Impact of bortezomib on bone health in myeloma: a review of current evidence.
Bone disease is a key feature in multiple myeloma (MM) and can have a substantial impact on patient morbidity and quality-of-life. The pathogenesis of lytic bone disease in MM is complex and associated with increased osteoclast activity and impaired osteoblast function. Lytic lesions rarely heal in MM; however, the proteasome inhibitor bortezomib has been linked to increased bone formation and osteoblastic activity. Various clinical studies have reported a positive effect of bortezomib on bone health, including fewer bone disease-related MM progression events, increases in bone volume, and improvements in osteolytic lesions. Alkaline phosphatase (total and bone isoenzyme), a marker of bone formation, is increased during bortezomib treatment; the degree of increase may be associated with treatment response. Bortezomib is associated with a reduction in Dickkopf-1, an inhibitor of osteoblast function. Increases of other bone-formation markers and decreases of bone-resorption markers, have also been observed. These clinical effects are supported by preclinical data suggesting bortezomib is associated with an increase in bone formation and osteoblast numbers/activity, arising from direct effects of bortezomib and proteasome inhibition. As reviewed here, a growing body of evidence indicates that bortezomib exerts a positive effect on bone metabolism in MM and has a bone anabolic effect.
Stem Cell Transplant and Myeloma Program, University of Utah, UT 84132, USA. maurizio.zangari@hsc.utah.edu
Maurizio
M
Zangari
Evangelos
E
Terpos
Fenghuang
F
Zhan
Guido
G
Tricot
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001847:Bone Diseases / Q000188:drug therapy* / Q000473:pathology; D001897:Boronic Acids / Q000494:pharmacology* / Q000627:therapeutic use*; D000069286:Bortezomib; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib