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Effects of diabetes on the osseointegration of dental implants


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The increased prevalence of diabetes mellitus has become a public health problem. Hyperglycaemia entails a rise in the morbidity and mortality of these patients. Although a direct relationship with periodontal disease has already been shown, little is known about the results of dental implants in diabetics. The present paper reviews the bibliography linking the effect of diabetes on the osseointegration of implants and the healing of soft tissue. In experimental models of diabetes, a reduced level of bone-implant contact has been shown, and this can be reversed by means of treatment with insulin. Compared with the general population, a higher failure rate is seen in diabetic patients. Most of these occur during the first year of functional loading, seemingly pointing to the microvascular complications of this condition as a possible causal factor. These complications also compromise the healing of soft tissues. It is necessary to take certain special considerations into account for the placement of implants in diabetic patient. A good control of plasma glycaemia, together with other measures, has been shown to improve the percentages of implant survival in these patients.
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Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
Effects of diabetes on the osseointegration of dental implants
Ana Mellado Valero
, Juan Carlos Ferrer García
, Agustín Herrera Ballester
, Carlos Labaig Rueda
(1) Department of Prosthodontics and Occlusion. School of Dentistry. Valencia University
(2) Diabetes and Endocrinology Unit. Department of Internal Medicine. Valencia University General Hospital Consortium
(3) Department of Medicine. School of Medicine. Valencia University
Dr. Juan Carlos Ferrer García
Unidad de Diabetes. Servicio de Medicina Interna.
Consorcio Hospital General Universitario de Valencia.
Av. Tres Cruces s/n
46014 Valencia
Received: 4-06-2006
Accepted: 1-10-2006
Mellado-Valero A, Ferrer-García JC, Herrera-Ballester A, Labaig-Rueda
C. Effects of diabetes on the osseointegration of dental implants. Med
Oral Patol Oral Cir Bucal 2007;12:E38-43.
© Medicina Oral S. L. C.I.F. B 96689336 - ISSN 1698-6946
The increased prevalence of diabetes mellitus has become a public health problem. Hyperglycaemia entails a rise in the
morbidity and mortality of these patients. Although a direct relationship with periodontal disease has already been
shown, little is known about the results of dental implants in diabetics.
The present paper reviews the bibliography linking the effect of diabetes on the osseointegration of implants and the
healing of soft tissue. In experimental models of diabetes, a reduced level of bone-implant contact has been shown,
and this can be reversed by means of treatment with insulin. Compared with the general population, a higher failure
rate is seen in diabetic patients. Most of these occur during the first year of functional loading, seemingly pointing to
the microvascular complications of this condition as a possible causal factor. These complications also compromise the
healing of soft tissues. It is necessary to take certain special considerations into account for the placement of implants
in diabetic patient. A good control of plasma glycaemia, together with other measures, has been shown to improve the
percentages of implant survival in these patients.
Key words: Diabetes Mellitus, hyperglycaemia, osseointegration, implant.
El incremento en la prevalencia de la diabetes mellitus se ha convertido en un problema de salud pública. La hiperglu-
cemia conlleva un aumento en la morbilidad y mortalidad de estos pacientes. Aunque ya se ha demostrado una relación
directa con la enfermedad periodontal, poco se conoce sobre el resultado del implante dental en el sujeto diabético.
En el presente trabajo se revisa la bibliografía que relaciona el efecto de la diabetes sobre la oseointegración de los im-
plantes y la cicatrización de los tejidos blandos. En modelos experimentales de diabetes se ha demostrado una reducción
en los niveles de contacto hueso-implante, que puede ser revertida mediante tratamiento con insulina. En el paciente
diabético, comparado con la población general, se observa un mayor índice de fracaso. La mayoría de ellos se producen
durante el primer año de carga funcional, lo que parece señalar a las complicaciones microvasculares de la enfermedad
como posible factor causal. Dichas complicaciones comprometen también la cicatrización de los tejidos blandos. Se hace
necesario establecer unas consideraciones especiales para la colocación de implantes en el paciente diabético. El buen
control de la glucemia plasmática, junto con otras medidas, ha demostrado mejorar los porcentajes de supervivencia
de los implantes en estos pacientes.
Palabras clave: Diabetes Mellitus, hiperglucemia, oseointegración, implante.
Indexed in:
-Index Medicus / MEDLINE / PubMed
-EMBASE, Excerpta Medica
-Indice Médico Español
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
© Medicina Oral S.L. Email:
Diabetes Mellitus is a group of metabolic disorders charac-
terized by an increase in plasma glucose levels. This hyper-
glycaemia is the result of a defect in insulin secretion, insulin
action, or both. It is one of the main causes of morbidity and
mortality in modern society and has become an alarming
public health problem. In the last decade, diabetes affected
approximately 140 million individuals and it is expected to
affect over 220 million by 2010 and more than 300 in 2025
(1). The prevalence of diabetes mellitus in Spain is estimated
at 6.2% for the 30 65 age group and 10% for 30 to 89-year-
olds, 90% of whom will be Type 2 diabetics (2).
Chronically high levels of plasma glycaemia lead to the
onset of chronic vascular complications of this condition, a
frequent cause of morbidity and mortality in these patients
(Figure 1). The treatment of diabetes aims at achieving
optimal metabolic control so as to avoid or delay these com-
plications (3). Over the last few years, special importance
has been given to the relationship between diabetes and oral
pathologies. Periodontal disease, frequently co-existing with
diabetes, is considered to be a further complication of this
disease. It affects both patients with type 1 and type 2 diabe-
tes mellitus, and it increases the risk of severe periodontitis
by a factor of 3 to 4 times (4).
The impact of diabetes on dental implants has not yet been
cleared up. The present article will review the implications
of diabetes and glycaemic control for the prognosis and evo-
lution of dental implants, in order to establish, if possible,
a series of special considerations for these subjects.
