International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - 5(4), February, 2013

Pages: 73-81

Date of Publication: 28-Feb-2013

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Author: Karmajeet Rath, Biswa Bhusan Mohanty, Sanjay Kumar, Pramila Nayak, Jagannath Sahoo

Category: Healthcare

Abstract:Inhibitors of HMG-CoA reductase enzymes, which are statins, are well known and much prescribed drugs for lowering of cholesterol and used for dyslipidemia. But, they have also been shown across various studies to stimulate bone formation. In bone cells, these inhibitors have been known to increase the gene expression of bone morphogenetic protein-2, thereby helping in osteoblastic differentiation, with some effects also on osteoclastic inhibition. The findings that statins can increase bone formation and thereby mass of bone, can be helpful in preventing bone fractures and improving osteoporosis, which is a condition of marked bone loss. Hence, it is reviewed herein that HMG-CoA reductase inhibitors can be a great way, probably a futuristic drug for osteoporotic treatment and prevention. Keywords: HMG-CoA reductase inhibitors, osteoporosis

Keywords: HMG-CoA reductase inhibitors, osteoporosis, osteoblasts, statins, bone metabolism, fracture

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There has been a remarkable increase in the knowledge about osteoporosis since the past 25 years or so. Osteoporosis is seen to occur more in females than in males, although mortality is higher in men, which are caused by osteoporotic fractures 1, 2, 3. Added to this, post menopausal women have a higher frequency of osteoporotic fractures and osteoporotic incidences 4 . Bone is a metabolically active organ in which mineral and organic components will be important to determine the mechanical function of skeleton5,6 . Bone turnover is under the control of certain defined agents as well as processes, which regulate the formation of bones and also resorption of bone. These are two basic but important processes by which the bone remodelling is occurg. New bone formation is basically a function of the osteoblasts, agents which act by increasing or decreasing the replication of cells in the lineage of osteoblasts, or modifying the differentiated function of the osteoblast. It would therefore be beneficial for stimulating the osteoblastic activity at local sites in bone by an oral anabolic agent, resulting in bone formation, where and when needed. Osteoporosis is defined clinically as reduced bone mass, to such a level where it will result in fracture, with minimal trauma7 . This term will also suggest that there is parallel loss of both bone mineral and matrix that will render the mineralised bones incapable of withstanding minor trauma, without leading to fractures. Osteoporosis is a disease condition which is affecting about 30 million people in United States and about 100 million people worldwide. Unless the bone mass falls below 30% to 50% lower than the normal value, fractures do not occur.

Bone mass is the net result of a balance between bone formation and resorption. This balance is mostly regulated by genetic as well as environmental factors. Genes regulating bone mass are vitamin D receptor gene, estrogen receptor gene, interleukin-6, transforming growth factor B and gene encoding type 1 collagen 8,9,10,11. Environmental factors include nutritional status, exercise, drugs like glucocorticoids and contraceptive pills, neoplastic diseases such as myeloma, leukemia, lactation, parity, alcohol, smoking, weight loss and long hip axis length. Although the exact pathophysiology of osteoporosis is unknown, an imbalance between bone formation and resorption presumably causes bone mass to decline in adulthood and osteoporosis occurs when the amount of bone removed from the skeleton by bone resorbing osteoclasts exceeds the amount formed by osteoblasts during the coupled process of remodelling. Treatment of osteoporosis is aimed towards restoring this balance.

Bone remodelling is well established throughout the literature and involves both systemic and non systemic factors. It is well known that in this procedure an important role is played by the system of receptor activator of nuclear factor kappa b ligand – osteoprotegerin 6, some cytokines and bone morphogenic proteins. Mesenchymal stem cells are pluripotent cells with a high mitotic index and are involved in the differentiation of adipocytes under the regulation of genes and transcription factors. Adipose tissue is considered as a separate endocrine gland, responsible for the secretion of adipokines such as leptin, adiponectin and hormones such as vitamin D3, estrogen, etc and in involved in the pathogenesis of some entities. Leptin is considered to exert a control over the RANKL/OPG axis by decreasing the expression of RANKL and increasing OPG to bring out preosteoblasts and mononuclear cells into the circulation. 12,13. There is diversion of adipocyte into an osteoblast, which is a multifactorial process regulated by various factors.

