Table I.
Summary of characteristics of several approved and experimental agents for treating osteoporosis.
| Therapeutic Agents | Mechanism of Action | |
|---|---|---|
| Antiresorptive | Osteoanabolic | |
| Estrogens [88] | ↓ osteoclastogenic cytokines ↓ RANKL ↑ OPG |
↑ OB proliferation ↓ OB apoptosis ↑ IGF and TGFβ |
| Bisphosphonates [14] | ↓ farnesyl pyrophosphate synthase ↓ OC function and life span |
- |
| SERMs [15] | ↓ OC recruitment | ↑ osteoblastogenesis ↑ TGF-β |
| Calcitonin [12] | ↓ OC proteolytic enzyme secretion | - |
| Statins [67] | ↓ HMG-CoA reductase in OCs ↓ mevalonate pathway in OCs |
↑ BMP-2 and VEGF in OBs |
| Strontium ranelate [88] | ↓ osteoclastogenesis ↑ OPG |
↑ calcium-sensing receptor stimulation ↑ osteoblastogenesis |
| Teriparatide (rhPTH 1-34) Abaloparatide (rhPTHrP) [16] | - | ↑ PTH1R signaling in OBs ↑ cAMP-PKA dependent intracellular Ca2+ IGF-1, ↑ IGF-2, TGF-β, Wnt, RUNX2 |
| Anti-TNFα MoAbs [28] | ↓ inflammatory osteoclastogenesis | ↓ sclerostin and DKK1 ↑ Wnt signaling |
| Denosumab [41] | ↓ RANKL signaling in OCs | - |
| Romosozumab [56] | ↓ RANKL production in OBs | ↓ sclerostin ↑ Wnt signaling in OBs |
| TGF-β [63] | ↓ OC function and survival | ↑ OBP recruitment ↑ extracellular matrix and ossification |
| GH [64] | - | ↑ OB differentiation and function |
| IGF-1 [64] | - | ↑ mTOR activation ↑ OB differentiation |
| rhBMP-2 [66] | - | ↑ osteoblastogenesis |
| Anti-DKK1 MoAb [68] | - | ↑ LRP6 coreceptor signaling ↑ Wnt/β-catenin pathway |
| Src tyrosynkinase inhibitors [71] | ↓ Src kinase activity ↓ OC survival and function |
↑ OB differentiation ↓ Src kinase expression |
| Tph-1 inhibitor LP533401 [74] | - | ↓ peripheral serotonin biosynthesis ↑ CREB in OBs ↑ bone formation |
| Proteasomal inhibitors [70] | ↓ NF-𝜅B signaling ↓ RANKL induced osteoclastogenesis |
- |
| SFRP1 antagonists [72] | - | ↓ SFRP1 activity ↑ Wnt signaling |
| Odanacatib [75] | ↓ cathepsin K activity in OCs | - |
| MSCs [76] | - | ↑ bone forming cell number and function |
| sncRNAs [78, 79] | - | - |
| miRNAs 20a-5p mmu-miR-17-5p |
↓ RANKL ↓ osteoclastogenesis |
- |
| mmumiR-29a-3p | - | ↓ Dkk-1 and histone deacetylase-4 ↑ β-catenin and Runx2 acetylation ↑ OB mineralization |
| hsa-miR-133a-3p hsa-miR-194-5p |
↓ OC related gene expression ↓ NF-kB pathway signaling |
- |
| Vitamins and natural products [85, 88] | ↓ ROS ↓ inflammatory bone resorption |
- |