QUINTESSENCE INTERNATIONAL Etiologic factors of hyposalivation and consequences for oral health Peter Tschoppe, Dr Med Dent1/Michael Wolgin, Dr Med Dent2/ Nicole Pischon, Dr Med Dent Habil2/ Andrej M. Kielbassa, Dr Med Dent Habil3 Hyposalivation is represented by a reduced salivary flow rate and can be caused by etiolog- ic factors such as systemic diseases and intake of various medications or by radiotherapy following head and neck cancer. The aim of this review was to compile data about the qualitative and quantitative changes of salivary components during hyposalivation, and to summarize their consequences for oral health. A Medline/PubMed/Scopus search was con- ducted to identify and summarize articles published in English and German that reported on etiology of hyposalivation and changes in the salivary composition due to hyposalivation of different origins. The search revealed 94 articles, 71 of which were original articles. Apart from the reduction of the salivary flow rate, the quality of saliva is strongly altered because of systemic diseases, medications, and radiotherapy, including increased viscosity and pH shift to more acidic values and changes in salivary protein compositions. Furthermore, hypo - salivation may be accompanied by pronounced shifts in specific microbial components, in particular toward a highly acidogenic microflora. Moreover, therapy of hyposalivation is often restricted to palliative treatment (ie, saliva substitutes or gels). To prevent tooth tissue de - mineralization, clinicians should consider saliva substitutes that are supersaturated with calcium and phosphates and contain fluoride. (Quintessence Int 2010;41:321–333) Key words: caries, drugs, hyposalivation, microflora, periodontitis, radiotherapy, saliva substitutes, Sjögren syndrome, xerostomia Physiologic amounts of salivary secretion are tion.2 Furthermore, this fluid is implicated in a essential for oral health.1 Saliva influences wide variety of digestive events including various events in the oral cavity such as lubrication of mucosa, bolus formation, and caries protective, digestive, and immunologic enzymatic digestion of food.3 Saliva’s protec- processes. The ability to promote remineral- tive role to the human organism is exhibited ization and to reduce demineralization by delivering antimicrobial peptides and pro- makes saliva a major player in caries protec- teins to the oral epithelium.4 Saliva is predominately secreted from three major paired salivary glands: parotid, sublingual, and submandibular (in all, about 1Assistant Professor, Department of Operative Dentistry and 90% of the total saliva production).3 In addi- Periodontology, CharitéCentrum 3, University School for Dental Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. tion, hundreds of minor salivary glands (eg, 2Lecturer, Department of Operative Dentistry and Periodon - buccal, labial, palatal), which are spread over tology, CharitéCentrum 3, University School for Dental all parts of the oral mucosa, contribute to Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. secretion of saliva. Regulation of salivary 3Professor and Head, Department of Operative Dentistry and secretion is reflex controlled by both the sym- Periodontology, CharitéCentrum 3, University School for Dental pathetic and parasympathetic divisions of Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. the autonomic nervous system.5 The impuls- Correspondence: Dr Michael Wolgin, Abteilung für Zahnerhaltungskunde und Parodontologie, CharitéCentrum 3 es, induced by action of gustation, mastica- für Zahn-, Mund- und Kieferheilkunde, Charité- tion, or smell are forwarded from afferent Universitätsmedizin Berlin, Assmannshauser Strasse 4-6, 14197 receptors to the salivary nuclei (salivation Berlin, Deutschland. Fax: 49 30 450 562 932. Email: michael. 3 [email protected] center) in the medulla oblongata. The VOLUME 41 • NUMBER 4 • APRIL 2010 321 © 2009 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER. QUINTESSENCE INTERNATIONAL Tschoppe et al amounts of organic nonprotein compounds Table 1 Reference points for unstimulated (UWS) and stimulated (SWS) whole saliva in such as uric, amino, or fatty acids, and glu- adults7,9 cose can be also detected in saliva.7 More than 309 proteins, which include acidic and UWS SWS basic proline-rich proteins, amylase, high- Hypersalivation > 1.0 mL/min > 3.5 mL/min and low-molecular-weight glycoproteins, Normal salivation 0.1–1.0 mL/min 0.5–3.5 mL/min agglutinin, cystatins, histatins and statherin, Hyposalivation < 0.1 mL/min < 0.5 mL/min could be identified in saliva.10 Salivary pro- teins have a wide range of functional proper- ties. Different groups of saliva proteins take part in immunologic reactions (lysozyme, parasympathetic and sympathetic nerve lactoferrin, lactoperoxidase, immu no