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IJCRR - 6(16), August, 2014

Pages: 07-19

Date of Publication: 20-Aug-2014


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BISPHOSPHONATES IN DENTISTRY AN ASIAN PERSPECTIVE - EVIDENCE BASED REVIEW

Author: Vanaja Krishna Naik, Aruna Balasundaram, Harinath P., Caroline Jacob

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Abstract:Bisphosphonates are drugs with high affinity to bone, which accumulates in the bone matrix for a longer time and affects bone turnover. These are commonly prescribed in the management of malignant metastatic bone disorders and for several benign conditions such as osteoporosis and Paget's disease. The objective of this review is to provide a comprehensive report on the drug bisphosphonate, clinical applications and its potential adverse effects, with special focus on Asian literature. Frequencies of patients who are on bisphosphonates are increasing in dental clinics these days. However regarding the use of this drug and its clinical implication from Asian countries are sparse, presumably due to under-reporting of cases or possibly wrong diagnoses. Hence we have made an attempt to reinforce the existing knowledge about this topic in Asian context along with latest information for the readers.

Keywords: Bisphosphonates, osteonecrosis of the jaws, Asian perspective, Dental uses, Periodontitis.

Full Text:

iNTRODUCTION
Dental clinicians have a distinctive and obligatory responsibility to treat the patient as a whole, not just the dental concern. Hence thorough medical histories are of paramount importance, which allows the clinician to identify systemic diseases and take necessary precautions during dental treatment. Further it is a good routine to elicit drug history at every dental visit of the patient1 . Patients on bisphosphonates [BPs] are increasingly seen in the dental clinics2 . These patients should be informed about the possibility of osteonecrosis of the jaws following any form of oral surgical procedures. The reported cases of osteonecrosis from Asian countries are sparse. Is it because of inherent protection of population against osteonecrosis or under-reporting of the cases or wrong diagnosis This review discusses comprehensively about the drug bisphosphonate and its pharmacotherapeutics, clinical uses and potential adverse effects with special focus on Asian literature.

CLASSIFICATION OF BISPHOSPHONATES
BPs are classified as Nitrogen and non-nitrogen containing2, 3,4. Novel synthetic bisphosphonate: Disodium dihydrogen4-[(methylthio) phenylthio] methane bisphosphonate [TRK-530]: has an antioxidant methylthio-phenylthio group in the R2 side chain and has both anti-resorptive and anti-inflammatory effect9 . Mechanism of action of bisphosphonates Bone is a dynamic hard tissue undergoing constant remodelling. During bone resorption, bone morphogenetic protein and insulin growth factors are released which direct the migration, differentiation and osteoid production of new bone from local and circulating stem cells.10 Most commonly used BPs is nitrogen containing, which are extremely bone selective. The basic action of BPs is to inhibit bone resorption, turnover and renewal, thus reducing serum calcium levels. They bind to the mineral crystals on bone surfaces and a repeated dose accumulates in the bone matrix. During the bone remodelling BPs are released from the bone surface and are internalized by osteoclasts. This affects the protein prenylation which is important for the activity and survival of osteoclasts, subsequently leading to apoptosis.5,11,12

THERAPEUTIC USES
 MEDICAL APPLICATIONS

The earliest medical applications of bisphosphonates were in the treatment of Fibrodysplasia ossificans progressiva, in patients who had undergone total hip repl acement surgery and for bone imaging. Subsequently it became treatment of choice in various bone diseases, such as Paget’s disease, osteolytic bone diseases, osteoporosis, 13,14,15,16 hypercalcemia of malignancy and in metastases of malignant tumours, further this was applied in paediatrics in the management of brittle bone disorders and osteogenesis imperfecta.13Finally interesting observations such as antiparasitic and analgesic effects are found with BPs.

