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Abstract

Dental clinicians are confronted with an increasing number of medically compromised patients who require implant surgery for their oral rehabilitation. However, there are few guidelines on dental implant therapy in this patient category, so that numerous issues regarding pre- and post-operative management remain unclear to the dental clinician. Therefore, the aim of the present review is to offer a critical evaluation of the literature and to provide the clinician with scientifically based data for implant therapy in the medically compromised patient. This review presents the current knowledge regarding the influence of the most common systemic and local diseases on the outcome of dental implant therapy, e.g., abnormalities in bone metabolism, diabetes mellitus, xerostomia, and ectodermal dysplasias. Specific pathophysiologic aspects of the above-mentioned diseases as well as their potential implications for implant success are critically appraised. In line with these implications, guidelines for pre- and post-operative management that may assist in the successful implant-supported rehabilitation of this patient category are proposed.

(I) Introduction

Treatment of partial and total edentulism with dental implants has evolved into a predictable procedure for the majority of patients and is expected to play a significant role in oral rehabilitation in the future. The long-term outcome studies which are now available for many of the implant techniques used indicate that successful integration and restoration of implants are now the expected therapeutic outcome. Today, in the general population, long-term success rates of over 90% to 95% are considered to be realistic treatment outcomes (Arvidson et al., 1992; Fugazzotto et al., 1993; Mericske-Stern and Zarb, 1993; Spiekermann et al., 1995). However, clinicians must temper their enthusiasm for implant dentistry with thorough knowledge and understanding of the physiologic implications of existing systemic diseases or systemic therapies for treatment outcome and patient well-being. In line with these implications, endosseous implant therapy can greatly improve the function and esthetics of carefully selected partially or completely edentulous patients. Before any form of endosseous implant therapy is considered in any patient, the medical history must be thoroughly reviewed and, if appropriate, a physical examination performed. An existing systemic disease or ongoing systemic therapy may complicate or contra-indicate implant dentistry. An increased knowledge of the underlying disease process has improved the management of patients suffering from bone metabolism abnormalities, diabetes mellitus, xerostomia, and ectodermal dysplasias. This review aims to compile and critically discuss current knowledge of the clinically relevant impact of the most common systemic diseases on the success of implant therapy. We have classified the clinical studies presented here according to the ranking system of the NHS Research and Development Centre of Evidence-Based Medicine. This system proposes different levels of evidence (LE), ranging from the lowest level (LE 5, corresponding to an expert’s opinion without explicit critical appraisal) to the best achievable level (LE 1, corresponding to information based on a systematic review) of evidence (for further information, see NHS Research and Development Centre of Evidence-Based Medicine, 2002). Issues regarding pre-treatment evaluation and post-treatment maintenance protocols for general dental implant patients are beyond the scope of this review and are discussed elsewhere (Hillenburg et al., 1991; Meffert, 1994; Lord, 1995; Lang et al., 1996; Silverstein et al., 1998; Beikler and Flemmig, 2001). Moreover, the treatment of peri-implant complications (e.g., peri-mucositis, peri-implantitis) is not discussed here but has been reviewed elsewhere (Mombelli and Lang, 1992; Jovanovic, 1994; Meffert, 1994, 1996; Mombelli, 1997; Beikler and Flemmig, 2001).

(II) Metabolic Bone Disease

Bone mass depends on the equilibrium between bone formation and resorption within a remodeling unit, as well as on the number of remodeling units activated within a given period of time in a defined area of bone. Any changes in the rates of formation and resorption that result in bone resorption exceeding bone formation can cause a decrease in bone mass (Krane and Holick, 1991). Deposition of bone during periodontal regeneration for the purpose of supporting dental implants, however, may depend upon cellular mechanisms that are determined, in part, by systemic, i.e., genetic, molecular, or pharmacological factors associated with low bone mass (Garnero and Delmas, 1997). Some but not all of these factors can be modified. Age and sex represent major non-modifiable risk factors for low bone mass, whereas smoking, alcohol, certain medications, nutrition, and exercise may be modifiable.

(A) Classification of osteoporosis

Osteoporosis is a skeletal condition characterized by decreased mineral density (mass/volume unit) of normally mineralized bone (Glaser and Kaplan, 1997). The World Health Organization has established diagnostic criteria for osteoporosis based on bone density measurements determined by dual-energy x-ray absorptiometry (World Health Organisation, 1994). According to these criteria, a patient is classified as having low bone mass, e.g., osteopenia, if the bone mineral density measures between 1 and 2.5 standard deviations below the mean of a young population. Osteoporosis, however, has been defined as a bone mineral density level of 2.5 standard deviations or below from the mean of a young population (World Health Organisation, 1994; Glaser and Kaplan, 1997). It has been classified into two categories, primary and secondary osteoporosis (Krane and Holick, 1991; Glaser and Kaplan, 1997). Primary osteoporosis is further divided into three types: post-menopausal osteoporosis (type I), age-related osteoporosis (type II), and idiopathic osteoporosis (type III). Secondary osteoporosis refers to those patients in whom a causative factor or disease can be identified (see Fig. 1).