1. Effect of hyperglycaemia
Chronic hyperglycaemia affects different tissue structures,
produces an inflammatory effect and, in vitro, has been
shown to be a stimulus for bone resorption. Bone loss in
diabetes does not seem to depend so much on an increase in
osteoclastogenesis as in the reduction in bone formation (5).
Hyperglycaemia inhibits osteoblastic differentiation and al-
ters the response of the parathyroid hormone that regulates
the metabolism of phosphorus and calcium (6). In addition,
it produces a deleterious effect on the bone matrix and its
components and also affects adherence, growth and accu-
mulation of extra-cellular matrix (7). Mineral homeostasis,
production of osteoid and, in short, bone formation has
been shown to be clearly diminished in various experimental
models of diabetes (8) (Fig. 2).
2. Differences by type of diabetes
Type 1 diabetes mellitus is an auto-immune disease affecting
the beta cells in the pancreas that produce insulin, thus
making it necessary to use exogenous insulin to ensure
survival and prevent or delay the chronic complications of
this illness. Type 2 diabetes mellitus, on the other hand, is a
multi-factorial disease resulting from environmental effects
on genetically predisposed individuals and is related with
obesity, age and a sedentary lifestyle. In these patients, there
is a defect in the secretion of insulin together with a greater
or lesser degree of insulinopenia. The treatment of type 2
diabetics includes, in stages, measures relating to their diet
and lifestyle, oral hypoglycaemic drugs either alone or in
combination, and insulin.
In both type 1 and type 2 diabetes, the therapeutic goal
focuses on maintaining blood-glucose at normal or near-
normal levels. Glycosylated haemoglobin (HbAc1) is used
Erectile dysfunction
Periodontal disease
Ischaemic heart disease
Peripheral arterial disease
Cerebrovascular disease
Fig. 1. Late-onset complications of diabetes.
Surgery for placement of
the implant (osteotomy)
Clot formation
Bone resorption
Formation of bone matrix
Bone apposition
Maintenance of
Alteration in protein synthesis
Formation of collagen
Alkaline phosphatases
Bone remodelling
Bone metabolism alterations
Changes in diabetic status
Fig. 2. Possible alterations in bone healing in diabetic patients.
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
to verify the mean glycaemia of a patient over the last 2 or
3 months, thanks to the correlation between HbAc1 and
mean levels of glycaemia shown in Table 1.
Type 1 diabetes produces a reduction in bone mineral density
through mechanisms that have not yet been sufficiently clari-
fied; it has been attributed to both a lower formation of bone
and also to a greater rate of bone loss (9). This alteration
has not been demonstrated in patients with type 2 diabetes
and, in some studies, it even seems that there is greater bone
mineral density than in the control subjects (10,11). Expe-
rimental models of type 2 diabetes have shown a reduction
in both bone formation and bone resorption, which might
explain this apparently contradictory effect (5).
3. Effects of insulin on bone
Insulin directly stimulates the formation of osteoblastic
matrix. In experimental models of diabetes, the normogly-
caemia levels obtained by treatment with insulin brought
about growth in bone matrix and formation of osteoid
similar to control subjects (12). While hyperglycaemia may
reduce bone recovery by as much as 40% following circular
osteotomies, treatment with insulin normalizes this recovery
index, indicating that the deterioration of the bone is strictly
related to poor control of diabetes (6).
Although there are articles analyzing the success and failure
rates for implants in diabetic patients, only experimental
studies with animals have shown the effect of diabetes and
insulin therapy on the osseointegration of implants.
1. Results of osseointegration of implants in experimental
models of diabetes:
The analysis of the effect of diabetes on implants has revea-
led an alteration in bone remodelling processes and deficient
mineralization, leading to less osseointegration. Some stu-
dies have shown that, although the amount of bone formed
is similar when comparing diabetes-induced animals with
controls, there is a reduction in the bone-implant contact
in diabetics (13, 14). One study that analyzed the placement
of implants in the femurs of diabetic rodents observed bone
neoformation comparable to that of the control group in the
region of the periosteum, whereas it was significantly lower
in the endosteum and medullar canal, and bone bridges
between the endosteum and the implant surface were only
observed in a small number of cases (15).
The reduction in the levels of bone-implant contact confirms
that diabetes inhibits osseointegration. This situation may
be reversed by treating the hyperglycaemia and maintaining
near-normal glucose levels (16).
In the light of the articles published, there is a higher proba-
bility that the implants will integrate in areas predominated
by cortical bone. Nonetheless, further studies are necessary
in humans to determine the biological factors affecting
osseointegration in diabetic patients.
2. Effect of insulin on bone and osseointegration of implants
in experimental models
Various researchers have confirmed that osteopenia associa-
ted with diabetes induced in animals can be reversed when
treatment with insulin is applied (17).
When implants are placed in the tibia of diabetic rats, a
reduction of 50% is observed in the bone formation area
and on the contact surface between bone and implant. If
insulin is used, the ultra-structural characteristics of the
bone-implant interface become similar to those in the
control group. These results suggest that metabolic control
is essential for osseointegration to take place, as constant
hyperglycaemia delays the healing of the bone around the
implants (18). Although numerous studies have shown that
insulin therapy allows regulation of bone formation around
the implants and increases the amount of neoformed bone,
it was not possible to equal the bone-implant contact when
compared with non-diabetic groups (19).
Diabetes is currently classified as a relative contraindication
for implant treatment. Compared with the general popula-
tion, a higher failure rate has been seen in diabetic patients
with adequate metabolic control (20).
Reviewing the literature published in the last 10 years, the
survival rate for implants in diabetic patients ranges between
88.8% and 97.3% one year after placement, and 85.6% to
94.6% in functional terms one year after the prosthesis was
inserted. In a retrospective study with 215 implants placed
in 40 diabetic patients, 31 failed implants were recorded, 24
of which (11.2%) occurred in the first year of functional
loading. This analysis shows a survival rate of 85.6% after
6.5 years of functional use. The results obtained show a
higher index of failures during the first year after placement
of the prosthesis (21). Another study carried out with 227
implants placed in 34 patients shows a success rate of 94.3%
at the time of the second surgery, prior to the insertion of the
prosthesis (22). In a meta-analysis with two implant systems
placed in edentulous jaws, failure rates of 3.2% were obtai-
ned in the initial stages, whereas in the later stages (from 45
months to 9 years), this figure increases to 5.4% (23).