PERIODONTAL APPLICATIONS:
The potential dental applications of BPs have been explored not only for the treatment or prevention of periodontal bone loss but also as a diagnostic aid to detect bone loss associated with periodontal disease and cessation of bone loss following treatment. However this application did not come into routine use for reasons possibly related to cost, accessibility and full-body irradiation due to intravenous administration.3 The anti-resorptive effects of systemic3,8,17-,23 and topical24-30 BPs have been applied in the management of periodontitis.31-33 Takaishi Y et al 2001 reported clinical effect of etidronate 200 mg daily for two weeks, followed by off-periods of 10 weeks or more for 2-3 years and suggested marked improvement in the appearance of gingival tissue, depth of periodontal pockets and radiographic appearance of alveolar bones. They concluded that the effect may be owing to the anti-resorptive and the anti-inflammatory action of etidronate.34 On the contrary Graziani F 2009 conducted a study to determine the efficacy of adjunctive short term intramuscular neridronate in non surgical periodontal therapy and found no additional short term improvements in periodontal conditions of chronic periodontitis patients when compared to periodontal treatment alone.8 A Chinese report in 2011 summarized the mechanism of bone regulation and local delivering system of BPs in the management of peri-implant bone loss and suggested that calcium phosphate ceramics, polylactic acid, fibrinogen film and collagen membrane can be used as BPs carriers35 Sharma A and Pradeep A R 2012 conducted series of studies with the objective of assessing the clinical efficacy of 1 % alendronate gel as local drug delivery agent in adjunct to mechanotherapy in the treatment of chronic periodontitis, chronic periodontitis with diabetes mellitus, aggressive periodontitis, and in the treatment of degree II furcation involvement. The results of these studies indicated probing depth reduction, attachment gain and improved bone fill.24,25,28,30 Basma Mostafa et al 2012 conducted a study to evaluate the combined effect of systemic bisphosphonates, calcium and vitamin D supplements along with surgical periodontal therapy on the alveolar bone in osteoporotic post menopausal females with chronic periodontitis. They found that this combination showed better improvement in treatment outcomes as in clinical and radiographic parameters.36 Bisphosphonate coating on dental implant surface: The BP coated implants have been studied to investigate its effects on osseintegration.37-40Yoshinari M41 2002 conducted a study to evaluate the bone response to titanium implants coated with thin calcium-phosphate followed by bisphosphonate and they concluded that there was highest percentage of bone contact with these test implants group compared to the control group, suggesting the promotion of osteogenesis on surfaces of dental implants Despite the listed applications in dentistry the usage of BPs is not popular, possibly because of the major adverse effects as osteochemonecrosis. Although the local delivery of BPs in the management of periodontitis and periimplantitis are reported, these needs to be interpreted with caution as there are very few reports to support this mode of delivery and also there were no reports on short and long term soft and hard tissue adverse effects, besides most of the data are from few centres. Hence further long term, multicentre, multiethnic, prospective studies should be encouraged. The comparison of Asian studies24, 28, 30, 22 with that of western studies23, 42,19,39,40, 43 are outlined in table 6, which focuses only on human studies. TOXICITY: Bps have been reported to cause several adverse effects such as skeletal and non skeletal. Although skeletal adverse effects as BRONJ has drawn major attention, there are non skeletal effects such as oesophagitis like symptoms, oesophageal cancer, fever, flu like symptoms, potential renal failure, risk of atrial fibrillation, cardiovascular and valvular calcifications with iv and oral bisphosphonates. However few of these non skeletal adverse effects have not been reported in Asian literature. The most sinister skeletal adverse effect of BPs is BRONJ, bisphosphonate related osteonecrosis of the jaws. Patients may be considered to have BRONJ if they have exposed bone in the maxillofacial region for atleast 8 weeks are currently on or have taken bisphosphonates and have no history of radiotherapy to the jaws 44 The risk factors for developing BRONJ can be systemic and local. The systemic factors such as malignancy, patients on long term concurrent corticosteroid therapy, reduced immunity as in diabetics and smokers. In addition the route of administration, dose and potency of BPs predisposes the patient to develop BRONJ. Further the local risk factors as dentoalveolar surgeries with osseous modifications in areas of thin mucosa overlying tori and mylohyoid ridge and patients with dental abscesses who are on iv bisphosphonates are susceptible to BRONJ. Incidence of BRONJ: Patients undergoing oral bisphosphonate therapy are at a considerably lower risk for BRONJ than oncology patients on monthly IV bisphosphonates. The incidence of BRONJ in patients on oral BPs varies from 0.01 to 0.04%45 the incidence of BRONJ in patients with IV bisphosphonates is about 0.8-12%45. The incidence of BRONJ in Asian population was unknown till 2010. The first few reported cases of BRONJ in Asia were from South Korea. W.Park.N et al 201046 reported 5 cases of BRONJ caused by oral BPs in Asian population. Authors concluded that irrespective of race elderly women undergoing steroid therapy have an increased incidence of BRONJ even with oral BPs. Another

