Biphasic calcium phosphate with or without hyaluronic acid vs. deproteinized bovine bone mineral for maxillary sinus augmentation. A randomized clinical trial

Abstract

Introduction. The implant-prosthetic rehabilitation of the atrophic maxilla requires the creation of sufficient volumetric quantity of bone, through regeneration techniques, necessary to position the implants. Although the purpose of the regenerations is the same in the upper and lower jaws, the techniques, and above all their predictability, vary greatly. Within this wide variability, the balance probably hangs in favor of the upper posterior maxilla. Maxillary sinus augmentation (MSA) is probably the most predictable and best performing technique. The technique has been further developed and modified during the years and its indications and directions have been refined by several authors. We distinguish now between a one stage procedure, with simultaneous insertion of the implants, or a two stage procedure, when the residual bone height is less then 4mm, but the basic procedure has essentially remained the same as was firstly described. In addition to being aimed at obtaining the quantity of bone necessary for implant positioning, the regenerative techniques should also allow gaining adequate bone quality, suitable not only for receiving the implant in its volume, but also for giving adequate stability immediately and over time. The biomaterial used can be a key factor in determining the quality of the regenerated bone. In general, there are two types of materials that can be used in MSA techniques: autogenous bone and bone substitutes, with the latter further distinguishable into allogeneic, xenogenic or synthetic. The exclusive use of autologous bone for MSA provides for the removal of large quantities of bone, with the need to open a second surgical site and a significantly increased morbidity and consequent discomfort of the patient. Bone substitutes avoid this inconvenience and, very often, are used in combination with limited quantities of autologous bone, taken in the

proximity of the area to be regenerated, so as not to give up the osteogenic qualities of the latter. The bone substitute of choice in the MSA, perhaps because the most documented in the scientific literature, is the anorganic bovine bone mineral (ABBM). The present randomized controlled study aims to evaluate and compare, histomorphometrically and clinically three different bone substitutes such as: ABBM, Tricalcium Phosphate (TCP) with or without the addition of hydroxyapatite that were used for lateral MSA. This study population will be followed until the 3rd year. This study describes histological differences between the three groups at 9 months. Patients and methods. All the patients enrolled in the study received a session of oral hygiene and a periodontal examination before the surgical procedure to obtain a more favorable oral environment for wound healing. A CBCT was mandatory for all included cases to verify that the maxillary sinus was clear and that the residual bone height was 3 mm or less. Local anesthesia was administered, a mid-crestal incision with mesial and distal release were performed to access the lateral bone wall of the maxillary sinus, subsequently, ultrasound bone surgery (Piezosurgery ®, Carasco, Italy) with specific tips was used for the bone window osteotomy. The Schneiderian membrane was reflected and lifted up medially with flat sinus curettes. Once the sinus membrane was completely lifted a bioabsorbable pericardium membrane (Smartbrane, Regedent AG, Zurich, Switzerland) was applied to protect it. The randomization sealed envelopes were opened and the clinician allocated the patients to one of the three experimental groups: 1) Control group that received Demineralized Bovine Bone Mineral (Bio-Oss Cancellous, Geistlich, Wolhunsen, Switzerland); 2) Test group 1 that received TCP with particle size ranging from 250 to 1000 μm (Osopia, Regedent, Zurich, Switzerland); 3) Test group 2 that received TCP as in test group1 plus crosslinked Hyaluronic Acid (Hyadent BG, Regedent, Zurich, Switzerland) with a ratio 2 to 1. The sinus was grafted with the biomaterial corresponding to the group, the bony window was repositioned, stabilized and covered with a resorbable pericardium membrane. Nine months after the MSA a CBCT analysis was required to evaluate the total bone height gain. Depending on the treatment plan, between one and three implants, bone level (BL) or tissue level (TL), of two different

manufacturers (Institut Straumann AG, Basel, Switzerland and Sweden & Martina, Due Carrare, Italy) were positioned. While preparing the osteotomy implant site a bone biopsy was harvested using a trephine. The implant insertion torque was measured in Ncm for each implant. Twenty-four bone biopsies, obtained from 24 maxillary sinuses, were fixed by immediate immersion in 10% buffered formalin and processed (Precise 1 Automated System; Assing, Rome, Italy) to obtain thin ground sections. The specimens were dehydrated in an ascending series of alcohol rinses and embedded in glycol-methacrylate resin (Technovit 7200 VLC; Kulzer, Wehrheim, Germany). Results. Three biopsy samples were not analyzed (one for each group) because the biopsies were damaged during their removal from the trephine. A total of 21 biopsies were examined, specifically 7 for each group. All biopsy samples at low magnification showed a certain amount of new bone formation. All samples, belonging to the control group, showed two different portions: the preexisting bone could be seen at the bottom of the samples (crestal portion), while at the top of the sample (apical portion) some residual particles can be observed. Residual graft particles (RGP) were completely surrounded by newly formed bone in the area close to the preexisting bone with a thickening the cortical bone layer, while the particles were only partially surrounded by new bone in the areas located more apically. Notably, the most apical portion of the samples showed less newly formed bone with a predominance of non-mineralized tissue between the residual graft particles. The percentages of new bone, residual biomaterials and non-mineralized tissues were 25.98%, 32.19% and 41.99% respectively. Discussion. While the percentage of new augmented bone in the three groups at histological exam wasn’t statistically significant, the difference in the percentage of non-mineralized tissue and residual graft material was statistically significant. It is not easy to analyze the results of a study on MSA, especially the histological ones, in fact it is almost impossible to find studies that make a comparative analysis between the exact same materials, different biomaterials are often used in combination with others. For example, ABBM is often used with autologous bone (AB) or other biomaterials, calcium phosphate, in addition to being often used in combination with other materials, is sometimes used in its form of beta tricalcium phosphate alone or, as in our study, mixed with HA. In general, CaP-based grafting materials have a rather unpredictable rate of resorption,

thus are less able to maintain the grafted volumes, and have a greater structural fragility, probably, as our results show, due to the greater presence of residual non-mineralized tissues43. The advantage of using these biomaterials is their ability to stimulate osteoblastic proliferation and differentiation thanks to their composition, structure and crystallinity which is similar to that of calcium hydroxyapatite, the main inorganic component of the bone. Conclusions. MSA is a safe and predictable procedure from the biological and clinical point of view and with a high comfort perceived by the patient. The use of ABBM or BCP has not influenced the outcomes in terms of bone gain in this study, with values that were comparable and not statistically significant when measured radiographically. Histomorphometric results suggest better bone quality for ABBM with an higher mineral component visible in the histologic sections of the control group when compared with test groups 1 and 2 with a more accentuated non mineralized tissues component.