N=Embase n=223 Duplicates, n=Total publications for overview n=Excluded, n=201 Not human, n=10 Not low BMD or osteoporosis, n=8 Not raloxifene, n=17 No relevant outcomes, n=19 Case reports, n=9 Narrative reviews, n=135 Not Japan, n=Publications for full-text review n=Excluded, n=11 Systematic reviews, n=2 Multicountry study with no country-level analysis, n=1 Antiresorptive therapy study with no drug-level analysis, n=1 Participants with osteoporosis/osteoarthritis with no disease-level evaluation, n=1 Conference abstract, n=1 Participants on dialysis, n=3 Published in non-peer-reviewed PTPRC/CD45RA Protein manufacturer journal, n=Included publications n=Figure 1 Flow diagram of literature-search results. Databases were Medline by way of PubMed and embase. Searches were limited to human species and publications from 1980 onwards. Abbreviation: BMD, bone mineral density.In the eight publications24,29,32,33,36?9 that reported findings for BMD in the femoral neck, total hip, total neck, or other regions from the hip, BMD increased, remained the identical, or decreased; few on the increases in BMD had been statistically significant.Fracture incidenceFracture incidence (vertebral or nonvertebral) was reported in three in the 15 publications, including publications from two randomized controlled trials31,35 and one observational study.40 Nevertheless, only the observational study, which was asubmit your manuscript | dovepressClinical Interventions in Aging 2014:DovepressTable 1 Study and participant characteristicsTherapy and dose, n 52 L-BMD #2.five SD of YAM and Japanese diagnostic criteriac Japanese diagnostic criteriad Mean (SD) age, years Study period, weeks Disease definition ObjectiveDovepressAuthorsEnrolled, nRandomized controlled trials Morii et al35 302aAssess security and efficacy of RLX (double-blind, placebo-controlled)Iwamoto et al31 52 52Clinical Interventions in Aging 2014:9 52 L-BMD #2.five SD of YAM and Japanese diagnostic criteriad L-BMD #2.5 SD of YAM (osteoporosis) or two.five SD ,L-BMD #2.0 SD of YAM (osteopenia)d L-BMD #2.0 SD of YAM 104 RLX 60 mg/day, 92a RLX 120 mg/day, 95a Placebo, 97a RLX 60 mg/day, 61 ALN 5 mg/day, 61 RLX 60 mg/day, 32 RLX 60 mg + ALF 1 g/day, 28 RLX 60 mg/day, 45 ALF 1 g/day, 44 RLX 60 mg + ALF 1 g/day, 48 RLX 60 mg/day, 16 HRT, 16 Handle, 14f RLX 60 mg/day, 42g ALF 1 g/day, 46g RLX 60 mg + ALF 1 g/day, 45g RLX 60 mg/day am, 20 RLX 60 mg/day pm, 19 52 L-BMD #2.5 SD of YAM (osteoporosis) or two.5 SD ,L-BMD #2.0 SD of YAM (osteopenia)d Japanese Recommendations for the Prevention and Treatment of Osteoporosisi 65 (6)b 65 (6)b 64 (7) 69 (7) 70 (8) 72 (9)e 70 (11)e 64 (7) 65 (7) 65 (8) 71 (three) 72 (3) 73 (three) 64 (7) 65 (7) 65 (7) 77 (ten)h 78 (7)h RLX 60 mg/day, 50 RLX 60 mg/day, 68 70 (9)j 52 72 (ten) 52 L-BMD #2.five SD of YAM and Japanese diagnostic criteriad L-BMD #2.5 SD of YAM and Japanese diagnostic criteriad RLX 60 mg/day, 73 RLX 60 mg/day, 6,970l RLX 60 mg/day, 198 63 (eight) 70 (9)m 52n 104 156 52 71 (9)bMajima et alGorai et alCompare effects of RLX and ALN on L-BMD, bone turnover, and lipid metabolism Assess efficacy of RLX + ALF on BMD and bone turnover Assess adherence to RLX, ALF, and RLX + ALFHayashi et alGorai et alAndo et alCompare atheroprotective and osteoprotective effects of RLX and HRT when switching from HRT to RLX (age-matched controlsf) Assess efficacy of RLX + ALF on BMD and bone turnover and impact of RLX on serum PTH Assess effects of RLX dosing time on coagulation, fibrinolysis, and bone turnoverObservational LILRA2/CD85h/ILT1, Human (HEK293, His-Avi) research Majima et al36Majima et alMajima et al38 70 (.