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However, the relationship between the baseline cholesterol level and incident fracture rate under the treatment using the bone resorption inhibitors has not been documented. We investigated the relation between vertebral fracture incident and the baseline cholesterol levels and cholesterol-lowering effect of N-BP and SERM in osteoporosis through a prospective randomized open-label study design. Patients with osteoporosis (<jats:italic>n<\/jats:italic>\u2009=\u20093986) were allocated into two groups based on the drug used for treatment: minodronic acid (MIN) (<jats:italic>n<\/jats:italic>\u2009=\u20091624) as an N-BP and raloxifene (RLX) as an SERM (<jats:italic>n<\/jats:italic>\u2009=\u20091623). Serum levels of cholesterol and incidence of vertebral fracture were monitored for 2\u00a0years. The vertebral fracture rates between the two groups were compared using the pre-specified stratification factors. The patients receiving MIN with baseline low-density lipoprotein (LDL)-cholesterol level of\u2009\u2265\u2009140\u00a0mg\/dL, high-density lipoprotein cholesterol level\u2009&lt;\u200940\u00a0mg\/dL, age group of\u2009\u2265\u200975\u00a0years, and T score of BMD\u2009\u2265\u2009-3 SD had significantly lower vertebral fracture rates than those receiving RLX (incidence rate ratios (IRR) 0.45 [95% confidence interval (CI) 0.30 0.75, <jats:italic>p<\/jats:italic>\u2009=\u20090.001], 0.25 [95% CI 0.09 0.65, <jats:italic>p<\/jats:italic>\u2009=\u20090.005], 0.71 [95% CI 0.56 0.91, <jats:italic>p<\/jats:italic>\u2009=\u20090.006], 0.47 [95% CI 0.30 0.75, <jats:italic>p<\/jats:italic>\u2009=\u20090.0012], respectively). The cholesterol-lowering effect was stronger in the RLX group than in the MIN group, regardless of prior statin use. These results indicated that MIN treatment was more effective in reducing fracture risk in patients with higher LDL cholesterol levels, although its cholesterol-lowering ability was lesser than the RLX treatment.<\/jats:p><jats:p><jats:italic>Trial registration<\/jats:italic> University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR), No. UMIN000005433; date: April 13, 2011.<\/jats:p>","DOI":"10.1007\/s00223-023-01060-9","type":"journal-article","created":{"date-parts":[[2023,1,28]],"date-time":"2023-01-28T05:22:51Z","timestamp":1674883371000},"page":"430-439","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effect of Bone Resorption Inhibitors on Serum Cholesterol Level and Fracture Risk in Osteoporosis: Randomized Comparative Study Between Minodronic Acid and Raloxifene"],"prefix":"10.1007","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2490-3442","authenticated-orcid":false,"given":"Hiroaki","family":"Ohta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3013-7775","authenticated-orcid":false,"given":"Yukari","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3257-4063","authenticated-orcid":false,"given":"Teruki","family":"Sone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-5235","authenticated-orcid":false,"given":"Shiro","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-2747","authenticated-orcid":false,"given":"Satoshi","family":"Soen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7660-5562","authenticated-orcid":false,"given":"Satoshi","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-1095","authenticated-orcid":false,"given":"Hiroshi","family":"Hagino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8700-4009","authenticated-orcid":false,"given":"Masao","family":"Fukunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitaka","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Orimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6599-6185","authenticated-orcid":false,"given":"Masataka","family":"Shiraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Adequate Treatment of Osteoporosis (A-TOP) research group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,28]]},"reference":[{"key":"1060_CR1","first-page":"69","volume":"28","author":"V Baldini","year":"2005","unstructured":"Baldini V, Mastropasqua M, Francucci CM, D\u2019Erasmo E (2005) Cardiovascular disease and osteoporosis. 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Yukari Uemura has received a consultancy fee from Teijin Pharma Ltd. and Daiichi Sankyo and outsourcing fees from Chugai Pharmaceutical Co. Teruki Sone has received research grants from Asahi Kasei Pharma Corp., Astellas Pharma, Taisho Toyama Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pizer, and Teijin Pharma Ltd., and consulting fees from Kissei pharmaceutical Co. Ltd., Shimadzu Corp., and Takeda Pharmaceutical Co. Ltd. Shiro Tanaka has received lecture fees from Bayer Yakuhin, Amgen Astellas BioPharma K.K. and Research Institute of Healthcare Data Science. He has received consultation fees from Boehringer Ingelheim. He has also received outsourcing fee from Public Health Research Foundation and Satt and grants from Novo Nordisk Pharma Ltd., the Japan Agency for Medical Research and Development, the Japanese Ministry of Health Labor and Welfare, and the Japanese Ministry of Education, Science, and Technology. He had engaged in a research project of the Japan Agency for Medical Research and Development. Satoshi Soen received lecture and consultancy fees from Asahi Kasei Pharma Corp., Astellas Pharma, Chugai Pharmaceutical Co., Daiichi Sankyo, Eisai Co. Ltd., Eli Lilly Japan, Ono Pharmaceutical Co., Pfizer, and Takeda Pharmaceutical Company Ltd. Satoshi Mori declares no COI. Hiroshi Hagino has received lecture fees or grants outside the submitted work from Amgen Inc., Asahi Kasei Pharma Corp., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan Co., Ltd., Mitsubishi Tanabe Pharma Corp., Mochida Pharma Corp., Ono Pharmaceutical Co., Ltd., Pizer Inc., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Co., Ltd., and UCB Japan. Masao Fukunaga has received consulting fees from Asahi Kasei Pharma Corp and lecture fees from Daiichi Sankyo, MSD, and Chugai Pharmaceutical Co. Toshitaka Nakamura has received personal fees and others from Asahi Pharma, Teijin Pharma, Daiichi-Sankyo Pharma, UCB Pharma, AMGEN, ASTELAS, Chugai Pharma, and MERCK. Hajime Orimo declares no COI.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was registered at the University Hospital Medical Information Network- Clinical Trials Registry (UMIN-CTR) under the identification number UMIN000005433; date: April 13, 2011. The protocol was approved by the Central Ethical Committee for Adequate Treatment of Osteoporosis group (Chairman Dr. Rikushi Morita) and was reviewed by the institutional review board of each participating institution. The trial was conducted in accordance with the principles of the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"Written informed consent was obtained prior to patient enrollment after a thorough explanation of the trial objectives, duration, and procedures.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent"}}]}}