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Multivariate analysis of factors influencing outcomes of regenerative
therapy: A retrospective study
Shyuan-Yow Chen, DDS,a Hom-Lay Wang, DDS, MSD,b Gerald N. Glickman, DDS,
MS,c Yu Shyr, PhD,d and R. Lamont MacNeil, DDS, MdentScea

Department of Dentistry, Cathay General Hospital, Taipei, Taiwan, bDepartment of
Periodontics/Prevention/Geriatrics, School of Dentistry, University of Michigan,
Ann Arbor, MI, cDepartment of Endodontics, School of Dentistry, University ofWashington, Seattle, WA, dDivision of Biostatistics, Department of Preventive
Medicine, School of Medicine, Vanderbilt University, Nashville, TN ， ande
Department of Periodontology, School of Dental Medicine, University ofConnecticut Health Center, Farmington, CT, USA
Purpose: The purpose of this cross-sectional retrospective study was to determine the association between adefined set of clinical factors and treatment outcomes following regenerative therapy in a university-based
specialty training program in Periodontics.
Materials and Methods: Data were collected from 131 sites in 82 patients who received various forms ofregenerative therapy including barrier and/or bone grafting procedures. Clinical endpoints used in theanalyses were reductions in probing pocket depth (PD) and radiographically detectable bone loss (RBL).
Multivariate and univariate statistical analyses were used to determine the association between six
patient-related factors and four outcome variables. The factors studied were: (1) age, (2) gender, (3) smoking,(4) use of bone allografts, barrier, or combined therapies, (5) position of margins of adjacent restorations, and(6) endodontic status of treated teeth. The four outcome variables were reduction in: (1) buccal PD, (2)lingual PD, (3) average PD, and (4) RBL.
Results: Results indicated an overall improvement in clinical health following therapy. A statisticallysignificant reduction (p<0.01) was found for buccal PD (-1.53 ± 0.22 mm), lingual PD (-1.28 ± 0.22 mm) andaverage PD (-1.41 ± 0.20) while a 0.72 ± 0.23 mm reduction in RBL (p<0.01) was also noted. Multivariate
analysis indicated that only two factors, increased age and smoking, had statistically significant negative
effects on treatment outcomes. Univariate analysis indicated a statistically significant negative influence for1) increasing patient age on buccal PD, lingual PD, and RBL reduction and 2) smoking on RBL reduction.
Comparable clinical outcomes were found whether absorbable or non-absorbable barrier materials wereused.
Conclusion: In summary, the findings suggest that increased age and smoking appear to be factors associatedwith poor or sub-optimal regenerative outcomes. (Int Chin J Dent 2002; 2: 48-59.)

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CHEN ET AL

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Although regenerative procedures, such as guided tissue regeneration (GTR) have become an accepted
component of the periodontal surgical armamentarium, treatment outcomes remain largely unpredictable asevidenced by clinical studies which report varying success rates.1-7 For example, Cortellini et al., using
ePTFE (expanded-polytetrafluoroethylene) barrier material to treat 40 human intrabony defects, reported again of 2 mm or more probing attachment level in almost 90% of the treated sites.3 Other researchers haveobserved less favorable results6,7 including Selvig et al. who found comparable outcomes following GTR
therapy surgery and conventional (non-GTR) flap debridement surgery.7 These apparent inconsistencies in
GTR treatment outcomes suggest that it is important to study factors (i.e. risk factors), which may adversely
influence or limit treatment success.
Over the last decade, there has been an increasing interest in the identification of conditions or factors
which may influence the initiation, progression, and/or treatment of periodontal diseases. Recent studies
have reported age, gender, race, socio-economic status, smoking and general health states as risk indicators
for periodontal disease.8-11 Similar studies have also been conducted to define factors/conditions that may
compromise or limit GTR therapy.

