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The viability of early loading

has now been assessed by a

number of studies, some of
which followed patients for
up to 10 years.
According to the well-
established Brnemark protocol,
the placement of an implant-
retained dental prosthesis requires
two surgical procedures separated
by a 4- to 6-month healing period.
During the rst procedure,
implants are placed into the arch
and submerged under the soft
tissue to provide a stress-free
healing period during which
osseointegration can occur.
Primary stability and the absence of
early loading have been considered
fundamental prerequisites for
successful osseointegration.
During the second procedure,
implants are re-exposed and
prepared for attachment of the
Although success rates with
traditional methods are high and
therapeutic outcomes are
predictable, patients are sometimes
reluctant to undergo treatment
because the procedure calls for
either the use of a transitional
removable prosthesis or no
prosthesis at all. Among patients
who do undergo the procedure,
management can be difcult since
postoperative changes during
healing lead to discomfort and
frequent prosthesis adjustments.
What is the Clinical Evidence
for the Success of Early
Evidence is now mounting
that, under certain
circumstances using a one-stage
surgical protocol involving the
rigid connection of implants,
immediate loading with a
xed provisional prosthesis can
be successful.
A one-stage surgical protocol
with early loading of dental
implants is now gaining credibility
for certain cases. The implants are
connected via a bar placed in the
arch that minimizes rotational
movements and transfers loads to
the implants in a vertical direction,
ensuring that osseointegration is
Early Loading of
Dental Implants
Providing Continuing Education as a Service to Dentistry Worldwide.
In This Issue
Early Loading of
Dental Implants 1
Periodontal Page 4
In Practice 5
Hygiene Page 6
Clinical Practice 7
Health Care Trends 8
Harvard School of
Dental Medicine
Continuing Education
Program 9
The Colgate Update 10-12
Chester Douglass, DMD, PhD; U.S.A.
Professor of Oral Health Policy and
Epidemiology, Harvard School of Dental
Medicine and School of Public Health
Associate Editors
John J. Clarkson, BDS, PhD; Ireland
Saskia Estupian-Day, DDS, MPH
Pan American Health Organization; Wash., D.C.
Kevin Roach, BSc, DDS, FACD; Canada
Zhen-Kang Zhang, DDS, Hon. FDS,
RCS (Edin.); China
International Advisory Board
Per Axelsson, DDS, Odont.Dr.; Sweden
Irwin Mandel, DDS; U.S.A.
Roy Page, DDS, PhD; U.S.A.
Gregory Seymour, BDS, MDSc, PhD,
MRCPath; Australia
Volume 10, Number 2, 2000

A Summary Journal of Advances in Dentistry and Oral Health Care

foramina, an area noted for
increased implant failure rates.
While the recently reported
high success rates of
immediately loaded implants
are promising, longer term
data suggest that treatment
plans should take into
account the possible failure
of implants placed into
immediate function.
Placement of Implants for
Early Loading
The survival of an implant
depends on a number of factors
(see gure on next page),
including the density of the bone
into which it is submerged and the
intimacy of contact with the bone.
Implants loaded at the time of
placement should intimately
engage dense cortical bone at both
their apical and crestal aspects, and
they must exhibit primary stability.
If the whole implant is not covered
by bone, the standard 2-stage
procedure is preferable.
The authors of the above-
reported studies concluded that
mandibular implants loaded early
can be successfully osseointegrated.
Despite the ndings of one study in
which implants were successfully
placed into maxillary sites,
practitioners are cautioned not to
extrapolate results to the maxilla,
particularly the posterior region
where bone quality can be poor.
Also, regardless of the time of
loading, good oral hygiene and
control of smoking habits can make
the difference between success and
failure with implants in the long run.
page 2
not compromised. In addition, the
bar provides rigidity and strength
to the provisional prosthesis.
The viability of early loading has
now been assessed by a number of
studies, some of which followed
patients for up to 10 years. Although
some studies report early loading
success rates equal to the standard 2-
stage procedure, clinical investigators
who have conducted longer-term
studies report some failures and are
more cautious in recommending the
technique (see table).
An 18-month study compared
the outcome of clinical
rehabilitation for 16 patients
receiving either immediate loading
of implants via a xed cross-arch
supraconstruction, or a traditional
2-stage treatment that allowed four
months of healing.
Both groups
received titanium implants in the
interforaminal mandibular area.
