articol-alsheri-2017

ORAL IMPLANTOLOGY
A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-




                                                                                                                                                                                  Review Article
IMPLANT DISEASES

Mohammed Alshehri1a*
¹Dental Department, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

BDS, AEGD, SSC-ARD, SF-DI, Consultant in Cosmetic Restorative and Implant Dentistry
a




                                                                                                                                                    Received: February 01, 2017
                                                                                                                                                     Revised: February 23, 2017
                                                                                                                                                      Accepted: March 06, 2017
                                                                                                                                                      Published: March 07, 2017

Academic Editor: Constantinus Politis, MD, DDS, MM, MHA, PhD, Professor and Chairperson, University of Leuven, Leuven, Belgium


Cite this article:
Alshehri M. A comprehensive review of systemic factors associated with periimplant diseases. Stoma Edu J. 2017;4(1):37-43.


ABSTRACT                                                                                           DOI: 10.25241/stomaeduj.2017.4(1).art.3
Background: A variety of systemic factors have been associated with peri-implant diseases.
Objective: The aim of the present comprehensive review was to assess current literature regarding
the systemic factors associated with the etiology of peri-implant diseases.
Results: Both normal and premalignant oral mucosa cells (NOK and POE9i) displayed uptake
of PLGAChiNPs in a time and concentration-dependent manner, both in 2D and 3D models. A
higher and more rapid uptake of PLGAChi NPs by precancerous cell line POE9i was observed
when compared to NOKs. Interestingly, DPCs did not display internalized PLGAChi NPs, even at the
highest concentration of 200 g/mL.
Data source: Databases were searched till January 2017 using different combinations of the following
key words: “acquired immune deficiency syndrome”; “cancer”; “diabetes mellitus”; “genetic”; “peri-
implant diseases”; “peri-implantitis”, “renal”; and “risk-factors”.
Study selection: Clinical studies assessing the systemic factors associated with the etiology of peri-
implantitis were included. Letters to the Editor, case-reports, case-series, in-vitro studies, studies on
animal models and commentaries were excluded.
Data extraction: The pattern of the present comprehensive review was customized to primarily
summarize the pertinent information.
Data synthesis: Poorly-controlled diabetes mellitus (DM) is a significant risk factor for peri-implant
diseases; however, under optimal glycemic control dental implants can osseointegrate in patients
with DM. Osteoporosis and rheumatoid arthritis have been associated with peri-implant diseases;
however, implant surface modifications and optimal oral hygiene maintenance are essential
parameters that can facilitate osseointegration in these patients. Although irradiation is a significant
risk-factor for peri-implant diseases; studies have shown that osseointegration and survival of
implants is possible in cancer patients. There is a weak evidence that HIV infection is no more a
contradiction for implant therapy. Although systemic diseases are significant risk-factors for dental
implant failure, proper management of the systemic disorder and optimal oral hygiene may support
osseointegration and survival of dental implants in medically-compromised patients.
Keywords: acquired immune deficiency syndrome, cancer, diabetes mellitus, genetic, peri-implant
diseases.

1. Introduction                                                                                       implants.4, 5 According to a consensus report from
Although studies1-3 have reported implant                                                             the 6th European Workshop on Periodontology,
success and survival rates of up to 100%; a                                                           peri-implantitis is defined as the presence of
number of systemic factors have been reported                                                         inflammation of the peri-implant mucosa and
to jeopardize the success and survival of dental                                                      concurrent loss of supporting alveolar bone.6

*Corresponding author:
Dr Mohammed Alshehri, BDS, AEGD, SSC-ARD, SF-DI, Dental Department, King Khalid, University Hospital, King Saud University, Riyadh, Saudi Arabia.
Tel/Fax: +96.655.380.333 / +966.114.672.428, e-mail: dr_mzs@hotmail.com




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                 A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-IMPLANT DISEASES



                 Mombelli et al.7 described peri-implantitis as a site-     also been associated with the etiology of peri-
Review Article   specific inflammatory condition, which displays            implantitis cannot be disregarded (Fig. 1).17-21
                 clinical and radiographic features that are similar        Considering the length of the article, the author
                 to those in patients with chronic periodontitis.           dedicated the present article to comprehensively
                 Data regarding the prevalence of peri-implantitis          review the systemic risk-factors associated with
                 is inconsistent. In the study by Koldsland et              the etiology of peri-implantitis. The aim of the
                 al.,8 the prevalence of peri-implantitis ranged            present comprehensive review was to provide
                 between 11.3% and 47.1%; whereas Mombelli                  an overview of current literature regarding the
                 et al.9 reported peri-implantitis in 20% of their          systemic conditions associated with the etiology
                 study population during 5 to 10 years of follow-           of peri-implantitis.
                 up. In the study by Zitzmann and Berglundh,6
                 the frequency of peri-implantitis varied between           2. Materials and methods
                 28% and at least 56% of the participants and               2.1. Focused question
                 12% and 43% of individual implants. Peri-implant           The addressed focused question was “Which
                 diseases are categorized into two types namely,            systemic conditions are associated with the
                 peri-implant mucositis and peri-implantitis. Peri-         etiology of peri-implant diseases?”
                 implant mucositis is characterized by inflammation         2.2. Literature search strategy
                 of soft tissues around the implant without any             PubMed/Medline, Scopus, EMBASE, ISI Web of
                 signs of peri-implant alveolar bone loss.6 Patients        knowledge and Google-Scholar databases were
                 with peri-implant mucositis exhibit bleeding on            searched from till January 2017 using the following
                 probing (BOP), peri-implant probing depth ≥                key words: “arthritis”, “cancer”, “diabetes mellitus”;
                 4mm and/or suppuration.10,11                               “acquired      immune      deficiency     syndrome”;
                 A variety of factors, local as well as systemic            “renal disorders”; “osteoporosis”, “peri-implant/
                 factors have been associated with the etiology of          periimplant” and “genetics”.
                 peri-implantitis.12-16 It is well known that poor oral     Clinical studies assessing the local risk-factors
                 hygiene, tobacco smoking, poor bone quality and            associated with the etiology of peri-implant
                 quantity, jaw location and bruxism are among               diseases were included.
                 the most common local factors associated with              2.3. Eligibility criteria
                 the etiology of peri-implantitis. Nevertheless,            Results from only clinical studies were included.
                 the contribution of systemic factors such as               Letters to the Editor, historic reviews, case-reports,
                 immunosuppression (as observed in patients                 case-series, in-vitro studies, studies on animal
                 with acquired immune deficiency syndrome,                  models and commentaries were excluded. The
                 osteoporosis, poorly-controlled diabetes mellitus          pattern of the present comprehensive review was
                 and cancer) and use of medications (such as                customized to primarily summarize the pertinent
                 bisphosphonates and corticosteroids) that have             information.




