Osteoporosis (OP) is a systemic skeletal disease characterized by low bone mineral density and deterioration of bone architecture, resulting in bone strength reduction and increased fracture susceptibility. Estrogen deficiency in post-menopausal women is possibly responsible for the instability between bone formation and resorption, which is managed by specific osteoclastogenic cytokines that may be leading to resorption. This study aims to estimation of the concentrations of interleukins −8, −17, −22, beside to certain parameters in blood serum and explained their roles in the development of osteoporosis pathogenicity in postmenopausal women. Materials and Methods A case-control study included 108 Iraqi postmenopausal women participants their ages ranged between 45 and 70 years. All participants subjected to the DEXA scan, 58 samples were osteoporotic patients, whereas 50 were healthy controls. Blood samples collected from all participants in order to assess the levels of interleukins −8, −17, −22, CBC, CRP, RF, and ACPA. Results The concentrations of IL-8, −17, −22, ESR, PLT, CRP, RF and ACPA exhibited a positive correlation with OP development. Conversely, WBC and HGB concentrations showed a negative association with osteoporosis. Conclusion A remarkable relationship was obtained between the values of IL-8, 17, −22, CRP, RF, ACPA, ESR, PLT and osteoporosis but in contrary with WBCs and HGB. IL-8, −17, and − 22 can be linked to specific inflammatory diseases associated with the postmenopausal period, may act as one of the main biomarkers for osteoporosis due to their ability to stimulate osteoclastogenesis and bone resorption, and may be considered potential prognostic factors for osteoporosis.