Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field. Keywords: vasculitis, osteoporosis, glucococorticoids, bone, fracture risk, fractures, large vessel vasculitis, AAV Introduction Systemic vasculitides frequently present as acute inflammation of various sized blood vessels which can lead to stenosis and aneurysm of the aorta and its branches in large vessel vasculitis (LVV) or necrosis of arterioles, capillaries and venules in small vessel vasculitis (SVV). Untreated large and small vessel vasculitis can lead to rapid organ damage and consequent threat to life. Hence many conditions require strong immunosuppression most commonly with a prolonged course of high dose Glucocorticoids (GC). Long-term sequelae are frequently a result of acute and chronic inflammation, failure to suppress inflammatory activity or secondary to immunosuppression, in particular GC (1, 2). Osteoporosis and increased fracture risk are known comorbidities of prolonged and high cumulative GC doses (3, 4). It is unclear how much the disease process and the inflammation itself contribute to accelerated bone loss or if the increased fracture risk is mainly a result of the negative impact of GC on bone health and muscle strength. This narrative review will explore the mechanism for rapid bone loss and increased fracture risk in vasculitis, summarize current fracture data in various vasculitis subgroups and outline recent developments which can prevent or mitigate this issue. Mechanism of Bone Loss and Increased Fracture Risk in Vasculitis Bone undergoes continuous remodeling and restructuring to maintain its strength and function. In healthy individuals, a precisely coordinated process of bone resorption through osteoclasts SUV39H2 and bone formation by osteoblasts allows the repair of damaged bone and replacement of old bone with newly formed mineralized osteoid. Disruption of this remodeling cycle and an increase in bone resorption and/or suppression of bone forming activity leads to systemic bone loss and osteoporosis (5). The most important factors influencing bone turnover in systemic vasculitis are shown in Figure?1 and DMOG discussed in detail below. Open in a separate window Figure?1 Pathogenesis of bone loss in vasculitis; Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis specific cells and antibodies are highlighted in orange. Primed neutrophils express PR3 [proteinase 3] or MPO [myeloperoxidase] which bind ANCAs and trigger further neutrophil activation and through CD4+ T-lymphocytes stimulation further ANCA production by B-lymphocytes. Key cells and cytokines in the pathogenesis of large vessel vasculitis LVV are highlighted in gray. Dendritic cells in the adventitia trigger the inflammatory cascade by activation of T-lymphocytes, predominantly T helper 1 (Th1) and Th17 cells, and express interferon and IL17. Primed neutrophils and Th cells promote proinflammatory cytokine production (Interleukin-6 (IL6), IL1 and Tumour Necrosis DMOG Factor (TNF)-alpha) which stimulates osteoclastogenesis through increased RANKL production by stromal cells and through direct osteoclast stimulation. Inflammatory cytokines also inhibit the formation of osteoblasts by increased DKK1 and Sclerostin expression. Glucocorticoids suppress osteoblastogenesis by RUNX2 suppresion and stimulates osteoclast proliferation and longevity. BMD, bond mineral density; RANK4, receptor activator of nuclear factor kappa-B (ligand); PR3, proteinase 3; ANCA, anti-neutrophil cytoplasmic antibody; FcR, Fc gamma receptor; OC, osteoclast; TNF, tumuor DMOG necrosis factor alpha; IL, interleukin; MPO, myeloperoxidase; RUNX2, runt-related transcription factor 2; DKK1, Dickkopf WNT Signaling Pathway Inhibitor 1; CTLA 4,.