Studies Referencing Hydrogen and Bone/Musculoskeletal

Database:

Primary Topic: Bone/Muscle/Tendon

Secondary Topic: Muscular Dystrophy/Osteoarthritis (OA)/Osteogenesis/Osteonecrosis/Osteoporosis/Rheumatoid Arthritis (RA) (or Any)

Tertiary Topic: Bone Loss/Fracture/Mineralization Rate/Psoriasis-Associated Arthritis/Sprain/Tendon Adhesion/Rhabdomyolysis (or Any)

Osteoporosis and Bone Loss

● Hydrogen can help protect bones from bone loss (691: Cai et al 2013) due to

• Diabetes (387: Guo et al 2017),
• ovariectomy (243: Wu et al 2019; 698: Guo et al 2013),
• microgravity (732: Sun et al 2013), .

Arthritis

● Hydrogen helps to alleviate both

• Osteoarthritis (OA) (20: Lu et al 2021; 55: Cheng et al 2020; 342: Wan et al 2018; 499: Lin et al 2016),
• Rheumatoid Arthritis (RA) (35: Xu et al 2021; 505: Meng et al 2016; 636: Ishibashi et al 2014; 770: Ishibashi et al 2012; 840: Itoh et al 2011; 238: Terasaki et al 2019; 1179: Tian et al 2022),
• and Psoriasis-Associated Arthritis (554: Ishibashi et al 2015).

Bone and Joint Injury and Repair

● Hydrogen has been shown to

• enhance bone regeneration after fracture (225: Ozawa et al 2019; 44: Antoniac et al 2020; 1072: Zhao et al 2018),
• inhibit osteoclastogenesis (101: Liu et al 2020; 711: Li et al 2013; 243: Wu et al 2019; 732: Sun et al 2013),
• protect chrondrocytes from oxidative stress (832: Hanaoka et al 2011),
• and enhance mineralization rate and osteogenesis (3: Carnovali, Mariotti, and Banfi 2021).

● Hydrogen has been shown to

• reduce pain and swelling,
• improve range of motion, and aid in healing of ankle (72: Javorac et al 2020; 73: Javorac, Stajer, and Ostojic 2020) and toe (1081: Tarnava 2021) sprain.

● Hydrogen has been shown to

• reduce swelling and improve range of motion after soft tissue injury (659: Ostojic, Stojanovic, and Hoffman 2014; 660: Ostojic et al 2014).
• Additionally, hydrogen has shown promise in tendon repair, as it can reduce tendon adhesion and inflammation (317: Meng et al 2018).

● Hydrogen can protect bones from osteonecoris due to corticosteroid toxicity (i.e. Prednisone (402: Li et al 2017; 552: Huang, Jiao, and Yan 2015)) and radiotherapy (53: Chen et al 2020).

● Hydrogen has been shown to effectively prevent graft injury in osteochondral graft tissue (186: Han et al 2019; 676: Yamada et al 2014).

Muscular Dystrophy

● Hydrogen can alleviate motor deficit and muscle degeneration caused by Muscular Dystrophy (390: Hasegawa et al 2017; 839: Ito et al 2011).

Rhabdomyolysis

● Hydrogen can help protect against kidney injury resulting from the rapid breakdown of damage muscle tissue in rhabdomyolysis (630: Gu et al 2014).

Mode of Action

Hydrogen shows multiple modes of action, including quenching cellular ROS (55: Cheng et al 2020; 402: Li et al 2017; 552: Huang, Jiao, and Yan 2015; 698: Guo et al 2013; 691: Cai et al 2013; 35: Xu et al 2021; 505: Meng et al 2016; 636: Ishibashi et al 2014; 770: Ishibashi et al 2012; 832: Hanaoka et al 2011; 732: Sun et al 2013; 711: Li et al 2013; 317: Meng et al 2018; 238: Terasaki et al 2019),

increasing the activity of endogenous antioxidant enzymes (691: Cai et al 2013; 505: Meng et al 2016; 390: Hasegawa et al 2017; 317: Meng et al 2018),

upregulating cellular protection mechanisms (832: Hanaoka et al 2011),

counteracting inflammation and apoptosis (20: Lu et al 2021; 55: Cheng et al 2020; 342: Wan et al 2018; 499: Lin et al 2016; 402: Li et al 2017; 243: Wu et al 2019; 698: Guo et al 2013; 691: Cai et al 2013; 505: Meng et al 2016; 636: Ishibashi et al 2014; 840: Itoh et al 2011; 711: Li et al 2013; 390: Hasegawa et al 2017; 317: Meng et al 2018; 238: Terasaki et al 2019; 554: Ishibashi et al 2015; 1179: Tian et al 2022),

and restoring mitochondrial function (691: Cai et al 2013; 711: Li et al 2013; 839: Ito et al 2011).

