Teriparatid 750 mg

▎ Teriparatid Structure

▎ Teriparatid Kev Tshawb Fawb

Teriparatid txhais li cas?

Teriparatid yog ib tug recombinant human parathyroid hormone (PTH) analog tsim los ntawm thawj 34 amino acids ntawm tib neeg parathyroid hormone. Nws tswj cov pob txha metabolism los ntawm kev ua kom lub cev ua haujlwm ntawm endogenous parathyroid hormone. Teriparatid yog thawj cov tshuaj hluavtaws anabolic pom zoo rau kev mob pob txha loj. Nws cov qauv nthuav tawm siab homology nrog endogenous PTH, ua kom lub zog ntawm PTH receptor los hloov cov kev ua haujlwm ntawm osteoclast metabolic.

Yuav ua li cas yog lub mechanism ntawm kev txiav txim rau Teriparatid?

Cov teebmeem ntawm osteoblasts:

Txhawb osteoblast proliferation: Teriparatid txhawb kev loj hlob ntawm osteoblast precursor hlwb, nce osteoblast tooj. Hauv kev tshawb fawb tsiaj, kev tswj xyuas tsis tu ncua ntawm teriparatide ua rau muaj kev loj hlob ntawm mesenchymal qia hlwb muaj peev xwm sib txawv rau hauv osteoblasts hauv cov pob txha pob txha. Qhov no tau ua rau ntau lub hlwb kom sib txawv rau hauv cov laus osteoblasts, muab cov cellular txaus rau kev tsim cov pob txha. Nyob rau hauv vitro cell kab lis kev cai thwmsim pom tau hais tias kev faib tus nqi ntawm osteoblast precursor hlwb nyob rau hauv lub Teriparatid-kho pab pawg neeg yog ho siab tshaj nyob rau hauv lub tswj pab pawg neeg, qhia tias Teriparatid ncaj qha txhawb kev loj hlob ntawm osteoblast precursor hlwb ^[1,2].

Txhim kho Osteoblast Kev Ua Haujlwm: Teriparatid tsis tsuas yog nce osteoblast tus lej tab sis kuj txhawb nqa lawv cov haujlwm. Nws upregulates cov kev qhia ntawm cov noob txuam nrog cov pob txha matrix synthesis nyob rau hauv osteoblasts, xws li cov encoding hom I collagen thiab osteocalcin, uas qhia tau hais tias muaj ntau ntau ntau. Hom I collagen, thawj cov organic tivthaiv ntawm cov pob txha matrix, txhawb kev tsim cov txheej txheem matrix muaj zog dua los ntawm kev sib txuas ntxiv. Osteocalcin plays lub luag haujlwm tseem ceeb hauv pob txha pob txha los ntawm kev txhawb nqa calcium ion deposition hauv matrix, yog li txhim kho pob txha mineralization. Los ntawm cov txheej txheem no, osteoblasts synthesize thiab secrete pob txha matrix zoo dua, txhawb kev tsim cov pob txha tshiab ^[2,3].

Inhibition ntawm osteocyte apoptosis: Nyob rau hauv ib txwm muaj lub cev muaj zog, osteocytes raug apoptosis tom qab ua tiav cov haujlwm tshwj xeeb ntawm pob txha. Teriparatid inhibits cov txheej txheem apoptotic no, ua kom ntev osteocyte lifespan. Teriparatid ua kom muaj feem cuam tshuam ntawm cov xov tooj ntawm tes, xws li PI3K / Akt txoj kev. Thaum ua kom muaj zog, txoj hauv kev no txwv cov kev qhia ntawm apoptosis-txog cov proteins, ua kom osteoblasts txhawb nqa lawv cov pob txha tsim ua haujlwm thiab tswj kev txuas ntxiv thiab ruaj khov ntawm cov pob txha tsim ^[1,3].