                  Figure 1. Systemic factors associated with peri-implant diseases.




   38                                                              Stoma Edu J. 2017;4(1):37-43. http://www.stomaeduj.com
      A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-IMPLANT DISEASES



3. Results                                                two main categories of BPs are the “non-nitrogen”




                                                                                                                      Review Article
3.1. Diabetes mellitus                                    and “nitrogen-containing” BPs.40 Non–nitrogen-
Diabetes mellitus (or diabetes) is a common               containing BPs are metabolized rapidly, whereas
metabolic disorder characterized by hypergly-cemia        nitrogen-containing BPs are much more potent and
due to impaired insulin secretion, insufficient insulin   are not metabolized.41 These drugs act by inhibiting
action, or both.22 The main types of diabetes include     osteoclastic activity and inducing their apoptosis.18
type 1 diabetes and type 2 diabetes. Type 1 diabetes      BPs may be administered by either oral or
is associated with pancreatic beta (β)-cell destruction   intravenous routes. Oral BPs are used in the treatment
and accounts for 5-10% of the subjects with diabetes.     of diseases such as osteoporosis and Pagets’
Type 2 diabetes is associated with a relative, rather     disease; while intravenous BPs are administered to
than an absolute insulin deficiency and accounts          patients with breast cancer, multiple myeloma, bone
for 90-95% of all individuals with diabetes.23            metastasis and malignant hypercalcemia. The chief
Individuals with poorly-controlled diabetes are more      complication observed in patients under either oral
susceptible to develop complications after implant        or intravenous BP therapy is osteonecrosis of the jaw
therapy compared to individuals with well-controlled      (ONJ).42 It has been suggested that all patients under
diabetes.24                                               bisphosphonate therapy who are expected to receive
Chronic hyperglycemia has been related with tissue        dental implants should be informed of the possible
damage, since endothelial cells take up glucose           risks of development of ONJ and consequent
passively in an insulin-independent manner.25,26          implant loss beforehand; and an informed-consent
Hyperglycemia is also associated with an altered          must be obtained prior to installation of dental
host resistance, for example, defective migration         implants in these individuals.14,15
of polymorphonuclear leukocytes, impaired                 Although, the risk of developing ONJ in patients
phagocytosis and an exaggerated inflammatory              using BPs is estimated to be minimal (approximately
response to microbial products.27                         0.09%), there still exists a controversy over the
The treatment of diabetes focuses on the attainment       placement of dental implants in patients treated
of an optimal glycemic control in order to impede         with BPs.43 Results from case-reports44-47 have
complications.                                            shown that dental implants can osseointegrate
Individuals with diabetes are more susceptible to         and remain functionally stable in patients under
periodontal disease, which is also recognized as the      BP therapy. Similar results have been reported
sixth complication of diabetes.28-32                      in retrospective studies.48,49 Results by Bell and
The underlying pathophysiology that increases             Bell50 showed comparable implant survival rates
the risk of periodontal bone loss in subjects with        between patients using BPs and controls, that is,
diabetes is poorly understood; however it has been        95% and 96.5% respectively. Brooks et al.47 placed
associated with the formation and accumulation of         10 implants in a patient on bisphosphonate therapy
glucose-mediated advanced glycation end-products          out of which, 9 implants osseointegrated successfully
(AGEs).                                                   giving a success rate of 90%. Likewise, results from
AGEs accumulate in the plasma and tissues (including      a case-report by Wang et al.44 also showed implant
the periodontium) during the process of normal            healing to be uneventful with no alterations in the
aging, but to an accelerated degree in subjects           healing process of dental implants in a patient
with diabetes.33 AGEs contribute to periodontal           using BPs. Fugazzotto et al.51 showed that a history
destruction by activating receptors called “Receptor      of bisphosphonate therapy was not associated
for AGEs (RAGE)” located on the periodontium              with the occurrence of ONJ following installation of
and by reducing the production of matrix proteins,        immediately-loaded dental implants.
such as collagen and osteocalcin by gingival and          In their systematic review, Javed and Almas18
periodontal fibroblasts.34-38                             reported that the incidence of implant failure in
It has been suggested that the pathogenesis of            patients taking BPs is minimal.
diabetes and its complications are associated with        The authors also concluded that placement of dental
an increased RAGE expression.29,39                        implants in patients taking BPs can have a positive
Other cell types with RAGE expression include             outcome.18
glomerular epithelial cells (podocytes), endothelial      3.3. Osteoporosis and rheumatoid arthritis
cells, vascular smooth muscle cells, inflammatory         Osteoporosis is a metabolic disease of bone
mononuclear phagocytes and lymphocytes.39                 characterized by low bone mineral density
Therefore, an impaired glycemic status may                (BMD) and reduced bone mass due to impaired
negatively affect the outcome of implant therapy. In      bone metabolism and imbalanced osteoblastic
a systematic review, Javed and Romanos19 reported         and osteoclastic activities.52,53 In osteoporotic
that under optimal glycemia control, dental implants      bone, osteoblasts demonstrate impaired pro-
can osseointegrate and remain functionally stable         liferative, synthetic and reactive ability to cellular
over long durations in patients with diabetes.            mediators.52,54,55
3.2. Bisphosphonates                                      Underlying causes of osteoporosis include pre- and
Bisphosphonates (BPs), (such as alendronate,              postmenopausal estrogen deficiency, excessive
risendronate, ibandronate, and clodronate) are            glucocorticoid intake, eating disorders such as
important group of drugs used for the treatment           anorexia nervosa and celiac disease.56,57 Although
of metabolic and oncologic pathologies involving          the bone quality and strength are compromised in
the skeletal system. The mode of action of BPs            osteoporotic patients; osteoporosis is not considered
depends on the drugs’ chemical structure. The             a contraindication for implant the-rapy.58,59 In a recent



