Statins, bone formation and osteoporosis: hope or hype?

Tsartsalis, Athanasios N.; Dokos, Charalambos; Kaiafa, Georgia; Tsartsalis, D.; Kattamis, Antonios; Hatzitolios, Apostolos; Savopoulos, Christos

doi:10.14310/horm.2002.1339

Cited by 48 publications

(43 citation statements)

References 67 publications

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“…Hydrophobic statins (simvastatin, lovastatin) enter the liver via the hepatic portal vein, while hydrophilic statins (rosuvastatin, pravastatin, fluvastatin) require active transport into the cell 17) . Simvastatin is administered by gavage and requires hepatic conversion to metabolically active β-hydroxy acid to become medicinally active.…”

Section: Discussionmentioning

confidence: 99%

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Ohira

Koji

Sasaki

et al. 2015

J. Hard Tissue Biology.

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The aim of this study was to investigate the effects of local administration of fluvastatin-gelatin complex on the healing of bone defects in low-turnover osteoporosis mice. Gelatin was used as a carrier of the fluvastatin. A fluvastatin-gelatin complex solution was created by dissolving each concentration of fluvastatin in a 75mg/mL gelatin solution. The gelatin solution was mixed with air, then lyophilized for 1 day and crosslinked by dry heating to make a fluvastatin-gelatin complex sponge. After crosslinking, the complex sponge was cut into pieces 1 mm diameter × 1 mm high to fit the bone defect area. The amount of fluvastatin in the sponge was adjusted to control (0 nmol), 0.1 nmol, 0.2 nmol, and 0.4 nmol. Using 20-week-old low-turnover osteoporosis model mice (SAMP6) and normal model mice (SAMR1), cylindrical and bone defects were made in sites 1.0 mm in diameter and depth, 1 mm of 3 mm from both sides of the distal end of the femur. The complex sponge was then inserted into each site, and the wound was closed. Radiographic analysis and histologic examinations were then performed. In SAMP6, the bone volumes of the bone defect areas in the 0.1nmol and 0.2nmol groups were significantly higher compared with those of the control and 0.4nmol groups at 14 and 21 days. Histological observation showed that the volume of newly formed bone increased in the 0.1nmol and 0.2nmol groups compared to those in the control and 0.4nmol groups at 14 and 21 days. The bone volumes of newly formed bone in SAMR1 were higher than were those in SAMP6, and the optimum concentration of fluvastatin was different between SAMP6 and SAMR1. The present study suggests that local administration of a fluvastatin-gelatin complex sponge provides improvement in bone healing in low-turnover osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Ohira

Koji

Sasaki

et al. 2015

J. Hard Tissue Biology.

View full text Add to dashboard Cite

show abstract

“…Hydrophobic statins (simvastatin, lovastatin) enter the liver via the hepatic portal vein, while hydrophilic statins (rosuvastatin, pravastatin, fluvastatin) require active transport into the cell. 23) Simvastatin is administered by gavage and requires hepatic conversion to metabolically active â-hydroxy acid to become medicinally active. Therefore, for local administration, simvastatin would first have to be hydrolyzed to simvastatin acid 24,25) .…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Effect of Local Administration of Fluvastatin using a Fluvastatin-gelatin Complex in Senile Osteoporosis Model Rat

Yasuda

Koji

Satô

et al. 2014

J. Hard Tissue Biology.

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Statins, inhibitors of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase, were recently reported to promote the differentiation of osteoblasts produced by the stimulation of bone morphogenetic protein-2 (BMP-2). The aim of this study was to investigate the osteogenic effect of a local administration of fluvastatin in senile osteoporosis model rats using a fluvastatin-gelatin complex. The gelatin-hydrogel was put into cylindrical titanium tubes 1.5 mm in diameter and 2.2 mm high. It was then crosslinked by ultraviolet irradiation, after which it was lyophilized. Subsequently, the carriers were placed in the fluvastatin solution (300 μM) for one day to bind the alkaline gelatin and acidic statin electrostatically (fluvastatin-gelatin complex; statin group). A control group consisted of the carriers immersed in sterilized water. Specimens of both the statin group and the control group were implanted into the femur of 15-week-old male senile osteoporosis model rats (SHRSP). Radiographic analysis, histologic examination, and immunohistochemical staining (BMP-2 and Runx2) were then performed. At 14 and 21 days, the bone volumes of the newly formed bone in the statin group was significantly higher compared to those of the control group (P<0.05). Histological observation showed that a high level of new bone formation was present in the statin group compared to that of the control group during all time periods. At 7 days, positive immune reactions with BMP-2 and Runx2 were seen in the statin group. The local administration of the fluvastatin-gelatin complex facilitated bone formation in senile osteoporosis model rats.

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“…In addition, at 8 weeks postovariectomy, serum BALP level increased by 38.7% and OPG level showed a similar pattern (Miyazaki et al, 2004). The RANKL/OPG pathway is shared by statins, osteoporosis and adipogenesis (Tsartsalis et al, 2012). A significant decrease in trabecular number with widening of the trabecular spaces occurred in the OVX rats' femur 6 weeks post-ovariectomy…”

Section: Discussionmentioning

confidence: 80%

左卡尼汀(而非辅酶q10)提高阿托伐他汀在切除卵巢的老鼠的抗骨质疏松作用

Murad

2016

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Statins' therapy in osteoporosis can aggravate muscle damage. This study was designed to assess which agent, L-carnitine or coenzyme Q10, could enhance the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. Methods: Forty-eight female Sprague Dawley rats were used; forty rats were ovariectomized while eight were sham-operated. Eight weeks post-ovariectomy, rats were divided into ovariectomized-untreated group and four ovariectomized-treated groups (n=8) which received by gavage (mg/(kg·d), for 8 weeks) 17β-estradiol (0.1), atorvastatin (50), atorvastatin (50)+L-carnitine (100), or atorvastatin (50)+coenzyme Q10 (20). At the end of therapy, bone mineral density (BMD), bone mineral content (BMC), and serum levels of bone metabolic markers (BMMs) and creatine kinase (CK) were measured. Femurs were used for studying the breaking strength and histopathological changes. Results: Treatment with atorvastatin+L-carnitine restored BMD, BMC, and bone strength to near normal levels. Estrogen therapy restored BMD and BMC to near normal levels, but failed to increase bone strength. Although atorvastatin and atorvastatin+coenzyme Q10 improved BMD, BMC, and bone strength, they failed to restore levels to normal. All treatments decreased BMMs and improved histopathological changes maximally with atorvastatin+L-carnitine which restored levels to near normal. Atorvastatin aggravated the ovariectomy-induced increase in CK level while estrogen, atorvastatin+L-carnitine, and atorvastatin+coenzyme Q10 decreased its level mainly with atorvastatin+L-carnitine which restored the level to near normal. Conclusions: Coadministration of L-carnitine, but not coenzyme Q10, enhances the anti-osteoporotic effect of atorvastatin while antagonizing myopathy in ovariectomized rats. This could be valuable in treatment of osteoporotic patients. However, further confirmatory studies are needed.

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Statins, bone formation and osteoporosis: hope or hype?

Cited by 48 publications

References 67 publications

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect

Osteogenic Effect of Local Administration of Fluvastatin using a Fluvastatin-gelatin Complex in Senile Osteoporosis Model Rat

左卡尼汀(而非辅酶q10)提高阿托伐他汀在切除卵巢的老鼠的抗骨质疏松作用

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