Biphosphates Summary

Biphosphates are drugs used for treating bone disorders characterized by excessive bone resorption.
Its clinical efficacy stems from two properties; their ability to bind strongly to bone material and there inhibitory effects on mature osteoclasts.

There general action is binding to hydroxyapatite crystals and acting on osteoblasts, particularly in in areas of high bone turn over resulting into antiresorptive effect.

Biphosphates are divided into two categories; nitrogen-containing and non-nitrogen containing.

Nitrogen containing BPs examples are; alendronate,ibandronate, pamidronate,risendronate and zoledronate

Non nitrogen containing BPs  examples are; clodronate and etidronate.

Nitrogen containing act by inhibiting fernesyl pyrophosphate (fpp) synthase, an enzyme in cholesterol synthesis, preventing the prenylation of small GTP binding protein causing osteoclast inactivation.

Non-nitrogen containing BPs are metabolized into ATP analogs that block osteoclast function and induce osteoclast apoptosis.

Several research have been done in both vitro and vivo conditions showing that effects of BPs depend on the conc. Of the dose. Low conc. Lead to increased growth and have induction effect as high conc. Had an inhibitory effect on osteoclast.

Long term use BPs has shown good safety profile although some studies has associated BPs with osteonecrosis of the jaw and atypical subtrochanteric femoral fractures.