Jan Lindhe. Clinical Periodontology

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REGENERATIVE PERIODONTAL THERAPY . 685

Table 28-3. Clinical outcomes and weighted mean of GTR treatment of mandibular degree II furcations

Authors

Type of Study

Treatment

Defect

Depth

(mm)

H-CAL

Gain (mm)

H-OPAL

Gain (mm)

Furca

closed

Pontoriero et al. 1988

Controlled clinical trial

e-PTFE

4.4 ± 1.2 3.8 ± 1.2

14 (67%)

Becker et al. 1988

Case cohort

e-PTFE

8.3 ± 2.3

1.8 ± 1.5

Schallhorn & McClain

1988

Case cohort

e-PTFE

NA NA

3.1 ± 1.7

5 (31%)

Lekovic et al. 1989

Controlled clinical trial

e-PTFE

NA NA

0.2 ± 0.5

Lekovic et al. 1990

Controlled clinical trial

e-PTFE

4.2 ± 0.2

0.1 ± 0.1

Caffesse et al. 1990

Controlled clinical trial

e-PTFE

± ?

NA NA

Anderegg et al. 1991

Controlled clinical trial

e-PTFE

4.2 ± 2.2

1.0 ± 0.8

Yukna 1992

Controlled clinical trial

e-PTFE

± ?

FDDMA

±?

Blumenthal 1993

Controlled clinical trial

e-PTFE

4.4 ± 0.9

1.8 ± 1

1.7 ± 0.5

4 (33%)

Collagen

4.5 ± 0.9 2.5 ± 0.8 2.5 ± 0.7

1 (8%)

Bouchard et al. 1993

Controlled clinical trial

e-PTFE

2.8 ± 1.3 2.2 ± 1.4

4 (33%)

Conn. Graft

1.5 ± 1.5 1.5 ± 1.1

2 (17%)

Machtei et al. 1993

Controlled clinical trial

e-PTFE

2.3 ± 1.7

NA NA

Parashis & Mitsis 1993

Controlled clinical trial

e-PTFE

5.7 ± 0.7 4.7 ± 1.5

4 (44%)

Van Swol et al. 1993

Controlled clinical trial

Collagen

5.1 ± 1.4

2.3 ± 1

± ?

Wallace et al. 1994

Controlled clinical trial

e-PTFE

NA NA

± ?

Black et al. 1994

Controlled clinical trial

e-PTFE

4.3 ± 2

0.8 ± 2.2

NA NA

Collagen

4.4 ± 1.5

1.5 ± 2

NA NA

Laurell et al. 1994

Case cohort

Polylactic Acid

3.3 ± 1.4

9 (47%)

Machtei et al. 1994

Controlled clinical trial

e-PTFE

7.7 ± 1.8 2.6 ± 1.7

NA NA

Mellonig et al. 1994

Controlled clinical trial

e-PTFE

8.4 ± 1.2

4.5 ± 1.6

1 (9%)

Wang et al. 1994

Controlled clinical trial

Collagen

6.0 ± 2.7 2.0 ± 0.4

± ?

Hugoson et al. 1995

Controlled clinical trial

e-PTFE

5.9 ± 1.3 1.4 ± 2.2

4 (11%)

Polylactic Acid

5.6 ± 1.4

2.2 ± 2

13 (34%)

Poison et al. 1995

Case cohort*

Polylactic Acid

5.4 ± 0.2 2.5 ± 0.1

Weighted Mean

423 5.4

1.3 t 2.3

1.4$ 1.9

± 1 ^

H-CAL = Horizontal Clinical Attachment. H-OPAL = Horizontal Open Probing Attachment. NA = data not available. e-PTFE = expanded

Polytetrafluoroethylene. FDDMA = Freeze Dried Dura Mater Allograft. Conn. Graft = Connective Tissue Graft. t N = Mean (340) ± S.D. (

302); $ N = Mean (325) ± S.D. (316);

N = Mean (186) ± S.D. (177). * Mandibular and maxillary molars.

volved sites would represent a considerable progress

in periodontics.

Mandibular

degree

II furcations

Pontoriero et al. (1988) reported a controlled random-

ized clinical trial in which significantly greater

amounts of horizontal clinical attachment (H-CAL)

gain (3.8 ± 1.2 mm) were obtained in 21 mandibular

degree II furcations treated with e-PTFE membranes

as compared to that in a control group treated with

open flap debridement alone (H-CAL gains of 2.0 ± 1.2

mm). Complete closure of the furcation was observed

in 67% of the test sites and in only 10% of the control

sites. Other studies, however, have failed to confirm

these promising results to the same extent (Becker et

al. 1988, Lekovic et al. 1989, Caffesse et al. 1990).

