CONTEXT: Adipokines have been linked to bone phenotypes recently, but with conflicting results. Few such studies have been conducted in adolescents. OBJECTIVE: The aim of the study was to examine the associations of adiponectin and leptin with multiple bone phenotypes in Chinese adolescents and estimate the genetic contribution to these associations. DESIGN AND SETTING: This was a cross-sectional study conducted in rural China. PARTICIPANTS: A total of 675 males and 575 females aged 13-21 yr were included. OUTCOME MEASURES: Fat mass (FM), lean mass (LM), bone area (BA), bone mineral content (BMC), cross-sectional area (CSA), and section modulus (SM) were measured by dual-energy x-ray absorptiometry. Plasma adipokine concentration was determined using sandwich immunoassays. RESULTS: Adiponectin was inversely associated with all BMCs in males (P < 0.01), but not in females, after adjusting for LM, body weight, or BMI singly, or for LM and FM simultaneously. No such relationships were observed for CSA or SM in both genders. Leptin was inversely associated with all BAs, total-hip BMC, CSA, and SM in both genders, when adjusting for body weight or BMI. These associations, except for whole-body BA and lumbar spine BA in females, disappeared when simultaneously adjusting for LM and FM. By Cholesky decomposition models using twin design, significant genetic correlations were detected between adiponectin and total-hip BMC in males and between leptin and total-hip BMC in both genders. CONCLUSIONS: We demonstrated that adiponectin and leptin were inversely associated with adolescent bone phenotypes but showed differential associations by gender, type of bone phenotypes, and adjustment of FM. This study also suggested that adipokines and bone phenotypes may share a common set of genes.