Dysfunctional skin and bone loss in lupus

Osteoporosis and osteopenia are conditions where bones become weak and more likely to break. People with lupus are at higher risk for these conditions due to certain disease features and steroid use. However, the broader mechanisms underlying osteopenia/osteoporosis in lupus are not fully understood. Many people with lupus are also photosensitive and have widespread skin dysfunction, including lesions and rashes. The skin, even without visible lesions, can produce inflammatory molecules called cytokines that enter the bloodstream and impact other parts of the body. Dr. Lu will test whether bone loss in lupus is due, at least in part, to photosensitive skin and a type of immune cell mainly found in the skin called Langerhans cells.

Osteoclastogenesis is the process of forming osteoclasts, which are cells that break down old bone tissue so new bone can form. This process is essential for healthy bone maintenance, but if unbalanced, can lead to bone diseases like osteoporosis. Dr. Lu , along with co-investigators Dr. Mehdi Rashighi (University of Massachusetts) and Dr. Baohong Zhao (Hospital for Special Surgery), will test whether skin from lupus patients and lupus mouse models, after ultraviolet radiation (UVR), produces molecules that promote osteoclastogenesis compared to skin from healthy individuals in humans and mice with and without UVR. Dr. Lu previously found that Langerhans cells may play a protective role in bone health. She will use mouse models to study how dysfunctional Langerhans cells may contribute to bone loss in lupus.

What this means for people with lupus:

Findings from Dr. Lu’s study could provide a new mechanism underlying osteopenia/osteoporosis in lupus and highlight the broader impact that the skin, even without lesions, has on the health of other parts of the body. This will emphasize the importance of controlling photosensitivity to protect from long-term fracture risk and improve the overall health of individuals with lupus.

Systemic lupus erythematous (SLE) patients are at higher risk for osteopenia and osteoporosis, even accounting for steroid use, and the cause of this bone loss is poorly understood. The majority of lupus patients are photosensitive, and there is widespread skin dysfunction in lupus with even non-lesional skin showing abnormalities that predispose to photosensitive responses. Here, we test the hypothesis that there is a unique skin-bone axis in lupus whereby the dysfunctional skin in lupus itself could potentially be a source of molecules that, upon reaching bone via the bloodstream, activates bone-destroying osteoclast cells, and whereby dysfunction of skin-protective immune cells called Langerhans cells contributes to a bone loss-promoting skin state. Our study will point to photosensitive skin and skin regulation as a driver of lupus bone loss, underscoring the importance of addressing photosensitivity for the long-term health of lupus patients.