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                 A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-IMPLANT DISEASES



                 systematic review, Javed et al.60 assessed the effect    dental implantation ranged from 6 to 15 months.
Review Article   of osteogenic coatings on the osseointegration of        The overall implant failure rate of 9.53% and
                 implants under induced osteoporotic conditions.          osseointegration success rates ranged between
                 Nearly 80% studies reported that osteogenic              62.5% and 100%.67 In another review, Javed et al.20
                 coatings around implant surfaces enhance bone            assessed the implant survival rate after oral cancer
                 formation, bone-to-implant contact (BIC) and bone        therapy. In total, 21 studies were included in this
                 volume (BV) under osteoporosis-like conditions.          review out of which, 16 studies reported that dental
                 This could possibly be accredited to the increase        implants can osseointegrate and remain functionally
                 in surface roughness of the implant caused by            stable in patients having undergone radiotherapy
                 osteogenic coatings, which facilitate the attachment     following oral cancer surgery.20 The authors
                 of osteoprogenitor cells to the implant surface.         concluded that dental implants can osseointegrate
                 Holahan et al.59 conducted a retrospective study         and remain functionally stable in patients having
                 to evaluate whether a diagnosis of osteoporosis          undergone oral cancer treatment.20
                 affected the survival rate of osseointegrated dental     3.5. Human immunodeficiency virus infection
                 implants. In this study59, a total of 3,224 implants     Human immunodeficiency virus (HIV) infection is
                 placed in 746 female patients aged at least 50 years     characterized by progressive immune system failure
                 old at the time of implant placement were assessed.      that gives rise to the development of opportunistic
                 The results showed that patients with a diagnosis of     infections and neoplasms. The virus invades CD4+
                 osteoporosis or osteopenia were not significantly        T lymphocytes, macrophages and dendritic cells,
                 more likely to develop implant failure compared to       and the CD4+ T cell counts gradually decrease as a
                 those without such a diagnosis.59                        result of direct cytopathic action or cytotoxic CD8+T
                 Krennmair et al.61 evaluated the implant treat-ment      lymphocyte-mediated attack. In a recent systematic
                 outcomes for patients suffering from autoimmune          review, Ata-Ali et al.68 attempted to answer the
                 rheumatoid arthritis (RA) with or without concomitant    following focused question “does HIV infection have
                 connective tissue diseases (CTD). In this study,61 34    an impact upon dental implant osseointegration?”
                 female patients (25 iso-lated RA; nine RA+CTD) were      The combinations of search terms resulted in a
                 included. At the mean duration of follow-up of nearly    list of 132 titles. Consequently, 101 studies were
                 46 month, all implants presented a survival rate of      excluded on the basis of the evaluation of the title
                 100%. In isolated RA patients, acceptable marginal       and abstract, thereby leaving 9 articles for eligibility
                 bone loss (MBL) (mean: 2.1 mm; SD: 0.5 mm), pocket       assessment. Amongst the studies included in this
                 depth (mean: 2.8 mm; SD:3.2 mm) and healthy soft-        systematic review, a total of 173 dental implants were
                 tissue conditions (plaque/bleeding/gingiva index         placed in 80 patients (135 implants in 56 HIV-positive
                 Grade 0 in 80%) were observed.61 Results from a case-    individuals and 38 implants in 24 HIV-negative
                 series report,62 showed a high implant survival rate     patients -control groups). A single loss of dental
                 during follow-up with a cumulative 3-year implant        implant osseointegration was recorded in an HIV-
                 success rate of 96.1%. In this study, RA patients        positive patient.68 In the study by Stevenson et al.69,
                 demonstrated acceptable MBL (mean: 2.1 +/- 0.5           40 dental implants were placed in 20 HIV-infected
                 mm) and satisfactory soft tissue conditions; whereas     patients. No implant osseointegration failures were
                 CTD patients showed increased MBL (mean: 3.1 +/-         recorded after 6 months of follow-up. Similarly, in
                 0.7 mm).                                                 another study of 39 dental implants placed in 24
                 The study62 concluded that a high implant and            HIV-infected patients, no implant osseointegration
                 prosthodontic success rate can be anticipated in         failures were recorded after 12 months of follow-
                 patients suffering from RA; however, the authors         up.70 Should dental implants placed in HIV positive
                 emphasized that optimal oral hygiene assists in          patients sustain bone levels in the long-term (5 years
                 ensuring stable long-term survival of dental implants    or longer) requires further investigations.
                 in patients with RA.62                                   3.6. Genetic factors
                 3.4. Irradiation                                         Jacobi-Gresser et al.71 assessed diagnostic markers
                 Osteoradionecrosis is usually observed several           to predict titanium implant failure.
                 years following radiotherapy and is associated with      The study reported that tumor necrosis factor-alpha
                 local trauma within the hypovascular–hypocellular        (TNF-α) and interleukin 1-beta (IL-1β) release on
                 hypoxic tissues (that occurs as a result of radiation-   titanium stimulation were significantly higher among
                 induced endarteritris).63 In this regard, the interval   patients with implant failure.
                 between the end of cancer therapy and placement          The results showed that IL-1β/TNF-α release and
                 of dental implants may contribute to the success         number of risk genotypes were significantly
                 or failure of osseointegration. Studies64-66 have        associated with implant failure.71
                 investigated the required time interval between          Vaz et al.72 examined IL-1 gene clusters in 155 patients
                 radiotherapy and implant installation that may           with 100 successful implants and 55 unsuccessful
                 influence osseointegration; however the results          implants.
                 remain debatable. In a systematic review, Zen Filho      The authors concluded that successful implants
                 et al.67 assessed the safety of dental implants placed   were associated with a negative genetic test and
                 in irradiated bone and to discuss their viability        that unsuccessful implants were associated with a
                 when placed post-radiotherapy. Eight publications        positive genetic test.72
                 were assessed in this systematic review67 and the        Casado and colleagues reported that the IL-6
                 results showed a total of 331 patients received 1237     genotype was 1.53 times more likely to convey peri-
                 implants. The time interval between irradiation and      implant disease if the individuals had the GC




