Abstract Parathyroid hormone related peptide (PTHrP) is a paracrine factor produced by osteoblast lineage cells, which has a role in the regulation of bone remodeling and fracture repair. Early preclinical and clinical studies indicated that exogenous administration of PTHrP could have anabolic activity on the skeleton similar to that seen with exogenous PTH, but had potent vasodilatory effects which limited its clinical utility. Abaloparatide (Abalo) is a synthetic PTHrP(1-34) analog with 70% homology to PTHrP and 40% homology with Parathyroid hormone (PTH). Like PTH and PTHrP, Abalo interacts with the PTH1 receptor, however Abalo has higher affinity for the RG subtype of the Receptor and lower affinity for the R0 conformation (vs. PTH), resulting in relatively greater stimulation of bone formation and lesser bone resorption in preclinical models. Short-term clinical studies confirmed that Abalo had potent dose dependent anabolic activity with increases in BMD at the higher doses that were equal to or larger than that seen with PTH. In the Abalo Pivotal Trial, 2463 postmenopausal women with osteoporosis were randomized to blinded daily subcutaneous Abalo vs. placebo or open label PTH1-34. At 18 months, spine BMD had increased similarly with Abalo and TPTD, however, hip BMD increments were faster and significantly larger with Abalo. Consistent with the BMD effects, over 18 months, Abalo reduced vertebral fracture incidence by 86% and nonvertebral fracture incidence by 43%. The fracture risk reductions were sustained after both groups transitioned to antiresorptive medication. Abalo is a potent anabolic agent for treatment of osteoporosis and can be considered as initial therapy in patients at high risk for fracture.
甲状旁腺激素相关肽(Parathyroid hormone related peptide, PTHrP)是一种由成骨细胞系细胞产生的旁分泌因子，在骨重塑和骨折修复中起调节作用。早期临床前和临床研究表明，外源性PTHrP对骨骼具有与外源性PTH相似的合成代谢活性，但具有强效的血管扩张作用，限制了其临床应用。Abaloparatide (Abalo)是一种合成的PTHrP(1-34)类似物，与PTHrP有70%的同源性，与甲状旁腺激素(PTH)有40%的同源性。与PTH和PTHrP一样，Abalo与PTH1受体相互作用，但Abalo对受体的RG亚型具有更高的亲和力，而对R0构象的亲和力较低(与PTH相比)，导致临床前模型中相对较大的骨形成刺激和较小的骨吸收。短期临床研究证实，Abalo具有强效剂量依赖性合成代谢活性，高剂量时BMD的增加等于或大于PTH。在Abalo枢纽试验中，2463名绝经后骨质疏松症妇女被随机分为盲法每日皮下注射Abalo组、安慰剂组或开放标签PTH1-34组。在18个月时，脊柱骨密度增加与Abalo和TPTD相似，然而，Abalo的髋关节骨密度增加更快且明显更大。与骨密度效应一致，在18个月的时间里，Abalo将椎体骨折发生率降低了86%，非椎体骨折发生率降低了43%。两组过渡到抗吸收药物治疗后，骨折风险持续降低。阿巴洛是一种治疗骨质疏松症的强效合成代谢剂，可作为骨折高危患者的初始治疗药物。
{"title":"Abaloparatide Treatment for Osteoporosis","authors":"F. Cosman","doi":"10.1530/ENDOABS.59.S4.1","DOIUrl":"https://doi.org/10.1530/ENDOABS.59.S4.1","url":null,"abstract":"Abstract Parathyroid hormone related peptide (PTHrP) is a paracrine factor produced by osteoblast lineage cells, which has a role in the regulation of bone remodeling and fracture repair. Early preclinical and clinical studies indicated that exogenous administration of PTHrP could have anabolic activity on the skeleton similar to that seen with exogenous PTH, but had potent vasodilatory effects which limited its clinical utility. Abaloparatide (Abalo) is a synthetic PTHrP(1-34) analog with 70% homology to PTHrP and 40% homology with Parathyroid hormone (PTH). Like PTH and PTHrP, Abalo interacts with the PTH1 receptor, however Abalo has higher affinity for the RG subtype of the Receptor and lower affinity for the R0 conformation (vs. PTH), resulting in relatively greater stimulation of bone formation and lesser bone resorption in preclinical models. Short-term clinical studies confirmed that Abalo had potent dose dependent anabolic activity with increases in BMD at the higher doses that were equal to or larger than that seen with PTH. In the Abalo Pivotal Trial, 2463 postmenopausal women with osteoporosis were randomized to blinded daily subcutaneous Abalo vs. placebo or open label PTH1-34. At 18 months, spine BMD had increased similarly with Abalo and TPTD, however, hip BMD increments were faster and significantly larger with Abalo. Consistent with the BMD effects, over 18 months, Abalo reduced vertebral fracture incidence by 86% and nonvertebral fracture incidence by 43%. The fracture risk reductions were sustained after both groups transitioned to antiresorptive medication. Abalo is a potent anabolic agent for treatment of osteoporosis and can be considered as initial therapy in patients at high risk for fracture.","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122364144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.11227-9
