Category Archives: Statins

Diosgenin and Lovastatin Prevent Bone Loss in Ovariectomized Rat


Osteoprotective effect of Monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis.

This experiment established the ovariectomized (OVX) rat model of postmenopausal osteoporosis and examined the effect of the oral administration of different dosages of dioscorea, red mold dioscorea (RMD), and soy isoflavones on bone mineral density (BMD). Three months after osteoporosis had been induced and 4 weeks after feeding had begun, the tibia and femur BMD of OVX rats administered RMD showed significant increases compared with that of all other groups of OVX rats. Closer examination using microcomputed tomography also revealed that the RMD-administered rats had denser trabecular bone volume and a higher trabecular number compared to all other rat groups. Reconstructed 3D imaging indicated increases in cancellous bone mineral content, cancellous bone mineral density, and cortical bone mineral content of the proximal tibia in OVX rats. These findings indicate that administration of monacolin K and phytoestrogen diosgenin could prevent bone loss induced by estrogen deficiency.

Chiang SS, Chang SP, Pan TM
J. Agric. Food Chem. Sep 2011
PMID: 21800902

Garlic < Lovastatin < Estrogen Effective in suppressing Bone loss in Ovariectomized Rats


Effects of garlic oil on postmenopausal osteoporosis using ovariectomized rats: comparison with the effects of lovastatin and 17beta-estradiol.

The purpose of this study was to examine the antiosteoporosis effects of garlic oil in an ovariectomized (Ovx) rat model of osteoporosis and to compare its efficacy with lovastatin (a synthetic hypocholesterolemic drug) and 17beta-estradiol (a potent antiosteoporotic agent). Animals were divided into five groups: sham-operated control, ovariectomized, ovariectomized supplemented with lovastatin, ovariectomized supplemented with garlic oil and ovariectomized supplemented with 17beta-estradiol. In our study, the development of a high rate of bone turnover and osteoporosis in the ovariectomized animals were confirmed by significant alterations of serum alkaline phosphatase activity, serum tartrate-resistant acid phosphatase activity, urinary excretion of calcium, phosphate, hydroxyproline and urinary calcium to creatinine ratio, when compared with the sham-operated control group. Supplementation of these animals with either garlic oil or lovastatin or 17beta-estradiol, in addition to their hypocholesterolemic effect, could counterbalance all these changes. The results revealed that all three compounds significantly protected the hypogonadal bone loss as reflected by higher bone densities and higher bone mineral contents than the ovariectomized group of animals. The results emphasize that, like 17beta-estradiol, the hypocholesterolemic compounds garlic oil and lovastatin are also effective in suppressing bone loss owing to estrogen deficiency and their efficacy in the order of lower to higher is garlic < lovastatin < 17beta-estradiol.

Mukherjee M, Das AS, Das D, Mukherjee S…
Phytother Res Jan 2006
PMID: 16397916

Risedronate, Atorvastatin, Estrogen, Raloxifene, and Clomiphene Compared in Ovariectomized Rats


Comparative effects of risedronate, atorvastatin, estrogen and SERMs on bone mass and strength in ovariectomized rats.

The aim of this study was to investigate bone protective effects of risedronate, atorvastatin, raloxifene and clomiphene citrate in ovariectomized rats.
Our study was conducted on 63 rats at Experimental Research Center of Celal Bayar University. Six-month-old rats were divided into seven groups. There were five drug administered ovariectomized groups, one ovariectomized control group without drug administration and one non-ovariectomized control group without drug administration. Eight weeks postovariectomy, rats were treated with the bisphosphonate risedronate sodium, the statin atorvastatin, the estrogen 17beta-estradiol and the selective estrogen receptor modulators (SERMs) raloxifene hydrochloride and clomiphene citrate by gavage daily for 8 weeks. At the end of the study, rats were killed under anesthesia. For densitometric evaluation, left femurs and tibiae were removed. Left femurs were also used to measure bone volume. Right femurs were used for three-point bending test.
Compared to ovariectomized group, femur cortex volume increased significantly in non-ovariectomized group (p=0.016). Compared to non-ovariectomized group, distal femoral metaphyseal and femur midshaft bone mineral density values were significantly lower in ovariectomized group (p=0.047). In ovariectomy+atorvastatin group, whole femur and femur midshaft bone mineral density and three-point bending test maximal load values were significantly higher than ovariectomized group (p=0.049, 0.05, and 0.018). When compared to the ovariectomized group, no significant difference was found with respect to femoral maximum load values in groups treated with risedronate, estrogen, raloxifene and clomiphene (p=0.602, 0.602, 0.75, and 0.927). In ovariectomy+risedronate group, femur midshaft bone mineral density values were significantly higher than the values in ovariectomized group (p=0.023). When compared to ovariectomized group, no significant difference was found with respect to femur midshaft bone mineral density values in groups treated with estrogen, raloxifene and clomiphene (p=0.306, 0.808, and 0.095).