Based on 18 months of observation
on 88 implants, no xtures were
lost, no clinical complications
developed as a result of either
procedure, and all implants were
clinically stable. Bone resorption
around implants, which were
installed according to either
protocol, was within the same range.
A smaller study with a follow-
up of one to ve years reported
treatment outcomes for
immediately loaded titanium
dental implants in 10 edentulous
The authors placed at
least 10 implants, a minimum of
ve of which were submerged in
each patients jaw. The non-
submerged implants were loaded
the day of the surgery via a
provisional rigid bridge with a cast
framework. A total of 107 implants
were placed. Of the 69 immediately
loaded implants, 67 integrated; 37
of 38 submerged implants
integrated. The authors concluded
that immediate loading may prove
to be a valuable alternative to
A recent large retrospective
multicenter study evaluated the
long-term viability of immediately
loaded implant-retained over-
dentures supported by four
interforaminal implants rigidly
connected by a U-shaped bar.
study involved 226 patients, who
were followed for an average of 6.4
years. The authors reported a
success rate of 96.9%, a gure
comparable to those reported for
the 2-stage procedure.
Ten-year follow-up data for 10
patients given a xed provisional
prosthesis loaded at the time of
mandibular implant placement
were recently reported.
patients were given both
immediately loaded and submerged
implants, and seven of the patients
were edentulous. In all patients, the
immediately loaded implants
successfully supported xed
provisional prostheses during the 3-
month healing period. Ultimately,
however, four of the immediately
loaded implants failed, while none
of the submerged implants failed.
Three of the four failed implants
were located distal to the mental
Comparison of Four Studies Assessing Success with Early Loading of Dental Implants
Study Follow-up Number of Patients Number of Implants Implant Survival
Randow; et al.
18 months 16
88 100%0
Tarnow; et al.
15 years 10
69 97.1%
Chiapasco; et al.
213 years 226
776 96.9%
Schnitman; et al.
10 years 10
28 84.7%
A success rate of 95% after ve years should be expected in the interforaminal area of the
2 a
MK II xtures, Nobel Biocare AB.
6 patientsNobel Biocare; 1 patientITI
Bonet; 2 patientsAstra Tech TiOblast; 1 patient3iii Implant, Implant Innovations.
titanium screw implant systems were usedTPS, ITI, Ha-Ti and NLS.
Nobel Biocare.
page 3
Preliminary Guidelines for
Early Loading
In cases where early loading is
deemed appropriate, Tarnow
suggested a set of guidelines to
help achieve clinical success:
Immediate loading should
be attempted in edentulous arches
only to create cross-arch stability.
Implants should be at least
10 mm long.
A diagnostic wax-up should
be used for template and
provisional restoration fabrication.
A rigid metal casting should
be used where possible.
A screw-retained provisional
restoration should be used where
If cemented, the provisional
restoration should not be removed
during the 4- to 6-month healing
All implants should be
evaluated with Periotest
(a measure
of the degree of resistance to
perpendicular force) at stage 1, and
the implants that show the least
mobility should be utilized to provide
resistance to rotational forces.
The widest possible anterior-
posterior distribution of implants
should be utilized to provide
resistance to rotational forces.
Cantilevers should be avoided
in the provisional restorations.
The emergence of a 1-stage
early loading protocol does not
imply that submersion is no longer
necessary, but rather suggests that
it is not always essential. The
2-stage procedure remains the
treatment of choice. However,
under the right circumstances
successful early loading can reduce
the length of prosthetic
rehabilitation. OC
Intimate initial fit
Dense cortical bone
High percentage of implant in contact
with bone cortex
No micromovement during bone remodeling
Factors associated with the survival of early loaded implants
1. Tarnow D, Emitaz S, Classi A.
Immediate loading of threaded implants at
stage 1 surgery in edentulous arches: Ten
consecutive case reports with 1- to 5-year
data. Int J Oral and Maxillofac Implants
2. Chiapasco M, Gatti C, Rossi E,
Haeiger W, Markwalder T. Implant-
retained mandibular overdentures with
immediate loading. A retrospective
multicenter study on 226 consecutive cases.
Clin Oral Implants Res 1997;8:48-57.
3. Schnitman P, Wohrle P, Rubenstein J,
DaSilva J, Wang N. Ten-year results for
Brnemark implants immediately loaded
with xed prostheses at implant placement.