 

retrospective study conducted by Hong JW 2010,47 suggested the prevalence of BRONJ to be 0.05 to 0.07%. The authors concluded that the prevalence of oral BRONJ in Korea is similar to that reported previously in Western populations. The BRONJ is clearly an uncommon complication of oral BP administration, however the sheer volume of prescriptions of this drug throughout Asia may mean that many cases are likely to present in future. The summary of incidence of BRONJ in Asian literature46-49 and comparison with that of western literature is outlined in table 7. Although the reported incidence of BRONJ in western literature50-54 is more, we have outlined only a few, as it is beyond the scope of this review to list them all Aetio-pathogenesis of BRONJ: The incidence of BRONJ is more in jaw bones compared to rest of the skeleton owing to its vascularity. However this view has been challenged by Bauss F and Pfister T, 200855 suggesting similar uptake of ibandronate by spine, femur and jaw bones. Hence the aetiology for BRONJ remains unclear. The alternative explanation could be the initiation of BRONJ is in the mucosa rather than in bone. This view has been supported by Landesberg 2008,56 who showed pamidronate inhibits oral keratinocyte wound healing. Further Kim et al 201157,58 in their in vitro study showed that BPs can cause aging of keratinocyte and result in defective re-epithelialisation inside the mouth and they hypothesised that this could be contributing factor towards poor mucosal healing. Primarily the action of BP is said to be on bone cells3 . However few reports suggests bps inhibit angiogenesis by hampering vascular endothelial growth factor and also endothelial proliferation, thus reduced capillary tube formation, vessel sprouting and loss of blood vessel resulting in avascualr necrosis. However the anti angiogenic property of BPs has been challenged by a histological study who reported normal vascularity in bones exposed to BPs4,59,60 CLINICAL FEATURES: BRONJ can be presented in various forms such as unexplained pain, numbness, altered sensation to frank necrosis of the bone depending on the severity of the condition. The procedures such as placement of dental implants, minor oral surgical procedures, periodontal non surgical and surgical procedures and ill-fitting dentures can lead to BRONJ.6 Frequently non healing sockets presentation following extraction is common.6

 

Diagnosis of BRONJ:
Several investigative procedures are available for detecting early BRONJ [see box 2], yet there are no confirmatory tests available till date. The lab based investigation such as tissue biopsy is useful to rule out the possibility of metastatic malignant lesions. In addition panoramic radiographs may also be useful in cases of suspected metastases, though they are non specific. If there is a sequestrum shown on the radiograph this could help to differentiate from metastatic lesions.

 

Differential diagnosis58:
The diagnosis of potential BRONJ case needs the elimination of other possibilities such as Osteoradionecrosis, infectious osteomyelitis, neuralgia induced cavitational osteonecrosis, bone tumours, periapical pathology due to carious lesion, periodontal disease causing exposure of bone but with no history of bisphosphonate use, mucositis. “Concept of drug holiday”4,58,45,63 Temporarily withdrawing BPs for the purpose of reducing the risk of BRONJ following dental extractions has been recommended. Drug holiday can be three months before and after the extraction, with physician’s approval. Besides the dental purpose this concept has place even to reduce the non skeletal adverse events.64

Management of patients with established BRONJ:6,62,65
The exposed and sharp edges of necrotic bone should be debrided under local anaesthesia, If associated with infection, such as erythematous tender areas with suppuration and/or sinus tracts, systemic antibiotics are administered.59,66 The management of these patients may range from pain control till surgical resection of the jaws. Teeth with extensive carious lesion should undergo endodontic therapy instead of extraction. The endodontically treated teeth can be used as an abutment for over denture. Grade III mobile teeth can be extracted atraumatically and the patient should be followed up weekly for the first four weeks, then monthly until the sockets are healed and also there could be an indication for the empirical use of systemic antibiotics. Amoxicillin is the drug of choice, however the combination of amoxyllin and / clindamycin could offer extra benefit of bone penetration and wider spectrum of activity.60 PRINCIPLES IN THE CLINICAL USE OF BISPHOSPHONATES: Pre treatment evaluation Patient should be assessed by dentist before starting of the BP therapy. This requires communication between the physician/oncologist, patient and the dentist. As per the western literature about 41% 45 of physicians warn their patients about the risk of BRONJ and Asian literature does not provide any data on this issue. Benefits and risks:45,65,67 The issue of BRONJ must be dealt with caution as we cannot ignore the beneficial effects of bisphosphonates, such as prevention of morbidity and mortality in osteoporotic patients. Besides in-vitro research has suggested the bisphosphonates may have anti-tumour effects in breast cancer, prostate and lung cancers via alteration of adhesion of malignant cells to the extracellular matrix. Alternative bone modifiers may be considered, however their costs, potential adverse effects and the suitability influence the final decision