Molecular biology and genetics reveal that both vascular and osteoblast biology have a common pathway of RANK/RANKL/OPG 14. Mundy and colleagues in 1999 reported first that there was an anabolic effect of statins in human bone cells and cultured mouse. Simvastatin and lovastatin enhanced the expression of bone morphogenetic protein- mRNA15 . Statins as potential drugs for osteoblastic activites Several experiments have illustrated the effect of statins in bone metabolism in vitro and vivo. Chan in 2000 demonstrated that there was negative effect of statin on bone repair. But in contrast, there were many other studies which showed beneficial effects. The administration of statins has anabolic effects on the bone by suppressing osteoclasts and promoting osteoblastic activities. Hence, statins can effectively work on bone formation and increase the bone mass density by inhibiting it, thereby helping in prevention of osteoporosis and aiding in fracture healing. Most of these studies have been done in different doses in animal models, apart from showing actions of cholesterol lowering in animals. Some also have shown remarkable increase in required growth factors such as TGFb-1 and VGF or Vascular Growth Factor, possibly showing a path for the statins and bone interaction. There have been more studies in cell cultures, in vitro, which support the findings that statins have a potential mechanism on bone metabolism. There is expression in certain genes like BMP-2, COLLIA1, Osteocalcin, etc while the RANKL gene is depressed are affected by statins, which might be the reason for the bone formation. In 2007, Hughes A 17 found that the statins of hydrophobic nature and hydrophilic nature have inhibited osteoclastic action in vitro, while some other studies have shown lipophilic agents like simvastatin to have better action 18. It was the pleiotropic effect of statins which led many clinicians to study the use of statins in bone metabolism. A meta analysis by Uzzan et al 19 , found that statins have a positive effect on bone mass density in different bones of the body. It was concluded that there was statistically significant but modest positive effect of statins on BMD. More data is still needed to support the use of statins in prevention of bone fracture. Most of the literatures showed an increase in BMD and also in bone markers. All the available data from various literatures, starting from the experimental studies to the observational studies showed that there is surely some positive effect of statins on BMD. One meta analysis by Bauer et al 20 also showed the beneficial effect of statins on fracture risk. It was demonstrated by Chuengsamarn et al 21 that statins could inhibit bone resorption and stimulate bone formation, with a dual action on bone metabolism. It might be possible for statins to gain a position as a drug used for prevention and management of osteoporosis, so much so that statins is being frequently prescribed by clinicians for other treatments. Possibly in the future, drugs will be up in circulation, which will target the different pathophysiological and biochemical cascades as in statins with alterations of doses and could be used for different bone disorders like osteoporosis.

Two recently elucidated pathways may explain how statins can be helpful in building up bone. The first mechanism is through the inhibition of mevalonate production. Many laboratories and researchers noted that cholesterol synthesis and osteoclast activation involved same biochemical cascade. The synthesis of cholesterol is done in plenty of steps. HMG-CoA is converted into mevalonate by enzyme HMG-CoA reductase. This enzyme is inhibited by statins. Then the mevalonate is converted to geranyl phosphate, which is in turn converted to farnesyl pyrophosphate by the enzyme farnesyl pyrophosphate synthese, which is inhibited by bisphosphonate drugs. Then the cholesterol is synthesised22, 23,24. Osteoclasts use the intermediate molecules of farnesyl pyrophosphate and geranyl pyrophosphate from farnesyl pyrophosphate to modify and activate the key intracellular proteins glutamyl transpeptidases and GTP-ase in a process called prenylation25. Bisphosphonates like alendronate and risedronate inhibit farnesyl synthase, preventing the formation of lipid products 26 .


Statins are as efficacious in not allowing osteoclast activation, even in experimental set ups, the action being due to mevalonate production. This will reduce the bone resorption and there is restoration of bone resorption and formation. In many clinical trials, it has been noted that fragility related fractures are reduced27, 28, and 29 . B. Another mechanism which has statins affecting skeleton is that of activation of bone morphogenetic protein-2 promoter. This is a kind of protein which is a growth factor, which leads the osteoblasts into proliferating, maturing and thereby creating a new bone30. In an experiment, when lovastatin was injected into organ cultures of calvarial bones from the neonate mice, thrice a day for 5 days, volume of bone increased by as much as 50%, in comparison to placebo. Histological studies showed enhanced bone formation and osteoid accumulation. 31 .