Int J Oral and Maxillofac Implants
4. Randow K, Ericsson I, Nilner K,
Petersson A, Glantz P. Immediate functional
loading of Brnemark dental implants. An
18-month clinical follow-up study. Clin
Oral Implants Res 1999;10:8-15.
5. Bain CA. Smoking and implant failure
Benets of a smoking cessation protocol.
Int J Oral Maxillofac Implants
6. Olive J, Aparicio C. The Periotest
method as a measure of osseointegrated
oral implant stability. Int J Oral Maxillofac
Implants 1990;5:390-400.
From Periodontal Page
1. Davies J. Mechanisms of osseointegration.
Int J Prosthod 1998;11(5):391-401.
2. Cochran D, Schenk R, Buser D, Wozney
J, Davies J. Recombinant human bone
morphogenetic protein-2 stimulation of bone
formation around endosseous dental
implants. J Periodontol 1999;70(2):139-150.
Factors Associated with the Survival of Early Loaded Implants
page 4
How Does Peri-Implant
Actually Work?
Osseointegration involves
three stages
(see gure):
Stage 1. Osteoconduction
Following the placement of an
implant, wound healing is initiated.
Fibrin, produced as a result of
transient blood clotting at the
wound site, adheres to the surface
of the implant, forming a scaffold
into which osteogenic cells derived
from undifferentiated connective
tissue cells can migrate. As healing
continues, the brin scaffold
retracts, making it critical that the
implant surface be able to retain its
brin attachment and allow the
differentiating osteogenic cells to
reach and remain at the implant
The mechanical and chemical
properties of the implant surface
have a profound inuence on
osteoconduction because they
inuence the anchorage of the
brin scaffold through which
osteogenic cells reach the implant
surface. A rough implant surface,
for example, promotes osteocon-
duction by providing both a larger
surface area and sites into which
the brin can become entangled.
Stage 2. De Novo Bone Formation
De novo bone formation is
initiated when the osteogenic cells
have fully differentiated. The four-
stage process begins with the
secretion of a collagen-free organic
matrix that provides nucleation sites
for calcium phosphate
mineralization. Following nucleation,
calcium phosphate crystal growth
begins at the developing interface,
and collagen ber assembly is
initiated. In the nal stage, the
collagen compartment calcies.
New bone is thus separated
from the implant surface by a layer
of non-collagenous bone proteins
known as the cement line. Bonding of
the new bone with the implant
occurs by fusion or micromechanical
interlocking of the cement line
matrix with the implant surface.
Stage 3. Bone Remodeling
During remodeling, bone
tissue is sculpted by absorption and
deposition, and secondary osteons
form. When these osteons impinge
on the implant surface, de novo bone
formation occurs on the
transcortical implant. Bone
remodeling is particularly important
for the long-term stability of the
transcortical portion of the implant,
since cortical bone can necrose as a
result of surgical trauma.
Osseointegration and Peri-Implant
Bone Defects
Successful endosseous implant
placement depends upon the stability
of the implant in alveolar bone. In
some cases, such as placement of
implants into extraction sites or areas
where bone resorption has occurred,
parts of the implant are not covered
by bone tissue.
A recent study
indicates that
rhBMP-2 encourages the formation
of new bone in the absence of
other exogenous growth factors by
stimulating precursor cells to
become mature bone-forming cells
and begin osseous tissue formation.
The addition of rhBMP-2 to
implants in canine mandibles
resulted in signicantly more
contact between bone and implant,
and a signicantly larger area of
new bone compared with control
implants without rhBMP-2.
Histologically, the rhBMP-2-
stimulated bone was normal and
indistinguishable from
surrounding bone.
The development of new
techniques for the stimulation of
bone formation will help
practitioners optimize
osseointegration, leading to more
successful treatment outcomes. OC
Osseointegration of Dental Implants
Bone remodeling
Cyclical bone resorption/deposition
Formation of secondary osteons
De novo
bone formation
Secretion of collagen-free organic matrix
Calcium phosphate crystal growth
Collagen fiber assembly
Calcification of collagen
Adhesion of fibrin to implant surface
Migration of osteogenic cells
through fibrin
References on page 3
page 5
Implant Surface
Over the last 30 years, a wide
selection of commercially
manufactured endosseous dental
implants has become available to
practitioners. Early studies
indicated that implant anchorage
could be achieved with direct
contact between bone and
titanium. Currently, the three best
documented implant surfaces are
the smooth machined-titanium
surface, the rough plasma-sprayed
titanium (TPS) surface, and a
surface coated with rough, porous
Comparing Surface Types
Biomechanical tests and
histological assays have been
developed that evaluate and compare
the ability of different implant
surfaces to interface with bone.
