Teriparatid 750mg

▎ ebiyitibwa Teriparatid Enzimba y’ebiwuka

▎ ebiyitibwa Teriparatid Okunoonyereza ku bimera

Ennyonyola ya Teriparatid eri etya?

Teriparatid ye recombinant human parathyroid hormone (PTH) analog ekoleddwa mu amino acids 34 ezisooka eza human parathyroid hormone. Kitereeza enkyukakyuka y’amagumba nga kikoppa ebikolwa by’omubiri eby’obusimu obuyitibwa endogenous parathyroid hormone. Teriparatid lye ddagala erisooka erya synthetic anabolic drug erikkirizibwa okujjanjaba obulwadde bw’amagumba obw’amaanyi. Ensengekera yaayo eraga enkolagana ey’amaanyi ne PTH ey’omunda, okusobozesa okukola kw’ekirungo kya PTH okukyusa emirimu gy’okukyusakyusa amagumba.

Enkola ki ey’okukola ku Teriparatid?

Ebikosa osteoblasts:

Atumbula okukula kw’amagumba: Teriparatid asitula okukula kw’obutoffaali obusookerwako mu magumba, n’eyongera ku muwendo gw’amagumba. Mu kunoonyereza ku bisolo, okugaba teriparatide mu biseera ebitali bimu kyanguya nnyo okukula kw’obutoffaali obusibuka mu mesenchymal obusobola okwawukana mu osteoblasts mu busimu bw’amagumba. Kino kyasobozesa obutoffaali obusingawo okwawukana ne bufuuka osteoblasts ezikuze, ne kiwa obutoffaali bungi okusobola okukola amagumba. Okugezesa okukuza obutoffaali mu vitro kwalaga nti omuwendo gw’okugabanya kw’obutoffaali obusookerwako obw’amagumba mu kibinja ekyajjanjabwa Teriparatid gwali waggulu nnyo okusinga mu kibinja ekifuga, ekiraga nti Teriparatid etumbula butereevu okukula kw’obutoffaali obusookerwako obw’amagumba ^[1,2]..

Enhanced Osteoblast Activity: Teriparatid tekoma ku kwongera ku muwendo gwa osteoblast wabula era esitula emirimu gyazo. Kisitula okwolesebwa kw’obuzaale obukwatagana n’okusengejja amagumba mu magumba mu bitundu by’amagumba, gamba ng’ebyo ebiwandiika ekika kya I kolagini ne osteocalcin, ebiraga okweyongera ennyo mu miwendo gy’okwolesebwa. Ekika kya I kolagini, ekitundu ekikulu eky’ebiramu mu matrix y’amagumba, kiyamba mu kutondekawo enkola ya matrix enywevu ennyo okuyita mu kweyongera kw’okusengejja. Osteocalcin ekola kinene nnyo mu kukola eby’obuggagga bw’amagumba nga etumbula okuteekebwa kw’amasannyalaze ga calcium ion munda mu matrix, bwe kityo n’eyongera ku mineralization y’amagumba. Okuyita mu nkola zino, osteoblasts zigatta era ne zifulumya matrix y’amagumba mu ngeri ennungi, ne ziyamba okutondebwa kw’amagumba amapya ^[2,3]..

Okuziyiza okufa kw’amagumba: Mu mbeera z’omubiri eza bulijjo, obutoffaali bw’amagumba buyita mu kufa oluvannyuma lw’okumaliriza emirimu egy’enjawulo egy’okukola amagumba. Teriparatid enyigiriza enkola eno ey’okufa, n’eyongera ku bulamu bw’obutoffaali bw’amagumba. Teriparatid ekola amakubo agakwatagana ag’obubonero bw’obutoffaali, gamba ng’ekkubo lya PI3K/Akt. Nga kikola, ekkubo lino linyigiriza okwolesebwa kwa puloteyina ezikwatagana n’okufa, okusobozesa osteoblasts okuyimirizaawo emirimu gyazo egy’okukola amagumba n’okukuuma okugenda mu maaso n’okutebenkera kw’okutondebwa kw’amagumba ^[1,3]..

