A Strategy against the Osteonecrosis of the Jaw Associated with Nitrogen-Containing Bisphosphonates (N-BPs): Attempts to Replace N-BPs with the Non-N-BP Etidronate.

Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) can occur when enhanced bone-resorptive diseases are treated with nitrogen-containing BPs (N-BPs). Having previously found, in mice, that the non-N-BP etidronate can (i) reduce the inflammatory/necrotic effects of N-BPs by inhibiting their intracellular entry and (ii) antagonize the binding of N-BPs to bone hydroxyapatite, we hypothesized that etidronate-replacement therapy (Eti-RT) might be useful for patients with, or at risk of, BRONJ. In the present study we examined this hypothesis. In each of 25 patients receiving N-BP treatment, the N-BP was discontinued when BRONJ was suspected and/or diagnosed. After consultation with the physician-in-charge and with the patient's informed consent, Eti-RT was instituted in one group according to its standard oral prescription. We retrospectively compared this Eti-RT group (11 patients) with a non-Eti-RT group (14 patients). The Eti-RT group (6 oral N-BP patients and 5 intravenous N-BP patients) and the non-Eti-RT group (5 oral N-BP patients and 9 intravenous N-BP patients) were all stage 2-3 BRONJ. Both in oral and intravenous N-BP patients (particularly in the former patients), Eti-RT promoted or tended to promote the separation and removal of sequestra and thereby promoted the recovery of soft-tissues, allowing them to cover the exposed jawbone. These results suggest that Eti-RT may be an effective choice for BRONJ caused by either oral or intravenous N-BPs and for BRONJ prevention, while retaining a level of anti-bone-resorption. Eti-RT may also be effective at preventing BRONJ in N-BP-treated patients at risk of BRONJ. However, prospective trials are still required.

Clinical outcomes of open and closed management after surgical treatments in patients with medication-related osteonecrosis of the jaw.

CONTEXT AND PURPOSE: To achieve success following surgical treatment of MRONJ, complete wound closure has been considered necessary; open wound management has not been generally recommended. Therefore, various closure techniques using local flaps have been reported. However, these techniques often increase surgical invasiveness, and there is minimal evidence regarding whether complete wound closure is preferable to open wound management following surgical treatment of MRONJ. The aim of this study was to clarify whether complete wound closure is necessary for successful healing following surgical treatment of MRONJ. PROCEDURES: This retrospective study included 52 patients with stage 2 and 3 MRONJ who underwent surgical treatment. Twenty-seven of the 52 patients received open wound management, while the remaining 25 received complete wound closure management. The outcomes of both groups were evaluated at the 6-month follow-up visit; 'success' was defined as complete mucosal covering without symptoms and 'failure' was defined as the presence of residual bone exposure or progression of disease. MAIN FINDINGS: In the open wound group, 23 patients (85.1%) exhibited 'success' and four patients (14.8%) exhibited 'failure'; in the closed wound group, 21 patients (84.0%) exhibited 'success' and four patients (16.0%) exhibited 'failure'. These outcomes were not significantly different between groups. PRINCIPAL CONCLUSIONS: Although complete wound closure has many advantages with respect to the healing process, open wound management is also acceptable for patients with difficulty achieving complete wound closure, as well as for surgeons who wish to reduce surgical invasiveness.

Osteogenesis by gradually expanding the interface between bone surface and periosteum enhanced by bone marrow stem cell administration in rabbits.

OBJECTIVE: We investigated whether administration of mesenchymal stem cells (MSCs) promotes bone formation at the gap created by periosteal distraction. STUDY DESIGN: A mesh plate was placed subperiosteally in rabbit parietal bones. Following elevation of the mesh plate, rabbit MSCs were administered into the gap. Controls received phosphate-buffered saline (PBS). The volume, height, bone mineral density (BMD), and bone mineral content (BMC) of newly formed bone were examined using microcomputed tomography. Histological analysis was performed by hematoxylin and eosin staining and immunohistochemistry for type I collagen and osteocalcin. RESULTS: The experimental group showed significantly increased volume, height, BMD, and BMC in newly formed bone tissues at the gaps compared with the control group (P < .05). The newly formed bone tissues showed both type I collagen and osteocalcin expression in the MSC-administration group. CONCLUSION: Mesenchymal stem cell administration may be useful to induce osteogenesis at sites of periosteal distraction.