The data are overwhelming
that implants with a
roughened surface provide
greater bone-to-implant
contact compared to implants
with a smoother surface.
A recent meta-analysis evaluated
more than 100 studies of patients
who received implants with a variety
of different surfaces.
Implants with a
relatively smooth surface were
compared to rough surfaces and
hydroxyapatite-coated surfaces to
determine if differences existed in
their success rates under various
clinical conditions (see table).
For both predominantly and
partially edentulous patients, the
use of smooth surfaces has been
more frequently reported. However,
rough surfaces had a superior
success rate for all implants
regardless of their location in the
arch. For overdenture placement,
rough implants were superior to
smooth in almost all locations.
For single tooth restorations,
the success of rough and smooth
implants was not signicantly
different. This nding may be
related to the fact that, in most
instances, adjacent natural teeth
were present and less alveolar bone
resorption may have occurred than
in an edentulous arch. For patients
with multiple indications that
combine implants placed under
ideal conditions and implants
placed under less-than-ideal
conditions, smooth and
hydroxyapatite surfaces were
superior to rough.
Clinical success rates with
dental implants also vary according
to their location in the arch.
Mandibular placement is typically
more successful than maxillary
placement because of better bone
quality. Strategies to improve success
rates in these areas, particularly the
posterior maxilla, include the use of
longer, wider implants, placement of
additional implants, and the use of a
rougher implant surface.
The success of implants with
rough or smooth surfaces is
inuenced by both their
location in the arch and the
dental status of the patient.
Early Loading of Implants
with Rough Surfaces
Rough surfaces may also be
advantageous for implants that are
to be loaded early. In a recent
animal study, four different TPS
implants were evaluated; one
ordinary TPS and three with
different hydroxyapatite coatings.
The implants were left unsplinted,
and single gold crowns were xed
onto each implant two days after
placement. Free-standing implants
under masticatory loading face a
more demanding mechanical
environment than do splinted
implants, and the micromotion
that results can lead to brous
encapsulation instead of direct
bone apposition.
Tests showed that 39 of 40
implants successfully osseo-
integrated. Periotest showed that
the 39 implants had excellent
primary stability. Standardized
periapical radiographs revealed
radiolucency only in the failed
implant. The authors reported an
average crestal bone loss of 1.3
mm, a nding comparable to others
in the literature. Bone loss was the
same for all of the surfaces. OC
1. Cochran D. A comparison of endosseous
dental implant surfaces. J Periodontol
2. Corso M, Siroto C, Fiorellini J, Rasool F,
Szmukler-Moncler S, Weber H-P. Clinical
and radiographic evaluation of early
loaded free-standing dental implants with
various coatings in beagle dogs. J Prosthetic
Dent 1999;82:428-435.
Comparative Success of Implants
with Different Surfaces Under Various Clinical Situations
Over- Partially Single Multiple
Edentulous dentures Edentulous Tooth Indications
All locations R > S R > S R > S R = S S > HA > R
Maxilla only R > S R = S HA > S > R
Mandible only R = S S > R R > S R = S S > R > HA
R=rough; S=smooth; HA=hydroxyapatite.
Adapted from Cochran.
page 6
Risk Assessment for
Periodontal Disease
It has been clearly established
that bacteria are essential in caus-
ing periodontal disease. However,
individual risk factors involved in
the amplication and progression
of periodontal disease leading to
tooth loss have also been identi-
ed. The three most important fac-
tors determined to date are 1)
smoking, 2) compliance with oral
care regimens and oral hygiene,
and 3) genetic susceptibility.
Smoking has been established
as a major risk factor in affecting a
patients response to bacterial
plaque. It has a more dominant
effect on attachment and tooth
loss than poor compliance and
severe gingival inammation. The
negative inuence of smoking is
clear, although the mechanisms of
action are not yet well understood.
Unless bacterial plaque is
routinely removed by practicing
compliance with oral care regimens
and oral hygiene, immature bacteria
accumulate on teeth, and plaque
continues to grow until it contains
harmful pathogens that contribute
to the destruction of tissue and the
supporting tooth structures.