Deep initial pockets, good oral hygiene, absence of gingival

inflammation, absence of Actinobacillus actinomycetemcomitans infection, as well as the presence ofconnective tissue cells on the inner surface of the retrieved membrane have been shown to be associated withenhanced periodontal regeneration.12 Machtei et al. suggested that good oral hygiene and frequent recall
visits were essential for long-term stability of GTR outcomes.13 Weigel et al. also concluded that a low
incidence of gingival inflammation was a requirement for GTR success14 while Tonetti et al. reported that
control of oral hygiene and residual periodontal infection were important to achieve favorable results
following both GTR and access flap surgical procedures.15 In addition, factors such as tissue gain under themembrane, radiographic width of the defect angle, full mouth bleeding score, and presence or absence of flap
coverage of the newly formed tissue have also been correlated with varying outcomes following regenerative
therapy.16 Hence, there is an emerging body of evidence that if certain operator and patient dependent
variables are recognized and controlled, GTR therapy can become a more predictable treatment form.
Our knowledge to date regarding risk factors associated with sub-optimal GTR therapy outcomes has been
derived largely from clinical studies conducted by highly trained clinicians in well-controlled research
environments. Relatively little is known regarding factors which may be operative in a private practicesetting or other less controlled treatment locations or situations. The purpose of this study was to identify
factors associated with GTR treatment outcomes in a university-based advanced specialty training programin periodontics and to compare overall therapy outcomes with those of previously published reports. This
information will be valuable since periodontal treatment in such programs, while supervised by trained
periodontists, is performed by residents with varying and limited levels of clinical training, and these results
may often differ from that of highly trained or experienced periodontists.

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MATERIALS AND METHODSPatient Population and Selection
This cross-sectional retrospective study utilized records of 713 previously treated patients from the
University of Michigan, School of Dentistry, Graduate Periodontic Clinic patient pool. A record wasconsidered eligible for analysis if the following criteria were fulfilled: (1) evidence of pre-surgicalinterproximal infrabony defects (≥3mm from the alveolar crest to the depth of defects) in periapicalradiographs, (2) treatment of identified infrabony defects during the surgical corrective phase with aregenerative

procedure

involving

eitherosseousgrafting(i.e.

decalcified

freeze-driedboneallografts-DFDBA), GTR barrier/membrane or a combination of osseous grafting/GTR membranes, (3)availability of periapical radiographs taken at least 6 months after the regenerative surgery, and (4) absence ofantibiotic use for 6 months prior to the surgical therapy. Based on these criteria, the eligible sample size was
reduced to 82 patients including 36 males and 46 females ranging in age from 25 to 82 years old, with a mean
age of 53 years. In total, 131 individual osseous defects were analyzed (i.e. 131 sites in 82 patients). The
re-evaluation period after regenerative therapy ranged from 6 to 75 months, with a mean of 31 months.
Periodontal Treatment
Although treatment regimens varied due to multiple providers and different treatment protocols, eachpatient received standard initial therapy which included oral hygiene instruction and scaling and root planing.
If periodontal surgery was indicated upon re-evaluation of initial therapy, it was performed following
contemporary regenerative surgical principles. Surgical therapy was supervised by educationally-qualified
faculty periodontists but performed by graduate students in either their first or second year of specialty
training. In general, the surgical procedure involved the elevation of a full thickness mucoperiosteal flap withintracrevicular incisions, preserving as much keratinized marginal tissue as possible. Following thoroughdefect debridement and root planing, defects were treated by one of the three aforementioned regenerativetechniques. Postsurgical protocols included daily rinsing with 0.12% chlorhexidine for the first 2 weeks andsystemic doxycycline (100 mg/day) for 7 days. Sutures were removed 7 to 10 days after surgery andnon-absorbable GTR barriers were retrieved 4 to 6 weeks after surgery. Following completion of the surgicaltherapy, patients were placed on a 3-month recall for supportive periodontal treatment.
Data Collection
All information was collected from patients' charts and radiographs. Outcome variable sets included (1)pre- and post-surgical probing depths (PD), measured in millimeters (mm) as measured with a Michigan “O”
periodontal probe as the distance from the gingival margin to the base of the periodontal sulcus/pocket (bothbuccal and lingual sides were measured at interproximal contact areas) and (2) pre- and post-surgicalradiographic bone loss (RBL), recorded in millimeters at interproximal areas on non-standardized periapicalradiographs as the distance from the cemento-enamel junction to the most apical point of the alveolar bonewithin the infrabony defect. Treatment variables sets included: (1) age, i.e. < or > 45 years (2) gender, i.e.
female or male, (3) history of smoking versus non-smoking (smoking = smokes more than one year of
duration), (4) use of DFDBA, a GTR membrane (either non-absorbable or absorbable) or combination

