The numerous signals that regulate bone remodeling originate not only from bone cells (Figure ) but also from beyond the bone microenvironment (Figure ). Systemic influences on bone remodeling are seen in multiple bone diseases. Rheumatoid arthritis, for example, is an autoimmune condition that causes joint inflammation and destruction but also increases the risk of osteoporosis twofold . This hints at immune-bone crosstalk. Furthermore, sex hormones have long been thought to control the bone remodeling process due to the link between estrogen decline and postmenopausal osteoporosis . Sex hormones also regulate the immune system .