BISPHOSPHONATES
The bisphosphonates are
synthetic organic compounds that are incorporated directly into the hydroxyapatite
of bone and then inhibit osteoclastic bone resorption. This antiresorptive
action makes them useful in the pharmacological treatment of hypercalcemia,
osteo-porosis, and Paget’s disease.
The bisphosphonates have a
common structure, P-C-P, which is similar to the structure of the native
pyrophos-phate P-O-P found in bone hydroxyapatite. The differ-ent compounds in
clinical use vary by the attachments to the R component of the native molecule.
The bisphosphonates inhibit
osteoclastic resorption of bone by binding to the hydroxyapatite crystals of
bone. When osteoclasts first attach to bone in the active resorp-tive sites,
the bisphosphonates are released from that bone. The release of these compounds
locally prevents further osteoclastic attachment to those resorptive sur-faces.
The bisphosphonates also may inhibit resorption by inducing apoptosis of
osteoclasts and by inhibiting release of interleukins and other compounds
involved in bone re-sorption. The net result of actions of these compounds is
inhibition of bone osteoclastic resorption. This action al-lows new bone
formation to catch up in the remodeling process and can result in a net gain in
bone density.
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