Successful dental implant therapy relies on a bone—implant interface that is mechanically strong and capable of dynamic remodeling in response to functional loads. There are a number of medical conditions or therapies that can affect either bone metabolism or the resistance of bone to infection. However, their effects are often mitigated by local factors or individual responses so the impact of these conditions is not clear-cut. This article will review a number of these conditions and therapies and describe existing studies that have studied these conditions to guide practitioners in their implant practice.
Key points
- •
Implant’s long-term survival and medical status.
- •
Implant success rate and medical status.
- •
Implant’s long-term survival and systemic diseases.
- •
Implant success rate and systemic diseases.
Introduction
The long-term success of implants is the result of successful osteointegration—continued remodeling of bone and soft tissue around the implant—and the maintenance and health of a soft tissue seal around the emerging implant components. A number of diseases or therapies can affect any of these processes. However, whether they consistently affect the survival of implants is influenced by a number of individual factors such as extent of a disease, dosage and duration of therapy, and personal response to treatment, and these are responsible for the variable results reported in different studies. This article will discuss major categories of disease or therapies that have been associated with decreased implant longevity and suggest possible reasons for these observations. However, as will be seen, the effect of both disease and therapy is not clear-cut and in many situations, their metabolic impact is theoretic and conflicting results are described.
Gastroesophageal reflux disease and proton pump inhibitor use
Proton pump inhibitors (PPIs) are a group of drugs used to reduce the clinical manifestations of gastroesophageal reflux disease or acid reflux. Chronic use of PPIs has been linked to decreased integration and longevity of dental implants through 3 possible mechanisms: decreased bone density, reduced absorption of nutrients, and changes in oral microbiota. Chronic use of PPIs leads to an increase in gastrin levels, which leads to an increase in the secretion of parathyroid hormone (PTH), responsible for maintaining serum calcium levels by increasing the resorption of bone by stimulating osteoclasts. This may impact bone density due to persistent resorption of bone.
Decreasing gastric acid changes the gastric pH, which has been shown to increase the proliferation of gut microbiota and the quantity and type of oral bacteria, leading to increased susceptibility to periodontal and peri-implant pathology. It also decreases the absorption of vitamin B12, magnesium, iron, and, especially, calcium. ,
Multiple studies have evaluated the relationship between chronic PPI consumption and dental implant failure rates and an association between PPI use and increased risk for implant failure has been identified. Failure rates range from 6.8% to 19.3% for PPI users versus 3.2% to 14.3% for non-users. One of the studies estimated the failure rate to be 4.30 times higher for PPI users than non-users. Ursomanno, in 2020, suggested that PPIs were associated with greater loss of crystallized bone formation around implants examined by radiographs.
In 2022, a systematic critical appraisal was performed to evaluate the influence of PPI on tissue attachment around teeth and dental implants. The data were insufficient to perform a meta-analysis or systematic review and PPIs may exert a protective effect on periodontal tissues. However, a systematic appraisal from 2024 concluded prolonged PPI usage increases the risk of dental implant failure. Given this conclusion, surgeons should consider asking the primary care providers for alternative medications such as histamine 2-receptor antagonists or over-the-counter antacids, in patients at a higher risk for implant failure. Patients might also taper their use once symptoms resolve. Since chronic PPI use is considered a risk factor for implant success, more frequent maintenance visits should be recommended. Prospective clinical trials are needed to increase our understanding of the association between chronic use of PPIs, dental implants, and bone density, and the impact of dose, duration, and individual characteristics on implant success.
Inflammatory bowel disease
Inflammatory bowel disease (IBD) is a term that includes 2 separate conditions: Crohn’s disease (CD) and ulcerative colitis (UC). The suggested mechanisms how IBD possibly compromises integration and longevity of dental implants are multiple. Secondary to inflammation, the underlying disease can trigger an increased basal cytokine response that affects the oral biome in favor of anerobic, gram-negative organisms that can be harmful to the oral and periodontal tissues. , Malnutrition can also affect the quantity and quality of bone formation and thereby integration and longevity of dental implants. In addition, increased concentrations of inflammatory factors play a destructive role in regular bone metabolism, changing the pattern of bone resorption and apposition and leading to osteoporosis. , Finally, antigen-bound antibodies present in IBD can modify the process of osseointegration.
Medications to treat IBD can also affect bone metabolism. Monoclonal antibodies have been implicated in medicine-related osteonecrosis of the jaws (MRONJ), while immunosuppressant therapy increase the risk of postoperative infections, and long-term use of corticosteroids plays an important role in UC bone loss. ,
In 2019, a systematic review and meta-analysis by Duttenhoefer and colleagues evaluated dental implants in immunocompromized patients, including CD. Two prospective and 2 retrospective studies were included. The pooled odds ratio from these studies was 8.12 with a 95% confidence interval, which suggests that CD has a significant effect on early implant failure resulting in an increase, but not statistically significant, implant loss. There were no conclusions on the longevity of implants. The data for UC are unavailable so no conclusions can be derived. Based on this systematic review, when recommending implant therapy to IBD patients, a multidisciplinary approach should be adopted so that the therapeutic side effects are taken into consideration and weighed against the success of implant placement. There is no clear conclusion about the effects of IBD and implant therapy. More prospective clinical studies are needed.
Selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors (SSRIs) as a medication class is used to treat psychiatric and nonpsychiatric conditions such as depression, anxiety, post-traumatic stress disorder, migraine headaches, and fibromyalgia. Serotonin receptors are widely distributed throughout the body, including within bone. With an estimated nearly 1 in 5 patients over age 60 taking SSRIs, it is important to consider the implications SSRI use has on dental implant longevity.
Serotonin receptors are present in osteoblasts and osteoclasts. By antagonizing the serotonin receptor, SSRI’s cause increased osteoclast differentiation while simultaneously decreasing osteoblast differentiation. Moderately strong retrospective cohort studies (Level 4) demonstrate lower dental implant survival rates at 90 mo post placement in patients taking SSRI’s. In a 20-year retrospective cohort study, Carr and colleagues divided patients into those with a history of SSRI use, those taking SSRI’s at time of implant placement and use of SSRI’s during the post-operative period. The SSRIs evaluated were citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline. It was found that patients who had a preoperative history of sertraline use were 60% more likely to experience implant failure compared to patients without history of SSRI use.
Further investigation is necessary to ascertain the direct effects of SSRIs on osseointegration in short-term and long-term implant stability. Duration of SSRI therapy and dose should be evaluated in the future.
Diabetes
Diabetes is a metabolic disease manifesting as impaired blood glucose control secondary to underproduction or insensitivity to insulin. The association between diabetes and periodontal disease is well-documented. Multiple systematic reviews have explored the survival rate of dental implants in diabetics compared to nondiabetic patients. In 2019, a systematic review by Souto-Malor and collegaues found no difference in implant survival rate between diabetic and nondiabetic patients. This was further explored in 2022 by Wagner, who also demonstrated no significant difference in survival rates in the first few years. However, long-term survival was lower in diabetic patients. There was no difference in short- or long-term implant survival in prediabetics compared to controls, but these data were derived from only 2 studies. Limited data exist related to implant survival in type I diabetics. However, one study did evaluate implant failure in this population and found no difference in failure rates.
A prospective cohort study by Oates and colleagues assessed dental implant survival 1 y after loading in diabetic patients with varying degrees of glycemic control. Patients were grouped based on HbA1c levels, including a poorly controlled group, with HbA1c greater than 8.1%. Dental implants were placed in edentulous patients’ anterior mandibles and restored with overdentures. Patients were evaluated at 3, 6, and 12 mo after loading. It was found that there was no difference in implant survival among diabetic groups compared to control. An additional observational cohort study evaluated posterior mandibular implants placed in patients with HbA1c ranging from 8% to 12%. These patients received single-unit fixed restorations and were evaluated at 2 mo, 4 mo,1 y, and 2 y post-operation. They demonstrated a 96.2% survival rate at 2 y. This is one of the few studies aimed at following patients with known elevated HbA1c and implant placement. All patients in both studies received antibiotics 1-w post-operation and chlorhexidine gluconate 0.12% oral rinses 1 to 2 w post-operation.
While overall survival appears to be similar between diabetic and nondiabetic patients, it was found that diabetic patients have statistically significantly increased marginal bone loss. ,
It appears that much of the data regarding dental implants in diabetic patients are mixed. It is difficult to differentiate between patients with a spectrum of glucose control, but in general, well-controlled diabetic patients have similar outcomes to patients without diabetes. Most studies have relatively short follow-up windows, and further studies are needed to better characterize longer-term implant survival, complications, post-operative antibiotic use, and implant loading guidelines.
Human immunodeficiency virus
Human immunodeficiency virus (HIV) infection is a global pandemic with a worldwide public health impact. HIV targets and destroys CD4 helper lymphocyte cells in the immune system, making affected individuals more susceptible to opportunistic infections. Currently, there are 7 classes of drugs to treat HIV infection. The treatment for HIV infection—also referred to as Highly Active Antiretroviral Therapy (HAART) —has transformed the disease from an acute life-threatening condition to a manageable chronic or long-term disease. Consequently, patients with HIV who are being treated with HAART increasingly need functional and esthetic dental care.
HIV infection or some of the drugs used in HAART regimen (tenofovir disoproxil fumarate and protease inhibitors) have been associated with osteoporosis and osteopenia in the long-term. Other than that, there is little else known about this relationship.
