About two million
patients per year in the United States - more than 50% of all
cancer patients - receive radiotherapy at some stage during their
illness, either alone or in combination with chemotherapy, surgery, and
Radiotherapy destroys cancer cells using high-energy ionizing
radiation to damage DNA and induce cell death. Radiotherapy targets tumor cells but also causes damage to nearby
healthy tissues. While this side effect has been improved by
computer-assisted guidance, patients who receive radiation remain at
high risk of losing bone density and suffering from broken bones within
the radiation field during their lifetimes.
‘Suppressing a bone specific protein via its neutralizing antibody alleviates radiation-induced bone loss in an animal model.’
New research from Perelman School of Medicine at the University of
Pennsylvania and the Children's Hospital of Philadelphia may hold a clue
to curtailing this feared side effect: suppressing a bone specific
protein via its neutralizing antibody alleviates radiation-induced bone
loss in an animal model.
"Our study showed that activating the
Wnt/b-catenin pathway can overcome radiation-induced DNA damage and
death of bone-making cells," said senior author Ling Qin, an
associate professor of Orthopedic Surgery at Penn. "This study has
clinical relevance in that it demonstrates an antibody that can block
sclerostin(Scl-Ab), a circulating factor that can inhibit bone
formation, can ameliorate radiotherapy-induced osteoporosis."
published their findings in the Journal of Bone & Mineral Research
A Phase II study underway at other centers using Romosozumab
(Scl-Ab) for general osteoporosis is showing promise and this encouraged
the team to determine whether weekly treatment with Scl-Ab could
prevent radiotherapy-induced osteoporosis in mice.
They found that
Scl-Ab blocked deterioration of trabecular, or spongy, bone after
radiation by partially preserving the number and activity of
bone-forming cells. Scl-Ab accelerated DNA repair in bone cells after
radiation by reducing the number of DNA double-strand-break markers and
increasing the amount of DNA-repair proteins. This protected the bone
cells from turning on a radiation-induced, cell-death process.
Using cell-lineage tracing, the team demonstrated that radiation
damage to progenitor bone cells mainly involves shifting their fate to
become fat cells and stops their ability to proliferate, but not
inducing cell death. Scl-Ab treatment partially blocked the lineage
shift, but had no effect on the loss of proliferation potential.