What is bisphosphonates mechanism of action?

Before talking about the topic of “bisphosphonates mechanism of action”, some basic properties of bisphosphonates are introduced. They are a new kind of medicine to treat various bone diseases and calcium metabolic diseases. It can inhibit osteoclast activity through the way specifically binding to hydroxyphosphonite in bone, and thus inhibit bone resorption. 

Bisphosphonates are a large family, including alendronate sodium, hydroxyedronate sodium, ibandronate sodium, and zoledronic acid, which are active in the field of anti-glucocorticoid-induced osteoporosis. All of them have appeared on the market in China.

The use of bisphosphonates

Bisphosphonates are used in the treatment of osteoporosis, osteitis deformans, hypercalcemia and bone pain caused by bone metastasis of malignant tumors. In particular, it is very suitable for treating this kind of osteoporosis which is characterized by a reduction in bone mass and destruction of bone structure, leading to bone fragility and increased fracture rates. 

Osteoporosis is a systemic bone disease, and bone destruction is also a common complication of various solid tumors, such as breast cancer, and hematopoietic malignancies. Both of them can cause hypercalcemia and bone pain. Therefore, the prevention and treatment of abnormal bone metabolism diseases has aroused extensive attention in the medical field.

Bisphosphonates mechanism of action

Bisphosphonates can inhibit osteoclast bone resorption, which can be tightly adsorbed on the surface of hydroxyapatite and are not easily degraded by pyrophosphatase. The bidirectional process of dissolving hydroxyapatite into amorphous calcium phosphate and transforming amorphous calcium phosphate into hydroxyapatite was inhibited after bisphosphonate was combined with hydroxyapatite in bone.

The mechanism of anti-bone resorption may be related to the following three aspects.

1. Bisphosphonates can directly change the morphology of osteoclasts to inhibit their function.

2. It directly interferes with bone absorption when it combines physicochemically with bone matrix.

3. It has the function of directly inhibiting the production of osteoblast-mediated cytokines. 

Studies have shown that bisphosphonate can be adsorbed on the binding site of minerals, thus interfering with the attachment of osteoclasts, resulting in changes in the ultrastructure of osteoclasts. In particular, alendronate sodium can selectively bind to the active site under the attachment surface of the end bone of osteoclasts, making osteoclasts unable to play their role, which can explain the reason why the half-life of bisphosphonates in bone is very long.

Bisphosphonates can prevent experimental arterial, kidney, and skin calcification and reduce tartar formation when applied topically. Systemic application of bisphosphonates, such as etidronate, can not only inhibit ectopic calcification, but also inhibit ectopic ossification. Certain bisphosphonates can also delay mineralization in normally calcified tissues such as bone with enough doses.

The ability of bisphosphonates to inhibit calcium phosphate formation in vitro is closely related to its effect on ectopic calcification in vivo. They strongly inhibit bone resorption both in vivo and in vitro. Bisphosphonates have been studied to inhibit the adhesion of breast and prostate cancer cells to non-mineralized extracosseous cell matrix. 

The notices when taking bisphosphonates

After discussing the topic of “bisphosphonates mechanism of action”, the notices must be introduced.

1. Because bisphosphonates can increase bone density and reduce the level of blood calcium, it is necessary to ensure normal blood calcium before using this product. Hypocalcemia with bisphosphonates will lead to osteoporosis, fracture, fracture delay and other adverse effects.

2. Bisphosphonates can produce local stimulation of esophageal mucosa. In patients with oral bisphosphonates, esophageal adverse reactions have been reported including esophagitis, esophageal ulcers, esophageal erosion, occasional bleeding, and rare esophageal stenosis or perforation.

3. Whether oral or injectable bisphosphonates, renal function should be checked before medication. Patients with severe renal function impairment should not take medication.

The State Food and Drug Administration issued a warning that bisphosphonate drugs may cause serious adverse reactions such as jaw necrosis, esophageal cancer and kidney failure on April 15, 2011 in China. So we should pay attention to the safety of bisphosphonate drugs and be alert to related risks.

Conclusion: 

This brings us to conclude our essay on the theme of "Bisphosphonates mechanism of action”. This medicine can restrain osteoclast bone resorption because it can tightly attach to the surface of hydroxyapatite and inhibit the dissolution and destruction of bone trabeculae by osteoclasts. With the in-depth study of the mechanism of bisphosphonates, more discoveries and innovations will emerge in the future and make greater contributions to the development of the medical field.