HbAc1 (%) mg/dl mmol/l
6 135 7,5
7 170 9,5
8 205 11,5
9 240 13,5
10 275 15,5
11 310 17,5
12 345 19,5
Table 1. Correlation between the level of glycosylated haemoglobin
(HbAc1) and mean levels of glycaemia (mg/dL, mmol/L ).
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
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A prospective study with 89 well-controlled type 2 diabetics
in whose jaws a total of 178 implants had been placed reveals
early failure rates of 2.2% (4 failures), increasing to 7.3%
(9 further failures) one year after placement, indicating a
survival rate of 92.7% within the first year of functional
loading. The 5-year survival rate was 90% (24).
The fact that most failures occur after the second-phase
surgery and during the first year of functional loading might
indicate microvascular involvement is one of the factors
implicated in implant failures in diabetic patients (25, 26).
The percentages of failures in these studies are shown gra-
phically in Figure 3.
The microvascularization alteration associated with diabetes
leads to a diminished immune response and a reduction in
bone remodelling processes (24, 27). Most of the articles
revised conclude that, despite the higher risk of failure in
diabetic patients, maintaining adequate blood glucose levels
along with other measures improves the implant survival
rates in these patients (20, 25).
1. Healing and risk of post-operative infection:
The repercussions of diabetes on the healing of soft tis-
sue will depend on the degree of glycaemic control in the
peri-operative period and the existence of chronic vascular
Patients with poor metabolic control have their immune
defences impaired: granulocytes have altered functionality
with modifications in their movement towards the infec-
tion site and a deterioration in their microbicide activity,
with greater predisposition to infection of the wound. In
addition, the high concentration of blood-glucose and in
body fluids encourages the growth of mycotic pathogens
such as Candida.
The microangiopathy arising as a complication of diabetes
may compromise the vascularization of the flap, thus de-
laying healing and acting as a gateway for the infection of
soft tissue (28).
time (years)
Early failure
Late failure
2nd surgery
Placement: 1st surgery
Placement of
1 year of functional loading
2.7 2.9
11.22.2 5.7 3.2
Fig. 3. Graph of the percentage of failures in diabetic patients.
The left axis shows the time elapsed since the placement of the implants. The right-hand axis reflects the different phases from the placement
of the implants until 1 year of functional loading after placement of the prosthesis.
The numbers in the columns indicate the percentages of failures in two distinct stages for each study. Early failures include up to one year
of functional loading. Late failures have been monitored for up to 5 years.
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
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2. Peri-operative measures:
In view of the studies revised, high levels of glucose in
plasma have a negative influence on healing and bone re-
modelling processes.
In order to ensure osseointegration of the implants, unders-
tood as the direct bond of the bone with the surface of the
implant subjected to functional loading, and to avoid delays
in the healing of gum tissue, it is necessary to maintain good
glycaemic control before and after surgery. To measure the
status of blood-glucose levels in the previous 6 8 weeks, we
have to know the HbA1c values. A figure of less than 7% for
HbA1c is considered a good level of glycaemic control (the
normal value for healthy individuals is 3.5 5.5% depending
on the laboratory).
Although there is some controversy over the use of an-
tibiotics in healthy patients, these are recommendable in
diabetic patients about to be subjected to implant surgery
(22). The antibiotic of choice is amoxicillin (2 gr per os 1
hour previously), as the pathogens most frequently causing
post-operative complications following the placement of
implants are Streptococci, Gram-positive anaerobes and
Gram-negative anaerobes. Clindamycin may also be used
(600 mg per os 1 hour previously), azithromycin or clari-
thromycin (500 mg per os 1 hour previously), and first-ge-
neration cephalosporins (cephalexin or cefadroxil: 2 gr per
os 1 hour previously) only if the patient has not had any
anaphylactic allergic reaction to penicillin (29). In addition
to antibiotic prophylaxis, the use of 0.12% chlorhexidine
mouthwash has shown a clear benefit by reducing the fa-
ilure rates from 13.5% to 4.4% in type 2 diabetics, during a
follow-up period of 36 months. This same study observed a
reduction of 10.5% in the failure rate when antibiotics were
administered pre-operatively (20).
There is evidence that hyperglycaemia has a negative in-
fluence on bone formation and remodelling and reduces
osseointegration of implants. Soft tissue is also affected by
the microvascular complications deriving from hyperglycae-
mia, vascularization of the tissue is compromised, healing
is delayed and wounds are more predisposed to infection.
This entails an increase in the percentage of failures in the
implant treatment of diabetic patients.
The bibliography reviewed recommends good glycaemic
control in the peri-operative period in order to improve the
survival rates for implants in diabetics. HbA1c figures of
less than 7% indicate appropriate glycaemia levels in the
preceding 6 8 weeks. Pre-operative antibiotic therapy and the
use of 0.12% chlorhexidine mouthwash are recommended
as both measures have been shown to reduce the percentage
of failures.
Although there is a higher risk of failure in diabetic patients,
experimental studies have shown that the optimization of
glycaemic control improves the degree of osseointegration
in the implants. Nonetheless, it is necessary to extend the
number of prospective studies in humans in order to clarify
the true impact of diabetes on the prognosis for osseinte-
1. Good glycaemic control:
HbA1c < 7%
Baseline and pre-prandial glycaemia (mg/dL): 80 - 110
Maximum post-prandial level of glycaemia (mg/dL): < 180
2. Pre-operative antibiotic therapy
3. 0.12% chlorhexidine mouthwash
Table 2. Recommendations to reduce the risk of implant failure in
diabetic patients
Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants Med Oral Patol Oral Cir Bucal 2007;12:E38-43. Diabetes and implants
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1. Zimmet P, Shaw J, Alberti KG. Preventing Type 2 Diabetes and the
dysmetabolic syndrome in the real world: a realistic view. Diabetes Metab
2. Goday A. Epidemiología de la Diabetes y sus complicaciones no coro-
narias. Rev Esp Cardiol 2002;55:657-60.
