Introduction

For centuries, dental practitioners have relied on partial dentures, complete dentures, and fixed prosthesis (such as bridges) for the replacement of missing teeth. Dental implants have revolutionized modern clinical practice and are a contemporary substitute to such traditional fixed and removable dental prosthesis. It is well known that dental implants can osseointegrate and remain functionally and aesthetically stable over long durations in patients with missing teeth. Studies have reported high success and survival rates of dental implants in systemically healthy individuals; however, dental implant therapy has also been reported to be successful among patients with systemic disorders, such as diabetes mellitus and acquired immune deficiency syndrome (AIDS). This chapter provides essential information on the osseointegration and survival of dental implants in medically challenged patients. In the present chapter, an evidence‐based approach was adopted to identify original research studies that had assessed the success and/or survival of dental implants in patients with systemic diseases. In this chapter, we compiled original studies from indexed databases (including PubMed, MEDLINE, OVID, ISI Web of Knowledge, Scopus, and EMBASE) with reference to their impact/influence on the survival and success of dental implants. These studies have formulated into individual subheadings focusing on specific focused questions and data has been presented using a systematic review approach. The content of this chapter is arranged on evidence‐based dental implant therapy among patients with systemic diseases. Moreover, each sub‐category discusses the outcomes of the respective studies and recommendations for future research are also presented.

Dental Implants in Patients with Diabetes Mellitus

It is well known that systemic disorders, such as poorly‐controlled diabetes mellitus (DM), jeopardize periodontal health and are also a significant risk factor for dental implant failure [1–3]. One explanation for this is that chronic hyperglycemia increases the formation and accumulation of glucose‐mediated advanced‐glycation‐end‐products (AGEs) in the periodontal and systemic tissues in patients with poorly controlled DM [4, 5]. These AGEs play a role in the pathogenesis and altered periodontal wound healing by activating the receptors for AGEs (RAGE) located on the periodontium [5] (Figure 24.1). In addition, it has been reported that endothelial cells take up glucose passively in an insulin‐independent manner, thereby causing tissue damage [6]. Also, chronic hyperglycemia has also been associated with alterations in host resistance by defective migration of polymorphonuclear leukocytes, impairment in phagocytosis, and exaggeration in inflammatory response to microbial products [7]. These factors may also be held responsible for the increase prevalence of peri‐implant diseases (peri‐implant mucositis and peri‐implantitis) in patients with poorly controlled DM as compared to non‐diabetic controls [8, 9]

On the contrary, glycemic control in patients diagnosed with DM has been reported to improve the overall health status [10]. Studies have reported that dental implants and osseointegrate and remain functionally stable in patients with well‐controlled DM in a manner contrast to patients with a poor metabolic control of DM [11–13]. For example, in a clinical study by Tawil et al. [11], implant survival rates were comparable among patients with well‐controlled diabetes and nondiabetic controls. Likewise, in an experimental study, Casap et al. [14] assessed the osseointegration of implant discs placed in tibial medullary spaces of 140 male diabetic and control rats. Histomorphometric results showed significantly higher trabecular bone volumes among controls and rats with well‐controlled diabetes, as compared to those with poorly‐controlled diabetes. Similar results were reported by de Molon et al. [15] A strict glycemic control has also been shown to reduce microvascular complications in diabetes [16]. It has been reported that maintenance of serum glycemic levels may help to improve the function of osteoblasts, and the progression of periodontal bone loss is markedly reduced in subjects with well‐controlled diabetes compared to individuals with poorly controlled diabetes in subjects with diabetes [17]. The serum and GCF concentrations of proinflammatory cytokines are also significantly reduced in subjects with well‐controlled diabetes compared to individuals with poorly controlled diabetes [18, 19]. Therefore, under optimal glycemic control, diabetic subjects can have a periodontal bone height similar to that of healthy individuals.

Although maintenance of serum glycemic levels plays an important role in successful osseointegration, there are other factors that may also assist in enhancing the implant survival rates in diabetic patients. Maintenance of periodontal healthy environment is essential for successful dental implant treatment [20]. Dental plaque is a major etiological factor in periodontal destruction and studies have reported higher scores of plaque index, BOP, and PPD in diabetic patients compared to nondiabetic controls [3, 21]. It has been reported that inflammatory periodontal diseases may increase insulin resistance in a way similar to obesity, thereby aggravating glycemic control [20]. Inflammatory reactions in the peri‐implant tissues have been associated with the presence of dental plaque around implants [22]. Periodontal therapy has been shown to improve glycemic control in hyperglycemic patients [23]. In high‐fat‐fed diabetic rats, periodontitis accelerated the onset of severe insulin resistance and impaired glucose homeostasis [24]. Therefore, control and treatment of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients and consequently could play an important role in the success of implant therapy.

