Advances in pathogenesis and therapeutic strategies for osteoporosis

Pharmacol Ther. 2022 Sep;237:108168. doi: 10.1016/j.pharmthera.2022.108168. Epub 2022 Mar 10.


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.

Keywords: Alpha-ketoglutarate; Autophagy; Cellular senescence; Gut microbiome; Hydrogen sulfide; Iron balance; Osteoporosis; Probiotics; Senolytics.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Density Conservation Agents* / therapeutic use
  • Bone Resorption* / drug therapy
  • Diphosphonates / pharmacology
  • Diphosphonates / therapeutic use
  • Humans
  • Osteoclasts
  • Osteoporosis* / pathology


  • Bone Density Conservation Agents
  • Diphosphonates