Table 2.
Potential agents for the treatment of osteoporosis targeting lipid metabolism disorders.
| Agents | Effects | Mechanism | References |
|---|---|---|---|
| Statins | Lower plasma cholesterol levels, especially low-density lipoprotein cholesterol; promote bone anabolism and decrease bone resorption | Inhibit the activity of HMGCR; regulate the sterol regulatory element binding protein-2 pathway; up-regulate bone morphogenetic protein-2 and protect osteoblasts from apoptosis; reduce RANKL/OPG ratio and inhibit osteoclast differentiation | 90,92,93 |
| Metformin | Regulate blood sugar and lipid; restore damaged bone structure and bone density | Up-regulate expression of osteogenic marker genes; decrease OPG/RANKL ratio and inhibit osteoclast differentiation | 94, 95, 96 |
| Vitamin C/E, PCSK9 inhibitors | Reduce the production of oxidized lipids; slow down atherosclerosis | Neutralize free radicals and remove hydroxyl free radicals; scavenge lipid peroxidation free radicals; reduce tissue oxidative damage | 98,99 |
| PCSK9 inhibitors | Lower plasma lipid level and reduce the intake of exogenous lipids by bone cells | Inhibit PCSK9 expression/function; increase LDLR expression in liver | 101,102 |
| Saroglitazar | Lose weight; improve alanine aminotransferase level in nonalcoholic fatty liver disease; improve blood glucose and lipid parameters in atherosclerosis | Activate the PPARγ signaling | 103,104 |
| LT175 | Lose weight; lower the levels of blood sugar, cholesterol, insulin, and triglycerides | Interact with a new recognition region of PPARγ | 105 |
| Bisphenol A diglycidyl ether | Enhance osteogenesis and inhibit fat formation | Inhibit the PPARγ signaling in mesenchymal stem cells | 106 |
| SR1664 | Enhance osteogenesis and inhibit fat formation | Block obesity-induced phosphorylation of S273; inhibit the PPARγ pathway | 107 |
Notes: HMGCR, HMG-CoA reductase; RANKL, receptor activator of nuclear factor-kappa B ligand; PCSK9, pro-protein convertase subtilisin/kexin 9; LDLR, Low-density lipoprotein receptor; OPG, osteoprotegerin; PPARγ, peroxisome proliferator-activated receptor gamma.