Approximately three-quarters of post-menopausal women and men over 50 years old lose post-cranial bone through bone demineralization at the rate of 1 to 2% per year. The remaining one-quarter of the population loses bone rapidly, with a rate of bone demineralization of about 5 to 8% per year (Elders et al., 1988; von Wowern et al., 1994; Hildebolt, 1997). In the United States, according to the WHO criteria, from 13 to 18% of women aged 50 or older have osteoporosis, and another 37 to 50% have osteopenia. This translates into 4 to 6 million women with osteoporosis and 13 to 17 million with osteopenia; in men over age 50, the corresponding numbers are 1 to 2 million with osteoporosis and 4 to 9 million with osteopenia (Looker et al., 1997). Due to the increasing life expectancy in developed countries, the number of osteoporotic or osteopenic individuals is likely to undergo a further increase (Lugero et al., 2000) and is, therefore, of increasing relevance to implant therapy in an aging population.

(B) The influence of metabolic bone disease on mandibular and maxillary bone

The concern that dental implants are at an increased risk for failure in osteoporotic patients is based on the assumption that the impaired bone metabolism affects the mandible or maxilla in a manner similar to its effects on other bones (Mori et al., 1997). However, since a potential relationship between osteoporosis and decreased oral bone mass or density is controversial (Krolner and Nielson, 1982; Kribbs et al., 1989; Kribbs, 1990; Payne et al., 1999), it is actually not easy to assess whether bone quantity and quality in the mandible and maxilla parallel those in the rest of the skeleton (Mori et al., 1997; Heersche et al., 1998). This problem is due to the fact that reported studies have been preliminary, most of them having involved small numbers of subjects, biased sample selection, and differing definitions and measurements of bone loss (i.e., interchangeable use of the terms “bone mass” and “bone density”) and osteoporosis, as well as to the cross-sectional nature of the study design (Hildebolt ,1997; Jeffcoat et al., 2000).

Another matter of concern is the assumption that impaired bone metabolism as it occurs in osteoporosis may affect osseointegration of implants (Mori et al., 1997). A more detailed look at the process of bone remodeling reveals that it is a non-uniform process. This process of bone remodeling differs from one bone to another, between cortical and trabecular bone, and from one trabecular bone site to another (Heersche et al., 1998). In contrast to cortical bone, trabecular bone is much more affected by metabolic changes of the skeleton and is lost at an annual rate of 0.7% and 1.2% in males and pre-menopausal females, respectively (Cann et al., 1985). After menopause, the decrease in cortical and trabecular bone density accelerates to 1% and 6%, respectively, i.e., the decrease in trabecular bone density after menopause exceeds that of cortical bone (Wakley and Baylink, 1987). For this reason, bone like the maxilla, which consists largely of trabecular bone, is more susceptible to rapid and severe atrophy under conditions of disuse and/or metabolic demand for calcium (Roberts et al., 1992) than the mandible, which consists primarily of cortical bone. However, the observation that osteoporotic fractures usually heal readily suggests that the repair process in osteoporotic patients remains satisfactory and less susceptible to endocrine regulation (Dao et al., 1993), thus indicating that bone remodeling processes after implant placement in osteoporotic patients may also not differ fundamentally from those seen in healthy patients.

(C) Dental implants and metabolic bone disease

Very few investigators have studied dental implants in individuals with metabolic bone disease, especially osteoporosis (Fujimoto et al., 1996). Case reports have indicated that dental implants can be successfully placed in osteoporotic patients (LE 4; Fujimoto et al., 1996). Implant success has been reported in glucocorticoid-dependent patients (LE 4; Steiner and Ramp, 1990; Cranin, 1991), even in those with steroid-induced osteoporosis, as well as in patients suffering from severe osteoporosis and chronic polyarthritis (LE 4; Friberg, 1994; Eder and Watzek, 1999).

However, following maxillary sinus augmentation, there is a significantly reduced implant success rate when there is a reduced relative bone mass density as compared with age- and sex-matched control patients treated by the same procedure (LE 3B; Blomqvist et al., 1996). Also, in women without estrogen supplementation, there is an increased failure rate for implants placed in the maxilla (LE 3B; August et al., 2001). However, in post-menopausal women receiving hormone replacement therapy, there is no significant difference in implant success rates as compared with women without hormone replacement therapy (LE 4; Minsk and Polson, 1998). The findings of this study support the assumption that osteoporosis does not necessarily rule out the use of endosseous implants, since all women, regardless of osteoporotic or hormone replacement status, had similar outcomes following dental implant treatment (Minsk and Polson, 1998).

