Jan Lindhe. Clinical Periodontology

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THE SURGICAL SITE

• 857

indicates small volumes of bone also in other edentu-

lous areas of interest. The minimum bone volume

required for implant surgery according to the stan-

dard protocol is about 7-9 mm of height, measured

from the level where the jaw is at least 4-6 mm wide.

Treatment planning

After having collected all clinical and radiographic

data, a final treatment planning is carried out by the

prosthodontist/restorative dentist. As the placement

of the implants is an important part of the treatment

strategy, the responsible surgeon/periodontist should

also take part in the detailed planning regarding im-

plant location, i.e. participate in a team approach. It is

important that the surgeon understands that the final

result will never be better than what he or she establ-

ishes when placing the implants as support for the

prosthetic construction. During the planning, the cli-

nicians involved should also discuss what they want

to achieve with the treatment as well as estimating

whether the wishes of the patient are realistic and can

be fulfilled via the proposed procedure. Unrealistic

expectations must be identified and discussed with

the patient, and alternative therapies suggested.

During the treatment planning, the earlier men-

tioned stone cast models are used to discuss what may

be the best position and direction of the future im-

plants. It is thereby the prosthodontist/restorative

dentist who best knows what the prerequisites are for

creating the desired prosthetic solution. The surgeon

should, however, evaluate via the clinical and radio-

graphic information obtained, whether suggested po-

sitions and directions are possible to establish in rela

tion to the available anatomy. Possible obstacles for

surgery must be identified, and alternative solutions

such as local grafting and/or bone augmentation (De

porter 2001) might be suggested in case it turns out to

be impossible to perform the first alternative during

implant placement. The skill of the surgeon will

thereby be important when having to improvise dur-

ing the stage one operation.

In order to study the anticipated esthetic and func

tional result, a wax-up may be produced on the stone

cast models, indicating the best positions and inclina

tions for the implants. This is specifically recom-

mended when working in the frontal region of the

maxilla, where the esthetic outcome is most obvious.

The wax-up can, of course, also be used to show the

patient the suggested treatment result, and it may later

be used to fabricate a surgical stent too. The latter is of

great help when, due to anatomic shortcomings, it is

not possible to strictly follow the originally proposed

guidelines for implant placement. The design of the

surgical stent should be such, though, that it will not

interfere with the surgical procedure. Furthermore, it

should also be possible to sterilize it.

Finally, the patient is once again informed about the

tentative treatment plan, possible complications, ex-

pected prognosis and protocol for annual check-ups.

After obtaining the consent of the patient for sug-

gested treatment, implant surgery can begin.

Summary: treatment planning

Based on the clinical and radiographic data collected,

final discussion regarding what is expected and

possible to perform is carried out. The prosthodon-

tist/restorative dentist conveys to the surgeon the

optimal therapy for the patient, so that a team ap-

proach to the treatment planning can be established.

In order to create acceptable function and esthetics, the

best position and direction of the implants must be

identified together with the number and type of im-

plants that can be inserted. A wax-up may thereafter

be fabricated in order to study the suggested treat-

ment result and to show the patient the presumed

outcome. Based on the waxing, a surgical stent may

be fabricated, the design of which should be simple

and possible to sterilize. After obtaining the consent

of the patient, the implant insertion can finally be

executed.

PRINCIPLE COMMENTS ON

IMPLANT PLACEMENT

The main purpose of the implant surgery is to establ-

ish the anchorage for the future fixed prosthetic con-

struction (Branemark et al. 1985). In order to create a

favorable and lasting result, it is first of all important

to understand that the jawbone is a living tissue that

cannot be violated during surgery. Secondly, a strict

protocol for the clinical handling must be followed,

based on collaboration with the general clini-

cian/prosthodontist responsible for the restorative

treatment. Consequently, all surgery must be per-

formed according to defined and correct techniques.

