Pedicled Myofascial Temporalis Flap for Closure of Large Maxillary Defects After Medication-Related Osteonecrosis of the Jaws. A Case Series

Pedicled Myofascial Temporalis Flap for Closure of Large Maxillary Defects After Medication-Related Osteonecrosis of the Jaws. 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A Case Series Sanne Werner Moeller Andersen, Liezl Dawson, Iben Poulsen, Simon Storgård Jensen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6462559/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Feb, 2026 Read the published version in Oral and Maxillofacial Surgery → Version 1 posted 7 You are reading this latest preprint version Abstract Background: Medication-related osteonecrosis of the jaws (MRONJ) located in the maxilla may lead to challenging oro-antral and oro-nasal defects too extensive to be predictably closed with local soft tissue flaps. The use of a pedicled myofascial temporalis flap (PMTF) is, however, well-established for closing large maxillary defects following ablative craniomaxillofacial surgery. Objectives: The purpose of the present study was to evaluate the use of PMTF for maxillary defect closure in patients with stage 3 MRONJ. Methods: A retrospective cohort study was conducted based on data from the Copenhagen ONJ cohort from 1 January 2005 to 31 December 2024. The inclusion criteria were consecutive patients with extensive maxillary defects after surgical treatment of MRONJ and closed with PMTF. Results: Seven patients met the inclusion criteria (three patients with cancer, two patients with osteoporosis, and two patients with cancer and osteoporosis). Lesions were assessed both clinically and radiographically. All patients healed uneventfully and reported significantly reduced pain after surgery. One patient developed a late complication at the donor site. Conclusions: The removal of necrotic bone combined with radical sinusotomy and closure of the defect with PMTF is a predictable method to treat extensive maxillary MRONJ lesions with a high success rate. Bisphosphonate-associated osteonecrosis of the jaws surgical flaps bone density conservation agents temporal muscle maxillary disease Figures Figure 1 Figure 2 INTRODUCTION Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive treatment (AR) and was first described in 2003 by Marx [ 1 ]. MRONJ is defined and staged according to a position paper from the American Association of Oral and Maxillofacial Surgeons (AAOMS) [ 2 ]. In addition to AR, consisting of bisphosphonates or denosumab, tyrosine kinase inhibitors, monoclonal antibodies, mammalian target of rapamycin inhibitors, radiopharmaceuticals, selective oestrogen receptor modulators, and immunosuppressants are associated with an increased risk of developing MRONJ [ 3 ]. The literature generally describes maxillary affections to account for one-quarter to one-third of MRONJ lesions [ 2 , 4 ]. A Swedish study also demonstrated that MRONJ affects the mandible in 75% of patients and the maxilla in 25%, and in 4.5% of patients, both the mandible and maxilla were affected [ 5 ]. The study did not identify any significant difference in healing rate after surgical treatment of MRONJ in the mandible or the maxilla (P = 0.156). In addition to the alveolar process, MRONJ affecting the maxilla may also involve the maxillary sinus and the nasal cavity. Involvement of the maxillary sinus is reported in 35.8% of maxillary lesions [ 4 ]. Wasserzug et al. reported that the presence of oroantral and oronasal fistulas is 32% and 10% of maxillary MRONJ cases, respectively [ 6 ]. When MRONJ involves the maxillary sinus, it is classified as stage 3 according to the AAOMS classification [ 2 ]. Diagnosing and treating MRONJ lesions in the maxilla is essential to avoid infection spread as nasal septal abscess [ 7 ], orbital cellulitis [ 8 ], or necrotic lesions extending to the skull base [ 9 ]. Maxillary MRONJ lesions are often more severe at the time of diagnosis than mandibular, probably caused by difficulty in early diagnosis and the hidden anatomical nature of maxillary MRONJ [ 10 , 11 ]. Resection of the maxilla (maxillectomy) can involve the removal of teeth, alveolar process, hard palate and parts of the maxillary sinus or nasal walls, which may lead to changed facial appearance, impaired masticatory function, impaired speech and swallowing, and nasal fluid leakage [ 12 ], ultimately affecting Health-Related Quality of Life (HRQoL) [ 13 ]. Maxillary resections can be classified according to Brown and Shaw, which categorise vertical and horizontal resections [ 14 ]. Closure of an oro-antral or oro-nasal defect has been described with the use of an obturator prosthesis [ 12 , 15 , 16 ], buccal fat pad [ 13 , 17 ], nasolabial flap [ 18 ], pedicled myofascial temporalis flap (PMTF) [ 19 ], and microvascular free flap [ 14 , 20 ]. There is currently no consensus regarding the treatment of choice for patients with maxillary stage 3 MRONJ, and a variety of therapeutic concepts exist, from conservative medical treatment to minor or major surgery with or without adjuvant therapy [ 2 , 21 ]. Nonetheless, there is an agreement that the goal of treatment should be infection control, pain reduction, elimination or minimising progression of MRONJ, and improvement of patients' HRQoL [ 2 ]. The use of PMTF has been described for many reconstructive scenarios in craniofacial reconstruction. The PMTF is well established and is considered a safe, reliable, quick, and predictable pedicle flap for reconstruction after a maxillectomy [ 19 , 22 ]. Temporal depression is a known common consequence following harvesting PMTF unless reconstructed [ 23 ]. Several materials and techniques have been described for the reconstruction of temporal depressions, such as porous high-density polyethylene (PHDPE) implants [ 24 ], polymethyl methacrylate (PMMA) [ 25 ], titanium implants (TI) [ 26 ], Mersilene mesh (MM) [ 27 ], autologous fat transplantation (lipofilling) [ 28 ], and polyetheretherketone (PEEK) [ 29 ] polyetherketoneketone (PEKK) [ 30 ]. A systematic review evaluated the most commonly used biomaterials (PHDPE and PMMA) for augmenting the depression on the donor side. PMMA was reported to have more complications [ 23 ]. PHDPE (Medpor®) is a non-resorbable, non-antigenic, hypoallergenic, easily shaped, customised and fixed alloplastic material available in multiple shapes and sizes [ 31 ]. Its pore size (100 to 250 µm) allows tissue ingrowth that stabilises the implant and contributes to its resistance to infection [ 32 ]. The PHDPE implant is considered safe, well-documented, and effective as a long-term repair option in the camouflage reconstruction of the iatrogenic temporal fossa depression because of its biocompatibility, customizability, strength, non-resorbability over time, and only requires a single-stage surgery [ 33 , 34 ]. However, the use of virtual surgical planning and the possibility for prefabrication of patient-specific implants (PSI) for the primary reconstruction of the donor site potentially will change towards PSI for temporal reconstruction [ 30 , 35 ]. To the authors' knowledge, no published data exist on the closure of maxillary stage 3 MRONJ-related defects with PMTF. The primary aim of the present case series is to document the results after treating extensive stage 3 maxillary MRONJ lesions and reconstructing the defect using the PMTF. The secondary aim is to describe the outcome of the PHDPE implant in reconstructing the temporal donor site depression. MATERIAL AND METHODS Patient selection A retrospective audit of all patients included in the Copenhagen ONJ Cohort, which comprises all consecutive MRONJ patients treated at the Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital, Denmark. Between 1 January 2005 and 31 December 2024, 934 patients were diagnosed with MRONJ and included in the cohort. The criteria for diagnosis of MRONJ were made according to the AAOMS position paper [ 36 ] until 2014, after 2014, according to the first update [ 37 ], and after 2022, according to the latest update of the AAOMS [ 2 ]. The Copenhagen ONJ Cohort has received ethical approval (protocol no. R-22046553, P-2022-856). All patients were offered treatment alternatives, and the surgical procedure was thoroughly explained. Patients provided signed informed consent. All patients have been treated according to the standards and ethical principles of Rigshospitalet, Copenhagen University Hospital, Denmark, in line with the Declaration of Helsinki (2013). Patient identification remained anonymous, and the study did not involve any experimental component. The inclusion criteria for this study were the presence of a maxillary stage 3 MRONJ lesion, where closure with PMTF was indicated due to the involvement of a minimum half of the maxilla with communication to the maxillary sinus, the nasal cavity, or both. This was based on radiological evaluation using Cone Beam Computed Tomography (CBCT), Computed Tomography (CT), Single Photon Emission Computed Tomography (SPECT), or a combination of these scans. Although MRONJ is a clinical diagnosis [ 37 ], supplementing radiological imaging is needed to evaluate the extent and type of pathology [ 6 , 38 , 39 ]. Routine imaging of patients with MRONJ in our clinic includes a panoramic radiograph (OPG) and a CBCT scan, supplemented with a SPECT/CT scan in cases where there is doubt about the extent of the MRONJ lesion (Fig. 1 B, Fig. 2 B to 2 D). Often, the extent of an MRONJ lesion cannot be properly assessed from an OPG alone [ 6 ]. This is also reflected by the fact that maxillary MRONJ lesions tend to be more advanced at the first examination [ 10 , 11 ]. The patient’s clinical data, including demographic data, main diagnosis, type and duration of antiresorptive treatment, Numeric Rating Scale (NRS), and Eastern Cooperative Oncology Group (ECOG) Performance Status, were recorded. The treatment plan was based on clinical findings, symptoms, radiographic evaluation (OPG, CBCT, CT, or SPECT scans), and the patient's general condition. Surgical procedure All patients underwent surgery in general anaesthesia supplemented with local anaesthesia (0.5% Marcaine Adrenaline) under sterile conditions. An incision was made on top of the maxillary alveolar process along the exposed bone and the teeth, which had to be removed, with releasing incisions medially and distally as necessary. Necrotic bone was removed, including the teeth involved. Pus, granulation tissue, or both were removed from the maxillary sinuses in conjunction with radical sinusotomy, leaving the sinus without mucosal coverage. Resection of necrotic bone was continued until vital bone was visible clinically. Holes for soft tissue suspension were drilled in the bony edge in the maxillary sinus wall, palatal bone, and through the remaining adjacent alveolar process for later stabilisation of the PMTF with sutures. All excised bone and soft tissue were sent for histopathological examination. The PMTF was raised through a preauricular approach with anterior temporal extension. After careful dissection and mobilisation, the PMTF was transposed to the oral cavity medially to the zygomatic arch. In neither of the cases was it necessary to remove the coronoid process. The PMTF was sutured (Ethicon Vicryl Suture 3 − 0, Johnson & Johnson) using the drill holes and the palatal mucosa. The remaining mucoperiosteal flap was mobilised to ensure tension-free closure and sutured partly on top of the PMTF, providing a partial two-layer closure with mattress sutures and interrupted single sutures (Ethicon Vicryl Suture 4 − 0, Johnson & Johnson). PHDPE implants were customised to the defect and stabilised with osteosynthesis screws to reconstruct the temporal donor site. Antibiotic treatment included Amoxicillin/Clavulanic acid 500/125 mg three times daily, starting one day preoperatively. From surgery until discharge, all patients received Cefuroxime 1500 mg intravenously, three times daily. After