Although a number of recent drugs have shown to prevent osteoporosis and have been used in the treatment, not one of them has been shown to stimulate bone formation and increase osteoblasts activity. It was suggested that drugs which inhibit HMG CoA reductase, which are statins, many have such effects and reduce the risk of osteoporotic fractures. 30. Many other reports have also suggested such an anabolic bone effect, which might show a new path towards the treatment of osteoporosis. 32. To aid in the proof of such an action, it was stated that statins as a class of unknown bone anabolic agents acted through increased production of one of the important bone growth factors, which is Bone Morphogenetic Protein-2, which directly stimulates the osteoblastic activity and bone formation. Lovastatin was found to be stimulating the BMP-2 promoter, from among 30,000 natural compounds tested. 33. Many other subsequent studies have also demonstrated similar effects through fluvastatin, simvastatin and mevastatin. 34, 35, 36. These studies showed that the drugs inhibiting HMG-CoA reductase commonly utilised nowadays for lowering blood lipid levels, also stimulate bone formation activity by osteoclasts through the increase of BMP-2 expression, which is a proven differentiator of osteoblasts. Chuengsamarn et al also carried out many experiments in form of prospective randomised trials on the impact of simvastatin on osteopenic patients and found that bone formation marker and BMD was significantly higher than in the statin group and the difference of bone resorption market was also significantly lower than in the statin group. 37 .

From such studies it can be very well concluded that simvastatin as well as other drugs in this particular group act as double therapeutic weapon by inhibiting the conversion of HMGCoA to mevalonate, which is required for cholesterol synthesis and also inhibits the stimulation of osteoclastic activity. Also, there is increase in the stimulation of osteoblastic activities, providing enough evidence that the simvastatin has a promising role in fighting against osteoporosis. But still more studies are required to find the particular doses and the effect dosage and mode of administration of these statin group of drugs to make it commercially viable. Current therapies of osteoporosis treatment include estrogen replacement therapy, bisphosphonates and selective estrogen receptor modulators and all of them aim at blunting the resorption of bone remodelling. Based on previous findings it was found by Bauer and Cummings that large databases showed association between statin usage and skeletal status, showing relationship between statin use, bone mineral density and subsequent fractures. 38,39. Even a study on post menopausal women has come out which shows an increase in the bone mineral density who are taking statins40. It has been shown to have a protective effect against non pathological fractures among older women. 41,42,43,44 A similar story was involved with the use of Hormone Replacement Therapy or HRT, which was prescribed to ladies around 2000, without much long term studies. Statins are also being pushed nowadays for prevention of fractures. But, with the proper tests and long term studies, it will be coming out clearly, whether the benefits are worth making public.

Authors acknowledge the great help received from the scholars whose articles cited and included in references of this manuscript. The authors are also grateful to authors / editors / publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed. Authors are grateful to IJCRR editorial board members and IJCRR team of reviewers who have helped to bring quality to this manuscript.


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21. Chuengsamarn S, Rattanamongkoulgul S, Suwanwalaikorn S, Wattanasirichaigoon S, Kaufman L. Effects of statins vs. non-statin lipid-lowering therapy on bone formation and bone mineral density biomarkers in patients with hyperlipidemia. Bone 2010;46:1011-1015

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38. Maeda T, Matsunuma A, Kawane T, Horiuchi N: Simvastatin promotes osteoblast differentiation and mineralization in MC3T3-E1 cells. Biochem Biophys Res Commun 2001, 280: 874-877.

39. Bauer DC, Mundy GR, Jamal SA, Black DM, Cauley JA, Harris F, Duong T, Cummings SR: Statin use, bone mass and fracture: an analysis of two prospective studies. J Bone Min Res 1999, 14:1188

40. Edwards CJ, Hart DJ, Spector TD: Oral statins and increased bone-mineral density in postmenopausal women. Lancet 2000, 355:2218-2219.

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Dr. Pramod Kumar Manjhi joined Editor-in-Chief since July 2021 onwards

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One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to for more details.

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‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to for more details.

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A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award

A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award

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Disclaimer: International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal.


International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal


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