Oral statins and increased bone-mineral density in postmenopausal women

Edwards, CJ; Dj, Hart; Spector, TD

doi:10.1016/s0140-6736(00)02408-9

Cited by 301 publications

(169 citation statements)

References 4 publications

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“…In vitro and in vivo studies in rodents (Mundy et al, 1999;Grasser et al, 2003;Luegmayr et al, 2004) and epi-demiological studies (Bauer, 2003) have found that statins, inhibitors of HMG-CoA reductase, increase bone density especially in postmenopausal women (Edwards et al, 2000). While these studies are difficult to interpret in detail because of complexity and confounding factors inherent in epidemiological studies, our analysis suggests that cholesterol levels regulate osteoclastogenesis at multiple levels.…”

Section: Role Of Cholesterol In Osteoclast Developmentmentioning

confidence: 68%

Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions

Kiesel

Miller

Abu‐Amer

et al. 2007

Developmental Dynamics

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Section: Role Of Cholesterol In Osteoclast Developmentmentioning

confidence: 68%

Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions

Kiesel

Miller

Abu‐Amer

et al. 2007

Developmental Dynamics

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“…This has been well-documented for polymers and copolymers of lactic and glycolic acid (Bergsma et al, 1993;Agrawal, et al, 1995;Suganuma and Alexander, 1993;Daniels et al, 1992;Daniels et al, 1994;Edwards et al, 2000;Meir et al, 2000). When biodegradable materials are implanted, however, the concentration of toxic byproducts is reduced via dilution in extracellular fluids and blood and by clearance via the circulatory and lymphatic systems.…”

Section: Discussionmentioning

confidence: 95%

Bioerodible devices for intermittent release of simvastatin acid

Jeon

Thomas

Puleo

2007

International Journal of Pharmaceutics

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The association polymer system of cellulose acetate phthalate (CAP) and Pluronic F-127 (PF-127) was used to create intermittent release devices for mimicking the daily injection of simvastatin that has been reported to stimulate bone formation. To enhance solubility in water, prodrug simvastatin was modified by lactone ring opening, which converts the molecule to its hydroxyacid form. CAP/ PF-127 microspheres incorporating simvastatin acid were prepared by a water-acetone-oil-water (W/ A/O/W) triple emulsion process. Devices were then fabricated by pressure-sintering UV-treated blank and drug-loaded microspheres. Using a multilayered fabrication approach, pulsatile release profiles were obtained. Delivery was varied by changing loading, number of layers, blend ratio, and incubation conditions. To determine the cellular effects of intermittent exposure to simvastatin acid, MC3T3-E1 cells were cultured with either alternating or sustained concentrations of simvastatin acid in the medium, and DNA content, alkaline phosphatase activity, and osteocalcin secretion were measured. For all three cell responses, cultures exposed to simvastatin acid showed higher activity than did control cultures. Furthermore, cell activity was greater for cells cultured with intermittent concentrations of simvastatin acid compared to cells that were constantly treated. These results imply that devices intermittently releasing simvastatin acid warrant further study for locally promoting osteogenesis.

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“…(14,15) Though not confirmed in prospective, randomized trials, observational studies suggest that lipid-lowering agents reduce fracture risk. (16,17) In animal models, diet-induced hyperlipidemia is associated with a reduction in BMD and BMC in both mice and canines. (9,18,19) High-density lipoprotein (HDL) functions as an anti-inflammatory and antiatherosclerotic agent through reverse cholesterol transport of oxidized lipids from lipid-laden cells.…”

Section: Introductionmentioning

confidence: 99%

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

Sage

Atti

et al. 2010

Journal of Bone and Mineral Research

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In hyperlipidemia, oxidized lipids accumulate in vascular tissues and trigger atherosclerosis. Such lipids also deposit in bone tissues, where they may promote osteoporosis. We found previously that oxidized lipids attenuate osteogenesis and that parathyroid hormone (PTH) bone anabolism is blunted in hyperlipidemic mice, suggesting that osteoporotic patients with hyperlipidemia may develop resistance to PTH therapy. To determine if oxidized lipids account for this PTH resistance, we blocked lipid oxidation products in hyperlipidemic mice with an ApoA-I mimetic peptide, D-4F, and the bone anabolic response to PTH treatment was assessed. Skeletally immature Ldlr À/À mice were placed on a high-fat diet and treated with D-4F peptide and/or with intermittent PTH(1-34) injections. As expected, D-4F attenuated serum lipid oxidation products and tissue lipid deposition induced by the diet. Importantly, D-4F treatment attenuated the adverse effects of dietary hyperlipidemia on PTH anabolism by restoring micro-computed tomographic parameters of bone quality-cortical mineral content, area, and thickness. D-4F significantly reduced serum markers of bone resorption but not bone formation. PTH and D-4F, together but not separately, also promoted bone anabolism in an alternative model of hyperlipidemia, Apoe À/À mice. In normolipemic mice, D-4F cotreatment did not further enhance the anabolic effects of PTH, indicating that the mechanism is through its effects on lipids. These findings suggest that oxidized lipids mediate hyperlipidemia-induced PTH resistance in bone through modulation of bone resorption. ß

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Oral statins and increased bone-mineral density in postmenopausal women

Cited by 301 publications

References 4 publications

Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions

Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions

Bioerodible devices for intermittent release of simvastatin acid

Hyperlipidemia induces resistance to PTH bone anabolism in mice via oxidized lipids

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