Ridge Preservation Using Composite Alloplastic

Materials: A Randomized Control Clinical

and Histological Study in Humans
Yaniv Mayer, DMD;* Hadar Zigdon-Giladi, DMD;† Eli E. Machtei, DMD‡

ABSTRACT
Aim: To evaluate (clinically, histologically, and histo-morphometrically) the use of composite materials (Biphasic
calcium sulphate [BCS] with b Tri-Calcium Phosphate (b-TCP) and Hydroxyapatite [HA]) in extraction socket sites
and compare it to un-disturbed natural healing.
Material and Methods: Prospective clinical trial of 36 patients (40 extraction sockets) were randomly assigned to either
test or control group. Alveolar ridge horizontal dimension was measured in the middle of the socket at crest and 3 and
6 mm subcrestally. Crestal vertical height was measured at baseline surgery and at 4 month re-entry, at which time bone
core biopsies were harvested from the center of the edentulous ridge. Histo-morphometric evaluation of the samples
was performed using hematoxylin & eosin stains and morphometric software.
Results: The change in horizontal ridge width was higher in the control compared to the experimental group:
2.28 6 2.36 mm versus 0.03 6 2.32 mm (p 5 .007) at 23 mm and 2.28 6 2.43 versus 0.035 6 3.05 (p 5 .02) at 26 mm,
for the experimental and control sites, respectively. The vertical distance form bone crest to neighboring horizontal line
interconnecting the neighboring teeth was minimal in both groups (0.307 6 2.01 mm versus 0.14 6 2.03 mm
[p 5 0.41]). Residual scaffolds occupied 15.99 6 11.4% of the volume in the grafted (test) sites while bone area fraction
was not statistically different among the groups (47.7 6 10.6% versus 52.6 6 11.6%, test versus control, respectively
p 5 .39). The percentage of connective tissue in the control group was significantly higher that test group (36.3 6 19.4%
versus 46.7 6 10.6% test versus control, respectively, p 5 .013).
Conclusion: Ridge preservation technique using a combination of two synthetic bone grafts b-TCP and HA with BCS
resulted in greater stability in the horizontal dimension after 4 months.
KEY WORDS: alloplast, beta TCP, bi phasic calcium sulphate, bone regeneration, bone resorption, socket
preservation

INTRODUCTION ated with extraction site wound healing that is charac-

The ultimate goal of implant dentistry is to restore terized by rapid bone resorption at this site.2,3 This in
missing teeth by placing implants in anatomically, turn may result in esthetic and restorative challenges
esthetically, and functional restorative positions.1 To associated with the reduce bone volume available for
this end, the challenge facing the dental team is associ- implant placement. Most of the alveolar changes in
extraction socket occur during the first year after tooth
*Doctor, School of Graduate Dentistry, Department of Periodontics,
Rambam Health Care Campus, Haifa, Israel; †Associate Professor,
extraction with two thirds of the bone loss occurring
Head of Lab of Bone Regeneration, School of Graduate Dentistry, on the buccal aspect. The apico-coronal bone height
Department of Periodontics, Rambam Health Care Campus, Haifa, may be reduced by approximately 0.8 mm after 3
Israel; ‡Professor, Head of the School of Graduate Dentistry, Depart-
ment of Periodontics, Rambam Health Care Campus, Haifa, Israel months of healing while after 12 months these negative
changes may reach 2 mm; the changes in the horizon-
Corresponding Author: Dr. Yaniv Mayer, Department of Periodon-
tics, School of Graduate Dentistry, Rambam Health Care Campus, tal dimensions are usually greater (up to 4–5 mm dur-
P.O. Box 9602, Haifa 31096, Israel; e-mail: dr.yaniv.mayer@gmail. ing the first year).4,5 Several studies which have
com
investigated the reasons for the morphologic alterna-
C 2016 Wiley Periodicals, Inc.
V tions concluded that the loss of bundle bone may be
DOI 10.1111/cid.12415 involved in these changes.6–8

