S y s t e m i c F a c t o r s A ff e c t i n g

P ro g n o s i s o f D e n t a l I m p l a n t s
Davis C. Thomas, BDS, DDS, MSD, MSc Med, MSca,*,
Depti Bellani, BDS, MDSb, Jack Piermatti, DMDc,
Priyanka Kodaganallur Pitchumani, BDS, MSd

KEYWORDS
 Implant prognosis  Implant failure  Dental implants  Osseointegration
 Implant survival  Implant success  Implant stability

KEY POINTS
 Endocrine factors seem to be the most vibrant affecting implant prognosis, out of the sys-
temic factors published in this regard to date.
 Smoking seems to be a crucial factor with both systemic and local effects contributing to
implant failure.
 Medication classes negatively affecting dental implant prognosis include selective seroto-
nin reuptake inhibitors and proton pump inhibitors.
 In general, systemic factors that may hamper and interfere with proper oral hygiene main-
tenance seem to be contributing to implant failure.
 Prophylactic antibiotics given prior to implant surgery seem to strongly favor implant sur-
vival rates.

INTRODUCTION

In medicine, all patients for planned surgical procedures are evaluated carefully for the
preoperative assessment of possible systemic factors that can affect the prognosis,
both during and after surgery. Following the same principle, in the recent past dental
literature, several authors have looked at these systemic factors that may predict and
affect implant success, survival, and prognosis. Although the literature seems not so
robust in all the various possible factors, emerging evidence points out to a number of
succinct systemic factors that can significantly affect both the short-term and long-
term prognosis of dental implants.

a
Department of Diagnostic Sciences, Center for Temporomandibular Disorders and Orofacial
Pain, Rutgers School of Dental Medicine, Newark, NJ, USA; b Private Practice, Navi Mumbai,
India; c Nova Southeastern University College of Dental Medicine, FL, USA; d Department of
Periodontics, University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA
52242, USA
* Corresponding author. Department of Diagnostic Sciences, Rutgers School of Dental Medi-
cine, 110 Bergen Street, Newark, NJ 07103.
E-mail address: [email protected]

Dent Clin N Am 68 (2024) 555–570

https://doi.org/10.1016/j.cden.2024.07.001 dental.theclinics.com
0011-8532/24/ª 2024 Elsevier Inc. All rights are reserved, including those for text and data mining,
AI training, and similar technologies.
556 Thomas et al

The available medical/dental/implant literature seems to indicate a crucial role

played by several factors including, but not limited to, medications (selective seroto-
nin reuptake inhibitor [SSRI] and proton pump inhibitor [PPI]), endocrine disorders,
and systemic factors affecting the patient’s ability to maintain optimal oral hygiene,
as the key players in determining implant prognosis. The effect of smoking seems
to be both local and systemic, and a cumulative effect results in poor implant prog-
nosis. Researchers and clinicians seem to prefer deferring implant placement until
such a point that the patient has either successfully quit smoking or reduced the habit
significantly to help the clinician’s comfort placing the implant. Some clinicians, within
their individual rights, totally reject the proposal for surgical implants if the patient re-
fuses to quit smoking. Systemic factors that affect a patient’s manual dexterity and/or
mental capability to maintain optimal oral hygiene can adversely affect the prognosis
of dental implants. These include conditions such as Down’s syndrome, movement
disorders, rheumatoid arthritis, and other conditions that pose a physical and/or
cognitive challenge. Even in this new medical era of trying to limit antibiotic usage,
the latest literature seem to indicate that prophylactic antibiotic usage is improving
implant success rates and prognosis. The authors have enumerated the most salient
systemic factors that have been proposed and shown to be affecting the prognosis of
dental implants.

