NPY and osteoporosis: The role of leptin in osteoporosis depends on the balance between its direct and indirect skeletal effects.80 Leptin inhibits bone formation through centrally mediated pathways while directly promoting osteogenesis through peripheral mechanisms.94–96 Alterations in leptin signaling exert differential effects on axial bones, appendicular bones, cortical bone, and trabecular bone, with leptin primarily associated with bone remodeling in OVX rats exhibiting bone loss.78 Within this central regulatory pathway, NPY acts as a key downstream effector.