The webinar “Exploring the interface between inflammatory and glucocorticoid induced bone loss”, given by Rowan Hardy, Lecturer at the University of Birmingham, UK, highlights recent advances in the understanding of both inflammation mediated bone loss and the impact of glucocorticoids on bone metabolism. Dr Hardy outlines the effects of glucocorticoid induced suppression of systemic inflammation so called “inflammatory osteoporosis” on bone and the antianabolic effects of therapeutic glucocorticoids. A deep dive into glucocorticoid metabolism explores the role of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1).
11β-HSD1 activates endogenous glucocorticoids (GC) and amplifies glucocorticoid action on a cellular level. When using animal models, 11β-HSD1 knockout mice were protected from corticosterone induced trabecular bone loss preserving trabecular thickness and trabecular number hence these mice seemed to be resistant to glucocorticoid induced osteoporosis. It was highlighted that 11 beta-HSD1-inhibitors have been investigated in diseases such as hypertension, Alzheimer disease, and Cushing’s syndrome, but the question remains open whether these inhibitors could help in reducing glucocorticoid mediated deleterious effects on bone health. Dr Hardy and team eventually examined the anti-inflammatory properties of oral administration of corticosterone in animal models of polyarthritis with global, myeloid and mesenchymal targeted transgenic deletion of 11β-HSD1. Interestingly, global deletion of 11β-HSD1 resulted in a profound glucocorticoid resistance in mice receiving corticosterone, which led to ongoing persistent synovitis and joint destruction. These effects however were not found in mesenchymal 11β-HSD1 deletion due to paracrine glucocorticoid signalling between cell populations. The concept of peripheral reactivation of GC and amplification of GC action by 11β-HSD1 at sites of inflammation introduce a new concept of therapeutic GC action and enhance our knowledge on the anti-inflammatory therapeutic effects of GC.
The webinar was followed by a vivid discussion on topics such as timing and dose dependent effects of GC on bone turnover in inflammatory arthritis, the potential extraskeletal effects of 11β-HSD1 deletion and the choice of inflammatory arthritis mouse models. Finally, the discussions and questions were continued in the online coffee shop session which allows ECTS members to share ideas and to network on topics which are of mutual interest.