Science of Alendronate

The chemical formula is C4H18NO10P2Na. Alendronate is classified as a bisphophonate, or diphophonate.

Bisphosphonates have the P–C–P chemical structure, which is analgous to the P–O–P patterns in native pyrophosphate. In the body, the alendronate attaches to the edges of the bone. The alendronate released during resorption stops the osteoclasts to form the ruffled border and to adhere to the bony surface. Now a second effect of alendronate on the body is to inhibit mineralization of bones. At extremes, slowing mineralization leads to a disease called osteomalacia, aka rickets. This is an area where alendronate does better than other bisphosphonates. A good osteoporosis drug inhibits resorption, but does not stop mineralization. The amount of alendronate you have to take to adequately retard resorption is about 1000 times what you would have to take to stop mineralization, while for the bisphosphonate drug etidronate, the effective dose for osteoporosis treatment carries a substantial risk of causing osteomalacia. Osteomalacia hardly ever happens on alendronate.

 

Pharmacokinetics

Bisphosphonates are not well absorbed in the digestive system (one to five percent of an oral dose), and absorption is best when the drug is given on an empty stomach. Alendronate is usually taken only with water and that the patient is advised to wait at least 30 minutes before ingesting food or other medications. Approximately 80 percent of the absorbed alendronate is cleared by the kidney, the remaining 20 percent being taken up by bone. Relative bone uptake is increased in conditions of high bone turnover, with less of the drug being excreted by the kidneys.

 

The half-life in the bloodstream is about an hour. The half-life in the body as a whole, however, is so long as to be meaningless - possibly over 10 years. This is one way bisphosphonates are different from other drugs. They are not metabolized in the sense that they are chemically broken down in the body, and they do not exit the body.