International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
Bootstrap Slider

Indexed and Abstracted in: Crossref, CAS Abstracts, Publons, CiteFactor, Open J-Gate, ROAD, Indian Citation Index (ICI), Indian Journals Index (IJINDEX), Internet Archive, IP Indexing, Google Scholar, Scientific Indexing Services, Index Copernicus, ResearchBib, Science Central, Revistas Medicas Portuguesas, EBSCO, BOAI, SOROS, NEWJOUR, ResearchGATE, Ulrich's Periodicals Directory, DocStoc, PdfCast, getCITED, SkyDrive, Citebase, e-Print, WorldCat (World's largest network of library content and services), Electronic Journals Library by University Library of Regensburg, SciPeople.

Search Articles

Track manuscript

Readers around the world

Full Html

IJCRR - Vol 06 Issue 16, August, 2014

Pages: 07-19

Date of Publication: 20-Aug-2014

Print Article   Download XML  Download PDF


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


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:

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.

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


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.

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

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.


1. Newman,Takei, Klokkevold, Carranza. Carranza’s Clinical Periodontology 11th edition: Perry R, Klokkevold and Brian L Mealey, Part 5, Chapter 27: influence of systemic condition on the periodontium. Elsevier publications, 2011: 315- 317.

2. Yazdana Arrain, Tahir Masud. Bisphosphonates and osteonecrosis of the jaw – current thoughts. Dent update 2009; 36:415-419.

3. Howard C. Tenenbaum, Avi Shelemay, Bruno Girard, Ron Zohar , Peter C Fritz. Bisphosphonates and Periodontics – Potential application for regulation of bone mass in the periodontium and other therapeutic/diagnostic uses. J Periodontal 2002;73:813-822.

4. Niall M.H McLeod, Peter A.Brennan, Salvatore L. Ruggierro. Bisphosphonate osteonecrosis of the jaw - A historical and contemporary review. The Surgeon 2012; 10: 36-42.

5. R.G.G. Russel, N.B. Watts, F.H. Ebetino, M.J. Rogers Mechansim of action of bisphosphonates – similarities and differences and their potential influence on clinical efficacy. Osteoporos Int 2008;19:733-759.

6. Kate Barker, Simon Rogers. Bisphosphonates associated osteonecrosis of the jaw – a guide for the general dental practitioners. Dental update 2006;33:270-275.

7. Ligia J. Dominguez, Antonio Galioto, Anna Ferlisi, Maria Adele Alessi, Mario Belvedere, Ernesto Putignano, Giuseppe Costanza, Maurizio Bevilacqua, Mario Barbagallo. Intermittent intramuscular clodronate therapy: a valuable option for older osteoporotic women: Age and Ageing 2005; 34: 633–645.

8. Graziani F, Cei S, Guerrero A, LA Ferla F, Vano M, Tonetti M, Gabriele M. Lack of short term adjunctive effect of systemic neridronate in non-surgical periodontal therapy of advanced generalized chronic periodontitis: an open label randomized clinical trial. J. Clin Periodontal 2009;36:419- 427.

9. Hisashi Shinoda, Sadaaki Takeyama, Keiko Suzuki, Shinobu Murakami, and Shoji Yamada Forum Mini review Pharmacological Topics of Bone Metabolism:A Novel Bisphosphonate for the Treatment of Periodontitis. J Pharmacol Sci 106, 555 – 558 (2008).

10. Robert E Marx. Bisphosphonate induced osteonecrosis of the jaws II edition. Chapter 2. Modes of action and pharmacokinetics of the bisphosphonate family. Page no: 9-21. Quintessence publishing, Inc.

11. Gideon A Rodan, Hervert A Fleisch. Bisphosphonates: mechanism of action. J. Clin Invest. 1996;97(12):2692- 2696.

12. Anke J. Roelofs, Keith Thompson, Sharon Gordon. Molecular Mechanisms of Action of Bisphosphonates: Current Status. Clin Cancer Res 2006;12:6222-6230.

13. R. Graham G. Russell. Bisphosphonates: Mode of Action and Pharmacology: Pediatrics 119, Supplement 2, March (2007) s150-s162.