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INT CHIN J DENT(DFDBA + barrier) therapy; (5) presence or absence of endodontic treatment before surgery determined bypresence or absence of permanent endodontic filling materials in periapical radiographs; and (6) presence orabsence of a subgingival versus supragingival restoration margin adjacent to the osseous defect. Due toinconsistent data entry in the patients' records, it was not possible to analyze other important clinicalinformation including plaque status, tooth mobility, amount of keratinized gingiva, and gingival recession.
Statistical Analysis
Data were analyzed using the SAS version 6.10 (SAS Institute, Cary, IN, USA) statistics program. All data
were reported as means ± standard error (SE). A multivariate analysis (using restricted/residual maximum
likelihood (REML)-based repeated measures model with compound symmetry covariance structure) wasused to test the differences of assessment parameters (all risk factors were simultaneously analyzed in themodel) over time. Tests concerning the differences of monitored parameters over time (e.g. PD and RBL)
with different levels of a single risk factor (e.g. smoking vs. non-smoking) were completed using univariate
analyses. All tests of significance were two-sided and statistically significant differences were recorded
when p≤0.05.

RESULTS
Table 1 summarizes the demographic and treatment information for the study population. Records of 82
patients (56.1% females and 43.9% males) were reviewed. The 131 test sites analyzed displayed thefollowing characteristics: 76 sites (58.0%) female versus 55 sites (42.0%) male; 39 sites (29.8%) in younger
age group (< 45 years) versus 92 sites (70.2%) in older age group (≥ 45 years); 48 sites (36.6%) in
non-smokers versus 83 sites (63.4%) in smokers; 63.4% of sites received DFDBA alone, 27% received
DFDBA plus membrane while 9.9% received membrane placement alone.
Table 2 shows the mean changes in PD and RBL before and after regenerative treatment. The initial mean
PDs were 6.27 ± 0.19 mm (buccal) versus 6.26 ± 0.18 mm (lingual) while the initial mean RBL was 5.07 ±0.20 mm. Statistically significant reductions in PD and RBL were noted following regenerative treatment.
Average PD reduction was 1.41 ± 0.20 mm (p<0.01) while a reduction of 0.72 ± 0.23 mm (p<0.01) was notedin RBL.
The relationship between four treatment outcome variables (i.e. buccal PD; lingual PD; average PD; andRBL) and six pre-clinical treatment factors (i.e. age, gender, smoking, use of bone grafts and/or membrane,
endodontic status and status of adjacent restorative margins) were tested utilizing a multivariate analysis
model. Only age and smoking were found to be correlated to buccal PD and RBL (Table 3). With respect tobuccal PD, non-smokers had more buccal PD reduction (0.91 ± 0.52 mm, p = 0.08, marginal significance)and more RBL reduction (1.41 ± 0.44 mm, p<0.01) than smokers. Within the limited data set in thisinvestigation, no other significant correlations were found among test factors in the multivariate analysis(Table 3).

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Table 1. Demographic information.
Variable

Frequency (131 sites in 82 pts)

GenderFemale
Male
Age
< 45
≥ 45
SmokingNoYes
1-9 cigarettes/day
10-19 cigarettes/day> 19 cigarettes/day
unknown
Endodontic Treatment(Pre-regenerative Therapy)
No
Yes
Restorative Status(Pre-regenerative Therapy)
Without restoration
Supra-gingival margin
Sub-gingival margin
Type of Regenerative Therapy
Barrier membrane alone
Bone graft alone
Combination of barrier
and bone graftType of Barrier Membranes
AbsorbableNon-absorbable

Percent (%)

76
55

58.0
42.0

39
92

29.8
70.2

48

36.6

9
10
19
45

6.9
7.6
14.5
34.4

120
11

91.6
8.4

24
78
29

18.3
59.5
22.1

13
83

9.9
63.4

35

26.7

19
29

14.5
22.1

Table 2. Mean changes in monitored parameters.
Before GTR
therapy(mm ± S.E.)
n = 131After GTR
therapy(mm ± S.E.)
n = 131

Changes(mm ± S.E.)

