Compromised osseous healing of dental extraction sites in zoledronic acid-treated dogs.

UNLABELLED: The goal of this study was to document how treatment with high doses of zoledronic acid affects dental extraction healing. Our results, showing significantly compromised osseous healing within the socket as well as presence of exposed bone and development of a sequestrum in one animal, provide a building block toward understanding osteonecrosis of the jaw. PURPOSE: The goal of this study was to document how treatment with a bisphosphonate affects the bone tissue following dental extraction. METHODS: Skeletally mature female beagle dogs were either untreated controls (CON) or treated with intravenous zoledronic acid (ZOL). Following the extraction of the fourth premolars, healing was allowed for 4 or 8 weeks. Properties of the extraction site were assessed using microcomputed tomography (micro-CT) and dynamic histomorphometry. RESULTS: The initial infilling of the extraction socket with bone was not affected by ZOL, but subsequent removal of this bone was significantly suppressed compared to CON. After 8 weeks of healing, the alveolar cortical bone adjacent to the extraction socket had a remodeling rate of ∼50% per year in CON animals while ZOL-treated animals had a rate of <1% per year. One ZOL-treated animal developed exposed bone post-extraction which eventually led to the formation of a sequestrum. Assessment of the sequestrum with micro-CT and histology showed that it had features consistent with those reported in humans with osteonecrosis of the jaw. CONCLUSIONS: These results, showing significantly compromised post-extraction osseous healing as well as presence of exposed bone and development of a sequestrum in one ZOL animal, provide a building block toward understanding the pathophysiology of osteonecrosis of the jaw.

Previously successful dental implants can fail when patients commence anti-resorptive therapy-a case series.

This article reports a type of localized osteonecrosis that can occur in patients who have had successful osseointegrated implants for many years and then commence anti-resorptive therapy. Eleven female patients were identified who had successful implant insertion, but who were placed on anti-resorptive therapy (bisphosphonates or denosumab) several years later and developed osteonecrosis around the implants. In each case, the osteonecrosis occurred only around the implants and not around the patient's remaining teeth. The implants of eight patients were removed with a sequestrum of bone tightly adherent to the implant. This is different from the normal pattern of implant failure. Implant failure can occur when patients with successfully integrated implants are later placed on anti-resorptive therapy, and the osteonecrosis takes a particular form where a sequestrum forms that remains adherent to the implant. Why the adjacent remaining teeth are not affected is unclear.

Osteonecrosis of the jaws and bisphosphonate therapy.

Bisphosphonates are a class of agents used to treat osteoporosis and malignant bone metastases. The efficacy of these agents in treating and preventing the significant skeletal complications associated with these conditions has had a major positive impact for patients and is responsible for their widespread use in medicine. Despite these benefits, osteonecrosis of the jaws has recently emerged as a significant complication in a subset of patients receiving these drugs. Based on a growing number of case reports and institutional reviews, bisphosphonate therapy may cause exposed and necrotic bone that is isolated to the jaw. This complication usually presents following simple dento-alveolar surgery, and can cause a significant adverse effect on the quality of life for most patients. The pathogenesis for this complication appears to be related to the profound inhibition of osteoclast function and bone remodeling.

Hyaluronidase activity of rabbit skin wound granulation tissue fibroblasts.

The objective of this work was to identify and compare hyaluronidase activities of normal dermal and dermal wound granulation tissue fibroblasts. Direct evidence of the fibroblast as a source of tissue hyaluronidase was obtained. Fourth passage rabbit dermal fibroblasts were harvested on culture days 4, 8, 14, 18, and 22. Hyaluronidase activity and [35S]-sulfate- or [3H]-glucosamine-labeled glycosaminoglycans (GAGs) were monitored. Hyaluronidase assays were performed on medium and cellular fractions at the designated intervals. Enzyme activity of cellular fractions for both normal dermal and 14-day post-wound granulation tissue fibroblasts increased progressively through culture day 8. Thereafter (days 14-22), an eight-fold drop in cellular activity was coupled with cell death and emergence of hyaluronidase activity in medium fractions. Marked increases in degradation of secreted matrix components were concurrent with lysis-induced release of hyaluronidase. In this culture system, hyaluronidase activity was confined exclusively to cellular fractions and was released into the medium only under non-physiological conditions conducive to cellular death and lysis. Accordingly, this work suggests that previously reported skin wound hyaluronidases may be of fibroblastic origin and that susceptible GAGs are not degraded extracellularly, but, rather, must be internalized as a prerequisite to depolymerization.

Surgical management of lingual nerve injuries.

Injuries to the lingual nerve remain a relatively uncommon event. However, given the frequency of surgical procedures in this anatomic region, it is likely that every oral and maxillofacial surgeon will be required to manage such an injury. When spontaneous recovery of lingual sensation is absent, microsurgical reconstruction can predictably achieve improved sensation in a majority of patients provided that such injuries are properly assessed and treated early. The quality of the sensory improvement is related to the age of the patient, the timing of surgery, the extent of the neural injury, and the quality of the repair.

Trigeminal nerve injury and repair.

Injuries to the inferior alveolar nerve (IAN) and the lingual nerve are relatively uncommon. However, there are certain routine surgical and non-surgical procedures that have the potential, albeit small, for injuring these neural structures. A review of the diagnosis, classification and management of these injuries is presented.