title: Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw.
abstract: OBJECTIVE
  Osteonecrosis of the jaw (ONJ) has been reported in patients with a history of aminobisphosphonate use. This study was conducted in order to define ONJ clinically and radiographically and gain insights into its pathophysiology.
  
  
  METHODS
  Eleven multiple myeloma (MM) patients with ONJ were included in the study. Patients underwent clinical, biochemical, radiographic, and molecular profiling. Ten MM patients on aminobisphosphonates without ONJ and five healthy volunteers were used as controls for biochemical and molecular studies.
  
  
  RESULTS
  MM patients with ONJ were treated with either pamidronate (n = 3), zoledronate (n = 4), or both agents sequentially (n = 4) for a mean of 38.7 months. Radiographic studies showed bone sclerosis and fragmentation on plain films and computerized tomography. Quantitative regional analysis of NaF-PET and FDG-PET scans confirmed an increased standardized uptake value (SUVmax) in areas of ONJ. The target to background ratio of SUVmax was significantly greater for NaF-PET compared with FDG-PET scan. Biochemical bone marker data and transcriptional profiling studies showed that genes and proteins involved in osteoblast and osteoclast signaling cascades were significantly down-regulated in patients with ONJ.
  
  
  CONCLUSIONS
  ONJ was associated with a mean duration of 38.7 months of aminobisphosphonate exposure. Radiographic and functional imaging confirmed sites of clinically established ONJ. Gene and protein studies are consistent with altered bone remodeling, evidenced by suppression of both bone resorption and formation.
authors.affiliation: The Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA. nraje@partners.org
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
authors.forename: Sook-Bin
authors.initials: SB
authors.lastname: Woo
authors.forename: Karen
authors.initials: K
authors.lastname: Hande
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Yap
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Sonia
authors.initials: S
authors.lastname: Vallet
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Treister
authors.forename: Teru
authors.initials: T
authors.lastname: Hideshima
authors.forename: Niall
authors.initials: N
authors.lastname: Sheehy
authors.forename: Shweta
authors.initials: S
authors.lastname: Chhetri
authors.forename: Brendan
authors.initials: B
authors.lastname: Connell
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.forename: Yu-Tzu
authors.initials: YT
authors.lastname: Tai
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szot-Barnes
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schlossman
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.forename: Annick D
authors.initials: AD
authors.lastname: Van Den Abbeele
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000009:adverse effects*; D016723:Bone Remodeling; D004164:Diphosphonates / Q000009:adverse effects*; D005260:Female; D019788:Fluorodeoxyglucose F18; D020869:Gene Expression Profiling; D006801:Humans; D007571:Jaw Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications*; D010012:Osteogenesis; D010020:Osteonecrosis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019788:Fluorodeoxyglucose F18