Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders

Table 1 Comparative literature analysis of the receptor activator of NF-kappaB/receptor activator of NF-kappaB ligand/osteoprotegerin axis

Ref.	Focus	Limitations	Contribution to present review
Boyce and Xing[26]	Overview of RANK/RANKL/OPG pathway in bone biology	Primarily mechanistic focus with limited discussion of clinical biomarker applications	Extends molecular insights to clinical biomarker relevance across diseases
Khosla[31]	Role of RANKL/OPG in osteoporosis pathophysiology	Focused on osteoporosis with limited multi-disease perspective and no discussion on circulating biomarkers	Provides multi-disease perspective and emphasizes circulating biomarker utility
Di Cicco et al[32]	Role of RANK/RANKL/OPG signaling in osteoarthritis and targeted therapies	Disease-specific focus with limited emphasis on circulating biomarkers and methodological variability	Expands to multi-disease biomarker applications and includes methodological considerations
Present review	Integrated molecular, clinical, and biomarker-focused approach		Combines molecular mechanisms, biomarker evaluation, methodological considerations, and clinical applicability

RANKL: Receptor activator of NF-kappaB ligand; RANK: Receptor activator of NF-kappaB; OPG: Osteoprotegerin.