THE REGENERATION OF EDENTULOUS ATROPHIC RIDGES: PROS, CONS, AND EFFECTIVENESS OF THREE DIFFERENT SURGICAL OPTIONS

INTRODUCTION During the three-year doctoral period, the candidate developed 3 research projects which, although different, are all related to one of the most controversial topics of advanced implant dentistry which include procedures to make it possible the use of dental implants also in case of severely atrophic edentulous ridges. During the last decade, a variety of surgical procedures have been proposed, each of them with specific indications, contraindications, advantages and disadvantages. Despite the publication of numerous systematic reviews and meta-analyses focused on this fascinating topic, much controversy is still present between clinicians and researches. The aims of the PhD candidate have been to focus on three main areas related to the correction of severely atrophic edentulous ridges in order to: 1) update the present knowledge on this particular field thank to a systematic analysis of the available literature; and 2) develop three different research projects specifically dedicated to regeneration/reconstruction procedures. More in detail, one line of research was focused on the evaluation of medium to long-term results of dental implants placed in severely atrophic jaws reconstructed with autogenous calvarial bone blocks covered with bovine bone mineral and collagen membranes. Seventy-two patients and 330 implants were involved in this retrospective study with a mean follow-up after implant loading of 8 years, ranging from 3 to 19 years. The second project, similar in structure to the previous one, was designed to evaluate retrospectively the medium and long-term results (with a mean follow-up of 10 years) of implants placed in atrophic edentulous ridges grafted with autogenous mandibular blocks covered with bovine bone mineral and collagen membranes. Seventy-five patients, 82 sites, and 182 implants were involved in this study. The third line of research allowed the candidate to design a prospective study which involved edentulous and atrophic patients treated with guided bone regeneration using CAD-CAM customized titanium meshes. The effectiveness of digitally customized titanium meshes in association with autologous bone particles and bovine bone mineral for the regeneration of atrophic edentulous sites, and the survival rate of implants placed in the reconstructed areas were evaluated. A histomorphometric analysis of mandibular regenerated bone were also performed. Forty-one patients, 53 sites, and 106 implants were involved in this study and the follow-up of implants before and after loading ranged from 2 to 23 months (mean: 11 months), and from 1 to 15 months (mean: 6 months), respectively. This latter research is of particular interest, as the literature supporting this particular technique is scarce, and available data are difficult to be compared, because they have been collected in a non- systematic way and mainly retrospectively. In all these studies, a dedicated questionnaire, adapted from the OHIP-14 survey, was performed to evaluate patients’ satisfaction (patient reported outcome measurements – PROMs) as regards the treatment received. It was therefore possible to elaborate a discussion of the results on two different levels: the first associated to the specific regenerative / reconstructive technique; the second allowed a comparison among the different treatment solutions. AIMS The aim of the first and second project, two retrospective longitudinal cohort studies, is to present the medium to long-term outcome of bone reconstructions with calvarium or mandibular grafts , respectively by evaluating: a) complication rate of the reconstructive procedure; b) bone resorption before implant placement; c) peri-implant bone resorption; d) implant-related complications; e) implant survival rate; and, f) patient’s satisfaction inquired with a dedicated questionnaire. The aims of the third project, a prospective, single-arm clinical study, are to evaluate: a) the effectiveness of digitally customized titanium meshes in association with autologous bone particles and BBM and covered with collagen membranes for the regeneration of atrophic edentulous sites; b) the survival rate of implants placed in the regenerated areas and, c) PROMs inquired with a dedicated questionnaire. MATERIALS & METHODS Project 1 – calvarium From 1998 to 2014, 72 patients presenting with severe bone defects were reconstructed with autogenous calvarial bone blocks covered with bovine bone mineral granules and collagen membranes. Four to 9 months later, 330 implants were placed and loaded 3 to 9 months later. The follow-up ranged from 3 to 19 years (mean: 8.1 years). Project 2 – ramus from 1997 to 2015, 75 patients presenting with bone defects of the jaws were grafted with autogenous mandibular bone blocks. One-hundred-eighty-two implants were placed 4 to 12 months later and loaded 3 to 10 months later: the mean follow-up was 10 years (range: 3-16 years). Project 3 – GBR with Ti-mesh 41 patients, presenting with 53 atrophic sites were enrolled between 2018 and 2019. GBR was obtained with titanium meshes filled with autogenous bone chips and bovine bone mineral (BBM). After a mean of 7 months (range: 5-12 months), meshes were removed and 106 implants placed. After a mean of 3.5 months (range: 2-5 months), implants were uncovered and prosthetic restorations started. RESULTS Project 1 – calvarium No patients developed severe complications, such as complete loss or resorption of the grafts. A dehiscence occurred in 6 patients, which developed a mild graft resorption. The mean peri-implant bone resorption before implant placement was 0.13 mm (SD ± 0.71). All patients received the planned number of implants. Three patients were lost during the follow-up. The survival rate of