James Q. Swift

Bisphosphonate-Related Osteonecrosis of the Jaw: Clinical Features, Risk Factors, Management, and Treatment Outcomes of 26 Patients

PURPOSE To report the clinical features, risk factors, management, and treatment outcomes of nitrogen-containing bisphosphonate (n-BIS)-related osteonecrosis of the jaw (BRONJ). PATIENTS AND METHODS Patients with suspected BRONJ were referred to the School of Dentistry for evaluation and treatment. RESULTS A total of 26 patients (9 men and 17 women, mean age 64 years) were diagnosed with BRONJ. Of the 26 patients, 23 had received n-BIS therapy for cancer and 3 for osteoporosis. BRONJ lesions were noted more frequently in the mandible and in the posterior sextants. Of the 26 patients, 16 had developed BRONJ after dentoalveolar procedures, and 10 had developed it spontaneously. The mean interval to development of BRONJ was shorter in the patients with cancer receiving intravenous n-BIS than in the patients with osteoporosis receiving oral n-BIS (37.1 versus 77.7 months, P = .02). Using the American Association of Oral and Maxillofacial Surgeons staging system, 2 patients were diagnosed with stage I lesions, 19 with stage II, and 5 with stage III lesions. The initial management of BRONJ was nonsurgical, with debridement performed at subsequent visits, if needed. The BRONJ lesions healed completely in 4 patients, healed partially in 8, remained stable in 7, and progressed in 7. The spontaneous lesions responded favorably to BRONJ management compared with lesions that developed after dentoalveolar procedures (P = .01). No significant difference was found in response to BRONJ management between patients who had continued or discontinued n-BIS therapy after the BRONJ diagnosis (P = .54). CONCLUSIONS Long-term n-BIS therapy and recent dental procedures are consistent findings in patients with BRONJ. Spontaneous BRONJ lesions respond favorably to current BRONJ treatment strategies.

Effect of NSAID administration on tissue levels of immunoreactive prostaglandin E2, leukotriene B4, and (S)-flurbiprofen following extraction of impacted third molars

&NA; Post‐operative pain and inflammation are frequently managed with non‐steroidal anti‐inflammatory drugs (NSAIDs). Despite the prevalence of their use, however, relatively little is known about in vivo tissue concentrations of inflammatory mediators at the site of tissue injury and their modulation by NSAIDs. This study compares the effect of oral administration of the NSAID flurbiprofen, to placebo, on tissue levels of immunoreactive prostaglandin E2 (iPGE2), leukotriene B4 (iLTB4), and (S)‐flurbiprofen within the surgical wound using implanted microdialysis probes in the dental impaction pain model. Twenty‐four healthy patients in need of extraction of partial to complete bony mandibular third molars were recruited for this randomized, double‐blind, placebo‐controlled study. Following pre‐operative administration of N2O/O2, midazolam i.v., and regional block anesthesia with 3% mepivacaine, each patient underwent surgical removal of their impacted third molars. Immediately following completion of the surgery, two semi‐permeable microdialysis probes (3 kDa molecular weight cut‐off) were implanted into each mandibular surgical site. Patients were taken to a recovery room and microdialysis samples and patient pain reports (visual analog scale, VAS) were collected at 30 min intervals for 4 h. Patients randomly received either flurbiprofen (200 mg orally) or placebo at the onset of post‐operative pain. Dialysate samples were collected, frozen, and later assayed for iPGE2, iLTB4, and (S)‐flurbiprofen levels. Results of this study show that flurbiprofen decreased post‐operative pain by approximately 70% compared to placebo‐treated patients (P<0.001). During the 4 h post‐operative timecourse of this study, flurbiprofen treatment significantly reduced peak tissue levels of iPGE2 (9.2±2.6 vs. 0.4±0.15 nM; P<0.001), without having a significant effect on peak tissue levels of iLTB4 (2.5±1.4 vs. 1.49±0.86 nM) compared to placebo treatment. Levels of (S)‐flurbiprofen significantly increased within the surgical wound exceeding therapeutic levels by 60 min after administration. Flurbiprofen is able to significantly suppress the local production of iPGE2 and provide significant analgesic efficacy without altering iLTB4 tissue levels in this model of acute post‐operative inflammatory pain. These data indicate that NSAIDs selectively alter eicosanoid levels within surgical wound and evoke analgesia at time points coincident with elevated wound levels of the drug. The combined use of microdialysis probes in awake patients who provide simultaneous pain reports may offer insight into peripheral mechanisms of inflammatory mediator release and pain.

