The active ingredient denosumab has been on the market since 2010 and is marketed by AMGEN under the trade names Prolia® and XGEVA®.
The human monoclonal IgG2 anti-RANKL antibody is used for the therapy of bone loss (osteoporosis) used.
The effectiveness is achieved by denosumab intervening in the so-called RANK / RANKL system of bone metabolism and thus reducing bone loss.
Prolia® is used at both Bone loss (osteoporosis) in women after the Menopause (Post menopause) who are prone to fractures, as well as in men with an increased risk of fractures, e.g. under hormone therapy Prostate cancer.
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By intervening in the RANK / RANKL system, which plays a central role in bone loss, the drug would potentially also be used in other diseases with a tendency to fracture, such as steroid-induced bone loss and the rheumatoid arthritis Act.
The Prolia® is administered as a syringe into the subcutaneous fat tissue. Usual pre-filled syringe doses are 60mg and 120mg. When used every six months, the active ingredient leads to increased bone mineral density and a reduction in the rate of vertebral fractures.
The effectiveness of the drug has been proven in two high quality studies.
The HALT study looked at 734 men, mean 75.3 years old, because of their Prostate cancer treated with hormones.
After two years, the patients taking Prolia® had increased bone density by an average of 5.6%; the placebo group (without medication) had a loss of 1.0%.
At the same time, 1.5% of the patients took Prolia® therapy Vertebral fractures without Prolia® it was 3.9%.
The FREEDOM study looked at 7,868 postmenopausal women osteoporosis.
On treatment, 2.3% of women developed a vertebral fracture and 0.7% of the femoral shaft fractures within three years, compared with 7.2% and 1.2% in the placebo group.
This corresponds to a similar effectiveness as zoledronate and teriparatide, which are also used to prevent bone fractures.
All bone are in constant renovation. Two types of bone cells are of particular importance for bone metabolism, the Osteoblasts (for bone building) and the Osteoclasts (for bone loss).
These communicate with each other through various signal molecules. The RANKL molecule formed by osteoblasts is such a signaling molecule. It binds to one immature progenitor cell osteoclasts (Pre-osteoclast), more precisely to the signal receiver (receptor) called RANK.
This process gives the pre-osteoclast the “command” to mature, develop into a mature osteoclast and begin to break down bone.
At the same time, the osteoblast secretes another signaling molecule, the Osteoprotegerin (OPG), which is supposed to prevent excessive bone loss in the function of a "catching molecule".
It binds to RANKL and thus prevents the signal from being transmitted to the RANK signal receiver.
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So usually becomes a Balance between bone building and bone loss receive.
This is exactly where Prolia® comes in. As a RANKL-binding antibody, it mimics the effect of osteoprotegerin (OPG) and thus prevents bone loss.
If there is an existing calcium deficiency, Prolia® must not be used. Before that, a normal calcium and Vitamin D levels are made in the blood.
The drug should not be used in children, adolescents and pregnant women. No data are available to prove the safety of use.
$config[ads_text2] not foundIn the elderly and in those with impaired kidney function the drug can be used without restriction.
For patients with impaired Liver function no data available.
A careful risk-benefit assessment should be made for breastfeeding mothers.
The most common side effects (<10%) are a Urinary tract infection With Itching and burning when urinating, an upper respiratory tract infection that causes pain, tingling, or numbness along the leg (Sciatica syndrome), a Cataract eyes, constipation, rash, and body aches.
Occasionally (<1%) kick a Inflammation of the intestinal pouches with abdominal pain, vomiting and fever (Diverticulitis), bacterial inflammation of the subcutaneous tissue, ear infection, and eczema.
Very rarely there is a dangerous calcium deficiency (Hypocalcemia). For this reason, the AMGEN company sent a “Rote-Hand-Brief” in 2012, in which a possible severe calcium deficiency with a possible fatal outcome was pointed out.
In another "Rote-Hand-Brief" from 2013, the company described rare cases of an unusual thigh fracture (atypical femoral fracture).
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The effect of Prolia® is also indirectly related to the immune system, which is why an increased risk of severe 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 have been performed.
However, the risk of interactions with other drugs is considered to be low.
Studies on Long term risk and Long-term benefits from Prolia® are not yet available.
Also studies showing the active ingredient Denosumab with similar drugs with a different mode of action such as the Bisphosphonates compare have not yet been carried out.
It is currently uncertain whether the drug will have an additional benefit over similar substances and is still being discussed.
