Persistent Bone-to-Implant Contact in Denosumab-Associated MRONJ: A Multimodal Human Retrieval Study

Background/Objectives: Evidence on the biological integrity of clinically stable dental implants involved in medication-related osteonecrosis of the jaw (MRONJ) is limited. This single-patient human retrieval study characterized the bone–implant interface within a mandibular sequestrum associated with high-dose denosumab therapy, with particular emphasis on the distinction between persistent bone-to-implant contact and biologically viable osseointegration. Methods: A spontaneously exfoliated mandibular sequestrum containing five implants that had remained clinically stable relative to the surrounding bone during earlier phases of MRONJ progression was retrieved from a patient receiving denosumab for metastatic prostate cancer. The specimen was examined by undecalcified histology and histomorphometry. Selected peri-implant and inter-implant bone regions were further evaluated using synchrotron radiation-based phase-contrast microtomography and neural-network-assisted segmentation of osteocyte lacunae. Bone-to-implant contact was quantified over the entire endosseous implant surface (EBIC) and from the first coronal bone contact to the implant apex (FBIC). Results: Persistent bone-to-implant contact was present around all five implants despite extensive osteonecrosis. Histology showed non-vital bone, empty osteocyte lacunae, microfractures, bacterial colonization, demineralized areas, Howship-like resorption lacunae without identifiable osteoclasts, and no detectable osteoblastic activity in the examined fields. Mean EBIC was 42.45 ± 13.41%, whereas mean FBIC was 84.40 ± 4.17%, indicating substantial residual physical contact apical to areas of coronal bone loss. In the sampled regions, peri-implant bone showed lower osteocyte lacunar volume and numerical density and broader relative mineralization distributions than inter-implant bone. Because the observations derived from one patient and non-independent anatomical regions, these comparisons are descriptive and hypothesis-generating. Conclusions: The clinical stability of an implant relative to the surrounding bone should not be interpreted as evidence of biological integrity of the peri-implant interface; at advanced stages, implants may become mobile together with the necrotic sequestrum despite retaining substantial histological bone-to-implant contact. Importantly, persistent histomorphometric contact should not be interpreted as evidence of biologically viable or functional osseointegration. These findings highlight a dissociation between the implant clinical stability, physical bone contact, and biological integrity of the peri-implant interface. Multimodal human retrieval analysis may help characterize the microstructural consequences of MRONJ, although the respective contributions of antiresorptive treatment, infection, peri-implant disease, and mechanical loading require investigation in larger, independently validated datasets.