Hydrogen Water Speeds Bone Fracture Healing in Osteoporosis Drug Users
- Authors
- Yuanming An, Haozhi Zhang, Yuantao Zhang, Shi'an Zhang, Lizhen Zheng, Hongwei Shao, Wanting Du, Liming Cheng, Wei Sun, Jinhui Ma, Yechun Ruan, Jiankun Xu, Ling Qin
- Journal
- Biomaterials
- Year
- 2026
- DOI
- 10.1016/j.biomaterials.2026.124287
- Study Type
- Rat
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Germany
- Health Condition
- Atypical Femoral Fractures
- Body System
- Musculoskeletal
TL;DR
Hydrogen-rich water improved healing in a rat model of bisphosphonate-associated atypical femoral fracture by reducing local senescence, inflammation, fibrosis, and impaired blood vessel formation without weakening bisphosphonate-supported bone mass.
Key Finding
Hydrogen-rich water significantly promoted healing of bisphosphonate-induced atypical femoral fractures in rats by reversing cellular aging and shifting immune responses toward anti-inflammatory patterns at the fracture site.
Summary
This study used rats to investigate whether hydrogen-rich water could help heal a specific type of bone fracture that occurs as a side effect of long-term bisphosphonate drugs (medications used to treat osteoporosis). The researchers found that hydrogen-rich water promoted healing of these difficult-to-heal fractures by reducing cellular aging and inflammation at the fracture site, while maintaining the bone-strengthening benefits of the bisphosphonate medication.
Practical Takeaway
This rat study suggests hydrogen-rich water may have potential as a treatment for a specific fracture complication caused by osteoporosis medications, but human studies would be needed to determine if these results apply to people. The findings are preliminary and limited to animal research.
Abstract
Long-term bisphosphonates (BPs) are widely used to treat osteoporosis, however, they are paradoxically associated with the development of atypical femoral fractures (AFFs), which often characterized by impaired healing. In this study, we induced an AFF model using zoledronate (ZOL) administration in ovariectomized (OVX) osteoporotic rats, following a unilateral femoral fracture. Here we identified that a local pro-senescent microenvironment causes persistent inflammation and impairs effective regeneration in rat AFFs. Molecular hydrogen has demonstrated anti-senescence and anti-inflammatory properties, yet its effects on AFF healing remain unexplored. Therefore, we treated the AFF rats with hydrogen rich water (HRW). The outcomes were assessed by radiographs, histology, micro-CT, and biomechanical tests. The fracture microenvironment was analyzed based on the indicators of senescence, fibrosis, macrophage polarization, cytokine expression, and angiogenesis. We found that HRW significantly promoted callus bridging and resolved the non-union gap in ZOL-induced AFFs, whereas the ZOL group exhibited persistent fibrous tissue. Micro-CT and biomechanical tests confirmed that HRW did not compromise the mechanical strength of the bone mass elevated by BPs. Instead, HRW specifically attenuated the local senescent microenvironment, with a reduction in both SA-β-gal activity and the expression of p16, p21 within the fracture gap. This was accompanied by clearance of pathological fibroblasts, a shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages, a rebalanced cytokine profile, and restored formation of osteogenesis-coupled type-H vessels. Our findings confirm that molecular hydrogen facilitates AFFs healing by locally reversing the senescent microenvironment, rather than boosting systemic bone formation. This creates a favorable niche for callus bridging, representing a novel therapeutic strategy for fracture delayed union or non-union.