However, a systematic review and meta-analysis by Sivakumar and colleagues in 2021 with a minimum follow-up of 6 mo, and a mean follow-up of 2.8 y calculated weighted implant survival values as 95.54% and 95.39%, respectively. These results are equivalent to systematic reviews on the survival of implants in healthy populations (96.4%). The review also found a study that reported a significant increase in implant failure rate when the CD4 was less than 200 cells/mm 3 . However, others did not report any significant correlation between implant success and CD4 cell count or viral load. ,
Duttenhoefer and colleagues in 2019 evaluated the relationship between HIV and dental implants in a systematic review and meta-analysis. In the 4 prospective studies, with 1 controlled study, none of the authors found significant correlations between HIV-related immunodeficiency and implant failure. Survival rates between 90.1% and 100% have been reported at an average follow-up of 31.7 mo. ,
Olivera and colleagues, in 2020, followed HIV patients with dental implants after functional loading for 12 y. They concluded that dental implant treatment in HIV-positive patients achieved long-term survival, with a success rate comparable with that observed in healthy patients.
The data in the literature clearly shows that implant placement and rehabilitation are not a contraindication for HIV-positive patients, and the survival rates of implants in HIV-positive patients are similar to those in HIV-negative patients.
Osteoporosis
Osteoporosis is defined as a loss in bone mineral density, most commonly measured by a dual-energy X-ray absorptiometry scan. The results from this radiographic examination are expressed as a T score and a normal value is 0. Less than −2.5 standard deviations traditionally measured at the lumbar spine and femoral neck is considered abnormal with an increased incidence of fractures. Osteoporosis affects much of the aging population, especially post-menopausal women. A change in bone architecture and trabeculation raises concern that the quality of bone in osteoporotic patients may affect implant survival in the long- and short-term.
However, a meta-analysis conducted by de Medeiros found that implants placed in patients with osteoporosis and osteopenia had no difference in survival longevity. This study identified a statistically significant difference in marginal bone height but not necessarily implant stability. A similar systematic review conducted by Lemos evaluated bone loss in patients with osteoporosis and at 1 y, marginal bone loss was significantly increased in the osteoporosis group (1.03 mm) compared with the control group (0.44 mm), but this degree of bone loss was not clinically significant, defined as 1.2 mm or more.
Another study evaluating osseointegration at a histologic level in osteoporotic patients revealed no difference in osseointegration at a microscopic level.
Currently, there are no randomized controlled trials available to compare outcomes and our meta-analyses reported here consist of level 1 evidence. Based on these findings, there is no evidence to support osteoporosis as a contraindication for dental implants. There is some evidence to support that people with low bone density may benefit from modified implant placement techniques such as under-drilling apically and the use of “soft bone” protocols, although further scientific evaluation is necessary.
Antiresorptive therapy
A significant number of diseases affect the balance of bone resorption and bone formation, such as osteoporosis, Paget’s disease, metastatic bone disease, multiple myeloma, and rheumatoid arthritis. Medications that alter bone metabolism, mainly agents that counteract bone resorption known as antiresorptive drugs, are on the rise. Antiresorptive drugs, regardless of their different mechanisms of action decrease bone remodeling and resorption by inhibiting differentiation and function of osteoclasts and/or increase their apoptosis. Any medication that modifies bone metabolism alters the homeostasis of the bone tissue potentially affecting implant longevity. , The most common antiresorptive drugs are bisphosphonates (BP) and denosumab (RANK ligand inhibitor). Other therapies include a sclerostin inhibitor (romosozumab), a synthetic PTH (teriparatide), antiangiogenic drugs, and hormone replacement therapy.
In 2022, the American Association of Oral and Maxillofacial Surgeons (AAOMS) updated their position paper on MRONJ to expand the number of medications with possible effects on bone metabolism. With respect to implants and antiresorptive therapy, most of the implant-related necrosis did not occur following initial implant surgery but presented late (>12 months) and often at sites where implants were placed prior to the initiation of anti-resorptive therapy. The risk for MRONJ after implant placement among patients treated with denosumab has been reported to be 0.5%. Because of the absence of better data, AAOMS cautions against implant placement in cancer patients exposed to antiresorptive therapies. For osteoporotic patients receiving anti-resorptive therapy, the AAOMS position paper recommends proper informed consent about the low-risk of MRONJ, but early and late implant failures were possible and regular long-term recall schedule was necessary. In 2023, International Team for Implantology (ITI) published a consensus report after a systematic review evaluating materials and antiresorptive drug-associated outcomes in implant dentistry. With regards to implant longevity, they concluded that, “The influence of low-dose bisphosphonate (BP) therapy on long-term implant survival has not been sufficiently documented to allow conclusions”. However, in the same year, Sulaiman and colleagues, in 2023, performed a systematic review and meta-analysis investigating the influence of BP on the rate of dental implant failure and marginal bone loss. There were 1727 implants in the BP group and 21,986 in the non-BP group. The meta-analysis and meta-regression results showed that implants in the BP group had a higher failure risk in comparison to the non-BP group (odds ratio [OR] 1.653, P =.047). The estimated implant survival in patients taking BPs after 5 and 10 ye was 94.2% (95% confidence interval [CI], 94.0 – 94.4) and 90.1% (95% CI, 89.8 – 90.3), respectively.
