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Advances in pathogenesis and therapeutic strategies for osteoporosis
Abstract
Osteoporosis, is the most common bone disorder worldwide characterized by low bone mineral density, leaving affected bones vulnerable to fracture. Bone homeostasis depends on the precise balance between bone resorption by osteoclasts and bone matrix formation by mesenchymal lineage osteoblasts, and involves a series of complex and highly regulated steps. Bone homeostasis will be disrupted when the speed of bone resorption is faster than bone formation. Based on various regulatory mechanisms of bone homeostasis, a series of drugs targeting osteoporosis have emerged in clinical practice, including bisphosphonates, selective estrogen receptor modulators, calcitonin, molecular-targeted drugs and so on. However, many drugs have major adverse effects or are unsuitable for long-term use. Therefore, it is very urgent to find more effective therapeutic drugs based on the new pathogenesis of osteoporosis. In this review, we summarize novel mechanisms involved in the pathological process of osteoporosis, including the roles of gut microbiome, autophagy, iron balance and cellular senescence. Based on the above pathological mechanism, we found promising drugs for osteoporosis treatment, such as: probiotics, alpha-ketoglutarate, senolytics and hydrogen sulfide. This new finding may provide an important basis for elucidating the complex pathological mechanisms of osteoporosis and provide promising drugs for clinical osteoporosis treatment.
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“In the bone environment of PMOP, osteoclasts are over-activated and mediate significantly enhanced bone resorption, leading to severe bone loss7.”
From Targeting Msx2 as a brake in the fusion fate of osteoclasts and an anabolic therapy in pre-clinical models of osteoporosis (2025) · cites this paper as [7]
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Cited by
Sorted by citations
Ma, Q., Wang, S., Xue, H., Ni, L., Yuan, P., Shen, Y., Zheng, B., Wang, Q., Zhang, J., Wang, H., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61938-0 · Cited by 16
Nrf2 signaling pathway: focus on oxidative stress in osteoporosis
Gu, H.-Y., Liu, N., Lin, F.-X., & Yin, J. (2025) · Osteoporosis International · doi:10.1007/s00198-025-07592-0 · Cited by 10
Metadata
- Authors
- Song, S., Guo, Y., Yang, Y., & Fu, D.
- Affiliations
- Shenzhen Technology University (CN)
- Huazhong University of Science and Technology (CN)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Fu, Dehao
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2022-09
- Volume
- 237
- Pages
- 108168
- ISSN
- 0163-7258 (ISSN-L)
- OpenAlex
- W4220992533
- Cited by
- 476
- References
- 313
- Citations by year
- 2026: 99 · 2025: 152 · 2024: 120 · 2023: 78 · 2022: 27
- FWCI
- 20.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81501196, 82070911, 81874026, 8170011029)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Keywords
- osteoporosis, bone homeostasis, bone resorption, osteoclasts, osteoblasts, gut microbiota, autophagy, iron balance, cellular senescence, probiotics, alpha-ketoglutarate, senolytics, hydrogen sulfide, bisphosphonates, selective estrogen receptor modulators
- MeSH terms
- Bone Resorption, Diphosphonates, Humans, Osteoclasts, Osteoporosis, Bone Density Conservation Agents
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