Gallium nitrate has been shown to be an effective treatment for patients with
cancer-related
hypercalcemia. Clinical studies have also suggested the
drug may have considerably broader use in other diseases associated with accelerated bone loss including
multiple myeloma, bone
metastases, Paget's disease, and
osteoporosis. The actions of
gallium nitrate on bone are quite distinct from those of
bisphosphonates. Preclinical studies show that
gallium preferentially accumulates in trace amounts in metabolically active regions of bone. When present,
gallium favorably alters the
mineral properties to enhance
hydroxyapatite crystallization and reduce
mineral solubility. The
drug also acts on the cellular components of bone to reduce
bone resorption by decreasing
acid secretion by osteoclasts. This effect appears to be mediated by inhibition of the
ATPase-dependent
proton pump of the osteoclast's ruffled membrane.
Gallium does not inhibit the development or recruitment of osteoclasts to bone tissue, unlike many
bisphosphonates that may induce osteoclast apoptosis. Together, these
pharmacologic actions may yield a skeletal system with increased
calcium and
phosphate content and improved biomechanical strength.
Gallium nitrate has potent antiresorptive effects on bone that can be achieved at considerably lower doses than are currently used for
cancer-related
hypercalcemia. Parenteral and oral formulations of
gallium appear to have high activity in bone resorptive disorders, and thus development should be vigorously pursued in these diseases.