Cataldo W. Leone, D.M.D., D.M.Sc., and Frank G. Oppenheim, D.M.D., Ph.D.:
Dental caries remains a widely prevalent bacterial infection despite tremendous advances in prevention and treatment, and continues to comprise a significant portion of total U.S. expenditures on health care. Why caries continues to be a major public health problem remains an unanswered question, but insight may be gained through assessment of the risk factors associated with the disease. The etiology and pathogenesis of dental caries are known to be multifactorial, but the interplay between intrinsic and extrinsic factors is still not fully understood. As in other host/parasite interactions, there appear to be marked variations in individual susceptibility to the disease. It therefore appears that intrinsic host factors play a key role in modulating the initiation and progression of caries. This report offers a critical evaluation of the role and effects of saliva in caries pathogenesis.
The general question addressed is: Is there clinical evidence that saliva has a protective effect against caries? Such an evaluation is complicated by the fact that saliva is a complex body fluid whose clinical and physical properties show considerable intra- and intersubject variability. In addition, a number of medical conditions lead to salivary alterations which, in turn, may increase the risk for caries. To develop a comprehensive search strategy, we addressed the following questions:
- Are individuals with altered salivary physiology at increased risk for dental carious lesions compared with individuals of the same age and dentition with normal salivary physiology?
- Are individuals with altered electrolyte biochemistry in saliva at increased risk for dental carious lesions compared with individuals of the same age and dentition with normal electrolyte biochemistry?
- Are individuals with altered macromolecules in saliva at increased risk for dental carious lesions compared with individuals of the same age and dentition with normal salivary macromolecular composition?
- Are individuals with medical conditions or diseases that affect saliva at increased risk for dental carious lesions compared with individuals of the same age and dentition who do not have such conditions/diseases?
To deal with these questions, we conducted a broad-based search in the MEDLINE and EMBASE databases to ensure that we found all potentially relevant information in English. Search dates depended on the database, but ranged from 1970 to August, 2000. One broad caries hedge was used with each of four saliva hedges developed for the four questions. This resulted in the retrieval of eight sets of literature and a total of 3,086 articles. In addition, we conducted hand searches of bibliographies and abstracts that were not retrieved initially (IADR/AADR, ICOB, ORCA). We also sought opinions and guidance from experts in the field.
Selection and Exclusion Criteria
Abstracts were then handscreened by one reviewer to identify duplicates and to exclude articles clearly inappropriate to our review (e.g., caries or salivary status not clearly defined). The literature sets were then merged into one new set of about 600 abstracts. Full-length articles were subjected to a second round of screening with additional inclusion criteria, resulting in the final number of articles formally reviewed and included in the evidence table. The additional criteria were English-language articles reporting original in vivo studies with a defined control group between 1986 and August, 2000, with >30 subjects. All longitudinal studies meeting these criteria were included. Otherwise, only articles satisfying AHRQ level II-3 or above were included. Consequently, purely descriptive studies of large subject populations were excluded from the evidence table, but they are described in the evidence report. Articles or portions of articles which dealt with salivary microbiology, fluoride treatment, or food and nutrition factors were deemed beyond the scope of the present review.
Data Collection and Analysis
We developed an extraction form to ensure complete and consistent collection and abstraction of data. This form was used to facilitate calibration and to produce a preliminary evidence table. Once agreement between the extractors was attained, data from the articles were entered directly into the evidence table. Two persons independently abstracted data from each article. Data were synthesized descriptively according to (1) general description; (2) experimental design; (3) caries status assessments; (4) saliva status assessments; and (5) clinical evidence for the presence or absence of a protective effect of saliva against caries. We focused on both quantitative and qualitative aspects of saliva to evaluate the relationship between caries and salivary status. Salivary parameters deemed important were salivary flow rate, buffer capacity, and the amounts of salivary constituents belonging to the immune and nonimmune defense systems. The data were not further analyzed quantitatively, and no meta-analysis was conducted.
The preponderance of the literature supports the belief that a normal salivary flow rate imparts a strong protective effect against caries. This effect remains consistent, for the most part, regardless of salivary source (whole saliva or glandular secretions) or stimulation status (stimulated or unstimulated; masticatory or gustatory stimulation). Significantly diminished salivary flow rate, on the other hand, is associated with a number of predisposing medical conditions, reflecting either the predisposing medical condition itself (e.g., Sjogren�s syndrome) or treatment of the condition (e.g., head and neck radiation; medications exhibiting xerostomic side effects). The overall result points clearly toward salivary gland hypofunction causing lowered secretion rates; this, in turn, tends to increase the caries risk. There is little evidence to suggest that normal healthy individuals have idiopathic alterations in salivary secretion rates.
There also is reasonably good evidence of protection against caries because of salivary buffering capacity. This parameter is usually measured using a salivary pH endpoint in acid-base titrations. Individuals with a lower (i.e., more acidic pH) value are deemed to have diminished buffer capacity, and they seem to be at increased risk for caries. The literature is somewhat unclear on this characteristic, however, because buffering capacity involves extrinsic factors, such as dietary and oral hygiene habits, as well as intrinsic factors, such as salivary bicarbonate content. As a consequence, buffer capacity appears to be a weak-to-moderate predictor of caries risk when considered as a single independent variable.
Surprisingly, the literature was almost equally divided for or against the protective role of salivary immunoglobulins, especially secretory IgA. Studies evaluating caries risk in subjects with humoral immunodeficiency do not report a consistent pattern. Some immunodeficient individuals appear to have increased susceptibility, while others demonstrate one or more compensatory salivary mechanisms (both immune and nonimmune) which may obviate any increased caries risk.
Finally, there is insufficient evidence on whether other physico-chemical characteristics of saliva provide a protective effect against caries. A small number of articles suggest that certain components of saliva are protective (e.g., salivary peroxidase, lysozyme, lactoferrin, histatins, and other antimicrobial proteins), but these associations have not been well-demonstrated. Large intra- and intersubject variability is a recurring issue, and it is not clear if this reflects human variation or limitations in experimental approaches.
Saliva provides a general protective function for exposed oral hard tissues, such as enamel and dentin, and a clinically significant decrease in salivary flow can be considered an etiologic factor contributing to caries risk. Consequently, clinicians should identify individuals with reduced salivary output and modify their treatment and prevention programs in ways that diminish the risk of caries. To a lesser degree of certainty, it can be concluded that individuals whose salivary buffering capacity is reduced are at higher caries risk. Thus, the general salivary parameters of flow rate and buffer capacity are clinically useful diagnostic indicators.
No convincing evidence is presently available, however, that other biological characteristics of saliva are useful in predicting an increased risk of caries. The role of the salivary immune and nonimmune systems remains uncertain, but it is likely that further research in this area will clarify such issues.