14. Luigi Sinigaglia, Massimo Verenna, Silvia Casari. Pharmacokinetic profile of Bisphosphonates in the treatment of metabolic bone disorders. Clinical cases in mineral and bone metabolism 2007;4(1):30-36.

15. You L, Sheng ZY, Chen JY, Pan L, Chen L. The safety and efficacy of early-stage bi-weekly alendronate to improve bone mineral density and bone turnover in chinese postmenopausal women at risk of osteoporosis J Int Med Res 2011;39(1):302-10.

16. Jeal W, Barradell LB, McTavish D. Alendronate. A review of its pharmacological properties and therapeutic efficacy in postmenopausal osteoporosis: Drugs. 1997 Mar; 53(3):415-34.

17. GL Borromeo, CE Tsao, IB Darby, PR Ebeling. A review of the clinical implication of bisphosphonates in dentistry. Australian Dental Journal 2011;56:2-9.

18. El-Shinnawi UM, El-Tantawy SI. The effect of alendronate sodium on alveolar bone loss in periodontitis (clinical trial): J Int Acad Periodontal. 2003 Jan;5(1):5-10.

19. Michael S. Reddy, Nico C. Geurs, John C. Gunsolley.Periodontal Host Modulation with Antiproteinase, Anti-Inflammatory, and Bone-Sparing Agents.A Systematic Review: Annals of Periodontology December 2003, Vol. 8, No. 1, Pages 12-37.

20. Menezes AM, Rocha FA, Chaves HV, Carvalho CB, Ribeiro RA, Brito GA. Effect of sodium alendronate on alveolar bone resorption in experimental periodontitis in rats. J Periodontol. 2005 Nov;76(11):1901-9.

21. Weinreb M, Quartuccio H, Seedor JG, Aufdemorte TB, Brunsvold M, Chaves E, Kornman KS, Rodan GA. Histomorphometrical analysis of the effects of the bisphosphonate alendronate on bone loss caused by experimental periodontitis in monkeys. . J Periodontal Res 1994 Jan; 29(1):35- 40.

22. G Thirumal Reddy, T M Pramod Kumar, and Veena. Formulation and evaluation of Alendronate Sodium gel for the treatment of bone resorptive lesions in Periodontitis Drug Deliv 2005 ; 12(4):217-22.

23. Jeffcoat MK, Cizza G, Shih WJ, Genco R, Lombardi A. Efficacy of bisphosphonates for the control of alveolar bone loss in periodontitis: J Int Acad Periodontol.2007 Jul; 9(3):70-6.

24. Anuj Sharma, A.R. Pradeep: Clinical efficacy of 1% Alendronate Gel in Adjunct to Mechanotherapy in the Treatment of Aggressive Periodontitis: A Randomised Controlled clinical Trial: J Periodontol 2012:83: 19-26.

25. Pradeep AR, Kumari M, Rao NS, Naik SB. 1% Alendronate Gel as Local Drug Delivery in the Treatment of Class II Furcation Defects: A Randomized Controlled Clinical Trial. J Periodontol. 2013 Mar;84(3):307-15.

26. Binderman I, Adut M, Yaffe A. Effectiveness of local delivery of alendronate in reducing alveolar bone loss following periodontal surgery in rats. J Periodontol. 2000 Aug;71(8):1236-40.

27. Yaffe A, Iztkovich M, Earon Y, Alt I, Lilov R, Binderman I. Local delivery of an amino bisphosphonate prevents the resorptive phase of alveolar bone following mucoperiosteal flap surgery in rats J Periodontol. 1997 Sep;68(9):884-9.

28. Sharma A, Pradeep AR. Clinical efficacy of 1% alendronate gel as a local drug delivery system in the treatment of chronic periodontitis: a randomized, controlled clinical trial. J Periodontol. 2012;83(1):11-8.

29. H R Veena, Deepak Prasad. Evaluation of an amino bisphosphonate (Alendronate) in the management of periodontal osseous defects. Journal of Indian Society of Periodontology 2010;14(1):40-45.