Analysis of a series of studies published between 1988

and 1996 demonstrates a great variability in the clini-

cal outcomes (Figs. 28-36 and 28-37). Table 28-3

summarizes the outcomes of 21 clinical trials in

which a total of 423 mandibular degree II furcations

were

treated with different types of non-bioabsorbable

and

bioabsorbable barrier membranes. The weighted

mean of the reported results shows a H-CAL gain of

3 ± 1.4 mm with a 95% confidence interval ranging

from 2.0 to 2.5 mm in defects with a baseline horizon-

tal probing depth of 5.4 ± 1.3 mm. The reported num-

ber of complete furcation closures after GTR range

from 0 to 67%. In three studies none of the treated

furcations were closed (Becker et al. 1988, Yukna 1992,

686 • CHAPTER 28

Fig. 28-36. (a) Right mandibular first molar presenting with a degree II furcation involvement. (b) Full thickness

buccal flaps have been raised, the defect debrided and the root carefully planed. (c) A non-bioabsorbable barrier

membrane has been placed to cover the defect. (d) After membrane removal, newly formed tissue appears to fill the

furcation completely (e) The regenerated tissue is covered with the flap. (f) Clinical appearance and surgery en-

try (

g) after 1 year shows that the degree II furcation is almost completely resolved.

Poison et al. 1995b), in seven studies fewer than 50%

were closed (Schallhorn & McClain 1988, Blumenthal

1993, Bouchard et al. 1993, Parashis & Mitsis 1993,

Laurell et al. 1994, Mellonig et al. 1994, Hugoson et al.

1995), and in only one study were more than 50% of

the treated furcations completely resolved (Pontoriero

et al. 1988).

A subset analysis of the studies reported in Table

28-3 indicated that furcations treated with non-bioab

sorbable barrier membranes (287) showed a gain in

horizontal clinical attachment of 1.8 ± 1.4 mm (95% CI

1.5-2.1 mm) as compared with 2.3 ± 1.2 mm H-CAL

gain (95% CI 2-2.6 mm) in 174 defects treated with

bioabsorbable barrier membranes. Five controlled

clinical trials compared treatment with non-resor-

bable e-PTFE membranes and treatment with differ-

ent types of bioabsorbable membranes (Table 28-4). In

particular, one investigation reported significantly

greater H-CAL gain in the non-bioabsorbable group

(

Bouchard et al. 1993), while another one (Hugoson et

al. 1995) showed a significantly greater H-CAL gain in

the bioabsorbable group. The remaining three inves-

tigations failed to detect any significant differences

between the outcomes of treatment with bioabsor-

bable or non-bioabsorbable membranes. Generally

the results indicate that the predictability of GTR in

the treatment of mandibular degree II furcations is

questionable, if the treatment objective is the complete

resolution of the furcation involvement.

Significant gain in vertical attachment level (V-

CAL) and reduction in pocket depth (PPD) was also

reported by several investigators following treatment

of mandibular degree II furcation defects (Pontoriero

et al. 1988, Lekovic et al. 1989, 1990, Blumenthal 1993,

Machtei et al. 1993, 1994, Black et al. 1994, Laurell et

al. 1994, Mellonig et al. 1994, Wang et al. 1994, Hu-

goson et al. 1995, Poison et al. 1995b). The reported

mean values ranged from 0.1 mm to 3.5 mm for V-CAL

gain and from 1 mm to 4 mm for PPD reduction.

The effect of using barrier membranes for the treat

ment of mandibular degree II furcations was investi-

gated in six controlled randomized clinical trials in

which GTR procedures were directly compared to flap

surgery (Table 28-5). Sixty-six furcations treated with

flap surgery and 87 treated with GTR were included.

Three of the four studies reporting H-CAL gains con-

cluded that GTR resulted in statistically significantly

greater horizontal attachment level gains than flap

surgery (Pontoriero et al. 1988, Van Swol et al. 1993,

Wang et al. 1994). The weighted mean of the results

reported in Table 28-5 indicated that the H-CAL in

furcations treated with GTR was 2.5 ± 1 mm (95% CI

REGENERATIVE PERIODONTAL THERAPY . 687

Fig. 28-37. (a) Left mandibular first molar presenting with a deep degree II furcation involvement. (b) Horizontal

loss

of tooth support of 7 mm was probed. (c) An e-PTFE barrier membrane has been trimmed and sutured to cover

the

furcation. (d) At membrane removal after 5 weeks, newly formed tissue fills the furcation completely. (e) At 1

year,

a 3 mm gain of tooth support was measured, but a residual 4 mm degree II furcation involvement was still

present.

Table 28-4. Controlled clinical trials comparing clinical outcomes of GTR procedures with e-PTFE non- bioab-

sorbable barrier membranes with different types of bioabsorbable barrier membranes in mandibular degree

furcations

Authors

Design

Treatment (GTR

C/GTR T)

N C/T

Defect Depth (mm)

H-CAL Gain (mm) H-OPAL Gain (mm)

GTR C GTR T GTR C GTR T GTR C GTR T

Yukna 1992 Intraindividual

(e-PTFE/FDDMA)

11/11

3.0±? 4.0±?

NA NA

1.0±? 2.0±?

