Statin Use, Bone Mineral Density, and Fracture Risk

Pasco, Julie A.; Kotowicz, Mark A.; Henry, Margaret J.; Sanders, Kerrie; Nicholson, Geoffrey C.

doi:10.1001/archinte.162.5.537

Cited by 159 publications

(74 citation statements)

References 15 publications

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“…There also has been a fourfold increase in the exposure to statins. We have reported previously that statins are protective against fracture, (37) but these observations have not been supported by data from randomized, controlled trials. (38) Fracture risk increases with decreasing BMD such that each standard deviation (SD) decrease in BMD is associated with a 1.5-to 3.0-fold increase in fracture risk.…”

Section: Incident Hip Fracture Rates For Men and Womenmentioning

confidence: 88%

Changes in hip fracture rates in southeastern Australia spanning the period 1994–2007

Pasco

Brennan

Henry

et al. 2011

Journal of Bone and Mineral Research

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Hip fracture incidence rates appear to be declining in Western populations. Utilizing comprehensive incident hip fracture data from radiology reports, we determined changes in hip fracture rates in southeastern Australia between 1994-1996 and 2006-2007 for residents aged 55 years or older. During this period, the population at risk increased by 47% for men and 40% for women. Although the absolute number of hip fractures increased by 53% in men and 4.4% in women, standardized hip fracture ratios were 0.92 [95% confidence interval (CI) 0.79-1.08] and 0.69 (95% CI 0.62-0.77), respectively. Marked reductions in hip fracture rates were observed for women: 32% for ages 75 to 84 years and 29% for ages 85 years or older. Data from the Geelong Osteoporosis Study were used to identify changes in body composition and lifestyle that might have influenced hip fracture risk in women during this period.

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Section: Incident Hip Fracture Rates For Men and Womenmentioning

confidence: 88%

Changes in hip fracture rates in southeastern Australia spanning the period 1994–2007

Pasco

Brennan

Henry

et al. 2011

Journal of Bone and Mineral Research

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“…In 2000, a first observational study found an inverse association between hip fractures and statin use (Wang et al, 2000c). After that, small retrospective studies (Chung et al, 2000;Meier et al, 2001;Pasco et al, 2002;Scranton et al, 2005) and a meta-analysis (Bauer et al, 2004) showed a lower risk of fractures. At the same time, a randomized trial (Bone et al, 2007) and three large population-based studies (van Staa et al, 2001;LaCroix et al, 2003LaCroix et al, , 2008 together with two previous cardiovascular prevention trials (Pedersen and Kjekshus, 2000;Reid et al, 2001), analyzed a posteriori, showed no benefits.…”

Section: F Statins and Bonementioning

confidence: 99%

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Gazzerro

Proto²,

Gangemi³

et al. 2011

Pharmacol Rev

390

370

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“…Numerous animal and human studies have been performed to elucidate the clinical importance of statins. The majority of experimental and epidemi ological studies have shown statins to have beneficial effects on bone metabolism, as evaluated by BMD (14)(15)(16) and fracture risk (17)(18)(19). Statins have therefore been proposed as potential agents in the treatment of osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin protects human osteosarcoma cells from oxidative stress-induced apoptosis through mitochondrial-mediated signaling

Zhao

Zhang

et al. 2011

Mol Med Report

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Abstract. Apoptosis of osteoblasts has been proposed as the common basis of osteoporosis, with oxidative stress as the major cause. This study was performed to investigate the protective effect of simvastatin (0.001-0.1 µM) on 100 µM hydrogen peroxide (H 2 O 2 )-mediated oxidative stress-induced apoptosis in human osteosarcoma (MG63) cells and the molecular mechanisms involved. Cell apoptosis was evaluated by observation of morphological changes and Annexin V-propidium iodide double staining followed by flow cytometric analysis. MTS assays were used to evaluate cell viability. To investigate the underlying molecular mechanisms, the expression of caspase-3, caspase-9 and Bcl-2 were analyzed by Western blotting. Following stimulation with H 2 O 2 for 24 h, a high proportion of MG63 cells underwent apoptosis, while a dosedependent inhibition of apoptosis was observed in the presence of simvastatin. A significant, dose-dependent reduction in the expression of caspase-3 and caspase-9 protein induced by H 2 O 2 in MG63 cells was observed in response to simvastatin and the Bcl-2 levels were increased. In conclusion, simvastatin protects MG63 cells from oxidative stress-induced apoptosis through downregulation of caspase-3 and caspase-9 activation and upregulation of Bcl-2 expression, suggesting a protective effect in osteoporosis. IntroductionOsteoporosis has been defined as a systemic skeletal disease characterized by gradual loss and microarchitectural deterioration of bone tissue, resulting in increased bone fragility and susceptibility to fracture (1). Osteoblasts are responsible for bone formation while osteoclasts are involved in bone resorption. Conditions such as postmenopausal osteoporosis are associated with significant changes in bone turnover; bone formation decreases and bone resorption increases or remains the same, resulting in net bone loss (2,3).Oxidative stress, resulting from excessive levels of reactive oxygen species (ROS), represents a major cause of cellular damage and death in a plethora of pathological conditions, including osteoporosis. This is associated with distinct increases in blood levels of oxidative stress markers (4-6). The main oxygen species responsible for oxidative stress are hydrogen peroxide (H 2 O 2 ), the free radical superoxide anion (O 2 -) and the hydroxyl radical (OH -). Osteoblasts produce antioxidants such as glutathione peroxidase that protect against ROS (7) and osteoclast-generated superoxide contributes to bone degradation (8). In ovariectomized rats, a model of postmenopausal osteoporosis, increased levels of lipid peroxidation and H 2 O 2 and decreased levels of enzymatic antioxidants were detected in tissue homogenates from the femora (9). Furthermore, antioxidant enzyme GPX1 gene polymorphisms are associated with low bone mineral density (BMD) and increased bone turnover markers (10).The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-COA) reductase inhibitor, simvastatin, is a widely used cholesterollowering drug that inhibits hepatic cholesterol biosynthesis. Recent...

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Statin Use, Bone Mineral Density, and Fracture Risk

Abstract: The substantial 60% reduction in fracture risk associated with statin use is greater than would be expected from increases in BMD alone.

Cited by 159 publications

References 15 publications

Changes in hip fracture rates in southeastern Australia spanning the period 1994–2007

Changes in hip fracture rates in southeastern Australia spanning the period 1994–2007

Pharmacological Actions of Statins: A Critical Appraisal in the Management of Cancer

Simvastatin protects human osteosarcoma cells from oxidative stress-induced apoptosis through mitochondrial-mediated signaling

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