Mode of action
All bones are in a state of constant remodeling. Two types of bone cells are particularly important for bone metabolism: osteoblasts (for bone formation) and osteoclasts (for bone resorption). These communicate with each other by means of various signal molecules.
The RANKL molecule formed by osteoblasts is one such signal molecule. It binds to an immature precursor cell of the osteoclasts (preosteoclast), more precisely to the signal receiver (receptor) called RANK. Through this process, the preosteoclast receives the “command” to mature, develops into a mature osteoclast and begins to resorb bone.
At the same time, the osteoblast secretes a further signal molecule, the osteoprotegerin (OPG), which is intended to prevent excessive bone resorption in the function of a “catch molecule”. It binds to RANKL and thus prevents signal transmission to the signal receiver RANK. This normally maintains a balance between bone formation and bone resorption. This is exactly where Prolia® comes in. As a RANKL-binding antibody, it mimics the action of osteoprotegerin (OPG) and thus prevents bone resorption.
When should Prolia® not be used?
Prolia® must not be used if there is a calcium deficiency. A normal level of calcium and vitamin D must be established in the blood beforehand. The drug should not be used in children, teenagers and pregnant women.
There are no data available to prove the safety of the application. In elderly patients and in patients with impaired kidney function the drug can be used without any restrictions. There are no data available for patients with impaired liver function. A careful risk-benefit assessment should be performed for nursing mothers.
Side effects
The most common side effects (<10%) are urinary tract infection with itching and burning sensation when urinating, upper respiratory tract infection, pain, tingling or numbness along the leg (sciatica syndrome), cataracts of the eyes, sluggishness of the bowels, constipation, skin rash and pain in the limbs. Occasionally (<1%) an inflammation of the intestinal pockets with abdominal pain, vomiting and fever (diverticulitis), bacterial inflammation of the subcutaneous fatty tissue, infection of the ears and eczema occur. Very rarely a dangerous calcium deficiency (hypocalcaemia) occurs.
For this reason, the company AMGEN 2012 sent a “Red-Hand Letter”, in which a possible severe calcium deficiency with possibly fatal outcome was pointed out. In another “Rote-Hand-Brief” of 2013 the company described rare cases of an unusual fracture of the femur (atypical femur fracture).The effect of Prolia® is also indirectly related to the immune system, which is why an increased risk of serious infection and cancer is currently being discussed. There is also a possible connection with the death of the jawbone.
