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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 4  |  Page : 167-174

Calcium sulfate applications in dentistry: A literature review


1 Department of Endodontics, Nova Southeastern University, College of Dental Medicine, Davie, Florida, USA
2 Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA
3 Department of Endodontics, Nova Southeastern University, Davie, Florida, USA

Date of Submission24-Nov-2020
Date of Decision27-Nov-2020
Date of Acceptance11-Dec-2020
Date of Web Publication18-Jan-2021

Correspondence Address:
Dr. James L Gutmann
Department of Endodontics, Nova Southeastern University, Davie, Florida
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/endo.endo_156_20

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  Abstract 


Calcium sulfate (CS) is a ubiquitous compound that has been incorporated in several medical and dental procedures. This can be attributed to its many advantageous characteristics, including being resorbable as well as its biocompatibility. Primarily, it was used to help treat a variety of osseous defects by acting as a bone substitute. Due to its unique properties, other therapeutic applications have been identified. Whilst the outcomes of these applications are varied, they have shown to be beneficial within the disciplines of endodontics, periodontics and oral & maxillofacial surgery. The aim of this review is to thoroughly discuss CS including its characteristics, chemical and physical properties, and known relative indications in dentistry. Clinical studies reporting the outcomes of CS for particular treatment modalities are further analyzed and discussed.

Keywords: Bone substitute, calcium sulfate, hemostasis


How to cite this article:
Sinjab YH, Sinjab KH, Navarrete-Bedoya C, Gutmann JL. Calcium sulfate applications in dentistry: A literature review. Endodontology 2020;32:167-74

How to cite this URL:
Sinjab YH, Sinjab KH, Navarrete-Bedoya C, Gutmann JL. Calcium sulfate applications in dentistry: A literature review. Endodontology [serial online] 2020 [cited 2021 Mar 2];32:167-74. Available from: https://www.endodontologyonweb.org/text.asp?2020/32/4/167/307310




  Introduction Top


Calcium sulfate (CS) is an inorganic compound known in the marketplace as gypsum plaster or plaster of Paris. It is made available in a liquid and powder form, and when mixed well, it assumes a solid texture with compressive strength greater than cancellous bone and tensile strength slightly less than cancellous bone.[1] Its earliest uses have been documented for treating bone fractures as early as the 10th century,[1] and over the last two centuries, clinicians found different ways to use it in both medical and dental surgery. Previous animal[2],[3] and human studies[4] determined that CS can perform wonders in the medical field and recommended further studies be done to learn more about its properties and various clinical uses. Later, in dentistry, clinical reports demonstrated favorable results when using CS in periodontal infrabony defects.[5] By the beginning of the 21st century, dental procedures began to take advantage of its resorbable and biocompatible characteristics and started incorporating it in several procedures, such as ridge augmentation after tooth extraction,[6],[7],[8] sinus augmentation,[9],[10],[11],[12] furcation[13] and periodontal intrabony defects,[14] periapical defects,[15] managing osteomyelitis,[16] and even during dental implant placement.[17] Other in vivo studies also reported beneficial outcomes when CS was used as a barrier for guided tissue regeneration (GTR).[18] Being readily available and relatively inexpensive, not to mention its vehicular ability to deliver medicine and growth factors, clinicians and researchers showed great interest in this product and were able to report favorable or even superior results when comparing CS to other available materials on the market.


  Chemical and Physical Properties Top


There are three different forms of CS based on the amount of water found within a single molecular unit; CS anhydrate, CS dihydrate, and CS hemihydrate.[19] Its natural form is found as CS dihydrate mineral and is transformed into CS hemihydrate after calcination is complete, which can be reversed simply by mixing with water.[20] The αα-hemihydrate form (dental stone) is used for diagnostic casts because of its hardness and relative insolubility, unlike the ββ-hemihydrate. The difference in crystal size, lattice imperfection, as well as surface area between the two forms gives each its own physical properties.