   40                                                            Stoma Edu J. 2017;4(1):37-43. http://www.stomaeduj.com
       A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-IMPLANT DISEASES



genotype and allele G.                                                  may support osseointegration and survival of dental




                                                                                                                                              Review Article
                                                                        implants in medically-compromised patients.
4. Conclusion
Although systemic diseases such as poorly controlled                    Conflict of interest and financial disclosure
DM, RA and osteoporosis are significant risk-factors                    The author reports no conflict of interest and there
for dental implant failure, proper management of                        was no external source of funding for the present
the systemic disorder and optimal oral hygiene                          study.

References

1. Carames J, Tovar Suinaga L, Yu Yc, Perez A, Kang M.                      2000;15(3):425-431.
    Clinical advantages and limitations of monolithic zirconia              [PubMed] Google Scholar (225) Scopus (117)
    restorations full arch implant supported reconstruction:            16. Wahlström M, Sagulin GB, Jansson LE. Clinical follow-up of
    case series. Int J Dent. 2015;2015:392496. doi:                         unilateral, fixed dental prosthesis on maxillary implants. Clin
    10.1155/2015/392496.                                                    Oral Implants Res. 2010;21(11):1294-1300.
    [Full text links] [Free PMC Article] [PubMed] Google Scholar            [PubMed] Google Scholar (34) Scopus (19)
    (16) Scopus (10)                                                    17. Vohra F, Al-Rifaiy MQ, Almas K, Javed F. Efficacy of systemic
2. Fenner N, Hämmerle Ch, Sailer I, Jung Re. Long-Term                      bisphosphonate delivery on osseointegration of implants
    Clinical, Technical, And Esthetic Outcomes Of All-Ceramic               under osteoporotic conditions: lessons from animal
    Vs. Titanium Abutments On Implant Supporting Single-Tooth               studies. Arch Oral Biol. 2014;59(9):912-920. doi: 10.1016/j.
    Reconstructions After At Least 5 Years. Clin Oral Implants              archoralbio.2014.05.016.
    Res. 2016;27(6):716-723 doi: 10.1111/clr.12654.                         [Full text links] [PubMed] Google Scholar (21) Scopus (10)
    [Full text links] [PubMed] Google Scholar (15) Scopus (5)           18. Javed F, Almas K. Osseointegration of dental implants in
3. Jeong MA, Jung MK, Kim SG, Oh JS. Implant stability                      patients undergoing bisphosphonate treatment: a literature
    measurements in the long-term follow-up of dentis                       review. J Periodontol. 2010;81(4):479-484.doi: 10.1902/
    implants: a retrospective study with Periotest. Implant Dent.           jop.2009.090587.
    2015;24(3):263-266. doi: 10.1097/Id.0000000000000239.                   [Full text links] [PubMed] Google Scholar (92) Scopus (53)
    [Full text links] [PubMed] Google Scholar (4) Scopus (2)            19. Javed F, Romanos GE. Impact of diabetes mellitus and
4. Romanos GE, Javed F, Delgado-Ruiz RA, Calvo-Guirado JL                   glycemic control on the osseointegration of dental
    Peri-implant diseases: a review of treatment interventions.             implants: a systematic literature review. J Periodontol.
    Dent Clin North Am. 2015;59(1):157-178. doi: 10.1016/j.                 2009;80(11):1719-1730. doi: 10.1902/jop.2009.090283.
    cden.2014.08.002                                                        [Full text links] [PubMed] Google Scholar (225) Scopus (132)
    [Full text links] [PubMed] Google Scholar (39) Scopus (20)          20. Javed F, Al-Hezaimi K, Al-Rasheed A, Almas K, Romanos
5. Tonetti MS. Risk factors for osseodisintegration. Periodontol            GE. Implant survival rate after oral cancer therapy: a
    2000. 1998;17:55-62.                                                    review. Oral Oncol. 2010;46(12):854-859. doi: 10.1016/j.
    [Full text links] [PubMed] Google Scholar (144) Scopus (74)             oraloncology.2010.10.004.
6. Zitzmann NU, Berglundh T. Definition and prevalence                      [Full text links] [Free PMC Article] [PubMed] Google Scholar
    of peri-implant diseases. J Clin Periodontol. 2008;35(8                 (63) Scopus (37)
    Suppl):286-291. doi: 10.1111/j.1600-051x.2008.01274.x.              21. Lu SY, Huang CC. Resolution of an active peri-
    Review.                                                                 implantitis in a chronic steroid user by bone
    [Full text links] [PubMed] Google Scholar (854) Scopus (468)            augmentation with PepGen P-15 and a barrier
7. Mombelli A, van Oosten MA, Schurch E, Jr., Land NP.                      membrane. J Oral Implantol. 2007;33(5):280-287. doi:
    The microbiota associated with successful or failing                    10.1563/1548-1336(2007)33[280:ROAAPI]2.0.CO;2.
    osseointegrated titanium implants. Oral Microbiol Immunol.              [Full text links] [PubMed] Google Scholar (12) Scopus (3)
