Two Bovine Xenografts in Lateral Window Sinus Augmentation With or Without Bone Marrow Blood

Background and rationale

After loss of posterior maxillary teeth, alveolar bone resorption combined with pneumatization of the maxillary sinus frequently leaves insufficient bone height for implant placement. Lateral window sinus floor augmentation is a well-documented and predictable procedure to restore this bone volume. Deproteinized bovine bone mineral (DBBM) is widely used as a graft material because of its osteoconductive properties and slow resorption, which help maintain the augmented space during bone formation. Bio-Oss is the most studied DBBM and is considered a reference material. InterOss is a DBBM with comparable physicochemical characteristics (particle size, morphology, and meso- and microporosity), but clinical and histological evidence comparing both materials in sinus augmentation is limited.

Adding autogenous bone to DBBM has been associated with a higher proportion of vital bone in sinus biopsies, likely due to its osteoprogenitor cell content, but autogenous bone harvesting adds donor-site morbidity. Bone marrow stromal cells can be isolated from the maxilla and mandible, and orofacial marrow cells have shown osteogenic and angiogenic potential comparable to or greater than iliac crest cells. Small-volume aspiration of mandibular marrow blood is a minimally invasive way to deliver these cells to the graft. This trial evaluates whether mixing DBBM with mandibular marrow blood increases vital bone formation, and whether InterOss performs comparably to Bio-Oss.

Study design

Randomized clinical trial with a 2x2 factorial design (graft material: Bio-Oss vs. InterOss; with vs. without mandibular marrow blood), conducted at the Postgraduate Program in Oral and Maxillofacial Implantology, Faculty of Medicine, Clínica Alemana - Universidad del Desarrollo, Santiago, Chile. The unit of analysis is the augmented sinus. Allocation is generated with a computer-generated random sequence (Microsoft Excel). In bilateral cases, each sinus is allocated to a different group. Surgeons are not blinded, as the marrow aspiration procedure is evident. The radiographic examiner and the pathologist performing histomorphometry are blinded to group allocation. Sample size was estimated in G*Power based on vital bone proportions reported in a previous sinus augmentation trial comparing two DBBMs, resulting in 10 sinuses per group (40 sinuses in total).

Surgical procedure (stage 1)

Under local anesthesia (2% lidocaine with 1:100,000 epinephrine), a full-thickness flap with a palatalized crestal incision and releasing incisions is raised. A lateral bony window is prepared with piezoelectric surgery, and the Schneiderian membrane is elevated with sinus curettes. The sinus is filled with approximately 1 to 1.5 g of large-particle (1-2 mm) DBBM according to group allocation. Membrane perforations are covered with a resorbable collagen membrane. Primary tension-free closure is achieved with 5-0 nylon sutures. Patients receive antibiotic prophylaxis (amoxicillin/clavulanic acid) and postoperative analgesia, with follow-up at 1 week and suture removal at 14 days.

Mandibular marrow blood harvesting

In the marrow blood groups, a modified University of Michigan protocol is followed. Through a small full-thickness flap in the retromolar/external oblique ridge area, the cortical bone is perforated to a depth of 4-5 mm with a round carbide bur to reach the medullary space. Approximately 0.5 mL of marrow blood is aspirated with a heparinized 21G catheter and syringe, collected in a heparinized container, and mixed with the DBBM immediately before grafting.

Implant placement and biopsy (stage 2)

Eight months after sinus augmentation, a control cone beam CT (CBCT) is obtained for implant planning and radiographic assessment. During implant placement, a bone core is harvested from the grafted area with a trephine bur (2.3 mm inner / 3.0 mm outer diameter) in a coronal-to-apical direction through the residual crest, approximately 7 mm deep.

Histomorphometric analysis

Specimens are fixed in formalin, decalcified in 5% formic acid for 10 days, embedded in paraffin, and sectioned along the long axis of the core. The two most central sections are stained with hematoxylin-eosin and analyzed under light microscopy. The proportions of vital new bone, residual graft particles, connective/fibrovascular tissue, and total bone (vital bone plus graft) are calculated relative to the total sample area.

Radiographic analysis

Preoperative and 8-month CBCT scans are analyzed in DICOM format with BlueSky Plan software. Residual and augmented bone heights are measured in sagittal and coronal views, each as the mean of three slices 1 mm apart. Sinus health and ostium patency are also assessed. Examiners are trained and calibrated beforehand (kappa index).

Rehabilitation and follow-up

Implants are restored approximately 6 months after placement. Patients are followed annually with clinical examination and CBCT.

Statistical analysis

Normality is assessed with the Shapiro-Wilk test. Histomorphometric results are expressed as percentages and radiographic measurements in millimeters. Categorical variables are compared with the chi-square test. Associations between variables are assessed with multiple linear or logistic regression as appropriate. Statistical significance is set at p < 0.05.