{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:40:07Z","timestamp":1760031607704,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["No. 20K20660"],"award-info":[{"award-number":["No. 20K20660"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Osteoporosis can increase the risk of fracture in elderly patients, and insufficient control affects quality of life. Rikkunshi-To (RKT) has been prescribed for elderly patients to improve gastrointestinal function. We postulated that RKT has preventive potential for the development of osteoporosis. Thus, we developed a simple method to evaluate osteoporosis using a continuous series of X-ray images of femurs in mice, and investigated the effects of RKT on the development of osteoporosis in these mice. Male senescence-accelerated mouse strain P6 (SAMP6) mice, a model of senile osteoporosis in humans, were fed diets with or without RKT (1%). We collected X-ray images of the whole body of each mouse weekly and measured the ratio of cortical thickness of the femur (C\/F index). The C\/F index in SAMP6 mice fed the normal diet was increased between 50 and 80 days old, but it was significantly decreased after 120 days old. On the other hand, the C\/F index in SAMP6 mice fed the RKT diet was increased between 50 and 80 days old; however, it remained unchanged throughout the experimental period. We also confirmed that the C\/F index in SAMP6 mice fed the RKT diet suddenly decreased on the replacement of the RKT diet with a normal diet, suggesting that we can collect data related to a series of continuous changes in bone mass, and that RKT is useful for the prevention of osteoporosis.<\/jats:p>","DOI":"10.3390\/life15040557","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:21:04Z","timestamp":1743398464000},"page":"557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prevention of Osteoporosis in SAMP6 Mice by Rikkunshi-To: Japanese Kampo Medicine"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8073-2871","authenticated-orcid":false,"given":"Kouichi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Department of Radiological Sciences, Faculty of Health Sciences, Morinomiya University of Medical Sciences, 1-26-16 Nanko-Kita, Suminoe-Ku, Osaka 559-8611, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiko","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Radiological Sciences, Faculty of Health Sciences, Morinomiya University of Medical Sciences, 1-26-16 Nanko-Kita, Suminoe-Ku, Osaka 559-8611, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41413-022-00219-8","article-title":"Bone remodeling: An operational process ensuring survival and bone mechanical competence","volume":"10","author":"Bolamperti","year":"2022","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1007\/s00198-022-06454-3","article-title":"Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: A systematic review and meta-analysis","volume":"33","author":"Xiao","year":"2022","journal-title":"Osteoporos Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.jsbmb.2013.09.008","article-title":"Prevention and treatment of postmenopausal osteoporosis","volume":"142","author":"Tella","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1097\/01.NPR.0000000000000090","article-title":"Osteoporosis management in primary care","volume":"48","author":"Jarrell","year":"2023","journal-title":"Nurse Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/14656566.2018.1428559","article-title":"New and developing pharmacotherapy for osteoporosis in men","volume":"19","author":"Gennari","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1007\/s00535-013-0896-9","article-title":"A randomized, placebo-controlled, double-blind clinical trial of rikkunshito for patients with non-erosive reflux disease refractory to proton-pump inhibitor: The G-PRIDE study","volume":"49","author":"Tominaga","year":"2014","journal-title":"J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1089\/acm.2016.0233","article-title":"Medicinal Plants for Management of Gastroesophageal Reflux Disease: A Review of Animal and Human Studies","volume":"23","author":"Salehi","year":"2017","journal-title":"J. Altern. Complement. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1002\/ptr.5001","article-title":"Hesperidin prevents androgen deficiency-induced bone loss in male mice","volume":"28","author":"Chiba","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1377\/hlthaff.2011.0233","article-title":"Medicare payment cuts for osteoporosis testing reduced use despite tests\u2019 benefit in reducing fractures","volume":"30","author":"King","year":"2011","journal-title":"Health Aff."},{"key":"ref_10","first-page":"30","article-title":"Osteoporosis Screening Using Chest Radiographs","volume":"35","author":"Ishikawa","year":"2018","journal-title":"Med. Imaging Inf. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Saeki, S., Yamamoto, K., Tomizawa, R., Meszaros, S., Horvath, C., Zoldi, L., Szabo, H., Tarnoki, A.D., Tarnoki, D.L., and Ishida, T. (2022). Utilizing Graphical Analysis of Chest Radiographs for Primary Screening of Osteoporosis. Medicina, 30.","DOI":"10.3390\/medicina58121765"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0047-6374(81)90084-1","article-title":"A new murine model of accelerated senescence","volume":"17","author":"Takeda","year":"1981","journal-title":"Mech. Ageing Dev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/j.exger.2009.09.009","article-title":"Site-specific bone loss in senescence-accelerated mouse (SAMP6): A murine model for senile osteoporosis","volume":"44","author":"Chen","year":"2009","journal-title":"Exp. Gerontol."},{"key":"ref_14","first-page":"677","article-title":"Ultrastructural changes in bones of the senescence-accelerated mouse (SAMP6): A murine model for senile osteoporosis","volume":"19","author":"Chen","year":"2004","journal-title":"Histol. Histopathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0197-4580(99)00008-1","article-title":"Senescence-accelerated mouse (SAM): A biogerontological resource in aging research","volume":"20","author":"Takeda","year":"1999","journal-title":"Neurobiol. Aging"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.jphs.2022.08.001","article-title":"Effects of Rikkunshi-To, a Japanese kampo medicine, on donepezil-induced gastrointestinal side effects in mice","volume":"150","author":"Yamamoto","year":"2022","journal-title":"J. Pharmacol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.jphs.2018.05.003","article-title":"Enhancement of ghrelin-signaling system by Rikkunshi-To attenuates teriparatide-induced pica in rats","volume":"137","author":"Yamamoto","year":"2018","journal-title":"J. Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.rcl.2022.02.003","article-title":"Osteoporosis Imaging","volume":"60","author":"Martel","year":"2022","journal-title":"Radiol. Clin. N. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3000605241274576","DOI":"10.1177\/03000605241274576","article-title":"A few-shot learning framework for the diagnosis of osteopenia and osteoporosis using knee X-ray images","volume":"52","author":"Xie","year":"2024","journal-title":"J. Int. Med. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s40618-014-0074-9","article-title":"The role of hip and chest radiographs in osteoporotic evaluation among south Indian women population: A comparative scenario with DXA","volume":"37","author":"Kumar","year":"2014","journal-title":"J. Endocrinol. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e241339","DOI":"10.1148\/radiol.241339","article-title":"AI and Chest Radiographs: A Dawning Era in Osteoporosis Screening","volume":"311","author":"Smith","year":"2024","journal-title":"Radiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s10916-023-02030-2","article-title":"Artificial Intelligence-enabled Chest X-ray Classifies Osteoporosis and Identifies Mortality Risk","volume":"48","author":"Tsai","year":"2024","journal-title":"J. Med. Syst."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1007\/s00223-017-0238-7","article-title":"Machine Learning Principles Can Improve Hip Fracture Prediction","volume":"100","author":"Kruse","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s00774-003-0471-1","article-title":"Consistency of low bone density across bone sites in SAMP6 laboratory mice","volume":"22","author":"Kasai","year":"2004","journal-title":"J. Bone Miner. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.bone.2004.03.027","article-title":"Morphological and mechanical properties of caudal vertebrae in the SAMP6 mouse model of senile osteoporosis","volume":"35","author":"Silva","year":"2004","journal-title":"Bone"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1359\/JBMR.050307","article-title":"Ovariectomy-induced bone loss varies among inbred strains of mice","volume":"20","author":"Bouxsein","year":"2005","journal-title":"J. Bone Miner. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1359\/jbmr.2001.16.9.1665","article-title":"Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice","volume":"16","author":"Alexander","year":"2001","journal-title":"J. Bone Miner. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e10807","DOI":"10.1002\/jbm4.10807","article-title":"Computed Tomography Provides Improved Quantification of Trabecular Lumbar Spine Bone Loss Compared to Dual-Energy X-Ray Absorptiometry in Ovariectomized Sheep","volume":"7","author":"Bisazza","year":"2023","journal-title":"JBMR Plus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1089\/ten.tec.2015.0383","article-title":"Guidelines for Dual Energy X-Ray Absorptiometry Analysis of Trabecular Bone-Rich Regions in Mice: Improved Precision, Accuracy, and Sensitivity for Assessing Longitudinal Bone Changes","volume":"22","author":"Shi","year":"2016","journal-title":"Tissue Eng. C Methods"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1053\/j.gastro.2008.02.078","article-title":"Rikkunshito, an herbal medicine, suppresses cisplatin-induced anorexia in rats via 5-HT2 receptor antagonism","volume":"134","author":"Takeda","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4827","DOI":"10.2174\/138161212803216933","article-title":"Rikkunshito and ghrelin secretion","volume":"8","author":"Takeda","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1152\/japplphysiol.00441.2007","article-title":"Hesperidin inhibits ovariectomized-induced osteopenia and shows differential effects on bone mass and strength in young and adult intact rats","volume":"104","author":"Horcajada","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Song, X., Chen, X., Jiang, R., Peng, K., Tang, X., and Liu, Z. (2021). Antiosteoporotic effect of hesperidin against ovariectomy-induced osteoporosis in rats via reduction of oxidative stress and inflammation. J. Biochem. Mol. Toxicol., 35.","DOI":"10.1002\/jbt.22832"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"261","DOI":"10.5142\/jgr.2013.37.261","article-title":"Ginseng saponins and the treatment of osteoporosis: Mini literature review","volume":"37","author":"Siddiqi","year":"2013","journal-title":"J. Ginseng Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Hwang, Y.H., Jang, S.A., Lee, A., Kim, T., and Ha, H. (2020). Poria cocos Ameliorates Bone Loss in Ovariectomized Mice and Inhibits Osteoclastogenesis In Vitro. Nutrients, 12.","DOI":"10.3390\/nu12051383"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Galanis, D., Soultanis, K., Lelovas, P., Zervas, A., Papadopoulos, P., Galanos, A., Argyropoulou, K., Makropoulou, M., Patsaki, A., and Passali, C. (2019). Protective effect of Glycyrrhiza glabra roots extract on bone mineral density of ovariectomized rats. Biomedicine, 9, Available online: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC6533940\/pdf\/bmdcn-9-8.pdf.","DOI":"10.1051\/bmdcn\/2019090208"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"104205","DOI":"10.1016\/j.jff.2020.104205","article-title":"Jujube fruit: A potential nutritious fruit for the development of functional food products","volume":"75","author":"Ahmed","year":"2020","journal-title":"J. Funct. Food"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"He, J., Li, X., Wang, Z., Bennett, S., Chen, K., Xiao, Z., Zhan, J., Chen, S., Hou, Y., and Chen, J. (2019). Therapeutic Anabolic and Anticatabolic Benefits of Natural Chinese Medicines for the Treatment of Osteoporosis. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01344"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1017\/S1368980019004828","article-title":"Trends in BMI among elderly Japanese population: Findings from 1973 to 2016 Japan National Health and Nutrition Survey","volume":"23","author":"Tarui","year":"2020","journal-title":"Public Health Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/557\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:05:02Z","timestamp":1760029502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/4\/557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["life15040557"],"URL":"https:\/\/doi.org\/10.3390\/life15040557","relation":{},"ISSN":["2075-1729"],"issn-type":[{"type":"electronic","value":"2075-1729"}],"subject":[],"published":{"date-parts":[[2025,3,29]]}}}