Effects of diabetes on the osseointegration of dental implants

Abstract

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.

Full text

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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
1
, Juan Carlos Ferrer García
2,3
, Agustín Herrera Ballester
2,3
, Carlos Labaig Rueda
1
(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
Correspondence:
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
E-mail: ferrer_juagar@gva.es
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
ABSTRACT
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.
RESUMEN
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
-SCOPUS
-Indice Médico Español
-IBECS

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INTRODUCTION
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.
EFFECT OF DIABETES ON BONE
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
1
LATE-ONSET COMPLICATIONS
OF DIABETES
MICROVASCULAR
COMPLICATIONS
MACROVASCULAR
COMPLICATIONS
Retinopathy
Nephropathy
Neuropathy
Peripheral
Autonomic
Erectile dysfunction
Periodontal disease
Ischaemic heart disease
Peripheral arterial disease
Cerebrovascular disease
Fig. 1. Late-onset complications of diabetes.
1
Surgery for placement of
the implant (osteotomy)
Clot formation
Bone resorption
Formation of bone matrix
Bone apposition
Mineralization
Maintenance of
osseointegration
Alteration in protein synthesis
Osteoclasts
Formation of collagen
Osteoblasts
Alkaline phosphatases
Bone remodelling
Bone metabolism alterations
Changes in diabetic status
Fig. 2. Possible alterations in bone healing in diabetic 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
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).
EFFECTS OF DIABETES ON OSSEOINTEGRA-
TION OF IMPLANTS
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).
IMPLANTS IN PATIENTS WITH DIABETES
MELLITUS
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 ).

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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).
SPECIAL CONSIDERATIONS FOR THE PLA-
CEMENT OF IMPLANTS IN DIABETIC PA-
TIENTS
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
complications.
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).
1
0
1
2
3
4
5
Shernoff
(1994)
Esposito
(1997)
Balshi
(1999)
Fiorellini
(2000)
Olson
(2000)
Farzad
(2002)
Peled
(2003)
time (years)
Early failure
Late failure
2nd surgery
Placement: 1st surgery
Placement of
pr
osthesis
1 year of functional loading
PHASES
2.7
2.7 2.9
2.2
3.1
11.22.2 5.7 3.2
2.2
7.3
5.1
3.7
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.

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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
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).
CONCLUSIONS
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-
gration.
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

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REFERENCES
1. Zimmet P, Shaw J, Alberti KG. Preventing Type 2 Diabetes and the
dysmetabolic syndrome in the real world: a realistic view. Diabetes Metab
2003;29:609-18.
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
1993;329:977-86.
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
1981;30:670-77.
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
1999;22:1196-200.
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
1984;33:825-31.
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
2000;20:366-73.
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
1997;8:843-47.
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.