Hasan Wan N W, Chin Kok Y, Jolly James J, Ghafar Norzana A, Soelaiman Ima N
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.
Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, 56000 Cheras, Kuala Lumpur, Malaysia.
Endocr Metab Immune Disord Drug Targets. 2018;18(5):450-457. doi: 10.2174/1871530318666180423122409.
Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling.
This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.
Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.
Mevalonate pathway can be exploited to develop effective antiosteoporosis agents.
骨质疏松症是一种隐匿性骨骼疾病，其特征为骨量降低和骨骼微结构破坏，导致骨折风险增加。这是由于骨重塑失衡所致，即骨吸收速率大于骨形成速率。甲羟戊酸途径先前已知参与胆固醇合成，是骨重塑的重要调节途径。
本综述旨在概述甲羟戊酸途径与骨代谢之间的关系，以及通过该途径发挥治疗潜力的药物。
甲羟戊酸途径产生蛋白质异戊二烯化所必需的法尼基焦磷酸和香叶基香叶基焦磷酸。蛋白质异戊二烯化增加有利于骨吸收而非骨形成。不含氮的双膦酸盐抑制产生法尼基焦磷酸的法尼基二磷酸合酶。它们被用作骨质疏松症的一线治疗药物。他汀类药物是一类著名的降胆固醇药物，抑制甲羟戊酸途径中的限速酶3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶。已证明其可增加人体骨密度并预防骨折。生育三烯酚是一组常见于棕榈油、米糠和胭脂树豆中的维生素E。它会导致HMG-CoA还原酶降解。许多研究表明，生育三烯酚在动物研究中可预防骨质流失，但其疗效尚未在人体中得到验证。
甲羟戊酸途径可用于开发有效的抗骨质疏松药物。
