Sclerostin: A Potential Link between Osteoporosis and Alzheimer's Disease.

BACKGROUND

Osteoporosis and Alzheimer's disease (AD) are age-related disorders with shared risk factors such as aging, oxidative stress, and neuroinflammation. Sclerostin, a glycoprotein secreted by osteocytes, inhibits Wnt/β-catenin signaling, leading to suppressed bone formation and increased resorption in osteoporosis. Recent findings reveal sclerostin is also expressed in the brain, where it may disrupt synaptic function and contribute to AD progression. Romosozumab, an anti-sclerostin monoclonal antibody approved for osteoporosis, is being explored for potential use in AD, though its ability to cross the blood-brain barrier remains a challenge.

SUMMARY: This review highlights the emerging connection between osteoporosis and AD, focusing on sclerostin as a shared molecular mediator. Understanding this link may open new avenues for dual-purpose therapies targeting sclerostin, with the potential to benefit both bone and brain health. Further studies are needed to clarify the causal mechanisms and therapeutic implications.

KEY MESSAGES: This review highlights sclerostin as a key molecular link between osteoporosis and AD, supporting the emerging concept of a bone-brain axis. Anti-sclerostin therapies like romosozumab may offer benefits beyond bone health, with potential in neurodegenerative disease treatment. Sclerostin may drive AD pathology by disrupting Wnt/β-catenin signaling and promoting β-amyloid and tau abnormalities.