Cov teebmeem ntawm Osteoclasts: Teriparatid cov teebmeem ntawm osteoclasts yog qhov nyuaj. Thaum lub sij hawm sib quas ntus dosing, nws cuam tshuam osteoclasts los ntawm indirect mechanisms. Nws txhawb osteoblast secretion ntawm osteoprotegerin (OPG), ib tug cytokine uas sib tw khi rau tus receptor activator ntawm nuclear factor κB ligand (RANKL). RANKL yog tus tswj hwm qhov tseem ceeb ntawm kev sib txawv ntawm osteoclast thiab ua kom muaj zog. Thaum OPG khi rau RANKL, RANKL tsis tuaj yeem khi rau RANK receptor nyob rau saum npoo ntawm osteoclast precursor hlwb, yog li inhibiting osteoclast sib txawv thiab maturation thiab txo cov pob txha resorption. Hauv cov neeg mob osteoporosis, qhov twg cov pob txha resorption ntau tshaj qhov tsim ua rau cov pob txha poob, teriparatide txo cov kev ua osteoclast los ntawm cov txheej txheem no. Qhov no restores qhov sib npaug ntawm resorption thiab tsim, txhawb pob txha nce ^[2,3].

Daim duab 1 Qhov chaw ntawm kev nqis tes ua rau kev kho mob osteoporosis thawj kab. Teriparatid, ib tug recombinant fragment ntawm parathyroid hormone, nkoos pob txha tsim los ntawm kev ua osteoblast kev ua si thiab, mus rau ib tug tsawg npaum li cas, inhibiting osteoclast recruitment ^[4].

Modulation of Bone Metabolism-Related Signaling Pathways:

Wnt/β-Catenin Signaling Pathway: Wnt/β-catenin signaling pathway plays lub luag haujlwm tseem ceeb hauv kev txhim kho pob txha thiab kev saib xyuas cov pob txha homeostasis. Teriparatid ua rau txoj hauv kev no, txhawb kev sib txuam hauv cov cellular thiab kev hloov pauv nuclear ntawm β-catenin. Nuclear β-catenin khi rau cov txheej txheem hloov pauv cuam tshuam, pib kev hloov pauv ntawm cov pob txha tsim cov noob caj ces thiab txhim kho kev qhia ntawm osteoblast-specific transcription factor Runx2. Runx2 ntxiv tswj kev sib txawv ntawm osteoblast thiab kev ua haujlwm, yog li txhawb kev tsim cov pob txha. Ua kom txoj hauv kev no tseem cuam tshuam kev sib txawv ntawm osteoblast rau adipocytes, ua kom muaj kev sib txawv ntau dua ntawm cov pob txha pob txha mesenchymal qia hlwb mus rau cov kab mob osteoblast, yog li ua rau cov pob txha loj ^[1,3].

PTH / PTHrP Receptor Signaling Pathway: Teriparatid, ib qho analog ntawm parathyroid hormone (PTH), feem ntau siv nws cov teebmeem los ntawm kev khi rau PTH / PTHrP receptor. Thaum khi, Teriparatid qhib cov kev taw qhia qis qis xws li cAMP/PKA txoj hauv kev thiab PLC/PKC txoj hauv kev. Ua kom txoj hauv kev no tswj hwm osteoblast thiab osteoclast muaj nuj nqi, txhawb kev tsim cov pob txha. Txoj kev cAMP/PKA txhim kho kev nthuav qhia ntawm osteoblast-txog cov noob los ntawm kev hloov pauv hloov pauv kev ua haujlwm, thaum PLC / PKC txoj hauv kev cuam tshuam cytoskeletal reorganization thiab cell motility, cuam tshuam rau osteoblast tsiv teb tsaws thiab ua haujlwm ^[2,5].

Cov ntawv thov Teriparatid yog dab tsi?

Kev Kho Mob Osteoporosis

Postmenopausal Osteoporosis: Teriparatid yog thawj tus neeg sawv cev hluavtaws anabolic pom zoo rau kev kho cov poj niam tom qab yug me nyuam nrog mob pob txha loj. Los ntawm stimulating pob txha tsim, nws ua rau cov pob txha loj, yog li txo qhov kev pheej hmoo ntawm pob txha. Hauv cov poj niam postmenopausal, kev siv teriparatide niaj hnub ua rau cov pob txha pob txha pob txha ntom ntom, txo qhov kev pheej hmoo ntawm pob txha pob txha los ntawm 65% thiab cov pob txha tsis muaj pob txha los ntawm 53% piv rau cov placebo. Ib qho kev soj ntsuam ntawm tus neeg mob-qib cov ntaub ntawv pom tau tias 56% txo qis hauv kev pheej hmoo ntawm pob txha pob txha piv rau kev tswj hwm. Tsis tas li ntawd, piv rau risedronate, Teriparatid txo qhov kev pheej hmoo ntawm cov pob txha tshiab thiab kev kho mob pob txha los ntawm 56% thiab 52%, feem, hauv cov poj niam uas muaj pob txha loj ^[3,6,7].

