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Discovery of how newborn mice repair bone fractures could improve treatments

Cell Press

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IMAGE: (A-D) This image shows H&E and Safranin O/Fast Green staining of sections through the fracture site during the healing process (P3–P9). Scale bar, 2 mm. (A'-D') Magnifications of the boxed... view more

Credit: Developmental Cell, Rot et al.

If you've ever broken a bone, there's a good chance you needed surgery, braces, or splints to realign the bone. Severe fractures in infants, on the other hand, can heal on their own through a process that has eluded scientists. A study published by Cell Press on October 27 in Developmental Cell reveals that a fractured arm bone in newborn mice can rapidly realign through a previously unknown mechanism involving bone growth and muscle contraction. The findings provide new insights into how human infants and other young vertebrates may repair broken bones and pave the way for more effective treatment strategies.

"Evolution has created a robust mechanism of bone regeneration, which may explain how wild animals can survive traumatic bone injuries," says senior study author Elazar Zelzer of the Weizmann Institute of Science. "Further investigation of the newly found regeneration program could lead to alternative approaches for the treatment of fractures that do not respond well to current practices."

The bone is one of the few organs that can regenerate itself in vertebrates. Although spontaneous regeneration occurs in infants, adults require interventions to return the bone to a straight position, as well as stabilization with metallic hardware or a cast. But standard treatment protocols have several side effects, including muscle atrophy and joint stiffness. Zelzer and his team suspected that a better understanding of natural regeneration in infants could help to improve interventions for fractured bones in adults.

In the new study, the researchers found that a fractured arm bone in newborn mice rapidly realigned through substantial movement of bone fragments rather than through bone remodeling--a slower process involving the simultaneous formation of new bone on one side and erosion of existing bone on the opposite side. "This finding challenges the traditional view of fracture healing and introduces an entirely new stage of bone repair to the classical four-stage model," Zelzer says.

The realignment process was driven by bone growth, which acted like a mechanical jack to generate the opposing forces required to straighten the two bone fragments. Moreover, treatment with a drug that paralyzed the muscles surrounding the fracture prevented normal bone growth and bone realignment, suggesting that muscle contraction plays a critical role in the repair process.

"Integrating this new knowledge into the current approach may improve future treatment," Zelzer says. "For example, treatment protocols may include age-based protocols and shorter periods of rigid immobilization to allow participation of muscle force in the healing process."

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Developmental Cell, Rot et al.: "A mechanical jack-like mechanism drives spontaneous fracture healing in neonatal mice."

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