A targeted healing agent for bones that won’t mend
Thursday, February 15, 2018
The human body contains 206 bones vulnerable to fractures of all kinds, and the average person has two fractures in a lifetime.
Broken bones are among the most common orthopedic problems. Fractures account for 16 percent of all musculoskeletal injuries in the United States annually. If not treated properly, serious fractures can have dangerous complications, such as damage to blood vessels or nerves and infection of the bone or surrounding tissue.
Whether a bone has been cut as part of a surgical procedure or fractured through an injury, all broken bones go through the same healing process. And this healing process depends on several factors — the type of break, patient age and diet, and how well the affected area is vascularized. The process takes six to 12 weeks to heal to a significant degree.
However, there is always the possibility that the fracture won't heal properly or quickly. Failure of bone fracture healing occurs in 5 percent to 10 percent of all patients. And researchers are working on a new technique to solve this problem.
Currently, surgeons can choose from a variety of treatment options to enhance bone growth, such as continued immobilization for a longer period, bone stimulation, surgery with bone grafting or the use of bone-growth proteins.
One restorative tactic, known as bone morphogenetic proteins (BMPs), is not likely to work well. Designed to promote spinal fusion and bone repair more than a decade ago, these protein molecules can overperform, causing excessive or misdirected bone growth.
And newer therapies have not been developed because it is assumed that bones heal without a problem. However, fracture nonunion may be increasing as more patients survive serious fractures.
Whether a genetic component may play a role in bones that don't heal is not fully known. What is known is that bone healing problems occur more frequently in:
- those with metabolic syndrome, such as diabetes
- the elderly, who are prone to bone injuries because of low bone density
- those suffering severe trauma
Because of the huge number of fractures that don't heal well each year, Kurt Hankenson, D.V.M., Ph.D., a professor of orthopedic surgery at Michigan Medicine, and a team of scientists from other institutions are examining a new therapeutic approach. They delivered additional Jagged-1, a potent osteoinductive protein known to activate the Notch signaling pathway that regulates bone healing, at the spot of a bone injury to enhance healing.
The results showed that rodents that received Jagged-1, applied via wet collagen sponge, realized improvements to skull and femoral bone injuries. Rodents treated with BMPs also benefited but developed the same problematic bone hypertrophy associated with human use of those proteins.
Hankenson and other researchers have been studying the capacity of the Jagged-1 ligand to promote bone-forming cells for years, claiming that the signaling is unique. This ligand typically binds to a delivery cell to activate bone healing in an adjacent cell, which helps ensure that a supplemental Jagged-1 dose, administered at the spot of injury, stays in place to carry out its intended function. Therefore, bone will only form where bone is supposed to form.
On the other hand, BMPs are soluble and can migrate from the site of delivery and settle elsewhere in the body, triggering other cells that aren't supposed to form bone.
Because the body produces Jagged-1 on its own, this potential new therapy would require a synthetic version of the ligand to be produced and administered to a patient. In future experiments, it will be important to define the mechanistic basis of this improved healing.
- Best exercises for gluteus medius strengthening
- Pectoralis minor: Far from a minor problem
- The importance of hip internal rotation
- Millions of high school students set for success: Celebrating Career and Technical Education Month
- The top 5 exercises you should be doing
- The Social Security shell game
- The addictive eye drops that kill
- Drug use rises among US workers amidst the pandemic
- Revenge travel: Making up for lost time, but at what cost?
- 7 ways to balance your work-from-home routine
- What to do when you notice your team ‘quiet quitting’
- Oklahoma City’s First Americans Museum: A celebration of native culture
See your work in future editions
Your content, Your Expertise,
Your Industry Needs YOUR Expert Voice & We've got the platform you needFind Out How