While risedronate sodium prevented the decrease in bone mineral density in ovariectomized rats, atorvastatin maintained mechanical characteristics of bone and also prevented the decrease in bone mineral density as risedronate sodium.

Uyar Y, Baytur Y, Inceboz U, Demir BC…
Maturitas Jul 2009
PMID: 19386450

Review: Statins and Bone Formation


Statins, bone formation and osteoporosis: hope or hype?

Osteoporosis is a major health problem affecting both men and women. Statins, besides their action as lipid-lowering agents, seem to have additional pleiotropic properties, among them a beneficial effect on bone mineral density. The entirety of experimental and the majority of clinical studies as well as the only relevant meta-analysis suggest that statins have an anabolic effect on bone metabolism. Statins, osteoporosis and adipogenesis share the same pathway, RANKL/OPG. It would appear that an imbalance in this pathway could be responsible for the manifestation of some metabolic disorders such as diabetes mellitus, atherogenesis, multiple myeloma, osteoporosis. Possibly in the future, drugs which can intervene in this biochemical and pathophysiological cascade, like statins, in a variety of doses, could be used for the management of ectopic ossification syndromes and other bone disorders, even as an additive treatment. Until then, further large longitudinal randomized controlled studies for each statin separately are required to confirm this hypothesis.

Tsartsalis AN, Dokos C, Kaiafa GD, Tsartsalis DN…
Hormones (Athens)
PMID: 22801558 | Free Full Text

All the available data from the literature, including evidence from experimental studies as well as from the vast majority of observational studies and the results of a single meta-analysis, suggested that there is a positive effect of statins on BMD, although another meta-analysis by Bauer et al72 showed evidence that the beneficial effects on BMD and on fracture risk are observational, while many limitations and the placebo-controlled trials did not demonstrate any clear-cut benefit. However, the in vitro and some clinical studies (Chuengsamarn et al71) suggest that statins inhibit bone resorption and stimulate bone formation, having a dual action on bone metabolism. Therefore, in the future statins might gain a position among drugs used for the prevention and management of osteoporosis, taking into account that clinicians already have a good deal of experience in prescribing statins, for other indications, and feel familiar with this drug family. Their anabolic and anti-resorptive effects on bone make them an ideal candidate for osteoporosis treatment.

Simvastatin Intensifies Bone Formation and Decreases Resorption in Ovariectomized Rats


Effects of simvastatin on the development of osteopenia caused by ovariectomy in rats.

Simvastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-determining enzyme for cholesterol synthesis which is used in the treatment of hypercholesterolemias, particularly in type IIa and IIb hyperlipoproteinemias, frequently in postmenopausal women. Inhibition of cholesterol synthesis by simvastatin may cause disorders of bone remodelling. The aim of the present study was to investigate the effects of simvastatin (3 mg and 6 mg/kg/day per os) administered for 4 weeks on the development of ovariectomy-induced osteopenia in 3-month-old female Wistar rats. The experiments were carried out on six groups of animals: I (C)–sham operated rats, II (S-3)–sham operated rats + simvastatin 3 mg/kg/day p.o., III (S-6)–sham operated rats + simvastatin 6 mg/kg/day p.o., IV (OVX)–ovariectomized rats, V (OVX + S-3)–ovariectomized rats + simvastatin 3 mg/kg/day p.o., VI (OVX + S-6)–ovariectomized rats + simvastatin 6 mg/kg/day p.o. In all the groups, we examined body weight gain, and macrometrical, histomorphometrical and mechanical parameters. Bilateral ovariectomy induced osteopenic skeletal changes in mature female rats. In cortical bone, ovariectomy intensified resorption processes at the marrow cavity, as indicated by a decrease in endosteal transverse growth and an increase in transverse cross-section surface area of the marrow cavity in the tibia. Intensification of resorption processes was observed in cancellous bone (a statistically significant decrease in the width of trabeculae in the epiphysis and metaphysis of the femur). Structural changes in the long bones resulting from bilateral ovariectomy were manifested by deterioration of mechanical properties of the shaft and neck of the femur. The force needed to fracture the neck and shaft of the femur was significantly smaller than that in sham operated rats. Simvastatin (3 and 6 mg/kg/day p.o.) slightly influenced bone remodelling in sham operated rats. Simvastatin (3 and 6 mg/kg p.o. daily) administered to ovariectomized rats intensified bone formation processes and decreased bone resorption processes induced by bilateral ovariectomy, showing stronger activity at 6 mg/kg.

Pytlik M, Janiec W, Misiarz-Myrta M, Gubała I
Pol J Pharmacol
PMID: 12856828 | Free Full Text

Statins and Fish Oil Improve Lipid in Bones


Statins and dietary fish oils improve lipid composition in bone marrow and joints.

There have been numerous efforts to alter the lipid content of cardiovascular tissues. Although equally important, only limited information is available about musculoskeletal tissues. I characterized joint and bone marrow lipids in patients having joint replacement surgery and explored the effects of fish oils and statins on lipid composition in bone marrow and joint fluid. Joint drainage catheters were used to collect marrow lipids from 84 patients having 128 hip and knee replacements for osteoarthritis, osteonecrosis, and femoral neck fractures (osteoporosis). Statins reduced the amount of lipid by 22% in patients with osteoporosis, 26% in patients with osteoarthritis, and 41% in patients with osteonecrosis compared with pretreatment lipid levels in the same patients. Taking fish oils reduced the amount of lipid in bone marrow by 20%. Lipid profiles of disturbed marrow and joint fluid from patients who took statins or dietary fish oil showed an increase in the proportion of unsaturated fatty acids and longer-chain fatty acids relative to pretreatment profiles. The ability to change the amount and character of bone and joint lipids may have major importance for strengthening bone, reducing the severity or preventing osteonecrosis, and enhancing joint lubrication.

Pritchett JW
Clin. Orthop. Relat. Res. Mar 2007
PMID: 17496750

Tocotrienol + Lovastatin Increases Bone Formation in Rats


Effects of tocotrienol and lovastatin combination on osteoblast and osteoclast activity in estrogen-deficient osteoporosis.

Statins are HMGCoA reductase inhibitors and had been demonstrated to stimulate bone formation in rodents after high oral doses. Observational studies on patients treated with oral statins were varied. Delta-tocotrienol had been found to stimulate the cleavage of HMGCoA reductase and inhibit its activity. Tocotrienols were found to have both catabolic and anabolic effects on bone in different animal models of osteoporosis. The current study aimed to ascertain the effects of delta-tocotrienol and lovastatin combination on biochemical and static bone histomorphometric parameters in a postmenopausal rat model at clinically tolerable doses. 48 Sprague Dawley female rats were randomly divided into 6 groups: (1) baseline control group; (2) sham-operated control group; (3) ovariectomised control group; (4) ovariectomised and 11 mg/kg lovastatin; (5) ovariectomised and 60 mg/kg delta-tocotrienol; (6) ovariectomised and 60 mg/kg delta-tocotrienol + 11 mg/kg lovastatin. These treatments were given daily via oral gavage for 8 weeks. Delta-tocotrienol plus lovastatin treatment significantly increased bone formation and reduced bone resorption compared to the other groups. Therefore, the combined treatment may have synergistic or additive effects and have the potential to be used as an antiosteoporotic agent in patients who are at risk of both osteoporosis and hypercholesterolemia, especially in postmenopausal women.

Abdul-Majeed S, Mohamed N, Soelaiman IN
Evid Based Complement Alternat Med 2012
PMID: 22927884 | Free Full Text