Researchers have developed an osteoporosis treatment that halted bone loss and promoted bone growth in a mouse model of the disease.
In a study published April 14 in Biomaterials, the researchers attached an osteoporosis drug to a bone-targeting carrier molecule to develop the novel osteoporosis therapeutic, an approach that they hope could one day be used to treat the disease in people.
Throughout life, the skeleton is constantly remodeled by bone resorption and reformation processes. When the body doesn't make enough new bone or breaks down too much, the skeleton becomes weak and brittle, a disease called osteoporosis. Worldwide, around 200 million people, particularly elderly people and post-menopausal women, are affected by this chronic bone disease.
"There are two main types of cells that help with bone remodeling. The bone-forming cells and the cells that promote bone degeneration," said the study's senior author Shyni Varghese, a professor of biomedical engineering, mechanical engineering and materials science and orthopedics at Duke University. A drug that can target both of these cell types is the best way to treat osteoporosis, she continued. "But the commonly used drugs to treat patients stop bone degeneration, but they do not promote bone formation."
In previous work, Varghese and colleagues identified adenosine, a naturally occurring molecule that binds to receptors in bone cells, as a potential treatment for osteoporosis because it influences both of these bone remodeling processes. But a major hurdle to developing this molecule as a drug is that cells throughout the body, not just in bones, have adenosine receptors.
"So if I just inject adenosine into the patient, it could go everywhere," Varghese explained. "The second challenge is that adenosine has a very short half-life, less than 10 seconds," meaning that it would be rapidly broken down in the bloodstream before it could reach the bones.
To overcome these challenges, the researchers developed a so-called nanocarrier, a drug delivery system made of several different compounds. One part of the nanocarrier temporarily binds to adenosine, releasing it upon delivery to the bones. The team also added a bone-targeting compound called alendronate, which when injected into mice, improved accumulation of nanocarriers in the spine by 45% and reduced non-target accumulation in the liver by 37% and in the kidneys by 11%, compared with a nanocarrier without this compound.
Next, the researchers evaluated the effectiveness of the nanocarrier system for treating osteoporosis in an animal model. To mimic post-menopausal osteoporosis, they removed the ovaries from 21 female mice. Starting four weeks after this surgery, the team injected mice twice per week with saline, nanocarriers with adenosine or nanocarriers without adenosine. In addition, seven mice with intact ovaries were injected with saline to serve as healthy controls.
After eight weeks of treatment, compared with healthy controls, the saline-treated mice that underwent surgery had greater bone loss, weaker bones and reduced new bone formation, indicative of osteoporosis. In mice treated with adenosine nanocarriers, these bone-health measures were much improved compared with those in animals treated with nanocarriers without this drug. For some measures of bone health, adenosine-treated mice were on par with healthy controls.
"The animals treated with the drug, adenosine, were in fact very similar to the controls, so that means we were managed to prevent the disease as well as promote bone formation," Varghese said.
In the future, the researchers hope that their approach could treat bone disease in humans.
"We need more drugs for osteoporosis," Varghese said. "Even though osteoporosis is not a life-threatening disease like heart disease or cancer, there is a lot of mortality because people who have osteoporosis can fall down and fracture their bones."
According to Varghese, the findings are proof-of-concept, and additional research showing that the therapy is safe and effective in humans would be needed to move it to clinical trials.
Because adenosine receptors are found throughout the body, it will be important to minimize non-target effects on other organs, she explained. The researchers are aiming to tweak the nanocarrier to improve its bone-targeting specificity or so that it only releases adenosine in response to bone-specific triggers.
The study, "Bone targeting nanocarrier-assisted delivery of adenosine to combat osteoporotic bone loss," published April 14 in Biomaterials, was authored by Jiaul Hoque, Yu-Ru V. Shih, Nivedita Sangaj, Neha Arjunji, Yuze Zeng, Shyni Varghese and Hunter Newman, Duke University.