3. Diabetes Control and Complications Trial Research Group. The effect
of intensive treatment on the development and progression of long-term
complications in insulin-dependent diabetes mellitus. New Engl J Med
4. Löe H. Periodontal disease: the sixth complication of diabetes mellitus.
Diabetes Care 1993;16:329-34.
5. He H, Liu R, Desta T, Leone C, Gerstenfeld LC, Graves DT. Diabetes
causes decreased osteoclastogenesis, reduced bone formation and enhanced
apoptosis of osteoblastic cells in bacteria stimulated bone loss. Endocri-
nology 2003;145:1447-52.
6. Santana RB, Xu L, Babakhanlou C, Amar S, Graves DT, Trackman PC.
A role for advanced glycation end products in diminished bone healing in
type 1 Diabetes. Diabetes 2003;52:1502-10.
7. Weiss RE, Gora A, Nimni ME. Abnormalities in the biosynthesis
of cartilage and bone proteoglycans in experimental diabetes. Diabetes
8. Nyomba BL, Verhaegue J, Tomaste M, Lissens W, Bouillon RB. Bone
mineral homeostasis in spontaneously diabetic BB rats. Abnormal vitamin
D metabolism and impaired active intestinal calcium absortion. Endocri-
nology 1989;124:565-72.
9. Levin M, Boisseau V, Avioli L. Effects of diabetes mellitus on bone mass
in juvenile and adult onset-diabetes. N Engl J Med 1976;294:241-45.
10. Krakauer J, McKenna M, Burderer N, Rao D, Whitehouse F, Parfitt
A. Bone loss and bone turnover in diabetes. Diabetes 1995;44:775-82.
11. Tuominen J, Impivaara O, Puukka P, Ronnenmaa T. Bone mine-
ral density in patients with type 1 and type 2 diabetes. Diabetes Care
12. Locatto ME, Abranzon H, Caferra D, Fernández MC, Alloatti R,
Puche RC. Growth and development of bone mass in untreated alloxan
diabetic rats. Effects of collagen glycosilation and parathyroid activity on
bone turnover. Bone Miner 1993;23:129-44.
13. McCracken M, Lemons JE, Rahemtulla F, Prince CW, Feldman D.
Bone response to titanium alloy implants placed in diabetic rats. Int J Oral
Maxillofac Implants 2000;15: 345-54.
14. Nevins ML, Karimbux NY, Weber HP, Giannobile WV, Fiorellini JP.
Wound healing around endosseous implants in experimental diabetes. Int
J Oral Maxillofac Implants 1998;13:620-29.
15. Ottoni CEC., Chopard RP. Histomorphometric evaluation of new bone
formation in diabetic rats submitted to insertion of temporary implants.
Braz Dent J 2004;15:87-92.
16. Kopman JA, Kim DM, Rahman SS, Arandia JA, Karimbux NY,
Fiorellini JP. Modulating the effects of diabetes on osseointegration with
aminoguanidine and doxycycline. J Periodontol 2005;76:614-20.
17. Goodman W, Hori M. Diminished bone formation in experimental
diabetes. Relationship to osteoid maduration and mineralization. Diabetes
18. Siqueira JT, Cavalher-Machado SC, Arana-Chavez VE, Sannomiva P.
Bone formation around titanium implants in the rat tibia: role of insulin.
Implant Dent. 2003;12:242-51.
19. Fiorellini JP, Nevins ML, Norkin A, Weber HP, Karimbux NY. The
effect of insulin therapy on osseointegration in a diabetic rat model. Clin
Oral Implants Res 1999;10:362-68.
20. Morris HF, Ochi S, Winkler S. Implant survival in patients with type 2
diabetes: placement to 36 months. Ann Periodontol 2000;5:157-65.
21. Fiorellini JP, Chen PK, Nevins M, Nevins ML. A retrospective study
of dental implants in diabetic patients. Int J Periodontics Restorative Dent
22. Balshi TJ, Wolfinger GJ. Dental implants in the diabetic patient: a
retrospective study. Implant Dent 1999;8:355-59.
23. Esposito M, Hirsch JM, Lekholm U, Thompson P. Failure paterns
of four osseointegrated oral implant systems. J Mat Sci Mater Med
24. Olson JW, Shernoff AF, Tarlow JL, Colwell JA, Scheetz JP, Bingham
SF. Dental endosseous implant assessments in a type 2 diabetic population:
a prospective study. Int J Oral Maxillofac Implants 2000;15:811-18.
25. Farzad P, Andersson L, Nyberg J. Dental implant treatment in diabetic
patients. Implant Dent 2002;11:262-67.
26. Peled M, Ardekian L, Tagger-Green N, Gutmacher Z, Matchei EF.
Dental implants in patients with type 2 diabetes mellitus: a clinical study.
Implant Dent 2003;12:116-22.
27. Beiker T, Flemmig T. Implants in the medically compromised patient.
Crit Rev Oral Biol Med 2003;14:305-16.
28. Mealey BL, Moritz AJ. Influencias hormonales: efectos de la diabetes
mellitus y las hormonas sexuales esteroideas endógenas femeninas en el
periodonto. Periodontology 2000 2004;7:59-81.
29. Beikler T, Flemming TF. Antimicrobials in implant dentistry. In: Anti-
biotic and antimicrobial use in dental practice. Newman M, van Winkelhoff
A, editors. 2001. Chicago: Quintessence p. 195-211.