discharge, postoperative peroral antibiotics were continued, Amoxicillin/Clavulanic acid 500/125 mg, three times daily for ten days. The patients were seen at regular follow-ups: 14 days postoperatively (for the removal of extraoral sutures), one month (for the removal of remaining intraoral sutures), and again at three, six, nine, and 12 months during the first year, after which they were seen yearly. Pain was monitored pre-operatively and at each follow-up using the numerical ranking scale (NRS), and the state of healing was documented. Statistical analysis Descriptive statistical analyses were performed due to the low number of patients and the explorative nature of the study. RESULTS Unpublished data from the Copenhagen ONJ Cohort (1 January 2005 to 31 December 2024) consisting of 934 patients revealed that the mandible was affected in 64.9%, the maxilla in 29.1%, and both jaws in 6% of the patients. Twelve patients met the inclusion criteria and were eligible for PMTF reconstruction. However, five patients in need of PMTF were either not suitable for the operation due to their health status (two patients) or unwilling to proceed with the operation, opting instead for a conservative treatment alternative (three patients). Thus, seven patients were treated with PMTF. The demographic data of patients treated with PMTF are summarised in Table 1 . Table 1 Demographic data of seven patients treated with pedicled myofascial temporalis flap for closure of large defects after maxillary MRONJ lesions. Characteristics Patient (n = 7) Age, years - mean ± SD (range) 77.5 ± 6.3 (67–84) Preoperative weight, kg – mean ± SD (range) 56.8 ± 13.8 (41-74.9) Gender n (%) Women 7 (100%) Men 0 ECOG Perfomance Status, n (%) 0 1 (14.3%) 1 2 (28.6%) 2 0 3 0 Missing data 4 (57.1) General diagnoses, n (%) Breast cancer 1 (14.3%) Osteoporosis 2 (28.6%) Multiple myeloma 1 (14.3%) Breast cancer and osteoporosis 3 (42.9%) Antiresorptive treatment, n (%) Bisphosphonates 5 (71.4%) Denosumab 2 (28.6%) Duration of antiresorptive treatment, months - mean ± SD (range) Bisphosphonates 49.9 ± 34.2 (12–96) Denosumab 120 Antiresorptive treatment stopped, n (%) Paused antiresorptive before operation 5 (71.4%) Comorbidity, n (%) Diabetes 1 (14.3%) Steroid (1 prior treatment and 3 current treated) 4 (57.1%) Chemotherapy (1 missing) 5 (71.4%) Previous or current tobacco user 4 (57.1%) Dental trauma, n (%) Tooth extraction before onset of MRONJ 3 (42.6%) Numeric Rating Scale (NRS) pain from the jaw- mean ± SD (range) NRS preoperative (1 missing) 2.0 ± 3.08 (0–5) NRS postoperative 0 Follow up, months - mean ± SD (range) 11.0 ± 12.47 (3–34) Time from operation to death (4 patients), months – mean ± SD (range) 19.5 ± 19.1 (6–33) * ECOG Performance Status: 0 = Fully active, able to carry on all pre-disease performance without restriction. 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work. 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3 = Capable of only limited self-care, confined to bed or chair for more than 50% of waking hours. 4 = Completely disabled. Cannot carry on self-care. Confined to bed or chair [ 58 ]. Operation details Histological examinations of the clinically non-vital bone all showed areas of necrotic bone, appositional bone growth, colonies of microorganisms, and acute and chronic inflammation. Examination of mucosal and soft tissue removed from the sinus and sinus tracts revealed acute and chronic inflamed tissue. No malignancies were identified histologically. The mean dimension of the resulting defects on the postoperative CT scan measured 1795,03 mm 2 ± 686,40 mm 2 . The largest dimension was 2311,92 mm 2 , and the smallest was 665 mm 2 . It was possible to close all defects with the PMTF. Patient outcome Postoperatively, all patients healed uneventfully intraorally after resection and complete closure with PMTF was achieved. One patient was previously treated with a bloc resection and primary wound closure due to MRONJ in the maxilla. Eight months postoperatively, a recurrence of the MRONJ lesion was diagnosed, affecting an area where PMTF was indicated (case 1 ). At a six-month follow-up, one patient had developed a local dehiscence in the temporal region, which dictated the removal of the placed PHDPE implant. The defect was closed with local flaps. The second postoperative healing was compromised, but the defect eventually healed by secondary intention after discontinuing dexamethasone and local treatment with methylrosaniline at the wound edges, zinc ointment, and application of Synalar (case 2 ). Thus, six out of seven PHDPE implants (85.7%) healed without complications. The mean observation period was 20.3 months ± 15.9 months (range 2.2 to 44.4 months). The mean pain score was reduced from NRS 2.0 (range 0–5) before surgery to NRS 0.0 one month postoperatively. Case presentation Case 1 An 84-year-old female patient, presented in Fig. 1 ., was diagnosed with breast cancer in 2009 and osteoporosis in 2011. Comorbidities: hypertension, hypercholesterolemia, chronic renal insufficiency, and uric acid gout. Treated with Alendronate 70 mg weekly for a total of 57 months prior to surgery, with no steroid treatment, but receiving Letrozole treatment due to breast cancer. NRS 2 at the initial visit and spontaneously developed stage 3 MRONJ. A) Clinical photos (facial and palatal) and OPG show stage 3 MRONJ in regions 21, 22, 23, 24, 25, and 26. B) Four months after bloc resection of the region 21 to 27, mucosal healing and no sign of necrosis on OPG. C) Eight months after surgery, clinical pictures show chronic infection in regions 11 to 25. OPG with osteolysis 17, 16, 15 and 11, 21, 22, 23. D) Eleven months after initial surgery, immediately before secondary surgery, planned for maxillectomy, left-side PMTF, right-side buccal fat pad and dental implant operation to achieve later dental rehabilitation. Clinical pictures show chronic infection in oral mucosa, exposed bone 17, 16, 15 and inferior conchae on the patient's left side. OPG shows osteolytic bone in the alveolar process bilateral in the maxilla, with the destruction of the sinus and nasal floor, likewise sinus reaction bilateral. E) Fourteen days post-second surgery, healing intra- and extraoral. Intraoral area of the temporal muscle with ongoing epithelisation. OPG shows maxillary resection and dental implants in place. F) Three months after the second surgery, prior to abutment surgery, healing both intra- and extraorally, with no signs of necrosis. OPG after abutment operation shows sign of osseointegration and no sign of bone loss around implants G) Prosthetic treatment six months after placement of dental implants, Atlantis® Cobalt Chrome acrylic bridge, OPG shows bridge in place, minor bone loss around dental implant 13. No sign of reaction in the right maxillary sinus. H) Three-year follow-up after prosthetic treatment, 3.5 years after the secondary surgery. Dental bridge in situ, no sign of intra- or extraoral infection, no necrotic bone, no pain or discomfort. OPG shows unchanged bone loss at dental implant 13 and only minor bone loss at dental implant 28, with no reaction in the maxillary sinus. Case 2 An 75-year-old female patient, presented in Fig. 2 ., with multiple myeloma received high-dose anti-resorptive treatment with Denosumab 120 mg every four weeks for 63 months prior to surgery. Simultaneously treated with steroids and chemotherapy, Lenalidomide. No pain. A) The clinical photo shows spontaneous stage 3 MRONJ that has developed in regions 17, 16, 15, and 14. B, C, D, E) CBCT shows periosteal reaction in the right maxillary sinus, sinusitis, osteolytic and osteosclerotic reaction in alveolar process in region of 17, 16, 15, 14, 13, right side in palatal, maxillary and zygomatic bone, with minor sequestrum formation. F) Clinically exposed bone on the day of surgery. G) Following the resection of bone and the removal of granulation tissue, the right side of the nasal and sinus cavities is exposed. H) Resected maxilla, Brown and Shaw classification IIb. I) Temporal muscle after incision. J) Elevation of the temporal muscle, sutures placed in lateral and medial fascia and used to pull the temporal muscle orally on the medial aspect of the zygomatic arch. K) Temporal muscle sutured to bony edges and remaining palatal mucosa. L) PHDPE implants in place fixed with osteosynthesis screws. M) Intraoral sutures. N) Extraoral sutures. O, P, Q) Follow-up 14 days post-surgery, extraoral after suture removal, intraoral and CBCT. R, S) Follow-up 30 days, extraoral healing, intraoral after suture removal. T) Spontaneously developed dehiscence at 3 months follow-up, exposed PHDPE implant. U) Follow-up three weeks after removal of PHDPE implant: extraoral, ischemic necrotic cutis. V) Six-month follow-up intraorally, tooth 11 removed one month prior, and removable prosthesis in place. X) Five months after removal of PHDPE implant – demarcation of necrotic skin and exposed calvaria bone, no infection, paused in dexamethasone. Y) One month after termination of dexamethasone, granulation of cutaneous edges, but unchanged exposed calvaria bone. Z) Three months after referral to plastic surgeons, treated in the special unit of wound care, treated by discontinuation of dexamethasone and local treatment with methylrosaniline at the wound edges, zinc ointment, and application of Synalar. Treatment resulted in hypergranulation over the former exposed bone. DISCUSSION This retrospective cohort study evaluated the healing outcomes of extensive stage 3 maxillary MRONJ lesions treated with PMTF and PHDPE implant placement for temporal donor defect reconstruction. To the authors' knowledge, no prior studies had reported maxillary stage 3 MRONJ defect closure using PMTF. This study presented the largest single-centre case series to date. Within the Copenhagen ONJ Cohort, maxillary involvement was common, yet only a small proportion of cases were managed using PMTF. These findings underscored the rarity of this treatment approach and highlighted the need for highly individualised treatment planning. The results contributed valuable clinical insights into an uncommon but potentially effective reconstructive strategy for severe stage 3 maxillary MRONJ cases. Aljohani et al. defined the accepted surgical treatment of MRONJ lesions as the complete removal of necrotic bone followed by the removal of sharp bone edges and meticulous primary wound closure [ 13 ]. This treatment principle was applied in the present study, and all seven patients recovered without complications related to the removal of necrotic bone and the closure of the resulting defect using the PMTF. The results emphasise the importance of completely removing necrotic bone and achieving a tension-free, watertight closure when treating patients affected by MRONJ. Reconstructing maxillary defects caused by MRONJ presents major functional and aesthetic challenges, alongside difficulties in prosthetic rehabilitation [ 40 ]. Compromised healing due to medical histories complicates this situation, especially the use of AR, making reconstruction more complex and healing outcomes unpredictable. Positive results have been previously achieved with obturation and surgical reconstruction [ 13 , 41 ]. The prosthetic obturator is a well-established and effective method for closing maxillary defects, including those associated with MRONJ [ 42 – 44 ]. It offers several advantages: requiring only a single surgery for resection and reconstruction, immediately restoring dentition, preventing nasal leakage, and improving speech, mastication, aesthetics, and overall HRQoL while also allowing for cavity surveillance [ 14 , 45 ]. Some concerns exist regarding the potential for MRONJ recurrence due to trauma from the removable prosthesis. However, studies suggest that patients tolerate obturators well, with no recurrence observed [ 13 , 16 , 44 ]. Aljohani et al. stated that obturators could be used for large defects that are possibly