Patients with periodontal disease
and clinical breakdown who
participate in a periodontal
maintenance program as
prescribed by their dentist or
hygienist present less attachment
loss and less tooth loss than those
who do not.
The same is true for
patients who perform adequate
oral hygiene at home compared to
those without a sufcient home
care regimen.
Oral hygiene and
compliance are behavioral factors,
which implies the ability to control
and/or modify their use. However,
changing habits requires
substantial and persistent
motivation on the part of the
individual. Thus, dental care
providers have the responsibility to
inform patients of their risk for
disease and the importance of
compliance in managing the risk.
Individuals with a specic
genetic susceptibility are more likely
affected by poor oral hygiene/
compliance and smoking, leading
to severe periodontal disease and
tooth loss. Genetically susceptible
individuals are those who produce
more interleukin 1(IL-1), an
inammatory mediator, in
response to bacterial plaque, which
results in rapid and extensive dam-
age to the surrounding tissues. A
study by Kornman and colleagues
found that 67% of patients with
severe periodontal disease had the
IL-1 genotype.
Patients can be
tested for the presence of IL-1
genotype by laboratory analysis of a
nger-stick drop of blood. While
this is not a test for periodontal
disease, it allows the dentist to con-
nect genetic information relative to
the overall risk assessment for the
individual patient, and to support
decisions regarding referrals and
restorative options.
Smoking and genotype have
been identied as the two
most important factors in
determining the prognosis of
periodontally involved teeth.
By acknowledging the impor-
tance of these factors, dental care
providers can consider each
patients risk, allowing for more
cost-effective planning and treat-
ment. The opportunity to identify
high-risk patients and treat them
more proactively is signicant. OC
1. Wilson TG Jr. Using risk assessment to
customize periodontal treatment. CDA
Journal 999;27(8):627-639.
2. Axelsson P, Lindhe J, Nystrom B. On
the prevention of caries and periodontal
disease. Results of a 15-year longtitudinal
study in adults. J Clin Periodontol 1991;
3. Haffajee A, Socransky S. Clinical risk
indicators for periodontal attachment
loss. J Clin Periodontol 1991; 18(2):117-
4. Kornman K, Crane A, et al. The inter-
leukin-1 genotype as a severity factor in
periodontal disease. J Clin Periodontol
1997; 24:72-77
Table 1. Risk Assessment for Patients with Advanced Periodontitis
Who are Candidates for Complex Restorations*
Risk of Losing Critical Abutment/Restoration
Smoking Status
Genotype Non-Smoker >10 Cigarettes/day
IL-1 negative minimal 3
IL-1 positive 3 8
*Patients with critical abutment teeth with moderate to poor prognosis; IL-1 is interleukin-1.
This issue, and every
issue of the Oral Care
Report, is accredited
for 2 hours of C.E.
See page 9 for details.
Revisiting the Basic
Tenets of the Safety of
Endodontic Therapy
The issue of the relationship
between oral and systemic disease
has been brewing over the last 100
years and persists as a topic of
debate. Recent articles and publicity
concerning the connection between
periodontal disease and
cardiovascular disease has led some
to recommend extractions of teeth
with infected necrotic pulps or
endodontically treated teeth. This
echoes of the early 1900s when the
focal infection theory led many to
advocate extractions for many
unsolved medical problems. In a
detailed article entitled, Root
Canal Therapy Safe and Effective,
published by the American
Association of Endodontists as a
part of their ongoing series of
newsletters for the dental
professional, ENDODONTICS:
Colleagues for Excellence, this
resurgence was described with the
phrase Focal infection ghost rises
from the grave.
The article denes focal
infections as secondary infections
caused by bacteria that have
traveled through the bloodstream
from an initial locus of infection,
or focus (see gure). Throughout
dental history, there have been
proponents of the concept that
infections beginning in oral sites
are responsible for many physical
and neurological ailments. Volume
10(1) of the Oral Care Report calls
attention to the current state of our
knowledge on the subject: while
there are some associations, cause and
effect relationships have not been
This treatise on safe and effective
root canal therapy
summarized the
course of history surrounding this
topic and the major inuences
behind the basic tenets.
Current Views About Focal
Theories of focal infection, as
dened historically,
are not
scientically supported, nor do
they justify extracting teeth solely
on the basis that they have infected
necrotic pulps or have been
endodontically treated. Recent
articles have linked extractions or
root canals with bacteremias and
an increased risk of infective
endocarditis in patients with
damaged heart valves; however, it
has been determined that the
infection arose at the time of the
dental procedure and was not
simply due to the presence of teeth
with infected necrotic pulps or
endodontically treated teeth.
