CO2 Therapy: A Breakthrough in Bone Healing and Density
What if a simple gas could dramatically improve how fast your bones heal—and even help protect against bone destruction? Recent research suggests that carbon dioxide (CO₂), often seen only as a waste product of metabolism, plays a surprisingly important role in maintaining bone health and accelerating recovery from fractures. Welcome to the world of CO₂ Therapy.
The Secret Storehouse: Bone as a CO₂ Reservoir
Most people don’t realize that their bones store vast amounts of carbon dioxide—not in its gaseous form, but as bicarbonate and carbonate ions embedded within the bone’s crystalline matrix. In fact, an average adult male carries around 126 liters of “potential” CO₂, with the majority stored in bone tissue.
This reservoir plays a role in acid-base regulation, buffering the body during periods of metabolic stress. But beyond buffering, bone CO₂ stores are biologically active, participating in bone remodeling and possibly even influencing recovery after injury.
CO₂ Therapy Speeds Up Bone Fracture Healing
In a landmark animal study by Oda et al. [ref1], researchers investigated the effects of transcutaneous CO₂ application—a method of applying CO₂ gas to the skin using a hydrogel—on rats with femur fractures.
Key Findings:
- After three weeks, the fracture union was examined in all rats. The group with the highest exposure to CO2, 15 x 20 minutes in three weeks, had a significantly higher healing rate. 90% were healed, while in the control group, only 20% had healed:
- Control: No CO₂: 20% fracture union in 3 weeks
- 5 x 20 minutes of CO₂ exposure: 30% union
- 10 x 20 minutes of CO₂: 60% union
- 15 x 20 minutes of CO₂: 90% union
- Histological analysis showed faster endochondral ossification, a key stage in bone regeneration.
- Biomechanical strength (including ultimate stress and stiffness) was significantly higher in the 15 x 20 minutes CO₂ group.
- Angiogenesis, or the growth of new blood vessels, was visibly increased near fracture sites in CO₂-treated groups.
These results suggest that CO₂ exposure supports bone regeneration by improving blood flow, oxygen delivery, and cellular signaling involved in bone formation.
CO₂ Therapy Suppresses Bone Destruction in Cancer
A second study, published in Oncology Reports [ref2], explored how CO₂ affects bone degradation in cases of breast cancer bone metastases. When tumors spread to bone, they often stimulate osteoclasts, the cells responsible for bone resorption.
What CO₂ Therapy Did:
- Suppressed expression of key osteolytic and osteoclast-promoting factors (like RANKL, IL-6, and PTHrP)
- Reduced tumor-induced bone loss by preserving bone volume in affected areas
- Lowered hypoxia in tumor tissues by triggering the Bohr effect, improving oxygen delivery through red blood cells
- Diminished osteoclast activity, evidenced by a decrease in TRAP-positive cells
These findings indicate that CO₂ Therapy may help prevent or slow down bone degradation in patients with metastatic cancer, potentially offering an adjunct to current osteoclast-inhibitor treatments like bisphosphonates and denosumab.
How Does CO₂ Therapy Work?
The mechanisms include:
- Enhanced microcirculation: CO₂ promotes blood flow, which is crucial for healing.
- Artificial Bohr effect: CO₂ causes hemoglobin to release more oxygen into tissues.
- Increased angiogenesis: Better blood vessel formation supports nutrient and oxygen delivery.
- Modulation of cellular signaling: CO₂ impacts the expression of growth factors and cytokines involved in bone remodeling.
A Non-Invasive, Accessible Tool
What makes CO₂ Therapy especially promising is its simplicity and non-invasiveness. Whether achieved through slow breathing, CO2 baths, inhalations, injections, or hydrogel-based skin applications, CO₂ Therapy offers a low-cost, low-risk method to support bone health.
While current studies are mostly preclinical, they lay the groundwork for new approaches to:
- Accelerate fracture healing
- Support osteoporosis management
- Mitigate bone loss in metastatic cancers
- Possibly enhance rehabilitation outcomes
As the evidence mounts, CO₂ is no longer just a metabolic byproduct. It’s a therapeutic ally for skeletal health.
CO₂ Therapy represents a paradigm shift in how we view and treat the skeletal system—bridging respiratory physiology, vascular biology, and orthopedics into one integrative approach.
Scientific References
Title: Effects of the duration of transcutaneous CO2 application on the facilitatory effect in rat fracture repair
Authors: Oda T, Iwakura T, Fukui T, Oe K, Mifune Y, Hayashi S, Matsumoto T, Matsushita T, Kawamoto T, Sakai Y, Akisue T, Kuroda R, Niikura T.
