Current global trends indicate that the general population’s expectancy of life is increasing worldwide. These demographic changes have been associated with an increase in the intake of medications for the treatment of highly prevalent medical conditions. Some of these medications may influence tissue metabolism and, therefore, the outcomes of implant therapy in certain cohorts. Interestingly, the impact of medication that may particularly alter bone homeostasis upon implant therapy outcomes has not been systematically explored.
The main goal of this systematic review was to assess the association of implant failure rate as the primary outcome with intake of oral or parenteral medications that may affect bone metabolism.
Secondary outcomes were:
- Timing of implant failure
- Marginal bone loss
- Biological and Mechanical/Technical complications
The present systematic review includes 17 investigations, one CCT had to be excluded due to missing reports on implant failures rates. The 16 remaining studies consisted of three RCTs, one PC and 12 RC including a total of 4,827 patients with 13,247 implants.
A total of five different categories of medications were identified upon completion of the systematic search: nonsteroidal anti-inflammatory medication (NSAIDs), antihypertensive medication (AHTNs), selective serotonin reuptake inhibitors (SSRIs), proton pump inhibitors (PPIs), and bisphosphonates (BPs). Sufficient data were available to perform meta-analyses of the primary outcomes for SSRIs, PPIs, and BPs. The heterogeneity of the study design and methodology in the selected studies did not allow for meta-analyses for any of the secondary outcomes. Limitation of this systematic review is related to differences in study design and medication regimens, in addition to confounding factors, such as comorbidity and polypharmacy among others reported in the literature. Therefore, the findings of this systematic review should be interpreted with caution.
- General Statement
Limited evidence on the effect of long-and short-term medication intake on dental implant therapy outcomes indicates that there may be an association between implant failure rate and the intake of certain medications that influence bone metabolism.
- Nonsteroidal antiinflammatory drugs (NSAIDs)
The association between nonsteroidal anti-inflammatory drug (NSAID) intake and implant failure rate is unclear.
This statement is based on the analysis of five studies (i.e., three RCTs, including a total of 191 patients, and two retrospective cohort studies, including a total of 81 patients) that revealed marked heterogeneity of the pharmacological regimen in the selected studies and a majority of studies reporting no implant failures in either the test or control groups, or both groups.
i.e., Ibuprofen, Flurbiprofen, Celecoxib, Acetylsalicylic, Rofecoxib, Nabumetone, Naproxen, Etodolac and others.
- Antihypertensive medication (AHTNs)
The association between the long-term intake of certain AHTNs and implant failure rate is unclear.
This statement is based on very limited available evidence of one retrospective study including 728 patients. Noteworthy, AHTNs exhibited a lower implant failure rate compared to the control population not taking AHTNs in this study.
i.e., Beta-blockers, Thiazide diuretics, Angiotensin-converting enzyme inhibitors, Angiotensin II receptor blockers and others.
- Selective serotonin reuptake inhibitors (SSRIs)
The intake of certain SSRIs is associated with a statistically significant increased implant failure rate.
This statement is based on the quantitative analysis of two retrospective cohort studies including a total of 790 patients, which suggested that implant failure rate was higher in subjects taking SSRIs as compared to a control population (Odd ratio: 2.92; average difference: 7.48%, C.I. [95%] = 6.96–8.00 with a p < 0.01, between 36 and 90 months of follow-up).
i.e., Citalopram, Dapoxetine, Escitalopram, Fluoxetine, Fluvoxamine, Indalpine, Paroxetine, Sertraline, Venlafaxine and Zimeline and others.
- Proton pump inhibitors (PPIs)
The intake of PPIs is associated with a statistically significant increased implant failure rate.
This statement is based on the quantitative analysis of two retrospective cohort studies including a total of 1,798 patients, which suggested that implant failure rate was higher in subjects taking PPIs as compared to a control population (Odds ratio: 2.02; average difference: 4.29%, C.I. [95%] = 3.81–4.77 with a p < 0.01, between 16 and 94 months of follow-up).
i.e., Omeprazole, Lansoprazole, Pantoprazole, Dexlansoprazole, Esomeprazole, Rabeprazole and others.
- Bisphosphonates (BPs) related to osteoporosis
The intake of BPs related to the treatment of osteoporosis was not associated with an increased implant failure rate.
This statement is based on the quantitative analysis of six cohort studies (i.e., five retrospective on oral BPs and one prospective using intravenous BPs including a total of 1,239 patients), which suggested that implant failure rate was higher in subjects taking BPs as compared to a control population (average difference: −0.13%, C.I. [95%] = −0.3 to 0.05, between 12 and 66 months of follow-up). Caution should be taken when interpreting these data due to the inherent risks associated with the occurrence of medication-induced osteonecrosis in patients taking BPs.
The effect of BP on implant outcomes in patients undergoing treatment of neoplastic diseases therapy was not evaluated, because implant therapy is usually contraindicated in this population.
i.e., Risedronate, Ibandronate, Alendronate, Zoledronic acid and others.
- What are the implications of the increasing intake of medication by the general population in daily practice?
Clinicians and patients considering implant therapy should be aware of possible medication-related implant failures. Hence, a comprehensive assessment and understanding of the patient’s medical background and current medications, as well as a personalized informed consent, should be considered integral components of all phases of contemporary implant therapy (initial and supportive therapy).
- What considerations should be taken in daily clinical practice pertaining medication intake-related implant failure?
Clinicians should consider the association between increased implant failure rate and the intake of proton pump inhibitors (PPIs) or selective serotonin reuptake inhibitors (SSRIs) in their routine risk assessment as part of comprehensive implant therapy. Clinicians should proceed with caution when implant therapy is considered in patients taking bisphosphonates (BPs) related to osteoporosis. Standard implant therapy is contraindicated in patients receiving high-dose bisphosphonates (BPs) for the treatment of neoplastic diseases.