While there is no doubt that
bacteria are integrally involved with
the development of pulpitis and
any ensuing peri-radicular
periodontitis, endodontic therapy
performed under aseptic
conditions can thoroughly
eliminate bacteria from the root
canal system. The use of
bactericidal irrigating solutions and
gutta-percha with sealant may also
be helpful. Safe and effective root
canal therapy is realistic; unnecessary
extractions should be avoided.OC
1. American Association of Endodontists.
Root canal therapy safe and effective.
ENDODONTICS: Colleagues for Excellence
1994; (Fall/Winter):1-4.
2. Miller W. Gangrenous tooth pulps as
centers of infection. Dental Cosmos 1888;
3. Rosenow E. Immunological and
experimental studies on pneumococcus
and staplyococcus endodocarditis. J Infect
Dis 1909; 6:245.
4. Hunter W. The role of sepsis and
antispesis in medicine and the importance
of oral sepsis as its chief cause. Dental
Register 1911; 65:579.
5. Meinig GE. Root canal cover-up
exposed. Ojai: Bion Publishing 1993.
6. Kirk EC. Editorial. Dental Cosmos
1930; 72:408.
7. Cecil R, Angevine D. Clinical and
experimental observations on focal
infection with an analysis of 200 cases of
rheumatoid arthritis. Ann Int Med 1938;
8. Joshipura K, Ritchie C, Douglass C.
Strength of evidence linking oral
conditions and systemic disease. Compend
Cont Educ Dent 2000; In press.
page 7
Presence of
bacteria in the
Focal infection
Infection initiated in a secondary
site by bacteria that have
traveled through the bloodstream
from a focus of infection
Focus of infection
Localized area
of initial infection
Infection: Invasion and proliferation of bacteria, or
other pathogenic microorganisms, in body tissues
and the bodys reaction to their presence
page 8
bacteremia incidence of 68.7%,
whereas heavy trauma produced
an incidence of 93.4%. By
comparison, endodontic therapy
resulted in an incidence of only
6 out of 50, or 12%. The authors
concluded that for patients
with a history of valvular heart
disease, endodontics should
be the treatment of choice
whenever possible.
In a similar study by
Baumgartner et al.,
blood samples
were taken from 30 patients after
various non-surgical endodontic
procedures. The incidence of
bacteremia produced by these
procedures was determined and
quantied, and the results again
showed that bacteremia was not
produced when endodontic
manipulations were conned to
the root canal system.
Endodontic therapy is safe
and effective compared to
extraction for controlling the
risk of bacteremia.
The results of these studies
indicate that modern endodontic
therapy produces a remarkably low
incidence of bacteremia. In
patients susceptible to bacteremia,
and at risk for valvular heart
disease, endodontic therapy can be
recommended as a safe procedure
compared to extraction, especially
when the manipulation is conned
to the root canal system.
1. Bender IB, Seltzer S, Yermish M. The
incidence of bacteremia in endodontic
manipulation. Oral Surg 1960; 13:353-360.
2. Baumgartner J, Heggers J, Harrison J.
The incidence of bacteremias related to
endodontic procedures. I. Non-surgical
endodontics. J Endod 1976; 2:135-140.
The Incidence of
Bacteremia Related
to Endodontic
With the renewed emphasis
on oral and systemic disease,
perhaps we need to be reminded of
studies conducted some time ago
that claried the relationship
between endodontic procedures
and bacteremia, particularly when
compared to the alternative of
dental extractions.
Bender, Seltzer and Yermish
randomly assigned 50 adult
patients, ranging in age from 19 to
78 years, to receive endodontic
therapy conducted within the
connes of the root canal, versus
endodontic therapy which
purposely went beyond the
connes of the root canal. Cultures
were taken from the root canal at
the time of therapy and blood
samples were collected before,
immediately after and 10 minutes
after the endodontic therapy. The
results showed that if the
manipulations were kept within the
connes of the root canal, there
was no demonstrable bacteremia in
26 cases. Of the 24 cases in which
manipulation was purposely
conducted beyond the apex of the
canal, six (or 25%) displayed
immediate positive blood cultures.
