Bisphosphonate Mechanism

Normal bone physiology

Bones are living tissues that undergo constant remodelling. In a healthy bone that has finished growing, the breakdown of old bone (by osteoclasts) and the formation of new bone (by osteoblasts) is a carefully regulated process.

What happens in osteoporosis and bone damage?

When osteoporosis occurs or when cancer affects the bones, the proportion of osteoclasts and osteoblasts becomes unbalanced and more bone is broken down than is replaced. This can cause the bones to weaken and become more prone to fracture, even on minor trauma or injury.

How do bisphosphonates help?

Bisphosphonates reduce the number and action of the osteoclasts, slowing the process of bone breakdown. Bisphosphonates cannot replace lost bone but can strengthen existing bone and reduce the damage that is caused by the disease process.

Bisphosphonate molecules adhere to calcium and since the largest store of calcium in the human body is found in bones, high levels of bisphosphonates accumulate. The osteoclasts ingest the bound bisphosphonates and are eventually destroyed.

Bisphosphonate types

Bisphosphonates can be divided into two classes, which include:

  • The nitrogenous bisphosphonates such as palmidronate, alendronate and zoledronate
  • The non-nitrogenous bisphosphonates such as etidronate, clodronate and tiludronate.

The two types of bisphosphonates differ in their mechanism of action for killing osteoclast cells. The non-nitrogenous bisphosphonates are taken up by the osteoclasts, which then die. Nitrogenous bisphosphonates bind and block the enzyme farnesyl diphosphate synthase in the HMG-CoA reductase pathway (also known as the mevalonate pathway). This prevents formation of farnesol and geranylgeraniol, metabolites that are important for connecting some small proteins to the cell membrane. This phenomenon is known as prenylation. Prenylation is an important part of bone health and remodelling.

Benefits of treatment

Some examples of the benefits bisphosphonate therapy provides include:

  • Bone pain is relieved when bisphosphonates are used to treat Paget’s disease.
  • In cancer patients with bone damage, bisphosphonates reduce the risk of pathological fracture.
  • IA bone mineral density test (X-ray) is used to measure progress in osteoporosis therapy. An increased bone mineral density suggests the condition is improving. This test is taken every year or alternate years and detects the amount of calcium and minerals in the bones.
  • Bisphosphonates correct and prevent abnormally high blood levels of calcium.
  • In cancer patients with bone damage, bisphosphonates reduce the need for radiation therapy.
  • Bisphosphonates improve the chances of bones healing and becoming stronger, therefore improving the patient’s quality of life.

Further Reading

Last Updated: Jun 17, 2023

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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