Pharmacology of peripheral neuropeptide and inflammatory mediator release

Research conducted in the last 10 years has increased our knowledge on pain mechanisms substantially. Although many local tissue mediators, including neuropeptides, are known to exert pro-inflammatory effects, comparatively little is known about the actual tissue levels of these inflammatory mediators and their pharmacologic regulation. This article describes two new methods, clinical microdialysis and superfusion of dental pulp, which provide data on the pharmacology of peripheral neuropeptide and inflammatory mediator release. Collectively, these methods provide a biochemically based approach toward determining the mechanisms and management of orofacial pain.

Randomized Effectiveness Study of Four Therapeutic Strategies for TMJ Closed Lock

For individuals with temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock), interventions vary from minimal treatment to surgery. In a single-blind trial, 106 individuals with TMJ closed lock were randomized among medical management, rehabilitation, arthroscopic surgery with post-operative rehabilitation, or arthroplasty with post-operative rehabilitation. Evaluations at baseline, 3, 6, 12, 18, 24, and 60 months used the Craniomandibular Index (CMI) and Symptom Severity Index (SSI) for jaw function and TMJ pain respectively. Using an intention-to-treat analysis, we observed no between-group difference at any follow-up for CMI (p ≥ 0.33) or SSI (p ≥ 0.08). Both outcomes showed within-group improvement (p < 0.0001) for all groups. The findings of this study suggest that primary treatment for individuals with TMJ closed lock should consist of medical management or rehabilitation. The use of this approach will avoid unnecessary surgical procedures.

Skeletal stability following mandibular advancement and rigid fixation

Twenty non-growing subjects underwent sagittal ramus osteotomies and rigid fixation. Cephalograms were analyzed before surgery, immediately after surgery and at least six months following surgery to evaluate skeletal stability. A mean horizontal relapse of 0.42 mm (8%) and a mean vertical increase in lower face height of 0.2 mm were found six months after surgery. Both were statistically insignificant. The mean backward rotation of the mandible of 0.55 degrees found six months after surgery was statistically significant (P less than 0.015), but was considered to be clinically insignificant. The results of this study show that surgical mandibular advancement with rigid fixation is a very reliable and stable procedure.

Effect of intra-articular versus systemic anti-inflammatory drugs in a rabbit model of temporomandibular joint inflammation

PURPOSE In an attempt to better understand the time course of inflammatory mediator production or release in inflammatory joint disease, a rabbit model of acute temporomandibular joint (TMJ) inflammation was established. This model was used to evaluate the effects of specific anti-inflammatory agents administered either systemically (intraperitoneal, IP) or locally (intra-articular, IA) on the modulation of in vivo tissue levels of two prototypic inflammatory mediators, prostaglandin E2 (PGE2) and bradykinin (BK). MATERIALS AND METHODS An experimental model of inflammation was created by administering carrageenan (carra) into one joint and an equivalent volume of saline (control) into the contralateral joint of 42 male New Zealand White rabbits. The development of hyperthermia was assessed by placement of a microthermister probe into the joint space. The inflammatory mediators, immunoreactive PGE2 (iPGE2) and BK (iBK), were recovered with microdialysis probes, and samples were assayed in conjunction with specific pharmacologic interventions. In the first part of the study, the time course for the release or production of iBK and iPGE2 was determined. In the second part, the effects of IP versus IA administration of dexamethasone and a nonsteroidal anti-inflammatory drug, ketorolac tromethamine, were compared. Dexamethasone and ketorolac were administered at 3 hours and 1 hour, respectively, before the peak release of the inflammatory mediators. RESULTS The onset of IA hyperthermia, an index of inflammation, was evident by 90 minutes post-carra and reached a maximum of 1.2 degrees C above core temperature by 150 minutes post-carra. Intra-articular levels of iPGE2 and iBK peaked at 240 minutes (3.35+/-1.9 nmol/L) and 270 minutes (0.45+/-0.29 nmol/L), respectively, after the induction of inflammation in the superior joint space. iBK levels within the superior joint space were significantly decreased by dexamethasone and ketorolac. Ketorolac (50 microg) decreased iBK and iPGE2 levels when given IA or IP. With dexamethasone (3 mg), the levels of iBK were significantly reduced, and iPGE2 levels were not changed. CONCLUSIONS This study shows that the rabbit model of TMJ inflammation, with concurrent collection of iBK and iPGE2 via microdialysis, is a reproducible and reliable method to investigate the time course of inflammatory mediator release and their modulation by either the local or systemic administration of anti-inflammatory medications.

Considerations for the use of alloplastic temporomandibular joint replacement in the growing patient.