... The implants may be affected by many biological complications after the initial integration phase, among which the progressive implant bone loss is generally caused by peri-implant diseases, especially by peri-implantitis with increasing high prevalence as implant therapy is implemented widespread (Lindhe et al., 2008). Moreover, there are studies concerning that type 2 diabetes mellitus (T2DM) patients with dental implants showed very similar psychosocial profiles, clinical as well as microbiological, and salivary biomarkers to those of non-diabetic individuals (Tatarakis et al., 2014), and previous researchers have confirmed that diabetic patients with poor blood glucose control have a higher failure rate of implant repair (Mellado-Valero et al., 2007). ...
... Numerous previous studies indicate that macrophages in the adipose tissue interstitium of T2DM might produce a large number of proinflammatory factors (Chawla et al., 2011;Esser et al., 2014), which may affect bone integration. Moreover, hyperglycemia may change the biological function of bone cells to affect bone formation, bone mineralization, and bone reconstruction (Javed and Romanos, 2009), increasing the osteoclast activity and promoting the bone resorption (Catalfamo et al., 2013) to weaken the osseointegration ability of implants in patients with T2DM (Mellado-Valero et al., 2007). Therefore, poor blood glucose control is a high-risk factor for oral implant treatment, and the development of an intervention strategy that can not only effectively control blood sugar but also improve the function of damaged bone cells, so as to improve the osseointegration ability of implants, is particularly important for improving the probability of implantation success in patients with diabetes. ...
... Periodontitis is one of the major complications of diabetes including teeth loosening and falling, which affects the physiological functions of teeth of patients seriously (Chee et al., 2013). Although implant treatment is the most important way to repair the lost tooth, hyperglycemia induced a higher failure rate of implant repair (Mellado-Valero et al., 2007). Macrophages in the adipose tissue of T2DM patients correlated with bone integration including bone formation, bone mineralization, and bone reconstruction (Javed and Romanos, 2009) as well as osteoclast activity and promote bone resorption (Catalfamo et al., 2013) and hyperglycemia may impair bone integration of T2DM patients with implants. ...
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AdipoRon is an oral active synthetic small molecule with biological functions similar to adiponectin (APN). It is an APN receptor agonist that can improve insulin resistance and glucose intolerance. However, the role of AdipoRon in bone metabolism and related molecular mechanisms remains to be investigated. To explore the effect of AdipoRon on bone absorption and bone integration of type 2 diabetes mellitus (T2DM) mice with implants, we established surgery-induced model of osseointegration of dental implantation in T2DM mice of C57BL/6 db/db and normal mice homologous to diabetic mice. Micro-CT was used to analyze the femurs with the implant in the mice to detect the bone mass, H&E, and tartrate-resistant acid phosphatase (TRAP), and Safranin O-fast green staining was performed to analyze the bone formation and bone resorption. Bone integration-related markers as Rankl, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) were also measured using immunohistochemistry. Our results indicated that diabetic mice showed a lower bone mass and decreased the osteoblast differentiation. AdipoRon attenuated diabetes-impaired bone volume (BV)/total volume (TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone integration-related markers variation and promoted bone hyperplasia as well as repressed the osteoclast formation, especially in diabetic mice. AdipoRon may improve the osseointegration of dental implants in mice with T2DM by promoting osteogenesis and inhibiting bone resorption, and AdipoRon may serve as a promising oral strategy to improve the osseointegration ability of patients with diabetes.
... Die Ursachen dieser histomorphometrischen Veränderungen wurden bereits mehrfach untersucht. So zeigte sich in diabetischen Tieren eine reduzierte Osteoblastenexpression, eine verminderte Osteoidproduktion, und eine beeinträchtigte Knochenapposition an Implantaten (Verhaeghe et al., 1990, Iyama et al., 1997, Mellado-Valero et al., 2007, Schlegel et al., 2013 (Brownlee, 2001, Wu et al., 2015. Zahlreiche Entzündungsreaktionen werden wiederum durch AGE-Rezeptoren (RAGE) induziert, sodass es durch deren Aktivierung zu einer gesteigerten Cytokinproduktion kommt (Brownlee, 2001 Osteoblasten und tragen so zu einer mangelhaften Knochenbildung bei (Alikhani et al., 2007). ...
Der Erfolg einer Versorgung mit dentalen Implantaten hängt von der Osseointegration in den Kieferknochen ab. Die Osseointegration kann durch pathologische Prozesse, die den Knochenstoffwechsel beeinflussen, beeinträchtigt werden. Hierzu gehören eine Therapie mit Bisphosphonaten, eine Erkrankung mit Diabetes mellitus oder Osteoporose, und eine stattgehabte Radiotherapie. Um den Einfluss dieser Kompromittierungen zu erfassen wurde eine systematische Literaturrecherche durchgeführt, die die Osseointegration von Implantaten unter kompromittierten Wundverhältnissen im Tiermodell untersucht.
... [10]. High failure rates are found in the first year in diabetic patients [14]. Overall implants failure are associated with various health-related conditions and contributing factors that lead to the destruction of the implant (Table 2) [10]. ...
... Mellado-Valero et al reviewed several studies and concluded that hyperglycemia had a negative effect on formation and regeneration of bone and decreased the bone-implant contact area. They also concluded that maintaining the blood glucose level within the normal range would enhance osseointegration and increase the success of implant treatment (12). Gomez-Moreno et al (2014) evaluated peri-implantitis in type II diabetic patients, and assessed the changes in peri-implant tissue in patients with variable levels of hyperglycemia. ...
