New Therapeutic Approach Speeds Bone Fracture Repair

by NCN Health And Science Team Posted on December 7th, 2018

Houston, Texas, USA : For a child, recovering from a broken bone is typically a short-lived, albeit painful, convalescence. But for older adults, it can be a protracted and potentially life-threatening process.

Finding ways to speed bone repair is a public health priority that could save both lives and health care expense. The Centers for Disease Control and Prevention reports that more than 800,000 patients a year are hospitalized because of fall injuries, including broken hips, and these hospitalizations cost an average of $30,000.

“Delayed fracture healing is a major health issue in aging, and strategies to improve the pace of repair and prevent the need for additional surgeries to achieve healing substantially improve patient outcomes,” said senior author Benjamin Alman, M.D., chair of the Department of Orthopedic Surgery at Duke.

Duke Health researchers previously showed that introducing bone marrow stem cells to a bone injury can expedite healing, but the exact process was unclear.

Now, the same Duke-led team believes it has pinpointed the “youth factor” inside bone marrow stem cells—it’s the macrophage, a type of white blood cell, and the proteins it secretes that can have a rejuvenating effect on tissue. The findings are published in Nature Communications.

After tissue injury, the body dispatches macrophages to areas of trauma, where they undergo functional changes to coordinate tissue repair.

During fracture healing, macrophages are found at the fracture site. But when they’re depleted, fractures will not heal effectively. Macrophage populations and characteristics can change with aging.

“We show that young macrophage cells produce factors that lead to bone formation, and when introduced in older mice, improves fracture healing,” said Gurpreet Baht, Ph.D., assistant professor in orthopedic surgery and a lead author of the study.

“While macrophages are known to play a role in repair and regeneration, prior studies do not identify secreted factors responsible for the effect,” Alman said. “Here we show that young macrophage cells play a role in the rejuvenation process, and injection of one of the factors produced by the young cells into a fracture in old mice rejuvenates the pace of repair. This suggests a new therapeutic approach to fracture rejuvenation.”

Citation: Linda Vi et al, Macrophage cells secrete factors including LRP1 that orchestrate the rejuvenation of bone repair in mice, Nature Communications (2018). DOI: 10.1038/s41467-018-07666-0

A second study concluded that old bones can regain youthful healing power.

Old bones can regain youthful healing power

Broken bones in older people are notoriously slow to heal, but researchers at Duke Medicine have identified a potential way to speed the process.

In studies using mice, the researchers not only traced what signals go wrong when aged bones heal improperly, they also successfully manipulated the process by both circulating blood and transplanting bone marrow from a young mouse into an older mouse, prompting the bones to heal faster and better.

The findings reported in the journal Nature Communications, address one of the largest problems draining health care resources. According to the Centers for Disease Control and Prevention, fractures are the most common and costly nonfatal injuries to adults over age 65. They account for more than one-third of that population’s nonfatal injuries, and 61 percent of total nonfatal care costs.

The work builds on earlier research by the Duke-led team and others, which identified an important role for a protein called beta-catenin in the healing process. The protein requires precise modulation for successful bone fracture repair. In older people, beta-catenin levels are elevated during the early phases of bone repair, leading to the production of tissue that is more like scar than bone, which is not good for bone healing.

Using mice as a surrogate for humans, the researchers found that they could manipulate beta-catenin levels by exposing older animals to the blood circulation of younger animals, essentially correcting the intricate formula necessary for healthy bone repair.

“It’s not that bone cells can’t heal as efficiently as we age, but that they actually can heal if they are given the right cues from their environment,” said senior author Benjamin A. Alman, M.D., chair of the Department of Orthopaedic Surgery at Duke University School of Medicine. “It’s a matter of identifying the right pathway to target, and that’s what’s exciting about this work.”

The researchers replicated the findings using bone marrow cell transplantation between young and old mice, again demonstrating that young hematopoietic cells are able to recalibrate the beta-catenin signaling during early fracture repair, restoring healthy bone-healing in old mice.

Alman said the findings suggest that drug therapies might be able to decrease beta-catenin levels or modulate the inflammatory process to improve fracture repair, both in older adults and perhaps in people who have received bone implants.

“The next steps are to figure out what’s making beta-catenin go up in older adults, so that we can target that cause,” Alman said, “and to explore drugs that can be used in patients to change beta-catenin levels safely and effectively.”

Citation for second study: “Exposure to a youthful circulaton rejuvenates bone repair through modulation of β-catenin” Nature Communications.  DOI: 10.1038/ncomms8131

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