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Progress on novel compounds for the treatment of bone metabolism-related disorders: focus on osteoporosis and beyond
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DOI：10.3389/fchem.2026.1861883.png)
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Abstract
En 中文
Bone metabolism-related disorders represent a significant global health burden; due to their high prevalence and substantial socioeconomic costs; particularly osteoporosis. Conventional antiresorptive and anabolic agents have well-established clinical utility; such as bisphosphonates; denosumab; teriparatide; and romosozumab. Nevertheless; their long-term clinical use remains limited by safety concerns and inadequate efficacy in a subset of patients. In this review; we highlight recent chemical innovations designed to mechanistically reprogram the skeletal microenvironment and overcome those longstanding barriers. We also analyze how the metabolic coupling signals govern bone bioenergetics; particularly within the Wnt and RANKL axes. We place specific focus on three emerging and transformative strategies: proteolysis-targeting chimeras (PROTACs); bone-targeted senolytics; and direct metabolic modulators. Ultimately; we provide a multidisciplinary roadmap for the development of next-generation therapeutics to achieve durable skeletal restoration in patients with bone metabolic disorders.
Keywords:
osteoporosis
clinical translation
PROTACs
bone metabolism
Wnt signaling
senolytics
compounds
RANKL inhibition
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