Blumenthal 1993

Intraindividual

(e-PTFE/Collagen)

12/12

4.4 ± 0.9 4.5 ± 0.9 1.8 ± 1 2.5 ± 0.8 1.7 ± 0.5 2.5 ± 0.7

Bouchard et al. 1993

Intraindividual

(e-PTFE/Conn. Graft)

12/12

NA NA

2.8 ± 1.3*

1.5 ± 2 2.2 ± 1.4 1.5 ± 1.1

Black et al. 1994

Intraindividual

(e-PTFE/Collagen)

13/13

4.3 ± 2 4.4 ± 1.5 0.8 ± 2.2 1.5 ± 2

NA NA

Hugoson et al. 1995

Intraindividual

(e-PTFE/Polytetra-

fluoroethylene)

38/38

5.9 ± 1.3 5.6 ± 1.4

1.4 ± 2.2* 2.2 ± 2.0*

NA NA

Weighted Mean

86/86

4.9±1.4§

5±1.3§

1.6±1.9#

2±1.7# 1.3±1#

1.4±0.9#

GTR C = Guided Tissue Regeneration Control Treatment. GTR T = Guided Tissue Regeneration Test Treatment.

N Cif = Number of defects in the Control (C) and in the Test (T) treatment arm.

H-CAL = Horizontal Clinical Attachment. H-OPAL = Horizontal Open Probing Attachment. NA = data not available.

e-PTFE = expanded Polytetrafluoroethylene. FDDMA = Freeze Dried Dura Mater Allograft. Conn. Graft = Connective Tissue Graft.

= Difference between treatments statistically significant. § N = Mean (74) ± S.D. (63); * N = Mean (75) ± S.D. (75); # N = Mean (35) ± S.D. (24).

2.1-2.9 mm) while the flap surgery resulted in a mean

H-CAL gain of 1.3 ± 1 mm (95% CI.0.8-1.8 mm). These

results indicate an added benefit from GTR in the

treatment of mandibular degree II furcations.

Maxillary degree

furcations

Results reported in three controlled studies (Metzeler

et al. 1991, Mellonig et al. 1994, Pontoriero & Lindhe

1995a) comparing GTR treatment of maxillary degree

furcations with non-bioabsorbable e-PTFE mem

branes

and with open flap debridement, indicate that

GTR

treatment of such defects is generally unpredictable.

Metzeler et al. (1991) in a study including 17

pairs of

degree II furcations measured CAL gains of

688 • CHAPTER 28

Table 28-5. Controlled clinical trials comparing clinical outcomes of GTR procedures with access flap proce

dures in mandibular degree II furcations

Authors

Design

(GTR Treatment)

N C/T

Defect Depth (mm)

H-CAL Gain (mm) H-OPAL Gain (mm)

Access

Flap

GTR

Access

Flap

GTR

Access

Flap

GTR

Pontoriero et al. 1988

Intraindividual (e-PTFE)

21/21

4.0 ± 0.8

4.4

1.2

2.0 ± 1.2* 3.8 ± 1.2*

NA NA

Lekovic et al. 1989

Intraindividual (e-PTFE)

6/6

NA NA NA

-0.1 ± 0.3

0.2 ± 0.5

Caffesse et al. 1990

Parallel (e-PTFE)

6/9

5.3 ± ?

4.8

0.3 ± ? 0.8 ± ?

NA NA

Van Swol et al. 1993

Parallel (Collagen)

10/28

5.7 ± 2.5

5.1

0.7 ± 1.2* 2.3 ± 1*

0.8 ± ? 1.7 ± ?

Mellonig et al. 1994

Intraindividual (e-PTFE)

6/6

7.5 ± 2.3

NA NA

1.1 ± 1.3* 4.5 ± 1.6*

Wang et al. 1994

Intraindividual

(Collagen)

12/12

5.6 ± 2.7

• 1

2.7

1.1 ± 0.6* 2.0 ± 0.4*

1.5 ± ? 2.5 ± ?

Weighted Mean

66/87

5.4±1.8§5.5±1.5$

1.3±1^

2.5±1#

1±1°

2.3±1.2t

N C/T = Number of defects in the Control (C) and in the Test (T) treatment arm.

H-CAL = Horizontal Clinical Attachment. H-OPAL = Horizontal Open Probing Attachment. NA = data not available.

e-PTFE = expanded Polytetrafluorethylene. * = Difference between treatments statistically significant.

§ N = Mean (60) ± S . D. (54); $ N = Mean (81) ± S. D. (72);

N = Mean (49) ± S.D. (43); # N = Mean (70) ± S. D. (61); N = Mean (39) ± S.D. (17); N

= Mean (57) ± S.D. (17).

1.0 ± 0.9 mm in the GTR treated sites versus 0.2 ± 0.6

mm in the control sites. Following re-entry, horizontal

probing attachment gains (H-OPAL) of 0.9 ± 0.4 mm

and 0.3 ± 0.6 mm were detected in the GTR and flap

treated furcations, respectively. No differences were

found and none of the furcations of the two groups

were completely resolved. Similarly, Mellonig et al.

