H3c

Osteoclas

Figure 6 Bisphosphonate (BP) antiosteoclast actions. Administered BPs, such as pamidronate, are rapidly sequestered in bone. Osteoclasts release BP into the resorption cavity to produce a high local concentration and endocytose sufficient to induce osteoclast apoptosis (nitrogen-containing BPs) or inactivity (clodronate or etidronate) and arrest of bone resorption.61 Other cells in the body are only exposed to a transient and low level of BPs. Thus, BPs have exquisite specificity for osteoclasts.

Sequestered bisphosphonates

Bone

Figure 6 Bisphosphonate (BP) antiosteoclast actions. Administered BPs, such as pamidronate, are rapidly sequestered in bone. Osteoclasts release BP into the resorption cavity to produce a high local concentration and endocytose sufficient to induce osteoclast apoptosis (nitrogen-containing BPs) or inactivity (clodronate or etidronate) and arrest of bone resorption.61 Other cells in the body are only exposed to a transient and low level of BPs. Thus, BPs have exquisite specificity for osteoclasts.

For approval, it is necessary to show that an NCE reduces skeletal complications of malignancy, usually through the evaluation of new 'skeletally related events,' that can include interventions for bone pain, fracture, surgery for nerve compression, and hypercalcemia. Trials are usually of 1-2 years' duration.

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