difficult to successfully cover with regional flaps and for patients with poor health status. All the patients in their study indicated a high satisfaction response with the prosthetic obturator and no MRONJ recurrence over the 3 to 18-month follow-up period [ 13 ]. This was, however, a small sample size and a short follow-up period. Conversely, a comparative study by Moreno et al. found that surgical reconstruction yielded superior functional outcomes, particularly in cases involving larger horizontal defects [ 46 ]. The stability and retention of the obturator are primarily determined by the defect's location and size, the supporting surface area of the remaining palate, and the condition of the remaining teeth [ 43 ]. Poor stability and retention results in a loose-fitting denture, which increase the risk of traumatic ulceration leading to MRONJ recurrence. Large maxillary defects, especially in edentulous patients, make surgical reconstruction a viable option that would enhance patients' functionality and HRQoL [ 43 , 46 ]. The success of the obturator relies on the patient’s daily adherence to the hygiene of the prosthesis as well as the remaining communication [ 44 ]. However, this approach may not be feasible for patients with compromised dexterity or poor health. In such cases, surgical alternatives like the PMTF. PMTF provides immediate closure of oral-nasal and oral-antral communications, does not require teeth like the obturator for reconstruction, provides a stable base for the prosthesis, and following epithelialisation, the mucosa resembles the adjacent oral mucosa. Additionally, in combination with dental implants, an implant-retained prosthesis will restore occlusion and function [ 43 ]. All patients were given the option of surgery or a conservative alternative. Consequently, five patients chose conservative treatment due to their health status or preference, while seven patients underwent reconstruction with PMTF. There is an overall consensus that some kind of surgical reconstruction algorithm needs to be followed depending on the size of the maxillary defect [ 14 , 40 , 47 ]. A relevant surgical reconstructive ladder for maxillary MRONJ includes the primary use of local mucoperiosteal flaps. If this is insufficient, local flaps (buccal fat pad or PMTF) and, lastly, free flaps can be used to reconstruct defects related to MRONJ [ 17 , 18 , 20 , 48 ]. Compared to more conservative approaches, surgical interventions, with or without adjunctive therapies (parathyroid hormone, low-level laser therapy, ozone therapy, and hyperbaric oxygen therapy), are more effective in downgrading or healing MRONJ lesions at any stage [ 49 ]. Klingelhöffer et al., however, stated that surgical interventions might not be sufficient for long-term wound closure [ 41 ]. However, the study only used a mucoperiosteal flap for tension-free closure. Tension-free, water-tight closure with local mucoperiosteal flaps is a successful reconstruction method; however, having sufficient tissue to ensure this closure is impossible in large lesions, leading to healing complications and the recurrence of MRONJ [ 50 ]. The success of surgical reconstruction of MRONJ-associated defects is the use of multiple tissue layers for closure to ensure the long-term success of MRONJ treatment [ 18 , 48 ]. Nasolabial flaps have been reported as a successful treatment option for reconstructing small to medium-sized MRONJ lesions, with 68–93% success rates [ 18 , 51 ]. Lemound et al. found in a comparative study that nasolabial flaps had significantly better wound closure (P = 0.005) than mucoperiosteal flaps due to a multilayer closure in treating MRONJ-associated lesions [ 18 ]. The nasolabial flap technique is less time-consuming and simpler than reconstruction with free flaps. However, Rai et al. warn that the bulkiness of these nasolabial flaps makes dental rehabilitation difficult, with hair growth and scaring complicating rehabilitation even further [ 52 ]. This makes the buccal fat pad an intriguing treatment alternative. The use of the buccal fat pad flap underscores the success of this multiple-layer closure technique, as it has been the workhorse of numerous successfully treated small to medium-sized MRONJ maxillary defect closures in our department [ 17 ]. It is a simple and time-efficient technique, epithelialising within three to four weeks. However, it is limited once the defect size exceeds 50 mm diameter, beyond which a tight mucosal closure becomes problematic [ 17 , 53 ]. The buccal fat pad flap is limited in extension past the palatal midline, only covers the defect, and doesn’t add bulk [ 53 ]. When the extent of maxillary defects surpasses the capability of the buccal fat pad, PMTF may be considered the next reconstruction option [ 17 ]. The defect size in this study varied from 665 mm 2 up to 2311.92 mm 2 with a mean of 1795.03 mm 2 ± 686.40 mm 2 . This extends beyond the ability of the buccal fat pad flap, particularly when a defect requires additional volume for improved prosthetic rehabilitation. For this reason, the PMTF was utilised for reconstruction. The PMTF has not been described for the closure of defects related to MRONJ, but it has been successful for other reconstruction purposes [ 19 , 22 , 54 ]. The PMTF is used as an alternative when other flap attempts have failed [ 22 ]. The PMTF is an excellent option for reconstructing medium to large-sized intraoral defects due to its anatomical proximity, vascularity, and adequate bulk. With intraoral re-epithelisation expected within four to six weeks, there are no concerns regarding hair growth associated with the reconstructed defect [ 22 , 55 ]. The patient presented in case 1 was previously treated with a block resection and primary wound closure using a mucoperiosteal flap due to MRONJ in the maxilla. However, a recurrence of the MRONJ lesion occurred eight months postoperatively, resulting in a defect for which a PMTF was indicated. After reconstruction with a combination of PMTF of the left side with PHDPE implant placement to compensate for the temporal defect, buccal fat pad flap on the right side, and dental implant placement, the patient healed without complications. Three years after treatment, the patient was stable without pain (NRS = 0). This outcome highlights the importance of patient-specific treatment planning and the effectiveness of multiple-layer tissue closure for the treatment of advanced MRONJ-associated lesions. As with any kind of surgical reconstructive, PMTF may present potential complications. Spanio di Spilimbergo et al. published a case series on complications after 366 PMTF, divided into periods 1978–1993 (195 patients) and 1994–2012 (171 patients), describing total flap necrosis in 1.5% and 1.7%, intraoral dehiscence in 12.8% and 12.2%, permanent paralysis of the frontal branch of the facial nerve in 12.8% and 12.2%, trismus in 46.8% and 48%, and necessity of removal of alloplastic material from donor side in 17.1% and 7.9%, respectively. In the latter period, only PHDPE material was used in this study, emphasising the success of using this type of implant for donor site reconstruction [ 19 ]. Six out of seven PHDPE implants (85.7%) in our study healed without complications. Only one patient developed local dehiscence in the temporal region at a six-month follow-up. The PHDPE implant was removed, and the defect was closed with local flaps. The patient again had healing complications, but the defect eventually healed with the help of the special care unit for wound care. This outcome highlights how these patients' health can deteriorate over time and emphasises the importance of daily hygiene, nutrition, and regular follow-ups to prevent and address late complications. The results of the present case series support that the PMTF is a viable, safe technique with a low complication rate and high success rate in extensive hemi-maxillectomy cases where rehabilitation is not possible with other methods. It provides a watertight seal, allows for additional bone grafting for possible dental implant-supported rehabilitation, and improves the patient’s HRQoL. Furthermore, it is more cost-effective, has a shorter operation time, and requires only a single reconstruction team compared to reconstruction with free flaps [ 19 , 54 ]. The mean pain score was reduced from NRS 2.0 (range 0–5) before surgery to NRS 0.0 one month postoperatively. It is noteworthy that some patients had severe infection and pain prior to surgery, whereas others did not. This insidious progression of the disease contributes to a delayed presentation, as the lack of pain deprives patients of a crucial early warning sign. Consequently, patients often do not seek medical attention until the condition has advanced significantly, typically by which time extensive lesions have developed, involving large portions of the maxilla. This late presentation frequently results in the loss of substantial volumes of bone and adjacent teeth. Once the defect exceeds the capability of the PMTF, free flap reconstruction will be the next suitable treatment option. Several studies have reported on the reconstruction of MRONJ lesions using free flaps. Most reported on mandibular lesions with large soft tissue defects and poor vascularisation [ 20 , 56 , 57 ]. Mücke et al. report the successful reconstruction of an MRONJ lesion using an anterolateral thigh flap in one patient and radial forearm flaps in four patients [ 20 ]. These procedures are complex and often involve lengthy operative times with multiple teams, the risk of donor site morbidity, and intricate postoperative dental prosthetic rehabilitation. These are factors to take into account and are not indicated for the treatment of MRONJ patients with incurable malignancies, poor overall health, and limited life expectancy. A critical assessment needs to be made of the cost and benefit ratio and treatment efficacy of the reconstruction in extensive bony and soft tissue lesions in patients with good overall health status [ 13 ]. In all the cases in this study, mobilising sufficient PMTF and securing tight multi-layered closure of the defect to the sinus or nose or both were possible. There was no correlation between the size of the defects and the patients' healing outcome. The success rate of treatment was 100% after resection and reconstruction with PMTF, with no complications related to the flap procedure, but one patient had a complication related to the donor site reconstruction. There is a constant need to identify risk factors and establish the best possible regime for performing operations, including assessing which patients to operate on and which to exclude. One might wonder whether the risk of reconstruction justifies the potential for MRONJ recurrence and the associated costs, considering the patient's life expectancy. However, many of these patients suffer from chronic pain and facial disfigurement, which complicate everyday activities such as eating and speaking. Any opportunity to improve the quality of their remaining life should be welcomed within reasonable limits. Limitations This study presents several limitations. Firstly, its retrospective design resulted in incomplete data availability, which may have impacted the depth and breadth of the analysis. Additionally, the small sample size limits the generalizability of the results significantly. Although the findings are important, the limited number of patients could affect the overall reliability of the results and the strength of the conclusions drawn. CONCLUSION This study demonstrated that using PMTF for the closure of large oro-antral defects, oro-nasal defects, or both is a reliable method to treat MRONJ lesions with a high success rate (100%). The temporal defect reconstruction following PMTF transposition can be accomplished using a PHDPE temporal implant. Declarations Funding: None Human ethics declaration : Not applicable Consent to participate : All human participants sign a written consent to participate Clinical trial number : Not applicable Author Contribution Sanne Werner Moeller Andersen: conceptualisation, data curation, formal analysis, investigation, methodology, project administration, supervision, validation, visualisation, writing original draft, writing review, and editing.Liezl Dawson: writing original draft, writing review, and editing.Iben Poulsen: formal analysis, investigation, methodology, validation, writing review, and editing.Simon Storgård Jensen: supervision, validation, writing review, and editing.Thomas Kofod: conceptualisation, investigation, resources, supervision, validation, writing review, and editing. Availability of data and material: Not applicable. Code availability : Not applicable. Ethics approval : Ethic committee protocol no. R-22046553, P-2022-856. Consent to participate: All patients signed an informed consent. Consent for publication: Not applicable. Conflict of interest: Liezl Dawson, recipient of 1-year ITI scholarship. Other authors have no conflicts of interest to declare. References Marx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. Journal of oral and maxillofacial surgery 61(9): 1115-1117. https://doi.org/10.1016/s0278-2391(03)00720-1 Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D (2022) American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg 80(5): 920-943. https://doi.org/10.1016/j.joms.2022.02.008 King R, Tanna N, Patel V (2019) Medication-related osteonecrosis of the jaw unrelated to bisphosphonates and denosumab-a review. 