  Characteristics Top


CS is used in dentistry for its biocompatibility with bone[21] and its tolerance by the gingival tissue. It is an osteoconductive bone substitute that undergoes complete resorption inducing minimal to no inflammatory response when used to fill intrabony defects[5] or extraction sockets.[6],[8] It provides calcium ions that increase the activity of osteoblasts and later undergoes complete resorption within a short period of time. Although its quick resorption may cause less than favorable ridge dimensions, it can be left exposed (under 3 mm) acting as a membrane and protecting the contents within a socket during ridge preservation procedures. Later, the soft tissue will migrate over the exposed CS, filling the area with preferable keratinized tissue. Its regenerative properties, by providing a resorbable scaffold for bone growth, begin during the dissolution of the compound, where the inorganic calcium and phosphorus ions are released causing an increase in osteoblastic genesis and function.[2] Clinical recognition of these properties may have been dampened due to its poor handling as a paste and its rapid resorption, which may impact on the shaping of the grafted material and the anticipated outcomes, respectively..[20] Its rapid resorption rate has also been found to affect its osteoconductive properties in osteoporotic patients.[22],[23]

Radiographically, CS initially appears radiopaque when first placed and slowly transforms into newly formed uncalcified bone within the first 3 weeks and becomes radiolucent. Overtime, it undergoes complete resorption by 5–7 weeks through dissolution[24] and then gradually calcifies and becomes radiopaque again around the 12th week.[19] Histological studies reported CS often not being observed in most grafted sites after complete regeneration of the socket.[25] It also shows faster resorption rates when compared to other common bone grafting materials such as autogenous and freeze-dried bone.[24] In cases where an infection was present and CS was placed, it was able to drain out with the pus with no evidence of sequestrate present.[26]


  Clinical Applications Top


Being biocompatible, readily available, and relatively inexpensive, the demand of using alloplastic materials in dentistry has been studied to analyze their benefits and compare them with other materials available on the market. Over the years, several reports have been published showing various clinical application of CS in dentistry.

Extraction-socket grafting and ridge preservation

Ridge preservation before dental implant placement is commonly performed after tooth extraction to reduce the ridge width and height reduction caused by bone remodeling,[27] yet complete ridge preservation is never attained regardless of the material used.[28]

There are many options available for socket grafting. The use of autologous bone was originally considered to be the ideal grafting material[29] because it is replaced completely with vital bone, but studies have found that its fast resorption rate can cause significant loss in ridge dimensions.[30] Allografts have been found to resorb slower than autologous grafts and provide more dimensional stability to the ridge, and sites grafted with allograft showed less residual graft particles (approximately 15%)[31] when compared to xenograft materials (approximately 30%).[32]

Although CS and other alloplastic bone substitutes such as hydroxyapatite, calcium phosphate, and bioactive glass have different resorption rates, they have all shown significant increase in vital bone percentage compared to natural healing.[33] Hydroxyapatite has been found more suitable in long-term ridge preservation procedures due to being almost nonresorbable,[34] unlike CS which resorbs quickly and is preferred for socket grafting and future implant placement.[24] As for their ability to reduce ridge resorption, a literature review conducted by Majzoub et al.[35] comparing different materials used for socket grafting found minimal differences in resorption rate when comparing alloplastic grafts to both allogeneic and xenogeneic grafting materials.

Various studies reported favorable results, both clinically and histologically, when using CS for socket grafting. One prospective clinical trial performed on 10 patients compared the use of CS hemihydrate to natural socket healing in half of the patients.[6] Histological results reported 100% newly formed living bone in all the analyzed specimens with no residual particles after 3 months of healing. In the sites grafted with CS, the mean trabecular bone was found higher (58% vs. 46%) than nongrafted sites. However, no clinical data were reported in their results and discussion. Another clinical study compared both clinical and histological outcomes between natural healing and CS-grafted sockets in the anterior maxilla.[8] Clinically, the grafted sockets appeared to accelerate the healing process and minimize ridge resorption when compared to nongrafted sites. Those control sites showed greater dimensional changes than sites grafted with CS, with a mean of 0.7 mm and 1.2 mm greater vertical height and horizontal width loss, respectively. Their histological evaluation showed similar statistically greater trabecular and lamellar bone percentages in the grafted sites.

Unconventional methods have also been adapted to deliver CS into the socket. One case report used CS in the form of a putty which was injected into the socket, and the histological results showed good trabecular bone and newly formed bone bridging with the putty.[36] The same group compared the putty with another test group using xenograft and non-grafted control sites in a randomized clinical trial. Both groups had statistically significantly less reduction in mean ridge width with no statistically significant difference between them.[37] Another randomized clinical trial used a putty binder composing carboxymethylcellulose and CS that was equally mixed with a demineralized freeze-dried bone allograft (DFDBA) and covered the socket with a CS barrier.[38] When compared to sockets filled with bovine bone xenograft covered with a bovine collagen membrane, clinical outcomes showed no significant difference for both height and width changes. However, they reported that this mixture of putty carrier with allograft produced significantly more vital bone fill in addition to its ease of handling and placement. Based on the reported literature, it is clear that the results are in favor of using CS in the extracted socket for ridge preservation.