30. Pradeep AR, Sharma A, Rao NS, Bajaj P, Naik SB, Kumari M. Local drug delivery of alendronate gel for the treatment of patients with chronic periodontitis with diabetes mellitus: a double-masked controlled clinical trial. J Periodontol. 2012 Oct; 83(10):1322-8.

31. Philip M. Preshaw. Host response modulation in periodontics: Periodontology 2000, 2008;48:92–110. 32. Keith L. Kirkwood, Joni A. Cirelli, Jill E. Rogers and William V. Giannobile. Novel Host Response Therapeutic Approaches To Treat Periodontal Diseases: Periodontology 2000, 2007;43:294–315.

33. Salvi GE, Lang NP. Host response modulation in the management of periodontal diseases. J Clin Peridontol 2005; 32 (Suppl. 6): 108–129.

34. Takaishi Y, Miki T, Nishizawa Y, Morii H. Clinical effect of etidronate on alveolar pyorrhoea associated with chronic marginal periodontitis: report of four cases. J Int Med Res. 2001: Jul-Aug; 29(4):355-65.

35. Zang C, Zhai J, Meng Y, Liang X. Developments in research of local bisphosphonate delivery system of implant denture. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2011: Apr; 28(2):415-8. [Article in Chinese]

36. BasmaMostafa, Ebtehalhamdy, NermineNassif. Combined effect of systemic Bisphosphonates, calcium and vitamin D on alveolar bone in osteoporotic post menopausal females having chronic periodontitis following surgical periodontal therapy. Life science journal 2012;9(3):613-622.

37. Bastian Peter, Olivier Gauthier, Samia La?¨b, Bruno Bujoli, Je´roˆme Guicheux, Pascal Janvier, G. Harry van Lenthe, Ralph Mu¨ ller, Pierre-Yves Zambelli, Jean-Michel Bouler, Dominique P. Pioletti. Local delivery of bisphosphonate from coated orthopedic implants increases implants mechanical stability in osteoporotic rats: J Biomed Mater Res 76A: 133–143, 2006.

38. Ying Gao, Shujuan Zou, Xiaoguang Liu, Chongyun Bao, Jing Hua, The effect of surface immobilized bisphosphonates on the fixation of hydroxyapatite-coated titanium implants in ovariectomized rats: Biomaterials 30 (2009) 1790–1796 [Chinese].

39. Abtahi J, Tengvall P, Aspenberg P. Bisphosphonate coating might improve fixation of dental implants in the maxilla: a pilot study. Int J Oral Maxillofac Surg. 2010 Jul; 39(7):673- 7.

40. Abtahi J, Tengvall P, Aspenberg P. A bisphosphonate-coating improves the fixation of metal implants in human bone. A randomized trial of dental implants. Bone. 2012 May; 50(5):1148-51.

41. M. Yoshinaria, Y. Odaa, T. Inoueb, K. Matsuzakab, M. Shimono. Bone response to calcium phosphate-coated and bisphosphonate immobilized titanium implants: Biomaterials 23 (2002) 2879–2885.

42. Lane N, Armitage GC, Loomer P, Hsieh S, Majumdar S, Wang HY, Jeffcoat M, Munoz T. Bisphosphonate therapy improves the outcome of conventional periodontal treatment: results of a 12-month, randomized, placebo-controlled study. J Periodontol. 2005 Jul; 76(7):1113-22.

43. Rocha M, Nava LE, Vázquez de la Torre C, Sánchez-Márin F, Garay-Sevilla ME, Malacara JM. Clinical and radiological improvement of periodontal disease in patients with type 2 diabetes mellitus treated with alendronate: a randomized, placebo-controlled trial. J Periodontol. 2001 Feb;72(2):204- 9.

44. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE, Mehrotra B. American Association of Oral and Maxillofacial Surgeons Position Paper on Bisphosphonate Related Osteonecrosis Of The Jaws. Update: 2009; 67:2-12. Task Force On Bisphosphonate Related Osteonecrosis Of The Jaws.

45. Gareth Brock, Kate Barker, Christopher J Butterworth, Simon Rogers. Practical considerations for treatment of patients taking bisphosphonates medications: An Update. Dent Update 2011;38:313-326.