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Aust Endod J 35(3): 119-130. https://doi.org/10.1111/j.1747-4477.2009.00213.x Ruggiero SL, Dodson TB, Fantasia J, Goodday R, Aghaloo T, Mehrotra B, O'Ryan F (2014) American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw--2014 update. J Oral Maxillofac Surg 72(10): 1938-1956. https://doi.org/10.1016/j.joms.2014.04.031 Chiandussi S, Biasotto M, Dore F, Cavalli F, Cova MA, Di Lenarda R (2006) Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol 35(4): 236-243. https://doi.org/10.1259/dmfr/27458726 Schiodt M, Otto S, Fedele S, Bedogni A, Nicolatou-Galitis O, Guggenberger R, Herlofson BB, Ristow O, Kofod T (2019) Workshop of European task force on medication-related osteonecrosis of the jaw-Current challenges. Oral Dis 25(7): 1815-1821. https://doi.org/10.1111/odi.13160 Brown JS, Rogers SN, McNally DN, Boyle M (2000) A modified classification for the maxillectomy defect. Head Neck 22(1): 17-26. https://doi.org/10.1002/(sici)1097-0347(200001)22:13.0.co;2-2 Klingelhöffer C, Zeman F, Meier J, Reichert TE, Ettl T (2016) Evaluation of surgical outcome and influencing risk factors in patients with medication-related osteonecrosis of the jaws. J Craniomaxillofac Surg 44(10): 1694-1699. https://doi.org/10.1016/j.jcms.2016.08.001 Marx RE (2009) Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws. J Oral Maxillofac Surg 67(5 Suppl): 107-119. https://doi.org/10.1016/j.joms.2008.12.007 Okay DJ, Genden E, Buchbinder D, Urken M (2001) Prosthodontic guidelines for surgical reconstruction of the maxilla: a classification system of defects. J Prosthet Dent 86(4): 352-363. https://doi.org/10.1067/mpr.2001.119524 de Almeida FC, Moreira MS, Marcucci M, Marques MM, de Araujo ME, da Silva DP (2014) New uses for rehabilitation protocol for oral sinus communications in ARONJ patients. J Prosthodont 23(8): 649-653. https://doi.org/10.1111/jopr.12157 Kornblith AB, Zlotolow IM, Gooen J, Huryn JM, Lerner T, Strong EW, Shah JP, Spiro RH, Holland JC (1996) Quality of life of maxillectomy patients using an obturator prosthesis. Head Neck 18(4): 323-334. https://doi.org/10.1002/(SICI)1097-0347(199607/08)18:43.0.Co;2-# Moreno MA, Skoracki RJ, Hanna EY, Hanasono MM (2010) Microvascular free flap reconstruction versus palatal obturation for maxillectomy defects. Head Neck 32(7): 860-868. https://doi.org/10.1002/hed.21264 Cordeiro PG, Chen CM (2012) A 15-year review of midface reconstruction after total and subtotal maxillectomy: part I. Algorithm and outcomes. Plast Reconstr Surg 129(1): 124-136. https://doi.org/10.1097/PRS.0b013e318221dca4 Mücke T, Koerdt S, Jung M, Mitchell DA, Wolff K-D, Kesting MR, Loeffelbein DJ (2016) The role of mylohyoid flap in the treatment of bisphosphonate-related osteonecrosis of the jaws. Journal of cranio-Maxillofacial surgery 44(4): 369-373. Goker F, Grecchi E, Grecchi F, Francetti L, Del Fabbro M (2021) Treatment of medication-related osteonecrosis of the jaw (MRONJ). A systematic review. Eur Rev Med Pharmacol Sci 25(6): 2662-2673. https://doi.org/10.26355/eurrev_202103_25430 Mücke T, Jung M, Koerdt S, Mitchell DA, Loeffelbein D, Kesting MR (2016) Free flap reconstruction for patients with bisphosphonate related osteonecrosis of the jaws after mandibulectomy. Journal of cranio-Maxillofacial surgery 44(2): 142-147. Eckardt AM, Kokemüller H, Tavassol F, Gellrich NC (2011) Reconstruction of oral mucosal defects using the nasolabial flap: clinical experience with 22 patients. Head Neck Oncol 3: 28. https://doi.org/10.1186/1758-3284-3-28 Rai A, Datarkar A, Rai M (2014) Is buccal fat pad a better option than nasolabial flap for reconstruction of intraoral defects after surgical release of fibrous bands in patients with oral submucous fibrosis? A pilot study: a protocol for the management of oral submucous fibrosis. J Craniomaxillofac Surg 42(5): e111-116. https://doi.org/10.1016/j.jcms.2013.07.006 Dean A, Alamillos F, García-López A, Sánchez J, Peñalba M (2001) The buccal fat pad flap in oral reconstruction. Head Neck 23(5): 383-388. https://doi.org/10.1002/hed.1048 Browne JD, Butler S, Rees C (2011) Functional outcomes and suitability of the temporalis myofascial flap for palatal and maxillary reconstruction after oncologic resection. Laryngoscope 121(6): 1149-1159. https://doi.org/10.1002/lary.21747 Bradley P, Brockbank J (1981) The temporalis muscle flap in oral reconstruction. A cadaveric, animal and clinical study. J Maxillofac Surg 9(3): 139-145. https://doi.org/10.1016/s0301-0503(81)80034-3 Hanasono MM, Militsakh ON, Richmon JD, Rosenthal EL, Wax MK (2013) Mandibulectomy and free flap reconstruction for bisphosphonate-related osteonecrosis of the jaws. JAMA Otolaryngol Head Neck Surg 139(11): 1135-1142. https://doi.org/10.1001/jamaoto.2013.4474 Vercruysse H, Jr., Backer T, Mommaerts MY (2014) Outcomes of osseous free flap reconstruction in stage III bisphosphonate-related osteonecrosis of the jaw: systematic review and a new case series. J Craniomaxillofac Surg 42(5): 377-386. https://doi.org/10.1016/j.jcms.2014.01.005 Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. American journal of clinical oncology 5(6): 649-656. [Online]. Available: https://journals.lww.com/amjclinicaloncology/abstract/1982/12000/toxicity_and_response_criteria_of_the_eastern.14.aspx Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6462559","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":450643713,"identity":"e01ad767-af81-43f4-aba6-ff2ba418306d","order_by":0,"name":"Sanne Werner Moeller Andersen","email":"data:image/png;base64,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","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark","correspondingAuthor":true,"prefix":"","firstName":"Sanne","middleName":"Werner Moeller","lastName":"Andersen","suffix":""},{"id":450643714,"identity":"0f1a8a44-0fdd-4dff-8167-8baf3f503232","order_by":1,"name":"Liezl Dawson","email":"","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark","correspondingAuthor":false,"prefix":"","firstName":"Liezl","middleName":"","lastName":"Dawson","suffix":""},{"id":450643715,"identity":"7019447d-cb32-4177-b47e-9960fd600e17","order_by":2,"name":"Iben Poulsen","email":"","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark","correspondingAuthor":false,"prefix":"","firstName":"Iben","middleName":"","lastName":"Poulsen","suffix":""},{"id":450643716,"identity":"a580ca1f-e23e-4ebd-b9ac-1aaf40c7d59c","order_by":3,"name":"Simon Storgård Jensen","email":"","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark","correspondingAuthor":false,"prefix":"","firstName":"Simon","middleName":"Storgård","lastName":"Jensen","suffix":""},{"id":450643718,"identity":"b50cdfc4-872c-410d-86ea-e35678977b51","order_by":4,"name":"Thomas Kofod","email":"","orcid":"","institution":"Department of Oral and Maxillofacial Surgery, Rigshospitalet, Copenhagen University Hospital, Denmark","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"","lastName":"Kofod","suffix":""}],"badges":[],"createdAt":"2025-04-16 10:38:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6462559/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6462559/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s10006-026-01532-w","type":"published","date":"2026-02-26T15:57:39+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82177694,"identity":"f57a41a4-12d2-4d14-bb37-c74c08b89e4b","added_by":"auto","created_at":"2025-05-07 11:21:40","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":2721235,"visible":true,"origin":"","legend":"\u003cp\u003eCase 1, presents an 84-year-old female\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6462559/v1/7c03fa4aaad443bbec80fa0f.jpg"},{"id":82176463,"identity":"269aeba5-7e19-4795-aa95-f9d1720114ac","added_by":"auto","created_at":"2025-05-07 11:13:40","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":4352743,"visible":true,"origin":"","legend":"\u003cp\u003eCase 2, presents an 75-year-old female\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6462559/v1/fe273e4e1b5da7739e507e33.jpg"},{"id":103765622,"identity":"684050eb-a840-4e29-9da5-c7326b7da065","added_by":"auto","created_at":"2026-03-02 16:05:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":7840156,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6462559/v1/14e4e48e-ecaf-4842-8ccd-ed03d9b38f8f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePedicled Myofascial Temporalis Flap for Closure of Large Maxillary Defects After Medication-Related Osteonecrosis of the Jaws. A Case Series\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMedication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive treatment (AR) and was first described in 2003 by Marx [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. MRONJ is defined and staged according to a position paper from the American Association of Oral and Maxillofacial Surgeons (AAOMS) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In addition to AR, consisting of bisphosphonates or denosumab, tyrosine kinase inhibitors, monoclonal antibodies, mammalian target of rapamycin inhibitors, radiopharmaceuticals, selective oestrogen receptor modulators, and immunosuppressants are associated with an increased risk of developing MRONJ [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe literature generally describes maxillary affections to account for one-quarter to one-third of MRONJ lesions [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. A Swedish study also demonstrated that MRONJ affects the mandible in 75% of patients and the maxilla in 25%, and in 4.5% of patients, both the mandible and maxilla were affected [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The study did not identify any significant difference in healing rate after surgical treatment of MRONJ in the mandible or the maxilla (P\u0026thinsp;=\u0026thinsp;0.156). In addition to the alveolar process, MRONJ affecting the maxilla may also involve the maxillary sinus and the nasal cavity. Involvement of the maxillary sinus is reported in 35.8% of maxillary lesions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Wasserzug et al. reported that the presence of oroantral and oronasal fistulas is 32% and 10% of maxillary MRONJ cases, respectively [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. When MRONJ involves the maxillary sinus, it is classified as stage 3 according to the AAOMS classification [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiagnosing and treating MRONJ lesions in the maxilla is essential to avoid infection spread as nasal septal abscess [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], orbital cellulitis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], or necrotic lesions extending to the skull base [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Maxillary MRONJ lesions are often more severe at the time of diagnosis than mandibular, probably caused by difficulty in early diagnosis and the hidden anatomical nature of maxillary MRONJ [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eResection of the maxilla (maxillectomy) can involve the removal of teeth, alveolar process, hard palate and parts of the maxillary sinus or nasal walls, which may lead to changed facial appearance, impaired masticatory function, impaired speech and swallowing, and nasal fluid leakage [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], ultimately affecting Health-Related Quality of Life (HRQoL) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Maxillary resections can be classified according to Brown and Shaw, which categorise vertical and horizontal resections [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClosure of an oro-antral or oro-nasal defect has been described with the use of an obturator prosthesis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], buccal fat pad [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], nasolabial flap [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], pedicled myofascial temporalis flap (PMTF) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and microvascular free flap [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere is currently no consensus regarding the treatment of choice for patients with maxillary stage 3 MRONJ, and a variety of therapeutic concepts exist, from conservative medical treatment to minor or major surgery with or without adjuvant therapy [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Nonetheless, there is an agreement that the goal of treatment should be infection control, pain reduction, elimination or minimising progression of MRONJ, and improvement of patients' HRQoL [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe use of PMTF has been described for many reconstructive scenarios in craniofacial reconstruction. The PMTF is well established and is considered a safe, reliable, quick, and predictable pedicle flap for reconstruction after a maxillectomy [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Temporal depression is a known common consequence following harvesting PMTF unless reconstructed [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Several materials and techniques have been described for the reconstruction of temporal depressions, such as porous high-density polyethylene (PHDPE) implants [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], polymethyl methacrylate (PMMA) [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], titanium implants (TI) [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], Mersilene mesh (MM) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], autologous fat transplantation (lipofilling) [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], and polyetheretherketone (PEEK) [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] polyetherketoneketone (PEKK) [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. A systematic review evaluated the most commonly used biomaterials (PHDPE and PMMA) for augmenting the depression on the donor side. PMMA was reported to have more complications [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePHDPE (Medpor\u0026reg;) is a non-resorbable, non-antigenic, hypoallergenic, easily shaped, customised and fixed alloplastic material available in multiple shapes and sizes [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Its pore size (100 to 250 \u0026micro;m) allows tissue ingrowth that stabilises the implant and contributes to its resistance to infection [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The PHDPE implant is considered safe, well-documented, and effective as a long-term repair option in the camouflage reconstruction of the iatrogenic temporal fossa depression because of its biocompatibility, customizability, strength, non-resorbability over time, and only requires a single-stage surgery [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. However, the use of virtual surgical planning and the possibility for prefabrication of patient-specific implants (PSI) for the primary reconstruction of the donor site potentially will change towards PSI for temporal reconstruction [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo the authors' knowledge, no published data exist on the closure of maxillary stage 3 MRONJ-related defects with PMTF. The primary aim of the present case series is to document the results after treating extensive stage 3 maxillary MRONJ lesions and reconstructing the defect using the PMTF. The secondary aim is to describe the outcome of the PHDPE implant in reconstructing the temporal donor site depression.\u003c/p\u003e"},{"header":"MATERIAL AND METHODS","content":"\u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePatient selection\u003c/span\u003e \u003c/p\u003e \u003cp\u003e A retrospective audit of all patients included in the Copenhagen ONJ Cohort, which comprises all consecutive MRONJ patients treated at the Department of Oral and Maxillofacial Surgery, Copenhagen University Hospital, Denmark. Between 1 January 2005 and 31 December 2024, 934 patients were diagnosed with MRONJ and included in the cohort. The criteria for diagnosis of MRONJ were made according to the AAOMS position paper [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e] until 2014, after 2014, according to the first update [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], and after 2022, according to the latest update of the AAOMS [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe Copenhagen ONJ Cohort has received ethical approval (protocol no. R-22046553, P-2022-856). All patients were offered treatment alternatives, and the surgical procedure was thoroughly explained. Patients provided signed informed consent. All patients have been treated according to the standards and ethical principles of Rigshospitalet, Copenhagen University Hospital, Denmark, in line with the Declaration of Helsinki (2013). Patient identification remained anonymous, and the study did not involve any experimental component.\u003c/p\u003e \u003cp\u003eThe inclusion criteria for this study were the presence of a maxillary stage 3 MRONJ lesion, where closure with PMTF was indicated due to the involvement of a minimum half of the maxilla with communication to the maxillary sinus, the nasal cavity, or both. This was based on radiological evaluation using Cone Beam Computed Tomography (CBCT), Computed Tomography (CT), Single Photon Emission Computed Tomography (SPECT), or a combination of these scans.\u003c/p\u003e \u003cp\u003eAlthough MRONJ is a clinical diagnosis [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], supplementing radiological imaging is needed to evaluate the extent and type of pathology [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Routine imaging of patients with MRONJ in our clinic includes a panoramic radiograph (OPG) and a CBCT scan, supplemented with a SPECT/CT scan in cases where there is doubt about the extent of the MRONJ lesion (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB to \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Often, the extent of an MRONJ lesion cannot be properly assessed from an OPG alone [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This is also reflected by the fact that maxillary MRONJ lesions tend to be more advanced at the first examination [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe patient\u0026rsquo;s clinical data, including demographic data, main diagnosis, type and duration of antiresorptive treatment, Numeric Rating Scale (NRS), and Eastern Cooperative Oncology Group (ECOG) Performance Status, were recorded. The treatment plan was based on clinical findings, symptoms, radiographic evaluation (OPG, CBCT, CT, or SPECT scans), and the patient's general condition.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eSurgical procedure\u003c/span\u003e \u003c/p\u003e \u003cp\u003eAll patients underwent surgery in general anaesthesia supplemented with local anaesthesia (0.5% Marcaine Adrenaline) under sterile conditions. An incision was made on top of the maxillary alveolar process along the exposed bone and the teeth, which had to be removed, with releasing incisions medially and distally as necessary. Necrotic bone was removed, including the teeth involved. Pus, granulation tissue, or both were removed from the maxillary sinuses in conjunction with radical sinusotomy, leaving the sinus without mucosal coverage. Resection of necrotic bone was continued until vital bone was visible clinically. Holes for soft tissue suspension were drilled in the bony edge in the maxillary sinus wall, palatal bone, and through the remaining adjacent alveolar process for later stabilisation of the PMTF with sutures. All excised bone and soft tissue were sent for histopathological examination.\u003c/p\u003e \u003cp\u003eThe PMTF was raised through a preauricular approach with anterior temporal extension. After careful dissection and mobilisation, the PMTF was transposed to the oral cavity medially to the zygomatic arch. In neither of the cases was it necessary to remove the coronoid process. The PMTF was sutured (Ethicon Vicryl Suture 3\u0026thinsp;\u0026minus;\u0026thinsp;0, Johnson \u0026amp; Johnson) using the drill holes and the palatal mucosa. The remaining mucoperiosteal flap was mobilised to ensure tension-free closure and sutured partly on top of the PMTF, providing a partial two-layer closure with mattress sutures and interrupted single sutures (Ethicon Vicryl Suture 4\u0026thinsp;\u0026minus;\u0026thinsp;0, Johnson \u0026amp; Johnson). PHDPE implants were customised to the defect and stabilised with osteosynthesis screws to reconstruct the temporal donor site.\u003c/p\u003e \u003cp\u003eAntibiotic treatment included Amoxicillin/Clavulanic acid 500/125 mg three times daily, starting one day preoperatively. From surgery until discharge, all patients received Cefuroxime 1500 mg intravenously, three times daily. After discharge, postoperative peroral antibiotics were continued, Amoxicillin/Clavulanic acid 500/125 mg, three times daily for ten days. The patients were seen at regular follow-ups: 14 days postoperatively (for the removal of extraoral sutures), one month (for the removal of remaining intraoral sutures), and again at three, six, nine, and 12 months during the first year, after which they were seen yearly. Pain was monitored pre-operatively and at each follow-up using the numerical ranking scale (NRS), and the state of healing was documented.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eStatistical analysis\u003c/span\u003e\u003c/h2\u003e \u003cp\u003eDescriptive statistical analyses were performed due to the low number of patients and the explorative nature of the study.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eUnpublished data from the Copenhagen ONJ Cohort (1 January 2005 to 31 December 2024) consisting of 934 patients revealed that the mandible was affected in 64.9%, the maxilla in 29.1%, and both jaws in 6% of the patients. Twelve patients met the inclusion criteria and were eligible for PMTF reconstruction. However, five patients in need of PMTF were either not suitable for the operation due to their health status (two patients) or unwilling to proceed with the operation, opting instead for a conservative treatment alternative (three patients). Thus, seven patients were treated with PMTF. The demographic data of patients treated with PMTF are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic data of seven patients treated with pedicled myofascial temporalis flap for closure of large defects after maxillary MRONJ lesions.