Reports on osseointegration in animals with osteopenia or osteoporosis are as rare as human studies. In calcium-deficient rats (Nasu et al., 1998) and rabbits with steroid-induced osteoporosis (Fujimoto et al., 1998), osseointegration was found to occur around implants. Moreover, in osteoporotic rabbits, considerable bone contact with implants occurred, despite the fact that new bone formation around implants was delayed (Mori et al., 1997). It is noteworthy, however, that, under persistent calcium deficiency, the bone mass surrounding the implants decreased significantly (Nasu et al., 1998; Pan et al., 2000). In steroid-induced osteoporosis in rabbits, the trabecular volume and mineral apposition rates were found to be significantly reduced compared with those of healthy control animals (Lugero et al., 2000). In rats that had undergone ovariectomy, the cortical bone area in contact with the implant was only slightly decreased in comparison with the control sham-operated group (Pan et al., 2000). However, both the bone volume around the implant and the implant-bone contact were significantly decreased in the cancellous bone (Pan et al., 2000).

Cyclosporin A, a potent inhibitor of T-helper lymphocyte proliferation, is widely used after organ transplantation and has shown promise in the treatment of various autoimmune diseases (Kahan, 1989). Besides the other well-known adverse effects of cyclosporin A, post-transplantation osteoporosis is frequently observed (Guo et al., 1998) and has been reported to occur in 24% of cases in the first 3 months post-surgically (McDonald et al., 1991). In addition, in vivo studies indicate that cyclosporin A accelerates bone remodeling and results in bone loss (Schlosberg et al., 1989; Fu et al., 2001). In cyclosporin-A-treated rabbits, a significant decrease in the bone area next to the implant was recorded, whereas the degree of bone-to-implant contact was comparable in test and control groups (Duarte et al., 2001). However, from a clinical point of view, patients under cyclosporin A medication may not be considered ideal candidates for implant therapy due to their suspected compromised general health and immune status. Although human case reports and animal studies indicate that implant therapy is successful in osteoporotic subjects, the success rates are still unclear.

(D) Special considerations for implant therapy in patients with metabolic bone disease

It appears prudent for clinicians to adhere to the following guidelines when oral implants are to be placed in osteoporotic patients (see Fig. 2):

Prior to implant surgery, a careful assessment of nutrition and systemic health in patients at risk for metabolic bone disease is recommended (Cooper, 2000). Patients should undergo an endocrinologic, orthopedic, or obstetric examination and be treated, if necessary. Physiological doses of vitamin D (from 400 to 800 IU/day) and calcium (1500 mg/day) are recommended during the post-operative period (Cooper, 2000). In all cases, a balanced pre-operative and post-operative diet should be recommended. Patients should attempt to give up smoking, since smoking is an important risk factor for osteoporosis (Melton, 1997) and implant failure (Bain and Moy, 1993).

In cases of insufficient bone volume, the implant sites should be augmented before or during implant surgery (Nasu et al., 1998). Various bone augmentation methods are available (Hermann and Buser, 1996; Tatum, 1996; Harris, 1997; Weber et al., 1997; Rissolo and Bennett, 1998). In addition, the occlusal load should be properly distributed throughout the dentition to avoid overloading the implant, which may contribute to implant loss. The healing period should be extended by 2 months, i.e., 8 vs. 6 months in the maxilla and 6 vs. 4 months in the mandible (Fujimoto et al., 1996; Lugero et al., 2000) before construction of the prosthodontic appliance.

Preference should be given to implant designs that will have close bone-implant contact on insertion to ensure primary stabilization in less dense osteoporotic bone. In contrast to the concept of early mobilization in orthopedic treatment of fractures in osteoporotic patients, aimed at improving bone formation by mechanical stimulation, there is actually no precedent for advocating immediate or “provisional” loading of dental implants to enhance osteogenesis in osteoporotic bone (Cooper, 2000). If accelerated peri-implant bone loss with no clinical signs of peri-implant disease occurs during the maintenance phase, the patient should be examined for occlusal overload and referred to a medical specialist, e.g., an endocrinologist, for re-evaluation of the osteoporotic/osteopenic therapy regimen.