Txiv neej Osteoporosis: Nws kuj tau pom zoo los kho cov txiv neej osteoporosis. Quattrocchi E et al. pom tau hais tias nyob rau hauv cov txiv neej osteoporosis cov neeg mob, Teriparatid (20μg thiab 40μg txhua hnub txhaj tshuaj) ua statisticically nce nyob rau hauv lumbar qaum pob txha ntxhia pob zeb ceev: 5.9% nyob rau hauv 20μg pab pawg neeg thiab 9.0% nyob rau hauv 40μg pab pawg neeg (ob P < 0.001). Ntawm lub caj dab femoral, pob txha ceev tau nce 1.5% hauv 20μg pawg (P = 0.021) thiab 0.9% hauv pawg 40μg (P <0.001) ^[7].

Glucocorticoid-Associated Osteoporosis: Teriparatid kuj yog siv los kho cov kab mob osteoporosis ntawm cov txiv neej thiab poj niam uas muaj pob txha, pab cov neeg mob no ua rau cov pob txha loj thiab txo cov pob txha poob thiab pob txha muaj feem cuam tshuam nrog kev siv glucocorticoid ^[8].

Fracture Healing Support: Rau cov neeg mob pob txha, kev txhim kho pob txha ntawm qhov chaw pob txha yog qhov tseem ceeb rau kev kho, lub luag haujlwm teriparatide tuaj yeem ua tiav. Nws tau raug kawm nyob rau hauv ob qho tib si tsiaj qauv thiab cov neeg mob ua tus neeg sawv cev muaj peev xwm los txhim kho pob txha kho. Thaum xav tau kev tshawb fawb ntxiv, kev tshawb nrhiav uas twb muaj lawm qhia tau tias nws muaj peev xwm los txhawb kev kho pob txha ^[3].

Alveolar Bone Regeneration: Cov kev tshawb fawb cuam tshuam qhia tias Teriparatid yuav siv tau rau cov pob txha alveolar regeneration nyob rau hauv tej yam kev mob xws li jawbone necrosis, mob periodontitis, kho hniav implant osseointegration, thiab orthodontic hniav txav, qhov twg nws txhim kho pob txha alveolar tsim. Txawm li cas los xij, kev sim tshuaj rau tib neeg ntxiv yog xav tau los ua pov thawj nws daim ntawv thov thiab kev cuam tshuam tsis zoo thoob plaws ntau yam kab mob hauv qhov ncauj ^[9].

Cev xeeb tub- thiab Lactation-Related Osteoporosis: Hauv cov neeg mob uas cev xeeb tub- thiab lactation-related osteoporosis (PLO), kev kho mob nrog Teriparatid (20μg / hnub) ua ke nrog calcium thiab vitamin D tau ua rau muaj kev nce ntxiv hauv lumbar qaum pob txha pob txha pob txha ntawm 12 thiab 24 lub hlis piv rau calcium thiab vitamin. Thaum 12 lub hlis, qhov nruab nrab nce hauv lumbar pob txha pob txha pob txha pob txha yog 20.9 ± 11.9% hauv pawg teriparatide piv rau 6.2 ± 4.8% hauv pawg tswj hwm (P <0.001). Thaum 24 lub hlis, qhov nruab nrab nce hauv lumbar pob txha pob txha pob txha pob txha pob txha yog 32.9 ± 13.4% hauv 7 tus neeg mob kho Teriparatid thiab 12.2 ± 4.2% hauv 6 tus neeg mob tswj (P = 0.001). Tsis muaj kev kho mob pob txha tshiab tshwm sim thaum kho ^[10].

Cov ntawv thov tshwj xeeb: Teriparatid tau tshaj tawm hauv cov ntaub ntawv tshawb fawb txog cov pob txha tshwj xeeb, xws li hypoparathyroidism-associated osteodystrophy (ABD) nrog hypercalcemia. Ib tug poj niam uas muaj hnub nyoog 51 xyoos uas muaj kev lim ntshav-dependent tsim hypercalcemia tom qab-parathyroidectomy, tau lees paub los ntawm pob txha biopsy raws li ABD. Tom qab 12 lub hlis ntawm kev kho Teriparatid, cov ntshav cov calcium hauv cov ntshav tau zoo, sawv cev rau thawj cov ntaub ntawv ntawm Teriparatid daws ABD-txog hypercalcemia ^[11].