Those for the standard protocol of the Branemark

Implant System have been presented in detail else-

where (Adell et al. 1985, Lekholm & Jemt 1989). In

connection with the treatment of partially edentulous

jaws, some factors are of specific interest as have been

discussed by, for example, Palacci et al. (1995). With-

out giving a step-by-step presentation of how to insert

the implants, the aim of the current section is to gen-

erally inform about some surgical technique aspects.

Flap design

In principle, two different flap designs can be used:

vestibular or crestal incisions. At present there is no

information available to indicate that one of the two

techniques is more advantageous than the other. Con

sequently the surgeon should select the method best

suited for the individual situation. As a rule of thumb,

the wider the top of the crest the more convenient it is

to use a crestal incision. If the crest is high and narrow,

858 • CHAPTER 37

Fig. 37-4. The structure that can

clearly be identified both radiog-

raphicly (a) and clinically (b) is

the top of the alveolar crest, as

seen in a radiograph (white thin

arrow) and clinical picture (black

thin arrow). In the pictures, the

upper border of the mental foram

ina is also marked correspond-

ingly with curved white and black

arrows, respectively.

a buccal approach might be better. The decision about

whether or not to place the incision within the crevicu

lar area of close-standing teeth must be based on the

space available for the implants. A general recommen

dation when placing implants close to teeth is to make

the incision within the pocket region in order to get

sufficient width of the mucosa for its nutrition and to

obtain full mucosa coverage of the implant. However,

whenever possible it is suggested that the gingiva of

the neighboring teeth be avoided; this gives a better

esthetic result for the appearance of the soft tissue

margin of those teeth later on.

When elevating the mucosa, it is also necessary to

properly raise the periosteum with the flap, specifi-

cally when releasing the soft tissue on the lingual side

of the mandible. In this way it is possible to prevent

the soft tissue from being caught by the burs or im-

plants, should the lingual cortex be accidentally per-

forated during the subsequent drilling or implant in-

stallation. It is also important to detach the flap prop-

erly on the buccal side of both the maxilla and the

mandible. Thereby, it will be possible to inspect any

concavities and/or protrusions of the jaws, contours

of tooth roots and nerve entrances, structures that may

later influence the positioning of the implants. Fur-

thermore, it will facilitate the irrigation of the bone

during drilling.

In connection with the raising of the flap, a point

also to consider is whether and when it is necessary to

adjust the top of the alveolar crest. As a general rule

of the two-stage surgical protocol, no bone should be

removed from start, except when the crest is very thin.

Instead, it is recommended when working in the man

dible that a correction of possible sharp bone edges

first takes place after the implants have been placed,

i.e. at the end of stage one surgery. If possible, a few

mm of bone ought to be left above the level of inserted

cover screws to avoid early loading of the implants

from provisional dentures. In the maxilla, the trim-

ming should in most situations be postponed until the

second stage surgery, after checking that inserted im

plants have become osseointegrated. This avoids any

unnecessary removal of bone which could otherwise

lead to impaired prosthesis retention if, due to implant

losses, the patient has to return to a conventional

removable denture. In connection with an immediate

implant loading technique, the bone around the im-

plant head should be carefully adjusted so attached

abutments do not have to be unnecessarily long to

compensate for surrounding bone and soft tissues.

Bone drilling

It is of utmost importance to keep in mind that the

bone tissue should not be exposed to adverse friction

heat formation during drilling (Branemark et al. 1985).

This may easily take place, though, as the threshold

level for osteocyte damage lies around 47°C, i.e. only

about 10°C above the body temperature (Eriksson &

Adell 1986). Consequently, all surgery must be per-

formed at a minimum rise of temperature, which can

be achieved via the use of an intermittent drilling

technique, together with sharp burs, executed in a

sequence of preparation steps under profuse saline

irrigation (Adell et al. 1985). Whenever extremely

dense bone is present, which mostly occurs in the

symphysis region of the mandible, it is furthermore

recommended to use an extra wide twist drill with a

diameter of 3.15 mm, before pretapping and/ or insert

ing the implants (Friberg 1994). However, when work

ing in softer bone qualities, the drilling must be per-

formed with the highest precision, as otherwise the

entrance of the implant site may be widened too much,

resulting in an unstable implant from the start. To

minimize the risk of initial instability, an adjusted

surgical technique using either thinner drills or wider

diameter implants has been recommended (Bahat

1993, Friberg 1994, Watzek & Ulm 2001).