(III) Diabetes Mellitus

The prevalence of diagnosed diabetes mellitus (DM) in 1988–1994 was estimated at 5.1% for US adults over 20 years of age (10.2 million people when extrapolated to the 1997 US population). According to American Diabetes Association criteria, the prevalence of undiagnosed DM was 2.7% (5.4 million) (Harris et al., 1998). Thus, DM is one of the most frequent metabolic disorders, affecting an estimated 15.3 million individuals in the US. Among men and women over 65 years of age, where the prevalence of edentulism is highest, an estimated 18.4% of all individuals have some form of diabetes (Balshi and Wolfinger, 1999). Furthermore, analysis of recent data indicates that the incidence of the most common type of diabetes mellitus, i.e., type 2, may be increasing by up to 6% per year, with more than 500,000 new cases diagnosed annually (Rees, 2000). Analysis of the epidemiological data regarding diabetes mellitus indicates that all dentists will encounter patients with diabetes mellitus and that clinicians who perform intra-oral surgery, such as implant placement, should have a thorough knowledge of this disease.

Diabetes mellitus is associated with a wide range of systemic complications such as retinopathy, nephropathy, neuropathy, micro- and macrovascular disease, and altered wound healing (Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 1997). In the oral cavity, diabetes mellitus is associated with xerostomia, increased levels of salivary glucose, swelling of the parotid gland, and an increased incidence of caries and periodontitis (Murrah, 1985; Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 1997; Rees, 2000). The risk for developing periodontitis in type 2 diabetics is 2.9 to 3.4 times higher than in non-diabetics (Klokkevold, 1999). Although there has been some conflicting evidence, this increased susceptibility to periodontitis may be due to inadequately controlled or non-controlled diabetic patients being more prone to infection (Larkin et al., 1985) due to compromised host defense systems, e.g., significantly lower chemotaxis, phagocytosis, and decreased bacterial killing of PMNs (Wilson and Reeves, 1986; Delamaire et al., 1997; Geerlings and Hoepelman, 1999). In addition, microvascular disease may adversely affect the blood supply and also contribute to the high susceptibility of diabetics to infection (Larkin et al., 1985; el Askary et al., 1999).

(A) Effect of diabetes mellitus on the healing response to dental implants

Although there are various reports on bone formation in diabetic patients, only animal studies have addressed the impact of diabetes on the healing response to endosseous implants (Nevins et al., 1998; Takeshita et al., 1998; Fiorellini et al., 1999; McCracken et al., 2000). In diabetic animal models, bone-to-implant contact has been shown to be significantly reduced compared with that in non-diabetic controls (Nevins et al., 1998; Takeshita et al., 1998; Fiorellini et al., 1999). Also, the bone density adjacent to the implant in uncontrolled diabetic animals was found to be slightly, though not statistically significantly, lower than or similar to that of control animals (Nevins et al., 1998; Gerritsen et al., 2000). In insulin-controlled diabetic animals, however, the bone density was greater than that in non-diabetic control animals (Fiorellini et al., 1999). Although the total bone-to-implant contact was lower in diabetic than in non-diabetic rats, osseointegration was reduced primarily in the trabecular bone, whereas no differences were seen in the cortical bone (Iyama et al., 1997; McCracken et al., 2000). Analysis of these data indicates that, although the healing process in uncontrolled diabetic animals is impaired, osseointegration can occur, especially when initial bone contact is present (McCracken et al., 2000). It appears that osseointegration is more predictable in areas with abundant cortical bone, i.e., the mandible, than in the maxilla, where trabecular bone prevails. However, more detailed well-controlled pre-clinical and clinical studies in man are needed to determine the biological pathways that may affect osseointegration in diabetic patients.

(B) Dental implants in patients with diabetes mellitus

Several studies have specifically addressed the failure rate of dental implants in the diabetic patient. In various retrospective studies (LE 4—Balshi and Wolfinger, 1999; Fiorellini et al., 2000; Smith et al., 1992; LE 3B—Kapur et al., 1998), the observed implant success rates ranged from 85.6% (Fiorellini et al., 2000) to 94.3% (Balshi and Wolfinger, 1999). Data from a meta-analysis of two implant systems placed in edentulous mandibles revealed an early implant failure rate of 3.2%, whereas late failures (from 45 months to 9.5 years) increased by between 5.2 and 5.4% (Esposito et al., 1997).

A prospective study of 89 well-controlled type 2 diabetic patients with 178 dental implants placed in the mandible revealed an early failure rate of 2.2% after implants were uncovered and a failure rate of 7.3% one year after implantation (LE 3B; Shernoff et al., 1994). The five-year results of that prospective study revealed a survival rate of 90% (Olson et al., 2000). It is noteworthy, however, that statistical analysis of the data revealed that fasting plasma glucose and HbA_1c values at baseline and follow-up (when implants were uncovered), subject’s age, baseline diabetic therapy, and smoking history were not statistically significant predictors of implant success or failure (Olson et al., 2000).

