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.
Keywords: Osteoporosis, osteoclastic lineage, novel bone-anabolic agents.
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