Barrier membrane

Procedures requiring the use of barrier membranes for both GTR and guided bone regeneration (GBR) favor the use of resorbable over nonresorbable materials to avoid the need for a second surgery to remove the membrane. Therefore, many absorbable materials, including CS, have been developed to be used in such procedures. An in vitro study found CS to enhance tissue coverage and compatibility with gingival fibroblast, as well as facilitate cellular attachment when compared to polytetrafluoroethylene (PTFE) and polylactic acid membranes.[21] A split-mouth study comparing the adjunctive use of CS as a barrier to cover a socket filled with bioactive glass material showed favorable results when compared to control sites that were grafted with bioactive glass alone.[39] These test sites showed significantly greater bone fill upon re-entry (mean 6.43 vs. 4.00 mm) and less alveolar bone height resorption (mean 0.38 vs. 1.00 ± 2.25 mm). However, horizontal bone changes were found similar between the test and control groups (mean 3.48 mm vs. 3.06 mm), considering the fact that a full-thickness flap was done in both sites, which can cause increased bone remodeling when compared to flapless extraction sites. However, studies conducting GTR and GBR procedures mostly report using PTFE and collagen membranes and more studies are required for a more definitive outcome.

Periodontal defects

Clinical studies using CS in periodontal infrabony defects have shown favorable results both clinically and radiographically.[5],[14] However, most studies aim to use autologous and allogeneic bone graft materials when grafting such defects hoping to achieve true regeneration. The addition of CS to autologous bone graft has been found to show similar clinical outcomes when compared to autologous graft alone,[40] yet combining it with DFDBA showed superior results when compared to CS alone.[13],[41]

While all clinical results were only reported through clinical and radiographic outcomes, this is because histologic results are the only method that can prove true regeneration in these defects and is made more possible through animal studies. When comparing the outcomes of using DFDBA, CS, or the combination of both to periodontal surgery alone, the placement of any of these graft materials in a surgically created three-walled defects in dogs showed significant improved regeneration of both alveolar bone and cementum.[41] However, the outcomes from using CS, while significantly better than nongrafted sites, was less significant than sites grafted with DFDBA alone or in combination with CS.

Similarly, a clinical study aiming to treat Class II furcation defects found that adding either DFDBA or doxycycline showed greater outcomes when compared to CS alone, although the combination with DFDBA was more effective in the treatment outcome.[13] Another study looking into Class II/III furcation defects used a composite graft containing CS as a vehicle for carrying doxycycline hyclate and mixed with tricalcium phosphate.[42] They reported a defect fill 3.7 times greater than nongrafted sites and 4 times more likely to have ≥50% defect fill. Later, the same group used the same composite graft to treat only Class III furcation defects and compared it to surgical debridement alone.[43] They found that the graft was able to significantly gain clinical attachment, reduce gingival recession, and show greater vertical defect and volumetric fill than control sites. The added benefit of CS as a vehicle to carry and deliver agents to the surgical site makes it valuable for treating such difficult defects.

Osteomyelitis management

The adjunctive delivery of antibiotic therapy for treating osteomyelitis using CS as a carrier has shown promising results. One in vitro study showed how the use of dried CS implants proved effective in carrying and delivering 11 different antibiotics that are used against osteomyelitis.[16] Several animal[44],[45] and human[46],[47],[48],[49] studies reported encouraging results with the use of locally-delivered, antibiotic-impregnated CS in the surgically debrided sites with osteomyelitis. Furthermore, while CS has been shown to prevent the recurrence of diabetic foot osteomyelitis, it was unable to improve the healing rate or reduce the postoperative amputation rate or healing time.[50] In dentistry, a clinical study using vancomycin-impregnated CS in the surgically-debrided osteomyelitis sites of the jaw reported positive results.[51] Radiographically, CS was found to promote the formation of new bone by 3 months for 10 out of 12 patients, and all the patients had no recurrence of infection during a mean of 10.8-month follow-up.