P value

PD (Buccal)

6.27 ± 0.19

4.74 ± 0.17

-1.53 ± 0.22

0.0001

PD (Lingual)6.26 ± 0.18

4.98 ± 0.16

-1.28 ± 0.22

0.0001

PD (Average)---1.41 ± 0.20

0.00015.07 ± 0.20

4.35 ± 0.21

-0.72 ± 0.23

0.0025RBL††Radiographic bone loss at proximal contact points.

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Table 3. Effects of selected clinical factors on GTR outcome (Multivariate analysis).
Changes (mm) ± S.E.: Pre- and Post-regenerative therapy
PD (Buccal)
Intercept-3.11 ± 1.43 (p<0.05)
SexF
0.26 ± 0.51 (p=0.61)
M
0.00
Age
0.05 ± 0.02 (p<0.01)*
SmokingNo-0.91 ± 0.52 (p=0.08)†
Yes
0.00
Endodontic treatment
No-1.07 ± 0.75 (p=0.16)
Yes
0.00
Regenerative therapy
Graft-0.04 ± 0.65 (p=0.95)
Graft/Memb 0.53 ± 0.67 (p=0.43)
Memb
0.00
Status of restorative marginNo-0.12 ± 0.67 (p=0.86)
Supra-0.16 ± 0.50 (p=0.75)
Sub
0.00

PD (Lingual)

PD (Average)

RBL-0.40 ± 1.42 (p=0.78)-1.87 ± 1.32 (p=0.16)-1.17 ± 1.27 (p=0.36)

0.22 ± 0.49 (p=0.65)
0.00
0.001 ± 0.02 (p=0.97)

0.27 ± 0.47 (p=0.58)
0.00
0.03 ± 0.02 (p=0.14)-0.68 ± 0.44 (p=0.12)
0.00
0.04 ± 0.02 (p<0.05)*-0.53 ± 0.49 (p=0.28)
0.00-0.73 ± 0.47 (p=0.13)
0.00-1.41 ± 0.44 (p<0.01)*
0.00-0.50 ± 0.78 (p=0.54)
0.00-0.84 ± 0.70 (p=0.24)
0.00-0.001 ± 0.69 (p=0.99)
0.00

0.13 ± 0.71 (p=0.86)-0.35 ± 0.76 (p=0.65)
0.00

0.05 ± 0.60 (p=0.93)
0.03 ± 0.63 (p=0.96)
0.00-0.53 ± 0.63 (p=0.40)
0.35 ± 0.67 (p=0.60)
0.00-0.67± 0.71 (p=0.35)-0.51± 0.54 (p=0.35)
0.00-0.32 ± 0.62 (p=0.61)-0.21 ± 0.47 (p=0.66)
0.00-0.78 ± 0.63 (p=0.22)-0.42 ± 0.48 (p=0.39)
0.00*Statistically significant at p<0.05 level. †Marginal significant level.

In univariate analysis, tests concerning the differences of PD and RBL over time among different levels ofa single risk factor, such as age < 45 vs. age ≥ 45 and smoking vs. non-smoking, were completed (Table 4).
The results are as follows:
Age < 45 vs. age ≥ 45
The younger age group (< 45) had more buccal PD reduction (1.55 ± 0.53 mm, p<0.01), more average PD
reduction (1.08 ± 0.48 mm, p<0.05), and more RBL reduction (1.09 ± 0.48 mm , p < 0.05) than the older age(≥45) group. No significant findings were found for lingual PD.
Smoking vs. non-smoking
Non-smokers showed 1.25 ± 0.45 mm more RBL reduction than smokers (p<0.01). No significant
findings were found when considering PD measurements.
Endodontically-treated teeth before regenerative therapy vs. non-endodontically treated teeth before
regenerative therapy
There was a marginal significance for more buccal PD reduction (1.33 ± 0.74 mm, p = 0.08) in
non-endodontically treated teeth when compared to endodontically treated teeth. No differences were notedin RBL.
Absorbable membrane vs. non-absorbable membrane
Buccal PDs were reduced 1.19 ± 0.54 mm (p<0.05) at sites treated with absorbable barriers whencompared to sites treated with non-absorbable membranes sites. However, no significant findings were noted

