or maybe you won’t feel it, depending on how bad a fracture it is.
You don’t have to be old and suffering from osteoporosis, or brittle bones, to crack a limb, as all players of sport know. What many do not realise is that genetic and environmental factors, including diet and lifestyle over many years, contribute to bone strength, and that osteoporotic bone deterioration can start young. Lack of exercise is one of the key factors.
A great deal of new research into bone density and flexibility has been prompted by space travel, since those who spend a long time in space cannot walk or run. Because of lack of gravity, their skeletons cease to carry a load, and they have to do what is called “resistance training” with pulleys and exercise bikes to force their muscles to place strain on their bones.
Bone loss, especially in the legs, occurs even in a short one-month space flight, accentuated by the excretion of calcium in the urine due to weightlessness. On earth our bodies produce vitamin D after exposure to the sun, but in space, astronauts are shielded from ultraviolet waves and they have to take in this bone-strengthening vitamin in their diet.
These findings, along with new research into osteoporosis in older people, have changed our understanding of the age-old problem of bone fractures. Brittle bones are not merely the accompaniment of age, but nor are our bones simply destined to deteriorate: they can restore themselves.
Some fractures are so insidious that the pain is ascribed to a mere muscular ache, but if it isn’t properly treated, you may suffer long- term consequences such as swelling, persistent aches and disability. Several studies in animal models such as mice and sheep have shown that a fracture should be completely immobilised (that is, splinted or put in a cast) within the first 24 hours.
Motion at the site of the fracture leads to the formation of a kind of bone scar tissue, or what researchers call cartilage intermediate, whereas rigidly stabilised fractures appear to heal fully by regeneration of the bone cells. It has been known for centuries that broken bones must be kept still and allowed to heal naturally, but modern science is now exploring the molecular processes that make this happen.
“In the event of injury, bones heal by generating new bone rather than scar tissue. Thus, it can be described as a regenerative process,” wrote Dr Jochen Hecht of the Max Planck Institute for Molecular Genetics, Berlin, in a 2006 study of fracture healing in sheep. Hecht and colleagues aimed to find out how the genes of sheep influenced the pace and efficiency of healing.
Skeletal regeneration is similar to what happens when bones develop in the embryo, with both processes following similar molecular principles. While many other body parts grow only once and never again — for example, the heart and kidneys — bone, like skin, hair and semen, can simply renew after loss.
“The newly formed bone is completely interconnected with the old bone and shows extraordinary mechanical stability,” reported Hecht. “The sequences we have identified in this work are a valuable resource for future studies on musculoskeletal healing and regeneration.”
The study offers an important head start towards our understanding the genetic basis of tissue regrowth. Research into regenerative medicine has become one of the frontiers of 21st century bioscience. The movement is being spurred on by new funding in the US, along with a relaxation of the restraints on stem cell research under President Barack Obama.
Stem cells are the blank slates of body architecture: they are unspecialised, but will differentiate into specialised cells to build particular organs such as the lungs, liver and heart. Bone marrow is particularly rich in stem cells and these are the cells from which all blood cells derive, which is why people with leukaemia (cancer of the blood) need new marrow.
Amazingly, marrow from a donor can restart the healthy reproduction of blood in the recipient of a transplant. This probably has to do with the proliferation of stem cells, although the precise molecular actively is as yet not well understood.
Only in the past decade or so has it fully dawned on medical scientists that bone regeneration is a vital indicator of the power of the body to repair itself — indeed, regrow itself — after an injury. If bones can heal by generating new bone rather than scar tissue, what is the molecular process that makes this possible, and could the same kind of process be invoked to regrow, say, entire limbs or even organs such as the heart?
In one spectacularly successful operation during May this year, physicians helped a 14-year-old boy to create his own cheek bones after he had been born without them. The operation at the Children’s Hospital Medical Centre in Cincinnati involved using stem cells taken from the fat tissue of the boy and combining them with growth protein and donor tissue to allow his body to build viable cheek bones.
Leader of the reconstructive team Dr Jesse Taylor explained that pigs had been used in the initial research to blend and refine several techniques in surgical practice. Regenerative surgery differed from implanting bone from a dead or living donor, or borrowing bone from one part of the body to graft into another, Taylor said.
Tissue rejection and disfigurement are two possible outcomes of transplants and grafting. The new procedure avoids these problems because it uses the patient’s very own cells.
More than four months after the surgery, computer tomography (CT) scans show the teenager’s cheek bones have filled in normally with viable bone.