implants at the end of the observation period was 98.5%. The mean peri-implant bone resorption ranged from 0.00 mm to 4.87 mm (mean: 1.11 mm). Finally, 90% of the patients were very satisfied as regards the treatment received. Project 2 – ramus Post-operative recovery was uneventful in the majority of patients. An early dehiscence occurred in three patients, but with no significant bone loss, while 3 experienced temporary paresthesia. The mean vertical and horizontal bone resorption before implant placement was 0.18 mm (standard deviation (SD)=0.43) and 0.15 mm (SD=0.42), respectively. The mean peri-implant bone loss ± standard deviation was 1.06±1.19 (range 0.00 to 5.05) at patient level, and 1.11±1.26 (range 0.00 to 5.20) at implant level. Two implants in 2 patients lost integration and were removed; 10 implants in 7 patients developed peri-implantitis, but healed after surgical treatment. The cumulative implant survival and success rates were 98.11% and 85.16%, respectively. PROMs were very positive: 95.5% of patients would have undergone the procedure again. Project 3 – GBR with Ti-mesh out of 53 sites, 11 underwent mesh exposure: 8 of them were followed by uneventful integration of the graft, while 3 by partial bone loss. The mean vertical and horizontal bone gain after reconstruction was 4.78±1.88mm (range 1.00 to 8.90mm), and 6.35±2.10mm (range 2.14 to 11.48 mm), respectively. At the time of implant placement, mean changes of initial bone gain were -0.39±0.64mm (range -3.1 to +0.80mm), and -0.49±0.83mm (range –3.7 to +0.4mm), in the vertical and horizontal dimensions, respectively. Reduction of bone volume was significantly higher (P<0.001 for both dimensions) in the exposed sites. At histologic analysis, mesh appeared well osseointegrated, except that in sites where membrane exposure occurred. In all sites, newly formed tissue resulted highly mineralized, well-organized and formed by 35.88% of new lamellar bone, 16.42% of woven bone, 10.88% of osteoid matrix, 14.10% of grafted remnants and 22.72% of medullary spaces. Blood vessels were the 4 % of the tissue.The mean follow-up of implants after loading was 10.6±6.5months (range: 2 to 26months). The survival rate of implants was 100%. PROMs were very positive: 92.5% of patients would have undergone the procedure again. DISCUSSION These three projects have offered, on one side, a relevant opportunity to evaluate the short, medium, and long-term outcomes of both reconstructions with autogenous bone blocks and guided bone regeneration with an innovative, customized, titanium mesh. On the other side, “intrinsic” methodologic limits have appeared during the development of this PhD thesis, such as: o heterogeneity of patient samples and type of defects; o retrospective and prospective type of study; o duration of the observation period; o presence/absence of evaluation of bone gain and with different methods; o different methods used to evaluate bone resorption before implant placement. Despite these limits, results from these three researches offered relevant information as regards the behaviour of the transplanted /regenerated bone as well as the behaviour of peri-implant bone over time. Although the three projects significantly differ among them as regards details in the reconstructive procedures, it must be underlined that many aspects are in common. Therefore, to reduce redundancies it has been decided to write a “unified” discussion which will make it possible a direct comparison of pros, cons, indications and contra-indications of each of them. More in detail, each of the following issues will be discussed reporting and comparing obtained from each study: 1. bone gain; 2. complication rate of the reconstructive procedure; 3. bone resorption before implant placement; 4. peri-implant bone resorption; 5. survival rate of implants and implant-related complications; 6. patient’s satisfaction inquired with a dedicated questionnaire. CONCLUSION Despite the descriptive nature of the first two retrospective longitudinal cohort studies and the variability of the selected patients (including different patients anamnesis, defects locations, defect morphologies, and prosthetic rehabilitations), medium- to long-term results seem to confirm the efficacy of reconstruction of atrophic ridges using autogenous bone blocks taken from both the calvarium and the mandibular ramus covered by a protective layer of bovine bone mineral and stabilized by a collagen membrane. The use of autogenous calvarial grafts may be prefer in case of severely deficient edentulous ridges, when the ramus can offer an insufficient quantity of bone. The low postoperative morbidity, the stability over time of the augmented bone, the high survival rate of implants placed in a prosthetically driven way, leading to very satisfactory prosthetic restorations, confirmed the long-term reliability of these procedures. Preliminary results of the third prospective study, on the other hand, despite the limited number of patients, implants, short follow-up, and the non-negligible incidence of Ti-mesh exposures, seem to demonstrate that CAD-CAM customized Ti-meshes may represent a reliable GBR option for the correction severely atrophic edentulous ridges in terms of vertical bone gain, limited peri-implant bone resorption and survival rate of implants. It is however worth noting that if on one hand it is possible to simplify the reconstructive procedure thanks to the customization of Ti-meshes, on the other hand surgeons have to face the non-negligible incidence of Ti-mesh exposures and the higher complexity of their removal at the time of implant placement. Therefore, studies involving a higher sample of patients and with longer follow-ups are necessary. PROMs seem to validate the use of all the regenerative and reconstructive procedures, with high value of patient’ satisfaction.