Fall 2006 - College of Dental Medicine - Columbia University

Seeking Scientific Evidence ofBisphophonates have been used for almost 20 yearsin preventing and treating postmenopausal andsteroid-induced osteoporosis, Paget’s disease ofbone, hypercalcemia of malignancy, and multiplemyeloma, and in preventing bone metastases associatedwith breast, prostate, lung, and other soft tissuetumors. Bisphosphonates strengthen bone and preventfractures by inhibiting bone loss (resorption) inskeletal long bones, but may act somewhat differentlyon the jaw bones, interfering with theosteoblast/osteoclast balance important to boneremodeling. Recent research has related the biochemicalinteraction that makes BPs very effectiveinhibitors of bone resorption to the chemical structureand molecular action of inorganic phosphate,which regulates bone metabolism by initiatingosteoclast destruction. BPs are currently approvedfor the treatment and prevention of skeletal-relatedevents in breast cancer patients with bone metastases,as well as in cases of prostate, lung, and othersoft-tissue cancers. Breast cancer accounts forapproximately 30 percent of all new cancer cases inwomen, half of whom develop bone metastases,with 40 to 70 percent experiencing bone pain,pathological fracture, or spinal cord compression.Associate Professor of ClinicalDentistry Regina Landesberg,DMD, PhD, is an oral andmaxillofacial surgery researchscientist at CDM.IN 2003, A LETTER TO THE JOURNAL OF ORALAND MAXILLOFACIAL SURGERY DESCRIBED ASTILL UNCOMMON CONDITION, OSTEO-NECROSIS OF THE JAW (ONJ), AS “AGROWING EPIDEMIC.” THE CONCLUSIONWAS BASED ON THE CASES OF SEVERALDOZEN CANCER PATIENTS WHO HADBEEN RECEIVING INTRAVENOUS BISPHOS-PHONATE THERAPY AND PRESENTEDWITH “PAINFUL BONE EXPOSURE [IN THEJAW] ... [THAT WAS] UNRESPONSIVE TOSURGICAL OR MEDICAL TREATMENTS.”Investigators at the College of Dental Medicine(CDM) have been awarded one of the first NIH-supportedgrants to study the incidence and risk factorsfor developing osteonecrosis of the jaw in cancerpatients undergoing bisphosphonate therapy to preventbone metastases. Associate Professor of ClinicalDentistry in the Division of Oral and MaxillofacialSurgery Regina Landesberg, DMD, PhD, andProfessor and Director of the Division of OralBiology and the Center for Clinical Research inDentistry John T. Grbic, DMD, MS, MMSc, are coinvestigatorsfor the two-year study grant.Our knowledge of ONJ comes primarily from casereports that are limited by the lack of a consistentdefinition for ONJ. ONJ is characterized by anexposure of the jaw bone that fails to heal and isoften found at the site of a previous invasive surgicalprocedure, such as an extraction. Other symptomsinclude: painful, swollen, or infected gums; mouthsores that heal poorly; loose teeth; numbness andtingling in the lips or jaw, or a “heavy” feeling jaw.Such a lesion may, however, be painless and notapparent to the patient. Because these case reportslacked the scientifically based examination necessaryto draw accurate conclusions on the concomitantrisk factors, predictive markers, etiology, and pathognesison ONJ, Drs. Landesberg and Grbic, workingwith colleagues from the College of Physicians &Surgeons as well as the Mailman School of PublicHealth, have designed a clinical study to investigatethese and other variables that could contribute tothe condition.16primus2006