globulin, bundles, which separately innervate the sali- defensin),7,11–13 taste perception (carbonic vary glands, form the efferent part of the anhydrase),7 digestion (amylase),7 and many secretory reflex arch by using acetylcholine other processes in the oral cavity. Saliva con- as neurotransmitter.5 tains steroid; nonsteroid; protein; and peptide Saliva contains two major types of protein hormones, such as cortisol, testosterone, secretion: amylase-containing serous and progesterone, estradiol, and aldosterone.7 mucin-containing mucous secretion. The Numerous studies have shown correlations enzyme amylase takes part in initial diges- between serum and saliva levels of different tion, while mucin assists in lubrication and hormones.14–16 The measurement of salivary serves to protect oral surfaces. The physical hormones for diagnostic aims is a widely and chemical characteristics of saliva vary in accepted, noninvasive, and stress-free different salivary glands. The sublingual method compared to plasma and serum col- glands produce mucin-rich viscous saliva; in lection.7,16–18 contrast, the serous parotid glands secrete a The purpose of the present review is to watery, amylase-rich fluid.6 summarize what is known about the qualita- The daily secretion of saliva normally tive and quantitative changes of salivary com- ranges between 1.0 and 1.5 L at a rate of on ponents during hyposalivation and to dis- average 0.5 mL/min (normal salivation; Table cuss the possibilities of their rational therapy. 1).7 The decreased flow of saliva is termed hyposalivation (hypoptyalism), which can be caused by water/metabolite loss, damage of salivary glands and interference with neural DATA SOURCES transmission (see Table 1). Common reasons AND STUDY SELECTION of decreased salivary secretion could be chron- ic inflammation of the salivary glands, Sjögren A search of Medline/PubMed/Scopus data- syndrome, radiation treatment, dehydration, bases for articles written in English and psychologic factors, and medications.5,8 The German from March to May 2009 was per- increase of saliva is termed hypersalivation formed. The following primary key words/ (see Table 1). Hypersalivation has an phrases were used in the search strategy: unknown origin; however, hypersalivation was hyposalivation / dry mouth / xerostomia / described in patients with herpetic stomatitis, saliva composition / qualitative changes / aphthous stomatitis, ulcerative gingivitis, and quantitative changes / drugs / age / systemic those who wear dentures.9 diseases, disorders / Sjögren syndrome / The various components of saliva are Sicca syndrome / radiation, radiotherapy / organic and inorganic substances, proteins/ cariogenic microflora / periodontopathogen- poly peptides, hormones, and lipid mole- ic microflora / oral health. These terms were cules. Whole saliva is composed mostly of used alone or were combined with each water, which contains ions, such as sodium, other. A few older and/or basic references potassium, magnesium, calcium, chloride, were obtained by hand search and cross-ref- carbonate, and phosphate ions.7 Small erencing from the available literature. 322 VOLUME 41 • NUMBER 4 • APRIL 2010 © 2009 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART OF THIS ARTICLE MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER. QUINTESSENCE INTERNATIONAL Tschoppe et al The authors examined the results returned by the Medline/PubMed/Scopus search to identify potentially relevant ication A ed ge abstracts. Publications that did not report M ? about etiology of hyposalivation or changes in salivary composition due to hyposalivation icho l Ant Deh of different origins were not further consid- a rgic y- t o line drati n th cts on e a c ffe N ered. Finally, 94 full-text articles were select- p ti e eu s m e r m y s o e S im t p p c a s s m fe t ed, 71 of which were original. o h d r f l u e y o s y i n e a r c a s h a a v c i e a l s v d e n i n a l n g l e g a D a p g s l e A a f g s y r o L i y e n Hyposalivation m f v s i i l p o l t l t r h e a a e s a s t t g s i i a e y o c ETIOLOGY OF v f n m p F a d o ib D o a p r lo n r a o b e HYPOSALIVATION Ir re si o r n s o n i h e ch f atio t t v ym Degener c o e a ells ru i rs of gland c t d ib es a Hyposalivation represents a reduced saliva le d R or temporary flow rate, and diagnosis of hyposalivation e can be made by means of saliva flow rate as ise measurements. The saliva flow rate varies ic d stem from person to person and is influenced by a Sy large number of factors, such as degree of hydration, body position, exposure to light, Fig 1 Various possible etiologic factors of hyposalivation. previous stimulation, circadian rhythms, or gland size.10 However, when the conditions during sampling of saliva are uniform, the flow is remarkably stable for every individual.