    1987;2(4):145-151.                                                  22. Classification and diagnosis of diabetes. Diabetes Care.
    [Full text links] [PubMed] Google Scholar (1713) Scopus                 2015;38 Suppl S8-S16. doi: 10.2337/dc15-s005.
    (1035)                                                                  [Full text links] [PubMed] Google Scholar (778) Scopus (476)
8. Koldsland OC, Scheie AA, Aass AM. Prevalence of peri-                23. Diagnosis and classification of diabetes mellitus. Diabetes
    implantitis related to severity of the disease with different           Care. 2005;28 Suppl 1:S37-S42. https://doi.org/10.2337/
    degrees of bone loss. J Periodontol. 2010;81(2):231-238.                diacare.28.suppl_1.S37
    doi: 10.1902/jop.2009.090269.                                           [Full text links] [PubMed] Google Scholar (13301) Scopus
    [Full text links] [PubMed] Google Scholar (298) Scopus (161)            (806)
9. Mombelli A, Müller N, Cionca N. The epidemiology of peri-            24. Fiorellini JP, Chen PK, Nevins M, Nevins ML. A retrospective
    implantitis. Clin Oral Implants Res. 2012;23 Suppl 6:67-76.             study of dental implants in diabetic patients. Int J
    doi: 10.1111/j.1600-0501.2012.02541.x. Review.                          Periodontics Restorative Dent. 2000;20(4):366-373.
    [Full text links] [PubMed] Google Scholar (347) Scopus (192)            [PubMed] Google Scholar (199) Scopus (97)
10. Khammissa RA, Feller L, Meyerov R, Lemmer J. Peri-implant           25. Ceriello A, Motz E. Is oxidative stress the pathogenic
    mucositis and peri-implantitis: clinical and histopathological          mechanism underlying insulin resistance, diabetes, and
    characteristics and treatment. SADJ. 2012;67(3):122, 124-               cardiovascular disease? The common soil hypothesis
    126. Review.                                                            revisited. Arterioscler Thromb Vasc Biol. 2004;24(5):816-823.
    [PubMed] Google Scholar (30) Scopus (13)                                doi: 10.1161/01.ATV.0000122852.22604.78. Review.
11. Jankovic S, Aleksic Z, Dimitrijevic B, et al. Prevalence                [Full text links] [Free article] [PubMed] Google Scholar (1364)
    of human cytomegalovirus and Epstein-Barr virus in                  26. Zhang Y, Qu Y, Niu T, Wang H, Liu K. O-GlcNAc modification
    subgingival plaque at peri-implantitis, mucositis and healthy           of Sp1 mediates hyperglycaemia-induced ICAM-1
    sites. A pilot study. Int J Oral Maxillofac Surg. 2011;40(3):271-       up-regulation in endothelial cells. Biochem Biophys
    276. doi: 10.1016/j.ijom.2010.11.004                                    Res Commun. 2017;484(1):79-84. doi: 10.1016/j.
    [Full text links] [PubMed] Google Scholar (23) Scopus (14)              bbrc.2017.01.068.
12. Tsigarida AA, Dabdoub SM, Nagaraja HN, Kumar                            [Full text links] [PubMed] Google Scholar (0) Scopus (1)
    PS. The influence of smoking on the peri-implant                    27. Soory M. Hormone mediation of immune responses in
    microbiome. J Dent Res. 2015;94(9):1202-1217. doi:                      the progression of diabetes, rheumatoid arthritis and
    10.1177/0022034515590581.                                               periodontal diseases. Curr Drug Targets Immune Endocr
    [Full text links] [Free PMC Article] [PubMed] Google Scholar            Metabol Disord. 2002;2(1):13-25.
    (24) Scopus (18)                                                        [PubMed] Google Scholar (53) Scopus (28)
13. Ferreira SD, Silva GL, Cortelli JR, Costa JE, Costa FO.             28. Löe H. Periodontal disease. The sixth complication of
    Prevalence and risk variables for peri-implant disease in               diabetes mellitus. Diabetes Care. 1993;16(1):329-334.
    Brazilian subjects. J Clin Periodontol. 2006;33(12):929-935.            [PubMed] Google Scholar (1377) Scopus (638)
    doi: 10.1111/j.1600-051x.2006.01001.x.                              29. Lamster IB, Lalla E. Periodontal disease and diabetes
    [Full text links] [PubMed] Google Scholar (363) Scopus (168)            mellitus: discussion, conclusions, and recommendations.
14. Degidi M, Nardi D, Piattelli A. 10-year prospective cohort              Ann Periodontol. 2001;6(1):146-149. doi: 10.1902/
    follow-up of immediately restored XiVE implants. Clin                   annals.2001.6.1.146
    Oral Implants Res. 2016 Jun;27(6):694-700. doi: 10.1111/                [PubMed] Google Scholar (62) Scopus (15)
    clr.12642.                                                          30. Javed F, Näsström K, Benchimol D, et al. Comparison of
    [Full text links] [PubMed] Google Scholar (12) Scopus (4)               periodontal and socioeconomic status between subjects
15. Miyata T, Kobayashi Y, Araki H, Ohto T, Shin K. The influence           with type 2 diabetes mellitus and non-diabetic controls.
    of controlled occlusal overload on peri-implant tissue. Part 3:         J Periodontol. 2007;78(11):2112-2119. doi: 10.1902/
    a histologic study in monkeys. Int J Oral Maxillofac Implants.          jop.2007.070186.