Fiorellini et al.(2000) also failed to show any association between dental implant loss and patient gender, age, positive smoking history, type and level of diabetic control, type of prosthesis, implant length, implant system, or implant position (LE 4). To what extent the duration of diabetes mellitus is associated with implant failure needs to be elucidated, since the present data are equivocal (Fiorellini et al., 2000; Olson et al., 2000).

It is interesting, however, that various reports indicate an increased failure rate after about one year (LE 4—Fiorellini et al., 2000; LE 1B—Morris et al., 2000; LE 3B—Shernoff et al., 1994), suggesting that the risk for implant failure is associated with the uncovering of implants and with the early phase of implant loading. This suggests that the microvascular disease leading to a diminished immune response and reduced bone turnover might be a contributing factor to implant failure (Olson et al., 2000), and that diabetes is one of several risk factors for implants that had survived until prosthetic loading (Morris et al., 2000).

(C) Special considerations for implant therapy in patients with diabetes mellitus

Although dental implant therapy seems to be a helpful tool in restoring the dental status of diabetic patients, it appears prudent for clinicians to adhere to the following guidelines:

Patients who do not demonstrate strict metabolic control should be examined for the causative mechanism, and the glycemic control should be re-assessed and optimized prior to implant surgery (see Fig. 3). A glycosylated hemoglobin level around 7 mg/% seems to be sufficient for safe elective surgery (Blanchaert, 1998). However, dental implant surgery should be performed only by operators experienced in the management of possible peri- and post-operative complications, e.g., hypoglycemic crisis during surgery (Blanchaert, 1998).

Although the use of pre- or peri-operative antibiotic prophylaxis in implant dentistry in systemically healthy patients is controversial, there is general agreement in advocating the use of antibiotics in compromised, e.g., diabetic, patients undergoing implant therapy (Blanchaert, 1998; Balshi and Wolfinger, 1999; Morris et al., 2000). In implant surgery, streptococci, anaerobic Gram-positive cocci, and anaerobic Gram-negative rods are the pathogens most likely to cause post-operative wound-healing problems (for overview, see Dent et al., 1997; Beikler and Flemmig, 2001). Thus, the antibiotic selected for prophylaxis should be bactericidal and of low toxicity, e.g., penicillin or amoxicillin (Garg, 1992; Sbordone et al., 1995). In cases of penicillin allergy, clindamycin, metronidazole, or a first-generation cephalosporin may be an alternative choice (Peterson, 1990; Garg, 1992). A first-generation cephalosporin is recommended, however, only if the patient’s allergic reaction to penicillin is not anaphylactic (Peterson, 1990). If antibiotics are given for the prophylaxis of post-operative wound infection, it is highly recommended that the first dose be administered pre-operatively (e.g., for penicillin V PO, 1 hr pre-op) (Burke, 1961; Dajani et al., 1997), so that sufficient antibiotic tissue concentrations cna be achieved during surgery.

Besides antibiotic prophylaxis, it has been reported that the use of a chlorhexidine digluconate (0.12%) rinse at the time of placement reduced the failure rate from 13.5% to a remarkable 4.4% in type 2 diabetic patients (LE 3B; Morris et al., 2000). Therefore, it seems prudent for clinicians to use chlorhexidine rinses peri- and post-operatively at the time of implant placement.

Hydroxyapatite plasma-spray-coated implants have been found to have a higher survival rate than titanium implants in type 2 diabetic patients, i.e., 97.9% vs. 84.7% after 36 months (Morris et al., 2000). This is noteworthy, since hydroxyapatite (HA) plasma-spray-coated implants are more susceptible to failure through microbial contamination, dissolution, and fracture of the HA from the titanium surface (Johnson, 1992). Therefore, long-term studies are needed to evaluate the success of HA-coated implants in diabetic patients.

The placement of dental implants in diabetic patients remains controversial. Definitive guidelines with objective criteria, including type of diabetes, age at onset, and level of long-term metabolic control, have not yet been determined. Screening for diabetes and ensuring that implant patients are under good metabolic control are recommended to increase the chances of successful osseointegration. Poorly controlled diabetic patients are more difficult to manage, and a delay in surgery is recommended until better control is achieved (Smith et al., 1992). The placement of dental implants in patients with metabolically controlled diabetes appears to be just as successful as in the general population (Proceedings of the 1996 World Workshop in Periodontics, 1996).

