Researchers at Spaulding Rehabilitation, a component of the Mass General Brigham healthcare system, conducted a new study that sheds light on the association between menopause and osteoarthritis (OA), a disorder that affects millions of postmenopausal women. This study, which came out on January 16 in Nature Ageing, sheds light on the molecular mechanisms that explain why OA affects postmenopausal women more than men and looks into possible treatment targets to lessen its effects. 

Osteoarthritis is a degenerative joint condition that causes cartilage tissue degradation, preventing smooth bone articulation. The two main parts of cartilage are the extracellular matrix, which gives the structure its shape, and chondrocytes, which are the cells that live in the cartilage and keep it healthy. The degeneration of these components causes joint pain, limited mobility, and a lower quality of life.

Ageing is the most important risk factor for OA, and studies have long shown that female sex considerably increases this risk, especially after menopause. "Our findings reveal novel pathways that may represent promising new therapeutic targets," explained senior study author Fabrisia Ambrosio, PhD, MPT, director of Spaulding Rehabilitation's Discovery Centre for Musculoskeletal Recovery. This study looks into how changes in hormones during menopause affect joint damage. This paves the way for new treatments that can slow or stop the progression of OA, which will improve the quality of life for millions of women around the world. 

The researchers used a mouse model of menopause to carefully examine alterations related to knee OA at the molecular-to-whole-organism levels. The study discovered that cartilage degeneration began around the outset of menopause, echoing clinical data in human patients. To further comprehend the subtle changes in cartilage, the researchers used an advanced computational framework known as 'network medicine.' 

Their research showed that the loss of oestrogen and progesterone during menopause speeds up the breakdown of extracellular matrix and chondrocytes. However, they proved that restoring these hormones to pre-menopausal levels prevents cartilage deterioration. These findings provide solid evidence that hormonal alterations have a direct role in osteoarthritis development." This study sheds light on why long-standing sex variations in osteoarthritis rates exist. "We hope that by protecting against cartilage degeneration in our models, we are laying the groundwork for developing effective treatments for older female humans," stated lead study author Gabrielle Gilmer, PhD, a graduate student researcher at Spaulding Rehabilitation. 

This study is particularly important since it not only finds new processes causing OA onset in postmenopausal women, but it also investigates potential therapies to mitigate these effects. Importantly, Ambrosio and her colleagues earlier emphasised the absence of trustworthy animal models for menopause in a Nature Ageing commentary last year. This constraint has historically hampered research into ageing-related disorders, delaying progress in therapeutic care. 

This study is a crucial step towards bridging the gap between preclinical findings and human applications because it successfully uses a menopause-specific animal model. Given the lack of disease-modifying therapies for OA, current strategies are mostly concerned with symptom management. Researchers have found hormonal mechanisms that control how quickly OA gets worse. This means that hormone-based therapies or focused pharmaceutical interventions may be useful as future treatments. 

Spaulding Rehabilitation experts' study makes a significant contribution to our understanding of the relationship between menopause and osteoarthritis. The findings emphasise the importance of oestrogen and progesterone in cartilage integrity and their potential for hormone-based therapies. As research progresses, these findings could lead to ground-breaking medicines that reduce the burden of OA in postmenopausal women, thereby enhancing their quality of life.