A new, promising medication, romosozumab, approved by the Food and Drug Administration in 2019 for the treatment of osteoporosis in patients with a high risk of fracture, has both antiresorptive and anabolic properties on bone. The drug is a humanized monoclonal sclerostin-neutralizing antibody. Clinical studies have shown a significant increase in bone formation markers, accompanied by a particular initially pronounced decrease in bone resorption. This dual mechanism of action leads to an increase in bone mineral density and a significant reduction in fracture risk. Preliminary studies have shown an improvement in bone regeneration and implant osseointegration; findings that support the view that sclerostin inhibition might be a promising therapy to promote implant osseointegration for patients with insufficient bone mass or bone defects. Romosozumab therapy is not without risk; clinical trials have shown increased potential for cardiovascular risk and cases consistent with MRONJ, associated with ill-fitting dentures and tooth extractions. ,
Another treatment worth our attention for future exploration of its relationship between dental implants and osseointegration is the combination of synthetic PTH, teriparatide, and BP. Teriparatide, a human recombinant form of PTH, was the first anabolic drug approved by the United States FDA for the treatment of osteoporosis. Preliminary studies have shown that intermittent use of teriparatide prior to antiresorptive therapy would be most effective for bone apposition and suggest that if used properly, teriparatide may be used in dentistry to improve outcomes in areas like periodontal therapy, implant retention, and orthodontic stability. We still need prospective human clinical data to answer questions related to safety, efficacy, dosing, and duration of use.
The data reviewed on the treatment for diseases that affect the balance of bone resorption and bone formation give us some important clinical information about its relationship with dental implant therapy:
- •
Placement of dental implants should be avoided on patients receiving parenteral antiresorptive therapy or antiangiogenic medications for the treatment of cancer.
- •
For osteoporosis patients, dental implant therapy is relatively safe. Informed consent should be provided to include the low-risk of MRONJ (OR 1.653), with estimated implant survival after 5 and 10 y of 94.2% and 90.1%, respectively, as well as early and late implant failure. These patients should be placed on a regular long-term recall schedule.
- •
The evidence on withholding antiresorptive therapy (drug holiday) for implant placement remains inconclusive, with some indications that there is an increased risk of vertebral and nonvertebral fractures during drug holidays in certain high-risk groups.
Clinicians should be aware of other medications affecting bone metabolism, including methotrexate, corticosteroids, and antiangiogenic agents, as they might impair wound healing and lead to complications.
New anabolic therapies like romosozumab and teriparatide are available for the treatment of diseases that affect the balance of bone resorption and bone formation. They need to be evaluated further in humans for their impact on dental implants and osseointegration.
Summary
The long-term success of dental implants is dependent on a multi-layered process that is incompletely understood. In the broadest of terms, it requires the bony implant site to recover from the surgical trauma of implant placement, provide sufficient mechanical stability for osseous integration, long-term preservation of bone remodeling ability to adjust to mechanical loads placed on implants, and physical, as well as immunologic barriers against infection and inflammation that produce bone loss. This article has attempted to summarize a number of disease states, as well as therapies with effects on bone metabolism. Whether they ultimately produce a clinically significant response is not always clear since there is a significant variability between patients and their medical status, as well as differences in therapies and individual responses to therapy. Patients taking PPIs and SSRIs had an increased incidence of implant failure, while patients with CD were potentially associated with early implant failure. However patients with well-controlled diabetes, HIV, and osteoporosis appear to have similar success rates to healthy patients. Anti-resorptive medications are still being studied and while a higher failure rate has been noticed in patients taking BP, the likelihood of developing osteonecrosis following implant placement is low.
Clinics care points
- •
There is significant variability between patients and their medical status, as well as differences in therapies and individual responses to therapy and their effects in bone metabolism, implant osseointegration and their long-term survival.
- •
Patients taking PPIs and SSRIs had an increased incidence of implant failure.
- •
Patients with CD were potentially associated with early implant failure.
- •
Patients with well-controlled diabetes, HIV, and osteoporosis appear to have similar success rates to healthy patients.
- •
Anti-resorptive medications are still being studied and while a higher failure rate has been noticed in patients taking BP, the likelihood of developing osteonecrosis following implant placement is low
Stay updated, free dental videos. Join our Telegram channel
VIDEdental - Online dental courses