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatient (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years - mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3 (67\u0026ndash;84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative weight, kg \u0026ndash; mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56.8\u0026thinsp;\u0026plusmn;\u0026thinsp;13.8 (41-74.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWomen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eECOG Perfomance Status, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (57.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneral diagnoses, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsteoporosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple myeloma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast cancer and osteoporosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (42.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntiresorptive treatment, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBisphosphonates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (28.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of antiresorptive treatment, months - mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBisphosphonates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49.9\u0026thinsp;\u0026plusmn;\u0026thinsp;34.2 (12\u0026ndash;96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDenosumab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAntiresorptive treatment stopped, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePaused antiresorptive before operation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidity, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSteroid (1 prior treatment and 3 current treated)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy (1 missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (71.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious or current tobacco user\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (57.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDental trauma, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTooth extraction before onset of MRONJ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (42.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumeric Rating Scale (NRS) pain from the jaw- mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS preoperative (1 missing)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.08 (0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNRS postoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFollow up, months - mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.0\u0026thinsp;\u0026plusmn;\u0026thinsp;12.47 (3\u0026ndash;34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime from operation to death (4 patients), months \u0026ndash; mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.1 (6\u0026ndash;33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e\u003cb\u003e*\u003c/b\u003eECOG Performance Status: 0\u0026thinsp;=\u0026thinsp;Fully active, able to carry on all pre-disease performance without restriction. 1\u0026thinsp;=\u0026thinsp;Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work. 2\u0026thinsp;=\u0026thinsp;Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3\u0026thinsp;=\u0026thinsp;Capable of only limited self-care, confined to bed or chair for more than 50% of waking hours. 4\u0026thinsp;=\u0026thinsp;Completely disabled. Cannot carry on self-care. Confined to bed or chair [\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e].\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eOperation details\u003c/span\u003e \u003c/p\u003e \u003cp\u003eHistological examinations of the clinically non-vital bone all showed areas of necrotic bone, appositional bone growth, colonies of microorganisms, and acute and chronic inflammation. Examination of mucosal and soft tissue removed from the sinus and sinus tracts revealed acute and chronic inflamed tissue. No malignancies were identified histologically. The mean dimension of the resulting defects on the postoperative CT scan measured 1795,03 mm\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;686,40 mm\u003csup\u003e2\u003c/sup\u003e. The largest dimension was 2311,92 mm\u003csup\u003e2\u003c/sup\u003e, and the smallest was 665 mm\u003csup\u003e2\u003c/sup\u003e. It was possible to close all defects with the PMTF.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003ePatient outcome\u003c/span\u003e \u003c/p\u003e \u003cp\u003ePostoperatively, all patients healed uneventfully intraorally after resection and complete closure with PMTF was achieved. One patient was previously treated with a bloc resection and primary wound closure due to MRONJ in the maxilla. Eight months postoperatively, a recurrence of the MRONJ lesion was diagnosed, affecting an area where PMTF was indicated (case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAt a six-month follow-up, one patient had developed a local dehiscence in the temporal region, which dictated the removal of the placed PHDPE implant. The defect was closed with local flaps. The second postoperative healing was compromised, but the defect eventually healed by secondary intention after discontinuing dexamethasone and local treatment with methylrosaniline at the wound edges, zinc ointment, and application of Synalar (case \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Thus, six out of seven PHDPE implants (85.7%) healed without complications. The mean observation period was 20.3 months\u0026thinsp;\u0026plusmn;\u0026thinsp;15.9 months (range 2.2 to 44.4 months). The mean pain score was reduced from NRS 2.0 (range 0\u0026ndash;5) before surgery to NRS 0.0 one month postoperatively.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eCase presentation\u003c/span\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eCase 1\u003c/span\u003e\u003c/strong\u003e \u003cp\u003eAn 84-year-old female patient, presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e., was diagnosed with breast cancer in 2009 and osteoporosis in 2011. Comorbidities: hypertension, hypercholesterolemia, chronic renal insufficiency, and uric acid gout. Treated with Alendronate 70 mg weekly for a total of 57 months prior to surgery, with no steroid treatment, but receiving Letrozole treatment due to breast cancer. NRS 2 at the initial visit and spontaneously developed stage 3 MRONJ. A) Clinical photos (facial and palatal) and OPG show stage 3 MRONJ in regions 21, 22, 23, 24, 25, and 26. B) Four months after bloc resection of the region 21 to 27, mucosal healing and no sign of necrosis on OPG. C) Eight months after surgery, clinical pictures show chronic infection in regions 11 to 25. OPG with osteolysis 17, 16, 15 and 11, 21, 22, 23. D) Eleven months after initial surgery, immediately before secondary surgery, planned for maxillectomy, left-side PMTF, right-side buccal fat pad and dental implant operation to achieve later dental rehabilitation. Clinical pictures show chronic infection in oral mucosa, exposed bone 17, 16, 15 and inferior conchae on the patient's left side. OPG shows osteolytic bone in the alveolar process bilateral in the maxilla, with the destruction of the sinus and nasal floor, likewise sinus reaction bilateral. E) Fourteen days post-second surgery, healing intra- and extraoral. Intraoral area of the temporal muscle with ongoing epithelisation. OPG shows maxillary resection and dental implants in place. F) Three months after the second surgery, prior to abutment surgery, healing both intra- and extraorally, with no signs of necrosis. OPG after abutment operation shows sign of osseointegration and no sign of bone loss around implants G) Prosthetic treatment six months after placement of dental implants, Atlantis\u0026reg; Cobalt Chrome acrylic bridge, OPG shows bridge in place, minor bone loss around dental implant 13. No sign of reaction in the right maxillary sinus. H) Three-year follow-up after prosthetic treatment, 3.5 years after the secondary surgery. Dental bridge in situ, no sign of intra- or extraoral infection, no necrotic bone, no pain or discomfort. OPG shows unchanged bone loss at dental implant 13 and only minor bone loss at dental implant 28, with no reaction in the maxillary sinus.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003e\u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eCase 2\u003c/span\u003e\u003c/strong\u003e \u003cp\u003eAn 75-year-old female patient, presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e., with multiple myeloma received high-dose anti-resorptive treatment with Denosumab 120 mg every four weeks for 63 months prior to surgery. Simultaneously treated with steroids and chemotherapy, Lenalidomide. No pain. A) The clinical photo shows spontaneous stage 3 MRONJ that has developed in regions 17, 16, 15, and 14. B, C, D, E) CBCT shows periosteal reaction in the right maxillary sinus, sinusitis, osteolytic and osteosclerotic reaction in alveolar process in region of 17, 16, 15, 14, 13, right side in palatal, maxillary and zygomatic bone, with minor sequestrum formation. F) Clinically exposed bone on the day of surgery. G) Following the resection of bone and the removal of granulation tissue, the right side of the nasal and sinus cavities is exposed. H) Resected maxilla, Brown and Shaw classification IIb. I) Temporal muscle after incision. J) Elevation of the temporal muscle, sutures placed in lateral and medial fascia and used to pull the temporal muscle orally on the medial aspect of the zygomatic arch. K) Temporal muscle sutured to bony edges and remaining palatal mucosa. L) PHDPE implants in place fixed with osteosynthesis screws. M) Intraoral sutures. N) Extraoral sutures. O, P, Q) Follow-up 14 days post-surgery, extraoral after suture removal, intraoral and CBCT. R, S) Follow-up 30 days, extraoral healing, intraoral after suture removal. T) Spontaneously developed dehiscence at 3 months follow-up, exposed PHDPE implant. U) Follow-up three weeks after removal of PHDPE implant: extraoral, ischemic necrotic cutis. V) Six-month follow-up intraorally, tooth 11 removed one month prior, and removable prosthesis in place. X) Five months after removal of PHDPE implant \u0026ndash; demarcation of necrotic skin and exposed calvaria bone, no infection, paused in dexamethasone. Y) One month after termination of dexamethasone, granulation of cutaneous edges, but unchanged exposed calvaria bone. Z) Three months after referral to plastic surgeons, treated in the special unit of wound care, treated by discontinuation of dexamethasone and local treatment with methylrosaniline at the wound edges, zinc ointment, and application of Synalar. Treatment resulted in hypergranulation over the former exposed bone.\u003c/p\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis retrospective cohort study evaluated the healing outcomes of extensive stage 3 maxillary MRONJ lesions treated with PMTF and PHDPE implant placement for temporal donor defect reconstruction. To the authors' knowledge, no prior studies had reported maxillary stage 3 MRONJ defect closure using PMTF. This study presented the largest single-centre case series to date. Within the Copenhagen ONJ Cohort, maxillary involvement was common, yet only a small proportion of cases were managed using PMTF. These findings underscored the rarity of this treatment approach and highlighted the need for highly individualised treatment planning. The results contributed valuable clinical insights into an uncommon but potentially effective reconstructive strategy for severe stage 3 maxillary MRONJ cases.