Bone: Heal Thyself


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Bones break; it happens. It also happens that bones are one of the few organs that are able to regenerate. Those unfortunate enough ever to have experienced a broken bone know the procedure only too well: A physician physically “yanks” the bone – or, in the case of severe fractures, operates – to realign it with its other half, applies a cast to keep the two firmly in place, and within about one month, the bone halves reunite.
(l-r) Prof. Eli Zelzer and Chagai Rot
Though the first recorded use of rigid bone setting dates as far back as ancient Egypt, Prof. Elazar Zelzer and PhD student Chagai Rot of the Weizmann Institute’s Molecular Genetics Department now suggest, in a paper published in Developmental Cell, that constant movement of the bones could actually result in effective healing.

“In terms of evolution, the need for medical intervention just doesn’t make sense,” says Zelzer. “It’s a paradox: Evolution ‘invested’ great effort in affording bones with regenerative capabilities, and an intact skeleton is crucial for functioning and survival. Yet we are unaware of any natural mechanism able to align bones when they break.”

The medical literature has indicated the existence of such a natural system for some time. Some physicians are also aware of the phenomenon: They sometimes send very young children home with just a bandage wrapped around the limb. Even in cases of severe fracture, after some time the bones have often completely aligned and healed on their own. Until now, doctors and researchers have assumed that the bones initially rejoin at an angle and then are sculpted through a process of bone remodeling as the bone heals, mature bone being removed from one side and new bone being formed on the other to achieve the correct alignment.

To investigate the process, the Weizmann scientists allowed young mice with fractured bones to move around freely without any intervention, X-raying their bones on a daily basis. To their surprise, not only did the bones realign naturally, but this occurred within just a few days. This fast turnaround occurred while the bones were still separated, leading the scientists to believe that it is something other than the process of remodeling that brings about bone alignment.

Natural healing process of fractured bones. (A) Healing begins with a collection of blood and inflammation at the fracture site. (B) Soft callus (purple) is formed, which develops into the bidirectional growth plate at the concave side of the fracture site. (C) The growth plate drives bone growth in opposite directions. The result is a jack-like mechanical effect that moves the fragments toward straightening (red arrows). (D) New bone tissue is formed (orange). (E) The shape of the bone is fine-tuned by remodeling


Further analysis of the healing bones in the active mice revealed yet another surprise: New tissue similar to growth plates – an area at either end of growing bones from which new bone tissue is produced – had formed, but on the concave side of the fracture. The researchers observed that bone tissue is produced from both sides of the plate, acting like a “mechanical jack” to generate opposing forces that straighten the two bone fragments. Only once they are precisely realigned do the bone halves proceed with the modeling process to reunite and reshape.

Acting on previous research in Zelzer’s lab suggesting that muscle contraction may also play a role in the process, the scientists injected the mice with Botox to paralyze the muscles. They found that although the fractured bone had reunited, the halves were not aligned properly, remaining at an angle. The reason, they found, was that in the absence of muscle contraction, the new growth plate didn’t form.

The fact that this natural mechanism was found to be less effective in adults suggests that this newly discovered paradigm has helped solve the longstanding mystery of why fractures heal so much faster in the young. Rot: “In terms of evolution, a rapid and efficient fracture-healing process may be more important in the young, to ensure their ability to reproduce; while there is less ‘survival’ advantage for adults who have already passed on their genes to their offspring.”

The scientists suggest that a better understanding of spontaneous realignment in fracture healing may provide a new line of thinking – even in older children and adults – and help physicians reevaluate current bone-setting procedures.
Prof. Elazar Zelzer's research is supported by the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Irving and Dorothy Rom Charitable Trust; and the estate of David Levinson.