46. W.Park.N, K.Kim.M, Y.Kim.Y, M.Rhee, H.J.Kim . Osteonecrosis of the jaw induced by oral administration of bisphosphonates in Asian population-5 cases. Osteoporos Int 2010;21:527-533.

47. Hong JW, Nam W, Cha IH, Chung SW, Choi HS, Kim KM, Kim KJ, Rhee Y, Lim SK. Oral bisphosphonate-related osteonecrosis of the jaw: the first report in Asia. Osteoporos Int. 2010 May; 21(5):847-53.

48. Kwon TG, Lee CO, Park JW, Choi SY, Rijal G, Shin HI. Os-teonecrosis associated with dental implants in patients undergoing bisphosphonate treatment. Clin Oral Implants Res. 2012 Dec 26. doi: 10.1111/clr.12088. [Epub ahead of print].

49. Yamazaki T, Yamori M, Ishizaki T, Asai K, Goto K, Takahashi K, Nakayama T, Bessho K. Increased incidence of osteonecrosis of the jaw after tooth extraction in patients treated with bisphosphonates: a cohort study. Int J Oral Maxillofac Surg. 2012 Nov; 41(11):1397-403. doi: 10.1016/j. ijom.2012.06.020. Epub 2012 Jul 26.

50. Assaf AT, Smeets R, Riecke B, Weise E, Gröbe A, Blessmann M, Steiner T, Wikner J, Friedrich RE, Heiland M, Hoelzle F, Gerhards F. Incidence of bisphosphonaterelated osteonecrosis of the jaw in consideration of primary diseases and concomitant therapies. Anticancer Res. 2013 Sep;33(9):3917-24.

51. Ulmner M, Jarnbring F, Törring O. Osteonecrosis of the Jaw in Sweden Associated With the Oral Use of Bisphosphonate. J Oral Maxillofac Surg. 2013 Aug 28.

52. Braun E, Iacono VJ. Bisphosphonates: case report of nonsurgical periodontal therapy and osteochemonecrosis. Int J Periodontics Restorative Dent. 2006 Aug;26(4):315-9.

53. Bedogni A, Bettini G, Totola A, Saia G, Nocini PF. Oral bisphosphonate-associated osteonecrosis of the jaw after implant surgery: a case report and literature review. J Oral Maxillofac Surg. 2010 Jul; 68(7):1662-6.

54. Hom-Lay Wang, Daniel Weber, Laurie K. McCauley. Effect of Long-Term Oral Bisphosphonates on Implant Wound Healing: Literature Review and a Case Report; Journal of Periodontology, March 2007, Vol. 78, No. 3, Pages 584-594.

55. Bauss F, Pfister T, Papapoulos S. Ibandronate uptake in the jaw is similar to long bones and vertebrae in the rat. J Bone Miner Metab 2008;26;406-408.

56. Regina Landesberg, Matthew Cozin, Serge Cremers, Victoria Woo, Stavroula Kousteni, Satrajit sinha, LeeAn Garrett Sinha, Srikala Raghavan. Inhibition of Oral mucosal cell wound healing by bisphosphonates. J Oral Maxillofac Surg 2008; 66:839-847.

57. Kim RH, Lee RS, Williams D, Bae S, Woo J, Lieberman M, Oh JE, Dong Q, Shin KH, Kang MK, Park NH. Bisphosphonates induce senescence in normal human oral keratinocytes. . J Dent Res. 2011 Jun;90(6):810-6.

58. Yazdana Arrail, Tahir Masud. A current update on osteonecrosis of the jaw and bisphosphonates. Dent Update 2011;38:672-678.

59. Cesar A. Migliorati, Jeffrey Casiglia, Joel Epstein, Peter L Jacobsen, Sook-Bin Woo. Managing the care of patients with bisphosphonate-associated osteonecrosis. An American Academy of Oral Medicine Position Paper. JADA 2005; Vol 136: 1658-1668.

60. Robin A Seymour, Graham Walton. Effects of Malignant disease and treatments on oral structures. Dent Update 2009;36:594-603.

61. Ho YF, Lin JT, Wu CY. Oral bisphosphonates and risk of esophageal cancer: a dose-intensity analysis in a nationwide population. Cancer Epidemiol Biomarkers Prev. 2012 Jun;21(6):993-5.

