ABSTRACT
AIM: To investigate the correlation between DKK1 polymorphisms with bone phenotypes and response to alendronate treatment. MATERIALS & METHODS: Five tag single nucleotide polymorphisms of DKK1 were analyzed in 639 Chinese postmenopausal women with osteoporosis or osteopenia. Bone mineral density (BMD), ß-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 ß-CTX levels (p < 0.05). rs2241529 polymorphisms of DKK1 had a small influence on the skeletal response to alendronate treatment (p < 0.05). CONCLUSION: DKK1 polymorphisms may correlate to baseline BMD and serum ß-CTX levels, but present a weak effect on the response to alendronate.
Subject(s)
Alendronate/therapeutic use , Bone Density Conservation Agents/therapeutic use , Bone Density/drug effects , Bone Remodeling/drug effects , Intercellular Signaling Peptides and Proteins/genetics , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Asian People , Biomarkers/blood , Bone Diseases, Metabolic/drug therapy , Bone Diseases, Metabolic/genetics , Bone Diseases, Metabolic/physiopathology , Collagen Type I/blood , Creatinine/blood , Genetic Association Studies , Humans , Osteoporosis, Postmenopausal/drug therapy , Osteoporosis, Postmenopausal/genetics , Osteoporosis, Postmenopausal/physiopathology , Peptides/blood , Polymorphism, Single Nucleotide , Prospective StudiesABSTRACT
Gorham-Stout disease (GSD) is an exceedingly rare disease characterized by progressive osteolysis and angiomatosis. We investigate the features of this disease and evaluate the effects of bisphosphonates (BPs) on it. The clinical, radiological, and pathological characteristics of 12 patients diagnosed with GSD were summarized. Immunohistochemical staining with specific lymphatic endothelial markers (D2-40), vascular markers (CD 31, CD 34), and vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed in specimens of bone biopsy. Patients were treated with either BPs or conjunction therapy of radiation and BPs. The effects of BPs were evaluated by the change of radiological progression, bone mineral density (BMD) and bone turnover biomarkers. To further evaluate the prognosis, a literature review was done. Idiopathic massive osteolysis was found in all patients, including 11 polyostotic and one mono-ostotic osteolysis. Soft tissue lymphangioma was presented in four patents. Four patients were complicated with chylothorax. Endothelial cells lining the proliferative vessels were positive for CD31 and CD34 and D2-40. Mild expression of VEGF and VEGFR-3 was also revealed. Stabilization in osteolysis and improvement in BMD were observed after single therapy with BPs or combined with radiotherapy. High mortality rate was found in patients with chylothorax. Spontaneous, progressive osteolysis is the most typical sign of GSD. BPs and radiotherapy can contribute to the clinical stabilization in bone lesion of GSD. The complicated chylothorax possibly indicates poor prognosis.
Subject(s)
Bone and Bones/diagnostic imaging , Osteolysis, Essential/diagnosis , Absorptiometry, Photon , Adolescent , Adult , Biopsy , Bone Density/drug effects , Bone Density/physiology , Bone and Bones/pathology , Child , Child, Preschool , Diphosphonates/pharmacology , Diphosphonates/therapeutic use , Female , Humans , Male , Osteolysis, Essential/diagnostic imaging , Osteolysis, Essential/drug therapy , Osteolysis, Essential/pathology , Retrospective Studies , Treatment Outcome , Young AdultABSTRACT
AIM: To investigate the association between SOST gene polymorphisms and response to alendronate treatment. MATERIALS & METHODS: 639 Chinese postmenopausal women with osteoporosis or osteopenia received alendronate treatment. Polymorphisms of SOST were analyzed. Bone mineral density (BMD), serum ALP and ß-CTX levels were measured. The correlation of SOST polymorphisms with changes of BMD and bone biomarkers after treatment was analyzed. RESULTS: rs1234612 and rs851054 polymorphisms were correlated to baseline lumbar spine BMD (p < 0.05). After 12 months of treatment rs1234612 and rs865429 polymorphisms were correlated to BMD changes at the lumbar spine (p < 0.05) or femoral neck (p < 0.05), respectively. CONCLUSION: The polymorphisms of SOST are genetic factors affecting bone health and response to alendronate in Chinese postmenopausal women.
Subject(s)
Alendronate/therapeutic use , Bone Morphogenetic Proteins/genetics , Genetic Markers/genetics , Osteoporosis/drug therapy , Osteoporosis/genetics , Polymorphism, Genetic/genetics , Postmenopause/drug effects , Postmenopause/genetics , Adaptor Proteins, Signal Transducing , Adult , Aged , Asian People/genetics , Biomarkers/metabolism , Bone Density/drug effects , Bone Density/genetics , Bone Density Conservation Agents/therapeutic use , Female , Humans , Lumbar Vertebrae/drug effects , Middle Aged , Prospective StudiesABSTRACT
AIM: To investigate the association between LRP5 gene polymorphisms and response to alendronate in Chinese osteoporotic women. MATERIALS & METHODS: Six hundred and thirty nine Chinese postmenopausal women with osteopenia or osteoporosis were included and received alendronate treatment. The A1330V polymorphism of LRP5 was investigated. Bone mineral density (BMD) and bone turnover markers (ALP and ß-isomerized carboxy-telopeptide of type I collagen [ß-CTX]) were measured before and after treatment. The correlation of LRP5 polymorphisms with changes in BMD and bone turnover biomarkers were analyzed after treatment. RESULTS: After 12 months of treatment, participants with CC and CT genotypes had a larger increase in lumbar spine BMD and a larger decrease in serum ß-CTX and ALP levels than those with TT genotype (all p < 0.001). No significant genotype-treatment interaction was found in hip BMD. CONCLUSION: The A1330V polymorphism of LRP5 is possibly correlated with response to alendronate treatment in Chinese women with osteoporosis, and the TT genotype could possibly predict a weak response to alendronate.