Background: Hyperglycemia in diabetic patients can affect the success of many dental treatments. Thus, many dental procedures are contraindicated in patients with uncontrolled diabetes mellitus (DM) due to the consequent delay in wound healing. This study aimed to assess the effect of a long-term control of blood sugar on tissue healing after implant placement. Methods: This cohort study evaluated 20 patients aged 50-60, referring to the School of Dentistry, Mashhad University of Medical Sciences for implant placement. All patients underwent blood sugar test and were divided into two groups of diabetic and non-diabetic patients regarding their HbA1c level. Bone loss, bleeding on probing (BOP), and pocket probing depth (PPD) of patients were measured 1 and 6 months after the implant placement. Data were analyzed using independent t test and chi-square test. Results: Blood sugar control had no significant effect on bone loss, BOP and PPD one and six month(s) after implant placement (P>0.05). Although PPD significantly increased in both groups over time (P=0.016 in the healthy group and P=0.007 in the diabetic group), the difference between the two groups was not significant (P>0.05). Conclusion: According to the results from this study, blood sugar control examined in the age range of our study had no significant effect on tissue healing one and six month(s) after the implant placement. However, further studies are required to explore this subject more thoroughly.
... Valero AM, Ferrer JC, Ballester AH (2007) 81 presented a review of literature on effects of diabetes on the osseointegration of dental implants. The increased prevalence of diabetes mellitus has become a public health problem. ...
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Edentulousness is on the decline, but it will increase dramatically in the adult population older than 55 years. Throughout the history of dentistry, clinicians and patient’s have struggled with options for replacing missing teeth. Treatment options have evolved from acrylic dentures to metal framework, removable partial dentures to fixed partial dentures. Recently, implants have joined the armamentarium of mainstream treatment in dentistry. The goal of modern dentistry is to restore the patient to normal function, speech, health and aesthetics, regardless of the atrophy, disease, or injury of the stomatognathic system. Responding to this ultimate goal, dental implants are an ideal option for people in good general oral health who have lost a tooth (or teeth) due to periodontal disease, an injury, or some other reasons. Dental implants are biocompatible metal anchors surgically positioned in the jaw bone underneath the gums to support an artificial crown where natural teeth are missing
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Background Type 2 diabetes mellitus (T2DM) is an important systemic disease, predisposing patients to inflammatory conditions including periodontitis and peri-implantitis and negatively affects dental implant success through various mechanisms. This study aimed to compare clinical and microbiological findings of individuals with dental implants with or without T2DM. Methods A total of 82 dental implants which were in function >3 years, were involved. The participants were divided into 2 groups; T2DM (n: 45 implants) and systemically healthy controls (n:37 implants). Periodontal indexes (Bleeding on probing (BOP), plaque index (PI), pocket depth (PD)), and radiographic bone loss were recorded around implants in function >3 years. Subgingival microbiological samples were also collected from the peri-implant sites. Pathogens include Fusobacterium nucleatum, Camphylobacter rectus, Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans, Treponema denticola, Prevotella intermedia, Peptostreptococcus micros, Eikinella corrodens, Prevotella nigrescens were evaluated. Results Peri-implant heatlh was determined in systemically healthy (54.1%) and type 2 diabetes patients (24.4%). Peri-implantitis was also evident in systemically healthy (8.1%) and T2DM (35.6%) groups. No differences was found in shallow peri-implant pockets in both groups in terms of the prevelance of all evaluated bacteria (p > 0.05). However, C. rectus, P. gingivalis, A. actinomycetemcomitans and T. forsythia were isolated more frequently in deep peri-implant pockets in systemically healthy patients compared to T2DM patients (p < 0.05). Conclusions Evaluted periodontal pathogens may not be affected by the presence of T2DM in implants. T2DM may not significantly alter the levels of specific periodontal pathogens in shallow and deep peri-implant pockets. C. rectus, P. gingivalis, A. actinomycetemcomitans and T. forsythia may be affected by T2DM in implants in deep pockets.
In hyperglycemia patients, suffering from insufficient vascularization and vascular network lesion, tissue regeneration, such as bone repair, is limited and maybe delayed by the secondary injury and hyperglycemic microenvironment. Typically, dental therapies involving guided bone regeneration is facing a difficult condition in the patients with diabetes. In this study, a hybrid membrane was endowed with biomimetic function to create an angiogenesis-inductive microenvironment by calcium ion release to overcome the limitations of bone tissue regeneration in diabetic patients. Biomineralized calcium resource was Janus-structured onto the surface of hybrid hydrogel by layer-by-layer technique to enhance vascularization and improve the bone regeneration in this study. The release of calcium ions from mineralized phases was controlled by the solubility of inorganic phases and the degradation of gels, promoting HIF-1α expression and creating a key role in angiogenesis stimulation. With highly enhanced calcium signaling and blood vessel formation, the hybrid hydrogel membranes improved the recruitment, proliferation and differentiation of mesenchymal stem cells and endothelial progenitors, confirmed by the enhancement of microvascular regeneration and new bone formation in the critical-sized calvarial defect in diabetic model in vivo. Our study demonstrates a translational potential of hybrid hydrogels engineered with inorganic minerals for orthopedic applications in hyperglycemia.
Objective: Urogynecology meshes, typically manufactured from polypropylene, are widely used in the surgical treatment of stress urinary incontinence and pelvic organ prolapse. However, mesh-associated complications such as mesh exposure can develop in women undergoing mesh implantations, for which diabetes is an independent risk factor. We aimed to define the impact of diabetes on the vaginal immune response to mesh by comparing diabetic vs. normoglycemic conditions longitudinally in a rat sacrocolpopexy model. Methods: Diabetes (blood glucose ≥ 300 mg/dL) was induced in middle-aged female Wistar rats with streptozotocin (STZ). A polypropylene mesh was implanted on the vagina via lumbo-sacrocolpopexy following bilateral ovariectomy and supracervical hysterectomy for 3-, 7- and 42-days. Sham-operated controls underwent the same procedures without mesh. Mesh-associated inflammation, immune cell populations and cytokine/chemokine profiles were examined in the excised vaginal tissues. Results: Diabetes was reliably induced starting on the 3rd day following STZ injection. Under both normoglycemic and diabetic conditions, mesh caused a prolonged inflammatory response in the vagina with increased proinflammatory chemokines MCP-1 and MIP-1α as compared to Sham. Major differences between the two conditions were found at the later stage (42 days post-surgery), including an increased inflammation with larger foreign body granuloma and more giant cells at the mesh-tissue interface, increased fraction of macrophages in the immune cell population, and higher proinflammatory chemokine IP-10 in the diabetic group. Conclusion: Polypropylene mesh implanted on the vagina induces prolonged inflammation at mesh-tissue interface. Diabetes increases the mesh-associated inflammation in the long term, which is related to a dysregulated macrophage response. Statement of Significance This study investigated the underlying mechanism accounting for the increased risk in women with diabetes for developing mesh complications such as mesh exposure. The significance includes: 1) It is the first study investigating vaginal host response to a prosthesis under the influence of diabetes; 2) the longitudinal study design elucidated dynamic changes of vaginal host response to mesh from early to late stages; 3) our findings may inform future mechanistic studies and studies investigating preventive/therapeutic strategies to improve the outcomes of women with diabetes receiving vaginal implants.