Sinus augmentation

Several animal and human clinical studies have shown promising outcomes when using CS in sinus augmentation for future implant placement. A previously published case series reported new bone formation 8-9 months after grafting with no residual bone grafting. Successful osseointegration of implants placed in CS grafted sinuses through both staged and simultaneous approaches was noted.[9],[10],[11],[52] However, there were some reports that demonstrated shrinkage of the grafted sites and some residual graft materials despite being very minimal. One clinical study involving 10 patients showed a mean radiographic shrinkage of 26.5% with a mean residual graft material of 8.8% after 4 months of healing.[53] Superior outcomes were almost always reported when comparing CS to other materials, although not always clinically significant. The histological reports from one clinical study comparing eight different materials to autologous bone grafting in 144 grafted sinuses showed CS to provide similar outcomes with less residual graft material than others [Table 1].[54]
Table 1: Comparison of histomorphometry outcomes from the different graft materials reported by Scarano et al., 2006

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While it has been proven to be successful on its own, several attempts were made to combine CS with other types of allografts due to its properties as a carrier. When CS combined with DFDBA, histological results showed residual graft particles from the allograft, yet no particles were found when CS was used alone.[12] This combination was found to cause less graft height loss when compared to CS mixed with an alloplastic grafting material (60% synthetic Hydroxyapatite (HA) and 40% (b-TCP) β-Tricalcium Phoshate), although the mean percentages of new bone and residual graft particles were not significantly different.[55] A further study reported significantly greater volume reduction when CS was combined with deproteinized bovine bone.[56] Reducing the healing time was also identified simply by combining a blend of the CS hemihydrate containing demineralized bone matrix particles and mixing with a solution of sterile water to obtain a putty-like consistency.[57] Using this combination for sinus augmentation and simultaneous implant placement, 3-month histologic findings showed newly formed bone surrounding the residual-grafted particles without inflammation, with a mean bone density of 34%, marrow space of 32%, and residual graft of 34%.

Peri-implant defects

There have been a limited number of clinical studies reporting the use of CS around dental implants. When compared to other grafting materials, histological and immunohistochemical analyses of animal models report no differences compared to CS when used for bone augmentation around titanium implants.[58] Clinically, case reports on the use of CS in treating peri-implant defects at the time of implant placement showed trabecular bone formation with the absence of any CS remnants through light microscopy, while histomorphometry showed 40% of new bone formation.[17] As for peri-implantitis treatment, one clinical case reported 2-year successful outcomes after using a mixture of CS and inorganic bovine bone following implant surface decontamination.[59]

Periapical defects

The ability of CS to fill periapical osseous defects has been analyzed using experimental animal studies. Murashima et al. surgically created different defects after root canal treatment in the beagle dog model: Type 1 - endo-perio-osseous defects, Type 2 - large osseous defect, and Type 3 - through-and-through osseous defect. The randomly selected test side was filled with medical-grade CS while the opposing wall was filled with the unfilled control side. Although CS was not observed at 8 weeks due its resorbable capability, the results for the Type 1 defect on both experimental and control sides showed no bone development at 8 and 16 weeks. However, Type 2 and 3 osseous defects had extremely higher values of bone volume, tissue volume, and mineral apposition rates on the experimental CS-filled side while the control side had lower outcomes.[60]

Yoshikawa et al. used CS to fill osseous defects made during root-end surgical procedures. The site was covered with four different membranes and compared with a negative control group; nonresorbable e-PTFE, resorbable polylactic acid coglycolic acid, resorbable collagen, and CS resorbable membrane. At the 4th week, woven bone and granulation filled all osseous defect groups, and by the 8th week, newly formed cancellous bone was then observed in all groups. By the 16th week, new cortical bone was observed in all groups regardless of the material. The use of a nonresorbable membrane showed higher effectiveness and bone regeneration in osseous regeneration after the surgical procedure, yet CS showed similar results, which allowed it to be substituted for the e-PTFE membrane.[61]

Delivery vehicle

Several studies reported the use of CS as a carrier to locally-deliver products such as platelet-rich plasma (PRP), platelet-derived growth factors (PDGFs), and other pharmaceutical medications.[20] CS itself does not contain any antimicrobial properties but can be used to carry and transport medications. Its efficiency as a carrier was analyzed in vitro using scanning electron microscopic analyses and osteoblast proliferation studies by combining it to PRP and PDGF. The cells that were cultured on CS and nonactivated PRP or CS and 50% nonactivated PRP plus 50% H2O exhibited statistically significant higher proliferation levels compared with CS alone or combined with collagen, thrombin, or thrombin-activated PRP groups. Statistical significance for proliferation levels was also reached when CS carried PDGF compared to CS alone. It was evident that CS had the highest level of osteoblastic proliferation when combined with PRP and PDGF.[62]

CS has also been used as a transporter to deliver pharmacologic agents such as antibiotic and has also been incorporated into acrylic bone cement to facilitate the release of antibiotics. One study combined CS with simvastatin for its ability to increase the expression of bone morphogenetic proteins (BMP-2) in osteoblasts for promoting bone growth.[63] In a study conducted on rats' calvaria, enhanced bone formation with radiopacity appeared radiographically at 8 weeks. However, the CS–simvastatin combination showed an intense soft tissue inflammation in the first 2–4 weeks which subsided and healed normally by the 5th week. Regardless of the delay and the intense soft tissue inflammation, the combination showed a dramatic increase in bone mineralization from the 5th to the 8th week when compared to either CS only and negative control groups.

