Bisphosphonates more commonly known as  Fosamax (alendronate), Boniva (ibandronate), and Actonel (risedronate), are prescription anti-resorptive agents that bind permanently to the hydroxyapatite crystalline structure in bone. Bisphosphonates are ca-apatite loving, bone binding analogs of pyrophosphate in which the oxygen has been replaced by a carbon atom. As a result of this chemical structure bisphosphonates will not break down.

Bisphosphonates attach to osteoclast bone digesting sites and halt osteoclast activity. Bisphosphonates reduce osteoclast bone resorption, which in turn maintains bone mineral density. Specifically, bisphosphonates inhibit the breakdown of bone. As such, bisphosphonates reduce or even stopped bone loss.

Trabecular bone is the spongy interior within bone. Trabecular bone serves most of the metabolic function of bone. As such, trabecular bone has a higher number of active remodeling sites than the outer cortical bone. Bisphosphonates prevent resorption and increase the strength of trabecular rich bones such as the spine (vertebrae) and hip (femoral trochanter).

Bisphosphonates reduce fracture rates by prolonging secondary mineralization. Essentially, bisphosphonates harden the remaining bone and increase bone mineralization density and therefore strength. They do so without effecting trabecular thickness or number, i.e. without increasing the amount of bone tissue. This helps explain why anti-resorptive agents reduce fracture risk, even in the absence of substantial increases in bone mineral density. The indication of treatment success when using bisphosphonate therapy is the absence of bone loss, not the extent of bone gain.

Diminished post menopausal estrogen decreases the activity of of osteoblasts and reduces the number of osteocytes. Bisphosphonates have a positive effect on osteoblasts and osteocytes by protecting these bone generating cells from self destruction (apoptotic). Osteoblasts are bone forming cells. Enabling osteoblasts to live longer improves the ability of these bone forming cells to repair micro cracks.

Osteocytes are mature bone cells located deep within bone. Osteocytes receive nutrients and function to maintain the bone matrix. If osteocytes die, the surrounding bone matrix is resorbed. Osteocytes also detect bone micro-damage and transmit signals leading to bone repair. Disruption of the osteocyte network would weaken this signaling mechanism, leading to micro-crack accumulation and increased bone fragility.

Bisphosphonates reduce bone fracture by preserving bone, maintaining osteocytes and prolonging the working time of bone forming osteoblast cells. Preventing bone resorption (withdrawl) reduces bone fracture.