Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are crucial regulators of bone homeostasis and longitudinal bone growth. GH primarily acts through IGF-I, which is synthesized in peripheral tissues and regulated by IGF binding proteins (IGFBPs). IGF-I enhances osteoblast function and bone formation. Adult GH deficiency leads to low bone turnover, osteoporosis, and increased fracture risk, while acromegaly, characterized by high bone turnover, can cause bone loss and vertebral fractures. GH and IGF-I secretion decrease with age, contributing to osteoporosis in conditions like anorexia nervosa and glucocorticoid-induced osteoporosis. GH and IGF-I influence bone remodeling through complex interactions involving chondrocyte proliferation, hypertrophy, and differentiation. Bone remodeling is a coordinated process of resorption and formation, while bone modeling is a process of uncoupled formation and resorption. GH and IGF-I exert anabolic effects on trabecular and cortical bone, promoting periosteal bone apposition and skeletal strength. These hormones are essential for bone mass acquisition during adolescence and for maintaining skeletal architecture in adulthood. GH acts through the GHR, a transmembrane receptor that activates signaling pathways such as Janus tyrosine kinase 2/STAT and ERK1/2. IGF-I signals through the IGF-IR, a tyrosine kinase receptor, and influences osteoblast function, bone formation, and differentiation. IGF-I also regulates bone resorption by modulating RANK-L and osteoprotegerin. IGF-II, though important in skeletal development, has unclear roles in the adult skeleton. IGFBPs regulate IGF-I availability and activity, with different IGFBPs having varying affinities for IGF-I. IGFBPs can sequester IGF-I or enhance its effects depending on the context. The ternary complex of IGF-I, IGFBP-3, and the acid labile subunit (ALS) is critical for IGF-I stability and availability. ALS is essential for IGF-I storage and release, and its absence leads to reduced IGF-I levels but only mild growth impairment. In GH deficiency, bone turnover is reduced, leading to osteoporosis and increased fracture risk. Recombinant human GH (rhGH) therapy increases bone turnover and BMD over time, with effects sustained for years. However, initial declines in BMD may occur, which can be mitigated by antiresorptive drugs like bisphosphonates. GH deficiency in childhood and adulthood has distinct clinical manifestations, with childhood-onset GHD showing more severe bone loss due to earlier onset and longer disease duration. GH and IGF-I are critical for bone development and maintenance, and their dysregulation contributes to various skeletal disorders. Understanding their mechanisms is essential for developing therapeutic strategies to treat bone-related conditions in GH deficiency and otherGrowth hormone (GH) and insulin-like growth factor-I (IGF-I) are crucial regulators of bone homeostasis and longitudinal bone growth. GH primarily acts through IGF-I, which is synthesized in peripheral tissues and regulated by IGF binding proteins (IGFBPs). IGF-I enhances osteoblast function and bone formation. Adult GH deficiency leads to low bone turnover, osteoporosis, and increased fracture risk, while acromegaly, characterized by high bone turnover, can cause bone loss and vertebral fractures. GH and IGF-I secretion decrease with age, contributing to osteoporosis in conditions like anorexia nervosa and glucocorticoid-induced osteoporosis. GH and IGF-I influence bone remodeling through complex interactions involving chondrocyte proliferation, hypertrophy, and differentiation. Bone remodeling is a coordinated process of resorption and formation, while bone modeling is a process of uncoupled formation and resorption. GH and IGF-I exert anabolic effects on trabecular and cortical bone, promoting periosteal bone apposition and skeletal strength. These hormones are essential for bone mass acquisition during adolescence and for maintaining skeletal architecture in adulthood. GH acts through the GHR, a transmembrane receptor that activates signaling pathways such as Janus tyrosine kinase 2/STAT and ERK1/2. IGF-I signals through the IGF-IR, a tyrosine kinase receptor, and influences osteoblast function, bone formation, and differentiation. IGF-I also regulates bone resorption by modulating RANK-L and osteoprotegerin. IGF-II, though important in skeletal development, has unclear roles in the adult skeleton. IGFBPs regulate IGF-I availability and activity, with different IGFBPs having varying affinities for IGF-I. IGFBPs can sequester IGF-I or enhance its effects depending on the context. The ternary complex of IGF-I, IGFBP-3, and the acid labile subunit (ALS) is critical for IGF-I stability and availability. ALS is essential for IGF-I storage and release, and its absence leads to reduced IGF-I levels but only mild growth impairment. In GH deficiency, bone turnover is reduced, leading to osteoporosis and increased fracture risk. Recombinant human GH (rhGH) therapy increases bone turnover and BMD over time, with effects sustained for years. However, initial declines in BMD may occur, which can be mitigated by antiresorptive drugs like bisphosphonates. GH deficiency in childhood and adulthood has distinct clinical manifestations, with childhood-onset GHD showing more severe bone loss due to earlier onset and longer disease duration. GH and IGF-I are critical for bone development and maintenance, and their dysregulation contributes to various skeletal disorders. Understanding their mechanisms is essential for developing therapeutic strategies to treat bone-related conditions in GH deficiency and other