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                     [Full text links] [PubMed] Google Scholar (153) Scopus (105)            2007;103(6):780-786. doi: 10.1016/j.tripleo.2006.10.010.
Review Article   31. Javed F, Al Amri MD, Al-Kheraif AA, et al. Efficacy of non-             [Full text links] [PubMed] Google Scholar (89) Scopus (57)
                     surgical periodontal therapy with adjunct Nd:YAG laser              48. Tallarico M, Canullo L, Xhanari E, Meloni SM. Dental implants
                     therapy in the treatment of periodontal inflammation among              treatment outcomes in patient under active therapy with
                     patients with and without type 2 diabetes mellitus: A short-            alendronate: 3-year follow-up results of a multicenter
                     term pilot study. J Photochem Photobiol B. 2015;149:230-                prospective observational study. Clin Oral Implants Res.
                     234. doi: 10.1016/j.jphotobiol.2015.06.013.                             2016;27(8):943-949. doi: 10.1111/clr.12662
                     [Full text links] [PubMed] Google Scholar (15) Scopus (11)              [Full text links] [PubMed] Google Scholar (9) Scopus (3)
                 32. Javed F, Al-Kheraif AA, Salazar-Lazo K, et al. Periodontal          49. Al-Sabbagh M, Robinson FG, Romanos G, Thomas MV.
                     inflammatory conditions among smokers and never-                        Osteoporosis and bisphosphonate-related osteonecrosis
                     smokers with and without type 2 diabetes mellitus.                      in a dental school implant patient population. Implant Dent.
                     J Periodontol. 2015;86(7):839-846. doi: 10.1902/                        2015;24(3):328-332. doi: 10.1097/id.0000000000000234.
                     jop.2015.150120.                                                        [Full text links] [PubMed] Google Scholar (8) Scopus (3)
                     [Full text links] [PubMed] Google Scholar (19) Scopus (14)          50. Bell BM, Bell RE. Oral bisphosphonates and dental
                 33. Wautier JL, Guillausseau PJ. Advanced glycation end                     implants: a retrospective study. J Oral Maxillofac Surg.
                     products, their receptors and diabetic angiopathy. Diabetes             2008;66(5):1022-1024. doi: 10.1016/j.joms.2007.12.040.
                     Metab. 2001;27(5 Pt 1):535-542.                                         [Full text links] [PubMed] Google Scholar (139) Scopus (73)
                     [Full text links] [PubMed] Google Scholar (324) Scopus (209)        51. Fugazzotto PA, Lightfoot WS, Jaffin R, Kumar A. Implant
                 34. Fong Y, Edelstein D, Wang EA, Brownlee M. Inhibition of                 placement with or without simultaneous tooth extraction in
                     matrix-induced bone differentiation by advanced glycation               patients taking oral bisphosphonates: postoperative healing,
                     end-products in rats. Diabetologia. 1993;36(9):802-807.                 early follow-up, and the incidence of complications in two
                     [PubMed] Google Scholar (35) Scopus (22)                                private practices. J Periodontol. 2007;78(9):1664-1669. doi:
                 35. Schmidt Am, Weidman E, Lalla E, et al. Advanced glycation               10.1902/jop.2007.060514.
                     endproducts (AGEs) induce oxidant stress in the gingiva: a              [Full text links] [PubMed] Google Scholar (137) Scopus (79)
                     potential mechanism underlying accelerated periodontal              52. Torricelli P, Fini M, Giavaresi G, Giardino R. Human osteoblast
                     disease associated with diabetes. J Periodontal Res.                    cultures from osteoporotic and healthy bone: biochemical
                     1996;31(7):508-515.                                                     markers and cytokine expression in basal conditions and in
                     [Full text links] [PubMed] Google Scholar (289)                         response to 1,25(OH)2D3. Artif Cells Blood Substit Immobil
                 36. Lalla E, Lamster IB, Stern DM, Schmidt AM. Receptor for                 Biotechnol. 2002;30(3):219-227.
                     advanced glycation end products, inflammation, and                      [PubMed] Google Scholar (27)
                     accelerated periodontal disease in diabetes: mechanisms             53. NIH consensus development panel on osteoporosis
                     and insights into therapeutic modalities. Ann Periodontol.              prevention, diagnosis, and therapy, March 7-29, 2000:
                     2001;6(1):113-118. doi: 10.1902/annals.2001.6.1.113.                    highlights of the conference. South Med J. 2001;94(6):569-573.
                     [PubMed] Google Scholar (146) Scopus (81)                               [PubMed] Google Scholar (2) Scopus (178)
                 37. Oldfield MD, Bach LA, Forbes JM, et al. Advanced                    54. Wong MM, Rao LG, Ly H, et al. In vitro study of osteoblastic
                     glycation end products cause epithelial-myofibroblast                   cells from patients with idiopathic osteoporosis and
                     transdifferentiation via the receptor for advanced glycation            comparison with cells from non-osteoporotic controls.
                     end products (RAGE). J Clin Invest. 2001;108(12):1853-                  Osteoporos Int. 1994;4(1):21-31.
                     1863. doi: 10.1172/JCI11951                                             [PubMed] Google Scholar (49) Scopus (41)
                     [Full text links] [Free PMC Article] [PubMed] Google Scholar        55. Neidlinger-Wilke C, Stalla I, Claes L, et al. Human osteoblasts
                     (451)                                                                   from younger normal and osteoporotic donors show
                 38. Sajithlal G, Huttunen H, Rauvala H, Munch G. Receptor for               differences in proliferation and TGF beta-release in response
                     advanced glycation end products plays a more important                  to cyclic strain. J Biomech. 1995;28(12):1411-1418.
                     role in cellular survival than in neurite outgrowth during              [Full text links] [PubMed] Google Scholar (115)