Literature Cited (numbered as per database):

● (3) Carnovali, Marta; Mariotti, Massimo; Banfi, Giuseppe. Molecular hydrogen enhances osteogenesis in Danio rerio embryos. 2021. Journal of Fish Biology. 10.1111/jfb.14670

● (20) Lu, Hongwei; Wang, Wei; Kang, Xiaodiao; Lin, Zeng; Pan, Jun; Cheng, Shaowen; Zhang, Jingdong. Hydrogen (H 2) Alleviates Osteoarthritis by Inhibiting Apoptosis and Inflammation via the JNK Signaling Pathway. 2021. Journal of Inflammation Research. 10.2147/JIR.S297622

● (35) Xu, Cong; Wang, Shuanghu; Wang, Hong; Liu, Kun; Zhang, Shiyu; Chen, Bin; Liu, Hao; Tong, Fei; Peng, Fei; Tu, Yingfeng; Li, Yingjia. Magnesium-Based Micromotors as Hydrogen Generators for Precise Rheumatoid Arthritis Therapy. 2021. Nano Letters. 10.1021/acs.nanolett.0c04438

● (44) Antoniac, Iulian; Adam, Razvan; Bita, Ana; Miculescu, Marian; Trante, Octavian; Petrescu, Ionut Mircea; Pogarasteanu, Mark. Comparative Assessment of In Vitro and In Vivo Biodegradation of Mg-1Ca Magnesium Alloys for Orthopedic Applications. 2020. Materials. 10.3390/ma14010084

● (53) Chen, Y.; Zong, C.; Jia, J.; Liu, Y.; Zhang, Z,; Cai, B.; Tian, L. A study on the protective effect of molecular hydrogen on osteoradionecrosis of the jaw in rats. 2020. International Journal of Oral and Maxillofacial Surgery. 10.1016/j.ijom.2020.04.011

● (55) Cheng, ShaoWen; Peng, Lui; Xu, BaiChao; Chen, WenSheng; Chen, YangPing; Gu, YunTao. Protective Effects of Hydrogen-Rich Water Against Cartilage Damage in a Rat Model of Osteoarthritis by Inhibiting Oxidative Stress, Matrix Catabolism, and Apoptosis. 2020. Medical Science Monitor. 10.12659/MSM.920211

● (72) Javorac, Dejan; Stajer, Valdemar; Ratgeber, Laszlo; Olah, Andras; Betlehem, Jozsef; Acs, Pongras; Vukomanovic, Boris; Ostojic, Sergej M. Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial. 2020. Research in Sports Medicine. 10.1080/15438627.2020.1868468

● (73) Javorac, Dejan; Stajer, Valdemar; Ostojic, Sergej M. Case Report: Acute hydrotherapy with super-saturated hydrogen-rich water for ankle sprain in a professional athlete. 2020. F1000 Research. 10.12688/f1000research.22850.1

● (101) Liu, Yong; Wang, De-Li; Huang, Yong-Can; Wang, Tian-Bing; Zeng, Hui. Hydrogen inhibits the osteoclastogenesis of mouse bone marrow mononuclear cells. 2020. Materials Science and Engineering C. 10.1016/j.msec.2020.110640

● (186) Han, Yunning; Qu, Pengwei; Zhang, Kaihong; Bi, Yikang; Zhou, Lu; Xie, Di; Song, Hongqiang; Dong, Jun; Qi, Jianhong. Storage solution containing hydrogen improves the preservation effect of osteochondral allograft. 2019. Cell and Tissue Banking. 10.1007/s10561-019-09758-7

● (225) Ozawa, Yasumasa; Gojoubori, Takahiro; Ota, Hirotaka; Takemoto, Tomoko; Suguro, Hisashi; Nishida, Tetsuya; Satou, Shuuichi; Asano, Masatake. Bone regeneration is enhanced by the combined use of acid‐electrolyzed functional water with hydroxyapatite/collagen composite. 2019. Journal of Biomedical Materials Research Part B Applied Biomaterials. 10.1002/jbm.b.34513

