Biomechanical analysis of alveolar bones with compromised quality supporting a 4-unit implant bridge; a possible association with implant-related sequestration (IRS).

OBJECTIVES: This study aimed to investigate the strain in the bone surrounding dental implants supporting a 4-unit bridge and assess the role of excessive strain as a possible risk factor for implant related sequestration (IRS) or peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ). MATERIALS AND METHODS: A 3D-mandibular model was constructed using computed tomography and segmented it into cortical and cancellous bones. The 4-unit implant-supported bridges replacing the mandibular posteriors were constructed, and each featuring two, three, and four implants, respectively. The Young's modulus was assigned based on the quality of the bone. A maximum occlusal force of 200 N was applied to each implant in the axial and in a 30-degree oblique direction. RESULTS: The maximum principal strain of the fatigue failure range (> 3000 µÎµ) in the bone was analyzed. The volume fraction of fatigue failure was higher in poor-quality bone compared to normal bone and oblique load than in axial load. An increasing number of implants may dissipate excessive strain in poor-quality bones. CONCLUSIONS: Occlusal force applied to poor-quality bone can result in microdamage. Given that unrepaired microdamage may initiate medication-related osteonecrosis of the jaw, long-term occlusal force on fragile bones might be a risk factor. CLINICAL RELEVANCE: When planning implant treatment for patients with compromised bone status, clinical modifications such as strategic placement of implants and optimization of restoration morphology should be considered to reduce excessive strain which might be associated with IRS or PI-MRONJ.

Effect of agents affecting bone homeostasis on short- and long-term implant failure.

OBJECTIVES: To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures. MATERIALS AND METHODS: Electronic searches for bisphosphonates, denosumab, methotrexate, corticosteroids, romosozumab, sunitinib, and bevacizumab were performed using PubMed, MEDLINE (OVID), EMBASE (OVID), Cochrane Central Register of Controlled Trials (Cochrane Library), Cochrane Oral Health Group Trials Register (Cochrane Library) and Web of Science (Thomson Reuters). Manual searches were also conducted to complement the digital searches for recent issues. RESULTS: Previous publications suggested that bisphosphonates do not compromise the survival of dental implants. However, one study documented an increased risk of implant failure in patients who had received high-dose of intravenous bisphosphonate therapy after implant rehabilitation. There has been an issue of MRONJ around implants in patients who have successfully received implant therapy before and after antiresorptive therapy, leading to late implant failure. Despite evidence on the detrimental effects of denosumab, methotrexate and corticosteroids on bone metabolism, their role in implant survival is not conclusive. CONCLUSIONS: At present, there is insufficient evidence to establish a potential connection between agents that affects bone homeostasis and implant failure. However, some studies have reported negative results for implant therapy. In addition, implant-related sequestration in patients who received anti-resorptive therapy, despite of successful osseointegration, is also noticeable. Although limited studies are available at present, clinicians should still carefully consider the potential hazards and take appropriate precautions to minimize the risks associated with the medications and implant therapy.

Group 3 ITI Consensus Report: Materials and antiresorptive drug-associated outcomes in implant dentistry.