The routine use of antibiotics in oral implantology is widespread; however, there is a controversy over the use of antimicrobial agents in healthy candidates for dental implant therapy [25]. In diabetic patients undergoing implant surgery, the use of antimicrobial agents reduces the risk of surgical wound infection and improves the implant survival rate. It has been shown that a preoperative antibiotic cover in diabetic patients improves the implant survival rate by 10.5% compared to healthy candidates for implants (improvement with antibiotics was 4.5%) [26]. In another study, data for 2973 implants were investigated with reference to success of osseointegration at different stages of implant treatment [27]. The results showed that at each stage of treatment, the implant survival rate was notably higher in subjects, who had received preoperative antibiotics [27]. It has been reported that the use of chlorhexidine mouth‐rinse is effective at reducing the viability of Porphyromonas gingivalis infection and peri‐implant mucositis [28]. A twice‐daily use of an antiseptic mouthwash has been suggested for the maintenance of dental implants [29]. In conclusion, dental implants can osseointegrate and remain functionally stable in patients with DM provided the glycemic levels are maintained. Nevertheless, the role of routine dental hygiene maintenance and regular dental checkups in this regard should not be overlooked.

Dental Implants in Patients with Cardiovascular Diseases

Cardiovascular diseases (CVD) are a group of diseases that include atherosclerosis, congestive heart failure, coronary artery disease, hypertension, and vascular stenosis. It has been proposed that restricted supply of oxygen and nutrients to tissues may negatively affect osseointegration in patients with CVD [30]. To our knowledge from indexed literature, only a limited number of studies have assessed the influence of CVD on osseointegration of dental implants [31]. It has been reported that the risk of stroke is 80% higher for nonsmoking patients with up to 24 teeth as compared to individuals who had 25 or more teeth [32]. Likewise, results from another study reported an association to exist between periodontitis and increased risk of ischemic stroke compared with patients without periodontitis, gingivitis, or tooth loss [33]. The correlation between periodontitis and CVD has several possible pathophysiologic links. An increased systemic burden of bacteria, endotoxin, and other bacterial products could induce an abundant production of proinflammatory cytokines, cause inflammatory cell proliferation into large arteries, and increase the production of clotting factors (such as fibrinogen) through the liver, which may contribute to atherogenesis and thromboembolic events [34, 35]. Moreover, periodontopathogenic microbes may induce platelet aggregation that may be thrombogenic when entering the systemic circulation as in periodontitis [36, 37]. Furthermore, bacterial toxins (lipopolysaccharides) may also damage the endothelial cells by attacking the arterial lining [38]. These results indicate that there is a relationship between periodontitis and CVD. Since a previous history of periodontitis is a significant risk factor for peri‐implant diseases [39], it is hypothesized the outcome of dental implant therapy is compromised in patients with CVD compared with systemically healthy controls.

Results from a retrospective analysis of patients with certain types of CVD showed no statistically significant difference in the implant failure rates among patients with and without CVD [31]. This study concluded that patients with controlled CVD are not at an increased risk of failure of osseointegration [31]. In another retrospective study, influence of CVD on implant failure, up to one week after the second stage of surgery was evaluated [40]. The results showed that there was no statistically significant association between CVD and failure of osseointegration [40]. Alsaadi and co‐workers [41] CVD were not associated with an increased incidence of early implant failures. In another retrospective analysis, the authors reported that CVD such as hypertension and ischemic heart diseases are not significantly associated with early implant loss [42]. Although results from a publication showed that a history of CVD is associated with dental implant failure [43]; it has also been reported that oral rehabilitation with dental implants among patients with or without CVD is a valid treatment [44]. Table 24.1 summarizes the outcomes of studies that have assess the influence of CVD on the survival of dental implants. In conclusion, it seems that dental implants can osseointegrate and remain functionally stable in patients with CVD; however, further long‐term follow‐up studies are needed in this regard.

