If you have osteoporosis you’ve probably heard of, and may have been treated with, a class of drugs that are used to prevent and treat bone loss: bisphosphonates. Dr. Tuhina Neogi and her research team are using new methods to look at how the long-term effects of using these drugs may be related to the progression of knee osteoarthritis (OA).
Dr. Neogi’s 2-year Arthritis Foundation-funded project, “Bisphosphonate Effects in Knee Osteoarthritis,” is looking at the relationship of bisphosphonate treatment and the structural changes in the knee associated with OA progression. To do this, Dr. Neogi and her team are looking at how knee joint space width, three-dimensional (3D) bone shape, and bone marrow lesions change in OA patients over time.
Dr. Neogi is interested in this research for several reasons. First, the long-term effects of bisphosphonates on knee OA is controversial due to conflicting study results and concerns about changing bone properties over time. “Bisphosphonates are used to maintain and improve bone density by improving or rebuilding (remodeling) bone in patients with osteoporosis. It helps to reduce the risk of fractures. However, remodeling bone in patients with OA may not be the same as remodeling bone in patients with osteoporosis. Changing the bones by making them stiffer may not be good for OA. On the other hand, bisphosphonates may have beneficial effects on chondrocytes (cells in the cartilage). Thus, the benefits versus the risks are not clear.”
Dr. Neogi is also interested in looking at the data in new ways to reduce the confusion found in earlier studies with conflicting or inconclusive results. Earlier studies used only x-rays to evaluate structural changes in OA. She and her team are also using magnetic resonance imaging (MRI), focusing on bone marrow lesions that can cause pain in OA, and 3-D bone shape, which can provide a more global assessment of what is going on in the joint. “Structural changes associated with OA are traditionally assessed as joint-space width on x-rays, which lack sensitivity to change. It takes a long time for joint width changes to be detected by x-rays. MRI can provide insights into how OA is changing over much shorter periods of time, and is therefore likely a better way to assess a drug’s effects on OA.”
The team is also using data from a large United Kingdom (UK) medical database to determine if taking bisphosphates can slow the progression of knee OA and make a difference in if, or when, a knee replacement may be needed. “About 97% of knee replacements are performed because of OA and is therefore a good indicator of people who have progressed to “end-stage” knee OA,” Dr. Neogi explained. Dr. Neogi and her team began this project by analyzing the data from a UK database that included information from about 13 million patients. She explained it was important to use the UK data because patients there have universal healthcare, so no one would be excluded because they could not afford or have access to medical treatment. The team chose two sets of patient groups to compare. One group included newly diagnosed OA patients who were new users of bisphosphonates. The second group included newly diagnosed OA patients who were similar to the first set (like age, sex, weight, etc.), except they were not users of bisphosphonates. After comparing the long-term data, the team found that significantly fewer patients in the bisphosphonate treatment group went on to have knee replacement surgery than the non-users.
The team is now analyzing the data from the MRI studies using data from a nationwide research study sponsored by the National Institutes of Health that is looking at knee osteoarthritis. While the analyses are not finished, they are seeing results that are similar to the UK database results. Subjects who were taking bisphosphonate treatment had less severe structural progression.
The different approaches to looking at OA outcomes are showing results pointing in the same direction. While bisphosphonate treatment may not work for everyone and additional work needs to be done on these projects, Dr. Neogi feels that her team’s research results may support some promising long-term effects of bisphosphonates and this drug class could potentially be a therapeutic option for millions of Americans with knee OA.
Dr. Neogi is a professor of medicine at Boston University School of Medicine and a professor of epidemiology at the Boston University School of Public Health.