 Definition of the drug:

Prolia (denosumab) is a monoclonal antibody, monoclonal antibodies are made to target and destroy only certain cells in the
body, this may help to protect healthy cells from damage.

Denosumab is used to increase bone mass in women and men with a high risk of bone fracture caused by receiving treatments
for certain types of cancer.

 Mechanism of action:

Denosumab binds to RANKL, a transmembrane or soluble

protein essential for the formation, function, and survival of
osteoclasts, the cells responsible for bone resorption,
Denosumab prevents RANKL from activating its receptor
"RANK" on the surface of osteoclasts , this will
inhibit osteoclast formation, function, and survival, by that
decreasing bone resorption and increasing bone mass and
strength in both cortical and trabecular bone.

 Pharmacodynamics:
In clinical studies, treatment with 60 mg of Prolia resulted in
reduction in the bone resorption by approximately 85% by 3
days, with maximal reductions occurring by 1 month. After
discontinuation of Prolia treatment, markers of bone
resorption increased to levels 40% to 60% above pretreatment
values but returned to baseline levels within 12 months.
  Pharmacokinetics:

Absorption: For a 60 mg subcutaneous dose, maximum serum denosumab concentrations (Cmax) of 6 μg/ml occurred in 10
days.

Biotransformation: Denosumab is composed solely of amino acids and carbohydrates as native immunoglobulin and is
unlikely to be eliminated via hepatic metabolic mechanisms. Its metabolism and elimination are expected to follow the
immunoglobulin clearance pathways, resulting in degradation to small peptides and individual amino acids.

Denosumab pharmacokinetics was not affected by the formation of binding antibodies to denosumab and was similar in men
and women. Age , race and disease state (low bone mass or osteoporosis; prostate or breast cancer) do not appear to
significantly affect the pharmacokinetics of denosumab.

 Oral manifestations
Osteonecrosis of the Jaw (ONJ): ONJ, which can occur spontaneously, is generally associated with tooth extraction, and has
been reported in patients receiving Prolia "denosumab" .

An oral exam should be performed by the prescriber prior to initiation of Prolia.

Good oral hygiene should be maintained during treatment with Prolia.

Patients who are suspected of having or who develop ONJ should receive care by a dentist.

 References:
 https://www.medicines.org.uk/emc/medicine/23127
 http://www.proliahcp.com/who-to-treat/range/index.html
 http://www.rxlist.com/prolia-drug/clinical-pharmacology.htm
 https://www.drugs.com/prolia.html

Done by: Mahdi Jamal AlShammari , University number: 20142050282 , Seat: 19 , Day: Monday