Dental Implants in Patients with Hepatic Disorders

Aspartate aminotransferase (AST) is a pyridoxal phosphate‐dependent transaminase enzyme, which plays an essential role in the metabolism of amino acids [45]. AST is mainly found in the liver but is also present in other tissues including heart, red blood cells, and skeletal muscles. When body tissue or an organ such as the liver is diseased, additional AST is released into the bloodstream, thereby elevating its levels. In this regard, assessment of AST levels is commonly performed for the diagnosis of hepatic disorders [45, 46]. Elevated AST levels in the saliva and gingival crevicular fluid have been associated with periodontal inflammatory parameters (probing depth and gingival bleeding) [47, 48]. It has been reported that salivary AST levels are significantly higher in patients with chronic periodontitis (CP) [49]; however, mechanical debridement of plaque and calculus from teeth surfaces results in a statistically significant decrease in salivary AST levels in patients with CP [49]. Similarly, increased AST activity in the peri‐implant sulcular fluid, have been associated with peri‐implant bleeding on probing and bone loss [50, 51]. Since levels of AST in blood are significantly higher in patients with hepatic disorders and that increased AST activity has been associated with periodontal and peri‐implant diseases [49], it is hypothesized that the outcomes of implant therapy are compromised in patients with hepatic disorders. Following a vigilant review of pertinent indexed literature, no studies that had assessed the influence of hepatic disorders on the success and survival of dental implants were identified. However, it is imperative to interpret this outcome with caution as the possible contribution of elevated AST levels toward the initiation and progression of peri‐implant diseases (peri‐implant mucositis and peri‐implantitis) cannot be disregarded.

Dental Implants in Patients with Psychological Disorders

It has been reported that scores of periodontal inflammatory parameters (including bleeding on probing, probing depth, and dental calculus index) are poorer among patients with psychiatric disorders, such as schizophrenia and mood disorders [52]. Porphyromonas gingivalis (P. gingivalis) (a classical microbe associated with the etiology of periodontal disease) can transmigrate to the brain and modulate an innate inflammatory response [53]. In patients with Alzheimer’s disease, P. gingivalis inhibits the local interferon‐gamma response by preventing entry of immune cells into the brain [54]. Moreover, an increased number of missing teeth has also been associated with an increased incidence and prevalence of dementia [55]. Since patients with psychological/psychiatric disorders are more susceptible to periodontal disease [52, 55]; it is hypothesized that the outcome of dental implant therapy is compromised in patients with psychological/psychiatric disorders as compared to healthy individuals.

A limited number of studies have assessed the success and survival of dental implants in patients with psychological/psychiatric disorders [56–61]. In the retrospective study, personal grief and depression were nominated as significant risk‐factors associated with dental implant failure [56]. In the study by Addy et al. [58], dental implant retained prostheses were provided to 3 patients with psychiatric disorders. The study concluded that psychiatric disorders are not a contraindication to dental implant therapy [58]. Results from a five‐year follow‐up study showed that dental implant retained prosthesis can remain functionally stable in patients with Schizophrenia [59]. Similarly, results from another case report showed successful implant surgery in the maxilla in a 72‐year‐old patient with Parkinson’s disease; however, follow‐up results were not reported in this study [61]. On the contrary, in another case report, Kromminga et al. [60] concluded that outcomes of dental implant therapy are compromised among patients with psychological disorders.

The literature with respect to the success and survival of dental implants in patients with psychiatric/psychological diseases is sparse and inconsistent. However, poor oral hygiene status, oral parafunctional habits such as bruxism, habits such as repeated insertion of fingers in the mouth and behavioral issues are common in patients with psychiatric/psychological diseases. Such factors may complicate dental implant therapy in these patients and jeopardize the long‐term success and survival of dental implants.

Dental Implants in Patients with HIV/Acquired Immune Deficiency Syndrome

In a mono‐centric study, 66 HIV‐infected patients with a stable disease with good oral hygiene, requiring implant rehabilitation, were included [62]. In this study, each patient received at least 1 dental implant with a total of 190 implants placed in the study population. The primary outcome variables were implanting failure, prosthetic failure, peri‐implant marginal bone loss, and biological complications including peri‐implantitis, pus discharge, pain, and paresthesia [62]. The peri‐implant status was assessed at the time in intervention and after 12 months of follow‐up. At follow‐up, there was no evidence of fractures of fixtures or paresthesia and implant failure occurred in patients (15 out of the 190 fixtures) [62]. The study concluded that dental implant therapy is a suitable therapeutic strategy for oral rehabilitation in HIV‐infected patients provided the disease is well‐controlled and appropriate infection control protocols are adopted [62]. Similar results were reported in another study [63]. In total, 13 studies were identified [62–74]. The study participants ranged between 1 and 68 patients and the duration of follow‐up ranged between 4 weeks and 10 years. Results from nearly 50% of the studies were based on case reports and case series [65–67,71–74]. All studies reported that dental implants can remain functionally stable in HIV‐positive patients with stable disease (Table 24.2). There is insufficient evidence to determine whether in the long‐term, dental implants can remain functionally stable in HIV+ patients and patients with AIDS. Hence, further studies are warranted in this regard.