Parathyroid hormone treatment helps slow the progression of osteoarthritis

Cornell researchers found that pre-treatment with parathyroid hormone, commonly used to increase bone mass in osteoporosis, may help improve cartilage health and slow the progression of osteoarthritis.

The team led by Marjolein van der Meulen, Director of the School of Biomedical Engineering. James M. And Marsha McCormick at Cornell College of Engineering, has also identified gene expression signatures that could potentially be used for early detection of degenerative joint disease.

The results were published in Science Advances. Co-authors of the article are Adrien Antoinette and Sofia Zimyan.

Van der Meulen specializes in studying the role of mechanics in the skeleton and how the musculoskeletal system - bones, cartilage, joints - responds to loading, using techniques of applying weight and compression to the lower leg and knee joint.

The load has its pros and cons. It increases bone mass and can be used as a therapy for osteoporosis. At the same time, stress also damages the cartilage in the joints, similar to the degeneration seen in osteoarthritis. Van der Meulen and her laboratory are increasingly focused on the role that bone plays in the development of joint damage.

In the new study, the team followed a two-step process. They first treated the mice daily with parathyroid hormone, a drug prescribed for osteoporosis, to increase bone mass for eight weeks. In the second phase, the team applied daily stress to the mouse's tibia and used another osteoporosis treatment, alendronate, which effectively turns off the bone's ability to repair itself (remodel) for six weeks.

The figure shows the extent of cartilage damage after 6 weeks of daily loading and treatment compared to a control knee with no loading and no cartilage damage. The cartilage is colored red and the bone is bluish-green. In general, pretreatment with parathyroid hormone before exercise and treatment with alendronate during exercise showed the least cartilage damage (loss of red-stained tissue) and better cartilage preservation. Source: Science Advances (2024). DOI: 10.1126/sciadv.adk8402

Researchers found that parathyroid hormone directly improved cartilage health and slowed the progression of damage, while alendronate reduced subchondral bone changes associated with osteoarthritis.

"Even after six weeks of damage, the effect of the eight-week pre-treatment was still significant. Parathyroid hormone did more than just increase bone mass, as it turns out it also works on cartilage," van der Meulen said. "The mice's knees had thicker cartilage after eight weeks, which was unexpected. Thicker cartilage likely protects against joint damage later."

The team repeated the experiment and used transcriptomics to analyze gene expression in RNA isolated from the cartilage, bones and lymph nodes of mice. Joint damage was reflected in early transcriptomic changes, and both treatments combined resulted in early modulation of immune signaling.

"Gene expression studies showed that both drugs together had the greatest effect in reducing the expression of genes associated with cartilage damage, particularly altering the expression of immune genes," Zimyan said.

The next step is to determine whether parathyroid hormone treatment can slow or even reverse the progression of osteoarthritis once it appears and use gene signatures to develop early diagnostics for the disease.

"The findings suggest that these treatments may be useful for humans as well. And the good news is that these treatments are already approved by the FDA, although not for this use," van der Meulen said.