A single injection of kisspeptin rapidly boosts a bone-building marker in postmenopausal women with low bone density. Osteoporosis affects over 3.5 million people in the UK, with one in two women over 50 expected to suffer a fracture. Existing drugs have side effects and limits on how long they can be used, and no new treatments are in late-stage development. The researcher has already shown that kisspeptin—a natural brain hormone that controls reproduction—raises levels of osteocalcin, a marker of bone formation, within 90 minutes in young men. This study tests whether the same happens in 20 postmenopausal women with osteopenia or osteoporosis. If kisspeptin also stimulates bone formation in women, it could become a novel osteoporosis treatment. Unlike current drugs that mainly slow bone loss, kisspeptin might rebuild bone. That would address a major gap: there is no licensed drug that safely and durably builds new bone for long-term use. The annual UK cost of fragility fractures is £4.4 billion, so even a modest reduction in fractures would have substantial health and economic impact.
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In the UK over 3.5million people have osteoporosis, a skeletal disease characterised by reduced bone strength, leading to increased susceptibility to fractures. Owing to a lower peak bone mass and faster bone loss during menopause, women are at greater risk for osteoporosis than men. Indeed, one in two women and one in five men aged over 50 will have an osteoporotic fracture in their lifetime. The annual UK cost of fragility fractures is around £4.4billion and accompanied by an enormous personal burden on individuals who fracture. Several drugs are licensed to reduce fracture risk. However, common side-effects and concerns about duration of treatment frequently limit their use. Despite this, there are no new osteoporosis treatments in late-stage clinical development. The neuropeptide kisspeptin is a critical endogenous activator of the reproductive axis, with emerging animal evidence revealing favourable effects on bone. We have recently shown that kisspeptin administration acutely (within 90minutes) and potently increases the osteoanabolic marker, osteocalcin, in healthy young men. This suggests that kisspeptin could be a novel osteoporosis treatment. Therefore, I propose to investigate the acute effects of kisspeptin on anabolic and resorptive parameters of bone metabolism in 20 postmenopausal women with osteopenia or osteoporosis for the first time. Participants will attend twice, receiving both subcutaneous kisspeptin and placebo, followed by blood sampling over 8-hours for bone parameters. Given the promising data from animal models and the exciting clinical findings in men, results from my proposal have the potential to identify kisspeptin as a potential osteoporosis treatment.
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