{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:42:34Z","timestamp":1775108554724,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Postmenopausal osteoporosis is an age-related condition in which estrogen deficiency drives low-grade inflammation and oxidative stress, disrupting the homeostatic balance between bone formation and resorption. Since osteopenia represents a critical intermediate stage, preventive strategies are essential to mitigate its progression. Preclinical studies suggest that hydrogen sulfide (H2S), a gaseous mediator with antioxidant properties, protects bone metabolism by supporting osteoblast function and suppressing osteoclast activity. Building on this evidence, we conducted the first exploratory clinical trial assessing the effects of inhalation therapy with sulfurous mineral waters on systemic biomarkers in postmenopausal women with osteopenia. Thirty-eight eligible participants underwent a daily inhalation of sulfurous waters (14.6 mg\/L sulfide) for 12 consecutive days. Biomarkers of oxidative stress, inflammation, and bone turnover were assessed at baseline, immediately post-treatment, and five days after cessation in the serum of patients. The treatment was well tolerated and did not cause any early adverse effect. Serum H2S levels, measured in a subset of participants, significantly increased, confirming systemic bioavailability. Sulfurous water inhalation induced a marked change in oxidative stress, with malondialdehyde levels declining by up to 37% from baseline. Pro-inflammatory cytokines, particularly IL-8 and MIP-1\u03b1, were significantly decreased (up to 50\u201370%) at the end of the treatment. Reference bone turnover markers P1NP and CTX-1 did not show significant changes; however, BALP exhibited a significant increase, suggesting the activation of pathways linked to biomineralization. These findings provide preliminary human evidence that inhaled sulfurous waters enhance systemic H2S bioavailability and modulate redox and inflammatory pathways associated with bone remodeling in osteopenic women, supporting the rationale for further controlled pharmacodynamic investigations evaluating the potential of H2S in bone health.<\/jats:p>","DOI":"10.3390\/ijms27073163","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T13:23:17Z","timestamp":1774963397000},"page":"3163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Changes in Oxidative Stress, Inflammatory and Bone Metabolism Biomarkers Following Sulfurous Water Inhalation in Osteopenic Women"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8126-5040","authenticated-orcid":false,"given":"Laura","family":"Gambari","sequence":"first","affiliation":[{"name":"SSD Lab RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6348-4960","authenticated-orcid":false,"given":"Emanuela","family":"Amore","sequence":"additional","affiliation":[{"name":"SSD Lab RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5760-3791","authenticated-orcid":false,"given":"Livia","family":"Roseti","sequence":"additional","affiliation":[{"name":"SSD Lab RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Carpentieri","sequence":"additional","affiliation":[{"name":"SSD Lab RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Ripamonti","sequence":"additional","affiliation":[{"name":"SSD Medicina e Reumatologia, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Lisi","sequence":"additional","affiliation":[{"name":"SSD Medicina e Reumatologia, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-3215","authenticated-orcid":false,"given":"Paolo","family":"Spinnato","sequence":"additional","affiliation":[{"name":"SC Radiologia Diagnostica e Interventistica, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliana","family":"Nervuti","sequence":"additional","affiliation":[{"name":"SC Chirurgia Vertebrale, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonietta","family":"Gesuele","sequence":"additional","affiliation":[{"name":"SC SAIteR, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Naldi","sequence":"additional","affiliation":[{"name":"SSD Medicina e Reumatologia, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-6745","authenticated-orcid":false,"given":"Brunella","family":"Grigolo","sequence":"additional","affiliation":[{"name":"SSD Lab RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5127-9561","authenticated-orcid":false,"given":"Francesco","family":"Grassi","sequence":"additional","affiliation":[{"name":"SSD Lab RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano 1\/10, 40136 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aibar-Almazan, A., Voltes-Martinez, A., Castellote-Caballero, Y., Afanador-Restrepo, D.F., Carcelen-Fraile, M.D.C., and Lopez-Ruiz, E. 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