3. Results
3.1. Diabetes mellitus
Diabetes mellitus (or diabetes) is a common
metabolic disorder characterized by hypergly-
cemia due to impaired insulin secretion, insufficient
insulin action, or both. 22 The main types of diabetes
include type 1 diabetes and type 2 diabetes. Type
1 diabetes is associated with pancreatic beta (β)-
cell destruction and accounts for 5-10% of the
subjects with diabetes.
Type 2 diabetes is associated with a relative, rather
than an absolute insulin deficiency and accounts
for 90-95% of all individuals with diabetes. 23
Individuals with poorly-controlled diabetes are
more susceptible to develop complications after
implant therapy compared to individuals with well-
controlled diabetes. 24
Chronic hyperglycemia has been related with tissue
damage, since endothelial cells take up glucose
passively in an insulin-independent manner. 25,26
Hyperglycemia is also associated with an altered
host resistance, for example, defective migration
of polymorphonuclear leukocytes, impaired
phagocytosis and an exaggerated inflammatory
response to microbial products. 27
The treatment of diabetes focuses on the
attainment of an optimal glycemic control in order
to impede complications.
Individuals with diabetes are more susceptible to
periodontal disease, which is also recognized as
the sixth complication of diabetes. 28-32
The underlying pathophysiology that increases
the risk of periodontal bone loss in subjects with
diabetes is poorly understood; however it has been
associated with the formation and accumulation
of glucose-mediated advanced glycation end-
products (AGEs).
AGEs accumulate in the plasma and tissues
(including the periodontium) during the process
of normal aging, but to an accelerated degree
in subjects with diabetes. 33 AGEs contribute to
periodontal destruction by activating receptors
called “Receptor for AGEs (RAGE)” located on the
periodontium and by reducing the production of
matrix proteins, such as collagen and osteocalcin
by gingival and periodontal fibroblasts. 34-38
It has been suggested that the pathogenesis of
diabetes and its complications are associated with
an increased RAGE expression. 29,39
Other cell types with RAGE expression include
glomerular epithelial cells (podocytes), endothelial
cells, vascular smooth muscle cells, inflammatory
mononuclear phagocytes and lymphocytes. 39
Therefore, an impaired glycemic status may
negatively affect the outcome of implant therapy.
In a systematic review, Javed and Romanos 19
reported that under optimal glycemia control,
dental implants can osseointegrate and remain
functionally stable over long durations in patients
with diabetes.
3.2. Bisphosphonates
Bisphosphonates (BPs), (such as alendronate,
risendronate, ibandronate, and clodronate) are
Stomatology Edu Journal
important group of drugs used for the treatment
of metabolic and oncologic pathologies involving
the skeletal system. The mode of action of BPs
depends on the drugs’ chemical structure. The
two main categories of BPs are the “non-nitrogen”
and “nitrogen-containing” BPs. 4 0 Non–nitrogen-
containing BPs are metabolized rapidly, whereas
nitrogen-containing BPs are much more potent
and are not metabolized. 41 These drugs act by
inhibiting osteoclastic activity and inducing their
apoptosis. 18 BPs may be administered by either
oral or intravenous routes. Oral BPs are used in
the treatment of diseases such as osteoporosis
and Pagets’ disease; while intravenous BPs are
administered to patients with breast cancer,
multiple myeloma, bone metastasis and malignant
hypercalcemia. The chief complication observed in
patients under either oral or intravenous BP therapy
is osteonecrosis of the jaw (ONJ). 42 It has been
suggested that all patients under bisphosphonate
therapy who are expected to receive dental
implants should be informed of the possible risks
of development of ONJ and consequent implant
loss beforehand; and an informed-consent must
be obtained prior to installation of dental implants
in these individuals. 14,15
Although, the risk of developing ONJ in patients
using BPs is estimated to be minimal (approximately
0.09%), there still exists a controversy over the
placement of dental implants in patients treated
with BPs. 43 Results from case-reports 44-47 have
shown that dental implants can osseointegrate
and remain functionally stable in patients under
BP therapy. Similar results have been reported
in retrospective studies. 48,49 Results by Bell and
Bell50 showed comparable implant survival rates
between patients using BPs and controls, that is,
95% and 96.5% respectively. Brooks et al. 47 placed
10 implants in a patient on bisphosphonate
therapy out of which, 9 implants osseointegrated
successfully giving a success rate of 90%. Likewise,
results from a case-report by Wang et al. 44 also
showed implant healing to be uneventful with
no alterations in the healing process of dental
implants in a patient using BPs. Fugazzotto et al. 51
showed that a history of bisphosphonate therapy
was not associated with the occurrence of ONJ
following installation of immediately-loaded
dental implants.
In their systematic review, Javed and Almas 18
reported that the incidence of implant failure in
patients taking BPs is minimal.
The authors also concluded that placement of
dental implants in patients taking BPs can have a
positive outcome. 18
3.3. Osteoporosis and rheumatoid arthritis
Osteoporosis is a metabolic disease of bone
characterized by low bone mineral density
(BMD) and reduced bone mass due to impaired
bone metabolism and imbalanced osteoblastic
and osteoclastic activities. 52,53 In osteoporotic
bone, osteoblasts demonstrate impaired pro-
liferative, synthetic and reactive ability to cellular
A COMPREHENSIVE REVIEW OF SYSTEMIC FACTORS ASSOCIATED WITH PERI-IMPLANT DISEASES
41