TNFSF11 Inhibition and Fertility: a Prospective Study
Status:
Completed
Trial end date:
2019-01-01
Target enrollment:
Participant gender:
Summary
The receptor activator of NF-kB ligand (RANKL) system is considered important for bone
homeostasis and comprises three important factors. RANKL exist in three isoforms but the
predominant function is mediated by the transmembrane ligand that binds to a specific
receptor (receptor activator of NF-KB (RANK)) on a neighbour cell that subsequently activates
NFKB and regulates cell cycle OPG is an endogenous secreted protein that binds RANKL and
inhibits its signalling.
Thus, the RANK/RANKL system is vital for activation of the bone resorbing cells
(osteoclasts). In bone the bone synthesizing cells (osteoblasts) express RANKL that signals
to RANK on the immature osteoclasts. This induces proliferation and activation of the cells
they start to proliferate and resorp bone. OPG is produced by somatic cells in the bone and
this production is regulated by sex hormones, TGF-B and various other substances. Today a
human made recombinant antibody against RANKL, Denosumab is used to treat osteoporosis as it
inhibits RANKL signalling and thus causes less bone resorption in humans.
RANKL, RANK and OPG are expressed in the testis and this pathway appears to be a novel
regulator of germ cell proliferation. Decreased semen quality is a major factor of male
infertility. Semen quality is a measure of the ability of the sperm to accomplish
fertilization. Evaluation of male fertility potential is today basically conducted through
semen analysis. There is no treatment for men with no sperm in the ejaculate and there exist
no drug that can increase sperm counts.Therefore, drugs that can lower RANKL
expression/activity for instance an antibody against RANKL such as Denosumab may be used for
this new indication: A new treatment option of infertile men with impaired semen quality.