Osteoporosis statins

Statins lower plasma cholesterol levels by inhibiting HMG-CoA reductase in the mevalonate pathway (Fig. 4). Some research has shown that certain statins (but not all) stimulate BMP-2 expression in osteoblasts, increase bone formation and mimic N-BP in that they inhibit bone resorption. The use of statins in osteoporosis is presently being investigated. 

Interest in the role of HMG-CoA reductase inhibitors (statins) in the treatment of osteoporosis came from boneforming properties seen in animal studies. However, controlled clinical trials are needed. 

There has also been considerable interest in the use of statins in other clinical indications, including cancer [75], neurological disorders [76], osteoporosis [77], atrial fibrillation [78], asthma [79], angiogenesis [80], immunomodulatory effects [81], coagulation and thrombosis [82,83]. Whether these effects can all be attributed to the cholesterol-lowering activity or are a consequence of depletion of other isoprenoid species remains to be determined. 

PUFAs are potent inhibitors of the HMG-CoA reductase enzyme and similar to statins are useful in the treatment of hyperlipidemias (99-102). Statins enhance plasma AA levels and decrease the ratio of EPA to AA significantly (100). This finding suggests that PUFAs mediate many actions of statins (103) and that this could be one mechanism by which they lower cholesterol levels. Statins and PUFAs have many overlap actions such as the inhibition of IL-6 and TNF-a production and NF-kB activation plus the ability to enhance eNO production thus, both possess anti-inflammatory actions and both are useful in atherosclerosis, coronary heart disease, osteoporosis, stroke, Alzheimer s disease, and inflammatory conditions such as lupus and cancer (3, 4, 94, 104-121). These similar and overlap actions strongly indicate that the molecular mechanisms of actions of statins and PUFAs are similar, if not identical. Furthermore, when a combination of statins and PUFAs are given together, a synergistic beneficial effect was seen in patients with combined hyperlipemia (122). 

Gonyeau M. Statins and osteoporosis a clinical review. Pharmacotherapy 2005 25 229-243. 

Many of the enzymes in the sterol biosynthesis pathway have selective-inhibitors (Fig. 3). These include some extremely important classes of drugs such as Statins , used to treat high cholesterol, bisphosphonates, used to treat osteoporosis, allylamines (e.g., terbinafine) and azoles used to treat fungal infections, and morpholines which are used as fungicidal agrochemicals. 

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