C. H. Gouveia, L. Capelo, Bianca Neofiti-Papi, A. Zallone
{"title":"Thyroid and Bone","authors":"C. H. Gouveia, L. Capelo, Bianca Neofiti-Papi, A. Zallone","doi":"10.1016/b978-0-12-801238-3.11227-9","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.11227-9","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122379669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.11207-3
W. Cawthorn
{"title":"Bone Marrow Adipose Tissue","authors":"W. Cawthorn","doi":"10.1016/b978-0-12-801238-3.11207-3","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.11207-3","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126542848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/B978-0-12-801238-3.11275-9
Abul Fajol, H. Komaba, M. Fukagawa
{"title":"FGF23 and Klotho in Chronic Kidney Disease","authors":"Abul Fajol, H. Komaba, M. Fukagawa","doi":"10.1016/B978-0-12-801238-3.11275-9","DOIUrl":"https://doi.org/10.1016/B978-0-12-801238-3.11275-9","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124992789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-814081-9.09983-0
{"title":"Copyright","authors":"","doi":"10.1016/b978-0-12-814081-9.09983-0","DOIUrl":"https://doi.org/10.1016/b978-0-12-814081-9.09983-0","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"96 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133049054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.62269-9
T. Rosol
{"title":"Animal Models of Cancer-Associated Hypercalcemia","authors":"T. Rosol","doi":"10.1016/b978-0-12-801238-3.62269-9","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.62269-9","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123665337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.11187-0
R. Yasuhara, Y. Usami, M. Enomoto-Iwamoto
{"title":"Wnt Signaling in Cartilage Development","authors":"R. Yasuhara, Y. Usami, M. Enomoto-Iwamoto","doi":"10.1016/b978-0-12-801238-3.11187-0","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.11187-0","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"91 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124605558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.11172-9
Fanxin Long
{"title":"Osteoblast Differentiation","authors":"Fanxin Long","doi":"10.1016/b978-0-12-801238-3.11172-9","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.11172-9","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133943315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.11226-7
Alexandre Chamouni, F. Oury
{"title":"Bone and Metabolic Control","authors":"Alexandre Chamouni, F. Oury","doi":"10.1016/b978-0-12-801238-3.11226-7","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.11226-7","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132964481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 1900-01-01DOI: 10.1016/b978-0-12-801238-3.11551-x
X. Guo, Y. Hu, A. Dinescu
{"title":"Bone Structure and Function","authors":"X. Guo, Y. Hu, A. Dinescu","doi":"10.1016/b978-0-12-801238-3.11551-x","DOIUrl":"https://doi.org/10.1016/b978-0-12-801238-3.11551-x","url":null,"abstract":"","PeriodicalId":302927,"journal":{"name":"Encyclopedia of Bone Biology","volume":"35 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"1900-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133411052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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