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when comparing lingual PD and only a marginal significance was found with the use of absorbable barriers
when considering average PD reduction (p = 0.06) and RBL reduction (p = 0.06).
Table 4. Effects of selected clinical factors on GTR outcome (Univariate analysis).
Changes (mm) ± S.E.: Pre- and Post-regenerative therapy
PD (Buccal)
AgeIntercept-1.17 ± 0.30 (p<0.01)< 45-1.55 ± 0.53 (p<0.01)*
≥ 45
0.00
Smoking (General)
Intercept-1.35 ± 0.34 (p<0.01)
No-0.72 ± 0.52 (p=0.17)
Yes
0.00
Smoking (Quantified)Intercept-2.13 ± 0.70 (p<0.01)
0 cig/day
0.05 ± 0.80 (p=0.95)
1-9 cig/day 1.16 ± 1.27 (p=0.36)
10-19 cig/d -0.01 ± 1.44 (p=0.99)> 19 cig/d 0.00
Endodontic treatment
Intercept-0.47 ± 0.71 (p=0.50)
No-1.33 ± 0.74 (p=0.08)†
Yes
0.00
Type of membrane
Intercept-2.29 ± 0.43 (p<0.01)
Non-absorb 1.19 ± 0.54 (p<0.05)*
Absorbable 0.00

PD (Lingual)

PD (Average)

RBL-1.15 ± 0.27 (p<0.01)-0.59 ± 0.49 (p=0.23)
0.00-1.17 ± 0.27 (p<0.01)-1.08 ± 0.48 (p<0.05)*
0.00-0.36 ± 0.27 (p=0.19)-1.09 ± 0.48 (p<0.05)*
0.00-1.12 ± 0.30 (p<0.01)-0.55 ± 0.47 (p=0.25)
0.00-1.23 ± 0.30 (p<0.01)-0.67 ± 0.46 (p=0.15)
0.00-0.18 ± 0.29 (p=0.55)-1.25 ± 0.45 (p<0.01)*
0.00-1.52 ± 0.60 (p<0.01)-0.12 ± 0.70 (p=0.87)
0.38 ± 1.07 (p=0.72)
0.30 ± 1.12 (p=0.79)
0.00-1.83 ± 0.60 (p<0.01)-0.05 ± 0.69 (p=0.94)
0.85 ± 1.09 (p=0.44)
0.10 ± 1.22 (p=0.93)
0.00-0.78 ± 0.54 (p=0.15)-0.64 ± 0.62 (p=0.31)
0.67 ± 0.98 (p=0.49)-0.50 ± 1.10 (p=0.64)
0.00-0.70 ± 0.70 (p=0.32)-0.71 ± 0.74 (p=0.34)
0.00-0.55 ± 0.64 (p=0.39)-1.08 ± 0.67 (p=0.12)
0.00-0.27 ± 0.67 (p=0.69)-0.48 ± 0.70 (p=0.50)
0.00-1.91 ± 0.43 (p<0.01)
0.57 ± 0.55 (p=0.30)
0.00-2.16 ± 0.38 (p<0.01)
0.91 ± 0.48 (p=0.06)†
0.00-0.97 ± 0.36 (p<0.01)
0.87 ± 0.45 (p=0.06)†
0.00*Statistically significant at p<0.05 level. †Marginal significant level.

