Management of maxillary osteonecrosis in a diabetic patient treated with a temporalis muscle flap and rehabilitated with Global D dental implants: a case report.

Introduction

Medication-related osteonecrosis of the jaw (MRONJ) is defined as an adverse drug reaction characterized by progressive destruction and necrosis of the mandibular and/or maxillary bone in patients exposed to medications associated with an increased risk of disease, in the absence of prior radiation therapy to the jaws [1].

The authors aim to describe a case of non-bisphosphonate-related osteonecrosis of the jaw (non-BRONJ), which includes all forms of jaw osteonecrosis associated with medications other than bisphosphonates.

Diabetes mellitus and maxillary osteonecrosis (MO) are linked through several pathophysiological mechanisms. Diabetes, particularly when poorly controlled, has been shown to increase the risk of developing osteonecrosis of the jaws. Glucose plays a key anabolic role in bone tissue; therefore, glucose deficiency, as in type I diabetes, or resistance to its action, as in type II diabetes, results in reduced bone mineralization and impaired bone formation [2].

The association between diabetes and maxillary osteonecrosis is primarily related to reduced vascularization and impaired angiogenesis. Diabetes-induced microangiopathy leads to decreased formation of new blood vessels, resulting in poor tissue oxygenation and delayed bone healing, thereby predisposing patients to osteonecrosis.

Furthermore, diabetes induces immune dysfunction and a chronic inflammatory state characterized by increased levels of pro-inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, which is associated with impaired immune cell function and an increased risk of infection. Chronic inflammation contributes to bone destruction and delays tissue repair [3]. These effects are mediated by altered osteoblastic and osteoclastic activity: hyperglycemia interferes with osteoblast function, reducing bone regenerative capacity, while simultaneously enhancing osteoclastic activity and bone resorption. In addition, diabetic patients exhibit compromised leukocyte function, increasing susceptibility to chronic oral infections. Diabetes-associated periodontitis may further accelerate maxillary bone loss. Hyperglycemia also alters collagen metabolism by accumulating advanced glycation end products (AGEs), which impair collagen and bone matrix quality, rendering bone more fragile and less responsive to regenerative stimuli [4].

Case Report

A 65-year-old woman was referred to the Complex Operative Unit of Oral Surgery and Odontostomatology AST-2, Ancona, Fabriano Hospital (Italy), for a clinically evident oroantral communication in the left palatal region. Her medical history was significant for dyslipidemia, hypertension, and poorly controlled type II diabetes mellitus.

Preoperative laboratory investigations revealed severe metabolic imbalance, with blood glucose levels ranging from 900 to 245 mg/dL, glycated hemoglobin (HbA1c) of 13.4%, hemoglobin of 10.6 g/dL, C-reactive protein levels ranging from 32.76 to 11.36 mg/ dL, thyroid-stimulating hormone (TSH) of 0.08 μIU/mL, serum potassium levels ranging from 3.28 to 3.80 mEq/L, and prothrombin activity of 141%. These findings confirmed poorly controlled diabetes mellitus associated with a chronic inflammatory state characterized by persistent moderate leukocytosis, predominantly involving neutrophils and monocytes.

The patient’s chronic medication regimen included atorvastatin, acetylsalicylic acid, pantoprazole, ranitidine, levosulpiride, amlodipine, doxazosin, and insulin therapy.

Intraoral clinical examination revealed osteonecrosis involving the palatal bone and part of the edentulous alveolar ridge of the left maxilla (Fig. 1).

Based on these findings, the lesion was classified as stage III medication-related osteonecrosis of the jaw (MRONJ) according to AAOMS criteria. Computed tomography (CT) performed in March 2022, with and without contrast enhancement, confirmed the presence of a bone sequestrum involving the left maxilla (Figs. 2–3).

An initial biopsy of the left maxillary sinus membrane and newly formed tissue at the left hard palate was performed. Histopathological examination revealed fragments of ulcerated mucosa with acute and chronic stromal inflammation, as well as necrotic bone containing lacunae colonized by filamentous bacterial aggregates consistent with Actinomyces species, associated with neutrophilic granulocytic inflammation.

In May 2022, the first surgical procedure was performed under general anesthesia to remove necrotic bone, restoring soft tissue volume and providing a well-vascularized bed for subsequent rehabilitation.

Following en bloc resection of the majority of the necrotic bone of the left maxilla (Figs. 4–5).

Reconstruction of the resulting defect was performed using a rotated pedicled regional temporalis muscle flap transposed into the osseous defect (Figs. 6–8).

