First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro.
OBJECTIVE
The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma.


METHODS
Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro.


RESULTS
Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment.


CONCLUSIONS
Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation.
Department of Clinical Cell Biology, IRS -CSFU, University of Southern Denmark Vejle Hospital, Vejle, Denmark. thomas.lund@slb.regionsyddanmark.dk
Thomas
T
Lund
Kent
K
Søe
Niels
N
Abildgaard
Patrick
P
Garnero
Per T
PT
Pedersen
Tina
T
Ormstrup
Jean-Marie
JM
Delaissé
Torben
T
Plesner
D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011719:Pyrazines / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D001897:Boronic Acids; D005938:Glucocorticoids; D011719:Pyrazines; D000069286:Bortezomib