UCLA Researchers in the Department of Dentistry have discovered that a novel drug combination results in a synergistic therapeutic effect for osteoporosis treatment.
BACKGROUND:
It is estimated that 10 million men and women in the U.S. suffer from osteoporosis; a metabolic bone disease that is characterized by low bone density and deterioration of the architecture of bone that increases the risk of fracture. Often labeled as a silent disease, osteoporosis manifests in the form of fracture, and increases in incidence as a function of age. While it was initially believed that the extended lack of calcium contributed to the development of osteoporosis, recent evidence suggests that bodily defenses like adipocytes in bone marrow may be impaired. Marrow adipocytes that reside in the bone marrow, normally secrete adipokines, that influence the remodeling of bone and promote resorption. However, under osteoporosis there is an inverse relationship to bone marrow adiposity and bone mass, that researchers believe may influence adipocyte deficiency. In the past few decades, there have been many pharmacologic advancements for osteoporosis, resulting in treatments like the use of bisphosphonates and estrogen receptor modulators. Unfortunately, these therapeutic options do not treat the underlying cause of osteoporosis, which either requires extended therapy or changes to the therapy used. It is therefore imperative that the new class of drugs targeted at osteoporosis, address the underlying mechanisms that promote osteoporosis.
INNOVATION:
UCLA researchers have designed a new small molecule drug combination for osteoporosis: that seeks to influence the inverse relationship between bone mass and marrow adiposity. Researchers found that the combination of two known small molecules synergistically promoted osteogenic differentiation and inhibited adipogenic differentiation of bone marrow mesenchymal stem/stromal cells in vitro. Importantly, using three different models of skeletal aging and osteoporosis, researchers found: 1) The combination of two known small molecules synergistically reduces acute osteoporosis induced by ovariectomy and inhibits obesity; 2) The combination of two known small molecules synergistically prevents bone loss induced by high-fat diets; and 3) The combination of two known small molecules synergistically prevents bone aging and osteoporosis in aging mice. This drug combination addresses current hurdles in the osteoporosis disease and will have broad therapeutic applications.
POTENTIAL APPLICATIONS:
• Osteoporosis
• Preventing bone loss and bone aging
ADVANTAGES:
• Combination therapy
• Intravenous delivery
DEVELOPMENT-TO-DATE: The prototype has been prepared and successfully demonstrated.