No implant site should be prepared in relation to

THE SURGICAL SITE

•

the inferior alveolar nerve without first having carried

out some kind of tomographic examination, as men-

tioned above. The only structure that can clearly be

identified both in radiographs and clinically is the top

of the alveolar crest (Fig. 37-4). Consequently, that

configuration has to be used as reference for all meas-

urements, both in X-rays and when drilling. During

the preparation of the site it is also of particular im-

portance to keep an eye on the depth references of the

drills in relation to the alveolar top and not only in

relation to the level of the starting point for drilling.

Furthermore, it must be pointed out that during the

preparation of the site, the reference point for depth

measurements may move in an apical direction, par-

ticularly if a narrow and drop-shaped alveolar crest is

present (Fig. 37-5). When this happens, a shorter im-

plant than originally intended must be considered, in

order to ensure that it is completely bone covered on

all sides and that it does not get into contact with the

nerve canal.

If, during drilling in the mandible, a perforation

through the lingual cortex occurs, this may be a pro-

blem, depending on where it takes place. If the perfo-

ration is located in the frontal region of the mandible,

e. in between the canines, and provided that the

periosteum has been properly released when raising

the flap on the lingual side, no real adverse complica-

tions can be expected. However, if instead such a

perforation occurs in the premolar or molar regions of

the mandible (Fig. 37-6), an obvious risk of damaging

the loop of the

versa facialis

or even

arteria submentalis

may arise, a condition which might lead to extensive

and even lethal bleeding.

Implant position

If possible with regard to the anatomic situation, the

implant should preferably be placed in tooth position

(

Fig. 37-7), both in a mesiodistal and in a buccolingual

direction. To achieve this, the starting point must in

most instances be located towards the buccal side of

the crest in the mandible, and towards the palate in

the maxilla, due to the presence of concavities that

often exist in the jaws. Depending on the extent of the

concavities, the starting point will be located either

close to the top of the crest, as in the case of a wide

alveolar process, or deeper down palatally or buccally (

Fig. 37-7), if the jaw is thin in its coronal portion.

The distance between two sites should not be less

than about 7 mm, measured from center to center (Fig.

37-8); otherwise there will be problems with the use of

the instruments, or with the oral hygiene of the abut-

ments later on. First the site closest to a tooth is

marked, starting approximately 3.5-4 mm away from

the prominence of that tooth. The following implant

positions are then marked in a distal direction until

reaching the area of minimum bone volume for im-

plants, i.e. 5 versus 7(9) mm (Figs. 37-2, 37-3). The

longest distance that can be accepted between two

Fig. 37-5. Schematic drawing showing maximum drill-

ing depth (x) without reaching the nerve, as measured

from the top of the crest, and implant site length (y), as

measured from the lowest bone level in the canal en-

trance.

Fig. 37-6. Sketches showing, in the premolar region of

the mandible, the relation between a perforating drill

tip and the loop of

vena facialis

arteria submentalis.

implants has not yet been properly defined. However,

the general rule is that the softer the bone, the closer

the implants should be inserted. As an alternative to

a reduced interimplant distance, and therefore in-

creased number of implants, it is sometimes also pos

sible to place wider diameter implants, as discussed

below.

The second guideline regarding placement of im-

plants in partially edentulous jaws is to insert at least

three implants, instead of just two, in order to avoid

overloading of the anchorage units (Rangert et al.

