Current Research

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) leads the Federal research effort on osteoporosis. Scientists at universities, medical centers, and other research institutions across the U.S. who are funded by NIAMS and other NIH components are pursuing a wide range of basic and clinical studies on the disease.

Significant advances in preventing and treating osteoporosis continue to be made. Such advances are the direct result of research focused on:

• Determining the causes and consequences of bone loss at the cellular and tissue levels
• Assessing risk factors
• Developing new strategies to maintain and even enhance bone density and reduce fracture risk
• Exploring the roles of such factors as genetics, hormones, calcium, vitamin D, drugs, and exercise on bone mass.

Some key areas of osteoporosis research supported by NIAMS and its partners at NIH are described below.

Genetic Studies
Researchers are studying genes involved in bone formation as well as genes that affect bone mass and the risk of osteoporosis-related fractures. For instance, in an effort that drew together the work of many scientists, a gene that was previously unsuspected of playing any role in bone has emerged as a possible key to restoring bone in cases of osteoporosis. Studying families with unusually dense, strong bones has revealed that an abnormality in a particular gene called LRP5 is responsible for the extra bone growth. Future work will focus on understanding how LRP5 functions, with the goal of using its actions to stimulate bone growth.

Scientists also continue to identify many genes that may affect bone mass. Experiments with genetically modified mice have been particularly useful in pinpointing areas of interest for human studies. Such efforts seem likely to identify targets for the development of new osteoporosis therapies. Results may also lead to the development of simple genetic tests that can detect early in life those individuals who are at greatest risk of developing the disease, which could in turn lead to effective targeting of prevention-based treatment strategies.

Bone Cell Biology
Study of the cells that control bone remodeling also continues to yield insights on the underlying causes of osteoporosis and point to possible new therapeutic targets. For example, bone-forming osteoblasts arise from precursor cells that give rise to different tissues. Some osteoblasts develop into osteocytes, the cells that are thought to be important for the response of bone to mechanical loading such as occurs with weight-bearing exercise. The complex balance between the generation of precursor cells, their development into osteoblasts and osteocytes, and ultimately their death, determines the rate of new bone formation. NIAMS is encouraging research that addresses the control of osteoblast differentiation and the generation of genetic resources to advance this research.

Study of Osteoporotic Fractures (SOF)
SOF, which is supported by NIAMS and the National Institute on Aging (NIA), is a multicenter study that has been following more than 9,000 postmenopausal Caucasian women since 1986 and has yielded comprehensive data about multiple risk factors for osteoporosis-related fractures. This study has provided the foundation for developing ways to identify people at greatest risk for osteoporosis and fractures decades in advance, and thus has greatly aided disease-prevention efforts. SOF investigators have added African American women to the group of patients they are following, and they hope to provide unique information on risk factors for osteoporosis and fractures in older African American women.

Osteoporosis in Men
Osteoporosis in men is undergoing major scrutiny in a seven-center study funded by NIAMS in partnership with the NIA and the National Cancer Institute. The study is following some 5,700 men aged 65 years and older at the start of the study, and will determine the extent to which the risk of fracture in men is related to bone mass and structure, biochemistry, lifestyle, tendency to fall, and other factors. The study will also try to find out whether high bone mass is associated with an increased risk of prostate cancer. Such a relationship already exists between high bone mass and breast cancer, another condition that is affected by sex hormones.

Evaluating and Assessing Bone Quality
Researchers supported through a recent NIAMS initiative are exploring factors that influence bone quality, in hopes of gaining a better understanding of how properties of bone other than its mass or density affect bone strength. They are also developing new methods to assess bone quality and bone strength and predict fracture risk using technologies such as ultrasound and magnetic resonance imaging. Key goals of this initiative include improving the ability to identify individuals at risk for osteoporosisrelated fractures and providing useful markers of the effect of drug interventions to improve and facilitate the drug development process. NIAMS partnered with the American Society for Bone and Mineral Research, the French Institute of Health and Medical Research (INSERM), and the NIH National Institute of Biomedical Imaging and Bioengineering in sponsoring a scientific meeting to bring together leading scientists from around the world in order to move this critical research field forward.