(

1994) treated eight pairs of maxillary degree II furca-

tions which resulted in H-OPAL gains of 1.0 mm (GTR

sites) and 0.3 mm (flap treated sites). No differences

were found and none of the treated furcations were

completely closed. Pontoriero & Lindhe (1995a), on

the other hand, in a study on 28 maxillary degree II

furcations found a significant gain in CAL (1.5 mm)

and horizontal bone (1.1 mm) in buccal degree II

furcations.

Although these three investigations show a slight

clinical improvement following treatment of degree II

maxillary furcations with GTR, the results are gener-

ally inconsistent.

Degree III fir reations

Four investigations on the treatment of mandibular

degree III furcations (Becker et al. 1988, Pontoriero et

al. 1989, Cortellini et al. 1990, Pontoriero & Lindhe

1995b) indicate that the treatment of such defects with

GTR is unpredictable. A controlled study of Pontori-

ero et al. (1989) showed that only 8 out of 21 "through

and through" mandibular furcations treated with

non-bioabsorbable barrier membranes healed with

complete closure of the defect. Another ten defects

were partially filled, and three remained open. In the

control group, treated with open flap debridement,10

were partially filled and 11 remained open. Similar

results were reported by Cortellini et al. (1990) who,

in a case cohort of 15 degree III mandibular furcations,

found that 33% of the defects had healed completely,

33% were partially closed, and 33% were still through

and through following treatment. Becker et al (1988)

did not observe complete closure of any of 11 treated

degree III mandibular furcations. Similarly, in a con-

trolled clinical trial of Pontoriero & Lindhe (1995b) on

11 pairs of maxillary degree III furcations randomly

assigned to GTR or flap surgery, none of the furcation

defects were closed.

Factors affecting the clinical outcomes of GTR in

furcations

The studies considered above have demonstrated that

treatment of maxillary degree II furcations and maxil-

lary and mandibular degree III furcation involve-

ments with GTR is unpredictable, while clinical im-

provements can be expected treating mandibular de-

gree II furcations. The great variability in clinical out-

comes, following treatment of mandibular degree II

furcations with GTR, is probably related to the factors

discussed relative to intrabony defects.

Regarding defect factors, it was shown that first and

second mandibular molars and buccal and lingual

furcations respond equally well to GTR treatment

(

Pontoriero et al. 1988, Machtei et al. 1994). It was also

demonstrated that the preoperative horizontal pocket

depth is directly correlated with the magnitude of

attachment gain and bone formation in the furcation

area (Machtei et al. 1993, 1994). The deeper the base

line horizontal pocket, the greater was the H-CAL and

bone gain. The anatomy of the furcations in terms of

height, width, depth and volume, however, did not

correlate with the clinical outcome (Machtei et al.

1994). Anderegg et al. (1995) demonstrated that sites

with a gingival thickness of > 1 mm exhibited less

gingival recession post surgery than sites with a gin-

gival thickness of < 1 mm. The authors concluded that

the thickness of the gingival tissue covering a barrier

REGENERATIVE PERIODONTAL THERAPY •

689

Table 28-6. Summary of controlled clinical trials evaluating the combined effects of decalcified freeze-dried

bone allografts (DFDBA) and barrier membranes in deep intrabony defects

Authors

Design

(GTR Treatment)

Gains in CAL

(mm)

Significance

Residual PD

(mm)

Significance

GTR GTR

DFDBA DFDBA

Chen et al. 1995

Intraindividual

(Collagen)

2.0 ± 0.4 2.3 ± 0.5

P > 0.05,NS

4.2 ± 0.4 4.2 ± 0.5

P > 0.05,NS

Mellado et al. 1995

Intraindividual

(e-PTFE)

2.0 ± 0.9 2.0 ± 1.4

P = 0.86,NS

NA NA NA

Gouldin et al. 1996

Intraindividual

(e-PTFE)

2.2 ± 1.4 2.4 ± 1.6 NS 3.7 ± 1.6 3.7 ± 1.8 NS

Weighted Mean

45 2.1

1.1 2.3

1.4 3.8

1.3

3.8

1.5

= Defects per treatment arm. CAL = Clinical Attachment Level. PD = Pocket Depth. e-PTFE = expanded Polytetrafluoroethylene.

DFDBA = Decalcified Freeze Dried Bone Allograft.

NS = not significant. NA = Data not available. § N = Mean (34) ± S.D. (34).

material must be considered if post-treatment reces-

sion is to be minimized or avoided.

Based on present evidence, it seems that mandibu

lar degree II furcations in the first or second molars,

either buccal or lingual, with deep pockets at baseline

and a gingival thickness of > 1 mm, may benefit from

GTR treatment.

