Statins and Bone Formation.

Abstract

The main therapy needed most in the bone field is an anabolic agent for the treatment of osteoporosis. Current drugs on the market, which included bisphosphonates, calcitonin, estrogen and related compounds, vitamin D analogues trabecular microarchitecture. Therefore, it would be desirable to have a satisfactory and universally and iprifalvone, are essentially bone resorption inhibitors that mainly act to stabilize bone mass. Patients with established osteoporosis have lost more than 50% of their bone mass at critical sites in the skeleton, and more over have marked disruption of acceptable drug that would stimulate new bone formation and correct this disturbance of trabecular microarchitecture characteristic of established osteoporosis. Recently inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which controls the first step in the biosynthesis of cholesterol, have been shown to stimulate bone formation in rodents both in vitro and in vivo. The effect is associated with an increased expression of the bone morphogenetic protein-2 (BMP-2) gene in bone cells. These statins drugs are widely used agents for lowering cholesterol and reducing heart attacks, however they are also known to elicit numerous pleiotropic effects including inhibition of proliferation and migration of smooth muscle cells, inhibition of tumor growth and anti-inflammatory activity. Some of these effects have been attributed to not only to the reduction of cholesterol synthesis by inhibition of the HMG-CoA reductase enzyme but also by the concurrent reduction in downstream metabolites of the mevalonate pathway such as mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate. The findings that statins are capable of increasing bone formation and bone mass in rodents suggests a potential new action for the statins, which may be beneficial in patients with established osteoporosis where marked bone loss has occurred. Recent clinical data suggests that they may reduce the risk of fracture in patients taking these drugs. However, their precise role can only be determined by appropriate randomized clinical trials, which demonstrate their efficacy in this regard in patients.

Following the mevalonate pathway to bone heal alley

“…In vivo, the effects are even more contradictory. Although there are studies which agree with the original findings of Mundy et al (Garrett et al 2001, Oxlund et al 2001, Sugiyama and Kawai 2001, Garrett and Mundy 2002, Kajinami et al 2003, Staal et al 2003, Wong and Rabie 2003, Kawane et al 2004, Stein et al 2005, Gutierrez et al 2006, Garrett et al 2007), some very conscientiously designed studies have not been able to demonstrate any such effects (Maritz et al 2001, von Stechow et al 2003, Yao et al 2006.…”

“…In vitro, the results seem reasonably clear, with most published studies pointing to an anabolic effect (Hoffman et al 1983, Mundy et al 1999, Garrett et al 2001, Llevadot et al 2001, Phillips et al 2001, Garrett and Mundy 2002, Bauer 2003, Hatano et al 2003, Staal et al 2003, Hwang et al 2004, Maeda et al 2004, Whang et al 2005, Benoit et al 2006. Furthermore, the effect on bone turnover seems to be closely correlated with the effectiveness to inhibit the mevalonate pathway, and as of yet the most probable direct mechanism seems to be an increased transcription of BMP-2.…”

Simvastatin rescues homocysteine-induced apoptosis of osteocytic MLO-Y4 cells by decreasing the expressions of NADPH oxidase 1 and 2

“…protein-2 (BMP-2) expression in osteoblasts and stimulates bone formation [10,11] as well as promotes mineralization [7,12] and suppresses apoptosis in osteoblastic MC3T3-E1 cells [13].…”

Preeclamptic cord blood hemolysis and the effect of Monascus purpureus and Saccharomyces cerevisiae in modulating preeclamptic stress

“…It is used to prepare fermented red yeast rice which is commonly consumed in many Asian countries (10,11). Other applications for M. purpureus are that lovastatin and other statin drugs produced from this yeast may be useful for treating or pre-venting osteoporosis (12,13). It contains Monacolin K, known as lovastatin, which is a commonly prescribed lipid-lowering drug that signifi cantly reduces high cholesterol.…”