Sukul Pritam, Fischer Dagmar-Christiane, Broderius Celine, Grzegorzewski Simon, Rahn Anja, Mittlmeier Thomas, Kreikemeyer Bernd, Reuter Daniel A, Schubert Jochen K, Miekisch Wolfram
Rostock Medical Breath Research Analytics and Technologies (ROMBAT), Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, Rostock, Germany.
Department of Pediatrics, Rostock University Medical Center, Rostock, Germany.
Commun Med (Lond). 2024 Dec 28;4(1):279. doi: 10.1038/s43856-024-00723-4.
Menopause driven decline in estrogen exposes women to risk of osteoporosis. Detection of early onset and silent progression are keys to prevent fractures and associated burdens.
In a discovery cohort of 120 postmenopausal women, we combined repeated quantitative pulse-echo ultrasonography of bone, assessment of grip strength and serum bone markers with mass-spectrometric analysis of exhaled metabolites to find breath volatile markers and quantitative cutoff levels for osteoporosis. Obtained markers and cutoffs were validated in an independent cohort of 49 age-matched women with six months apart seasonal follow-ups.
Here, within the discovery cohort, concentrations of exhaled end-tidal dimethyl sulfide (DMS), allyl-methyl sulfide, butanethiol and butyric acid are increased (p ≤ 0.005) pronouncedly in subjects with bone mineral density (BMD) at high-risk of osteoporosis and fracture, when compared to subjects with normal BMD. Increased age and decreased grip strength are concomitant. All changes are reproduced during independent validation and seasonal follow-ups. Exhaled metabolite expressions remain age independent. Serum markers show random expressions without reproducibility. DMS exhalations differs between patients with recent, old and without fractures. Metabolite exhalations and BMDs are down-regulated during winter. ROC analysis in discovery cohort yields high classification accuracy of DMS with a cutoff for osteoporosis, which predicts subjects at high-risk within the independent validation cohort with >91% sensitivity and specificity.
Non-invasive analysis of exhaled DMS allowed more reliable classification of osteoporosis risk than conventional serum markers. We identified associations of exhaled organosulfur and short-chain fatty acids to bone metabolism in postmenopausal osteoporosis via a gut-bone axis.
绝经导致雌激素水平下降，使女性面临骨质疏松风险。早期发病和隐匿进展的检测是预防骨折及相关负担的关键。
在一个由120名绝经后女性组成的发现队列中，我们将重复的骨定量脉冲回波超声检查、握力评估、血清骨标志物检测与呼出代谢物的质谱分析相结合，以寻找骨质疏松的呼出挥发性标志物和定量临界值。在一个由49名年龄匹配的女性组成的独立队列中对获得的标志物和临界值进行验证，该队列进行了为期六个月的季节性随访。
在此，在发现队列中，与骨密度正常的受试者相比，骨质疏松和骨折高风险受试者呼出的潮气末二甲基硫醚（DMS）、烯丙基甲基硫醚、丁硫醇和丁酸浓度显著升高（p≤0.005）。年龄增长和握力下降同时出现。所有变化在独立验证和季节性随访中均得到重现。呼出代谢物表达与年龄无关。血清标志物显示随机表达，无重现性。近期骨折、陈旧性骨折和无骨折患者的DMS呼出情况不同。冬季代谢物呼出量和骨密度下调。发现队列中的ROC分析得出DMS对骨质疏松的分类准确率较高，其临界值在独立验证队列中预测高风险受试者的敏感性和特异性均>91%。
与传统血清标志物相比，呼出DMS的非侵入性分析能够更可靠地对骨质疏松风险进行分类。我们通过肠-骨轴确定了绝经后骨质疏松症中呼出的有机硫和短链脂肪酸与骨代谢的关联。