GTR combined with other regenerative procedures

Compromised results after GTR may be obtained in

cases where the membrane collapses/falls (partially

or totally) into the defect and/or towards the root

surface, thereby reducing the space available for inva

sion of new tissue capable of forming periodontal

ligament and bone in particular. Reduced amounts of

regenerated bone due to membrane collapse were

noticed in early studies of GTR. In the study of

Gottlow et al. (1984), it was observed that collapse of

the membrane towards the root surface resulted in

new cementum formation on the entire exposed root

surfaces, whereas bone regeneration was minimal.

Although the authors reported that the degree of coro

nal regrowth of bone was unrelated to the amount of

new cementum formation, they did not comment on

what effect membrane collapse might have had. Re-

cent experimental studies, however, recognized the

negative effect of membrane collapse on periodontal

regeneration generally and on bone formation in par-

ticular (Caton et al. 1992, Haney et al. 1993, Sigurdsson

et al. 1994, Sallum et al. 1998). Haney et al. (1993)

observed a highly significant correlation between the

space provided by the membrane and the amount of

regenerated alveolar bone using a supra-alveolar de-

fect model in dogs. This finding corroborates that of

Cortellini et al. (1995c) who reported that clinical ap-

plication of self-supporting (reinforced with titanium)

e-PTFE membranes, which could be positioned more

coronally than ordinary e-PTFE membranes, yielded

statistically significantly more PAL-gain in intrabony

defects. A particular risk for membrane collapse exists

in cases where the configuration of the defect is inca-

pable of supporting/preserving the membrane at the

position where it was originally placed.

As already discussed, membrane materials must

possess certain characteristics in order to be efficient.

Among those it is important that the membrane is

capable of keeping its shape and integral features,

thereby maintaining the space created adjacent to the

root surface. The e-PTFE membranes reinforced with

titanium are the closest in meeting these requirements

but they have the disadvantage that they are non-re-

sorbable. At present there are no resorbable mem-

branes available that fulfill this requirement suffi-

ciently, which means that the placement of a resor-

bable membrane on, for instance, a wide one-wall

defect involves the risk of membrane collapse. The

collapse may be prevented by means of implantation

of a biomaterial into the defect to support the mem-

brane so that it preserves its original position. How-

ever, the biomaterial to be used for this purpose must

not interfere with the process of periodontal regenera

tion and ideally it may also promote bone regenera-

tion.

As previously described, periodontal regeneration

has been attempted with a variety of grafting materi-

als, among which demineralized freeze-dried bone

allografts (DFDBA) apparently facilitated regenera-

tion in humans (Ouhayoun 1996). Schallhorn and

McClain (1988) reported on improved clinical results

in intrabony defects and degree II furcations, follow-

ing a combination therapy including barrier mem-

branes plus DFDBA and citric acid root conditioning.

In three controlled clinical trials, the treatment of a

total of 45 pairs of intrabony defects with DFDBA

grafting and GTR were compared to GTR alone (Table

28-6). The weighted mean of the results of the reported

investigations showed similar gain in CAL in the GTR

group (2.1 ± 1.1 mm, 95% Cl 1.6-2.6 mm) and in the

GTR plus DFDBA group (2.3 ± 1.4 mm, 95% Cl 1.7-2.9

mm). The differences between the two treatments did

690 • CHAPTER 28

Table

28-7.

Controlled clinical trials comparing clinical outcomes of GTR procedures with e-PTFE non- bioab

sorbable barrier membranes with or without the adjunctive use of grafts in mandibular degree II furcations

Authors

Design

Treatment

(GTR C/GTR T)

N C/T

Defect Depth (mm)

H-OPAL Gain (mm)

GTR C

GTR T

GTR C

GTR T

Lekovic et al. 1990

Intraindividual

(e-PTFE/e-PTFE + HA)

15/15 4.2 ± 0.2 4.3 ± 0.2 0.1 ± 0.1 1.6 ± 0.2

Anderegg et al. 1991

Intraindividual

(e-PTFE/e-PTFE + DFDBA)

15/15 4.2 ± 2.2 5.3 ± 2.6

1.0 ± 0.8* 2.4 ± 1.5*

Wallace et al. 1994

Parallel

(e-PTFE/e-PTFE + DFDBA)

7/10

6.0 ± ? 6.5 ± ? 2.3 ± ? 2.4 ± ?

Weighted Mean

37/40

4.5

1.2 §

5.2

1.4 t

0.9

0.5 § 2.1

0.9 #

GTR C = Guided Tissue Regeneration Control Treatment. GTR T = Guided Tissue Regeneration Test Treatment. N C/T = Number of defects in the

Control

e-PTFE = expanded Polytetrafluoroethylene. I-IA = Hydroxylapatite. DFDBA = Decalcified Freeze Dried Bone Allograft.

= Difference between treatments statistically significant. N = Mean (37) ± S.D. (30); t N = Mean (40) ± S.D. (30)

# N = Mean (35) ± S. D. (24).

not reach statistical significance, thus indicating no

added effect of combining DFDBA with barrier mate-

rials in the treatment of intrabony defects. Guillemin

et al.

(1993),

on the other hand, compared the effect of

DFDBA alone with a combination of barrier materials

and DFDBA in 15 pairs of intrabony defects. Both

treatments resulted in significant amounts of CAL

gains and bone fill at

months, but no difference was

found between the treatments.

