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Osteogenesis imperfecta (OI) is a group of hereditary disorders characterized by decreased bone mass and increased fracture risk. The majority of OI cases have an autosomal dominant pattern of inheritance and are usually caused by mutations in genes encoding type I collagen. OI cases of autosomal recessive inheritance are rare, and OI type XI is attributable to mutation of the FKBP10gene. Here, we used next-generation sequencing and Sanger sequencing to detect mutations in FKBP10and to analyze their relation to the phenotypes of OI type XI in three Chinese patients. We also evaluated the efficacy of zoledronic acid treatment in these patients. Two of the affected patients had novel compound heterozygous mutations, one patient with c.343C>T (p.R115X) in exon 2 and c.1085delC (p.A362fsX1) in exon 7, and the other patient with c.879C>G (p.Y293X) in exon 5 and c.918-3C>G in intron 5. In the third proband, we identified a homozygous single base-pair duplication, c.831dupC (p.G278RfsX95) in exon 5. In conclusion, we report for the first time that these novel pathogenic mutations of FKBP10can lead to the extremely rare type XI OI without contractures, which expands the genotypic spectrum of OI. The phenotypes of these patients are similar to patients with types III or IV OI, and zoledronic acid is effective in increasing BMD, inhibiting bone resorption biomarkers and reducing fractures of these patients.

Aim:To investigate the correlation between DKK1polymorphisms with bone phenotypes and response to alendronate treatment. Materials & methods:Five tag single nucleotide polymorphisms of DKK1were analyzed in 639 Chinese postmenopausal women with osteoporosis or osteopenia. Bone mineral density (BMD), β-CTX and ALP were measured before and after alendronate treatment. Results:Genotypes at rs1896367, rs1528877 and rs2241529 correlated to baseline BMD (p < 0.05). rs1528877 and rs2241529 polymorphisms correlated to baseline β-CTX levels (p < 0.05). rs2241529 polymorphisms of DKK1had a small influence on the skeletal response to alendronate treatment (p < 0.05). Conclusion:DKK1polymorphisms may correlate to baseline BMD and serum β-CTX levels, but present a weak effect on the response to alendronate.