HEMATOLOGICAL DISORDERS

Since local tissue bleeding could potentially impact the implant surgical procedures,
implementing a systematic protocol in these cases is paramount for the proper healing
and patient comfort.1–3 It must be noted that most of the related literature in this regard
has been extrapolated from the data dealing with surgical tooth extraction and post-
extraction healing.4 Individuals who suffer from infections, idiopathic purpura, radia-
tion therapy, bone marrow suppression, or cancers (such as leukemia) may be at
risk for platelet deficiency. Platelet deficiency is associated with the high risk of
bleeding.5 A potentially serious complication of dental implant placement in these pa-
tients, which happens infrequently, is upper airway obstruction brought on by severe
hemorrhage from the tissues in the floor of the mouth.6 Due to the potential for lingual
artery involvement as a result of inferior alveolar canal perforation or lingual cortical
plate involvement, the first mandibular premolar position is the most dangerous place
to place dental implants.7–9
In the field of oral implantology, blood disorders are among the most serious con-
ditions. Prolonged healing, reduced bone density, and prolonged healing times are
all consequences of anemia. This patient population has a high rate of intraoperative
bleeding, which could lead to increased discomfort and postoperative edema. The
risk of secondary infections is elevated in association with it. Chronic infections
are common, which reduces the long-term implant survival rate. A number of com-
plications caused by leukocyte disorders may jeopardize the implant’s success.
Among these, infection is the most frequent (it can happen at any point in the course
of treatment). The uncertainty of postsurgical edema and secondary infection is
elevated, and intraoperative bleeding is common, similar to what happens to patients
who have anemia.10 von-Willebrand disease appears to have some association
with implant failure, although the effect seems to be once the implant has been
“loaded.”11 Well-controlled leukemia is no longer considered an absolute contraindi-
cation for dental implants.12 Both bone reparative situations showed that osteogen-
esis is “sensitive” to anemia and/or the associated conditions, causing a delay in
bone healing.13
 Prognosis of Dental Implants 557

OSTEOPOROSIS

Multiple studies including systematic review with meta-analysis showed no difference

in the survival rate of implants in groups of patients with and without osteoporosis.
This was true at the implant level as well as the patient level.14,15 However, many of
the studies show that the patients with osteoporosis have increased peri-implant
bone loss compared to non-osteoporotic group.14 Research suggests that parenteral
bisphosphonates cause implant failure by hampering osseointegration.16 Recent liter-
ature shows that osteoporosis by itself is not a contraindication for implant placement.
However, it has been suggested that patients with osteoporosis may need a higher
level of maintenance of the bone surrounding the implants, due to possible increased
susceptibility to bone loss.14,15,17–19

ENDOCRINE FACTORS AND THEIR RELATIONSHIP TO DENTAL IMPLANT PROGNOSIS

The endocrine system regulates all biological functions of the body, utilizing hor-
mones as chemical messengers released into the bloodstream, targeting specific
receptors in order to elicit a physiologic response. The major endocrine glands
include the hypothalamus, pituitary, pineal, pancreas, ovaries, testes, thyroid, para-
thyroids, and the adrenals. Abnormalities of any of these glands or the receptors of
their respective hormones may manifest as metabolic disruption. Endocrine disor-
ders can cause a myriad of metabolic disease states; however, this section focuses
on those disorders that impact the prognosis and treatment outcomes of dental
implants.
Melatonin
There is increasing evidence in the literature for the efficacy of topical melatonin in
increasing the bone-implant contact, and thereby promoting osseointegration and
reducing late implant failure.20–23 The mechanism by which melatonin brings about
these apparent positive effects is thought to be by reducing bone resorption.20
Local application of melatonin at the osteotomy site was shown to improve the
implant stability and minimize the crestal bone resorption.24 The addition of mela-
tonin into autogenous bone graft material was shown to increase bone density
and thereby improve the hard and soft tissue characteristics around immediate im-
plants placed in the esthetic zone.25,26 It must be noted that the role of melatonin in
dental implant success remains equivocal. Further focused studies are necessary in
this regard.
Insulin
With respect to this section, our discussion will be limited to diabetes mellitus (DM).
This condition has a definite negative impact on all oral surgical procedures and the
resultant healing process. The main tenant of implant success is dependent on strict
glycemic control.27–29 There is current evidence suggesting that increased glycosy-
lated hemoglobin (HbA1C) levels are associated with increased bleeding on probing
around dental implants.30 Patients with DM were shown to have more implant-
related complications as compared to patients without DM.30 It must be noted that
DM is associated with an increased incidence of peri-implantitis, while there was a
lack of association with peri-implant mucositis.31 However, a relatively recent system-
atic review looking at the relationship between DM and peri-implantitis also reported
inconclusive correlation between the two.32 With regard to osseointegration, HbA1c
levels were not correlated with implant stability at 1 year after implant placement.32
With reference to DM and implant survival, the same study found that most of the
558 Thomas et al