In three studies on mandibular degree II furcations,

GTR treatment alone was compared with GTR treat-

ment combined with hydroxylapatite or DFDBA (Ta-

ble

28-7).

In one of these investigations, a statistically

significant improvement was found in terms of hori-

zontal open probing attachment levels (H-OPAL) in

the group of furcations treated with the combination

therapy (Anderegg et al. 1991).

In another of these

three studies the difference between the two treat-

ments was not statistically significant, but the combi-

nation therapy resulted in a greater extent of furcation

fill (Lekovic et al.

1990).

In the third investigation

(

Wallace et al.

1994),

the two treatments were equiva-

lent in terms of H-OPAL gains. The weighted mean of

the cited studies showed greater H-OPAL gains in the

cases treated with the combination therapy

(2.1 ± 0.9

mm,

95%

1.6-2.6

mm) when compared to GTR

treatment alone

(0.9 ± 0.5

mm,

95%

0.6-1.1

mm),

indicating a possible added benefit from the use of

grafting materials in combination with non-bioabsor-

bable barrier membranes for the treatment of

mandibular degree II furcations.

Promising clinical results with a PAL-gain of

1.0-5.5

mm were obtained in human case reports, in which

the GTR technique was combined with grafting of

Bio-Oss

for the treatment of intrabony periodontal

defects (Lundgren & Slotte

1999,

Mellonig

2000,

Pao-

lantonio et al.

2001).

The combined Bio-Os

and GTR

treatment resulted in greater PPD reduction, PAL gain

and defect fill than the mere implantation of Bio-Os

in case series (Camelo et al.

1998,

Hutchens

1999)

and

than flap surgery alone in a split-mouth study

(

Camargo et al. 2000).

In a recent randomized controlled clinical study

including

60 patients (Stavropoulos et al.

2002),

Bio-

Oss

alone or impregnated with gentamicin was used

as an adjunct to GTR in the treatment of one-wall or

two-wall intrabony defects, and the outcomes were

compared to those obtained following GTR alone or

flap surgery. Treatment with a membrane alone (Fig.

28-38)

resulted in a mean PAL gain of

2.9

mm, while it

was

3.8

and

2.5

mm, respectively, when Bio-Oss

grafts with or without gentamicin were placed in the

defects prior to membrane coverage (Fig. 28-39).

The

control defects treated with flap surgery demon-

strated a gain of PAL of only

1.5

mm. The clinical

improvements in defects treated with GTR alone or in

combination with Bio-Oss

grafting were signifi-

cantly better than those obtained with flap surgery,

whereas the differences between the groups treated

with membranes were not statistically significant.

In a controlled study (Pietruska

2001),

similar clini-

cal improvements were obtained when Bio-Oss

com-

bined with GTR was compared with biomodification

of the root surface with enamel matrix protein (Em-

dogain

Camelo et al.

(1998)

and Mellonig

(2000)

presented

histologic data indicating that the use of Bio-Oss

under a membrane may result in partial regeneration

of the periodontal apparatus, but in all the cases, most

of the defect was still occupied by deproteinized bone

particles. Bone was not observed near the root, and the

connective tissue fibers of the "new" periodontal liga-

ment were mostly oriented parallel to the root surface.

These results corroborate findings reported by Pao-

lantonio et al.

(2001),

who observed only limited bone

formation in the vicinity of the pre-existing bone in a

biopsy, taken from a site treated

8 months earlier with

Bio-Os

and a collagen membrane. Most of the space

in the defect was occupied by Bio-Oss ® particles em-

bedded in connective tissue. However, in a case report,

REGENERATIVE PERIODONTAL THERAPY • 691

Fig. 28-38. Right lateral maxillary incisor with an 8 mm deep pocket associated with an intrabony defect on the dis

tal aspect (a), as seen on the radiograph (b). Full thickness buccal and palatal flaps have been raised and the

defect

has been debrided (c). A bioabsorbable membrane has been adopted over the defect (d). The level of the

interdental

gingiva is maintained after 1 year (e) and the intrabony defect (f) is resolved.

where intrabony defects were treated with Bio-Oss

combined with intraoral autogenous bone and GTR,

new attachment formation had occurred consistently,

but a major portion of the regenerated osseous tissue

consisted of deproteinized bone particles (Camelo et

al. 2001). The effect of combining citric acid root bio-

modification with GTR treatment was evaluated in

two randomized controlled clinical trials in intrabony

defects. The first investigation (Handelsman et al.

1991) demonstrated significant amounts of CAL gains

in both the test (e-PTFE membranes and citric acid;

CAL gain 3.5 ± 1.6 mm) and control sites (e-PTFE

membranes alone; CAL gain 4.0 ± 1.4 mm). Less favor

able results following these two treatment modalities

were reported by Kersten et al. (1992) who found CAL

gains of 1.0 ± 1.1 mm in the test group, and CAL gains

of 0.7 ± 1.5 mm in the control group. Both studies,

however, failed to demonstrate any added effect of the

use of citric acid in combination with non-bioabsor-

bable barrier membranes.

