Women of a “certain age” are usually aware of osteoporosis. Many women and their physicians appreciate that with age there comes an unfortunate imbalance in that bone-making capability is exceeded by bone-losing tendency. This can lead to fractures, frailty, a dowager’s hump. However, osteoporosis strikes men as well, although at a later age. And studies suggest that men are treated for osteoporosis less frequently but may suffer more serious outcomes.

The statistics are startling: About 250,000 hip fractures occur each year in the US among adults aged 65 or older, one quarter of which are sustained by men. Within one year, 50,000 people who had one of those hip fractures will die, and fewer than half of those who survive will get up and walk again. Each year, that leaves about 100,000 survivors of hip fracture alive but significantly disabled.

Thus there is a significant opportunity to improve the health care system on several levels, including its costs, through research into the causes, treatment, and prevention of osteoporosis.

For Joy Wu, MD, PhD, Assistant Professor of Medicine (Endocrinology), osteoporosis is both a clinical focus and the target of her research. In the Stanford Osteoporosis and Metabolic Bone Diseases Clinic (stanfordhospital.org/osteoporosis), Wu and her colleagues Aimee Shu and David Karpf see patients with osteoporosis and metabolic bone disease, including bone loss associated with treatment of chronic diseases, such as asthma and cancer, and with organ transplantation.

Current therapies for patients with osteoporosis fall into two classes. The first line is antiresorptive drugs – bisphosphonates and denosumab -- which reduce fracture rates by more than 50% but may result in rare side effects, including atypical fractures. For patients taking these therapies, Wu and her colleagues have to determine the optimal length of time to treat, and then consider a “drug holiday” during which patients go off the therapy in order not to develop the side effects. Patients are then monitored for the signs of bone loss that will trigger restarting treatment.

The second line of drugs for Wu’s patients promotes bone formation. The only current drug in this class is teriparatide, or recombinant parathyroid hormone, which can significantly increase bone mass. While it carries a black box warning because of osteosarcoma in pre-clinical rodent studies, to date there has been no evidence of increased osteosarcoma in patients treated with teriparatide. Several new medications are on the horizon, so treatment options should increase for patients in the next few years.

Wu’s research is primarily in two areas. “The first is to understand how stem cells differentiate into osteoblasts – those are the cells that help your body make bone. We’re using mouse models to understand how to regulate the formation of osteoblasts because we hope that might help us develop new therapies or regenerative approaches to treating osteoporosis.

“My second area of research is about how bone regulates blood formation. Within the bone marrow, osteoblasts are very close to hematopoietic cells and it turns out that they actively communicate. It is becoming clear that osteoblasts can regulate the production of blood cells in bone marrow.

“The hope is that we can use medications that affect the bone to also have some beneficial effect on blood cells. For example, we did a clinical trial where we gave teriparatide to women with osteoporosis and we found that the number of hematopoietic stem cells increased in the blood. This tells us that a bone medication could have impact on blood production, and gives us a new approach to think about treating some blood disorders.”

There is clearly much work to be done in this area of research. Joy Wu is enthusiastic about the possibilities.