OBJECTIVES: To investigate the relationships between serum leptin, soluble leptin receptor (sLR) and bone mineral density (BMD) and bone biochemical markers and to evaluate association among these factors after hormone therapy (HT) in postmenopausal Korean women. METHODS: Serum leptin, sLR, biochemical markers, osteoprotegerin (OPG) and soluble receptor activator of NF-kB ligand (sRANKL) were measured by enzyme linked immunosorbent assay in 159 postmenopausal Korean women. The BMD at the lumbar spine (LS) and femoral neck (FN) was determined by dual energy X-ray absorptiometry, and changes of these factors were also measured in 70 postmenopausal women receiving HT. RESULTS: After adjustment for age and year since menopause, body mass index (BMI) was found to be significantly correlated with leptin (r=0.42, P<0.0001), sLR (r=-0.24, P<0.005), free leptin index (FLI, r=0.47, P<0.0001) and serum OPG was also correlated with serum leptin (r=-0.24, P<0.005) or sLR (r=-0.16, P<0.05). Serum leptin levels and FLI in obese women (BMI>25 kg/m2) were significantly higher than those in women with normal weight, whereas sLR levels were lower in the former women than in the latter women. After HT, serum leptin levels (P<0.005) and FLI (P<0.05) decreased significantly and decreased serum sLR levels (P<0.05) was found only in obese women. The percent changes in BMD at FN after HT were negatively correlated with the changes of sLR after HT. CONCLUSIONS: Circulating leptin system is not associated with BMD but BMI. Leptin and FLI decrease after HT and the changes of sLR reflects changes in BMD at FN after HT.