Alternative bone modifiers:
Denosumab58 is a monoclonal antibody, acts on the RANK ligand system, thus inhibiting osteoclastic resorption68. Stopeck A T 201069 conducted a randomized double blind study and found that denosumab compared to zoledronic acid reduced events such as skeletal fractures. Teriparatide [PTH 1-34]68 is a synthetic parathyroid hormone with anabolic effects on the bone. Although the net effect of excess PTH is to induce bone resorption, in low and intermittent doses it promotes bone formation by indirectly involving insulin growth factor 1, without stimulating bone resorption.70

Raloxifene is a selective estrogen-receptor modulator, which retains the beneficial effects on bone without deleterious effects on breast and uterus. This is approved for treatment of osteoporosis68,71 Strontium ranalate is composed of an organic ion, ranelic acid, bound to two atoms of strontium. This acts by blocking osteoclast differentiation and induces apoptosis and thus inhibiting bone resorption68. To conclude, there are plenty of evidence to suggest that bisphosphonates are used extensively by physicians and oncologists. In addition therapeutic application in dentistry have also been explored in invitro, animal and human studies. This review focussed on human studies alone. Available Asian literature based on randomized controlled clinical trials on the local drug delivery have shown promising results. However there is lack of evidence on the systemic use of bisphosphonates in the treatment of periodontal disease. Further, there are very few Asian literatures regarding BRONJ. This could be due to lack of communication between dentists and medical specialists. In our view pretreatment dental evaluation must be made mandatory and perhaps some guidelines by Asian authorities across the continent would be useful in assessing the incidence of BRONJ and prevention of the same

ACKNOWLEDGEMENTS
Authors acknowledge the immense help received from the scholars whose articles are 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.

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70. Pongthorn Narongroeknawin, Maria I. Danila, Lewis G. Humphreys Jr, Andrei Barasch, Jeffrey R.Curtis bisphosphonates associated osteonecrosis of the jaw with healing after teriparatide a review of the literature and a case report . Spec care dentist 2010;30(2):77-82.

71. Pasion EG, Sivananthan SK, Kung AW, Chen SH, Chen YJ, Mirasol R, Tay BK, Shah GA, Khan MA, Tam F, Hall BJ, Thiebaud DComparison of raloxifene and bisphosphonates based on adherence and treatment satisfaction in postmenopausal Asian women. J Bone Miner Metab. 2007; 25(2):105-13.

Announcements

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

COPE guidelines for Reviewers

SCOPUS indexing: 2014, 2019 to 2021


Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

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 editor@ijcrr.com 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 editor@ijcrr.com for more details.

Emerging Researcher Award:

‘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 editor@ijcrr.com for more details.


Best Article Award

A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
A study by Alice Alice entitled \"Strengthening of Human Milk Banking across South Asian Countries: A Next Step Forward\" is awarded Best article of Vol 14 issue 20
A study by Sathyanarayanan AR et al. entitled \"The on-task Attention of Individuals with Autism Spectrum Disorder-An Eye Tracker Study Using Auticare\" is awarded Best article of Vol 14 issue 19
A study by Gupta P. et al. entitled \"A Short Review on \"A Novel Approach in Fast Dissolving Film & their Evaluation Studies\" is awarded Best Article of Vol 14 issue 18.
A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
A study by Ali Nawaz et al. entitled \"A Comparative Study of Tubeless versus Standard Percutaneous Nephrolithotomy (PCNL) \? A Randomized Controlled Study\" is awarded Best Article for Vol 14 issue 16.
A study by Singh R. et al. entitled \"A Prospective Study to Find the Association of Astigmatism in Patients of Vernal Keratoconjunctivitis (VKC) in a Tertiary Health Care Centre in India (Vindhya Region MP)\" is awarded Best Article for Vol 14 issue 15
A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
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.



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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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