A prospective evaluation of the biochemical, metabolic, hormonal and structural bone changes associated with bortezomib response in multiple myeloma patients.
We prospectively evaluated the bone changes associated with proteasome inhibition using single agent bortezomib in relapsed or refractory myeloma patients. Ten patients received bortezomib 1.3 mg/m(2) per days 1, 4, 8 and 11 for three 21-day cycles, and 6 patients received 1 mg/m(2) per day with the same schedule. Bone architecture and metabolism changes were assessed by bone markers, micro-CT, bone histomorphometry, tetracycline labeling and serum parathormone levels. Bone parameter variations were compared by response to treatment. Microarchitectural changes were observed in all evaluable responsive patients. Bone alkaline phosphatase changes were associated with disease response (≥PR vs. others P=0.03 cycle 1, day 11) serum parathormone levels were also significantly increased (P=0.04 on days 11, 21, 33) in responding individuals. This study demonstrates that the myeloma control produced by proteasome inhibition is associated with bone changes and to a discrete pattern of hormonal variation.
Zangari
Maurizio
M
University of Utah, Salt Lake City, Utah, USA. maurizio.zangari@hsc.utah.edu
Yaccoby
Shmuel
S
Pappas
Lisa
L
Cavallo
Federica
F
Kumar
Naveen Sanath
NS
Ranganathan
Subramanian
S
Suva
Larry J
LJ
Gruenwald
J Michael
JM
Kern
Steven
S
Zhan
Fenghuang
F
Esseltine
Dixie
D
Tricot
Guido
G
D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D016723:Bone Remodeling / Q000187:drug effects*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*
D015415:Biomarkers; D001897:Boronic Acids; D010281:Parathyroid Hormone; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D000469:Alkaline Phosphatase