1
2 Clinical Implant Dentistry and Related Research, Volume 00, Number 00, 2016

To reduce the rate of the alveolar ridge dimen- erence for synthetic materials. It offers great potential
sional changes, different grafting materials were used for bone reconstruction since it has a chemical com-
in fresh extraction sockets and bone volume and lin- position similar to that of biological bone apatites.15
ear dimensional changes were tracked. Recently, Ten BCP has already proven its efficiency as bone substi-
Haggeler and colleagues in a systematic review were tution material in different human clinical applica-
able to show that the use biomaterials placed into the tions16–18; however, there are only few published
socket immediately after extraction contributed signif- clinical studies with long term follow-up.
icantly to the preservation of the alveolar ridge vol- In the present study, we set to examine the bene-
ume during healing.9 fit of combining the above two alloplastic materials
Bone grafts have long been used in reconstructive (BCP plus BCS) to benefit from the unique character-
surgery with the aim of increasing the bone volume istic of each material and to create an optimal bone
in the previous defect area. Alloplastic bone graft has regeneration material in extraction socket. As the
osteoconductive properties and is relatively safe and resorption kinetics of the two materials is different,
cost effective. Another important advantage of using we believed that the combination of these two materi-
synthetic materials (over autogenous bone graft) is als may create a scaffold with mechanical integrity
the lower morbidity associated with the augmentation which maintains its volume while creating a unique
procedure and would represent an important step for- microarchitecture with different pore sizes which may
ward in simplifying bone regeneration techniques. facilitate condition for blood vessels growth.
One of these alloplastic materials is calcium sulfate To do so, we have evaluated clinically, histologi-
(CS) which has enjoyed a longer history of clinical use cally, and histomorphometrically the use of composite
than most currently available biomaterials. It is well
allograft materials (BCS and BCP) in extraction
tolerated when used to fill bone defects and undergoes
socket sites and compare it to the natural socket heal-
rapid and complete resorption. CS possesses many of
ing process after tooth extraction in human.
the characteristics required from materials for bone
regeneration and, therefore, was widely used in many
regenerative procedures including periodontal regener- MATERIAL AND METHODS
ation, sinus augmentation, extraction socket preserva- Study Population and Design
tion, and for bone regeneration associated with dental
The research was initially approved by the institutional
implant placement.10–13 The mechanisms by which CS
enhances bone formation have not been completely IRB (Helsinki committee) and conducted from January
elucidated. It has been suggested that CS particles bind 2012 to December 2013. The nature of the study was
to adjacent bone and then resorbed, providing a conveyed and informed consent was obtained from all
mechanism to guide and enhance new bone growth.14 subjects prior to commencement.
Despite its many virtues, it does have some shortcom- Subjects requiring tooth extraction at the depart-
ings, mainly its rapid and complete resorption which ment of periodontology Rambam HCC were
is both a virtue and vice. approached to participate in the study. Those patients
A recently introduced biphasic calcium sulfate that have consented to participate were enrolled into
(BCS) has shown to be more stable with better han- this prospective clinical trial. To be included patients
dling properties than CS. BCS is an innovative granu- had to be 18 years or older with at least one tooth
lated powder form. Once it encounters saline, the scheduled for extraction and subsequently scheduled
granulated powder goes through a rapid and efficient for an implant-supported restoration. Subjects were
setting. This setting allows the in situ formation of a excluded if they had one or more of the followings:
rigid structure which is highly crystalline, despite the (i) history of systemic disease that would contraindi-
interfering harsh environment (blood, proteins, and cate oral surgical treatment; (ii) long-term nonsteroi-
saliva). dal anti-inflammatory drug therapy exceeding 100 mg
Biphasic calcium phosphate (BCP), an intimate daily; (iii) intravenous and oral bisphosphonate ther-
mixture of hydroxyapatite (HA) and beta-Tricalcium apy; (iv) pregnant or lactating women; (v) unwilling-
phosphate (b-TCP), was proposed in dentistry as ref- ness to return for the follow-up examination; (vi)
 Ridge Preservation Using Composite Alloplastic Materials 3

