Clinical Effectiveness of a Strontium Chloride– Containing Desensitizing
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QUINTESSENCE INTERNATIONAL
Clinical effectiveness of a strontium chloride– containing desensitizing agent over 6 months: A randomized, double-blind, placebo-controlled study Annett Kobler, Dr Med Dent1/Oliver Kuß, Dr Sc Hum2/ Hans-Günter Schaller, Prof Dr Med Dent1/ Christian R. Gernhardt, Dr Med Dent1
Objective: The aim of this multicenter study was to evaluate the clinical efficacy of a stron- tium chloride–containing desensitizer, Hyposen (Lege Artis), over 6 months. Method and Materials: A total of 142 patients with hypersensitivity in 9 dental practices and 2 clinical departments were included in the double-blind, randomized, placebo-controlled study. Each patient exhibited at least 2 hypersensitive and caries-free teeth with exposed dentin surfaces. One tooth was treated with strontium chloride (SR) as recommended by the manufacturer, another with a placebo. Levels of hypersensitivity were assessed after 2, 8, 12, and 24 weeks by cold air and tactile stimuli. After 6 months 132 patients could be reexamined. Results: A reduction of discomfort and pain was observed in 95 patients (72%) after treatment with SR. Statistical analysis showed a significant positive effect of SR compared to the placebo group (P < .05, McNemar test). Conclusion: Use of SR for desensitizing hypersensitive dentin is an effective alternative to existing desensitizing agents. (Quintessence Int 2008;39:321–325)
Key words: clinical investigation, dentin, dentin hypersensitivity, desensitizing agents, strontium chloride
Dentin hypersensitivity is defined as short, Mostly, these sensations dissipate quickly sharp pain arising from exposed dentin in and completely when the stimulus is over. response to stimuli—typically thermal, evapo- Unlike with the usual dentinal or pulpal pain, rative, tactile, osmotic, or chemical and patients are able to localize the pain. Dentin which cannot be ascribed to any other form hypersensitivity is probably caused by a of dental defect or disease.1 It can also arise change in fluid flow within the dentinal after periodontal therapy, gingival recession, tubules, which in turn excites the nerve end- shrinkage of swollen gingiva after curettage, ings at the pulp-dentin border. Consequently, and elimination of tissue by gingivectomy. It treatment success would depend on the pre- varies in degree from mild to sharp and vention of fluid flow across the dentinal excruciating pain2 and depends on the indi- tubules.4 For professional treatment, restora- vidual’s sensation and tolerance of pain as tive, as well as noninvasive, methods are used. well as emotional and physical factors.3 Desensitizing agents, such as potassium nitrate, potassium oxalate, silver nitrate, sodi- um citrate, fluorides, and strontium chloride, are available.5 After application of strontium 1Department of Operative Dentistry and Periodontology, Martin- chloride on exposed dentin surfaces, a Luther-University Halle-Wittenberg, Halle/Saale, Germany. chemical reaction was observed on the 2Institute of Medical Biometrics, Epidemiology, and Medical Informatics, Martin-Luther-University Halle-Wittenberg, Halle/ dentin surface. Following the substitution of Saale, Germany. calcium ions with strontium ions, the dentinal Correspondence: Dr Annett Kobler, Department of Opera- tubules were blocked by recrystallization of tive Dentistry and Periodontology, Martin-Luther-University strontium within the tubules.6,7 With X-ray Halle-Wittenberg, Große Steinstraße 19, 06108 Halle/ Saale, Germany. Fax: +49345/5573773. E-mail: annett.kobler@ refractometry, it was observed that strontium medizin.uni-halle.de apatite, produced by the chemical conver-
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Table 1 Material composition
Composition
SR desensitizer (Hyposen) Strontium chloride hexahydrate Purified water Benzyl alcohol Placebo Purified water Benzyl alcohol Protection varnish (Hyposen) Methacrylic acid copolymer Isopropyl alcohol Acetone
