There are new treatments being investigated for the management of osteoporosis. All show promise, but most still lack definitive data from phase III trials.
There are new treatments currently being investigated for the management of osteoporosis. All show promise, but most still lack definitive data from phase III trials for both safety and efficacy.
Bone remodeling is a process resulting from bone resorption carried out by osteoclasts coordinated with bone formation carried out by osteoblasts, Ernesto Canalis, MD, Professor of Medicine at the University of Connecticut School of Medicine and director of research at St. Francis Hospital and Medical Center, Hartford, CT, said at the American Association of Clinical Endocrinologists 19th Annual Meeting and Clinical Congress here.
In the menopause, bone remodeling is increased and agents that suppress bone resorption can stabilize bone mass. In contrast, he told delegates, agents that target the osteoblast can increase bone formation and bone mass.
Bisphosphonates are commonly used to decrease bone resorption, stabilize bone structure and reduce the risk of osteoporotic fractures. But there are new anti-resorptives being developed to target the formation, or the activity, of the osteoclasts.
The most promising is denosumab, an antibody to receptor activated nuclear factor kappa B with a mechanism of action that is quite different to that of the bisphosphonates. “It is given subcutaneously twice a year, which makes it quite appealing, and the fracture data are quite compelling,” Canalis said.
There are also new selective estrogen receptor modulators (SERMs), such as bazedoxifene, which has the best chance of coming to market. However, it and the other new SERMS seem to be quite comparable to raloxifen, which has been on the market for several years.
“In a young population of women with bone loss, SERMS do have appeal because they also can prevent invasive carcinoma of the breast,” he said.
Down the line we may see Cathepsin K inhibitors, such as odanacatib and Src kinase inhibitors are in the early phases of development.
“But if you want to gain bone mass, what you need to look for is an anabolic agent,” said Dr. Canalis. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis.
Novel approaches to anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists.
The ones that are currently the most appealing are antibodies that block inhibitors of Wnt signaling.
“Recent discoveries have demonstrated that the Wnt/Beta-catenin signaling pathway plays a central role in osteoblastic cell differentiation. Anabolic approaches being developed include the use of neutralizing antibodies to Wnt antagonists, such as sclerostin,” Canalis said.
Anabolic therapies have the potential to enhance bone mass, but their safety depends on their activity being targeted specifically to the skeleton to avoid unwanted non-skeletal effects.
“When you open Wnt, there is a concern about osteosarcoma. This has not occurred in people who have high bone mass syndrome and it may never occur with this approach, but it is something that we need to watch for,” Canalis noted.