                     retinoic acid-induced differentiation of neuroblastoma cells.       56. Abraham A, Cohen A, Shane E. Premenopausal bone
                     J Biol Chem. 2002;277(9):6888-6897. doi: 10.1074/jbc.                   health: osteoporosis in premenopausal women. Clin
                     M107627200.                                                             Obstet Gynecol. 2013;56(4):722-729.doi: 10.1097/
                     [Full text links] [PubMed] Google Scholar (57) Scopus (43)              grf.0b013e3182a8ae55
                 39. Kim W, Hudson BI, Moser B, et al. Receptor for advanced                 [Full text links] [Free PMC Article] [PubMed] Google Scholar
                     glycation end products and its ligands: a journey from the              (12) Scopus (7)
                     complications of diabetes to its pathogenesis. Ann N Y Acad         57. Corina M, Vulpoi C, Brănişteanu D. Relationship between
                     Sci. 2005;1043:553-561. doi: 10.1196/annals.1338.063.                   bone mineral density, weight, and estrogen levels in pre and
                     [Full text links] [PubMed] Google Scholar (101) Scopus (79)             postmenopausal women. Rev Med Chir Soc Med Nat Iasi.
                 40. Green JR. Bisphosphonates: preclinical review. Oncologist.              2012;116(4):946-950.
                     2004;9 Suppl 43-13. doi: 10.1634/theoncologist.9-90004-3.               [PubMed] Google Scholar (32) Scopus (13)
                     Review.                                                             58. Erdoğan O, Shafer DM, Taxel P, Freilich MA. A review of
                     [Full text links] [PubMed] Google Scholar (440) Scopus (300)            the association between osteoporosis and alveolar ridge
                 41. Frith JC, Mönkkönen J, Blackburn GM, Russell RG, Rogers                 augmentation. Oral Surg Oral Med Oral Pathol Oral
                     MJ. Clodronate and liposome-encapsulated clodronate                     Radiol Endod. 2007;104(6):738 E731-713. doi: 10.1016/j.
                     are metabolized to a toxic atp analog, adenosine 5'-(beta,              tripleo.2007.04.008. Review.
                     gamma-dichloromethylene) triphosphate, by mammalian                     [Full text links] [PubMed] Google Scholar (70) Scopus (37)
                     cells in vitro. J Bone Miner Res. 1997;12(9):1358-1367. doi:        59. Holahan CM, Koka S, Kennel KA, et al. Effect of osteoporotic
                     10.1359/jbmr.1997.12.9.1358.                                            status on the survival of titanium dental implants. Int J Oral
                     [Full text links] [PubMed] Google Scholar (465)                         Maxillofac Implants. 2008;23(5):905-910.
                 42. Vahtsevanos K, Kyrgidis A, Verrou E, et al. Longitudinal cohort         [PubMed] Google Scholar (99) Scopus (69)
                     study of risk factors in cancer patients of bisphosphonate-         60. Javed F, Vohra F, Zafar S, Almas K. Significance of osteogenic
                     related osteonecrosis of the jaw. J Clin Oncol.                         surface coatings on implants to enhance osseointegration
                     2009;27(32):5356-5362. doi: 10.1200/jco.2009.21.9584.                   under osteoporotic-like conditions. Implant Dent.
                     [Full text links] [PubMed] Google Scholar (293) Scopus (197)            2014;23(6):679-686. doi: 10.1097/id.0000000000000161.
                 43. Sambrook P, Olver I, Goss A. Bisphosphonates                            [Full text links] [PubMed] Google Scholar (31) Scopus (22)
                     and osteonecrosis of the jaw. Aust Fam Physician.                   61. Krennmair G, Seemann R, Piehslinger E. Dental implants in
                     2006;35(10):801-803.                                                    patients with rheumatoid arthritis: clinical outcome and peri-
                     [Full text links] [PubMed] Google Scholar (100) Scopus (74)             implant findings. J Clin Periodontol. 2010;37(10):928-936.
                 44. Wang HL, Weber D, Mccauley LK. Effect of long-term oral                 doi: 10.1111/j.1600-051x.2010.01606.x.
                     bisphosphonates on implant wound healing: literature                    [Full text links] [PubMed] Google Scholar (30) Scopus (14)
                     review and a case report. J Periodontol. 2007;78(3):584-594.        62. Weinlander M, Krennmair G, Piehslinger E. Implant
                     doi: 10.1902/jop.2007.060239. Review.                                   prosthodontic rehabilitation of patients with rheumatic
                     [Full text links] [PubMed] Google Scholar (173) Scopus (74)             disorders: a case series report. Int J Prosthodont.
                 45. Pirih FQ, Zablotsky M, Cordell K, Mccauley LK. Case report              2010;23(1):22-28.
                     of implant placement in a patient with paget's disease on               [PubMed] Google Scholar (16) Scopus (10)
                     bisphosphonate therapy. J Mich Dent Assoc. 2009;91(5):38-43.        63. Marx RE, Johnson RP. Studies in the radiobiology of
                     [PubMed] Google Scholar (11) Scopus (5)                                 osteoradionecrosis and their clinical significance. Oral Surg
                 46. Torres J, Tamimi F, Garcia I, et al. Dental implants in a patient       Oral Med Oral Pathol. 1987;64(4):379-390.
                     with Paget disease under bisphosphonate treatment: a case               [PubMed] Google Scholar (268) Scopus (399)
                     report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.           64. Schoen PJ, Raghoebar GM, Bouma J, et al. Prosthodontic
                     2009;107(3):387-392. doi: 10.1016/j.tripleo.2008.11.024.                rehabilitation of oral function in head-neck cancer patients
                     [Full text links] [PubMed] Google Scholar (23) Scopus (9)               with dental implants placed simultaneously during ablative
                 47. Brooks JK, Gilson AJ, Sindler AJ, et al. Osteonecrosis of the           tumour surgery: an assessment of treatment outcomes and
                     jaws associated with use of risedronate: report of 2 new                quality of life. Int J Oral Maxillofac Surg. 2008;37(1):8-16. doi:
                     cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.                10.1016/j.ijom.2007.07.015.