sion of the applied strontium chloride, seals term therapy with analgesics or corticoids, open dentinal tubules to a depth of 20 µm.6 and pregnant patients were excluded from From studies about the clinical efficacy of the study. A pregnancy during the retreat- strontium chloride–containing dentifrices, ment period induced no exclusion from the the positive properties are known.8 However, study. All subjects received professional there are no studies available about a stron- instruction about adequate oral hygiene. No tium chloride–containing substance that can recommendation about special dentifrices, be applied as a varnish or sealant. toothbrushes, or mouthrinses was given. The null hypothesis of this study was that All patients were provided verbal and writ- treatment of hypersensitive dentin with stron- ten information on the study and signed con- tium chloride would have no desensitizing sent forms to participate. All practitioners effect compared to a placebo. Therefore, the were calibrated by the authors during a train- aim of the present multicenter investigation ing session and received verbal and written was to evaluate the clinical efficacy of the information on the study design. strontium chloride–containing desensitizing Sensitive teeth were identified by the agent Hyposen (Lege Artis Pharma) in a response to an evaporative stimulus, a 3- to prospective, randomized, double-blind, and 5-second blast of air from a dental-unit placebo-controlled study over 6 months. syringe, and scraping with a dental explorer. The following descriptive scale was used for both tests:
METHOD AND MATERIALS (++) Severe pain (+) Moderate pain This multicenter, double-blind, randomized (–) No pain clinical investigation was conducted in 11 treat- ment centers. Two were assigned to a univer- Pain relief was assessed as positive if the sity dental school, and the other 9 were private clinical tests after the first treatment or after, practices. The aim of the study was to examine at most, 2 retreatments within 2 weeks result- whether it is possible to achieve pain relief of ed in a reduction of the pain sensation from diagnosed dentin hypersensitivity with stron- severe pain (++) to moderate pain (+) or from tium chloride (SR) treatment and compare it moderate pain (+) to no pain (–). This reduc- with that of a placebo treatment. The composi- tion had to be maintained for at least 3 tion of both materials is given in Table 1. months. A total of 142 men and women, aged 18 After the clinical examination, 2 teeth in to 60 years, who had at least 2 teeth with clin- each patient were chosen, in the left and ically diagnosed hypersensitivity were includ- right quadrant of the maxillary or mandibular ed in the study. These teeth had no caries or jaw, and randomly assigned to one of the restorations in these areas, and restorative blinded substances. treatment was not planned. Patients with The randomization lists were prepared at poor periodontal condition, those with long- the Department of Medical Epidemiology,
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Biometry, and Informatics of the Martin- Table 2 Treatment success with the Luther-University Halle-Wittenberg. According strontium chloride group to these lists, the teeth were assigned to compared with the placebo receive treatment with either SR or a placebo. group
At the beginning of the study, these lists were Hyposen Placebo success given to the 11 clinicians and not decoded success Positive Negative Total before the end of the study. Positive 30 65 95 The application of the placebo solution Negative 11 26 37 corresponded exactly to that of SR. The pro- Total 41 91 132 tection varnish was the same in both groups and was also applied in the placebo group. In the first session, the substance was applied. Other hypersensitive teeth were treated with unblinded SR. If there was no pain relief after the first treatment, the appli- cation was repeated up to 2 times within 2 weeks. If no pain reduction was achieved after the second retreatment, patients were RESULTS treated with unblinded SR. In this case, treat- ment success was assessed as negative. A total of 142 subjects (62% women, 38% The following timetable was used for all men) participated in the study. The median treatments and examinations: age was 41 years; the oldest patient was 60 years old and the youngest 18 years. Week 0—First treatment After 6 months, 132 patients could be Week 1—First control or retreatment reexamined (Table 2). In teeth treated with Week 2—Second control or retreatment SR, a reduction of discomfort and pain was Week 8—Control observed in 95 patients (72.0%). Regarding Week 12—Control placebo-treated teeth, improvements were Week 24—Control observed in 41 patients (31.1%). Thirty sub- jects experienced pain relief on both teeth The application of both substances fol- (SR and placebo), 26 subjects had no lowed the manufacturers’ instructions. After improvement in symptoms on both teeth, 65 cleansing and air drying of the sensitive subjects had pain relief with SR but not with dentin surfaces, the desensitizer or the the placebo, and 11 subjects had pain relief placebo solution was applied. When the with the placebo but not with SR. desensitizer was dried without the