Sclerostin is an osteocyte-derived regulator of bone formation targeted by newer anabolic agents. What is its mechanism of action?

• A It binds RANKL and prevents osteoclast precursor differentiation
• B It antagonizes Wnt signaling in osteoblasts, suppressing bone formation ✓
• C It activates the PTH receptor on osteoblast lineage cells
• D It stimulates FGF23 secretion from osteocytes

Explanation

Sclerostin, encoded by the SOST gene and produced mainly by mature osteocytes embedded in mineralized matrix, is an antagonist of canonical Wnt/beta-catenin signaling in osteoblasts. By blocking Wnt, it suppresses osteoblast differentiation and activity, reducing bone formation. Mechanical loading downregulates sclerostin, allowing bone formation at strained sites. Anti-sclerostin antibodies such as romosozumab exploit this pathway as anabolic therapy. It does not act on the RANKL or PTH pathways.

Reference: Williams Textbook of Endocrinology, 14th ed.

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