● (238) Terasaki, Yasuhiro; Terasaki, Mika; Kanazawa, Satoshi; Kokuho, Nariaki; Urushiyama, Hirokazu; Kajimoto, Yusuke; Kunugi, Shinobu; Maruyama, Motoyo; Akimoto, Toshio; Miura, Yoko; Igarashi, Tsutomu; Ohsawa, Ikuroh; Shimizu, Akira. Effect of H 2 treatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease. 2019. Journal of Cellular and Molecular Medicine. 10.1111/jcmm.14603

● (243) Wu, Gang; Pan, Lei; Sun, Jing; Chen, Guimin; Wang, Shaohai. Hydrogen gas protects against ovariectomy-induced osteoporosis by inhibiting NF-κB activation. 2019. Menopause. 10.1097/GME.0000000000001310

● (317) Meng, Jia; Yu, Pan; Tong, Jian; Sun, Wenshuang; Jiang, Hui; Wang, Yicun; Xue, Kaiwen; Xie, Farong; Qian, Hong; Liu, Naicheng; Zhao, Jianning; Bao, Nirong. Hydrogen treatment reduces tendon adhesion and inflammatory response. 2018. Journal of Cellular Biochemistry. 10.1002/jcb.27441

● (342) Wan, Wei-Lin; Lin, Yu-Jung; Shih, Po-Chien; Bow, Yu-Ru; Cui, Qinghua; Chang, Yen; Chia, Wei-Tso; Sung, Hsing-Wen. In Situ Depot for Continuous Evolution of Gaseous H2 Mediated by Magnesium Passivation/Activation Cycle for Treating Osteoarthritis. 2018. Angewandte Chemie International Edition. 10.1002/anie.201806159

● (387) Guo, Jialiang; Dong, Weichong; Jin, Lin; Wang, Pengcheng; Hou, Zhiyong; Zhang, Yingze. Hydrogen-rich saline prevents bone loss in diabetic rats induced by streptozotocin. 2017. International Orthopaedics. 10.1007/s00264-017-3581-4

● (390) Hasegawa, Satoru; Ito, Mikako; Fukami, Mayu; Hashimoto, Miki; Hirayama, Masaaki; Ohno, Kinji. Molecular hydrogen alleviates motor deficits and muscle degeneration in mdx mice. 2017. Redox Report. 10.1080/13510002.2015.1135580

● (402) Li, Jia; Ge, Zhaogang; Fan, Lihong; Wang, Kunzheng. Protective effects of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and apoptosis. 2017. BMC Musculoskeletal Disorders. 10.1186/s12891-017-1431-6

● (499) Lin, Yingni; Ohkawara, Bisei; Ito, Mikako; Misawa, Nobuaki; Miyamoto, Kentaro; Takegami, Yasuhiko; Masuda, Akio; Toyokuni, Shinya; Ohno, Kinji. Molecular hydrogen suppresses activated Wnt/β-catenin signaling. 2016. Nature Scientific Reports. 10.1038/srep31986

● (505) Meng, Jia; Yu, Pan; Jiang, Hui; Yuan, Tao; Liu, Naicheng; Tong, Jian; Chen, Haiyan; Bao, Nirong; Zhao, Jianning. Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress. 2016. American Journal of Translational Research. 27830032

● (552) Huang, Sheng-Li; Jiao, Jian; Yan, Hong-Wei. Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model. 2015. Experimental and Therapeutic Medicine. 10.3892/etm.2015.2883

● (554) Ishibashi, Toru; Ichikawa, Miki; Sato, Bunpei; Shibata, Shinji; Hara, Yuichi; Naritomi, Yuji; Okazaki, Ken; Nakashima, Yashuaru; Iwamoto, Yukihide; Koyanagi, Samon; Hara, Hiroshi; Nagao, Tetsuhiko. Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. 2015. Molecular Medicine Reports. 10.3892/mmr.2015.3707

● (630) Gu, Hongxia; Yang, Min; Zhao, Xiaomin; Zhao, Bing, Sun, Xuejun; Gao, Xin. Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-induced rhabdomyolysis and acute kidney injury in rats. 2014. Journal of Surgical Research. 10.1016/j.jss.2013.12.007

● (636) Ishibashi, Toru; Sato, Bunpei; Shibata, Shinji; Sakai, Takaaki; Hara, Yuichi; Naritomi, Yuji; Koyanagi, Samon; Hara, Hiroshi; Nagao, Tetsuhiko. Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study. 2014. International Immunopharmacology. 10.1016/j.intimp.2014.06.001

