Mechanism of increased risk of osteoarthritis in postmenopausal women identified

Osteoarthritis (OA) is a condition that disproportionately affects postmenopausal women, and the millions of people who suffer from it can reliably say that the condition is accompanied by pain, reduced mobility, and diminished quality of life.

While it has long been known that hormonal changes associated with menopause accelerate the development and progression of OA, a better understanding of the biological mechanisms underlying this relationship is critical to developing effective treatments.

The study, led by researchers at Spaulding Rehabilitation Center, part of Mass General Brigham Health System, provides new insight into the reasons behind this gender disparity. The study was published Jan. 16 in the journal Nature Aging.

“Our findings open new ways that may represent promising new therapeutic targets,” said senior study author Fabrisia Ambrosio, PhD, director of the Center for Musculoskeletal Rehabilitation at the Sean Adams Research Institute at Spalding Rehabilitation Center. – We hope that understanding how menopause-induced changes in sex hormone levels contribute to joint degeneration will pave the way for researchers to develop new strategies to slow or prevent the progression of OA, which could lead to improved quality of life for millions of women worldwide.”

OA is characterized by the breakdown of cartilage in the joints. Cartilage is made up of two main components: the extracellular matrix (the surrounding proteins that provide structure) and chondrocytes, a permanent cell population. In OA, the health of both of these components is compromised, preventing the bones from articulating smoothly.

Aging is the biggest risk factor for developing OA, with being female greatly exacerbating this risk over time. Currently, there are no disease-modifying treatments for OA, and interventions are largely limited to symptom management.

In a new study, Spalding scientists used a mouse model of menopause to comprehensively determine the changes associated with knee OA, from the molecular level to the whole body level. The observed changes were consistent with those seen in humans: loss of cartilage quality occurred at the onset of menopause, which was consistent with clinical findings.

The researchers then applied a sophisticated computational scheme called “network medicine” to better understand how protein interactions in cartilage change in OA. They found that menopause-induced loss of estrogen and progesterone promotes extracellular matrix degradation and chondrocyte destruction, while restoring levels of these hormones to premenopausal levels protects against cartilage destruction.

The study represents the first authored paper by a team of researchers that presents novel mechanisms of OA in older women and tests potential interventions. In a commentary published last year in Nature Aging, Ambrosio and colleagues highlighted the lack of reliable animal models of menopause, which they believe greatly complicates aging research and, as a result, clinical treatment recommendations.

This study provides insight into why the long-observed sex differences in the incidence of osteoarthritis may occur. Because the scientists were able to protect cartilage tissue from breaking down in their models, they have laid the groundwork for developing effective treatments for older women.

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Published: 21.01.2025

Updated: 20.01.2025

Medical author, Medical editor:

Stepan Yuk

Medical expert:

PhD. Olexandr Voznyak