The Role Of Denosumab

Raditya Pria Utama, Hesty Rohmatul Fajri

Abstract

ABSTRACT 

Osteoporosis is one of the most common chronic diseases. This condition makes bones in a person to become more porous and fragile, therefore greatly increase their risk of suffering a fracture. In Asia, the mortality rate that are associated with these fractures occurred between 10–20% of cases within a year.  Osteoporosis is a condition in which there is an imbalanced activity between osteoblast and osteoclast. Osteoblast and osteoclast are two types of bone cells that majorly involve in bone remodelling process. Osteoclasts adhere to the bone surface once it mature, after that osteoclast both produce and secrete chloride acid (HCl), which will acidify bones and dissolve the bone mineral. Receptor Activator of Nuclear Factor kappa B Ligand (RANKL) is one of the necessary  factors in bone remodelling process. It will activate and mature the osteoclast. Denosumab is a monoclonal antibody that will inhibit  the binding of RANKL to its receptor, decreasing osteoclastogenesis and bone-resorbing activity.  This inhibiting activity will theoretically increase the bone mass density in ones’ body, ergo will treat and prevent osteoporosis. Denosumab showed favourable effect on bone metabolism without having serious adverse events compared to control group. This paper reviews the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, and tolerability in the denosumab in the management of osteoporosis.

Keywords                   : Denosumab, RANKL, osteoporosis, treatment

Correspondence to      : radityapu@gmail.com

ABSTRAK 

Osteoporosis adalah salah satu jenis dari penyakit kronis yang sering terjadi. Penyakit ini menyebabkan tulang seseorang menjadi lebih berongga dan rapuh, kondisi ini meningkatkan risiko patah tulang pada orang-orang tersebut. Di Asia, mortality rate yang berhubungan dengan kejadian patah tulang ini berkisar antara  10 – 20% dalam satu tahun. Osteoporosis adalah suatu kondisi dimana terjadi ketidakseimbangan antara osteoblast dan osteoklas. Osteoblas dan osteoklas adalah dua tipe dari sel tulang yang berperan pada proses bone remodelling. Setelah matang, osteoklas akan menempel pada tulang untuk menghasilkan dan menyekresi HCl, yang dimana zat ini akan mengasamkan tulang dan meluruhkan mineral di tulang.  Receptor Activator of Nuclear Factor kappa B Ligand (RANKL) adalah salah satu faktor yang dibutuhkan dalam proses remodelling tulang. RANKL akan mematangkan dan mengaktifkan osteoklas. Denosumab adalah antibody monoclonal yang menghambat ikatan dari RANKL kepada reseptor dari RANKL, menurunkan proses osteoklasogenesis dan aktivitas penyerapan tulang. Secara teori proses ini akan meningkatkan massa dari tulang dan mencegah osteoporosis. Denosumab menunjukan efek yang sbaik pada metabolisme tulang tanpa menunjukkan efek samping yang serius. Makalah ini akan meninjau tentang farmakologi klinis, farmakodinamik , dan farmakokinetik, serta tolerabilitas dari denosumab dalam terapi osteoporosis.

Kata kunci                  : Denosumab, RANKL, osteoporosis, treatment

Korespondensi             : radityapu@gmail.com

Keywords

Denosumab, RANKL, osteoporosis, treatment

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DOI: http://dx.doi.org/10.30651/jqm.v3i2.2807