aid of an Statistical analysis revealed significantly air blast, a second layer was applied in the better values for SR than with the placebo same way. Subsequently, the Hyposen pro- (P < .001, McNemar test). tection varnish was applied in both groups and dried without an air blast. For optimal treatment success, patients were instructed not to eat any solid food, drink DISCUSSION acidic beverages, or brush their teeth for about 2 hours after the treatment was complete. The hydrodynamic theory proposed by The protocol was reviewed and accepted Brannström is considered to be the most by the Ethics Committee of the Martin-Luther- accepted theory that explains the excitement University Halle-Wittenberg. of pulpal nerve fibers by a stimulus applied to Statistical analysis was performed by the exposed dentin.9,10 Etiologic factors causing Institute of Medical Biometrics, Epidemiology, exposed dentin areas are abrasion, attrition, and Medical Informatics of the Martin-Luther- erosion, abfraction, and periodontal attach- University Halle-Wittenberg using the McNemar ment loss with a rapid loss of cementum or, test and a 5% level of significance. most often, a combination of factors. These
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defects in enamel, dentin, and cementum the subjects, an improvement in symptoms led to the opening of the dentinal tubules was diagnosed after treatment with SR, and may result in dentin hypersensitivity.11–13 whereas 31.6% of the the 72.0% also had an All subjects of this study showed on at improvement in symptoms with the placebo, least 2 teeth in different quadrants hypersen- as well as with the SR. In the literature, clini- sitive dentin areas that were located in the cal improvement that can be explained by cervical region of the tooth and did not need placebo response ranged from 30% to restorative treatment. A clinical examination 40%.5 The placebo effect is a complex psy- excluded inflammation of the pulp as the chophysiologic response caused by placebo cause of the discomforts. administration. The 2 main theories that The SR solution was applied according to explain the placebo effect are “classic condi- the manufacturer’s instructions. The placebo tioning” and the “expectancy theory.” was applied in the same way and covered Certainly, they interact with each other and with the same protective varnish. Both solu- patients learn to experience improvement tions had an identical smell, color, and tex- after medical treatment, and the expecta- ture. Therefore, the clinicians, as well as the tions through consulting a doctor bring patients, were not able to identify the applied symptomatic improvements. Especially in solutions. clinical studies, the Hawthorne effect is dis- Hyposen is a 10% strontium chloride hexa- cussed: Because of the concentrated atten- hydrate solution (see Table 1). Under toxico- tion and observation, people temporarily logic aspects, strontium can be stored in change their behavior or performance. bone after recrystallization to strontium Nocebo is the opposite effect of placebo apatite.14 An increasing calcium release into and is activated by negative expectations. It the blood plasma was thought to influence may induce negative adverse effects in the calcium homeostasis and cause stron- placebo treatments and reverse symptoms tium rickets. These effects could not be from positive ones to negative ones. The proved in recent investigations.15,16 The com- most recent literature suggests that in the position of the SR solution corresponds to a right circumstances, everybody may total quantity of strontium of 3.28% and meets respond to placebo, so we are not able to the guideline 2000/11/EG of 375 order of exclude these effects or distinguish patients cosmetic substances of a maximum of 3.5%. who react. However, the double-blind place- After application, according to the manufac- bo-controlled trial with 2 arms, an active turer’s instructions, there is no toxicologic risk group and a placebo group, is still the gold for the patient. Because of the penetration standard in clinical trial design.18,19 depth of 20 µm in the dentinal tubules, there The results of this study correspond to is also no toxicologic risk for the pulp.6 values in the literature of clinical investiga- Therefore, clinical use is unobjectionable. tions with strontium chloride–containing The significant positive therapeutic effect substances.20 Studies showed improve- of SR in the present study is caused, on one ments of the clinical symptoms for up to 78% hand, by blocking the dentinal tubules. The of the attended patients.1,21 But these were applied strontium chloride forms a