implant failures occurred within the first 12 months upon prosthetic loading of the
implant.32 A recent systematic review with meta-analysis of observational studies
concluded that patients with DM were more likely to have higher risk of peri-implanti-
tis.26 Further, some studies show increased failure rates of dental implants in patients
with DM,33,34 while others show no significant difference in failure rates among pa-
tients with DM.35 Since there is no clear-cut distinction between failure rates of pa-
tients with and without DM , the prudent clinician must ensure strict control of the
disease prior to dental implant surgery. The single most effective evaluation of a pa-
tient’s diabetes control is the HbA1c and should be checked in all patients with DM
prior to dental implant surgery.

Estrogen
Earlier studies regarding the role of estrogen on implant healing had shown that
lower hormonal levels were associated with compromised implant healing, specific
to the maxilla, not observed in the mandible.36 The same study also showed that
postmenopausal women who were not on hormonal supplements had higher failure
rates.36 Estrogen deficiency was shown to induce osteoporosis, which negatively
affected machined implant osseointegration.37 However, contradicting literature
based on animal studies does not indicate an increased failure rate in osteoporotic
animals, nor does it show increased failure rates in female individuals with estrogen
deficiency.38

Thyroid Hormones
Patients being treated for thyroid cancer, utilizing radioiodine therapy are advised to
wait for 2 weeks after cessation of the treatment, for surgical implant placement.39
There was no significant difference between the survival rates of implants in patients
with thyroid diseases as compared to healthy controls.40 A recent study suggested
that hypothyroidism does not pose a risk for implant failure. On the contrary, the au-
thors have proposed that reduction in the bone metabolic rate in hypothyroidism may
be protective of the dental implant.41

Parathyroid Hormone
Parathyroid hormone (PTH) plays a crucial role in maintaining calcium homeostasis
and bone remodeling. It has been hypothesized that various concentrations and vary-
ing duration of exposure to PTH may induce diverse effects on bone remodeling. PTH
is believed to induce bone apposition by downregulating sclerostin expression in os-
teocytes.42 Some studies suggest that serum PTH levels may be an indicator predict-
ing the condition of the bone around the implant, in conjunction with other factors.43
However, a relatively recent systematic review concluded that PTH supplementation
shows promising levels of efficacy on implant osseointegration.42 The same study
also warrants further investigation in application in humans.

VITAMIN D

Although termed as a vitamin, structurally vitamin D is a sterol, with effects similar to

those of corticosteroids, robustly affecting immunomodulation.44 It is considered an
important cofactor in bone metabolism. Although earlier suggestions were made as
to the important role vitamin D plays in the success of dental implants, the more recent
focused systematic reviews seem to indicate otherwise. Short-term follow-up studies
have shown that vitamin D deficiency results in mild marginal bone loss; however, it
 Prognosis of Dental Implants 559

lacks solid evidence.45–47 Long-term follow-up has been suggested to investigate the
effects of vitamin D levels on implant stability.

