TNFRSF11B and osteoporosis: Alteration of the RANK/RANKL/OPG system for increased osteoclastic activity and enhanced osteoblastic dysfunction is proposed as an important mechanism in the etiology of osteoporosis in BTM.[14,16] Hypogonadism, a common finding in BTM, is associated with enhanced RANKL activity.[17] The sex steroid hormones, androgen, and estrogens, via their respective nuclear receptors, regulate BMD in humans and mice.