1989). The reason for this is that the failure rate has

been reported to be higher with two than with three

or more implants (Jemt & Lekholm 1993), due to the

adverse biomechanics that can occur if only one rota

tional axis is present to distribute the loading forces.

Furthermore, the implants should be placed in a tri-

pod position (Fig. 37-8) instead of being inserted in a

Buccal

86o •

CHAPTER 37

Fig. 37-7. Schematic drawings showing implant posi

tions in mesial-distal and buccal-lingual

dimensions.

Indicated starting points for drilling are

marked with

black arrows.

straight line, thereby minimizing the transmission of

bending forces on to each individual implant (Rangert

et al.

1989).

If only one implant can be inserted, then

that sole anchorage should mainly be used to support

single crown restoration. The combination of im-

plants and teeth to support a fixed bridge construction

is possible (Gunne et al.

1992, Naert et al.

1992)

but

ought in most cases to be avoided due to the risk of

overloading the implant during function. The tooth

can move via its periodontal ligament, whereas the

implant is immobile due to its osseointegration. How-

ever, if a combination therapy is planned, an implant

as long as possible should be inserted and the combi-

nation should be done only with a tooth that has

sufficient and healthy periodontal support.

Implants should never be placed in the midline of

the maxilla or the mandible, as in these positions they

may either expand the suture, as between the two

maxillae, and/or may compromise the esthetics. Of

course, the implants should not be placed into impor

tant structures such as nerves, tooth roots and jaw

Fig. 37-8. Schematic drawing indicating a tripod place-

ment of the implants in order to minimize individual

load distribution onto each implant by creating several

rotational axes.

cavities either, as no damage of surrounding tissues

can be accepted just because of the wish to insert

implants for prosthetic anchorage.

Implant direction

After marking the position of the implant sites it is also

important, in the buccolingual and mesiodistal di-

mensions, to decide the direction/inclination of the

implants. The general principle is still to place the

implants within tooth position, which means that nor-

mally the long axis of the implant should be directed

through the crown or the occlusal surface of the bridge

to be. Regarding the buccolingual dimension (Fig.

37-

9),

the long axis of mandibular implants will

mainly

be directed towards the limbus part of the

incisors or

the palatal cusps of the teeth in the maxilla.

For

implants placed in the maxilla, the corresponding

inclination should be towards the incisive edges of the

frontal teeth or the buccal cusps of the premolars or

molars of the mandible. If the starting point of the

implant sites in upper jaws has been located close to

the top of the crest, and if a possible concavity on the

buccal side is present, the long axis of the implants

may easily be leaned too far buccally to avoid fenes-

trations. The equivalent for the mandible may be a too

lingually directed implant owing to the presence of

lingual concavities. Such adverse directions can, how-

ever, impair the esthetics and function of the future

bridgework (Fig.

37-7),

even though angulated abut-

ments may to some extent compensate for such a

surgical error. In addition, the inclination of the im-

plants will also be dependent on the existing jaw

relation. In Applegate-Kennedy Class I, for example,

the implants should be placed rather vertically in both

jaws. In Class II, the implants should mainly be placed

vertically in the maxilla and slightly in a buccal direc-

THE SURGICAL SITE • 861

Fig. 37-9. Schematic drawings showing the most favorable starting points and implant directions in buccal-lingual

dimension within (a) the mandible and (b) the maxilla. A = closest distance of a site to a tooth.

tion in the mandible, whereas in Class III, the implants

should be located somewhat buccally in the maxilla

and slightly lingual in the mandible. If there is too

adverse a relation between the jaws, it is recom-

mended that orthognathic surgery (Clokie 2001) be

discussed with the patient prior to or in combination

with the implant placement, in order to correct the

abnormal jaw relation. Otherwise, too unfavorable an

inclination of the implants may occur, impairing the

final prosthetic function and esthetics.

For the mesiodistal dimension (Fig. 37-10), the rule

is that the implant site closest to the last tooth is placed

parallel to the long axis of the root of that tooth. The

further distally the site is located into the molar region,

on the other hand, the more violated this rule must be.

