4. Discussion
bone loss, degenerative diseases, osteopenia, osteoporosis, osteoporosis/osteopenia, osteomalacia
BONE LOSS, PROLIFERATION, ADVERSE EFFECTS, OSTEOPENIA, OSTEOPOROSIS, POSTMENOPAUSAL OSTEOPOROSIS, OSTEOMALACIA
This study included pre-clinical studies using in vitro and in vivo models of postmenopausal osteoporosis, as well as clinical trials to confirm the positive effects of Osteo-F, a newly developed herbal formulation on osteoporosis/osteopenia based on the in silico prediction of the pharmacological effects and potential target pathway of Osteo-F on osteoporosis, with objectives for the experimental design and development of osteoporotic drugs with specific target profiles. We began with a computer-assisted network pharmacology analysis, which represents the virtual potential mechanism of a drug, with the objective of designing and developing osteoporotic drugs with specific target profiles [From those predicted results, we designed pre-clinical experiments to confirm the bone-forming property, thus providing convincing evidence for a clinical trial suitable for the amelioration of osteoporosis by the Osteo-F herbal formulation. One of the most important and widely used markers for osteoporosis is the level of BMD [It is regarded positively, given the fact that the current therapeutic treatments for osteoporosis have focused on anti-resorptive drugs targeting the inhibition of osteoclasts maturation, proliferation, and activity for decades [In postmenopausal women, degenerative diseases such as osteoporosis and osteomalacia naturally progress with age, and bone density tends to continuously decrease [Overall, the efficacy of Osteo-F as a treatment for osteoporosis has been proven through reliable data from osteopenia patients. In accordance with those results, the osteoanabolic mechanism of Osteo-F against osteoporosis was further authenticated. Various osteogenic-associated genes and molecules are responsible for the transcriptional mediator for the differentiation and maturation of osteoblasts. BSP-1 and OPN, bone-specific matrix genes, are considered key markers for producing the bone matrix [In a clinical trial to confirm the results of our pre-clinical study, supplementation with Osteo-F for 24 weeks resulted in a significant increase in the serum osteocalcin levels in postmenopausal women compared to the placebo. Osteocalcin, an osteogenic marker, helps predict the rate of bone loss and is used as an indicator of the rate of bone remodeling. Similar to our study, Filip et al. [Considering these observations, it is concluded that there is a coordinated regulation of bone growth by Osteo-F, which is consistent with the predicted result from the network pharmacology analysis. A randomized, double-blind, placebo-controlled clinical trial showed that Osteo-F has anabolic effects on osteoporosis. Administration of Osteo-F for 24 weeks induced increases in the Z-score of the lumbar spine and T-score of the total femur with no adverse effects. Serum OCN, PTH, and PTH/Ca ratios were significantly increased and decreased, respectively, in the Osteo-F group compared to the placebo group. The anabolic properties of Osteo-F were confirmed in differentiated osteoblast cells, revealing that Osteo-F markedly execrated the formation of the extracellular matrix with an increase of Ca nodules. Osteogenic genes and proteins at the early and late stages, including COL (