Relative to carrying and delivering antibiotics, positive outcomes were recorded when loading CS with tobramycin for treating osteomyelitis.[46],[49] In the study by Mousset et al. comparing the delivery of CS for 11 different antibiotics for treating osteomyelitis, great results were found for sodium fusidate, glycopeptides, and aminoglycosides due to their kinetic release, thermostability, and low systemic toxicity in high local concentration.[16] Although aminoglycosides and amoxicillin were 100% stable and released over a period of 3 weeks, other antibiotics such as glycopeptides, quinolone, sodium fusidate, and amoxicillin trihydrate were partially active even after 21 days, and cephalosporin and penicillin were determined unstable and their activity decreased at 10% after only 1 week. The best thermic stability drug was aminoglycosides and its antibacterial properties did not decrease for 21 days at 37°C.

Bibbo and Patel used human demineralized bone matrix and CS for treating intra-articular calcaneal fractures.[64] Promising treatment outcomes were reported when incorporating the composite graft with vancomycin and the authors concluded it to be a safe form of grafting material. Further studies by Benoit et al. combined vancomycin with a CS that was coated polylactide-co-glycolide polymer as a carrier in femoral condyles of rabbits.[65] The rate of elution of vancomycin was correlated with the coating depth of the polylactide-co-glycolide polymer. The coating of the CS carrier allowed the vancomycin to be slowly released at the site of both the bone and joint from 1 to 4 weeks without inducing toxicity.

Hemostasis

It is imperative to have a dry field during all endodontic procedures to prevent contamination of materials and increase the longevity of proposed treatment. Contaminant solutions such as saliva, saline, and blood, if exposed to cements and sealers, can significantly increase leakage and introduction of bacteria. Montellano et al. investigated the apical seal of MTA when exposed to contaminant solution such as saline, saliva, and blood.[66] The study was conducted on 90 single-canaled extracted human teeth. Out of the three contaminants solutions, the highest percentage of bacterial leakage was when MTA was contaminated with saliva, and the least leakage was with blood. Scarano et al. determined that CS was a superior hemostatic agent during the use of MTA as a root-end filling material over gauze tamponade or 20% ferric sulfate.[67] It is crucial that to note with the comparison of these hemostatic agents, ferric sulfate has a pH 0.21 and causes intravascular coagulation. Failure of removal from a surgical site can cause a significant adverse effects on bone healing and a foreign-body reaction that can ultimately lead to an acute inflammation and necrosis of the surrounding soft tissue.[68],[69] On the other hand, if CS remained around the apex after the completion of surgery, there would not have been any complications due to its biocompatibility and its resorbability. The results of the study showed that calcium sulfate was able to achieve adequate hemostasis when used in all 11 cases. The implanted gauze achieved hemostasis in only 3 out of the 10 cases, while the ferric sulfate was successful in 6 out of 10 cases.


  Potential Shortcomings Top


CS requires a dry environment to set since moisture can soften the material and render its useless.[1] Therefore, it is better used in contained areas or in surgical sites where saliva and blood can be managed efficiently during its setting time. Although its quick resorption rate is considered an advantage in some cases, this property makes CS difficult to have maintain its shape and the space it is attempting to graft.[20] CS is also unlikely to act as a barrier due to its rapid 4–8 weeks resorption.[26],[61],[70],[71] With all the favorable outcomes reported in the literature when using CS in osseous defects, these results were not achieved in osseous defects communicating with the periodontal pocket possibly due the inflammation present, the material being drained out or contaminated with saliva.[60] Another limitation to use CS is in osseous defects with thin walls that can resorb before they can contribute to bone formation.[5]


  Conclusions Top


Historically, CS has shown that its mixture can provide a multitude of uses in the dentistry due to its favorable properties and characteristics. With the literature reporting favorable results, this will eventually motivate clinicians all over the world to find new and improved ways to improve treatment modalities and enhance patient treatment outcomes. Future assessments, recognizing the both the attributes and shortcomings of CS, must include randomized prospective clinical trials within the wide range of applications indicated for this material.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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