Journal of Dental Implant Research 2024; 43(4): 61-66  https://doi.org/10.54527/jdir.2024.43.4.61
Clinical outcomes of using demineralized dentin matrix bone grafts and HA-coated implants in medication-related osteonecrosis of the jaw
Seung-Min Song1,§ , Jin-Won Choi1,§ , Pil-Young Yun1,2 , Jeong-Kui Ku1
1Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam,
2Department of Dentistry and Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea
Correspondence to: Jeong-Kui Ku, https://orcid.org/0000-0003-1192-7066
Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 13620, Korea. Tel: +82-31-787-2780, Fax: +82-31-787-4068, E-mail: kujk@snubh.org

§These authors contributed equally to this work.
Received: July 18, 2024; Revised: August 3, 2024; Accepted: August 6, 2024; Published online: December 30, 2024.
© The Korean Academy of Implant Dentistry. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Bisphosphonates and denosumab are key osteoclast inhibitors used in osteoporosis treatments. While effective, these drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Biofluorescence-imaging systems (BIS) were recently suggested to distinguish between pathologic and healthy bone during MRONJ surgery. This case report demonstrated a 79-year-old female with a ten-year history of bisphosphonate-developed MRONJ post-tooth extraction. BIS-guided surgery was performed, combined with hydroxyapatite (HA)-coated implants and a demineralized dentin matrix (DDM) graft. Follow-up at six months showed successful osseointegration and gingival healing without the recurrence of MRONJ or bone exposure. In conclusion, BIS is valuable for identifying pathologic bone in MRONJ surgery. The HA-coated implants and DDM have the potential for excellent tissue regeneration in MRONJ defects.
Keywords: Biofluorescence Imaging System, Hydroxyapatite coated dental implants, Demineralized dentin matrix, Medication related osteonecrosis of the Jaw
INTRODUCTION

Bisphosphonates and denosumab are crucial osteoclast inhibitors used in treating osteoporosis. Bisphosphonates disrupt osteoclast activity, while denosumab inhibits RANKL, preventing osteoclast precursor cells from maturing into osteoclasts1). These drugs are also used for preventing bone metastases in cancer patients, treating Paget’s disease, and bone dysplasia. However, these antiresorptive agents can cause osteonecrosis of the jaw (MRONJ). MRONJ is diagnosed when bone is exposed in the oral and maxillofacial region for more than 8 weeks in patients who have taken antiresorptive agents without a history of radiation therapy or metastatic disease to the jaws2). The prevalence of MRONJ varies from 0.7∼6.7% in cancer patients to 0.001∼0.1% in osteoporosis patients2,3).

The treatment of MRONJ includes both non-surgical and surgical approaches. Non-surgical methods such as debridement of necrotic bone surfaces with chlorhexidine and antibiotic therapy can be considered when surgery is not feasible, but these methods often yield inconsistent results and unpredictable disease progression4). Therefore, early surgical intervention is necessary to reduce disease progression and achieve predictable outcomes5). Partial resection can be an effective treatment for all stages of osteonecrosis. Recent studies have shown a high success rate of over 93% with surgical resection6,7). It is crucial to preserve as much healthy bone as possible while removing all necrotic bone to minimize complications and facilitate future reconstruction with implants. Distinguishing between necrotic and healthy bone is challenging. The limitations of visual assessment during surgery can lead to a recurrence rate of 33% in cases of MRONJ or osteoradionecrosis8).

To overcome these limitations, the use of BIS (Biofluorescence-imaging system) in MRONJ surgery has been attempted. Among various BIS device, Qray (Quantitative light-induced fluorescence (QLF) device, AIOBIO, Seoul, Republic of Korea) detects porphyrin, a bacterial byproduct, to identify dental caries and has been successfully applied to determine the extent of necrotic bone in MRONJ surgeries9-11). Kim et al. reported successful treatment outcomes using QLF in a case of oral mucosal necrosis with conservative surgery and found significant histological differences based on fluorescence9). They classified non-red fluorescence, excessive red fluorescence, and low red fluorescence areas, each with distinct histological features: non-red fluorescence indicated sclerotic lamellar bone tissue, excessive red fluorescence indicated inflamed tissue with bacterial invasion and bone resorption, and low red fluorescence indicated inflamed granulation tissue without bone tissue and bacterial colonies10). These findings suggest that QLF can distinguish infected bone from healthy bone, which is difficult to do visually. Ku et al. evaluated the condition of residual bone using QLF in a case where titanium mesh was exposed three weeks after vertical bone augmentation with autogenous bone12). They determined that the absence of red fluorescence indicated non-infected bone, allowing them to leave the titanium mesh in place and achieve secondary healing without complications.

After segmental resection, there is often insufficient bone for future implant placement, necessitating bone grafting. Dentin graft material can be a useful alternative in these situations. Dentin, composed of 70% hydroxyapatite, 18% collagen, 2% non-collagen proteins (NCP), and 10% body fluids, is similar to bone in composition13). Demineralized dentin matrix (DDM) has been shown to release growth factors and induce bone formation, similar to demineralized bone matrix, in various animal studies. Numerous studies have demonstrated the successful use of DDM in guided bone regeneration (GBR) and sinus augmentation procedures14,15). Hydroxyapatite (HA), mainly composed of calcium and phosphate, provides a favorable environment for bone cells to adhere to implants due to its similar thermal expansion coefficient to bone.16-18) HA-coated implants improve implant stability by releasing bone-inducing ions such as calcium and phosphate, promoting osteoblast proliferation and bone matrix deposition.19,20) Plasma-sprayed HA coatings can transform implant surfaces into highly crystalline structures with minimal impurities and high bonding strength21). This case report presents the clinical outcomes of using dentin-derived graft material and HA-coated implants in a patient undergoing MRONJ surgery.

