Bisphosphonates

Generality

Bisphosphonates - also known as bis-phosphonates or diphosphonates - constitute a class of drugs widely used to counteract the loss of bone mineral density.

These medicines owe their name to the presence of two phosphonate groups, in the chemical structure that characterizes the entire class of drugs.

From the chemical point of view, on the other hand, bisphosphonates can be considered as derivatives of pyrophosphate (chemical structure: P ₂ O ₇ 4-), in which the oxygen that binds both phosphorus atoms has been replaced with a carbon atom, so as to make this type of bond non-hydrolyzable.

Among the main bisphosphonates still used in therapy, we mention: alendronic acid (Alendros®, Fosamax®), etidronic acid (Etidron®), clodronic acid (Clody®), risedronic acid (Optinate®, Actonel ®), pamidronic acid (Aredia®) and zoledronic acid (Zometa®).

Therapeutic indications

As mentioned, bisphosphonates are active ingredients which are used to counteract the loss of bone mineral density. Therefore, the use of these drugs is indicated in the following cases:

Prevention and treatment of osteoporosis, both in women and in men (however, male osteoporosis is less frequent than female);
Hypercalcemia ;
Paget's disease (bisphosphonates are the drugs of first choice for the treatment of this pathology);
Other diseases that can lead to loss of bone mineral density (as happens, for example, in the case of hyperparathyroidism or lytic bone metastases).

Action mechanism

Although the exact molecular mechanisms, through which bisphosphonates are able to counteract the loss of bone mineral density, have not yet been precisely identified, these drugs - once taken, orally or parenterally - are absorbed and are absorbed. they deposit on the hydroxyapatite crystals present in the sites of reabsorption of the bone matrix. Once deposited at this level, bisphosphonates interact with osteoclasts (the cells responsible for bone resorption), inhibiting their proliferation, shortening their average life and decreasing their activity.

Thanks to this mode of action, therefore, bisphosphonates are able to limit the processes of bone resorption, favoring - albeit indirectly - the action of osteoblasts, which can thus give rise to well-mineralized bone tissue.

Side effects

The side effects induced by bisphosphonates, and the intensity with which they occur, can vary from patient to patient, both as a function of the active ingredient that is decided to be used, and depending on the sensitivity of each individual towards the same drug.

However, among the main side effects common to most of the active ingredients belonging to the bisphosphonate class, we recall:

Nausea;
Abdominal pain;
Diarrhea;
Esophagitis .
Osteonecrosis of the Jaw (demonstrated above all for high-dose intravenous administration, used for the treatment of some types of cancer).

This latter side effect can occur when bisphosphonates are taken orally with low amounts of water. For this reason, oral bisphosphonates should be taken in the morning immediately after waking up, with a sufficient amount of water to avoid irritation and possible esophageal erosion (approximately, approximately 200-250 ml of water). After that, the patient must stand upright for at least thirty minutes and avoid taking other liquids or food, so as to ensure optimal absorption of the drug.

Other side effects that may occur following the intake of bisphosphonates (both orally and parenterally) are:

Inflammation of the eye and / or conjunctiva;
Asymptomatic or symptomatic hypocalcemia (the latter, however, is a rarer form);
Mild increase in blood transaminase levels;
Allergic reactions in sensitive individuals.

Interactions with other drugs

Generally, the concomitant intake of bisphosphonates and antacid drugs or calcium-based supplements is not recommended, since these can negatively influence the absorption of the bisphosphonates themselves.

If, on the other hand, it is necessary to take the aforementioned drugs, then these, in general, should be administered at least thirty minutes after taking bisphosphonates.

Furthermore, it is also generally not advisable to take bisphosphonates and NSAIDs at the same time, as there is a greater risk of developing gastrointestinal damage.