MEDICATIONS AFFECTING DENTAL IMPLANT PROGNOSIS

Cardiovascular Medications
The utilization of antihypertensive medications correlates with an increased survival
rate of osseointegrated implants. The elevated survival rate of osseointegrated dental
implants has been linked to the utilization of antihypertensive drugs, which can be
attributed to their influence on bone metabolism.48 Beta-blockers, thiazide diuretics,
angiotensin-converting enzyme (ACE) inhibitors, and angiotension receptor blockers
(ARBs), among other antihypertensive medications, exert beneficial effects on bone
health.49,50 Bone cells express beta-adrenergic receptors, notably beta-2 receptors,
which when activated, promote bone resorption and inhibit bone formation.51 Indeed,
in addition to their cardiovascular impact, beta-blockers hinder the activity of beta-2 re-
ceptors involved in bone resorption, leading to enhanced bone accumulation.52 Hence,
beta-blockers have demonstrated favorable impacts on bone structure, metabolism,
and the healing process.48 This may be beneficial for implant survival, although not
shown in studies. Thiazide diuretics act by inhibiting the thiazide-sensitive sodium chlo-
ride cotransporter located in the distal tubules of the kidney, which reduces the excre-
tion of calcium and consequently promotes calcium absorption.53 Reduced urinary
calcium excretion may result in elevated serum calcium levels, potentially leading to
decreased PTH levels and subsequently reducing bone turnover, resulting in beneficial
effects on bone mineral density (BMD).54 Additionally, thiazide diuretics may exert a
direct beneficial impact on BMD by influencing the proliferation and differentiation of
osteoblasts.55 ACE inhibitors and ARBs suppress ACE activity, subsequently influ-
encing bone metabolism56; ARBs can also significantly increase BMD by inhibiting
bone resorption.57 Gingival enlargement may manifest around dental implants, partic-
ularly in rehabilitative scenarios for individuals who have undergone head and neck
cancer treatment. Clinicians should consider the possibility of gingival enlargement
in hypertensive patients prescribed calcium channel blockers before proceeding with
implant placement. Whether this drug-influenced gingival enlargement affects prog-
nosis of implants has not been shown.58 The utilization of renin–angiotensin system
(RAS) inhibitors is linked to increased implant stability upon implant exposure subse-
quent to implant therapy compared to individuals who do not use these inhibitors.59
RAS inhibitors were shown in animal studies to decrease periodontal inflammation
and cause an increase in the volume of the alveolar bone.60 Given that the success
of osseointegrated implants relies heavily on bone formation and remodeling, individ-
uals using antihypertensive drugs who have undergone dental implant treatment may
experience advantages. Angiotensin II type 1 receptor blockers (ARBs) and ACE inhib-
itors have demonstrated the ability to inhibit the release of osteoclast-activating medi-
ators via angiotensin II type 1 receptors on osteoblasts.61,62 They also enhance blood
flow in bone marrow capillaries, elevate free Ca21 ion levels in plasma while reducing
parathormone levels,63 and overall mitigate the detrimental effects of angiotensin II
on bones, particularly the activation of osteoclasts by angiotensin II.56,64,65 Propranolol
likely improves bone healing and osseointegration by reducing the number of osteo-
clasts, increasing collagen production, and promoting mineralization.66 Antihyperten-
sive medications like beta-blockers or ACE inhibitors might also have a beneficial
impact on reducing the rate of implant failure.67–69 Statins exhibit a notable positive in-
fluence on the process of implant osseointegration.70 Recent human studies have
shown that the systemic oral intake of lipophilic statins, such as simvastatin, led to
560 Thomas et al