(IV) Xerostomia

There are numerous pathologic conditions that are accompanied by reduced salivary flow (see Fig. 4), e.g., after therapeutic head and neck irradiation (Guchelaar et al., 1997; Fox, 1998), autoimmune diseases (Gonzales and Coleman, 1999) such as Sjögren’s syndrome (Boutsi et al., 2000), systemic lupus erythematosus (Rhodus and Johnson, 1990), progressive systemic sclerosis (Osial et al., 1983; Wood and Lee, 1988), primary or secondary amyloidosis (al Hashimi et al., 1987; Richey and Bennion, 1996), sarcoidosis (Drosos et al., 1989; Sack et al., 1998), infectious diseases such as HIV (Kordossis et al., 1998) and hepatitis C (al Hashimi, 2001), or diabetes mellitus (Darnell and Saunders, 1990; Rees, 2000), and can be induced by over 400 drugs, including tricyclic antidepressants, antihistamines, and diuretics (Sreebny and Schwartz, 1997). The most prominent causes of reduced salivary flow are therapeutic pharmaceutical side-effects (Schein et al., 1999).

(A) Influence of reduced saliva flow on intra-oral infections

A decrease in salivary flow rate can also be accompanied by a change in salivary composition. Alterations include a decrease in ptyalin content or an increase in mucin content, with the saliva becoming more viscous and ropy, thus contributing to plaque formation. These changes and the reduced antibacterial action of the saliva itself lead to a favorable environment for the growth of bacteria (Garg, 1992; al Hashimi, 2001) and to decreased bacterial clearance in the oral cavity (Melvin, 1991). An increased incidence of cervical and root caries has been reported as a major dental problem in patients with Sjögren’s syndrome (MacFarlane and Mason, 1974; Atkinson and Fox, 1993; Boutsi et al., 2000).

The relationship between salivary flow and periodontal disease is controversial, and the few studies that have investigated the periodontal status of patients with xerostomia have reported conflicting results (Tseng et al., 1990; Tseng, 1991; Najera et al., 1997; Boutsi et al., 2000).

In addition to bacterial infections, patients with xerostomia often suffer from fungal infections, e.g., recurrent oral candidiasis (al Hashimi, 2001), mostly characterized by angular cheilitis (19–35%) and acute erythematous candidiasis (38–65%) rather than by a pseudomembranous coating on the oral mucosa (Rhodus et al., 1997; Soto-Rojas et al., 1998). Patients wearing implant-supported overdentures should be instructed to take the dentures out at night, since candida species can lodge in the denture acrylate (van der Reijden et al., 1999). In cases with clinical manifestations of oral candidiasis, dentures should be cleaned in 0.2% chlorhexidine solution overnight or with a 1% chlorhexidine gel two times a day. Oral candidiasis can be further treated with a nystatin suspension (100,000 units/mL at 2–5 mL four times daily for 2 min each) or nystatin troches (200,000 units/troche four times per day) for two weeks (Pallasch, 2002). In cases of refractory candidiasis, amphotericin B lozenges (10 mg) may be used four times a day for two weeks (Budtz-Jørgensen and Lombardi, 1996). When using suspensions or lozenges, the patient has to be instructed to remove the dentures while undergoing treatment, to allow the active ingredient to reach all the tissues. Quantitative assays of candida in the oral cavity, along with cytology, can be useful in monitoring responses to antifungal therapy. Successful treatment would be expected to result in a decrease in fungal colonies from between 10,000 and 20,000 cfu/mL to a few hundred (Farah et al., 2000).

The adhesive action of a thin film of saliva between a denture base and the underlying soft tissues is considered to be one of the principal retention factors in conventional removable partial dentures (al Hashimi, 2001). In xerostomia, the lack of adhesive function can preclude the development and maintenance of an effective denture seal and can have an adverse effect on successful prosthetic reconstruction (Blanchaert, 1998). Moreover, the risk of candidiasis developing is higher in patients wearing removable dentures (Budtz-Jørgensen, 1974; Budtz-Jørgensen and Lombardi, 1996). Accordingly, in patients with severe xerostomia, fixed implant-supported bridges may be the preferred treatment modality (Esposito et al., 1998).

(B) Special considerations for implant therapy in patients with xerostomia

To date, there have been only a few reports on the use of implants in patients with xerostomia. These case reports indicate that these patients can be successfully treated with osseointegrated implants (Binon and Fowler, 1993; Payne et al., 1997). Since no clinical trials have been performed with dental implants in xerostomia patients, knowledge of patients’ susceptibility to peri-implantitis cannot be determined.