smokers (>10 cigarettes per day); (vii) Acute dento- mouth-rinse twice daily for 2 weeks. The patients
alveolar infection. received ibuprofen (400 mg three times a day for the
Subjects were randomly assigned to either the test first day) to manage postsurgical discomfort and
group (T) where a composite BCS/BCP was place in inflammation. Patients allergic to amoxicillin were
the socket following extraction or to the control prescribed clindamycin 300 mg bid. Sutures were
group (C) in which the sockets were left to heal with removed 14 days postoperatively.
no grafting material. The randomization algorithm
accounted for tooth position, arch, and smoking sta- Reentry Procedure and Bone Biopsy
tus. The operator was informed of the group alloca-
Four months after extraction a muco-periosteal flap
tion only after the tooth extraction.
was elevated in the former socket site. The dimensions
Surgical Procedure of edentulous ridge were measured and recorded (as
After administration of local anesthesia, a sulcular inci- described in surgical procedure section). Next, bone
sion was performed and muco-periosteal flaps were core biopsies (8–10 mm length and 2 mm in diameter)
raised around the nonrestorable teeth. The tooth was were harvested from the center of the edentulous ridge
carefully and gently luxated using a periotom. To using a trephine drill. The bone biopsy was transferred
ensure a-traumatic extraction, the roots of molar teeth immediately into 4% buffered formalin. Subsequently,
were separated by a fine straight bur before luxation dental implant was inserted after final preparation of
with a periotom. Extraction of the luxated tooth was the osteotome. Subject received the same drug pre-
performed with surgical forceps to minimize the scription as after the initial surgery. The bone cores
amount of mechanical pressure applied to the buccal were coded and sent for analysis at the bone research
bone. The extraction sockets were debrided and granu- laboratory in our center.
lation tissue was removed. Clinical measurements and
records were taken as follows: the horizontal dimen- Hitological Processing
sion of the socket was measured with a dental caliper All biopsies were fixed in 4% paraformaldehyde for 2
(3MTM ESPETM MDI Ridge Mapping Calipers) at days and decalcified in 10% EDTA, (Sigma-Aldrich,
three heights from the crest: 0, 3, and 6 mm. The ver- MS, USA) for 4 weeks, cut into two halves in the
tical distance was measured from the most coronal midline, embedded in paraffin, and sectioned (8 lm).
part of the ridge to a reference point on neighboring For determination of bone morphology, sections were
tooth (cemento-enamel junction [CEJ] or the pros- stained with Masson’s trichrome and Hematoxylin
thetic crown margins) with a standardized periodontal and Eosin (H&E).
probe (Williams, Hu- Friedy, Chicago IL, USA).
A 1:1 mixture of BCP (4BONE, Biomatlante ZA Histomorphometric Analysis
les Quatre Nations, France) and BCS (BOND BONE,
Histomorphometric evaluation of the samples was
MIS Implant Technologies Ltd., Israel) was used as
performed on two nonconsecutive sections from each
the grafting material in the T group. The extraction
specimen, under a light microscope (Zeiss Axioskop,
sockets were filled and slightly condensed. The sur-
Carl Zeiss, Jena, Germany) using software (image j)
gical protocol for the control group patients was sim-
for image analysis. The following values were meas-
ilar to the test group except that the extraction socket
ured: (i) total bone area (ii) connective tissue (iii)
was not grafted.
Next, two parallel vertical incisions were made residual bone graft. The measurements were expressed
beyond the muco-gingival junction (MGJ); the buccal as percentages of the total sample area.
flaps were coronally advanced to achieve primary clo-
sure and secured with the 5/0 Nylon suture material. Statistical Analysis
Patients were instructed not to brush the surgical sites To compare baseline and final measurement a two
for 1 week. Systemic Amoxicillin (500 mg three times tailed paired Student’s t-test was used. To compare
a day for 7 days) was prescribed and subjects were changes (baseline to reentry) between the T and C
instructed to rinse with 0.2% chlorhexidine gluconate groups we used un-paired student t-test.
6 Clinical Implant Dentistry and Related Research, Volume 00, Number 00, 2016