Part of the resected bone tissue was submitted for histopathological examination. Hemostasis and wound closure were achieved through layered suturing of the deep and superficial planes, with placement of a left coronal drain (Fig. 9).

At the 15-day follow-up, no signs of inflammation were observed at the surgical site, and healing was within normal limits.

Macroscopic examination revealed whitish tissue fragments, some exhibiting increased consistency; the largest fragment measured 2.0 × 1.8 cm. Three fragments showed increased consistency (specimens 1–3), while three were of soft consistency (specimens 4–6). Microscopic examination demonstrated mucosal fragments with epithelial hyperkeratosis. The lamina propria showed acute and chronic inflammatory infiltrates with focal abscess formation, along with fragments of compact lamellar bone and inflammatory-type polypoid tissue.

At six months postoperatively, clinical examination revealed healthy oral mucosa with complete soft tissue healing and no signs of inflammation (Fig. 10).

Follow-up CT performed 1 year postoperatively (June 2023) showed postoperative changes consistent with prior surgery, with no evidence of active infection or inflammation (Figs 11–12).

The inferior and lateral walls of the left maxillary sinus appeared occupied by tissue with heterogeneous density. At the same time, mild mucosal thickening was noted in the left ethmoidal cells and frontonasal recess. The remaining paranasal sinuses showed physiological pneumatization.

Panoramic radiography at further follow-up (July 2024) confirmed a marked reduction in vertical alveolar bone height in both jaws, particularly in the left maxillary arch, where absence of the sinus floor was evident (Fig. 13–14).

In October 2024, the patient underwent placement of maxillary implants in a day surgery setting. After loco-regional anesthesia with mepivacaine and epinephrine 1:100,000, a crestal mucoperiosteal incision was made extending from the right molar region to the contralateral premolar area. A full-thickness flap was elevated, and five Global D – In-Kone^® Universal Sa [2] implants were placed (dimensions and positions as described), achieving insertion torque values between 30 and 45 N·cm. The site was closed with interrupted 3-0 Vicryl sutures (Fig. 15).

Postoperative therapy included amoxicillin/clavulanic acid, ibuprofen, and bromelain-based anti-inflammatory treatment. Radiographic follow-up at two months (December 2024) demonstrated satisfactory osseointegration (Fig. 16).

At five months, healing abutments were placed, with healthy peri-implant soft tissues and no signs of inflammation (Fig. 17).

Definitive impressions were taken two weeks later.

A fixed full-arch prosthesis was subsequently delivered, consisting of a primary milled bar screw-retained to the implants and a secondary superstructure screw-retained to the bar, achieving satisfactory functional and esthetic rehabilitation (August 2025) (Figs 18–19).

Discussion

The current level of scientific evidence regarding the possible relationship between diabetes mellitus (DM) and non-BRONJ osteonecrosis remains inconclusive. It does not allow the establishment of a clear cause – and – effect relationship. However, several hypotheses may explain how this disease influences bone metabolism and, indirectly, the increased susceptibility to non-BRONJ in affected patients. It has been demonstrated that elevated blood glucose levels can induce increased osteoclast differentiation and promote apoptosis in osteoblasts [5].

Furthermore, hyperglycemia-induced hyperosmolarity suppresses the expression of osteocalcin, matrix metalloproteinase-13 (MMP-13), and vascular endothelial growth factor (VEGF), all of which are associated with osteoblast maturation [6]. Advanced glycation end products (AGEs) contribute to the inhibition of osteoblast adhesion to the bone matrix, which may exacerbate diabetic osteopenia by inhibiting bone matrix growth, differentiation, and mineralization [7].

According to the study by Molcho [8], microvascular complications of diabetes mellitus increase the susceptibility of the jaw bones to medication-related osteonecrosis of the jaw (MRONJ). In addition to the disease itself, pharmacological treatments used in diabetes management may also play an etiopathogenetic role in osteonecrosis. In particular, hypoglycemic agents such as thiazolidinediones appear to affect bone metabolism by suppressing osteoblastic activity and increasing osteoclastic bone resorption [9]. Diabetes is generally associated with microvascular bone ischemia, endothelial cell dysfunction, reduced bone turnover and remodeling, and increased apoptosis of osteoblasts and osteocytes [10].

Mogher Khamaisi, based on both in vivo and in vitro data, supports the concept that new bone formation and bone microarchitectural integrity are impaired under diabetic conditions, leading to an increased risk of fragility fractures and inadequate bone regeneration following injury. In addition, diabetes is associated with delayed wound healing [11].

