Nihon Pharmaceutical University

To investigate the association between milk intake frequency and fracture risk in groups based on blood 25(OH)D levels.

This secondary analysis of a prospective cohort study included data from 1209 postmenopausal Japanese women aged ≥ 50 years. Baseline milk intake frequency was obtained using a questionnaire. Blood 25(OH)D levels were measured using a competitive protein-binding assay. Information on fracture events was obtained from face-to-face interviews through follow-up or supplemental mail surveys.

Over a median follow-up period of 16.1 years (total: 17,427 person-years), 358 and 238 women sustained at least one clinical and osteoporotic fracture, respectively. The proportions of participants with milk intake < 1 glass/day and those with 25(OH)D levels < 15 ng/mL were 31.9% and 21.6%, respectively. In univariate Cox proportional hazard analyses, a 25(OH)D level < 15 ng/mL and a milk intake of < 1 glass/day were associated with an increased risk of clinical and osteoporotic fractures. Among participants with 25(OH)D levels < 15 ng/mL, the adjusted hazard ratios for milk intake < 1 glass/day compared to ≥ 1 glass/day were 1.99 (95% confidence interval: 1.32-2.99) and 2.11 (1.28-3.47) for clinical and osteoporotic fractures, respectively. In contrast, the HRs were not significant among those with 25(OH)D levels ≥ 15 ng/mL.

A clear positive association was identified between milk intake frequency and fracture risk among Japanese women after menopause with low 25(OH)D levels. Therefore, correcting vitamin D insufficiency would likely lower fracture risk. In addition, encouraging habitual milk intake may help prevent fractures, particularly among individuals with low 25(OH)D levels.

A synthetic route for the novel nucleosides 4′-methylsulfanyluridine (20a) and -cytidine (26) has been developed.This route consists of two steps; 1) preparation of 4′-O-benzoyloxy-xylofuranosylnucleoside 13 through electrophilic iodo-benzoyloxylation to 4′,5′-unsaturated uracil nulesoside 9 and replacement of the iodo-substituent at the 5′-position with the benzoyloxy group, 2) nucleophilic substitution of 13 with Me₃SiSMe leading to the 4′-α-methylsulfanylnucleoside 14a stereoselectively.The possible reaction mechanism of the 5′-deoxy-5′-iodonucleosides 10a and 10b with AgOBz is discussed.The transformation of the xylofuranosyl moiety of 14a into the ribonucleoside 20a was performed on the basis of the ring-opening of the O²,2′-anhydronucleoside 24 with benzoate ion.In this study, 4′-methylsulfanylcytidine 26 was also synthesized.