Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw.
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.
Raje
Noopur
N
The Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02114, USA. nraje@partners.org
Woo
Sook-Bin
SB
Hande
Karen
K
Yap
Jeffrey T
JT
Richardson
Paul G
PG
Vallet
Sonia
S
Treister
Nathaniel
N
Hideshima
Teru
T
Sheehy
Niall
N
Chhetri
Shweta
S
Connell
Brendan
B
Xie
Wanling
W
Tai
Yu-Tzu
YT
Szot-Barnes
Agnieszka
A
Tian
Mei
M
Schlossman
Robert L
RL
Weller
Edie
E
Munshi
Nikhil C
NC
Van Den Abbeele
Annick D
AD
Anderson
Kenneth C
KC
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
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D019788:Fluorodeoxyglucose F18