Reduced cellular glutathione content is a common finding in both experimental and human diabetes and is associated with increased oxidative stress. Recently, a novel non-traumatic rat model was used to investigate the relationship between oxidative stress and osteonecrosis development. In this model, glutathione levels were significantly reduced using the pro-oxidant buthionine sulfoximine. A high incidence of osteonecrosis was observed in this group of animals. These findings suggest that oxidative stress alone may be sufficient to promote the development of osteonecrosis [12–13].

Peravali reported a strong association between diabetes mellitus and maxillary osteomyelitis, which accounted for nearly 68% of all maxillary osteomyelitis cases, compared with only 20% of mandibular osteomyelitis cases [14].

This association may be explained by the fact that elevated blood glucose levels reduce immune system efficiency by altering the distribution of blood flow in lesions, thereby contributing to the development of osteonecrosis. It is often difficult to identify specific odontogenic causes, and a history of uncontrolled diabetes is considered an important etiological factor. Consequently, extensive maxillary necrosis may sometimes be attributed to pre-existing chronic maxillary sinusitis in the context of impaired blood flow and a weakened immune system due to infection.

These findings suggest that, in addition to impairing immune defense mechanisms, diabetes mellitus may significantly contribute to osteomyelitis by altering regional vascularization, as previously mentioned. A previous study reported a higher prevalence of maxillary osteomyelitis in uncontrolled diabetes (33.3%) compared with controlled diabetes (9.5%) [15]. Diabetes mellitus is known to suppress immune responses and shows a strong correlation with osteomyelitis. This correlation has also been demonstrated in other studies, in which diabetes was identified as one of the major contributing factors to the development of osteomyelitis (47.6%) [16].

Elevated blood glucose levels weaken and damage the walls of capillary blood vessels that supply nutrients to nerves ([17]). Moreover, diabetic patients exhibit impaired leukocyte chemotaxis, phagocytosis, and leukocyte lifespan, resulting in a reduced inflammatory response in tissues. This impaired immune response is caused by altered glucose metabolism, which leads to delayed and compromised wound healing. A literature review reported a maxillary-to-mandibular osteomyelitis incidence ratio of 1:16.5. This difference is attributed to the rich blood supply, thin cortical plates, and relative scarcity of medullary tissue in the maxilla, making maxillary osteomyelitis generally less frequent than mandibular osteomyelitis.

Bjurholm described that neurogenic reactions to vasoactive substances influence both the inferior alveolar artery and the periosteal vascular plexus [18]. In the soft tissues covering the buccal surface of the affected mandible, the vascular reaction may be explained by the axon reflex mechanism. The mental and buccal branches of the mandibular nerve mediate this process. It induces a classic inflammatory response by releasing neuropeptides from nerve endings, including substance P [19]. Stimulation of sensory C fibers may also activate osteoblastic activity, since osteoblasts express receptors for substance P. Accelerated new bone formation is mainly observed in areas where the periosteum has been elevated from the bone surface due to infectious processes. Therefore, subperiosteal bone deposition on the buccal surface of the bone, frequently observed in osteomyelitis, may be explained by this mechanism.

Many cases of osteomyelitis primarily affect the mandible due to odontogenic infections exacerbated by immunocompromised states and uncontrolled metabolic diseases such as diabetes mellitus, acquired immunodeficiency syndrome, and malnutrition. Diabetes mellitus represents a significant risk factor for increased osteomyelitis severity and secondary infections.

The microbiological etiology involves both Gram-positive and Gram-negative microorganisms, including Staphylococcus aureus, Staphylococcus epidermidis, Peptostreptococcus, Pneumococcus, hemolytic Streptococcus species, Escherichia coli, and Bacteroides. Coinfection with Mucorales and Aspergillus species may also be observed in osteomyelitis.

In the clinical case described, the initial biopsy sample revealed bacterial colonies, particularly Gram-positive Actinomyces species. Diabetes mellitus represents a major severity factor for osteomyelitis, especially in the maxilla. Commonly observed in immunocompromised patients, diabetes mellitus is an important comorbidity associated with the pathophysiological development of this disease. Poor glycemic control may have devastating consequences for the maxillofacial region and can be potentially fatal for the patient [20].

Conclusions

This clinical case highlights how diabetes mellitus may represent an important risk factor for the onset and progression of maxillary osteonecrosis by influencing healing processes and the response to surgical treatments. However, appropriate interdisciplinary management, optimal metabolic control, and careful surgical–prosthetic planning enabled a favorable outcome, with functional and esthetic restoration through implant-supported prosthetic rehabilitation.

This case emphasizes the importance of continuous monitoring and a personalized approach for diabetic patients undergoing implant procedures to reduce the risk of complications and promote long-term success.