\u003c/p\u003e \u003cp\u003eAljohani et al. defined the accepted surgical treatment of MRONJ lesions as the complete removal of necrotic bone followed by the removal of sharp bone edges and meticulous primary wound closure [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This treatment principle was applied in the present study, and all seven patients recovered without complications related to the removal of necrotic bone and the closure of the resulting defect using the PMTF. The results emphasise the importance of completely removing necrotic bone and achieving a tension-free, watertight closure when treating patients affected by MRONJ.\u003c/p\u003e \u003cp\u003eReconstructing maxillary defects caused by MRONJ presents major functional and aesthetic challenges, alongside difficulties in prosthetic rehabilitation [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Compromised healing due to medical histories complicates this situation, especially the use of AR, making reconstruction more complex and healing outcomes unpredictable. Positive results have been previously achieved with obturation and surgical reconstruction [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prosthetic obturator is a well-established and effective method for closing maxillary defects, including those associated with MRONJ [\u003cspan additionalcitationids=\"CR43\" citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. It offers several advantages: requiring only a single surgery for resection and reconstruction, immediately restoring dentition, preventing nasal leakage, and improving speech, mastication, aesthetics, and overall HRQoL while also allowing for cavity surveillance [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. Some concerns exist regarding the potential for MRONJ recurrence due to trauma from the removable prosthesis. However, studies suggest that patients tolerate obturators well, with no recurrence observed [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Aljohani et al. stated that obturators could be used for large defects that are possibly difficult to successfully cover with regional flaps and for patients with poor health status. All the patients in their study indicated a high satisfaction response with the prosthetic obturator and no MRONJ recurrence over the 3 to 18-month follow-up period [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This was, however, a small sample size and a short follow-up period. Conversely, a comparative study by Moreno et al. found that surgical reconstruction yielded superior functional outcomes, particularly in cases involving larger horizontal defects [\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe stability and retention of the obturator are primarily determined by the defect's location and size, the supporting surface area of the remaining palate, and the condition of the remaining teeth [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Poor stability and retention results in a loose-fitting denture, which increase the risk of traumatic ulceration leading to MRONJ recurrence. Large maxillary defects, especially in edentulous patients, make surgical reconstruction a viable option that would enhance patients' functionality and HRQoL [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe success of the obturator relies on the patient\u0026rsquo;s daily adherence to the hygiene of the prosthesis as well as the remaining communication [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. However, this approach may not be feasible for patients with compromised dexterity or poor health. In such cases, surgical alternatives like the PMTF. PMTF provides immediate closure of oral-nasal and oral-antral communications, does not require teeth like the obturator for reconstruction, provides a stable base for the prosthesis, and following epithelialisation, the mucosa resembles the adjacent oral mucosa. Additionally, in combination with dental implants, an implant-retained prosthesis will restore occlusion and function [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. All patients were given the option of surgery or a conservative alternative. Consequently, five patients chose conservative treatment due to their health status or preference, while seven patients underwent reconstruction with PMTF.\u003c/p\u003e \u003cp\u003eThere is an overall consensus that some kind of surgical reconstruction algorithm needs to be followed depending on the size of the maxillary defect [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. A relevant surgical reconstructive ladder for maxillary MRONJ includes the primary use of local mucoperiosteal flaps. If this is insufficient, local flaps (buccal fat pad or PMTF) and, lastly, free flaps can be used to reconstruct defects related to MRONJ [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCompared to more conservative approaches, surgical interventions, with or without adjunctive therapies (parathyroid hormone, low-level laser therapy, ozone therapy, and hyperbaric oxygen therapy), are more effective in downgrading or healing MRONJ lesions at any stage [\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e]. Klingelh\u0026ouml;ffer et al., however, stated that surgical interventions might not be sufficient for long-term wound closure [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. However, the study only used a mucoperiosteal flap for tension-free closure. Tension-free, water-tight closure with local mucoperiosteal flaps is a successful reconstruction method; however, having sufficient tissue to ensure this closure is impossible in large lesions, leading to healing complications and the recurrence of MRONJ [\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e]. The success of surgical reconstruction of MRONJ-associated defects is the use of multiple tissue layers for closure to ensure the long-term success of MRONJ treatment [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNasolabial flaps have been reported as a successful treatment option for reconstructing small to medium-sized MRONJ lesions, with 68\u0026ndash;93% success rates [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. Lemound et al. found in a comparative study that nasolabial flaps had significantly better wound closure (P\u0026thinsp;=\u0026thinsp;0.005) than mucoperiosteal flaps due to a multilayer closure in treating MRONJ-associated lesions [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The nasolabial flap technique is less time-consuming and simpler than reconstruction with free flaps. However, Rai et al. warn that the bulkiness of these nasolabial flaps makes dental rehabilitation difficult, with hair growth and scaring complicating rehabilitation even further [\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. This makes the buccal fat pad an intriguing treatment alternative.\u003c/p\u003e \u003cp\u003eThe use of the buccal fat pad flap underscores the success of this multiple-layer closure technique, as it has been the workhorse of numerous successfully treated small to medium-sized MRONJ maxillary defect closures in our department [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. It is a simple and time-efficient technique, epithelialising within three to four weeks. However, it is limited once the defect size exceeds 50 mm diameter, beyond which a tight mucosal closure becomes problematic [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. The buccal fat pad flap is limited in extension past the palatal midline, only covers the defect, and doesn\u0026rsquo;t add bulk [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. When the extent of maxillary defects surpasses the capability of the buccal fat pad, PMTF may be considered the next reconstruction option [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The defect size in this study varied from 665 mm\u003csup\u003e2\u003c/sup\u003e up to 2311.92 mm\u003csup\u003e2\u003c/sup\u003e with a mean of 1795.03 mm\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;686.40 mm\u003csup\u003e2\u003c/sup\u003e. This extends beyond the ability of the buccal fat pad flap, particularly when a defect requires additional volume for improved prosthetic rehabilitation. For this reason, the PMTF was utilised for reconstruction.\u003c/p\u003e \u003cp\u003eThe PMTF has not been described for the closure of defects related to MRONJ, but it has been successful for other reconstruction purposes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. The PMTF is used as an alternative when other flap attempts have failed [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The PMTF is an excellent option for reconstructing medium to large-sized intraoral defects due to its anatomical proximity, vascularity, and adequate bulk. With intraoral re-epithelisation expected within four to six weeks, there are no concerns regarding hair growth associated with the reconstructed defect [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe patient presented in case \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e was previously treated with a block resection and primary wound closure using a mucoperiosteal flap due to MRONJ in the maxilla. However, a recurrence of the MRONJ lesion occurred eight months postoperatively, resulting in a defect for which a PMTF was indicated. After reconstruction with a combination of PMTF of the left side with PHDPE implant placement to compensate for the temporal defect, buccal fat pad flap on the right side, and dental implant placement, the patient healed without complications. Three years after treatment, the patient was stable without pain (NRS\u0026thinsp;=\u0026thinsp;0). This outcome highlights the importance of patient-specific treatment planning and the effectiveness of multiple-layer tissue closure for the treatment of advanced MRONJ-associated lesions.\u003c/p\u003e \u003cp\u003eAs with any kind of surgical reconstructive, PMTF may present potential complications. Spanio di Spilimbergo et al. published a case series on complications after 366 PMTF, divided into periods 1978\u0026ndash;1993 (195 patients) and 1994\u0026ndash;2012 (171 patients), describing total flap necrosis in 1.5% and 1.7%, intraoral dehiscence in 12.8% and 12.2%, permanent paralysis of the frontal branch of the facial nerve in 12.8% and 12.2%, trismus in 46.8% and 48%, and necessity of removal of alloplastic material from donor side in 17.1% and 7.9%, respectively. In the latter period, only PHDPE material was used in this study, emphasising the success of using this type of implant for donor site reconstruction [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Six out of seven PHDPE implants (85.7%) in our study healed without complications. Only one patient developed local dehiscence in the temporal region at a six-month follow-up. The PHDPE implant was removed, and the defect was closed with local flaps. The patient again had healing complications, but the defect eventually healed with the help of the special care unit for wound care. This outcome highlights how these patients' health can deteriorate over time and emphasises the importance of daily hygiene, nutrition, and regular follow-ups to prevent and address late complications.\u003c/p\u003e \u003cp\u003eThe results of the present case series support that the PMTF is a viable, safe technique with a low complication rate and high success rate in extensive hemi-maxillectomy cases where rehabilitation is not possible with other methods. It provides a watertight seal, allows for additional bone grafting for possible dental implant-supported rehabilitation, and improves the patient\u0026rsquo;s HRQoL. Furthermore, it is more cost-effective, has a shorter operation time, and requires only a single reconstruction team compared to reconstruction with free flaps [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e]. The mean pain score was reduced from NRS 2.0 (range 0\u0026ndash;5) before surgery to NRS 0.0 one month postoperatively. It is noteworthy that some patients had severe infection and pain prior to surgery, whereas others did not. This insidious progression of the disease contributes to a delayed presentation, as the lack of pain deprives patients of a crucial early warning sign. Consequently, patients often do not seek medical attention until the condition has advanced significantly, typically by which time extensive lesions have developed, involving large portions of the maxilla. This late presentation frequently results in the loss of substantial volumes of bone and adjacent teeth. Once the defect exceeds the capability of the PMTF, free flap reconstruction will be the next suitable treatment option.