Osteonecrosis of the jaws is a major complication associated with long-term use of bisphosphonates. While osteonecrosis can arise from other precipitating conditions, bisphosphonate-induced jaw osteonecrosis (BJON) is highly associated with long-term administration of pamidronate (Aredia) and zoledronic acid (Zometa), which are two intravenous bisphosphonate formulations. The underlying pathogenesis of BJON and its site-specific presentation still remain to be fully elucidated. This review will discuss clinically available bisphosphonates, current opinions, pathogenesis, and management guidelines for bisphosphonate-induced jaw osteonecrosis.
OBJECTIVE-Long-term administration of intravenous bisphosphonates like pamidronate is associated with jaw osteonecrosis but axial and appendicular bones are unaffected. Pathogenesis of bisphosphonate-associated jaw osteonecrosis may relate to skeletal-site specific effects of bisphosphonates on osteogenic differentiation of bone marrow stromal cells (BMSCs) of orofacial and axial/appendicular bones. This study evaluated and compared skeletal site-specific osteogenic response of mandible (orofacial bone) and iliac crest (axial bone) human BMSCs to pamidronate.
MATERIALS AND METHODS-Mandible and iliac crestBMSCs from six normal healthy volunteers were established in culture and tested with pamidronate to evaluate and compare cell survival, osteogenic marker alkaline phosphatase, osteoclast differentiation in co-cultures with CD34 + hematopoietic stem cells, gene expression of receptor activator of NFκB ligand (RANKL) and osteoprotegerin, and in vivo bone regeneration.
BRESULTS-MandibleBMSCs were more susceptible to pamidronate than iliac crest BMSCs based on decreased cell survival, lower alkaline phosphatase production and structurally less organized in vivo bone regeneration. Pamidronate promoted higher RANKL gene expression and osteoclast recruitment by mandible BMSCs.CONCLUSION-Mandible and iliac crest BMSC survival and osteogenic differentiation are disparately affected by pamidronate to favor dysregulated mandible bone homeostasis.
Objectives
This is an open-pilot study to evaluate the feasibility, acceptability and efficacy of a pain-specific version of an established mind–body medicine program, the Relaxation Response [RR] Resiliency Program [R3P], in patients with chronic temporomandibular disorder [TMD].
Methods
Male and female with at least a six-month history of pain involving the masticatory muscles were sought in the Orofacial Pain Centers of the Massachusetts General Hospital [MGH] or through an advertisement sent to MGH employees from 2008 to 2010. Eligible participants underwent the R3P intervention [eight group sessions] after standard medical management. Pre- and post-group patients underwent objective measures of impairment [vertical and lateral range of motion with and without pain, temporomandibular joint and muscle pain palpation, and algometer measures] and completed psychosocial measures [Symptom Severity Index, Perceived Stress Scale, the Symptom Checklist-90-Revised and Short Form 36 Health Survey].
Results
Twenty-four subjects [16 females, 90% from MGH Orofacial Pain Centers,10% from among MGH employees], mean age 38 years, met eligibility criteria and participated in the study. The intervention was highly feasible and accepted by patients, as evidenced by a 92% rate of completion. Paired t-test analyses revealed improvement on self-reported pain measures: pain intensity [p<0.02], pain frequency [p<0.002], pain duration [p<0.027], pain tolerability [p<0.009] and on several objective tests.
Conclusions
The pain specific R3P is efficacious in reducing objective and subjective symptoms in patients with chronic refractory TMD. The comprehensive intervention, which combines educational information about pain with RR, cognitive behavioral and resiliency-enhancement skills, is accepted by patients and may be more efficacious than other treatments with fewer elements.
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