In the mandible, for example, it is recommended that

the most distal implants be placed in a slightly mesial

direction to facilitate the connection of the abutments

and the fabricated fixed bridge construction. Corre-

spondingly, when working in the premolar regions of

the maxilla, the last implant could be directed slightly

distally in order to follow the mesial wall of the max-

illary sinus, thereby allowing a longer implant to be

placed. An alternative to this procedure would be to

use some kind of sinus elevation technique

(

Hochwald & Davis 1992, Neukam & Kloss 2001).

Finally, it has to be stressed that if the surgeon is

inexperienced in directing implants, the use of a sur-

gical stent is strongly recommended, especially when

inserting implants in the front of the maxilla, where

the need for an esthetic result is obvious.

Cortical stabilization

As a general recommendation, inserted implants

should whenever possible be placed so they engage

two cortical layers (Ivanoff et al. 1996), i.e. one at the

marginal and another at the apical level of the implant.

The reason for this is that studies (Sennerby et al. 1992)

have shown how the cortical bone, and not the tra-

becular bone at least from start, provides the most

862 • CHAPTER 37

favorable anchorage of the implant. When working in

the maxilla, establishing bicortical stabilization (Adell

et al. 1985) is not a problem

per se

as the floor of the

nasal and/or sinosal cavities can easily be perforated

on purpose when drilling. However, at the same time

it is necessary to point out that, after perforating the

bases of the maxillae with the burs, it is important to

properly measure the canal depth so that the

implant

does not reach above the floor of the cavities

but only

engages the cortical layer with its apical tip.

In the frontal regions of the mandible, i.e. between the

men-

tal foraminae, it is not a problem to reach the

second

cortical layer either, especially when working

in a

slightly resorbed but low density jaw (shape

group

B/quality group 4; Lekholm & Zarb 1985).

However,

if denser bone is present as in the anterior

part of the

lower jaw, the implants do not have to

reach all the way down to the jaw base, as long as

the implants

obtain good initial stability. When

working above the

inferior alveolar nerve, on the

other hand, the require-

ment to engage two cortices

can rarely be met for

natural reasons and, therefore,

implants in these re-

gions will most often only be

monocortically stabi-

lized. It is not recommended to

try to establish any

contact with the cortex that

surrounds the inferior

alveolar nerve, as this may

easily result in compres-

sion of the nerve canal. In

some instances, however,

the lingual cortex of the

mandible can be reached and

used for stabilization,

especially when working with

wider diameter

implants. Other ways to overcome the problem with

impaired monocortical stabilization are

to be careful

with the countersinking within the corti- cal layer of

the entrance of the implant site, and to

decide on a

longer healing time before loading the

implants (

Sennerby et al. 1992, Friberg 1994). The

nerve

transpositioning technique may also be used as

alternative (Rosenquist 1994).

Fig. 37-10. Drawings showing implant directions in

mesial-distal dimension of posterior parts of the jaws.

In the maxilla, the most distal implant is directed dis

tally due to the orientation of the sinus wall to engage

more bone. In the mandible, the implant is tilted

mesially to provide better access for instruments dur

ing abutment and prosthetic procedures.

Implant selection

Depending on the specific condition of each site, the

surgeon selects the most suitable type of implant.

