ll ('l Medications, dry mouth and dental caries among older people: a longitudinal study William Murray Thomson A thesis submitted for the degree of Doctor of Philosophy Department of Dentistry The Universþ of Adelaide June 1999 l1 Table of Contents Page Abstract vl Declaration x Acknowledgments xl List of Tables xlu List of Figures X\ru 1. Review of the literature 1.1 Saliva and dry mouth I 1.1.1 The physiology of saliva secretion 1 1.1.2 Dry mouth terminology and definitions 3 1.1.3 Measuring salivary flow 4 1.1.4 Measuring xerostomia and salivary gland hypofunction 7 1.2 The role of saliva in protecting the dentition t4 1.3 Salivary fi.urction among older people 15 1.4 Medication in older populations 18 1.5 Medication and dry mouth 20 1.5.1 Capturing and anaþing medication data 20 1.5.2 Possible anaþical approaches 24 1.5.3 The challenge of poþharmacy among older people 29 1.5.4 Distinguishing the effects ofmedications and conditions 34 1.5.5 Reported associations between medications and dry mouth 36 1.6 Dental caries in older populations 40 1.6.1 Dental ca¡ies prevalence 40 1.6.2 Dental caries incidence and increment 48 1.7 Dry mouth and dental caries among older populations 53 1.8 Medication and dental caries in older populations 54 lll 1.9 Study hypotheses 56 2. Method 2.1 The general approach of the investigation 58 2.2 Sampling procedures and data collection 60 2.1.1 The Australian Longitudinal Study of Ageing (ALSA) 60 2.1.2 The South Australian Dental Longitudinal Study (SADLS) 63 2.1.2.1 Baseline recruitment of sample 63 2.1.2.2 The five-year datacollection 64 Medication recording and analysis 67 Xerostomia and hyposalivation 70 Measurement of xerostomia 70 The validation study 72 Measurement of salivary flow 73 The dental examination 74 2.1.2.3 Data analysis 82 3. Results 3.1 Baseline results (SADLS) 86 3.1.1 Participation rate and characteristics of the sample 86 3.1.2 Dental caries experience and number of missing teeth 89 3.1.3 Medication prevalence 92 3.1.4 Bivariate associations - medication and caries prevalence 95 3.1.5 Multivariate modelling of caries prevalence 100 3.2 Results at five years 105 3.2.1 Retention of the sample 105 3.2.2 Medication exposure 109 3.2.3 Exposure to cigarette smoking and alcohol 116 3.2.4 Salivary flow rate tt7 3.2.4.I Details of saliva collection 118 3.2.4.2 Flow rates and medication exposure 122 3.2.5 Xerostomia 128 3.2.5.1 The Xerostomia Inventory (XI) 128 3.2.5.2 Further testing ofthe XI - the validatíon study 133 lV 3.2.5.3 The occurrence of xerostomia 137 Prevalence 137 Severþ 144 3.2.6 Dental caries experience at five years t52 3.2.6.1 Retention of the dentate sample t52 3.2.6.2 Caries prevalence and severþ 154 3.2.6.3 Caries severity and medications 155 3.2.6.4 Five-year changes in disease experience r66 Tooth loss t66 Coronal caries 167 Root surface caries 168 3.2.7 Medications and five-year tooth loss, and dental caries 172 incidence and increment Medications and tooth loss 172 Medications and coronal caries 183 Medications and root surface caries t95 3.2.8 Summary: medications and five-year disease experience 207 4. Discussion 4.I Baseline findings 209 4.1.1 Sociodemographic characteristics and medication levels 2t0 4.1.2 Detailed medication comparisons - SADLS and ALSA 2tl 4.1.3 Duration of exposure to medications (ALSA) 215 4.1.4 Medications and caries at baseline 216 4.2 SADLS Findings at five years 2t9 4.2.1 Sample retention 2t9 4.2.3 Medications and their changes over the five-year SADLS 221 period 4.2.4 Salivary flow rate 221 4.2.5 Xerostomia 223 4.2.6 Medications and dry mouth 230 4.2.7 Dental caries experience over the five years of the SADLS 237 study ' 4.2.8 Clinical implications 247 References 249 v Appendices 1. The MedCap medication coding system 2. Medication data capture form (SADLS) 3. Xerostomia Inventory form 4. De Paola grids for tooth-surface transitions over the study period vl Abstract Much has been written about the role of certain medications as risk factors for both dry mouth and dental caries, and there has been general, uncritical acceptance of the relationship ¿rmong clinicians for many years. While there have been a number of recent reports on the association between drugs and dry moutt¡ movement towards a real consensus is slow because of methodological problems and differences among the various studies. In particular, there have been difficulties in the definition and measurement of dry mouth, and in assembling and analysing complex medication data- sets. There is currently no sound information which substantiates the medication-caries causative pathway. Consequentl¡ understanding of the putative medication/dry mouth/caries relationship is not well developed, possibly because researchers in this field face a number of difrcult challenges. First, a suitable method must be used for capturing and analysing medication data with sufficient flexibility to