When implants are considered to be viable therapeutic options in patients with xerostomia, it seems prudent for clinicians to adhere to the following guidelines (see Fig. 5):

Prior to implant placement, the underlying cause of the xerostomia needs to be properly diagnosed and treated. Any oral bacterial infections such as periodontitis, caries, or fungal infections such as candidiasis should be thoroughly treated prior to implant placement. After implant placement, maintenance intervals should be shortened to prevent the development of peri-implantitis due to the increased plaque formation in these patients.

Although a sufficient flow of saliva appears desirable, it is often difficult to achieve, depending on the cause and the remaining functional exocrinic units. Stimulation of salivary flow can be achieved by either physiological or pharmacological means. Physiological stimulation can be accomplished by gustatory and masticatory stimuli, such as sugar-free chewing gum. The benefit of saliva substitutes is limited and brief. However, some patients might benefit from these substances. For pharmacological stimulation, cholinergic agonists, e.g., pilocarpine and cevimeline, may be used. Common side-effects include those of other cholinergic medications, e.g., gastrointestinal disorders, sweating, tachycardia, bradycardia, increased pulmonary secretions, increased smooth-muscle tone, and blurred vision (Grisius, 2001). Contra-indications for these drugs include gall bladder disease, glaucoma, acute iritis, and renal colic (Grisius, 2001). Due to its mild β-adrenergic activity, pilocarpine is contra-indicated for individuals with heart disease, asthma, angina pectoris, chronic bronchitis, chronic obstructive pulmonary disease, or a history of myocardial infarction (Grisius, 2001). In contrast to the non-selective muscarinic agonist pilocarpine, cevimeline is believed to bind more specifically to the M1 and M3 receptors (the muscarinic receptor family consists of five subtypes, M1-M5) that predominate in the secretory glands, and not as much to M2 and M4 receptors, which primarily effect the cardiovascular and respiratory systems (Ship et al., 2002). Cevimeline reportedly has a 40-fold greater affinity for M3 receptors than does pilocarpine (Iwabuchi et al., 1994; Iwabuchi and Masuhara, 1994). It is important to note, however, that there are no reports supporting the theory that side-effects of cevimeline are less severe than those of pilocarpine, or that medically compromised individuals tolerate cevimeline better.

(V) Ectodermal Dysplasias

Ectodermal dysplasias (ED) represent a rare group of inherited disorders that occur in approximately 1 per 100,000 live births (Clarke, 1987). To date, more than 170 different pathologic clinical conditions have been recognized and defined as ED (Pinheiro and Freire-Maia, 1994, 1996). From a clinical point of view, EDs have been divided into two broad categories: an X-linked hypohydrotic form (Christ-Siemens-Touraine syndrome), characterized by the classical triad of hypodontia, hypohydrosis, and hypotrichosis and by characteristic facial features such as prominent supraorbital ridges, frontal bossing, and a depressed nasal bridge (Kearns et al., 1999); and an autosomal inherited hydrotic form (Clouston’s syndrome) that usually spares the sweat glands but affects teeth, hair, and nails (Kearns et al., 1999).

(A) Dental implants in patients with ectodermal dysplasia

In patients with ED, abnormal dentition with hypodontia or, more rarely, anodontia is the most common intra-oral feature. Some reports suggest that the most common complaint in childhood and adolescence is concern about abnormalities and facial appearance (Siegel and Potsic, 1990). Dental treatment aimed at functional, esthetic, and psychological rehabilitation is therefore an essential part of the management of ED and should start early in the patient’s life (Bergendal et al., 1991). The principal aims of dental treatment are to restore missing teeth and bone, establish a normal vertical dimension, and provide support for the facial soft tissues (Kearns et al., 1999). Conventional prosthodontic treatment (complete dentures, overdentures, or a combination of bridgework and removable partial dentures) often faces severe problems due to anatomical abnormalities of existing teeth and alveolar ridges, resulting in poor retention and instability of prostheses (Dhanrajani and Jiffry, 1998; Kearns et al., 1999). The shortcomings of removable prostheses, furthermore, include dental hygiene problems, speech difficulties, and dietary limitations (Dhanrajani and Jiffry, 1998). Moreover, progressive resorption of basal bone when the edentulous ridge is loaded at an early age may even aggravate the problem.

In ED patients ranging from 13 to 69 years of age, a 90% success rate has been reported for second-stage implant surgery (LE 4; Guckes et al., 1991). However, in the latter study, data on success rates in correlation to the patients’ ages and on the sample size were missing. Over a three-year observation period, in 52 patients between 7 and 68 years old, implant success rates were 87% in pre-adolescents (ages 7–11), 90% in adolescents (ages 12–17), and 97% in adults (older than 17) (Guckes et al., 1998).

