Novel therapy could reduce risk of bone fracture

For those with diabetes, hepatocyte growth factor could improve bone health

Monday, Nov 08, 2021 • Linsey Retcofsky : Contact

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From left, Kamal Awad and Venu Varanasi

Hepatocyte growth factor (HGF) could reduce the risk of bone fracture for people living with type 2 diabetes and hypertension, according to a new study from an international team of researchers at The University of Texas at Arlington and the University of Saskatchewan (USask).

The study, titled “Hepatocyte growth factor administration increases bone soluble phosphate and alters bone chemical structure in diabetic hypertensive rats,” was published in the Journal of Materials Research.

“HGF is a naturally occurring molecule that is known to regulate cell growth throughout the body,” said Kamal Awad, first author of the study and a postdoctoral research associate at the Bone Muscle Research Center at UT Arlington’s College of Nursing and Health Innovation. “It is also associated with bone regeneration, remodeling and the balance between osteoblast and osteoclast. We want to discover how HGF affects the chemical structure of the bone.”

Using an animal model, the researchers administered site-specific injections of HGF, then used the Canadian Light Source (CLS) at USask to study the bone chemical structure and changes to chemical bonding of calcium and phosphorous using XANES absorption spectroscopy technique.

The researchers found increases in soluble phosphate in the treated bones, indicating that HGF may stimulate bone into a remodeling phase in response to the effects of diabetes and hypertension and the drugs used in the treatment.

Natasha Boyes, co-author of the study and a doctoral candidate in the College of Kinesiology at USask, said remodeling is a process bones undergo throughout a person’s lifetime.

“Most people think bone should be hard, but hard bone can be very brittle” Boyes said. “What you want is bone with the right architecture. Any stimulus can cause bone to adjust its structure. For example, if you’re a runner, your bones will change and adapt to better cope with the pounding. That’s remodeling.”

Upon further investigation, the team hopes to develop a preventive therapy to reduce bone fracture risk in individuals with diabetes and hypertension.

According to the American Diabetes Association, diabetes interrupts the body’s ability to maintain vitamin D levels sufficient for calcium and phosphorus absorption and the maintenance of proper bone matrix density. Loss of bone density can lead to conditions such as osteopenia and/or osteoporosis.

The root issue of diabetes is the interrupting of proper regulation of blood glucose levels by insulin regulation in the body. This irregulation causes blood glucose levels to rise and this can harm cells associated with blood vessels in various tissues, including bone, and cause blood pressure to rise. In turn, hypertension induces prolonged and excessive inflammation that can perpetuate diabetic conditions. It is a cycle that can manifest in irregularities in calcium and phosphorous homeostasis in the bloodstream and major tissues, such as bone.

The contribution offered by this study, according to Venu Varanasi and Corey Tomczak, faculty and corresponding authors from UTA and USask, respectively, is the ability to elucidate exactly how calcium and phosphorous bonding within bone structures is affected by diabetic hypertensive conditions treated with HGF. It is the first study of its kind that has the sensitivity to identify changes in bone structure associated with this treatment of these conditions.

“Bones protect our internal organs and allow us to move; thus, maintaining healthy bones is crucial to an individual’s health,” Awad said. “Our long-term goal is to discover therapies to reduce fracture risk and speed up bone healing processes.”