Additionally, Pinch deficiency upregulates sclerostin and RANKL expression in hypertrophic zone chondrocytes, thereby establishing a dual regulatory mechanism: coordinated suppression of osteogenesis coupled with enhanced osteolytic activity, culminating in bone mass depletion.68,84 The human monoclonal antibody Denosumab (anti-RANKL neutralizing agent) has attained therapeutic approval for managing osteoporosis and malignancy-associated skeletal pathologies, demonstrating targeted RANKL inhibition efficacy across international clinical practice settings.85 Here, TNFSF11 is linked to osteoporosis.