handling characteristics of BCP by acting as a binder ligible vertical bone loss we found in both groups can
between HA and TCP particles. Furthermore, the be accredited to the surgical procedure we performed.
rapid resorption of BCP leaves porosity that would In all extraction sites (test and control groups), two
enhance the ingrowth of bone.24 parallel vertical incisions were made beyond the MGJ
A recently published meta-analysis evaluated and the buccal flaps were coronally advanced to
bone dimensional changes following ridge preserva- achieve primary closure. A recent meta-analysis con-
tion procedures and the influence of several variables ducted by Vignoletti and colleagues showed that
of interest on the outcomes of ridge preservation extraction procedure involved flap elevation had sig-
therapy.25 They found that alveolar ridge preservation nificantly less horizontal bone loss when compared to
is effective in limiting physiologic ridge reduction as flapless extraction.31 The authors explained this find-
compared with tooth extraction alone. The clinical ing by the primary intention healing which achieved
magnitude of the effect was 1.89 mm in terms of by the flap reflection. Still most of the clinicians to
bucco-lingual width. A recent systematic review con- date do not attempt to achieve primary closure due
ducted by Horowitz and colleagues demonstrated that to conflicting studies and concern about chair time,
there appears to be supporting ridge preservation healing time and morbidity.32
techniques as a whole; without significant difference This study has some limitations in terms of the
among various grafting materials.26 To the contrary, relatively small sample size and patient drop out dur-
other studies did not find advantage in terms of bone ing follow-up. Moreover, the study could have bene-
fill and bone composition following ridge preserva- fited from an additional two control groups: BCS and
tion technique in comparison to natural bone healing BCP separately. Although the harvesting of bone sam-
. They concluded that the bone graft materials only ple with trephine is a common method, it may affect
served as a scaffold and did not stimulate new bone the histologic specimens near the samples’ borders.
formation.27,28 In accordance with these results, in Therefore, for the purpose of this study only used
the present study extraction sites that were filled with sections from the middle of the core biopsy.
BCP/BCS showed no reduction in bucco-lingual Evaluating the nature of healing following ridge
width compared with 2.28 6 2.36 mm in the control preservation procedures demands harvesting a core
(extraction alone) sites. While most of the data con- biopsy and histological analysis. In the present study,
cerning alveolar ridge dimensional changes is based mature lamellar bone was observed in both test and
on teeth in the nonmolar region,2,3 in the present control specimens. Characteristics of vital bone includ-
study, 14/14 sockets in the test group, and 12/15 ing adequate neovascularization as well as osteocytes
socket in the control group were in the premolar and within the lacunae were found in all samples. Active
molar sites. This fact may influence the magnitude of bone remodeling was detected by the presence of
bone loss. The buccal plate in the anterior region is osteoclasts and reversing lines. Importantly, inflamma-
usually thin27 thus ridge alterations in the alveolar tory signs were not found. Percentage of bone fill,
dimension are more likely to occur in these sites.29,30 residual scaffold and connective tissue differ among
According to Avila-Ortiz and colleagues, vertical studies and depend on various parameters: surgical
ridge changes of 1.18 to 2.07 mm are to be expected procedure, material that was used to fill the socket and
in midbuccal and midlingual height, and 0.24 to healing period. Toloue and colleagues compared clini-
0.48 mm for mesial and distal height changes. Indeed, cally and histology bone healing following ridge preser-
vertical measurements in the current study were taken vation using CS and freeze-dried bone allograft
in the midbuccal and midlingual aspects using the (FDBA).33 Histological analysis (3 months following
neighboring tooth CEJ as reference. Our results ridge preservation) revealed an average of 32% new
showed only minimal changes in vertical bone height bone formation with 2.5% graft remaining for the CS
in both the control and test groups. These results can group and 16.7% new bone formation with 21% of
be attributed to the presence of bone and PDL in the graft remaining for the FDBA. Moreover, clinical
adjacent tooth that is responsible for maintaining measurements found nonsignificant changes in vertical
blood supply to the alveolar bone thus helping to dimensions and similar bucco-lingual bone resorption
preserve bone height at these sites. Moreover, the neg- in both groups. Additional study by Kumari and
 Ridge Preservation Using Composite Alloplastic Materials 7

colleagues, compared clinically and histologically nano- 7. Araujo M, Lindhe J. Dimensional ridge alternations fol-
crystalline CS bone grafts and medical-grade CS bone lowing tooth extraction. An experimental study in the
dog. J Clin Periodontol 2005; 32:212–218.
grafts in human extraction sockets. Higher percentage
8. Araujo M, Sukekava F, Wennstrom J, Lindhe J. Tissue
of new bone formation was reported (50%) and
modeling following implant placement in fresh extraction
residual graft was approximately half compared to our sockets. Clin Oral Implants Res 2006; 17:615–624.
finding (7%).34 9. Ten Haggeler JMAG, Slot DE, van der Weijden GA. Effect
of socket preservation therapies following tooth extraction
in non molar regions in human: a systematic review. Clin
CONCLUSION Oral Impl Res 2011; 22:779–788.
The results of this prospective clinical trial show that 10. Walsh WR, Morberg P, Yu Y, et al. Response of a calcium
ridge preservation technique using a combination of sulfate bone graft substitute in a confined cancellous
two synthetic bone grafts (b-TCP and Hydroxyapatite defect. Clin Orthop Relat Res 2003; 406:228–236.
11. Crespi R, Capparè P, Gherlone E. Magnesium-enriched
HA with BCS) is superior to natural healing process
hydroxyapatite compared to calciumsulfate in the healing
in terms of horizontal dimensional changes after 4
of human extraction sockets: radiographic and histomor-
months. Moreover, according to histological analysis, phometric evaluation at 3 months. J Periodontol 2009;
percentage of residual graft was relatively small with- 80:210–218.
out evidence for inflammatory response or graft 12. Kelly CM, Wilkins RM, Gitelis S, Hartjen C, Watson JT,
encapsulation. Kim PT. The use of a surgical grade calcium sulfate as a
bone graft substitute: results of a multicenter trial. Clin
Orthop Relat Res 2001; 382:42–50.
CONFLICT OF INTEREST STATEMENT 13. Deliberador TM, Nagata MJ, Furlaneto FA, et al. Autoge-
The authors declare that they do not have conflict of nous bone graft with or without a calcium sulfate barrier
in the treatment of Class II furcation defects: a histologic
interest regarding the present study. The study was
and histometric study in dogs. J Periodontol 2006; 77:
partially supported by an educational grant from the
780–789.
MIS implants technology. 14. Coetzee AS. Regeneration of bone in the presence of cal-
cium sulfate. Arch Otolaryngol 1980; 106:405–409.
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