Bisphosphonates

• Introduction.

• Classification of Bisphosphonates.

• Mechanism of action of Bisphosphonates.

• The defining dose of Bisphosphonates.

• Resistance causes of Bisphosphonates drugs.

• Side effects of Bisphosphonates drugs.

• Examples os Bisphosphonates drugs.

• Monographs

2.Classification of Bisphosphonates.

Bisphosphonates can be classified in two main ways:

Chemical structure: This divides them into two groups: nitrogen-containing bisphosphonates and non-nitrogen-containing bisphosphonates.

• Nitrogen-containing bisphosphonates are the more common type and are generally more potent in inhibiting bone resorption. Examples include alendronate (Fosamax) and risedronate (Actonel).

• Non-nitrogen-containing bisphosphonates are less commonly used because they can have side effects that interfere with bone formation. Etidronate (Didronel®) is an example of a non-nitrogen-containing bisphosphonate.

• Route of administration: This refers to how the medication is taken. Bisphosphonates can be administered either orally (by mouth) or intravenously (through a vein).

• Oral bisphosphonates are the most common type and are generally taken once a week.

• Intravenous bisphosphonates are typically used for people who cannot tolerate oral bisphosphonates or for those with certain other medical conditions.

3.Mechanism of action of Bisphosphonates.

There are two main mechanisms by which bisphosphonates work:

• Direct inhibition of osteoclasts: Nitrogen-containing bisphosphonates, the most common type, work by attaching to the mineral hydroxyapatite that makes up bone. Once attached, they are taken up by osteoclasts, the cells that break down bone. Inside the osteoclasts, bisphosphonates disrupt a key enzyme involved in their function, leading to their death and a decrease in bone resorption.

• Interference with osteoclast function: Non-nitrogen-containing bisphosphonates are less common and work by mimicking pyrophosphate, a natural molecule in bone that inhibits bone resorption. When osteoclasts ingest these bisphosphonates, they are unable to function properly and die.

• The exact mechanism of how bisphosphonates stimulate bone formation is not fully understood, but it is thought to be an indirect effect of their action on osteoclasts. By reducing bone resorption, bisphosphonates may create a more favorable environment for bone-forming cells called

4.The defining dose of Bisphosphonates

The defining dose of bisphosphonate medication depends on the specific drug, its form (oral or intravenous), and the medical condition being treated.

Here are some examples:

• Alendronate (Fosamax): This medication is typically taken orally once a week in a dose of 70 mg.

• Risedronate (Actonel): This medication is also taken orally, either once a week in a dose of 35 mg or once monthly in a dose of 5 mg.

• Zoledronic acid (Reclast): This medication is administered intravenously (into a vein) once a year in a dose of 5 mg.

5.Resistance causes of Bisphosphonates drugs.

Bisphosphonate resistance in treatment isn't fully understood, but there are theories about why it might happen:

• Suppressed Bone Turnover: Bisphosphonates work by slowing down bone breakdown. While this increases bone density, it can also suppress bone turnover too much, hindering the body's natural bone renewal process.

• Reduced Blood Supply: Long-term bisphosphonate use might affect blood flow to bones, potentially limiting the delivery of nutrients needed for healthy bone remodeling.

• Altered Bone Microarchitecture: Bisphosphonates might create a denser bone structure that's more brittle and prone to fracture despite increased density.

• It's important to note that bisphosphonate resistance seems to be specific to the type of bisphosphonate used and not necessarily the entire class. This means switching to a different bisphosphonate might still be effective.

6.Side effects of Bisphosphonates drugs.

Bisphosphonates are generally well-tolerated medications, but they can cause some side effects. Here's a breakdown of the most common and some rarer ones:

Common side effects:

• Gastrointestinal issues: This is the most common side effect, especially with oral bisphosphonates. It can include heartburn, indigestion, nausea, stomach upset, and diarrhea. To minimize these, doctors recommend taking bisphosphonates with a full glass of water and staying upright for at least 30 minutes after taking them.

• Flu-like symptoms: Intravenous bisphosphonates might cause temporary flu-like symptoms like fever, muscle aches, and fatigue. These usually go away within a few days.

• Bone, joint, and muscle pain: This is less common, affecting less than 5% of patients. The pain is usually mild, but can sometimes be severe.

• Less common side effects:

• Esophageal irritation: Bisphosphonates can irritate the esophagus, leading to heartburn, difficulty swallowing, or ulcers.

• Low calcium levels: Bisphosphonates can slightly decrease calcium levels in the blood.

• Atypical femoral fractures: This is a rare but serious side effect, more commonly associated with long-term high-dose use. It involves fractures in the upper thigh bone (femur) without a significant injury.

• Jawbone problems (osteonecrosis of the jaw): This is another very rare side effect, where bone tissue in the jaw dies. It's more likely in patients who have undergone dental procedures like tooth extractions while on bisphosphonates.

7.Examples os Bisphosphonates drugs.

1. Alendronate 

2. Risedronate

3. Ibandronate

4. Zoledronic acid

8. Monographs