Postmenopausal women having low bone mineral density have been considered to have experienced severe loss of bone in postmenopausal period.With highly advanced accurate non invasive bone mass measurements, early diagnosis of postmenopausal osteoporosis have become accurate easy and rapid.Bone mineral density (BMD) measurements were able to identify patients at risk of fracture.Biochemical markers of bone turnover such as serum bone alkaline phosphatase and serum osteocalcin (markers of bone formation), urinary deoxypyridinoline and urinary NTX (markers of bone resorption) are considered now a very important decisive diagnostic tools in diagnosis of osteoporosis.This study was designed to determine the correlation between plasma leptin and serum estrone in obese postmenopausal osteoporotic women before and six months after treatment with different therapeutic modalities in comparison with healthy premenopausal controls.Ninety postmenopausal osteoporotic women participated in thecurrent study.From each subject a blood and urine samples were assayed for biochemical markers of bone formation (serum alkaline phosphatase and serum osteocalcin) and bone resorption markers (urinary dexoypridinoline and urinary N-terminal type I collagen telopeptide, NTX) in addition to serum leptin and serum estrone levels at the baseline visit (before treatment) and 6 months after the initiation of treatment.All patients had a lumbar spine bone mineral densities determined by DEXA before and six months after treatment.For healthy perimenopausal women (controls). We verified that LS-BMD was more than two standard deviation (normal).Post menopausal osteoporotic women were randomly allocated to one of five treatment modalities.I-Hormone replacement therapy in the form of Estraderm TTS 50 applied twice/weeklyII-Alendronate (Bisphosphonate) treatment 10mg/day)III-Calcitonin (Nasal spray) 2001U/day.IV-Alpha calcidol (one alpha) 0.25ug/dayV-Combined HRT and alendronate therapy given to patients complaining from severe bone pain or from hip or spine fracture with disability.For each group of therapy LS-BMD as well as all biochemical markers of bone turnover were plotted in tables and figures showing the serum and urine levels of each markers together with the correlation between each other in addition to the T-scores and coupling index of all studied markers in relation to every kind of treatment. The current study showed that hormone replacement therapy remains the first choice "golden standard" for prevention of bone loss in early postmenopausal women with low bone density specially in the those with severe estradiol deficiency.All biochemical markers of bone turnover were decreased after different treatment modalities mainly with the combined therapy (HRT and alendronate) where serum alkaline phosphatase and osteocalcin decreased by 48% and 59% respectively while deoxypridinoline and NTX decreased by 42% and 61% respectively.For serum estrone levels, they were significantly increased by 50% after combined hormone replacement therapy and alendornate for 6 months and by 81% after hormone replacement therapy alone.The coupling index was maximal with combined therapy followed by an ascending orders of alendronate, alphacalcidol, HRT and calcitonin.No significant correlation was found between serum leptin and all biochemical markers nor bone turnover and mineral density in osteoporotic postmenopausal women in this study.