There is hope that a single drug could simultaneously treat diabetes and osteoporosis.
Beata Lecka-Czernik, a professor in the Department of Orthopaedic Surgery with a joint appointment in the Department of Physiology and Pharmacology at the University of Toledo’s Health Science Campus, studies the connection between bone health and metabolic processes, including disorders such as diabetes.
UT’s Health Science Campus is the former Medical College of Ohio.
Last fall, Ms. Lecka-Czernik received a five-year, $3.4 million grant from the National Institute on Aging to continue her work, which is aimed at developing a single therapeutic that could both normalize glucose levels and improve the mass and quality of bone.
Osteoporosis and Type 2 diabetes are widespread diseases impacting millions of people. The National Institutes of Health estimates that 26 million Americans have Type 2 diabetes and twice that many either have or are at high risk of developing osteoporosis.
Weak bones and diabetes are often seen together, and research has shown that diabetics suffer twice as many bone fractures as individuals without diabetes, said Ms. Lecka-Czernik. Her team has partnered with scientists from the Scripps Research Institute in Florida to study the connection between bone processes and energy metabolism.
“The bone is viewed by most people as something that does not bother you unless you break it. You don’t think about it as an organ that requires a lot of attention, but it is a living tissue that consists of many, many cells,” Ms. Lecka-Czernik said.
Bones are constantly changing or remodeling with cells that both build bone and deplete bone, and that process can adversely affect bone health as we age, she said.
“You can think of it almost like a road crew,” Ms. Lecka-Czernik said. “One crew tears up the old pavement, and the next crew comes along to lay new blacktop. In normal situations, they are coupled. As we age, the destruction crew speeds up but the paving crew slows down, particularly in post-menopausal women.”
Diabetes is a complex disease that affects the way the body turns food into energy. Most food is broken down into glucose and released into the bloodstream. However people with diabetes cannot metabolize the glucose and therefore the cells in the body can be depleted, she said.
“Because of the high level of glucose in the bloodstream, you have organs that are semistarving, which leads to damages in the liver, the kidney, and the heart,” she said.
A certain class of drugs used to treat diabetes also damages bone because of the way a particular protein called PPAR gamma is activated by the drug, she added.
Ms. Lecka-Czernik and her team have studied the effects of PPAR gamma protein in treating diabetes and osteoporosis.
PPAR gamma is a protein that has been found to activate other proteins important for insulin sensitivity, which helps people with diabetes. PPAR gamma protein can also control stem cells to become new bone cells. However when the PPAR gamma protein is hyper-activated in bones, which happens during the course of certain diabetes drug treatments, the stem cells create a fatty bone marrow instead of bone, which ultimately weakens the bone.
By determining the mechanism in which PPAR gamma affects the stem cells in bone, the research team developed a new compound that has insulin sensitivity properties but does not negatively impact the bone. The findings were published in several peer review articles, said Patrick Griffin a professor in molecular medicine and director at the Scripps Research Institute who has worked closely with Ms. Lecka-Czernik in the development of the new compound.
“Once we discovered the mechanism, we tailor-made a compound to take advantage of that mechanism and then we demonstrated in several publications that the hypothesis was correct. That you still maintain the insulin sensitization, but you don’t have the weight gain and you don’t have the fatty marrow happening. That part was proven with the collaboration between Beata’s lab and my lab,” he said.
In collaboration with researchers from the Scripps Research Institute who developed a new antidiabetic compound, Ms. Lecka-Czernik’s team found that activation of PPAR gamma protein with this new drug not only fails to negatively impact the bone, it actually builds new and stronger bone, which brings the hope that one drug can fight diabetes and osteoporosis simultaneously, she said.
“If you have one pill that can take care of two pathologies which are common and often seen together, that could have a big impact for health. It could also have an economic impact, especially for the elderly, who are spending a lot of money on prescription drugs,” she said. “Thirteen years ago this was science fiction. Now it seems like a real possibility.”
The new grant money will help researchers fine-tune the mechanism of action as it relates to bone maintenance, and their findings will be published in medical journals. Drug development is a long, arduous, and expensive process and the hope is that the research will advance these findings to the clinical phase of development. Ms. Lecka-Czernik is hopeful that this type of drug compound might ultimately be used to treat a variety of other diseases, such as prostate cancer.
“You start with something small and expand the field, and we don’t know yet what new things we will discover. We are the discovery lab, and this is what is exciting,” she said.
First Published February 4, 2022, 6:56 p.m.