enable meaningful analysis. Second, the analysis should be able to take poþharmacy into account: most older people take at least one medicatiorU and the majority of those take more than one, Third, xerostomia (the subjective perception of dry mouth and its consequences) and salivary gland hypoflrnction (as measured by salivary flow rate) should be measured separately, given the possibility that they may be largely discrete conditions. Fourttr, xerostomia should be measured as a continuous variable, so that an estimate of symptom severity can be obtained for each individual, and the possibility of bias due to misclassification is minimised. Fiftb a longitudinal design should be used, so that duration (and the time-ordering) of exposure to the various medications can be examined prospectively. Finaþ, participants should (ideally) comprise a representative sample so that results can be generalised to the larger population. The purpose of the current study was to systematically explore the relationship between medications, dry mouth and dental caries in a longitudinal study of older people. The aims were: (1) to develop a flexible, numerically-based system for the capture and epidemiological analysis of medication data; (2) to develop a valid multi- item method of measuring the symptoms of xerostomia which includes the wide range of xerostomia symptoms in a single quantitative measure; (3) to examine the vll prevalence of-and concurrence between- reduced salivary flow (SGH) and the symptom of dry mouth (xerostomia); (4) to examine the association between medication exposure and unstimulated whole-salivary flow rate and xerostomia severity while adjusting for multiple medication use; and (5) to examine the association between medication exposure and disease outcomes such as tooth loss and dental caries incidence and increment over five years. Method A hierarchical, five-digit numeric system was developed to facilitate the capture and analysis of unit-record-level medication information for both the baseline and five-year data collections. In the longitudinal medication analysis, participants were designated "continuous users" for a given medication category if they had been taking it at baseline and at five years, enabling examination of the association of dry mouth and long-term exposure to medications by comparing their outcomes with those of the remainder of the sample. Confirmation of the general medication prevalence patterns observed in the SADLS study was achieved by comparison with baseline data from the Australian Longitudinal Study of Ageing (ALSA). Dry mouth was not assessed at baseline in SADLS, but was measured at five years using three methods: unstimulated salivary flow was estimated using the "spit" method (and a flow rate of less than 0.1 mVmin was used as the case definition for salivary gland hypofunction,or SGH); a standard single dry-mouth question (How often does your mouthfeet dry\; and the severity of symptoms was estimated using a new, multi-item approach. The ll-item Xerostomia Inventory was developed and tested at the five-year stage of the SADLS study in order to allow the measurement of the severity of the full range of xerostomia symptoms (both experiential and behavioural) as a continuous scale score. A smaller validation study confirmed the validity and stability of the Xerostomia Inventory (XI) by examining scores over a six-month period in two groups with divergent symptom trajectories. Because of the potential difficulties posed by poþharmacy in examing the association of medications and dry moutl¡ a two-stage anaþical approach was employed: (1) Classification and Regression Tree (CART) analysis was used as an exploratory device in order to elucidate the relationships among the dependent and independent variables; and (2) linear regression analysis was used to veriS the observed associations. Dental caries data were collected at baseline and five years VlII using standard dental epidemiological methods, and estimates of caries incidence and increment were computed by comparing caries status at baseline and at five years for each surface. Tooth-loss incidence and increment were computed using a similar method, but at a tooth-by-tooth level. Although the associations of medication and caries prevalence at baseline were examined as an exploratory study, the principal outcome variables for the investigation were (a) the incidence and increment of tooth loss, and (b) the incidence and adjusted increment of coronal and root surface caries. Multivariate models were then used to identify the medication-exposure sub-groups which had experienced most oral disease over the study period, with particular attention paid to the medication combinations which had been shown to be associated with dry mouth, Results Medication data were available for 704 individuals at five ye¿us, of whom 528 were dentate and dentaþ examined.