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Summary: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. Among high-risk postmenopausal East Asian women, romosozumab followed by alendronate was associated with lower incidences of fractures vs alendronate alone. Romosozumab demonstrates potential to address an unmet need in osteoporosis management in Asia. Introduction: Romosozumab, a sclerostin antibody, exerts dual effect to increase bone formation and decrease bone resorption. The global ARCH study demonstrated superiority of romosozumab followed by alendronate in reducing fracture risk in high-risk postmenopausal osteoporotic women vs alendronate alone. We report outcomes among ARCH East Asian patients. Methods: In ARCH, 4093 postmenopausal osteoporotic women with fragility fracture were randomized 1:1 to monthly romosozumab 210 mg or weekly alendronate 70 mg for 12 months, both followed by open-label alendronate. Primary endpoints were incidence of new vertebral fracture (VF) at 24 months and clinical fracture at primary analysis (confirmed fractures in ≥ 330 patients and all patients had opportunity to attend month 24 visit). This post hoc analysis was not powered to detect fracture-rate differences. Results: This analysis included 275 patients from Hong Kong, Korea, and Taiwan. Romosozumab followed by alendronate reduced risk of new VFs at 24 months by 60% (P = 0.11) and clinical fractures at primary analysis by 44% (P = 0.15) vs alendronate alone. Romosozumab followed by alendronate significantly increased mean bone mineral density at 24 months from baseline by a further 9.0%, 3.3%, and 3.0% at the lumbar spine, total hip, and femoral neck vs alendronate alone. Adverse event (AE) rates, including positively adjudicated serious cardiovascular AEs (1.6% vs 1.4% at 12 months for romosozumab vs alendronate), were similar across treatment groups. Conclusions: Consistent with the global analysis, romosozumab followed by alendronate was associated with lower incidences of new vertebral, clinical, non-vertebral, and hip fractures vs alendronate alone among East Asian patients. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) play critical roles in osteoblast differentiation. To investigate the association between common single-nucleotide polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional study was conducted in healthy Korean men ( n = 237) and women ( n = 276) aged 20–39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray absorptiometry. SNPs of BMP2 (-1103C>A, c.584G>A, IVS1-2744A>G, c.893T>A), BMP4 (c.712T>C, IVS1-160C>T), and BMP6 (c.1283C>G, IVS4-6838A>G, IVS5 + 24C>T) were determined using the 5′-nuclease assay. Significant associations were observed between BMP2 c.584G>A, c.893T>A genotypes and male calcaneus as well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16% higher BMD at the calcaneus ( P for trend = 0.014), whereas women with this genotype had a 7% lower BMD at the distal radius than the other genotypes ( P for trend = 0.010). A significant association was also observed between BMP4 IVS1-160C>T and male calcaneus BMD ( P for trend = 0.024). When the association between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was significantly associated with low bone mass in female distal radius ( P for trend = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are associated with peripheral BMD in Korean men and women. However, this association is dependent on anatomical sites and gender. Thus, larger studies with complete coverage of SNPs are needed in the future. [ABSTRACT FROM AUTHOR]

To evaluate the effects of genetic polymorphisms of OPG, RANK, and ESR1, which regulate osteoclastogenesis, on bone mineral density (BMD), a cross-sectional study was conducted in 650 Korean postmenopausal women. BMDs of the distal radius and the calcaneus were measured by dual energy X-ray absorptiometry (DXA). Genetic polymorphisms of OPG 163 A > G, 1181 G > C; RANK 421 C > T, 575 T > C; and ESR1 1335 C > T, 2142 G > A were determined by matrix-assisted laser desorption/ionization—time of flight (MALDI-ToF) mass spectrometry. The differences between the BMDs of the genotypes of OPG, RANK, and ESR1 were analyzed by multiple linear regression model adjusted for age and body mass index. Women with the OPG 1181 CC genotype had higher BMDs at the distal radius (7%) and calcaneus (10%) than those with the GG genotype; and these differences were statistically significant ( P = 0.001 and P = 0.007, respectively). A significant association was also observed between RANK 575 T > C and calcaneus BMD ( P for trend = 0.017). No significant association was observed between BMDs and the polymorphisms of ESR1. The association between OPG 1181 G > C and BMD was profound in subjects with the RANK 575 TT or ESR1 2142 GG genotypes; women with OPG 1181 CC had higher BMDs at the distal radius (11%) and calcaneus (11%) than those with OPG 1181 GG only in women with RANK 575 TT genotype ( P = 0.002 and P = 0.021, respectively). These results suggest that OPG genetic polymorphisms, especially with the RANK 575 TT or ESR1 2142 GG genotypes, are related to low BMD in postmenopausal Korean women. [ABSTRACT FROM AUTHOR]