solid infil- mostly studies about the efficacy of stron- tration layer of 20 µm; therefore, pain arising tium chloride–containing dentifrices.20,22 The in response to external stimuli is prohibit- positive effect of strontium chloride in denti- ed.6,7,9 On the other hand, strontium is able to frices could be diminished by the abrasive- reduce the nerve activity of dental neurons ness of the dentifrices. Therefore, it could be and interrupt the pulp neural response, more difficult to form the 20-µm-deep infiltra- which certainly has a supporting effect.17 tion layer. For treatment with SR, the addi- The results of this study show a signifi- tional application of the temporary protec- cant positive effect of SR on dentin hyper- tion varnish prevents the fast removal of the sensitivity compared to the placebo over an active agent and supports the formation of observation period of 24 weeks; thus, the the insoluble layer. null hypothesis was rejected. For 72.0% of
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The protection varnish was applied in 8. Topbasi B, Turkmen C, Gunday M. An investigation both groups (SR and placebo), and this of the effect of a desensitizing dentifrice on denti- nal tubules in vitro and in vivo. Quintessence Int could be the reason for positive effects in the 1998;29:197–199. placebo group in the first controls. After 6 9. Brannström M, Astrom A.The hydrodynamics of the months, there should not be any effect of the dentine; its possible relationship to dentinal pain. varnish. Int Dent J 1972;22:270–285. 10. Brannström M. Dentin sensitivity and aspiration of odontoblasts. J Am Dent Assoc 1963;66:366–370. 11. Addy M, Pearce N. Aetiological, predisposing and CONCLUSION environmental factors in dentine hypersensitivity. Arch Oral Biol 1994;39(suppl):33S–38S. 12. Dowell P, Addy M, Dummer P. Dentine hypersensi- The application of Hyposen showed signifi- tivity: Aetiology, differential diagnosis and manage- cantly better results than did the placebo. ment. Br Dent J 1985;158:97–98. After 24 weeks, pain relief or painlessness 13. Kielbassa A. Dentine hypersensitivity: Simple steps was observed in 72% of all patients. for everyday diagnosis and management.Int Dent J 2002;52:394–396. 14. Dahl SG, Allain P, Marie PJ, et al. Incorporation and distribution of strontium in bone. Bone 2001;28: ACKNOWLEDGMENT 446–453. 15. Canalis E, Hott M, Deloffre P,Tsouderos Y, Marie PJ. The divalent strontium salt S12911 enhances bone This study was supported by Lege Artis Pharma, cell replication and bone formation in vitro. Bone Dettenhausen, Germany. 1996;18:517–523. 16. Omdahl JL, DeLuca HF. Strontium induced rickets: Metabolic basis. Science 1971;174:949–951. 17. Markowitz K, Kim S. The role of selected cations in REFERENCES the desensitization of intradental nerves. Proc Finn Dent Soc 1992;88:39–54. 1. Addy M, Urquhart E. Dentine hypersensitivity: Its 18. Ernst E. Placebo: New insights into an old enigma. prevalence, aetiology and clinical management. Drug Discov Today 2007;12:413–418. Dent Update 1992;19:407–412. 19. Koshi EB, Short CA. Placebo theory and its implica- 2. Kishore A, Mehrotra KK, Saimbi CS. Effectiveness of tions for research and clinical practice: A review of desensitizing agents. J Endod 2002;28:34–35. the recent literature. Pain Pract 2007;7:4–20. 3. McGrath PA. The measurement of human pain. 20. Pearce NX, Addy M, Newcombe RG. Dentine hyper- Endod Dent Traumatol 1986;2:124–129. sensitivity: A clinical trial to compare 2 strontium 4. Addy M. Tooth brushing, tooth wear and dentine desensitizing toothpastes with a conventional fluo- hypersensitivity—Are they associated? Int Dent J ride toothpaste. J Periodontol 1994;65:113–119. 2005;55:261–267. 21. Gernhardt C, Kuß O, Schaller H. Efficacy of a stron- 5. Kielbassa AM, Attin T,Hellwig E,Schade-Brittinger C. tiumchloride containing desensitizer Hyposen [in In vivo study on the effectiveness of a laquer con- German]. Dtsch Zahnarztl Z 2005;60:509–514. taining CaF2/NaF in treating dentine hypersensitiv- 22. Silverman G, Berman E, Hanna CB, et al. Assessing ity. Clin Oral Investig 1997;1:95–99. the efficacy of three dentifrices in the treatment of 6. Kun L. Biophysical study of dental tissues under the dentinal hypersensitivity. J Am Dent Assoc 1996; effect of a local strontium application [in German]. 127:191–201. Schweiz Monatsschr Zahnheilkd 1976;86:661–676. 7. Mishima H, Sakae T, Kozawa Y. Scanning electron microscopy and energy dispersive spectroscopy analysis of calciotraumatic lines in rat labial dentin after acute exposure to strontium chloride. Scanning Microsc 1995;9:797–803.
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