When developmental, traumatic, neoplastic arthritis or ankylosis results in an anatomically unsalvageable, functionally compromised temporomandibular joint (TMJ), total joint replacement (TJR) may provide the only management option. In the adult patient these situations are often dealt with by use of either autogenous or alloplastic modalities. However, any of these pathologic conditions when present in the growing patient present the reconstructive surgeon with not only the concerns of form and function, but also the consideration of adaptive facial growth. 1-3 Classically, pathologic, developmental, and functional disorders affecting the TMJ in children have been reconstructed with autogenous tissues. Autogenous costochondral grafts are reported as the “gold standard” for TMJ reconstruction in the growing patient. 4-8 The use of other autogenous bone/cartilage combinations has also been described in such cases. 9-12 In theory, these autogenous (eg, costochondral) allografts will “grow with the patient”; however, often, this so-called growth potential has been stated to be unpredictable or to result in ankylosis, either as the result of the allograft and/or fixation failure or because of the uncooperative nature of the young patient with physical therapy after reconstruction. 4,5,13-28 Recent studies have even questioned the necessity for using a cartilaginous graft to restore and maintain mandibular growth. 29,30 Long-term reports of mandibular growth in children whose TMJs were reconstructed with costochondral grafts show that excessive growth on the treated side occurred in 54% of the 72 cases examined, and growth equal to that on the opposite side occurred in only 38% of the cases. 26,31-35 Further

Gender Differences in Analgesia for Endodontic Pain

The purpose of this prospective clinical trial was to investigate the analgesic efficacy of three oral medication groups on postoperative endodontic pain in male and female dental patients, with an emphasis on analgesic differences between the sexes. Forty-three patients were administered ibuprofen 600 mg, placebo, or pentazocine 50 mg/0.5 mg naloxone in a randomized, double-blinded manner. Beginning immediately after endodontic treatment, patients took the assigned medication every 6 hours for 24 hours and recorded their degree of discomfort on a 100-mm visual analog scale. Statistical analysis of the data showed that ibuprofen 600 mg provided statistically significantly greater analgesia than placebo at 6 and 12 hours (P = 0.0014 and 0.0024), and pentazocine/naloxone provided statistically significantly greater analgesia than placebo at 12 hours (P = 0.0084). Sex-dependent differences were noted within the pentazocine/naloxone group, which showed significantly greater analgesia in females compared with males (P = 0.007).

Effects of four treatment strategies for temporomandibular joint closed lock

A previous randomized controlled trial (RCT) by Schiffman et al. (2007)(15) compared four treatments strategies for temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock). In this parallel group RCT, 106 patients with magnetic resonance imaging (MRI)-confirmed TMJ closed lock were randomized between medical management, non-surgical rehabilitation, arthroscopic surgery, and arthroplasty. Surgical groups also received rehabilitation post-surgically. The current paper reassesses the effectiveness of these four treatment strategies using outcome measures recommended by the International Association of Oral and Maxillofacial Surgeons (IAOMS). Clinical assessments at baseline and at follow-up (3, 6, 12, 18, 24, and 60 months) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing. TMJ MRIs were performed at baseline and 24 months, and TMJ tomograms at baseline, 24 and 60 months. Most IAOMS recommended outcome measures improved significantly over time (P≤0.0003). There was no difference between treatment strategies relative to any treatment outcome at any follow-up (P≥0.16). Patient self-assessment of treatment success correlated with their ability to eat, with pain-free opening ≥35mm, and with reduced pain intensity. Given no difference between treatment strategies, non-surgical treatment should be employed for TMJ closed lock before considering surgery.

Effects of Implant Healing Time on Crestal Bone Loss of a Controlled-load Dental Implant

The universally accepted concept of delay-loaded dental implants has recently been challenged. This study hypothesizes that early loading (decreased implant healing time) leads to increased bone formation and decreased crestal bone loss. We used 17 minipigs to study implants under a controlled load, with non-loaded implants for comparison. Radiographic and histological assessments were made of the osseointegrated bone changes for 3 healing times (between implant insertion and loading), following 5 months of loading. The effect of loading on crestal bone loss depended on the healing time. Early loading preserved the most crestal bone. Delayed loading had significantly more crestal bone loss compared with the non-loaded controls (2.4 mm vs. 0.64 mm; P < 0.05). The histological assessment and biomechanical analyses of the healing bone suggested that loading and bioactivities of osteoblasts exert a synergistic effect on osseointegration that is likely to support the hypothesis that early loading produces more favorable osseointegration.