However, blood samples taken 10
minutes after endodontic
manipulation revealed no positive
cultures in any of the 50 cases. In
previous studies, these investigators
found an 84.9% incidence of
bacteremia following the extraction
of teeth. Moreover, when
bacteremia was related to the
degree of extraction trauma, it was
found that mild trauma produced a
Editor-in-Chief Chester Douglass,
DMD, PhD; U.S.A.
Professor of Oral Health Policy and
Epidemiology, Harvard School of
Dental Medicine and School of Public
2000 Colgate-Palmolive Company.
All rights reserved.
Printed on Recycled Paper
The Oral Care Report
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for oral care professionals. The
Professional Continuing Education
Program is sponsored by Harvard
School of Dental Medicine and
underwritten by a grant from the
Colgate-Palmolive Company. Harvard
University does not endorse the prod-
ucts of any company. Medical writing
by BioMedCom Consultants, inc.,
Montral, QC (Canada).
Published by Professional Audience
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Address comments, queries and
address changes to:
The Oral Care Report
Dr. Chester W. Douglass
Department of Oral Health Policy
Harvard School of Dental Medicine
188 Longwood Ave.
Boston, MA 02115 USA
Fax # (617) 432-0047

page 9
Harvard School of Dental Medicine
This continuing education (CE) program is offered by the Department of Oral Health Policy and Epidemiology of
Harvard School of Dental Medicine.
All four issues of the Oral Care Report (OCR) each year contain multiple-choice, two-credit hour CE examinations sponsored
by Harvard School of Dental Medicine, an ADA Continuing Education Recognition Program (CERP) approved institution.
The 2000 Harvard certicate will be awarded to participants who pass at least 3 (formerly 2; please note this change in
OCR policy) quizzes between April 1, 2000 and March 30, 2001. Continuing education credits apply to all issues of OCR.
Please allow 46 weeks to receive notication of quiz results.
Mark only one answer
per question by lling in the box.
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Record your answers here:
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Department of Oral Health Policy
Harvard School of Dental Medicine
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Boston, MA 02115 USA
1. Which of the following is not a stage in de novo
bone formation?
a) Calcium phosphate crystal growth
b) Collagen ber assembly
c) Deposition of brin scaffold
d) Secretion of collagen-free organic matrix
2. Which of the following best describes the
sequence of events in osseointegration?
a) Osteogenic cell migration, bone bonding,
bone remodeling
b) Osteogenic cell migration, de novo bone
formation, bone remodeling
c) Bone resorption, de novo bone formation,
bone bonding
d) None of the above
3. Recombinant human bone morphogenic protein
(rhBMP-2) encourages new bone formation
a) in the absence of exogenous growth factors.
b) by stimulating precursor cells to differentiate
into bone-forming cells.
c) by encouraging more intimate contact
between bone and implant.
d) All of the above
4. In which of the following locations is early
loading of dental implants least likely to
a) Edentulous arch
b) Posterior maxilla
c) Anterior mandible
d) None of the above
5. Compared with traditional 2-stage implant
loading, success rates with early loading
a) are the same.
b) are the same short-term, but lower long-term.
c) are signicantly lower.
d) have not been directly compared.
6. The survival of early loaded dental implants
depends on
a) intimate initial t.
b) dense cortical bone.
c) high percentage of implant in contact with
bone cortex.
d) All of the above
7. In which of the following situations is a rough
implant surface not superior to a smooth
surface in most locations?
a) Single tooth restorations
b) Overdenture restorations
c) Predominantly edentulous arches
d) Partially edentulous arches
The Harvard School of Dental Medicines Professional Continuing Education Program
is available on the Internet at
The deadline for submission of this issues quiz: September 30, 2000
Copyright 2000 President and Fellows of Harvard College. All rights reserved.
8. Which of the following best describes
hydroxyapatite implant surfaces?
a) Similar to machined titanium
b) Smooth and porous
c) Rough and porous
d) None of the above
9. Which of the following implants is most likely to
be successful?
a) Smooth surface, placement in mandible
b) Smooth surface, placement in maxilla
c) Rough surface, placement in mandible
d) Rough surface, placement in maxilla
10. Risk factors associated with periodontal disease
a) smoking.
b) poor compliance with oral hygiene regimens.
c) genetic susceptibility.
d) All of the above
11. Genetic testing for susceptibility to periodontal
a) is useful for diagnosis.
b) is useful for selecting treatment strategies.
c) has no specic utility.
d) None of the above
12. The risk for periodontal disease from both
smoking and genetic susceptibility is
a) additive.
b) reduced.
c) greater than additive.
d) None of the above
13. The current state of knowledge surrounding the
focal infection theory supports
a) the extraction of all pulpless and
endodontically treated teeth.
b) the belief that oral infections lead to a
multitude of health problems.
c) research by Rosenow and Price as
scientically sound.
d) no relationship between pulpless or
endodontically treated teeth and
degenerative diseases.
