Fluvastatin Increases Heterotopically Induced Ossicles in Mice

Abstract

1. The aim of the present study was to evaluate the influence of fluvastatin (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor) on heterotopic ossification (HO) induced by HeLa cells. 2. C57Bl/6 mice were injected with 3 x 10(6) HeLa cells into right thigh muscles. Mice in the experimental group received fluvastatin 1.2 mg/kg per day for 17 consecutive days, while mice in the control group received placebo. Intact mice served as an additional control. Seventeen days post-HeLa cell grafting, blood samples were collected to measure total serum cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol and alkaline phosphatase (AP). 3. In all animals injected with HeLa cells, the mass of mineral deposited in the induced ossicle was established after hydrolysis of soft tissues surrounding the induced ossicles. In fluvastatin-treated mice, the mass of mineral deposited in heterotopically induced ossicles was significantly increased, when compared to mice receiving placebo. This was followed by a significant decrease of TG concentration; whereas the levels of serum AP were not significantly affected. 4. These results indicate that administration of statins may affect heterotopic ossification. This may also have clinical implication, because patients predisposed to HO and receiving statins during hypocholesterolemic treatment, may be at even greater risk of HO.

Simvastatin enhances bone formation around titanium implants in rat tibiae

“…Hence, not systemic but rather topical application of statin, with bioerodible carrier such as propylene glycol alginate (29) or gelatine hydrogel (30), seems to be an appropriate strategy for osteogenesis. In fact, several studies have revealed the effectiveness of locally applied statin for osteogenesis (7–10, 29). However, before the anabolic effect of locally applied statin can be introduced to implant dentistry, further studies into the carrier are needed.…”

“…In addition, local application of statin with an absorbable collagen sponge can enhance the bone healing of surgically created bone defects (7). Several studies have elucidated the relationship between locally applied statin and osteogenesis (8–10).…”

Fluvastatin increases tyrosinase synthesis induced by UVB irradiation of B16F10 melanoma cells.

“…by increasing expression of bone morphogenetic protein-2 (BMP-2), which leads to osteoblast differentiation and bone formation [1,2]. Administration of statins may also affect heterotopic ossification [3]. BMP-2 treatment of neural crest cells increases melanogenesis by promoting the synthesis of melanin [4].…”

Titanium membrane layered between fluvastatin-loaded poly (lactic-co-glycolic) acid for guided bone regeneration

“…No typical finding of inflammation or other adverse symptoms observed in this study indicated that the dose of statin used here (2.4 mg/kg) was in the normal range for bone formation. In previous studies, the concentration of FS ranged from 1.2–3.6 mg/kg, when applied topically to successfully enhance bone metabolism in mice [ 57 , 58 ]. The systemic bioavailability of FS is low, due to the first-pass effect at the intestinal and/or hepatic level [ 59 ].…”