Jaw Symptoms Research Articles

Post-Marketing Assessments of Serious Adverse Drug Reactions Reported by the Manufacturer to the FDA Differ Markedly with Those from an Independent Pharmacovigilance Program: Empirical Findings Based on Bisphosphonate-Associated Osteonecrosis Descriptions by the Research on Adverse Events and Reports Project and the Product Manufacturer.

Background: The Research on Adverse Events and Reports (RADAR) project, an independent pharmacovigilance project, has reported that post-marketing dissemination of clinical information on systemic adverse drug reactions (sADRs) in the FDA approved package labels of cancer drugs is often incomplete, delayed, or absent.Methods: We compared post-marketing clinical assessments describing one previously unreported sADR: zoledronate (Z) and pamidronate (P)-associated osteonecrosis (ON) of the jaw. Data sources included 1) information submitted to the FDA by the manufacturer in support of an FDA package insert revision, 2) RADAR investigators review of case reports of BPs associated ON of the jaw reported to the FDA MedWatch program and, 3) RADAR investigators review of medical and dental records of BP treated multiple myeloma (MM) patients with confirmed, clinically obvious ON of the jaw at a large NCI-designated comprehensive cancer center.Results: The manufacturers summary material indicated that ON occurs at a rate of < 1 per 10,000 BPs treated individuals; occurs 4x more frequently in cancer versus non-cancer patients; has multiple causes including trauma, infection, radiation therapy, and long-term corticosteroids; and causal relationship with BPs is unknown. Radar investigators found that not a single case of BPs associated ON of the jaw has been reported to the FDA's MedWatch program as of to date. RADAR investigators, however, identified 7 patients (on BPs) with confirmed ON of the jaw among 600 myeloma patients seen between March 2001 and June 2004 at our institution. Characteristics of these patients included presentation with localized jaw symptoms (n=7) requiring surgical and/or medical treatment.Conclusions: Independent toxicity assessments from the RADAR program suggest that ON is a serious, previously unrecognized ADR which can occur at a rate > 1% in MM patients, appears to be causally associated with prolonged BP therapy, and is difficult to treat. In comparison, materials submitted by the manufacturer to the FDA in support of a package insert revision as well as the FDA's MedWatch data (with 0 cases reported) indicate that this sADR is rare, has multiple etiologies, and its association with BP is unknown. The manufacturer has informed the FDA that it will conduct a retrospective single-site study to further evaluate this toxicity but this method is likely to be limited by underreporting. In contrast, our findings highlight the need for 1) a multi-site prospective study to identify the true extent of this problem in patients receiving BPs, 2) educating health care officials about the importance of reporting ADRs to the FDA MedWatch program and, 3) careful evaluation of the source of toxicity information when assessing discrepant reports of sADRs.

Bupropion-Induced Acute Dystonia

OBJECTIVE:To report a case of acute dystonia consisting of neck stiffness, trismus, and unilateral temporomandibular joint (TMJ) pain and subluxation secondary to an increase in sustained-release (SR) bupropion.CASE SUMMARY:A 44-year-old white man with a history of chronic low-back pain and tension headaches, taking no other medications, was started on bupropion SR 150 mg once a day for depression. The dosage was increased to 150 mg SR twice a day and eventually augmented with buspirone 15 mg 3 × a day. He developed bilateral trismus, inability to rotate his head laterally, and spontaneous left TMJ subluxation. Symptoms recessed with discontinuation of both medications and failed to reappear with a trial of buspirone 15 mg 3 × a day alone. A retrial of bupropion alone evidenced no adverse effects at a dosage of 150 mg SR once a day. However, when the dosage was increased to 150 mg SR twice a day, the patient reexperienced initial signs of neck stiffness, jaw muscle tightness, and left TMJ subluxation within 24–48 hours. Reduction of the bupropion dosage to 150 mg SR once daily stopped the symptoms; the patient has continued at this dosage without adverse effects for >1 year.DISCUSSION:Medication-induced focal dystonias usually present with dramatic head (most frequently oral—buccal) and neck muscle spasm with occasional jaw clenching, bruxism, and TMJ syndrome. In this case, the rapid onset of neck and jaw symptoms within 24–48 hours of an increase of bupropion SR from 150 mg once a day to 150 mg twice a day suggest that the patient may have been sensitized by an initial trial of bupropion and buspirone, or by the increased dose of bupropion alone. Both agents are reported to interact with both the dopaminergic and serotonergic systems. Although buspirone has been implicated in inducing acute dystonia, it did not do so in this case when used alone at a dose of 45 mg a day. During a second trial of bupropion SR 150 mg a day, neck and jaw symptoms recurred within 24–48 hours of increasing the dose to 150 mg SR twice a day. The symptoms receded when the bupropion dose was returned to 150 mg SR once a day, suggesting a dose—response relationship. The Naranjo probability scale indicated that this untoward reaction was probable.CONCLUSIONS:This case suggests that selected patients may experience dose-related acute dystonic adverse reactions to bupropion with or without buspirone augmentation. Dystonias, which usually follow administration of antipsychotics, have been linked to acute dopamine depletion and basal ganglion—derived γ synchronization dysfunction. Acute dystonia symptoms may begin within hours of starting or changing antipsychotic drug dosage; however, 90% of symptoms are observed during the first 3–5 days of starting or increasing dosage. To the best of our knowledge, there have been no reports of bupropion-induced dystonia.

Background factors in craniomandibular disorders: reported symptoms in adolescents with special reference to joint hypermobility and oral parafunctions

Correlations between craniomandibular disorders (CMD) symptoms and an inherited factor (general joint hypermobility) were studied in 193 adolescents (96 girls and 97 boys). They answered a questionnaire concerning CMD symptoms, oral parafunctions, head and jaw trauma and symptoms from other joints. Joint mobility was assessed by determining the Beighton score (0-9). Twenty-eight percent of the girls and 21% of the boys could perform four or more of the manoeuvres. Twenty-two percent of the girls and 3% of the boys were extremely hypermobile (score greater than or equal to 5). Eighty-nine percent were aware of some oral parafunction and the prevalences of oral habits were about the same in the two groups. Girls reported significantly more dysfunction symptoms than boys. No indication was found that oral parafunctions generally produced CMD but a systemic factor (joint hypermobility) seemed to play an important role when the masticatory system was exposed to local forces as in oral parafunction. This may be one explanation for the predominance of females among CMD patients.

Metastatic renal clear cell carcinoma of the jaws. Two cases illustrating clinical and pathological diagnostic problems

Two cases of metastatic renal clear cell carcinomas of the mandible are presented in which the jaw symptoms preceded the discovery of the primary lesions. Their presentation mimicked vascular abnormalities both clinically and on special investigations and both required biopsy, one of which was a major excision, for diagnosis. The histological differential diagnosis of metastatic renal clear cell carcinoma from other clear cell tumours arising in the orofacial tissues can also be difficult, often requiring specialised knowledge and techniques. These points illustrate that the differential diagnosis of a pulsatile soft tissue jaw tumour developing below intact mucosa and eroding bone, should include metastatic tumour as well as vascular anomaly, vasoformative tumour, extra nodal lymphoma and primary bone tumour.

Double-layer closure for temporomandibular joint discoplasty

Surgical TMJ disc repositioning has been used successfully to improve jaw function and reduce subjective jaw symptoms. The postauricular approach for the double-layered closure described here offers improvements to the standard correction