Osteoporosis (OP) is a systemic skeletal disorder that is characterized by reduced bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. The most frequent osteoporotic fractures are fractures of the hip, wrist, and spine. The exact causes of OP are still unknown; several factors contribute to the disorder. Subjects and Methods: This study consists of patient groups, this group (Group A) was composed of 80 postmenopausal women with OP and osteopenia and the patient group was subdivided into two group; First group (GroupA1) was composed of 50 postmenopausal women with OP and the second group (Group A2) composed of (30) Postmenopausal Women with osteopenia. In addition, to control group (20), 5 mL of venous blood sample were collected from each patient and healthy control in the population study, and the blood sample was transferred to a clean gel tube, left at room temperature for at least 30 minutes for clotting, then centrifuged for 5–10 minutes at 3000 rpm. Then, separated and divided into aliquots to obtain the serum, then its kept frozen at -20°C until analysis. The obtained serum was used to measure IL17A, FGF21, CXC12, calcium, and alkaline Phosphatase (ALP). Measurement of IL17A, FGF21 and CXC12 levels were performed by ELISA. The total calcium and serum ALK were measured by spectrophotometric-based method. Results: Serum levels of IL17A, FGF21 and CXC12 are significantly increased in Group A and subgroup (A1 and A2). Serum levels of total calcium and ALP are non-significant in Group A and sub group patients. Significant negative correlation between serum levels of IL17A and T score, FGF21 and T score, CXC12 and T score, IL 17A and Z score, IL17A and Calcium. Conclusions: Serum levels of IL17A, FGF21 and CXC12 is significantly increased in Group A and subgroup patients. Serum levels of total calcium and ALP are non-significant in Group A and sub group patients. Significant negative correlation exists between serum levels of IL17A and T score, FGF21 and T score, CXC12 and T score in Groups A and A1.