OBJECTIVES: The aim of Working Group 3 was to address the influence of both material- and anti-resorptive drug- related factors on clinical and biological outcomes and complications in implant dentistry. Focused questions were addressed on (a) implant materials other than titanium (alloy)s, (b) transmucosal abutment materials and (c) medications affecting bone metabolism were addressed. MATERIALS AND METHODS: Three systematic reviews formed the basis for discussion in Group 3. Consensus statements and clinical recommendations were formulated by group consensus based on the findings of the systematic reviews. Patient perspectives and recommendations for future research were also conveyed. These were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS: Zirconia is a valid alternative to titanium as material for implant and transmucosal components, allowing soft and hard tissue integration with clinical outcomes-identified by implant survival, marginal bone loss and peri-implant probing depths-up to 5-years comparable to titatnium. However, most of the evidence for zirconia implants is based on 1-piece implants limiting the indication range. Furthermore, based on expert opinion, zirconia transmucosal components might be preferred in the esthetic zone. In patients receiving low-dose bisphosphonate therapy, the rate of early implant failure is not increased, while the long-term effects remain poorly studied. Although it has not been sufficiently addressed, similar outcomes can be expected with low-dose denosumab. A drug holiday is not recommended when considering implant placement in patients treated with low-dose ARD. However, the specific therapeutic window, the cumulative dose and the administration time should be considered. Access to peri-implant supportive care is mandatory to prevent peri-implantitis-related medication-related osteonecrosis of the jaw (MRONJ) or implant-related sequestra (IRS). In patients receiving low-dose anti-resorptive drugs (ARD) therapy, the risk of complications related to implant placement is high, and implant procedures in this specific population should be strictly treated in a comprehensive multidisciplinary center. Finally, healthy dental implants should not be removed before low or high-dose ARD. CONCLUSIONS: Zirconia implants can be an alternative to titanium implants in selected indications. However, the current state of evidence remains limited, especially for 2-piece implant designs. Administration of low-dose ARD did not show any negative impact on early implant outcomes, but careful follow-up and supportive care is recommended in order to prevent peri-implant MRONJ and IRS. Implant placement in high-dose patients must be strictly considered in a comprehensive multidisciplinary center.

EMD-liquid contributes to tissue thickness gain in soft tissue augmentation using a collagen matrix.

OBJECTIVES: To investigate the function of enamel matrix derivative (EMD)-liquid compared to EMD-gel (original Emdogain® with polyglycolic acid-carrier) in inducing soft tissue regeneration using a rat dorsal model. MATERIAL AND METHODS: Four subcutaneous pouches were created through dorsal skin incisions in 18 female Wistar rats and randomly allocated to the following groups: (1) sterile saline + non-crosslinked collagen matrix (CM), (2) EMD-gel + CM, and (3) EMD-liquid + CM. After 2 and 4 weeks of healing, the specimens were harvested and stained with Goldner's trichrome, hematoxylin and eosin, and were immunohistochemically stained with an anti-CD31 antibody. RESULTS: The EMD-liquid group showed the thickest connective tissue compared to the other groups, with statistical significance both at 2 (p < 0.001) and 4 weeks (p = 0.011 and 0.023, respectively). The number of multinucleated giant cells was not significantly different among the groups for both periods. Moreover, there was a tendency to have more blood vessels over a longer period, and the highest number of blood vessels was observed in the EMD-liquid group at 4 weeks (p = 0.009 and 0036, respectively). CONCLUSION: EMD-liquid-treated CM is advantageous compared to using CM alone or EMD-gel-treated CM, owing to the histomorphometric results that show significantly increased soft tissue thickness and number of blood vessels when EMD-liquid was pre-primed to CM. CLINICAL RELEVANCE: EMD with a liquid carrier may be an appropriate biologic supplement to provide cell-inducing properties to the CM scaffold and is clinically more beneficial for phenotype modification therapy than CM only and EMD-gel-treated CM.

Is implant surgery a risk factor for osteonecrosis of the jaw in older adult patients with osteoporosis? A national cohort propensity score-matched study.

OBJECTIVES: This study aimed to investigate the association between dental implant therapy and osteonecrosis of the jaw (ONJ) in osteoporotic patients and the relationship between tooth extraction, dental implantation, and ONJ. MATERIAL AND METHODS: This retrospective cohort study used the Customized Health Information Data from the National Health Insurance Corporation in South Korea. The study population included patients older than 70 years with a history of osteoporosis; the cases included patients who had undergone dental implant surgery between July 2014 and July 2016 with specific procedure codes. The case and control cohorts were stratified by tooth extraction because it was the strongest risk factor to consider in this study. Each group of patients was matched using the propensity score. To investigate the relationship between dental implants and ONJ, a Cox proportional hazard model was applied to socio-economic factors, comorbidities, and bisphosphonates (BPs). All analyses were conducted using SAS statistical software. RESULTS: Based on the fully adjusted model, the propensity score-matched osteoporosis patients with dental implants had a 0.51 times hazard ratio of osteonecrosis. On the contrary, tooth extraction was associated with a higher risk of ONJ (HR = 5.89). The patients with rheumatoid arthritis (RA) and those using BPs had a higher HR, respectively, 6.80 and 4.09 HR (p < .001). CONCLUSIONS: Dental implantation was not a risk factor and patients with implants show rather lower ratios. However, older osteoporotic Korean patients who had undergone tooth extraction had higher risks of ONJ. A significantly higher risk of ONJ was associated with RA and BPs as well.

