Eran Regev

The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling

We have recently reported that in bone the cannabinoid CB1 receptor is present in sympathetic terminals. Here we show that traumatic brain injury (TBI), which in humans enhances peripheral osteogenesis and fracture healing, acutely stimulates bone formation in a distant skeletal site. At this site we demonstrate i) a high level of the main endocannabinoid, 2‐arachidonoylglycerol (2‐AG), and expression of diacylglycerol lipases, enzymes essential for 2‐AG synthesis;ii) that the TBI‐induced increase in bone formation is preceded by elevation of the 2‐AG and a decrease in norepinephrine (NE) levels. The TBI stimulation of bone formation was absent in CB1‐null mice. In wild‐type animals it could be mimicked, including the suppression of NE levels, by 2‐AG administration. The TBI‐ and 2‐AG‐induced stimulation of osteogenesis was restrained by the β‐adrenergic receptor agonist isoproterenol. NE from sympathetic terminals is known to tonically inhibit bone formation by activating osteoblastic β2‐adrenergic receptors. The present findings further demonstrate that the sympathetic control of bone formation is regulated through 2‐AG activation of prejunctional CB1. Elevation of bone 2‐AG apparently suppresses NE release from bone sympathetic terminals, thus alleviating the inhibition of bone formation. The involvement of osteoblastic CB2 signaling in this process is minimal, if any.— Tam, J., Trembovler, V., Di Marzo, V., Petrosino, S., Leo, G., Alexandrovich, A., Regev, E., Casap, N., Shteyer, A., Ledent, C., Karsak, M., Zimmer, A., Mechoulam, R., Yirmiya, R., Shohami, E., Bab, I. The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling. FASEB J. 22, 285–294 (2008)

Sunitinib related osteonecrosis of jaw: a case report

A 58-year-old woman presented to the Oral and Maxillofacial Surgery Clinic experiencing severe limited mouth opening and exposed bone in the socket of the right mandibular third molar 8 months following the extraction of the tooth. The patient had been treated during the year before her presentation with sunitinib, an antiangiogenic drug, for renal cell carcinoma. The clinical, radiographic, and histologic picture of a chronic nonhealing extraction socket was consistent with osteonecrosis of the jaw (ONJ), although she had never been treated with bisphosphonates or corticosteroids. The treatment with sunitinib was discontinued and the patient was treated with antibiotics and physiotherapy for 12 weeks with complete recovery. Sunitinib may cause osteonecrosis of the jaw after oral surgical interventions with no previous exposure to bisphosphonates. The pathogenesis may be related to its antiangiogenic mechanism and impaired wound healing. Full recovery may require long-term cessation of the insulting drug combined with prolonged antibiotic treatment.

Atraumatic Teeth Extraction in Bisphosphonate-Treated Patients

PURPOSE The purpose of this study was to suggest an alternative technique for atraumatic teeth extraction that would prevent bone exposure and the associated complication of osteonecrosis of the jaws in bisphosphonate (BP)-treated patients, without terminating the treatment. PATIENTS AND METHODS A total of 10 patients treated with BPs for multiple myeloma, metastatic breast cancer, and osteoporosis, requiring dental extractions of nontreatable teeth, were included in this study. The extractions were performed by means of orthodontic elastics placed around the roots, causing slow and gradual exfoliation of the teeth. RESULTS The technique was applied to 21 roots of 15 teeth. A total of 19 roots exfoliated spontaneously. Two roots had to be removed with minimal manipulation by forceps. The mean time required for exfoliation was 5.8 weeks. All sockets showed soft tissue secondary healing and there were no signs of inflammation or exposed bone during the 9-month follow-up. CONCLUSIONS Atraumatic extraction by use of elastics is a safe technique that may be used in BP-treated patients to prevent osteonecrosis of the jaws.

Lip carcinoma in renal allograft recipient with long-term immunosuppressive therapy

Five years after a kidney transplant and immunosuppressive therapy a 42-year-old woman had squamous cell carcinoma of the lower lip with an innocent appearance. We present this as the first case of lip squamous cell carcinoma in a kidney transplant recipient to be reported in the dental literature. We review the medical literature.

Sialolithectomy done with a CO2 laser: Clinical and scintigraphic results

PURPOSE This study reviews the results of sialolithectomy performed with the CO2 laser. PATIENTS AND METHODS Forty-nine patients were treated under local anesthesia at initial presentation in the outpatient clinic. RESULTS All patients had immediate relief after surgery. Clinical and scintographic follow-up of up to 28 months on 27 patients showed that all but 1 were asymptomatic. The single exception required excision of the submandibular gland because of two recurrences of sialoliths in Whartons duct. Although some glands had no function clinically and scintigraphically, they were asymptomatic and needed no further treatment. CONCLUSIONS Salivary glands that are nonfunctioning clinically and scintigraphically should only be removed when there is a recurrence of symptoms.