\u003c/p\u003e \u003cp\u003eSeveral studies have reported on the reconstruction of MRONJ lesions using free flaps. Most reported on mandibular lesions with large soft tissue defects and poor vascularisation [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e]. M\u0026uuml;cke et al. report the successful reconstruction of an MRONJ lesion using an anterolateral thigh flap in one patient and radial forearm flaps in four patients [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. These procedures are complex and often involve lengthy operative times with multiple teams, the risk of donor site morbidity, and intricate postoperative dental prosthetic rehabilitation. These are factors to take into account and are not indicated for the treatment of MRONJ patients with incurable malignancies, poor overall health, and limited life expectancy. A critical assessment needs to be made of the cost and benefit ratio and treatment efficacy of the reconstruction in extensive bony and soft tissue lesions in patients with good overall health status [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn all the cases in this study, mobilising sufficient PMTF and securing tight multi-layered closure of the defect to the sinus or nose or both were possible. There was no correlation between the size of the defects and the patients' healing outcome. The success rate of treatment was 100% after resection and reconstruction with PMTF, with no complications related to the flap procedure, but one patient had a complication related to the donor site reconstruction. There is a constant need to identify risk factors and establish the best possible regime for performing operations, including assessing which patients to operate on and which to exclude. One might wonder whether the risk of reconstruction justifies the potential for MRONJ recurrence and the associated costs, considering the patient's life expectancy. However, many of these patients suffer from chronic pain and facial disfigurement, which complicate everyday activities such as eating and speaking. Any opportunity to improve the quality of their remaining life should be welcomed within reasonable limits.\u003c/p\u003e \u003cp\u003e \u003cspan type=\"SmallCaps\" class=\"SmallCaps\" name=\"Emphasis\"\u003eLimitations\u003c/span\u003e \u003c/p\u003e \u003cp\u003eThis study presents several limitations. Firstly, its retrospective design resulted in incomplete data availability, which may have impacted the depth and breadth of the analysis. Additionally, the small sample size limits the generalizability of the results significantly. Although the findings are important, the limited number of patients could affect the overall reliability of the results and the strength of the conclusions drawn.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study demonstrated that using PMTF for the closure of large oro-antral defects, oro-nasal defects, or both is a reliable method to treat MRONJ lesions with a high success rate (100%). The temporal defect reconstruction following PMTF transposition can be accomplished using a PHDPE temporal implant.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNone\u003c/p\u003e \u003cp\u003e \u003cb\u003eHuman ethics declaration\u003c/b\u003e: Not applicable\u003c/p\u003e \u003cp\u003e\u003cb\u003eConsent to participate\u003c/b\u003e: All human participants sign a written consent to participate\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical trial number\u003c/b\u003e: Not applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSanne Werner Moeller Andersen: conceptualisation, data curation, formal analysis, investigation, methodology, project administration, supervision, validation, visualisation, writing original draft, writing review, and editing.Liezl Dawson: writing original draft, writing review, and editing.Iben Poulsen: formal analysis, investigation, methodology, validation, writing review, and editing.Simon Storg\u0026aring;rd Jensen: supervision, validation, writing review, and editing.Thomas Kofod: conceptualisation, investigation, resources, supervision, validation, writing review, and editing.\u003c/p\u003e\u003ch2\u003eAvailability of data and material:\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003cp\u003e \u003cb\u003eCode availability\u003c/b\u003e: Not applicable.\u003c/p\u003e \u003cp\u003e \u003cb\u003eEthics approval\u003c/b\u003e: Ethic committee protocol no. R-22046553, P-2022-856.\u003c/p\u003e \u003cp\u003e Consent to participate: All patients signed an informed consent.\u003c/p\u003e \u003cp\u003eConsent for publication: Not applicable.\u003c/p\u003e \u003cp\u003eConflict of interest: Liezl Dawson, recipient of 1-year ITI scholarship.\u003c/p\u003e \u003cp\u003eOther authors have no conflicts of interest to declare.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMarx RE (2003) Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: a growing epidemic. Journal of oral and maxillofacial surgery 61(9): 1115-1117. https://doi.org/10.1016/s0278-2391(03)00720-1 \u003c/li\u003e\n\u003cli\u003eRuggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D (2022) American Association of Oral and Maxillofacial Surgeons\u0026apos; Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. 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J Oral Maxillofac Surg 72(10): 1938-1956. https://doi.org/10.1016/j.joms.2014.04.031 \u003c/li\u003e\n\u003cli\u003eChiandussi S, Biasotto M, Dore F, Cavalli F, Cova MA, Di Lenarda R (2006) Clinical and diagnostic imaging of bisphosphonate-associated osteonecrosis of the jaws. Dentomaxillofac Radiol 35(4): 236-243. https://doi.org/10.1259/dmfr/27458726 \u003c/li\u003e\n\u003cli\u003eSchiodt M, Otto S, Fedele S, Bedogni A, Nicolatou-Galitis O, Guggenberger R, Herlofson BB, Ristow O, Kofod T (2019) Workshop of European task force on medication-related osteonecrosis of the jaw-Current challenges. Oral Dis 25(7): 1815-1821. https://doi.org/10.1111/odi.13160 \u003c/li\u003e\n\u003cli\u003eBrown JS, Rogers SN, McNally DN, Boyle M (2000) A modified classification for the maxillectomy defect. Head Neck 22(1): 17-26. https://doi.org/10.1002/(sici)1097-0347(200001)22:1\u0026lt;17::aid-hed4\u0026gt;3.0.co;2-2 \u003c/li\u003e\n\u003cli\u003eKlingelh\u0026ouml;ffer C, Zeman F, Meier J, Reichert TE, Ettl T (2016) Evaluation of surgical outcome and influencing risk factors in patients with medication-related osteonecrosis of the jaws. J Craniomaxillofac Surg 44(10): 1694-1699. https://doi.org/10.1016/j.jcms.2016.08.001 \u003c/li\u003e\n\u003cli\u003eMarx RE (2009) Reconstruction of defects caused by bisphosphonate-induced osteonecrosis of the jaws. J Oral Maxillofac Surg 67(5 Suppl): 107-119. https://doi.org/10.1016/j.joms.2008.12.007 \u003c/li\u003e\n\u003cli\u003eOkay DJ, Genden E, Buchbinder D, Urken M (2001) Prosthodontic guidelines for surgical reconstruction of the maxilla: a classification system of defects. J Prosthet Dent 86(4): 352-363. https://doi.org/10.1067/mpr.2001.119524 \u003c/li\u003e\n\u003cli\u003ede Almeida FC, Moreira MS, Marcucci M, Marques MM, de Araujo ME, da Silva DP (2014) New uses for rehabilitation protocol for oral sinus communications in ARONJ patients. J Prosthodont 23(8): 649-653. https://doi.org/10.1111/jopr.12157 \u003c/li\u003e\n\u003cli\u003eKornblith AB, Zlotolow IM, Gooen J, Huryn JM, Lerner T, Strong EW, Shah JP, Spiro RH, Holland JC (1996) Quality of life of maxillectomy patients using an obturator prosthesis. Head Neck 18(4): 323-334. https://doi.org/10.1002/(SICI)1097-0347(199607/08)18:4\u0026lt;323::AID-HED3\u0026gt;3.0.Co;2-# \u003c/li\u003e\n\u003cli\u003eMoreno MA, Skoracki RJ, Hanna EY, Hanasono MM (2010) Microvascular free flap reconstruction versus palatal obturation for maxillectomy defects. 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Eur Rev Med Pharmacol Sci 25(6): 2662-2673. https://doi.org/10.26355/eurrev_202103_25430 \u003c/li\u003e\n\u003cli\u003eM\u0026uuml;cke T, Jung M, Koerdt S, Mitchell DA, Loeffelbein D, Kesting MR (2016) Free flap reconstruction for patients with bisphosphonate related osteonecrosis of the jaws after mandibulectomy. Journal of cranio-Maxillofacial surgery 44(2): 142-147. \u003c/li\u003e\n\u003cli\u003eEckardt AM, Kokem\u0026uuml;ller H, Tavassol F, Gellrich NC (2011) Reconstruction of oral mucosal defects using the nasolabial flap: clinical experience with 22 patients. Head Neck Oncol 3: 28. https://doi.org/10.1186/1758-3284-3-28 \u003c/li\u003e\n\u003cli\u003eRai A, Datarkar A, Rai M (2014) Is buccal fat pad a better option than nasolabial flap for reconstruction of intraoral defects after surgical release of fibrous bands in patients with oral submucous fibrosis? A pilot study: a protocol for the management of oral submucous fibrosis. 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Available: https://journals.lww.com/amjclinicaloncology/abstract/1982/12000/toxicity_and_response_criteria_of_the_eastern.14.aspx\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"oral-and-maxillofacial-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"omfs","sideBox":"Learn more about [Oral and Maxillofacial Surgery](http://link.springer.com/journal/10006)","snPcode":"10006","submissionUrl":"https://submission.nature.com/new-submission/10006/3","title":"Oral and Maxillofacial Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Bisphosphonate-associated osteonecrosis of the jaws, surgical flaps, bone density conservation agents, temporal muscle, maxillary disease","lastPublishedDoi":"10.21203/rs.3.rs-6462559/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6462559/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e \u003cp\u003eMedication-related osteonecrosis of the jaws (MRONJ) located in the maxilla may lead to challenging oro-antral and oro-nasal defects too extensive to be predictably closed with local soft tissue flaps. The use of a pedicled myofascial temporalis flap (PMTF) is, however, well-established for closing large maxillary defects following ablative craniomaxillofacial surgery.\u003c/p\u003e\u003ch2\u003eObjectives:\u003c/h2\u003e \u003cp\u003eThe purpose of the present study was to evaluate the use of PMTF for maxillary defect closure in patients with stage 3 MRONJ.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eA retrospective cohort study was conducted based on data from the Copenhagen ONJ cohort from 1 January 2005 to 31 December 2024. The inclusion criteria were consecutive patients with extensive maxillary defects after surgical treatment of MRONJ and closed with PMTF.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003eSeven patients met the inclusion criteria (three patients with cancer, two patients with osteoporosis, and two patients with cancer and osteoporosis). Lesions were assessed both clinically and radiographically. All patients healed uneventfully and reported significantly reduced pain after surgery. One patient developed a late complication at the donor site.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e \u003cp\u003eThe removal of necrotic bone combined with radical sinusotomy and closure of the defect with PMTF is a predictable method to treat extensive maxillary MRONJ lesions with a high success rate.\u003c/p\u003e","manuscriptTitle":"Pedicled Myofascial Temporalis Flap for Closure of Large Maxillary Defects After Medication-Related Osteonecrosis of the Jaws. 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