Bone
metastasis is a frequent complication of
cancer, occurring in up to 70% of patients with advanced breast or
prostate cancer, while
bone disease is also the characteristic clinical feature of
multiple myeloma. Skeletal-related events can be devastating, with major effect on the quality of life and survival.
Bisphosphonates are the mainstay of therapeutic management of
bone disease of solid
tumors and myeloma, and
denosumab has recently been approved for patients with bone
metastases. Both act through inhibition of the osteoclast activity but do not restore bone formation.
Proteasome inhibition has direct bone
anabolic effects.
Proteasome inhibitors have been used in the management of patients with
multiple myeloma and
mantle-cell lymphoma during the last decade. In
multiple myeloma,
bortezomib, the first-in-class
proteasome inhibitor, has shown both in vitro and in vivo regulation of bone remodeling by inhibiting osteoclast function and promoting osteoblast activity.
Bortezomib also reduces
bone resorption but more importantly increases bone formation and bone mineral density, at least, in subsets of myeloma patients. Thus,
bortezomib is recommended for myeloma patients with extended
bone disease in combination with
bisphosphonates. This review focuses on the effects of the
proteasome system on bone metabolism and the implications into the better management of patients with
cancer and
bone disease.