Effect of enamel matrix derivative liquid combined with synthetic bone substitute on bone regeneration in a rabbit calvarial model.

OBJECTIVES: This study aimed to verify the effectiveness of EMD-liquid in combination with a synthetic bone substitute in a rabbit calvarial model. MATERIAL AND METHODS: Four 7-mm outer diameter circular slits were created in the calvaria of 10 New Zealand white rabbits, and polycarbonate cylinders were inserted into the slits. Two experimental groups were established: (1) EMD-liquid + bone substitute (Osteon III®; biphasic calcium phosphate (BCP), ß-TCP/HA = 40:60) and (2) saline + bone substitute (Osteon III®; BCP). The cylinders were filled with saturated graft materials and covered with polycarbonate caps. Micro-CT and histomorphometric evaluation were conducted. RESULTS: In the histomorphometric analysis, new bone formation was significantly higher in the bone substitute (BS) + EMD-liquid group than in the BS only group at both 5 and 10 weeks (p < 0.01). There were statistically significant differences in the material area between the bone substitute and bone substitute + EMD-liquid groups at only 5 weeks (p < 0.05). The BS + EMD-liquid group demonstrated reduced material area to a greater extent. In micro-CT analysis, the BS + EMD-liquid group (27.04 ± 8.06 at 5 weeks, 28.49 ± 9.22 at 10 weeks) showed a significantly higher percentage of mineralized tissue volume at both 5 and 10 weeks (p < 0.05) than the BS only group. CONCLUSION: EMD-liquid enhances new bone formation when combined with BCP bone substitute in an animal model. Moreover, the EMD-liquid + BS has significantly lesser material area than BS alone, indicating accelerated graft degradation. Further studies on types of graft materials are required to verify the effect of EMD-liquid and to optimize its regenerative potential. CLINICAL RELEVANCE: This study suggests that EMD-liquid may have beneficial effect on bone regeneration with synthetic bone substitute.

Axial Triangle of the Maxillary Sinus, and its Surgical Implication With the Position of Maxillary Sinus Septa During Sinus Floor Elevation: A CBCT Analysis.

The aim of this study was to measure the convexity of the lateral wall of the maxillary (Mx) sinus and identify the locational distribution of antral septa in relation to the zygomaticomaxillary buttress (ZMB), in order to suggest another anatomical consideration and surgical modification of sinus floor elevation procedures. This study was designed as a cross-sectional study, and a total of 134 patients and 161 sinuses containing edentulous alveolar ridges were analyzed. The angle between the anterior and lateral walls of the Mx sinus (lateral sinus angle [LSA]), and the angle between the midpalatal line and the anterior sinus wall (anterior sinus angle [ASA]) were measured. Mean LSAs and ASAs were 105.9° ± 9.86° and 58.4° ± 6.43°, respectively. No significant difference between left and right sides was found (LSA, P = .420; right = 105.5° ± 9.27°; left = 105.5° ± 9.27° and ASA, P = .564; right = 57.9° ± 6.80°; left = 58.8° ± 6.02°). The prevalence of septa was 37.3%, and it was most frequently noted in the second molar region (32.8%), followed by the first molar (20.9%), retromolar (16.4%), and second premolar regions (14.9%). Septa were most frequently located posterior to the ZMB (49.2%), while ZMB was mostly located in the first molar region (66.4%). Narrow LSAs may complicate the surgical approach to the posterior maxilla, especially when sinus elevation should be used in the second molar region. Considering the occasional presence of antral septa, membrane elevation may be complicated when a septum is encountered during the procedure. These results suggest that 3-dimensional examination of the convexity of the Mx sinus should be performed preoperatively to choose proper surgical techniques and minimize surgical complications.

