Title:Targeting NO Signaling for the Treatment of Osteoporosis
Volume: 23
Issue: 24
Author(s): Hema Kalyanaraman, Ghania Ramdani and Renate B. Pilz
Affiliation:
Keywords:
Osteoporosis, osteoclastic lineage, novel bone-anabolic agents.
Abstract: Osteoporosis is a major health problem, affecting over 10 million
people in the U.S. and leading to fractures associated with significant morbidity
and mortality. Normal bone mass is maintained by a balance between
the anabolic effects of osteoblasts and catabolic effects of osteoclasts. Most
osteoporosis therapies inhibit osteoclast activity; parathyroid hormone is the
only FDA-approved agent that increases osteoblast activity, but its efficacy
wanes over time, and there is a need for novel bone-anabolic agents. Nitrates,
which generate nitric oxide (NO) in vivo, prevent bone loss from estrogen-deficiency in rodents, and some clinical data suggest beneficial effects
of nitrates in post-menopausal osteoporosis. Here, we examine the
sources of NO and regulation of NO synthesis in bone cells, review the effects of NO in cells
of osteoblastic and osteoclastic lineage, and summarize existing preclinical and clinical data
to document the skeletal effects of NO in vivo. Based on the anabolic and anti-resorptive
effects of NO in bone, novel NO donors and other strategies to enhance NO production and
bioavailability in vivo may represent a new treatment strategy for osteoporosis.