Whenever possible, the longest implant should as a

rule be inserted, as shorter implants have a tendency

to show less favorable survival rates than longer ones

(

Friberg et al. 1991, Lekholm et al. 1994). However, it

has to be pointed out that all commercially available

Branemark System implants, including the 7 mm-long

ones, have survival rates exceeding 85% after 5 years

of follow-up (Lekholm 1992, Friberg et al. 2000). Con

sequently, it is the bone quality and not the implant

length that is of importance for the outcome of the

implant treatment. As a second rule, self-tapping im-

plants are often inserted in order to minimize the time

for the surgical procedure. If the bone site is very soft

(

quality 4; Lekholm & Zarb 1985), the longest and

widest standard implant, i.e. 4 mm or 5 mm in diame

ter, instead ought to be placed in order to enhance the

initial stability (Ivanoff et al. 1997). Conical implants

and implants having a rougher surface have lately

been introduced to achieve a better initial stability in

soft bone situations, but so far no long-term follow-up

results have been presented. If, on the other hand, the

bone is of good density, shorter self-tapping implants

or standard implants (after pretapping) of regular

diameters (3.75 mm) will be sufficient. The latter may

often be the case when working in frontal regions of

the mandible. Whatever type of implant is being used,

the overall aim is to reach initial stability of the im-

plant at installation, and to create a lasting anchorage

unit for the prosthetic construction via maintained

osseointegration (Sermerby & Rasmusson 2001).

Healing time

The factor of most importance for how long the heal-

ing time should be, i.e. the time required before im-

THE SURGICAL SITE • 863

plants are loaded, is the quality of the bone of the

implant site. The general and original principle has

been that the softer the bone the longer the healing

time. Within the mandible, the standard length of

healing is 3-4 months for bone of good quality. For the

maxilla the corresponding time is 5-6 months, as the

bone is normally more cancellous in that jaw (Adell et

al. 1985, Watzek & Ulm 2001). When soft bone is

present (quality 4; Lekholm & Zarb 1985), it is recom

mended to extend the healing time by a month or two

also in the mandible (Friberg 1994), especially if only

one cortical layer is engaged by the implant. As vari-

ations may exist between different regions of the same

jaw, e.g. between frontal and distal segments or even

between different sites within the same region

(

Watzek & Ulm 2001), it is important to also individu-

alize the healing and to allow the softest bone site to

decide the timing.

By the use of resonance frequency analysis (

Meredith et al. 1996) it has become possible to meas

ure the initial implant stability of each site, i.e. the

density of the bone surrounding the implant. The bone

quality can thereby be repeatedly analyzed over time

and the healing period individualized without using

any invasive technique for the tests. An implant sta-

bility quotient (ISQ) value of above 60 has thereby

been recommended (Sennerby & Meredith 2002) in

order to load oral implants directly after insertion. The

use of one-stage procedures for the surgical protocol

is a topic of currently increasing interest (Ericsson et

al. 1994, Bernard et al. 1995, Branemark et al. 1999).

Immediate loading of implants has, for example, been

suggested, both in the way of using provisional con-

structions (Balshi & Wolfinger 1997, Schnitman et al.

1997) and/or permanent bridges for early loading

(

Randow et al. 1995, Ericsson et al. 2000). The latter

means that the implants are unloaded only during the

time it takes to fabricate the prosthesis. Favorable

short-term outcome has also been presented for pro-

visional constructions in partially edentulous jaws

using temporary implants (Petrongaro 1997). How-

ever, before a general recommendation can be given

for immediate protocols in partially edentulous situ-

ations, more patients representing various shape and

quality groups as well as different partial jaw situ-

ations will have to be treated and followed for longer

periods.

Abutment selection

Due to the great variety of abutments being available

within different implant systems, it is difficult to give

any detailed recommendations on what type of abut-

ment should be selected. However, the rule of thumb

should be to choose the one that gives least interfer-

ence with the esthetics and function. The best choice

during second-stage surgery, if uncertain about what

to place, is to attach a healing abutment. This makes

possible for the prosthodontist/general practitioner

later change it to the individually best abutment,

when the swelling of the soft tissue has gone down.