Group 4 ITI Consensus Report: Risks and biologic complications associated with implant dentistry.

OBJECTIVES: The aim of Working Group 4 was to address topics related to biologic risks and complications associated with implant dentistry. Focused questions on (a) diagnosis of peri-implantitis, (b) complications associated with implants in augmented sites, (c) outcomes following treatment of peri-implantitis, and (d) implant therapy in geriatric patients and/or patients with systemic diseases were addressed. MATERIALS AND METHODS: Four systematic reviews formed the basis for discussion in Group 4. Participants developed statements and recommendations determined by group consensus based on the findings of the systematic reviews. These were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS: Bleeding on probing (BOP) alone is insufficient for the diagnosis of peri-implantitis. The positive predictive value of BOP alone for the diagnosis of peri-implantitis varies and is dependent on the prevalence of peri-implantitis within the population. For patients with implants in augmented sites, the prevalence of peri-implantitis and implant loss is low over the medium to long term. Peri-implantitis treatment protocols which include individualized supportive care result in high survival of implants after 5 years with about three-quarters of implants still present. Advanced age alone is not a contraindication for implant therapy. Implant placement in patients with cancer receiving high-dose antiresorptive therapy is contraindicated due to the associated high risk for complications. CONCLUSIONS: Diagnosis of peri-implantitis requires the presence of BOP as well as progressive bone loss. Prevalence of peri-implantitis for implants in augmented sites is low. Peri-implantitis treatment should be followed by individualized supportive care. Implant therapy for geriatric patients is not contraindicated; however, comorbidities and autonomy should be considered.

Bisphosphonates hinder osteoblastic/osteoclastic differentiation in the maxillary sinus mucosa-derived stem cells.

OBJECTIVES: Although bisphosphonates (BPs) are known to be associated with osteonecrosis of the maxilla, the precise effects of BPs on bone metabolism in human maxillary sinus mucosal cells (HMSMCs) are not yet known. The purposes of this study were to examine the effects of the BPs zoledronate (ZOL) and alendronate (ALN) on osteoblastic and osteoclastic differentiation in HMSMCs and to investigate the signaling pathways involved. MATERIALS AND METHODS: The effects of ZOL and ALN were assessed for osteoblast differentiation by alkaline phosphatase (ALP) activity, alizarin red staining, and RT-PCR for genes encoding Runx2 and osterix. Receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) was also examined. RESULTS: ZOL and ALN both suppressed osteoblastic differentiation, as evidenced by their effects on ALP activity, mineralization nodule formation, and the mRNA expression levels of osteoblastic transcript factors. The RANKL/osteoprotegerin ratio in HMSMCs was increased by ALN, whereas ZOL had the opposite effect. Conditioned medium obtained from ALN-treated HMSMCs stimulated osteoclast formation and upregulated NFATc1 expression, whereas conditioned medium from ZOL-treated cells did not. ALN was more cytotoxic and stimulated apoptosis more strongly than ZOL. BPs decreased the protein levels of the non-canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II. Moreover, recombinant human Wnt5a reversed the effects of BPs on osteoblastic and osteoclastic differentiation. CONCLUSION: This study is the first demonstration that BPs exert negative effects on osteoblastic and osteoclastic processes via the non-canonical Wnt pathway in HMSMSCs. CLINICAL RELEVANCE: It suggests that patients taking BPs during the period of maxillary sinus lifting and amentation should be given special attention.

Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro.

OBJECTIVE: To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate. MATERIALS AND METHODS: A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts. RESULTS: Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate. CONCLUSIONS: The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate. CLINICAL RELEVANCE: Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.