Since 2010, the active ingredient Denosumab is on the market, which is marketed by the company AMGEN under the trade names Prolia ® and XGEVA ® .
The human monoclonal IgG2 anti-RANKL antibody is used to treat bone loss ( osteoporosis ).
Efficacy is achieved by denosumab in the so-called RANK / RANKL system of bone metabolism and thus reduces bone loss.
Prolia ® is used in bone loss ( osteoporosis ) in menopausal women ( postmenopausal ) prone to bone fracture, and in men at risk of bone fracture, such as hormone therapy for prostate cancer.
By interfering with the RANK / RANKL system, which plays a key role in bone resorption, the drug would potentially also be effective in other diseases such as steroid-induced bone resorption and rheumatoid arthritis.
The Prolia ® is administered as a syringe into the subcutaneous fat tissue. Usual dosages as pre-filled syringe are 60mg and 120mg. The drug leads under half-yearly application to increased bone mineral density and to a reduction in the rate of vertebral fracture.
The effectiveness of the drug has been proven in two high-quality studies.
The HALT study examined 734 men, 75.3 years old on average, who are being treated with hormones because of their prostate cancer.
After two years, the bone mineral density had increased by an average of 5.6% in the patients treated with Prolia ®, and the placebo group ( without medication ) had lost 1.0%.
At the same time, 1.5% of the patients underwent vertebral fractures under Prolia ® therapy, 3.9% without Prolia ® .
The FREEDOM study examined 7868 postmenopausal women with osteoporosis.
Within three years of treatment, 2.3% of women experienced vertebral fracture and 0.7% femoral fracture, as opposed to 7.2% and 1.2% in the placebo group.
This corresponds to similar efficacy as zoledronate and teriparatide, which are also used to prevent bone fractures.
All bones are in a constant reconstruction. Two bone cell types are of particular importance for bone metabolism: osteoblasts ( for bone formation ) and osteoclasts ( for bone resorption ).
These communicate with each other through a wide variety of signal molecules. The RANKL molecule formed by osteoblasts is such a signaling molecule. It binds to an immature precursor cell of osteoclasts ( preosteoclasts ), more specifically to the signal receptor ( receptor ) called RANK.
Through this process, the preosteoclasts get the "command" to mature, develop into mature osteoclasts and begin bone resorption.
At the same time, osteoblast excretes another signal molecule, the osteoprotegerin ( OPG ), which is designed to prevent excessive bone loss in the function of a "trapping molecule".
It binds to RANKL and thus prevents the signal transmission to the signal receiver RANK.
Thus, a balance between bone formation and bone resorption is usually maintained.
This is exactly where Prolia ® comes in. It mimics the action of osteoprotegerin ( OPG ) as a RANKL-binding antibody and thus prevents bone loss.
If there is a calcium deficiency, Prolia ® must not be used. Previously, a normal level of calcium and vitamin D in the blood must be produced.
In children and adolescents, as well as pregnant women, the drug should not be used. There are no data showing the safety of the application.
In elderly patients and in patients with impaired renal function, the drug can be used without restriction.
There are no data available for patients with hepatic impairment.
For nursing mothers, a careful risk-benefit assessment should be carried out.
The most common side effects ( <10% ) are urinary tract infection with itching and burning when urinating, upper respiratory infection, pain, tingling or numbness along the leg ( sciatic nerve syndrome ), cataracts, constipation, constipation, rash and body aches.
Occasionally ( <1% ) 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.
Very rarely there is a dangerous calcium deficiency ( hypocalcaemia ). For this reason, the company AMGEN 2012 sent a "red-hand letter" in which a possible severe calcium deficiency with possible fatal outcome was pointed out.
In a further "Rote-Hand-Brief" from 2013, the company described rare cases of an unusual femoral fracture ( atypical femur fracture ).
The effect of Prolia ® is also indirectly related to the immune system, which is why an increased risk of a serious infection and the occurrence of cancer is currently being discussed. There is also a possible connection with the death of the jawbone.
No interaction studies were performed.
However, the risk of drug-drug interactions is considered low.
Studies on the long-term risk and long-term benefits of Prolia ® are not yet available.
Also, studies comparing the drug denosumab with similar drugs of other modes of action such as the bisphosphonates, have not yet been performed.
Whether the drug brings an added benefit over similar substances, is currently uncertain and is still being discussed.