- Maurizio Zangari1,*,
- Shmuel Yaccoby2,
- Lisa Pappas3,
- Federica Cavallo4,
- Naveen Sanath Kumar5,
- Subramanian Ranganathan5,
- Larry J. Suva5,
- J. Michael Gruenwald5,
- Steven Kern1,
- Fenghuang Zhan1,
- Dixie Lee Esseltine6 and
- Guido Tricot1
- 1 University of Utah, USA;
- 2 University of Arkansas for Medical Sciences, USA;
- 3 University of Utah, Huntsman Cancer Institute, USA;
- 4 University of Turin, Italy;
- 5 University of Arkansas, USA;
- 6 Millennium Pharmaceuticals
- ↵* Corresponding author; email:
Background. We prospectively evaluated the bone changes associated with proteasome inhibition using single agent bortezomib in relapsed or refractory myeloma patients.
Design and Methods. Ten patients received bortezomib 1.3 mg/m2 per day 1, 4, 8 and 11 x three 21-day cycles, and six patients received 1 mg/m2 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.
Results. 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.
Conclusions. This study demonstrates that the myeloma control produced by proteasome inhibition is associated with bone changes and to a discrete pattern of hormonal variation. (clinicaltrials.gov identifier: NCT00569868)
- Received July 26, 2010.
- Accepted October 13, 2010.
- Copyright © 2010, Ferrata Storti Foundation