Xaus

Teriparatid muaj txiaj ntsig zoo rau kev mob pob txha hnyav nrog kev pheej hmoo pob txha. Nws tau qhia rau cov neeg mob uas muaj keeb kwm ntawm ntau yam pob txha pob txha, pob txha pob txha tsis tshua muaj pob txha, thiab cov lus teb tsis tshua muaj rau cov kev kho mob osteoporosis.

Hais Txog Tus Sau

Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.

Scientific Journal Author

Susan V. Bukata yog ib tug kws tshawb fawb ntawm University of Rochester Tsev Kawm Ntawv ntawm Tshuaj thiab Kho Hniav, tshwj xeeb hauv orthopedics thiab musculoskeletal kab mob. Nws tau sau ntau cov ntawv tshaj tawm tsom rau cov pob txha biology, kho pob txha, thiab kev kho mob ntawm cov tshuaj anabolic xws li teriparatide hauv kev xyaum orthopedic. Nws txoj haujlwm tau ua rau muaj kev nkag siab txog cov tswv yim kho mob txhawm rau txhim kho pob txha thiab rov tsim dua tshiab. Susan V. Bukata muaj npe nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [1].

▎ Cov Lus Qhia Tseem Ceeb

[1] Bukata SV, Puzas JE. Orthopedic siv teriparatide. Daim Ntawv Qhia Txog Osteoporosis tam sim no 2010; 8(1): 28-33.DOI: 10.1007/s11914-010-0006-3.

[2] Hasegawa T, Miyamoto Y, Yamamoto T, Amizuka N. [Anabolic kev txiav txim ntawm teriparatide rau cov neeg mob osteoporotic]. Nkauj ntseeg tawm tshiab 2019; 153(1): 16-21.DOI: 10.1254/fpj.153.16.

[3] Marin F, Ma YL. Osteoporotic Fracture thiab Systemic Skeletal Disorders: Mechanism, Assessment, and Treatment. In: Takahashi HE, Burr DB, Yamamoto N, eds. Teriparatid. Singapore: Springer Singapore; 2022: 339-359.DOI: 10.1007/978-981-16-5613-2_22.

[4] Hanley D, Adachi J, Tswb A, Brown V. Denosumab: Mechanism of action and Clinical Outcomes. International Journal of Clinical Practice 2012; 66.DOI: 10.1111/ijcp.12022.

[5] Kim S. Mechanism thiab kev ua tau zoo ntawm parathyroid hormone nyob rau hauv osteoporosis. Phau ntawv Journal of the Korean Medical Association 2022; 65: 361-365.DOI: 10.5124/jkma.2022.65.6.361.

[6] Stroup JS, Kane MP, Abu-Baker A. Teriparatid hauv kev kho mob pob txha. American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists 2008; 65 6: 532-539 . https://api.semanticscholar.org/CorpusID:207290777.

[7] Quattrocchi E, Kourlas H. Teriparatid: kev tshuaj xyuas. Clinical Therapeutics 2004; 26 6: 841-854 : kuv. https://api.semanticscholar.org/CorpusID:20011673.

[8] Minisola S, Cipriani C, Grotta GD, et al. Hloov kho ntawm kev nyab xeeb thiab kev ua tau zoo ntawm teriparatide hauv kev kho mob pob txha. Therapeutic Advances in Musculoskeletal Disease 2019; DOI: 10.1177/1759720X19877994.

[9] Agnihotri R, Gaur S. Daim ntawv thov ntawm Teriparatid rau Alveolar pob txha Regeneration: Kev Ntsuam Xyuas Txheej Txheem. Phau ntawv Journal of International Society of Preventive and Community Dentistry 2021; 11(6): 639-643.DOI: 10.4103/jispcd.JISPCD_169_21.

[10] Lampropoulou-Adamidou K, Trovas G, Triantafyllopoulos IK, et al. Kev kho teriparatid hauv cov neeg mob uas cev xeeb tub- thiab lactation-Associated Osteoporosis. Calcified Tissue International 2021; 109(5): 554-562.DOI: 10.1007/s00223-021-00871-y.

[11] Peugh J, Khalil A, Chan MR, Hansen KE. Teriparatid Kev Kho Mob rau Hypercalcemia Associated With Adynamic Bone Disease. Jbmr Plus 2019; 3(7): e10176.DOI: 10.1002/jbm4.10176.

Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.  

Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.