Aims: To identify variables having a critical role in prostate cancer patients experiencing osteometastasis.
Background: Prostatic carcinoma is a multifactorial complex disorder that exhibits an increased propensity to
develop bone metastasis. An interplay of inflammatory and bone remodeling parameters promotes the formation
of pre-metastatic niches in bones of patients, which could render them more vulnerable to skeletal disabilities.
Objective: To evaluate the multi-dynamic inter-relationship of circulating variables in prostate cancer patients
Materials and Methods: Fifty-seven (n=57) men with clinically confirmed prostate cancer, fifty-nine (n=59)
with skeletal metastases, and one hundred (n=100) healthy subjects i.e., men aging from 53-84 years with no
clinical evidence of prostate were recruited from the Jinnah Hospital Lahore, Pakistan. Informed consent was
obtained, and a venous blood sample was drawn and stored at -70oC until assayed. Levels of variables were
evaluated using appropriate methods. Levels of Matrix Metalloproteinases (MMPs), Osteopontin (OPN), TGH-
β, and sRANKL were estimated by the ELISA method. Each sample was suspended and the given protocol was
employed. ELISA readings were obtained for the estimation of all variables.
Results: Highly significant (P˂0.05) differential expression of oxidative stress, inflammatory cytokines, and
bone remodeling variables were observed in localized and osteo-metastatic CA prostate patients. A strong positive
correlation was revealed among OPN, sRANKL, MMP-7, MMP-9, PSA, and TGF-β (OPN vs. MMP-7,
r=0.698* and OPN vs. MMP-9, r=0.765**, OPN vs. RANKL, =0.856*, sRANKL vs. MMP-9, r=0.825**, TGF-
β vs. RANKL, r=0.868* and PSA vs. TGF- β, r=0.752*); lower levels of OPG were estimated in metastasized
patients, showing that both osteolytic and osteoblastic phases of bone remodeling occur simultaneously.
Conclusion: The altered oxidative and inflammatory responses endorse Matrix Metalloproteinases (MMPs)
increased activity, RANKL/OPG imbalance, and enhanced bone matrix proteins turnover, which can foster the
process of osteo-metastasis. The perturbed RANKL/OPG drift and enhanced PSA levels are associated with
increased TGF-β activity to aggravate Epithelial Mesenchymal transition (EM) and osteo-tropism of prostate cancer.
Thus, designing novel targets of these major variables can minimize the incidence of prostate cancer patients.