DISCUSSION
Results from this study indicate that regenerative periodontal therapy conducted within the environment ofan educational training program can achieve statistically significant reductions in PD (buccal -1.53 mm andlingual -1.28 mm) and RBL (0.72mm). This finding is in general agreement with a number of the previous
studies,4,7,17,18 which have reported 0.8 to 4.5 mm probing attachment level (PAL) gain, 1.2 to 4.3 mm bonegain, and 19% to 73% bone fill after 6 to 12 months when regenerative techniques were used in treatment of
infrabony defects. More importantly, there is strong evidence that these clinical improvements can be
maintained long-term following therapy. Machtei et al. reported that the rate of stability (change in PD ≤ 0.9mm) was 90.9% and 90.4% for previously treated furcated and non-furcated sites respectively in their 4-year
longitudinal study.13 Weigel et al. also stated that 1.37 mm of new attachment could be maintained whencompared to baseline data and 63.2% (12/19) of treated sites maintained clinical attachment level within ± 1
mm during the four years of maintenance following GTR therapy; no significant change in bone height wasobserved.14 These findings are consistent with a 5-year longitudinal GTR study conducted by McClain and

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Schallhorn (1993).19
In this study, the older age group (age ≥ 45 yrs.) had less favorable regenerative outcomes when comparedto the younger age group (age under 45 yrs.). While it is not clear why aging may exert a negative effect upon
regenerative therapy, it has been suggested that aging may change intrinsic host factors thus compromising
the patient's ability to repair/regenerate tissues.9,11,20-25 Van Der Velden reported that aging is accompanied bya greater susceptibility to periodontal disease and a slower rate of wound healing.25 Several studies havereported that elderly patients tend to have slow wound healing when compared to younger individuals.26-29 In
contrast, Machtei et al. treated 30 patients aged from 27 to 66 years (mean 42.3 ± 9.8 years) with ePTFE
membrane and concluded that age was not a significant factor in influencing the success of GTR treatment.12
The differences in findings between these studies may be attributed to different populations studied andperiodontal defects treated. In Machtei’s study, 70 % of sites treated were in a younger age group (age under45), whereas 70.2% of sites treated in this study were in the older age group (age ≥ 45). In addition, Machtei
et al. analyzed only mandibular class II furcation involvement defects while all teeth types (single-rooted andmulti-rooted teeth) were analyzed in the present study.
Non-smokers in this study had better regenerative outcomes than smokers, a finding in agreement with
Tonetti et al. who reported that cigarette smoking is a factor strongly associated with reduced healing after
GTR treatment.30 According to Rivera-Hidalgo, smoking may inhibit host neutrophil function, reduce thecirculation of gingival blood flow, and increase the mean proportion of anaerobes in the periodontal pocket.31
Hanes et al. also showed that nicotine contained in cigarette binds to gingival fibroblasts and further affects
normal fibroblast function.32 However, the relationship between systemic effects of smoking and local
etiologic factors in periodontal destruction and GTR outcome remains ill-defined. It has been proposed thatsmoking may exert a direct influence on the periodontium primarily by interfering with the body’s response
mechanisms rather than by augmenting local destructive factors such as plaque infection.33 The level ofcigarette consumption may also be an important factor in determining the overall effect of smoking on thehealing response. Kaldahl et al. reported that heavy smokers (≥ 20 cigarettes/day) had less favorable
outcomes than the light smokers (≤ 19 cigarettes/day) when conventional periodontal therapy is used while
no difference was noted between past smokers and non-smokers.34 In this study, information on the amountof daily cigarette use was not available and thus it was possible only to compare nonsmokers and smokers interms of regenerative outcomes.
Using multivariate analysis, no significant correlations were found between clinical outcomes and gender,use of bone grafts, type of GTR barrier used, subgingival versus supragingival placement of restorative
margins, and endodontic status. Univariate analysis demonstrated weak but positive correlations between i)
non-endodontically treated teeth and ii) use of absorbable-type membranes with more favorable clinicaloutcomes. Non-endodontically treated teeth had more buccal PD reduction (1.33 ± 0.74 mm) whencompared to endodontically treated teeth but this difference was only marginally significant (p = 0.08). In
addition, it must be noted that the sample size of endodontically-treated teeth in this study was small (n = 11)
representing only 8.4% of total study sites.