Summary

A well-performed surgical protocol, based on preop-

erative examinations and treatment planning, consti-

tutes the prerequisite for a successful future implant

treatment result. The placement of the implant within

tooth position, both in mesiodistal and buccolingual

dimensions, is of primary importance. Secondly, the

implant should whenever possible engage two corti-

cal layers in order to establish maximum initial stabil

ity. Thirdly, implants as long and/or as wide as possi

ble due to anatomic conditions should also be consid

ered, to optimize the initial stability and the sub-

sequent osseointegration level. If surgery is per-

formed in the correct way and using a team approach,

the outcome of the surgical protocol can also be pre-

dictable and successful in partially edentulous situ-

ations, as seen in long-term follow-up studies (Naert

et al. 1992, Nevins & Langer 1993, Lekholm et al. 1999).

However, indications are at hand that the individual

skill level of the clinician/surgeon is an important

factor too for the treatment result, and consequently

not only the surgical technique and/or the type of

implant/implant system being utilized will influence

the clinical outcome (Esposito et al. 1998).

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CHAPTER 3

Alveolar Bone Formation

NIKLAUS P. LANG, MAURICIO ARAUJO AND THORKILD MARRING

Basic bone biology

Bone healing — general aspects

Bone grafting

Concept of guided tissue regeneration (GTR)

Animal studies

Human experimental studies

Clinical applications

Perspectives in bone regeneration with GTR

During embryogenesis, in the alveolar process of the

maxilla and the mandible, bone is formed within a

primary connective tissue. This process is termed

in-

tramembranous

bone formation and also occurs at the

cranial vault and in the midshaft of the long bones. In

contrast, bone formation in the remaining parts of the

skeleton occurs via an initial deposition of a cartilage

template that is subsequently replaced by bone. This

process is called

endochondral bone formation.

Alveolar bone lost as a result of disease, trauma or

extensive post-extraction bone modeling may pose

therapeutic problems in reconstructive and/or im-

plant dentistry. Thus, implant placement both in the

maxilla and in the mandible may be hampered by the

lack of sufficient amounts of alveolar bone tissue in

the recipient sites.

De novo

formation of alveolar bone

in such compromised sites may be necessary and

different regenerative therapies were developed to

allow for bone regrowth. Various apparently success-

ful regenerative methods may technically appear to be

markedly different. They all, however, have one as-

pect in common: the compliance with the principles

of bone biology.

BASIC BONE BIOLOGY

Bone is a specialized connective tissue that is mainly

characterized by its mineralized organic matrix. The

bone organic matrix is comprised of collagen, non-col

lagenous proteins and proteoglycans. Within this ma-

trix, ions of calcium and phosphate are laid down in

the ultimate form of hydroxyapatite. This composi-

tion allows the bone tissue (1) to resist load, (2) to

protect highly sensitive organs (e.g. the central nerv-

ous system) from external forces, and (3) to participate

as a reservoir of minerals that contribute to the body

homeostasis.

Bone cells

Osteoblasts

are the cells responsible for the formation

of bone. Thus, osteoblasts synthesize the organic ma-

trix components and control the mineralization of the

matrix. Osteoblasts are located on bone surfaces ex-

hibiting active matrix deposition and may eventually

differentiate into two different types of cells: bone

lining cells

and

osteocytes. Bone lining cells are elon-

gated cells that cover a surface of bone tissue and

exhibit no synthetic activity. Osteocytes are stellate-

shaped cells that are trapped within the mineralized

bone matrix but remain in contact with other bone

cells by thin cellular processes. The osteocytes are

organized as a syncytium that provides a very large

contact area between the cells (and their processes)

and the non-cellular part of the bone tissue. This ar-

rangement allows osteocytes (1) to participate in the

regulation of the blood-calcium homeostasis, and (2)

to sense mechanical loading and to transmit this infor

mation to other cells within the bone.

The osteoblasts are fully differentiated cells and

lack the capacity for migration and proliferation.

Thus, in order to allow bone formation to occur at a

given site, undifferentiated mesenchymal progenitor

cells

(osteoprogenitor cells)

must migrate to the site and

proliferate to become osteoblasts. Friedenstein (1973)

divided osteoprogenitor cells into

determined

and

in-

ducible osteogenic precursor cells.

The determined osteo-