Introduction: Diabetes, smoking, and periodontitis are considered risk factors for the survival of conventional dental implants; however, research about their impact on the oral health-related quality of life (OHRQoL) of patients treated with corticobasal implants is lacking. Materials and methods: Two hundred twenty-seven adult patients completed a postoperative OHRQoL questionnaire. Aspects of their oral health were examined in relation to periodontitis, diabetes, smoking, and against a control group with none of the conditions. A subgroup of 118 patients with pre- and postoperative OHRQoL data were studied for changes in their OHRQoL. The impact of the risk factors on the patients' posttreatment OHRQoL was examined through multiple regression analysis. The paired data were analyzed through Wilcoxon signed-rank test. Results: The satisfaction with the treatment was high and robust irrespective of periodontitis, diabetes, smoking, or more than one factors, P > 0.05 for all tests. The smokers' satisfaction was significantly higher than the nonsmokers, P = 0.003. The majority of the patients experienced a steady reduction in frequency to the full absence of oral health problems (P < 0.001 for all tests). The patients with periodontitis reported a significantly higher reduction in limitations related to food choice, P = 0.026. Posttreatment complications were few, mainly in the first postoperative year. Discussion: Our results provide reassurance to patients with periodontitis, diabetes, and smokers that corticobasal implants are an effective treatment option with the same benefits for their oral health quality of life as for patients without these risk factors.
Diabetes mellitus is among the diseases with great impact on health and society, not only for its high prevalence but also for its chronic complications and high mortality. The most precise method to investigate the prevalence of diabetes is by oral glucose tolerance testing. In Spain, the prevalence of diabetes in the 30–65 year-old population is estimated to be 6.5% among 30-to-65- year old, and 10.3% among the 30-to-89 year-old population. The ratio of known to unknown diabetes ranges from 1:3 to 2:3. The incidence of diabetes mellitus type 2 in Spain is 8/1000 persons per year, and the incidence of type 1 is 11 to 12 cases per 100,000 persons per year. The prevalence of chronic complications varies according to type of diabetes, time since onset and degree of metabolic control: neuropathy 25%, retinopathy 32% and nephropathy 23%. Diabetes is one of the most important causes of death in Spain, occupying third place for women and seventh for men.
To assess the influence of diabetes mellitus on bone metabolism, we measured skeletal mass in the forearms of 35 patients with juvenile diabetes on insulin and 101 stable patients with adult-onset diabetes, on diet alone, insulin, or oral hypoglycemic agents. There was a significant loss of bone mass in both juvenile and adult-onset diabetes (P less than 0.01) as compared to controls matched for age and sex. The decrease was already present in patients with diabetes of less than five years' duration. Bone loss and duration of the diabetes did not correlate; the greatest decrease in bone mass was observed in the patients receiving oral agents. These data are consistent with the hypothesis that the loss of skeletal tissue in diabetes reflects the underlying disease since it occurs early and is not related to severity as evidenced by the need for insulin, to duration, or to treatment with insulin or diet alone.
Calcium homeostasis was investigated in male BB rats with a diabetes duration of 3-4 weeks and compared with that in nondiabetic littermates either fed ad libitum or receiving selective semistarvation or an oral Ca supplement to obtain additional weight-matched and Ca intake-matched control groups. Diabetic rats had markedly increased food and Ca intake, so that their net Ca balance remained positive despite a 13-fold increase in urinary Ca excretion and a disappearance of active duodenal Ca absorption. Decreased duodenal Ca uptake correlated with decreased 1,25-(OH)2D3 levels (89 +/- 15 vs. 160 +/- 13 pg/ml in nondiabetic rats), decreased duodenal 9K Ca-binding protein concentrations (10 +/- 1 vs. 21 +/- 2 micrograms/mg protein), and decreased number of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-binding sites in duodenum, although the binding affinity was above normal. Nondiabetic Ca-supplemented rats exhibited a similar response: decreased 1,25-(OH)2D3 (95 +/- 8 pg/ml) and 9K Ca-binding protein (7 +/- 0.5 micrograms/mg protein) concentrations, decreased active duodenal Ca uptake, increased urinary Ca excretion, and a normal net Ca balance. Plasma vitamin D-binding protein levels were decreased by 62% in diabetic rats, due to a marked decrease in production rate, while the plasma half-time remained normal. The free 1,25-(OH)2D3 index was highest in diabetic rats, suggesting partial vitamin D resistance at the duodenal level. In semistarved rats, 1,25-(OH)2D3 levels and active Ca uptake remained normal, and the free 1,25-(OH)2D3 index was increased, together with suppressed vitamin D-binding protein levels. These studies indicate that nutritional abnormalities may contribute to but cannot totally explain the disturbances in vitamin D metabolism, transport, or action at the intestinal level.