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INT CHIN J DENTIn terms of treatment variables, no significant differences were noted among the three treatment groups,
e.g. DFDBA alone, GTR membrane alone, or GTR membrane combined with DFDBA. This finding is
consistent with a number of earlier clinical studies.5,7,35-37 Chen et al. failed to find any additional clinicalbenefit when DFDBA was used in conjunction with GTR barriers composed of bovine collagen.37 Gouldin etal.,38 in a six month study evaluating the use of GTR procedures in interproximal defects, found that either
using ePTFE alone or in combination with DFDBA resulted in similar outcomes. In contrast, Reynolds andBowers reported that concomitant use of DFDBA in GTR therapy results in significantly greater amounts of
new periodontal attachment formation.39 A number of protocol-related issues may partially explain thesevariations in findings, including differences in the measurement techniques used, the nature and extent of
osseous defects treated, variations in oral hygiene and compliance levels between patients, and different
commercial sources of DFDBA with varying levels of bioactive bone morphogenetic proteins within these
preparations. The finding in this study that periodontal sites responded equally well whether absorbable or
non-absorbable GTR barrier materials were used is also in general agreement with previous studies,including a recent report by Cortellini et al.40
There was no statistically significant influence on therapy outcomes when tissue responses adjacent totooth surfaces without restorations were compared with subgingival restorations or with supragingival
restorations. This finding may be due to the relatively small sample size for the first two groups (i.e. sites
with no restorations, n = 24, or with subgingival margin placement, n = 29). Some differences between thesegroups were expected based on previous reports which suggested a detrimental influence of subgingival
margins on periodontal health. Orkin et al. reported that tissues adjacent to crowns with subgingival margins
had greater bleeding and recession compared with control sites.41 Subgingival dental restorations are also
thought to adversely affect the periodontium by promoting the retention of plaque, favoring development of apathogenic flora, and/or by physically challenging the supracrestal attachment area.42,43 However, in thisstudy, these potentially negative influences were not detectable in therapy outcomes suggesting either a truelack of effect or to small sample size.
In comparison to controlled clinical studies, this study had a number of significant shortcomings and may
be better defined as a multi-case analysis. In addition to other deficiencies, this retrospective study lacked anegative control group (e.g. flap surgery alone), drew data from a relatively small treatment pool, usednon-standardized radiographs and non-calibrated measurement techniques, and used a variety of regenerativetechniques performed by a member of beginning periodontal surgeons. Importantly, it should be recognizedthat cross-sectional studies can not show causality. However, the data is interesting in that even with theseshortcomings in the treatment protocol, clinical outcomes approximated those published in numerous
previous studies with respect to two specific clinical endpoints of therapy, i.e. reduction in i) depth (PD) andii) radiographic bone loss (RBL). This finding suggests that regenerative therapy can be beneficial andrelatively successful when performed in a clinical environment by practitioners who are not "experts" in suchtreatment modalities.
In summary, within the parameters of this study, the following conclusions were drawn: 1) Regenerative

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therapy performed by multiple providers with varying levels of skill and experience resulted in an overall
statistically significant reduction in probing depth (PD) and radiographic bone loss (RBL), 2) Aging andsmoking appeared to exert negative influences on outcomes of regenerative therapy; 3) In univariate analyses,
a weak negative correlation could be found between endodontically treated teeth and favorable GTR
outcomes; 4) Adjunctive DFDBA grafting did not appear to significantly enhance regeneration; and 5) GTR
procedures utilizing absorbable versus non-absorbable barriers showed comparable outcomes.

ACKNOWLEDGMENT
The authors wish to thank Drs. Maria Korsnes and Marianne Ong for their assistance in this study.

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3. Cortellini P, Pini-Prato G, Tonetti M. Periodontal regeneration of human infrabony defects. I. Clinical measures. J
Periodontol 1993; 64: 254-60.
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Reprint request to:
Dr. Hom-Lay Wang
University of Michigan, School of Dentistry1011 N. University Ave., Ann Arbor, Michigan 48109-1078, USA
FAX: +1-734-936-0374
E-mail: homlay@umich.edu
Received on September 22, 2001. Revised on December 24, 2001. Accepted on December 26, 2001.
Copyright ©2002 by the Editorial Council of the International Chinese Journal of Dentistry.

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