CASE PRESENTATION

This case report presents a 79-year-old female patient who had taken bisphosphonates for over ten years for osteoporosis and experienced bone exposure for eight weeks following the extraction of teeth #33 and 34. Diagnosed with MRONJ (Fig. 1), the patient desired to resume eating as soon as possible. Thus, BIS-guided MRONJ surgery and simultaneous implant and bone graft procedures were planned.

Figure 1. Surgical procedure. (A) Exposed necrotic bone after incision and flap elevation. (B) Red-fluorescent on BIS image. (C) Removed necrotic bone. (D) Post-operative image after BIS guided MRONJ surgery. (E, F) Placement of the wing type implant placement. (G, H) Grafting with allogenic demineralized dentin matrix incorporated with rhBMP-2 (HuBT.BMP, Korea Tooth Bank, Republic of Korea). (I) Primary closure.

Under general anesthesia and routine draping, a crestal incision was made from the mandibular premolars to the opposite premolars, and a full-thickness flap was elevated to expose the anterior mandible. Necrotic bone was removed based on visual assessment and BIS (Qray pen-C, AIOBIO, Seoul, Republic of Korea) fluorescence evaluation. Following the protocol by Kim et al., only the bone emitting red fluorescence was considered necrotic and selectively removed11). (Fig. 2B-D) After confirming the absence of red fluorescence at all margins, HA-coated Safe 3.5 implants (3.5 mm width, 8.5 mm length, Withwell implant, Seoul, Republic of Korea) were placed in positions #33 and 43 with over 30 Ncm torque (Fig. 2E-F). The bone defects around the implants were grafted with allogenic demineralized dentin matrix incorporated with rhBMP-2 (HuBT.BMP, Korea Tooth Bank, Republic of Korea), and primary closure was achieved through periosteal releasing incisions (Fig. 2G-I).

Figure 2. Preoperative clinical images. (A) Body defect on #34-35 area. (B) Incomplete gingival healing with bony exposure.

Postoperatively, the patient was prescribed 500 mg cephalosporin twice daily, 500 mg NSAIDs, and 60 mg mucosal protectants for seven days. A liquid diet and 0.12% chlorhexidine mouthwash twice daily were recommended for two weeks. At two weeks post-surgery, satisfactory gingival healing was observed, and sutures were removed. At three months post-surgery, there were no signs of infection or recurrent osteomyelitis. Three months later, a secondary surgery was performed under local anesthesia. The implants showed normal gingival healing without bone exposure. Prosthetic treatment was planned, and at six months post-surgery, radiographs confirmed stable osseointegration without bone resorption (Fig. 3, 4).

Figure 3. Postoperative radiography. (A, B) Panoramic view and CBCT at immediately after the surgery (A) and 3 months post-surgery (B). (C) Panoramic and periapical view at 6 months post-surgery.

Figure 4. Postoperative images. (A) 2 weeks post-surgery. (B) 3 months post-surgery. (C) 2 weeks post-second surgery. (D) 6 months post-surgery.
DISCUSSION

This case report demonstrates the successful clinical outcomes of BIS-guided MRONJ surgery, followed by demineralized dentin matrix grafting and HA-coated implant placement. The BIS device, Qray pen-C, uses high-intensity blue light (around 420 nm) to detect porphyrin, emitting red fluorescence, effectively distinguishing necrotic bone from healthy bone. In this case, selective removal of necrotic bone while preserving healthy bone using fluorescence guidance enabled successful minimally invasive surgery. This is an important case as it preserved bone tissue for future prosthetic restoration.

The HA-coated wing-type implant used in this case (Safe 3.5, Withwell Implant, Seoul, Republic of Korea) has a wide fixture top design, providing better stress distribution and preventing soft tissue penetration, promoting bone formation below the wing, and preventing long-term bone resorption22,23). This design offers high fracture resistance, allowing the use of thin-diameter implants even in thin bone, with stable outcomes expected22). HA coating plays a crucial role in improving osseointegration of the implant. João et al. reported that HA coating on implants enhances protein absorption, cell adhesion, and proliferation, leading to improved osseointegration and increased implant success rates24). HA also releases bone-inducing ions like calcium and phosphorus, enhancing implant stability and promoting osteoblast proliferation and bone matrix deposition19,20). In this case, the HA-coated implant showed stable osseointegration without bone resorption during a six-month observation period.

The use of demineralized dentin matrix (DDM) is another significant aspect of this case. While many case reports have documented successful bone grafting using DDM, this case is unique because it solely used DDM for defect areas post-sequestrectomy. DDM has osteoinductive properties and promotes bone regeneration due to its similar chemical composition to bone25). Studies comparing bone regeneration have shown that autogenous tooth-derived bone graft material produces similar results to autogenous or xenograft bone when used in implant placement26). However, autogenous DDM requires prior extraction and processing of the patient's teeth, limiting its applicability and the amount of graft material available. To overcome these limitations, allogenic DDM has been developed, providing sufficient quantities and containing essential growth factors for effective bone regeneration for implant restoration27,28). In this case, the use of allogenic DDM material in areas with insufficient bone demonstrated excellent bone regeneration and stability. While this case highlights the success of minimally invasive BIS-guided MRONJ surgery combined with bone grafting and implants, it is a single patient case report. Therefore, well-designed studies involving a larger patient cohort are necessary to validate the efficacy and safety of this treatment protocol.

CONCLUSION

Biofluorescence-imaging system is useful for distinguishing pathologic bone in MRONJ surgery, and it suggests that HA-coated wing-type implants can induce successful osseointegration even in unfavorable bone quantity and quality conditions. Additionally, it has been confirmed that allogeneic demineralized dentin matrix has the potential to achieve excellent tissue regeneration in oral and maxillofacial bone defects.

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