In children with ED where no success can be achieved with conventional prosthetic appliances, implant therapy appears to be a viable option. Although there are only a few case reports in the literature about implants in children with ectodermal dysplasias, these reports indicate that implants are a successful adjunct to oral rehabilitation (LE 4; Bergendal et al., 1991; Smith et al., 1993; Davarpanah et al., 1997; Guckes et al., 1997; Ekstrand and Thomsson, 1988). In that context, stable implant conditions were reported after an observation period of 4 to 5.5 years in children with ectodermal dysplasia (LE 4; Bergendal et al., 1991; Smith et al., 1993; Guckes et al., 1997; Escobar and Epker, 1998).

Even the successful installation of dental implants for up to 4.5 years in one adult edentulous patient with Papillon-Lefèvre syndrome has been reported (LE 4; Ullbro et al., 2000). This is noteworthy, since these patients suffer from severe aggressive periodontitis, and implants would also be assumed to be at high risk for peri-implant infection. The reason for this successful treatment outcome might be that the periodontal infection has been successfully treated, or that all teeth have been lost (Tinanoff et al., 1986; Bullon et al., 1993; Ullbro et al., 2000). However, although there are no reports to date on dental implants in children with Papillon-Lefèvre syndrome, from a clinical-periodontal point of view, the treatment outcome of dental implants in these patients appears to be highly questionable and unpredictable.

(B) Special considerations for implant therapy in patients with ectodermal dysplasia

There are only a very few long-term reports of implant therapy in children with ectodermal dysplasia and its effects on the development of the maxillofacial structures. Therefore, it is recommended that implant installation be postponed whenever possible until the patient’s skeletal and dental growth has been completed (Bergendal et al., 1996; Dietschi and Schatz, 1997; Percinoto et al., 2001) (see Fig. 6).

Possible consequences of implant placement in the growing patient include movement of the implant, resulting in its being submerged or exposed, and limitations of jaw growth (in cases of a rigid prosthesis that crosses the midline) (Oesterle et al., 1993; Cronin and Oesterle, 1998; Dhanrajani and Jiffry, 1998). In particular, maxillary transverse growth at the midpalatal suture has been suggested to be adversely affected by rigid prosthetic devices (Oesterle et al., 1993). To avoid this potential interference with transverse maxillary growth, investigators have proposed dividing prosthetic bar attachments that cross the maxillary midline (Kearns et al., 1999). Since the transverse growth at the mandibular symphyseal suture usually ceases in the first 6 months, no interference with transverse mandibular growth is to be expected when implants are installed in the anterior mandible (Kearns et al., 1999).

The ankylotic nature of endosteal implants can lead to pseudopockets around the implants (Kraut, 1996), which may encourage peri-implant infections. Therefore, it seems prudent to shorten maintenance intervals to avoid peri-implant disease. In the edentulous child, implants may have high success rates (Kearns et al., 1999). However, it must be borne in mind that implants placed in girls after 15 and in boys after 18 years of age have a better prognosis than those in younger children (Oesterle et al., 1993; Cronin and Oesterle, 1998). Therefore, a risk/benefit assessment must be made for each individual, to optimize dental rehabilitation (Kraut, 1996). Further, if implants are considered in a young patient with ED, the patient’s skeletal and dental maturity, not chronological age, should be the determining factor for the time of implant placement (Dhanrajani and Jiffry, 1998). Parents should be informed about possible complications.

The published reports about implant application in young patients are as yet very limited, and long-term clinical studies are necessary to permit sound conclusions to be drawn. However, in adult patients with ED, implant therapy may be a viable option for dental rehabilitation.

(VI) Directions for Future Research

Although basic research and animal studies provide valuable and important information that serves in the formulation of clinical hypotheses, the proven correlations that exist between their results and clinicians’ ability to predict clinical treatment outcome are limited. For appraisal of the limits and options of dental implants in the medically compromised patient, additional reliable, clinically relevant, information is needed. However, most of the cited clinical studies do not adhere to the principles of good clinical practice. Therefore, well-controlled, randomized, prospective longitudinal trials that include a sufficient number of patients are urgently needed. Based on sound clinical evidence, more detailed guidelines can be developed that may aid in the improved predictability of dental implants in the special-patient category.

Figure 1.
Classification of osteoporosis (Wakley and Baylink, 1987; Glaser and Kaplan, 1997).

Figure 2.
Special considerations for dental implant therapy in patients with bone metabolic diseases.

Figure 3.
Special considerations for dental implant therapy in patients with diabetes mellitus.

Figure 4.
Causes of salivary hypofunction and xerostomia (modified from Sreebny and Schwartz (1997).

Figure 5.
Special considerations for dental implant therapy in patients with xerostomia.

Figure 6.
Special considerations for dental implant therapy in patients with ectodermal dysplasia.

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