Publications have been integrated for assessment.Clinical Interventions in Aging 2014:submit your manuscript | www.dovepressDovepressFujiwara et alDovepressPubMed n=Embase n=223 Duplicates, n=Total publications for critique 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 testimonials, n=2 Multicountry study with no country-level evaluation, 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 journal, n=Included publications n=Figure 1 Flow diagram of literature-search benefits. Databases had been Medline by means of PubMed and embase. Searches have been limited to human species and publications from 1980 onwards. Abbreviation: BMD, bone mineral density.In the eight publications24,29,32,33,369 that reported findings for BMD in the femoral neck, total hip, total neck, or other regions in the hip, BMD increased, remained the exact same, or decreased; couple of from the increases in BMD were statistically important.Fracture incidenceFracture incidence (vertebral or nonvertebral) was reported in three from the 15 publications, including publications from two randomized controlled trials31,35 and one observational study.40 Nonetheless, only the observational study, which was asubmit your manuscript | www.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 Imply (SD) age, years Study period, weeks Illness definition ObjectiveDovepressAuthorsEnrolled, nRandomized controlled trials Morii et al35 302aAssess safety and efficacy of RLX (double-blind, placebo-controlled)Iwamoto et al31 52 52Clinical Interventions in Aging 2014:9 52 L-BMD #2.Demethoxycurcumin Autophagy five SD of YAM and Japanese diagnostic criteriad L-BMD #2.S-23 Protocol 5 SD of YAM (osteoporosis) or 2.PMID:31085260 5 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 five 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.five SD of YAM (osteoporosis) or two.5 SD ,L-BMD #2.0 SD of YAM (osteopenia)d Japanese Guidelines for the Prevention and Treatment of Osteoporosisi 65 (six)b 65 (6)b 64 (7) 69 (7) 70 (eight) 72 (9)e 70 (11)e 64 (7) 65 (7) 65 (eight) 71 (three) 72 (three) 73 (three) 64 (7) 65 (7) 65 (7) 77 (10)h 78 (7)h RLX 60 mg/day, 50 RLX 60 mg/day, 68 70 (9)j 52 72 (10) 52 L-BMD #2.five SD of YAM and Japanese diagnostic criteriad L-BMD #2.five SD of YAM and Japanese diagnostic criteriad RLX 60 mg/day, 73 RLX 60 mg/day, six,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 ser.