Treatments for Osteoporosis
NIAMS is funding clinical studies of several combination therapies for osteoporosis, including low-dose hormone therapy plus alendronate and parathyroid hormone plus alendronate. Lower doses and combinations of drugs known to be effective may reduce the side effects and risks associated with current individual drug treatments and improve overall responsiveness to therapy. NIAMS is also supporting research examining the molecular and cellular mechanisms by which currently used osteoporosis drugs work, in the hope of advancing knowledge about their application to bone. In other studies, scientists are investigating novel approaches for preventing and treating osteoporosis. These include the cholesterol-lowering statin drugs, the hormone leptin (best known for its role in controlling obesity), and nitric oxide (a medication given to heart patients in the form of nitroglycerin), all of which were recently found to have unexpected effects on bone mass; dietary phytoestrogens (plant estrogens); and mechanical (vibrational) stimulation of bone. NIH-supported investigators are also conducting clinical studies of various treatments and preventive measures for osteoporosis from other conditions in children and adults—including osteoporosis resulting from cancer chemotherapy, depression, and glucocorticoid use—and testing therapies for osteoporosis in men.

UW-Madison Researchers Study Promising Osteoporosis Drug

Researchers Looking For Study Participants

May 31, 2007

MADISON, Wis. -- Research started at the University of Wisconsin-Madison could offer a breakthrough in the fight against osteoporosis. Current drugs can only slow the effects of osteoporosis, but a clinical trial being done at UW-Madison could bring something completely different.

A drug developed by biochemistry professor Hector Deluca, 2MD, is a Vitamin-D derivative drug that would work as a "road-patching" agent that would regenerate aging bones. The drug has been successful in rats and is now being tested in a clinical trial being run by Dr. Neil Binkley, who said the drug is at least potentially one of the most, if not the most, promising agents in the osteoporosis research pipeline.

"What we do with most of our osteoporosis medications is we slow down the jackhammer crew back down to a normal range so a normal amount of concrete can fill it in, and what we're talking about with 2MD is actually bringing in a bigger truck of concrete," Binkley said.

Katie Trachte of McFarland is one of 15 members in the UW-Madison of the clinical trial. "I thought I really need to pay attention. I'm a lot older than I want to be, and I better start doing something about it," Trachte said. "And I thought, 'Let's start here.'" Trachte's bones are only at a marginal stage of osteoporosis, but after seeing her mother and mother-in-law break hips because of the disease, she said she knows the importance of the research. If this would work, it would prevent osteoporosis, which I've seen so much in my lifetime. And I just think for women it would be wonderful," Trachte said.

Currently the phase two clinical trial is only about two months along, and Binkley said they hope to have results in about a year. Madison researchers are still looking for women to be part of the UW Health Osteoporosis Study. Post-menopausal women with borderline bone density are eligible. Those interested can contact the UW Health Osteoporosis Clinical Research Center at 608-265-6410 and ask about the 2MD study.

 

Nutritional Studies
Researchers are also continuing to explore the role of factors such as hormones, drugs, and exercise on bone mass in children and adults and to examine the influence of diet, hormones, and disease on the calcium in our bones. Recent studies have shown that although some substances, such as high levels of dietary protein, caffeine, phosphorus (which is present in soda), and sodium, can adversely affect calcium balance, their effects appear not to be important in individuals who have an adequate calcium intake.

Hope for the Future
With ongoing research, experts hope that osteoporosis will come to be considered a curable disease. Research has enhanced our knowledge about how to maintain a healthy skeleton throughout life and has led to progress in understanding the causes, prevention, diagnosis, and treatment of osteoporosis. Every research advance brings us closer to eliminating the pain and suffering caused by this disease.