an increase in BMD.71 Simvastatin, a semisynthetic derivative of lovastatin, was

observed to exert a beneficial influence on bone metabolism.72 Levels of bone alkaline
phosphatase, C-terminal telopeptide of type I collagen, and osteocalcin rose concur-
rently with the elevation in BMD.73–77 The intriguing potential impact of antihypertensive
medications on dental implant osseointegration arises when contemplating their bene-
ficial effects on bone formation, remodeling, and reduced risk of bone fractures.67
Implant survival rates in individuals with cardiovascular disease may be equivalent to
or greater than those observed in healthy patients.78 There is no conclusive evidence
that cardiovascular diseases by themselves are contraindications for implant
placement.17
Immunosuppressants
Cyclosporin A (CsA), an immunosuppressant, may impact the process of bone remod-
eling and inhibit osteoblast cell activity, which may reduce the likelihood of proper
bone healing.79,80 According to recent research, taking CsA prior to implant surgery
can disrupt the osseointegration around implants and lower bone quality, which
may lower the prognosis of implants.81 The use of CsA hinders bone healing process
around implant placement and increases bone loss.82 The potential for developing
osteoporosis secondary to CsA therapy has been mentioned in the literature.83 Immu-
nosuppressive medications may have an adverse effect on the long-term prognosis of
dental implants.17,79
Bisphosphonates
Systemic bisphosphonates have been linked to osteonecrosis of the jaw (ONJ).84 Due
to the possibility of bisphosphonate-induced ONJ, it is advised that these patients are
carefully evaluated, and risk assessment performed prior to surgical intervention
including implants.84,85 A position paper supporting the term medication-related
ONJ rather than bisphosphonate-induced ONJ was released in 2017 by the American
Association of Oral and Maxillofacial Surgeons.86 In patients receiving oral antiresorp-
tive medicines for longer than 3 years, the rate of medication-related ONJ can reach as
high as 0.5% after dental extractions. Currently, there is a lack of robust literature to
contraindicate implant placement in patients taking bisphosphonates. However, den-
tists who place implants must understand the risk associated with treating patients
receiving intravenous or oral bisphosphonate therapy.79
Nonsteroidal Anti-inflammatory Drugs
These medications inhibit the cyclooxygenase enzymes, thereby reducing prosta-
glandin synthesis, a crucial process for healthy bone formation and repair.87,88 A retro-
spective study showed a significant reduction in success rates of implants with
concomitant nonsteroidal anti-inflammatory drug (NSAID) treatment. The same study
also showed less than ideal results for patients who were on NSAIDs prior to implant
placement.17,89,90 Given the evidence available so far, further careful evaluation may
warranted for patients being treated for dental implants.
Antidepressants
SSRIs have been associated with a higher rate of implant failure.91–93 It is thought to be
a result of these medications decreasing the bone turnover and inducing greater
destruction of bone.92 SSRIs have been linked to decreased BMD and an increase
in bone fractures.69 Serotonin receptors are ubiquitous, presenting in multiple tissues
including, but not limited to, brain, neurons, the gastrointestinal tract, blood platelets,
and bone. Reduced bone density results from blocking serotonin reuptake, which also
 Prognosis of Dental Implants 561

causes an increase in osteoclast differentiation and a decrease in osteoblast prolifer-

ation.17 Because of their anti-anabolic skeletal effects, SSRIs have been shown to
negatively impact trabecular microarchitecture and BMD.68 It is prudent to further
evaluate patients on SSRIs for the appropriateness and risks of dental implants.

Proton Pump Inhibitors

A class of medications known as PPIs works by reducing the amount of gastric acid
produced. However, some authors have proposed an association between PPIs
and a higher risk of bone fractures, possibly due to changes in absorption of cal-
cium.67 Long-term PPI use can lower acidity, which can negatively impact the absorp-
tion of calcium, magnesium, iron, and vitamin B12.67,68 Emerging literature seems to
indicate an association between PPI treatment and implant failure.67–69,94,95

Glucocorticoids
Glucocorticoids act on osteoblasts causing apoptosis and promoting the differentia-
tion of adipocytes from bone marrow cells, which may suggest that these medications
have a deleterious effect on bone remodeling. Long-term use of systemic corticoste-
roids may also have a deleterious effect on osseointegration of dental implants.96–98
Long-term corticosteroid therapy seems to be reported in the literature as a strong
relative contraindication to dental implant placement.69,99

Prophylactic Antibiotics
The latest literature seems to indicate that prophylactic antibiotic usage is improving
implant success rates and prognosis. In a relatively recent narrative review on the sub-
ject, the authors recommend a prophylactic regimen somewhat similar to the prophy-
lactic infective endocarditis regimen to prevent early implant failure. However, they
add that the use of antibiotics has no statistically significant effect on postoperative
infections after implant placement.100 Similar results were reported in meta-analysis
performed recently on the topic.101,102 A network meta-analysis of randomized control
trials also have come to the same conclusions.103 Although the exact mechanism of
the protective nature of prophylactic antibiotics on surgical implants is not known,
the plausible explanation seems to be the antibiotic’s effect in eradicating initial bac-
terial colonization and subsequent development of infection.100 The recent consensus
report from the Spanish group of implantologists also seems to ratify this same philos-
ophy.104 Interestingly, allergy to penicillin/amoxicillin is being shown as more condu-
cive to implant failure.105–107 The mechanism of this phenomena is unknown but
proposed to have to do with the use of alternate antibiotics for prophylaxis in patients
with penicillin allergy.