   42                                                                         Stoma Edu J. 2017;4(1):37-43. http://www.stomaeduj.com
       A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-IMPLANT DISEASES



    [Full text links] [PubMed] Google Scholar (88) Scopus (60)         70. Oliveira MA, Gallottini M, Pallos D, et al. The success of




                                                                                                                                                Review Article
65. Schoen PJ, Raghoebar GM, Bouma J, et al. Rehabilitation                endosseous implants in human immunodeficiency virus-
    of oral function in head and neck cancer patients after                positive patients receiving antiretroviral therapy: a pilot study.
    radiotherapy with implant-retained dentures: effects of                J Am Dent Assoc. 2011;142(9):1010-1016.
    hyperbaric oxygen therapy. Oral Oncol. 2007;43(4):379-388.             [Full text links] [PubMed] Google Scholar (28) Scopus (19)
    doi: 10.1016/j.oraloncology.2006.04.009.                           71. Jacobi-Gresser E, Huesker K, Schütt S. Genetic and
    [Full text links] [PubMed] Google Scholar (97) Scopus (63)             immunological markers predict titanium implant
66. August M, Bast B, Jackson M, Perrott D. Use of the fixed               failure: a retrospective study. Int J Oral Maxillofac Surg.
    mandibular implant in oral cancer patients: a retrospective            2013;42(4):537-543. doi: 10.1016/j.ijom.2012.07.018.
    study. J Oral Maxillofac Surg. 1998;56(3):297-301.                     [Full text links] [PubMed] Google Scholar (47) Scopus (22)
    [Full text links] [PubMed] Google Scholar (46) Scopus (33)         72. Vaz P, Gallas MM, Braga AC, et al. IL1 gene polymorphisms
67. Zen Filho EV, Tolentino Ede S, Santos PS. Viability of dental          and unsuccessful dental implants. Clin Oral Implants
    implants in head and neck irradiated patients: a systematic            Res. 2012;23(12):1404-1413. doi: 10.1111/j.1600-
    review. Head Neck. 2016;38 Suppl 1:E2229-40. doi:                      0501.2011.02322.x.
    10.1002/hed.24098. Review.                                             [Full text links] [PubMed] Google Scholar (25) Scopus (15)
    [Full text links] [PubMed] Google Scholar (8) Scopus (5)           73. Casado PL, Villas-Boas R, De Mello W, Duarte ME, Granjeiro
68. Ata-Ali J, Ata-Ali F, Di-Benedetto N, Bagán L, Bagán JV.               JM. Peri-implant disease and chronic periodontitis: is
    Does HIV infection have an impact upon dental implant                  interleukin-6 gene promoter polymorphism the common
    osseointegration? A systematic review. Med Oral Patol Oral             risk factor in a Brazilian population? Int J Oral Maxillofac
    Cir Bucal. 2015;20(3):E347-356. Review.                                Implants. 2013;28(1):35-43 .doi: 10.11607/jomi.2867.
    [Full text links] [Free PMC Article] [PubMed] Google Scholar (8)       [PubMed] Google Scholar (21)
69. Stevenson GC, Riano PC, Moretti AJ, et al. Short-term
    success of osseointegrated dental implants in HIV-positive
    individuals: a prospective study. J Contemp Dent Pract.
    2007;8(1):1-10.
    [PubMed] Google Scholar (37) Scopus (16)



                                                                                   Mohammed ALSHEHRI
                                                                              BDS, AEGD, SSC-ARD, SF-DI
                                                                           Dental Department, King Khalid
                                                                             University Hospital King Saud
                                                                           University, Riyadh, Saudi Arabia



CV
Dr Alshehri graduated from the College of Dentistry, King Saud University in 2001. Academically, he has
acquired a Certificate in Advanced Education in General Dentistry at the University of Southern California,
School of Dentistry. Thereafter, Dr Alshehri joined the SBARD Program wherein he obtained the Saudi Specialty
Certificate in Advanced Restorative Dentistry. Subsequently, he was able to obtain a Certificate for Saudi
Fellowship in Dental Implant and is currently a Fellow of International Team for Implantology (ITI). Professionally,
Dr Alshehri has conducted multiple research projects, has obtained a number of patents and has made local
and international presentations. Currently, Dr Alshehri is a Consultant in Cosmetic, restorative and implant
dentistry at College of Medicine and University Hospitals and board member of the Saudi Dental Society.

Questions
Osteoradionecrosis is usually observed several years following radiotherapy; and is associated
with local trauma within the hypovascular–hypocellular hypoxic tissues.
q    a.    The first statement is true but the second statement is false;
q    b.    The first statement is false but the second statement is true;
q    c.    Both statements are true;
q    d.    Both statements are false.
Osteoporosis is a metabolic disease of bone characterized by:
q    a.    low bone mineral density;
q    b.    reduced bone mass due to impaired bone metabolism;
q    c.    imbalanced osteoblastic activity;
q    d.    all of the above.

The mode of action of bisphosphonates depends on the drugs’:
q    a.    Physical structure;
q    b.    Chemical structure;
q    c.    Half-life;
q    d.    Side-effects.
All of the following are local risk-factors of peri-implant diseases EXCEPT:
q    a.    Implant diameter;
q    b.    Tobacco smoking;
q    c.    Poor bone quality;
q    d.    Quantity of bone.



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