Root surface biomodification with tetracycline

alone and in combination with GTR was evaluated in

two controlled studies on degree II furcations (

Machtei et al. 1993, Parashis & Mitsis 1993). Both

investigations failed to show significant differences

between sites treated with non-bioabsorbable barrier

membranes alone or in combination with tetracycline

root surface biomodification. Similarly, the use of

other surface active chemicals like EDTA also failed to

692 • CHAPTER 28

Fig. 28-39. Left mandibular canine with an 8 mm deep pocket (a) associated with an intrabony defect on its mesial

aspect (b). The defect is debrided after flap elevation (c) and Bio-Os

particles are placed in the defect (d) prior to

placement of a bioabsorbable membrane. After 1 year (e) no gingival recession has occurred and the intrabony de

fect is almost resolved (f).

provide a significant added effect to GTR treatment in

humans (Lindhe & Cortellini

1996).

Evaluation of GTR

Several reports, case series and controlled clinical tri-

als have demonstrated successful results following

GTR treatment of a variety of periodontal defects (for

review see Cortellini & Tonetti 2000a, Sanz & Giovan

noli

2000,

Trombelli

1999).

These results have been

confirmed in animal experiments involving GTR

treatment of intrabony defects (Caffesse et al.

1988,

Caton et al.

1992),

furcation defects (Niedermann et al.

1989,

Caffesse et al.

1990,

Araujo et al.

1996)

and

recession defects (Gottlow et al.

1990,

Cortellini et al.

1991).

The effect of placing non-bioabsorbable or

bioabsorbable membranes on degree II and III furca-

tion defects as compared to that in control defects

treated without membranes was evaluated in dogs

(

Claffey et al.

1989,

Caffesse et al.

1990,

Pontoriero et

al.

1992,

Lindhe et al.

1995).

In both degree II and III

furcation defects, GTR treatment resulted in signifi-

cantly more gain of connective tissue attachment and

regrowth of alveolar bone than control therapy.

In the studies of Pontoriero et al.

(1992)

and Lindhe

et al.

(1995),

complete closure of through and through

furcation defects with the formation of a periodontal

ligament and regrowth of the alveolar bone was

achieved (Fig.

28-40).

It was suggested that the size of

the furcation defects as well as the shape of the sur-

rounding alveolar bone were determining for the out-

REGENERATIVE PERIODONTAL THERAPY •

Fig. 28-40. (a) Photomicro-

graph of a degree III furcation

in a dog 5 months after GTR

treatment in combination with

coronally displaced flaps. The

defect has become filled with

new bone (NB), and a peri-

odontal ligament (p) and new

cementum (NC) can be seen

along the entire surface of the

furcation defect. The arrows in

dicate the apical level of the

original defect. (b) A high mag-

nification of the cementum

formed on the root surface in a

healed bifurcation defect. Note

the cellular nature of the new

cementum (NC).

come of GTR treatment. The treatment failures were

consistently associated with recession of the covering

tissue flaps, which resulted in exposure of the furca-

tion defect. Provided this was prevented, even com-

paratively large furcation defects were successfully

regenerated by GTR therapy. The results also demon-

strated that bioabsorbable membranes provided a bar

rier which was equally as effective as that of non-

bioabsorbable Teflon membranes.

Histologic evidence in humans that regeneration of

the attachment apparatus on previously periodontitis

affected roots can be attained by means of the GTR

technique was provided in several reports (Nyman et

al. 1982, Gottlow et al. 1986, Becker et al. 1987, Stahl et

al. 1990a, Stahl & Froum 1991b, Cortellini et al. 1993a,

Parodi et al. 1997, Vincenzi et al. 1998, Sculean et al.

1999a). New cementum, periodontal ligament and

variable amounts of new bone formation were ob-

served in these studies, also above notches placed in

the root surface at the apical extent of calculus. Thus,

the GTR technique is fulfilling the criteria set by the

American Academy of Periodontology at the World

Workshop in Periodontics in 1996, and is also based

on a biologic concept that, according to the current

knowledge about periodontal wound healing, can ex-

plain why this method leads to periodontal regenera-

tion.

Long-term evaluation

A pertinent question with respect to regenerative

treatment is whether the achieved attachment gain

can be maintained over an extended period of time. In

a study in monkeys (Kostopoulos & Karring 1994),

periodontal breakdown was produced by the place-

ment and retention of orthodontic elastics on experi-

mental teeth until 50% bone loss was recorded. The

experimental teeth were endodontically treated and

subjected to a flap operation and all granulation

tissue

was removed. The crowns of the teeth were resected

at the level of the cemento-enamel junction and a

barrier membrane was placed to cover the roots before

they were submerged. Following 4 weeks of healing,

the membranes were removed. At the same time the

contralateral teeth which served as controls were en-

dodontically treated and subjected to a sham opera-

tion during which the crowns were resected at the

level of the cemento-enamel junction. Artificial com-

posite crowns were then placed on both the experi-

mental and the control roots. The sites were allowed

to heal for 3 months during which period careful

plaque control was performed. At the end of this

period cotton-floss ligatures were placed on both ex-

perimental and control teeth to induce periodontal

tissue breakdown. After another 6 months, the ani-

mals were sacrificed. With respect to attachment level,

bone level, pocket depth and gingival recession, simi-

lar results were recorded in histologic specimens of

experimental (Fig. 28-41) and control (Fig. 28-42) teeth.