PSYCHIATRIC DISORDERS

There are some significant inconsistencies in the evaluation of implants in patients

with neuropsychiatric disorders. In general, psychiatric disorders and mental disabil-
ities are not shown to be a strong contraindication for dental implant placement.108,109
Many of these patients may have related habits or physical/mental limitations that may
impact the factors such as oral hygiene, thereby affecting implant prognosis.109,110
However, treatment with implants can be a beneficial option for patients with such dis-
abilities, provided that oral hygiene is maintained.111–113 Patients with conditions, such
as schizophrenia and obsessive-compulsive disorder, showed a similar trend toward
higher implant failure.114
562 Thomas et al

MOVEMENT DISORDERS

Patients with movement disorders may have a lower implant survival rate, more early,
rather than late failures seem to occur. Rather than the direct effect of movement disor-
ders, the associated relative inability to maintain oral hygiene may be a more significant
factor leading to possible implant failure.115 In patients with acquired and congenital
neurologic disabilities, there were no higher implant failures observed.116 In a recent
meta-analysis, patients with neuropsychiatric disorders were found to have a higher pro-
pensity for implant failure, primarily due to inability to maintain proper oral hygiene.117

GENETIC DISORDERS

Some genetic disorders such as Down’s syndrome may negatively impact dental
implant prognosis, due to impairments in immunity, combined with cognitive impair-
ment.115,116,118–121 Other characteristics of these patients include macroglossia, par-
afunctional habits, and a history of periodontal disease, thereby conceivably affecting
implant survival. The majority of failures, however, seem to occur prior to implant
loading, that is, during the osseointegration phase.115,119–122

SMOKING

From the available current literature, it appears that smoking affects implant prognosis
negatively, due to its local and systemic effects. The risk of implant failure has been
found to be higher in smokers as compared to nonsmokers.123,124 The amount of mar-
ginal bone loss was found to be significantly higher in smokers as compared to the
controlled group of nonsmokers.125,126 In addition to these, the postoperative infection
risk was also found to be higher in smokers, compared to controls.127,128 It is interesting
to note that most of the literature points out to an increased marginal bone loss second-
ary to smoking at the implant site.129 Traditionally (maybe anecdotally) implantologists
are increasingly likely to defer or choose to refuse implant placement in smokers.

SUMMARY

The analysis of the most recent literature regarding implant prognosis and failures
seems to reveal the importance of, and the role played by, systemic factors. The
astute clinician has to carefully consider the systemic factors and elucidate a complete
medical history from the patient to aid in succinct treatment planning and take appro-
priate precautions preoperatively, intraoperatively, and postoperatively to ensure
optimal implant prognosis.

CLINICS CARE POINTS

 The planning phase of dental implants must include a careful evaluation and consideration
of systemic factors that can potentially affect implant prognosis.
 A sound knowledge of the latest literature showing the effect of these systemic factors on
implant prognosis is paramount to plan and manage any possible potential complications
with dental implants.
 Patient cooperation and compliance with instructions regarding variables potentially under
the control of the patient are also a significant factor in deciding implant prognosis.
 The clinician should carefully consider the risk–benefit ratio of prophylactic or interventional
antibiotic therapy.
 Prognosis of Dental Implants 563

ACKNOWLEDGMENTS

None.

DISCLOSURE

D. C. Thomas, D. Bellani, J. Piermatti, and P. Kodaganallur Pitchumani declare no con-

flict of interest. There was no funding for this study. Statement of institutional review
board approval or waiver: Institutional review and approval were not necessary for
this study.

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