Epidemiological and single-cell transcriptomic studies on the effects of vitamin A and inflammation on bone health

The overall aims of this project is to understand how vitamin A and inflammatory processes affect bone mass.

Increased levels of vitamin A are considered a risk factor for secondary osteoporosis and increased fracture susceptibility. The evidence for enhanced hip fracture risk (the most severe osteoporotic fracture) is however not consistent.

We will determine to what extent vitamin A is a risk factor for hip fractures by determining the observational and causal associations between fracture risk and serum levels of retinol, β-carotene and retinol binding protein in unique cohorts with by far the largest amounts of fracture cases.

In mechanistic studies, we will investigate how vitamin A preferentially enhances bone resorption on periosteal surfaces and the role of tissue macrophages for osteoclastogenesis.

Inflammation in the vicinity of the skeleton often causes enhanced local bone loss such as in rheumatoid arthritis but is also a risk factor for secondary osteoporosis. An often unforeseen effect by inflammation is local stimulation of new bone formation.

We will use a model with local periosteal inflammation and a combination of state-of-the-art techniques, including single-cell RNA sequencing, to decipher the mechanisms by which inflammatory processes stimulate not only local osteoclast and osteoblast activation but also systemic osteoclastogenesis causing secondary osteoporosis.

The studies on inflammation may identify new osteo-anabolic drug targets.