62. Yazdana Arrain, TahirMasud. A recent recommendation on bisphosphonate – associated osteonecrosis of the jaw: Dent Update 2008;35:238-242.

63. Joan otomo-corgel. Osteoporosis and osteopenia: implications for periodontal and implant therapy: Periodontology 2000, Vol. 59, 2012, 111–139.

64. Susan M. What is the optimal duration of bisphosphonate therapy? Cleveland Clinic Journal of Medicine 2011; 78(9): 619-630.

65. Salvatore Ruggiero, Julie Gralow, Robert E Marx, Mark M Schubert, Joseph M Huryn, Bela Toth, Kathryn Damato, Vicente Valero. Practical guidelines for the prevention, diagnosis, and treatment of osteonecrosis of the jaw in Patients with cancer. Journal of Oncology Practice 2006 vol 2, issue 1: 7 – 14.

66. Yoh Sawatari, Robert E Marx. Bisphosphonates and Bisphosphonate induced osteonecrosis. Oral Maxillofacial Surg Clin N Am 2007;19:487-498.

67. Marjorie K Jeffcoat Safety of oral bisphosphonates: controlled studies on alveolar bone Int J Oral Maxillofac Implant 2006;21:349-353.

68. Bertram G. Katzung, Susan B Masters, Antony J Trevor. Basic and Clinical pharmacology 11th edition Tata McGrawHill publication; 2010: Chapter 42 agents that affect bone mineral homeostasis: Daniel D Bikle, 753-772.

69. Stopeck AT, Lipton A, Brody JJ. Denosumab compared with Zolendronic acid for the treatment of bone metastases in patients with advanced breast cancer: A randomized double blind study. J Clin Oncol 2010;28:5132-5139.

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.


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

SCOPUS (2014, 2019, 2020, 2021 (Till June) currently under re-evaluation)

COPE guidelines for Reviewers

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 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.

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 for more details.

Best Article Award

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 Leow Jun Xian and 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 et al. entitled "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 COLAKOGLU 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 Arpita M. et al 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
Late to bed everyday? You may die early, get depression
Egg a day tied to lower risk of heart disease
88 Percent Of Delhi Population Has Vitamin D Deficiency: ASSOCHAM Report

List of Awardees

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

Awardees of COVID-19 Research

Woman Researcher Award

A Study by Neha Garg et al. entitled "Optimization of the Response to nCOVID-19 Pandemic in Pregnant Women – An Urgent Appeal in Indian Scenario" published in Vol 12 issue 09

A Study by Sana Parveen and Shraddha Jain entitled "Pathophysiologic Enigma of COVID-19 Pandemic with Clinical Correlates" published in Vol 12 issue 13

A Study by Rashmi Jain et al. entitled "Current Consensus Review Article on Drugs and Biologics against nCOVID-19 – A Systematic Review" published in Vol 12 issue 09

Emerging Researcher Award

A Study by Madhan Jeyaraman et al. entitled "Vitamin-D: An Immune Shield Against nCOVID-19" published in Vol 12 issue 09

Study by Dheeraj Kumar Chopra et al. entitled "Lipid-Based Solid Dispersions of Azilsartan Medoxomil with Improved Oral Bioavailability: In Vitro and In Vivo Evaluation" published in Vol 12 issue 19

RSS feed

Indexed and Abstracted in

Antiplagiarism Policy: IJCRR strongly condemn and discourage practice of plagiarism. All received manuscripts have to pass through "Plagiarism Detection Software" test before forwarding for peer review. We consider "Plagiarism is a crime"

IJCRR Code of Conduct: We at IJCRR voluntarily adopt policies on Code of Conduct, and Code of Ethics given by OASPA and COPE. To know about IJCRRs Code of Conduct, Code of Ethics, Artical Retraction policy, Digital Preservation Policy, and Journals Licence policy click here

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.

Company name

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


148, IMSR Building, Ayurvedic Layout,
        Near NIT Complex, Sakkardara,
        Nagpur-24, Maharashtra State, India

Copyright © 2021 IJCRR. Specialized online journals by ubijournal .Website by Ubitech solutions