This indicates that the new connective tissue attach-

ment formed with GTR is not more susceptible to

periodontitis than the naturally existing periodon-

tium.

In a long-term follow-up study, Gottlow et al. (1992)

assessed the stability of new attachment gained

through GTR procedures. Eighty sites in 39 patients,

which 6 months after surgery exhibited a gain of

clinical attachment of 2 mm (2-7 mm), were moni-

tored during additional periods of 1 to 5 years. Of the

80 sites, 65 were monitored for 2 years, 40 for 3 years,

17 for 4 years and 9 sites for 5 years. The results of this

study and those of other trials indicate that attachment

gain obtained following GTR treatment can be main-

tained on a long-term basis (Becker & Becker 1993,

McClain & Schallhorn 1993).

An investigation on intrabony defects demon-

strated that the stability of sites treated with GTR was

694 • CHAPTER

Fig. 28-41. Microphotograph of test specimen

with a reformed connective tissue attachment.

After 6 months of ligature induced periodonti

tis, loss of attachment has occurred from the

coronal cut root surface to the level indicated

by the arrow.

Fig. 28-42. Microphotograph of control speci-

men with a naturally existing periodontium.

After 6 months of ligature induced periodonti

tis, loss of attachment has occurred from the

coronal cut tooth surface to the level indicated

by the arrow.

dependent on participation of the patients into a recall

program, and on the absence of bacterial plaque,

bleeding on probing and re-infection of the treated

sites with periodontal pathogens (Cortellini et al.

1994). In addition, the susceptibility to disease recur-

rence at sites treated with non-bioabsorbable barrier

membranes was compared to that at sites treated with

root planing in a controlled clinical trial (Cortellini et

al. 1996a). The results indicated that patient factors

such as compliance with oral hygiene, smoking hab-

its, and susceptibility to disease progression rather

than the employed treatment modality, were the major

determinants of stability of the treated sites.

A few studies have evaluated the long-term prog-

nosis for furcation defects treated with regenerative

therapy. Sixteen mandibular degree II furcation de-

fects, following coronal flap positioning and citric acid

root biomodification with and without implantation

demineralized freeze-dried bone allografts

(DFDBA),

were determined as completely resolved

with bone fill

assessed by re-entry surgery. They were

re-evaluated

after 4-5 years (Haney et al. 1997), when

12 of the 16

sites exhibited recurrent degree II furca

tions and all

16 sites demonstrated probable buccal

furcation

defects. The investigators concluded that

these

findings question the long-term stability of bone

regeneration in furcations following coronally ad-

vanced flap procedures.

The long-term stability of mandibular furcation de-

fects regenerated following GTR alone or in combina-

tion with root surface biomodification with citric acid

and bone grafting, was also evaluated by McClain &

Schallhorn (1993). Out of the 57% of the furcation

defects which were assessed as completely filled at 6

and 12 months, only 29% were completely filled after

4 to 6 years. However, 74% of the furcations treated

with GTR in combination with the placement of

DFDBA were completely filled at both the short and

long-term evaluation, suggesting that the results ob-

tained with the combined procedure were more stable

over time. Long-term results of GTR treatment of

mandibular degree II furcations with e-PTFE mem-

branes were also reported by Machtei et al. (1996). The

teeth were followed up to 4 years and compared with

non-furcated molars. Improvements assessed in ver-

tical (V-CAL) and horizontal (H-CAL) clinical attach-

ment levels after treatment were maintained also after

4 years, suggesting that changes obtained in degree II

furcation defects by GTR are stable. Only 9% of the

treated defects were unstable, which was similar to

that observed for non-furcated molars. Good oral hy-

giene as reflected in low plaque scores and elimination

of periodontal pathogens were closely related to the

long-term stability. On the basis of these results, it was

concluded that furcation defects treated with mem-

brane barriers can be maintained in health for at least

4 years, provided good oral hygiene and frequent

recall visits are established.

CONCLUSIONS

GTR represents the most well-documented regenera-

tive procedure for obtaining periodontal regeneration

in intrabony defects and in degree II furcations. GTR

has demonstrated significant clinical improvements

beyond that achieved with only debridement in such

defects. Regarding degree II maxillary furcations, the

results following GTR treatment are inconsistent, and

the treatment of degree III furcation defects is unpre-

dictable. An added benefit may be obtained by the use

of grafting materials in combination with GTR in some

situations.