● (659) Ostojic, Sergej M.; Stojanovic, Marko D.; Hoffman, Jay R. Effectiveness Of Molecular Hydrogen In The Management Of Musculotendinous Injuries. 2014. Medicine and Science in Sports and Exercise. 10.1249/01.mss.0000493783.80014.95

● (660) Ostojic, Sergej M.; Vukomanovix, Boris; Calleja-Gonzalez, Julio; Hoffman, Jay R. Effectiveness of Oral and Topical Hydrogen for Sports-Related Soft Tissue Injuries. 2014. Postgraduate Medicine. 10.3810/pgm.2014.09.2813

● (676) Yamada, Takuya; Uchida, Kentaro; Onuma, Kenji; Kuzuno, Jun; Ujihira, Masanobu; Inoue, Gen; Sato, Bunpei; Kurokawa, Ryosuke; Sakai, Rina; Takaso, Masashi. Hydrogen supplementation of preservation solution improves viability of osteochondral grafts. 2014. Scientific World Journal. 10.1155/2014/109876

● (691) Cai, Wen-Wen; Zhang, Ming-Hua; Yu, Yong-Sheng; Cai, Jin-Hua. Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast. 2013. Molecular and Cellular Biochemistry. 10.1007/s11010-012-1450-4

● (698) Guo, Ji-Dong; Li, Li; Shi, Ya-Min; Wang, Hua-Dong; Hou, Shu-Xun. Hydrogen water consumption prevents osteopenia in ovariectomized rats. 2013. British Journal of Pharmacology. 10.1111/bph.12036

● (711) Li, Dong-Zhu; Zhang, Qin-Xiang; Dong, Xiao-Xian; Li, Huai-Dong; Ma, Xin. Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells. 2013. Journal of Bone and Mineral Metabolism. 10.1007/s00774-013-0530-1

● (732) Sun, Y.; Shuang, F.; Chen, D.M.; Zhou, R.B. Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. 2013. Osteoporosis International. 10.1007/s00198-012-2028-4

● (770) Ishibashi, Toru; Sato, Bunpei; Rikitake, Mariko; Seo, Tomoki; Kurokawa, Ryosuke; Hara, Yuichi; Naritomi, Yuji; Hara, Hiroshi; Nagao, Tetsuhiko. Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: an open-label pilot study. 2012. Medical Gas Research. 10.1186/2045-9912-2-27

● (832) Hanaoka, Teruyasu; Kamimura, Naomi; Yokota, Takashi; Takai, Shinro; Ohta, Shigeo. Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide. 2011. Medical Gas Research. 10.1186/2045-9912-1-18

● (839) Ito, Mikako; Ibi, Tohru; Sahashi, Ko; Ichihara, Masashi; Ito, Masafumi; Ohno, Kinji. Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. 2011. Medical Gas Research. 10.1186/2045-9912-1-24

● (840) Itoh, Tomohiro; Hamada, Nanako; Terazawa, Riyako; Ito, Mikako; Ohno, Kinji; Ichihara, Masatoshi; Nozawa, Yoshinori; Ito, Masafumi. Molecular hydrogen inhibits lipopolysaccharide/interferon γ-induced nitric oxide production through modulation of signal transduction in macrophages. 2011. Biochemical and Biophysical Research Communications. 10.1016/j.bbrc.2011.06.116

● (1072) Zhao, Daoli; Brown, Andrew; Wang, Tingting; Yoshizawa, Sayuri; Sfeir, Charles; Heineman, William R. In vivo quantification of hydrogen gas concentration in bone marrow surrounding magnesium fracture fixation hardware using an electrochemical hydrogen gas sensor. 2018. Acta Biomaterialia. 10.1016/j.actbio.2018.04.032

● (1081) Tarnava, Alex. Supersaturated Hydrogen-Rich Water Hydrotherapy for Recovery of Acute Injury to the Proximal Phalanges on the 5th Toe: A Case Report. 2021. Journal of Science and Medicine. 10.37714/josam.v2i4.57

● (1179) Tian, Yan; Kang, Xing; Yang, Hao; Zhang, Shuting; Wang, Yu; Fan, Weiping. Hydrogen alleviates collagen-induced arthritis (CIA) in mice by inhibiting IL-22 levels. 2022. Chinese Journal of Cellular and Molecular Immunology. 35603647