14. The focal infection theory states that an oral
infection travels which route?
a) Bloodstream, focus, secondary site
b) Focus, secondary site, bloodstream
c) Focus, bloodstream, secondary site
d) None of the above
15. Factors which may contribute to safe and
effective endodontic therapy include the use of
a) gutta-percha with sealant.
b) aseptic conditions.
c) bactericidal irrigating solutions.
d) All of the above
launch to provide information on side effects of the
drug, and to give reassurance to the doctors who will
be prescribing it. Phase IV also includes studies aimed
at widening the indicated population. If the
formulation or dose regimen is changed, new studies
must be performed. Similarly, labeling changes require
Phase IV studies.
Good Clinical Practice (GCP) guidelines
provide the standards by which clinical
trials are designed, implemented and
reported, so that there is public
assurance that the data are credible,
and that the rights, integrity and
condentiality of subjects are protected.
Good Clinical Practice (GCP) guidelines provide
the standards by which clinical trials are designed,
implemented and reported, so that there is public
assurance that the data are credible, and that the
rights, integrity and condentiality of subjects are
To operate in a standardized environment,
sponsors and Contract Research Organizations have
developed Standard Operating Procedures covering all
aspects of clinical research. These procedures strive to
make clinical trials more reliable and less dependent
on the people involved in data acquisition, monitoring,
and reporting, thus resulting in more objective
research results.
There has been increased standardization of NDA
scientic nomenclature regarding technical
requirements, formats and procedures, and there is a
more standardized environment with increasing
interactions with international health authorities. We
are denitely living in a global world, not only
concerning environmental issues, but also for oral
pharmaceutical research issues.
Practitioners who use oral medications should
know that obtaining market approval for new products
requires controlled clinical trials within an on-going
dental practice setting. Patients enrolled in these
clinical trials are more closely followed and
documented than other patients. Thus, the clinical
research process is heavily regulated by the U.S. Food
and Drug Administration (FDA) and is divided into
four distinct clinical phases.
Phase I: After pre-clinical (toxicity) testing in
animals, Phase I clinical trials start with healthy subjects
to test how the new drug will be tolerated, thus
producing pharmacokinetic and pharmacodynamic
data. This information is an initial requirement for
conducting dose-ranging studies on patients with the
condition being treated.
Phase II may be divided into two sequences: Phase
IIa refers to short- to medium-range pilot studies in
diseased patients, providing preliminary evidence of
efcacy, pharmacodynamic effects and initial dose
ranging data. Phase IIb is the critical efcacy phase, in
which dose-response studies produce denitive proof of
efcacy, usually under placebo-controlled conditions.
Phase IIb ends with a minimum effective dose, a
maximum-tolerated dose, and at least two independent
pivotal studies as proof of clinical efcacy.
Phase III: With a well-conducted Phase IIb, Phase
III becomes primarily the expansion phase. Phase III
studies, usually long-term, use less specialized doctors
on a more general population of patients. The main
objective for these studies is to establish a complete
safety prole in the general population. Phase III
studies utilize a random sample of patients where
possible, and are highly controlled to facilitate the
interpretation of results. If everything goes well in
Phase III, a New Drug Application (NDA) is usually
prepared for FDA submission. Toward the end of the
Phase III trials, special studies are often needed to
satisfy the requirement of the FDA Biopharmaceutical
Division with regard to possible adverse drug
interactions and, as well, to conrm the bioequivalence
between the formulations used in the clinical trials and
the formulations to be marketed.
Finally, there are Phase IV studies, usually
performed after the drug is on the market.
Comparisons with similarly marketed drugs are a part
of classic Phase IV studies. Frequently there are Phase
IV surveillance studies performed early after product
page 12
Assuring That New Pharmaceutical Products
Are Safe and Ef fective
Eric Vander Elst, MD and Chester W. Douglass, DMD, PhD
The Oral Care Report (ISSN 1520-0167) is available on the Internet at