The pathogenesis of osteopenia in clinical diabetes remains uncertain. Thus, bone formation, mineralization, and resorption were measured over a 10-day period using double-tetracycline labeling of bone in control (C, N = 18), untreated diabetic (I-, N = 14), and insulin-treated diabetic (I+, N = 16) rats. Diabetes was induced by the intravenous (i.v.) injection of streptozotocin (STZ), 90 mg/kg, in citrate buffer. Bone and matrix (osteoid) formation and apposition were decreased by 50% from C values in I- rats (P less than 0.05), but were unchanged in I+ rats. Osteoid seam width and osteoid area were also less in I- (P less than 0.05), but similar in I+, when compared with C. In untreated diabetic rats that continued to actively form new bone, osteoid maturation and mineralization were not diminished when adjusted for the rate of bone formation. However, 5 of 14 untreated and 2 of 16 insulin-treated diabetic animals showed no uptake of tetracycline into bone (Chi-square, 8.54; P less than 0.05), suggesting a defect in mineralization in a subset of diabetic rats. Measurements of serum glucose, calcium, and phosphorus concentrations, of urinary excretion rates for glucose, calcium, and phosphorus, and of creatinine clearance failed to correlate with the changes in bone growth and histology observed. The results indicate heterogeneity in the response of bone in diabetes, and suggest that bone formation and osteoid volume are reduced early in the course of this disorder. These data in short-term diabetes support previous observations in both man and rat that indicate a state of low bone turnover in diabetes.
Proteoglycans synthesized in developing cartilage and bone were investigated in control and streptozotocin-induced (65 mg/kg, i.v.) diabetic rats. Ten days after streptozotocin injection, animals were implanted subcutaneously with demineralized bone matrix particles. This system induces formation of cartilage and bone on days 7 and 14, respectively. Two hours before they were killed, animals were injected with 35SO4 and the labeled proteoglycans were extracted from the explants and metaphyses by either a direct associative extraction (0.5 M GuCl2) or a direct dissociative extraction (4.0 M GuCl2). These procedures extract 80-90% of the total counts incorporated. To characterize the proteoglycans, extracts were subjected to cesium chloride density gradient centrifugation and molecular sieve chromatography. These data showed that (1) there is less proteoglycan made in diabetic bone; (2) the proteoglycan aggregate is of a smaller molecular weight in bone than in cartilage; (3) 10% of the proteoglycan synthesized in diabetic bone was in the form of aggregates compared with 48% of the control bone; (4) aggregates did form in the diabetic cartilage, and their molecular weight was smaller than in normal cartilage. This investigation shows that proteoglycans, structurally important macromolecules of cartilage and bone, are altered in experimental diabetes. This metabolic abnormality may be an important factor contributing to decreased bone formation observed in diabetes.
There have been conflicting reports about the effect of diabetes on bone density. In 1978, we studied 109 patients, 46 with type I and 63 with type II diabetes; approximately 12 years later we restudied 35 of the 66 surviving patients. In the original study, radial bone density did not differ significantly between patients with either type of diabetes but was significantly lower than in nondiabetic control subjects. In eight osteopenic patients, bone formation rate and other histological indexes of osteoblast recruitment and function were markedly depressed compared with those in nondiabetic control subjects. In patients remeasured approximately 2.5 years (41 patients) and approximately 12.5 years (35 patients) after baseline, bone loss had continued at the expected rate in patients with type I diabetes, with maintenance of the same deficit, but was slower than expected in patients with type II diabetes, such that the initial deficit had been completely corrected. In six of the eight patients who had undergone bone biopsy, one with type I and five with type II diabetes, the mean bone mineral density z-score of the spine and femoral neck approximately 12 years later was > 0 and in one subject was significantly higher than normal at both sites. Based on these data and on previous studies, we propose that in patients with diabetes, low bone formation retards bone accumulation during growth, metabolic effects of poor glycemic control lead to increased bone resorption and bone loss in young adults, and low bone turnover retards age-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)
Body and skeletal growth and development were studied in alloxan-treated and age-matched control rats, between 3 and 23 weeks of age. For both groups the growth of the skeletal and body weights were in phase, with a maximum at 7 weeks of age. The growth data was assessed according to Parks' theory of feeding and growth. Alloxan-treated rats showed an important reduction in body and bone mass, with a greater impact on soft tissues. As expected, the asymptotic body and skeletal weights were reduced respect to controls. The time needed to attain 63% of mature food intake (Brody's 'time constant') was also reduced, indicating that maturation occurred at an earlier age than controls. The diabetic state is characterized by a reduced food conversion efficiency. Despite hyperfagia, alloxan-treated rats showed circa one-half the body and skeletal weights of age-matched controls. The following adverse effects of alloxan diabetes on bone tissue were observed: (a) a decrease in trabecular bone volume (femoral metaphyses) and cortical width (femoral diaphyses), (b) increased bone collagen glycosylation as a function of extracellular glucose concentration, (c) increased resistance of bone collagen to collagenase hydrolysis, (d) decreased rate of bone resorption except under strongly stimulated parathyroid function, (d) significantly lower ashes/bone matrix ratio in diabetic rats with more than 10 weeks of diabetes, and (e) no histological evidence of osteomalacia.
Periodontal disease is a chronic inflammatory condition characterized by destruction of the periodontal tissues and resulting in loss of connective tissue attachment, loss of alveolar bone, and the formation of pathological pockets around the diseased teeth. Some level of periodontal disease has been found in most populations studied and is responsible for a substantial portion of the tooth loss in adulthood.
Wound healing has been shown to be altered in diabetes mellitus. The aim of this study was to identify the effects of streptozotocin-induced diabetes on osseointegration. Diabetes was induced in 40-day-old rats by intraperitoneal injection of 70 mg per kg streptozotocin. At 14 days postinjection, implants were placed in the femora of 10 diabetic and 10 age-matched normal rats. Animals were sacrificed at 28 and 56 days following implantation. Histometric results indicated that the quantity of bone formation was similar for diabetic and control animals (P > .05). However, less bone-implant contact was observed for diabetic compared to control animals at both 28 and 56 days (P < .0001). This study demonstrates that the process of osseointegration is affected by streptozotocin-induced diabetes.