Journal: J Orthop Sci. 2020 Sep;25(5):886-891. doi: 10.1016/j.jos.2019.09.017. Epub 2019 Oct 18. PMID: 31635930.
Link to full text: Effects of the duration of transcutaneous CO2 application on the facilitatory effect in rat fracture repair 
Abstract: Background: Carbon dioxide therapy has been reported to be effective in treating certain cardiac diseases and skin problems. Although a previous study suggested that transcutaneous carbon dioxide application accelerated fracture repair in association with promotion of angiogenesis, blood flow, and endochondral ossification, the influence of the duration of carbon dioxide application on fracture repair is unknown. The aim of this study was to investigate the effect of the duration of transcutaneous carbon dioxide application on rat fracture repair.
Methods: A closed femoral shaft fracture was created in each rat. Animals were randomly divided into four groups: the control group; 1w-CO2 group, postoperative carbon dioxide treatment for 1 week; 2w-CO2 group, postoperative carbon dioxide treatment for 2 weeks; 3w-CO2 group, postoperative carbon dioxide treatment for 3 weeks. Transcutaneous carbon dioxide application was performed five times a week in the carbon dioxide groups. Sham treatment, where the carbon dioxide was replaced with air, was performed for the control group. Radiographic, histological, and biomechanical assessments were performed at 3 weeks after fracture.
Results: The fracture union rate was significantly higher in the 3w-CO2 group than in the control group (p < 0.05). Histological assessment revealed promotion of endochondral ossification in the 3w-CO2 group than in the control group. In the biomechanical assessment, all evaluation items related to bone strength were significantly higher in the 3w-CO2 group than in the control group (p < 0.05).
Conclusions: The present study, conducted using an animal model, demonstrated that continuous carbon dioxide application throughout the process of fracture repair was effective in enhancing fracture healing.
Title: Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis
Authors: Takemori T, Kawamoto T, Ueha T, Toda M, Morishita M, Kamata E, Fukase N, Hara H, Fujiwara S, Niikura T, Kuroda R, Akisue T.
Journal: Oncology Reports, 40, 2079-2087. https://doi.org/10.3892/or.2018.6608
Link to full text: Transcutaneous carbon dioxide application suppresses bone destruction caused by breast cancer metastasis
Abstract: Hypoxia plays a significant role in cancer progression, including metastatic bone tumors. We previously reported that transcutaneous carbon dioxide (CO2) application could decrease tumor progression through the improvement of intratumor hypoxia. Therefore, we hypothesized that decreased hypoxia using transcutaneous CO2 could suppress progressive bone destruction in cancer metastasis. In the present study, we examined the effects of transcutaneous CO2 application on metastatic bone destruction using an animal model. The human breast cancer cell line MDA-MB-231 was cultured in vitro under three different oxygen conditions, and the effect of altered oxygen conditions on the expression of osteoclast-differentiation and osteolytic factors was assessed. An in vivo bone metastatic model of human breast cancer was created by intramedullary implantation of MDA-MB-231 cells into the tibia of nude mice, and treatment with 100% CO2 or a control was performed twice weekly for two weeks. Bone volume of the treated tibia was evaluated by micro-computed tomography (µCT), and following treatment, histological evaluation was performed by hematoxylin and eosin staining and immunohistochemical staining for hypoxia-inducible factor (HIF)-1α, osteoclast-differentiation and osteolytic factors, and tartrate-resistant acid phosphatase (TRAP) staining for osteoclast activity. In vitro experiments revealed that the mRNA expression of RANKL, PTHrP and IL-8 was significantly increased under hypoxic conditions and was subsequently reduced by reoxygenation. In vivo results by µCT revealed that bone destruction was suppressed by transcutaneous CO2, and that the expression of osteoclast-differentiation and osteolytic factors, as well as HIF-1α, was decreased in CO2-treated tumor tissues. In addition, multinucleated TRAP-positive osteoclasts were significantly decreased in CO2-treated tumor tissues. Hypoxic conditions promoted bone destruction in breast cancer metastasis, and reversal of hypoxia by transcutaneous CO2 application significantly inhibited metastatic bone destruction along with decreased osteoclast activity. The findings in this study strongly indicated that transcutaneous CO2 application could be a novel therapeutic strategy for treating metastatic bone destruction.
