Ralston Stuart H
Rheumatic Diseases Unit, Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK.
Best Pract Res Clin Rheumatol. 2008 Mar;22(1):101-11. doi: 10.1016/j.berh.2007.11.005.
Several rare inherited osteolytic disorders have been described that show phenotypic overlap with Paget's disease of bone (PDB). Familial expansile osteolysis, early-onset familial PDB and expansile skeletal hyperphosphatasia are related disorders caused by mutations affecting the TNFRSF11A gene, which encodes the receptor activator of NFkappaB (RANK). The mutations result in failure of normal processing of RANK and osteoclast activation. Inactivating mutations in the TNFRSF11B gene, which encodes osteoprotegerin, cause idiopathic hyperphosphatasia which is a severe disorder that shares phenotypic similarities with PDB. The syndrome of hereditary inclusion body myopathy, PDB and frontotemporal dementia is caused by mutations in the gene encoding for valosin-containing protein which is involved in regulating degradation of ubiquitinated proteins. Anecdotal reports indicate that osteoclast inhibitors such as bisphosphonates are effective for suppressing bone turnover and improving symptoms in these disorders, although the long-term effects on clinical outcomes are unclear.
已经描述了几种罕见的遗传性骨溶解疾病，它们在表型上与佩吉特骨病（PDB）有重叠。家族性膨胀性骨溶解、早发性家族性PDB和膨胀性骨骼高磷酸酶血症是相关疾病，由影响TNFRSF11A基因的突变引起，该基因编码核因子κB受体激活剂（RANK）。这些突变导致RANK正常加工失败和破骨细胞活化。编码骨保护素的TNFRSF11B基因的失活突变会导致特发性高磷酸酶血症，这是一种与PDB有表型相似性的严重疾病。遗传性包涵体肌病、PDB和额颞叶痴呆综合征是由编码含缬酪肽蛋白的基因突变引起的，该蛋白参与调节泛素化蛋白的降解。轶事报道表明，破骨细胞抑制剂如双膦酸盐可有效抑制这些疾病中的骨转换并改善症状，尽管对临床结局的长期影响尚不清楚。