Ebikosa Osteoclasts: Ebikosa Teriparatid ku osteoclasts bizibu. Mu kiseera ky’okugaba dose ezitali zimu, kikwata ku bitundu ebizimba amagumba okuyita mu nkola ezitali butereevu. Kitumbula okufulumya osteoblast osteoprotegerin (OPG), cytokine eyesibye mu kuvuganya ku receptor activator ya nuclear factor κB ligand (RANKL). RANKL ye regulator enkulu ey’enjawulo y’amagumba n’okukola. OPG bw’esiba ku RANKL, RANKL tesobola kwesiba ku RANK receptor ku ngulu w’obutoffaali obusookerwako obw’amagumba, bwe kityo n’eziyiza okwawukana n’okukula kw’amagumba n’okukendeeza ku kuddamu kw’amagumba. Mu balwadde b’amagumba, ng’okuddamu kw’amagumba kusukka okutondebwa ekivaako okufiirwa amagumba, teriparatide ekendeeza ku mirimu gy’amagumba okuyita mu nkola eno. Kino kizzaawo bbalansi wakati w’okuddamu okunyiga n’okutondebwa, ne kitumbula okugaggawala kw’amagumba ^[2,3]..

Ekifaananyi 1 Ebifo ebikolebwamu obujjanjabi bw’obulwadde bw’amagumba obw’olunyiriri olusooka. Teriparatid, ekitundu ekigatta obusimu bwa parathyroid, kisitula okutondebwa kw’amagumba nga kyongera ku mirimu gy’amagumba era, ku kigero ekitono, kiziyiza okuwandiika kw’amagumba ^[4]..

Okukyusakyusa amakubo g’obubonero agakwatagana n’enkyukakyuka y’amagumba:

Wnt/β-Catenin Signaling Pathway: Ekkubo ly’obubonero bwa Wnt/β-catenin likola kinene nnyo mu nkula y’amagumba n’okukuuma homeostasis y’amagumba. Teriparatid ekola ekkubo lino, n’etumbula okukuŋŋaanyizibwa mu butoffaali n’okukyusakyusa kwa nyukiliya kwa β-catenin. Nuclear β-catenin yeekwata ku nsonga z’okuwandiika ezikwatagana, n’etandika okuwandiika obuzaale obukwatagana n’okutondebwa kw’amagumba n’okutumbula okwolesebwa kw’ensonga y’okuwandiika eya osteoblast-specific transcription factor Runx2. Runx2 eyongera okulungamya okwawukana n’enkola y’amagumba, bwe kityo n’etumbula okutondebwa kw’amagumba. Okukola ekkubo lino era kuziyiza okwawukana kw’amagumba okutuuka ku adipocytes, okukakasa okwawukana okunene okw’obutoffaali bw’amagumba obuyitibwa mesenchymal stem cells okutuuka ku lunyiriri lw’amagumba, bwe kityo ne kyongera ku bunene bw’amagumba ^[1,3]..

PTH/PTHrP Receptor Signaling Pathway: Teriparatid, analog of parathyroid hormone (PTH), okusinga ekola ebikolwa byayo nga yeesibye ku PTH/PTHrP receptor. Ku kusiba, Teriparatid ekola amakubo g’obubonero wansi nga ekkubo lya cAMP/PKA n’ekkubo lya PLC/PKC. Okukola kw’amakubo gano kutereeza enkola y’amagumba n’amagumba, ne kitumbula okutondebwa kw’amagumba. Ekkubo lya cAMP/PKA lyongera okwolesebwa kw’obuzaale obukwatagana n’amagumba nga likyusakyusa emirimu gy’ensonga y’okuwandiika, ate ekkubo lya PLC/PKC likwata ku kuddamu okutegeka amagumba n’okutambula kw’obutoffaali, ne likosa okutambula kw’amagumba n’enkola ^[2,5]..

Ebikozesebwa bya Teriparatid bye biruwa?

Obujjanjabi bw’obulwadde bw’amagumba

Obulwadde bw’amagumba oluvannyuma lw’okuggwaamu amaanyi: Teriparatid ye ddagala erisooka erya synthetic anabolic agent eryakkirizibwa okujjanjaba abakyala abava mu nsonga abalina obulwadde bw’amagumba obw’amaanyi. Nga kisitula okutondebwa kw’amagumba, kyongera ku bunene bw’amagumba, bwe kityo ne kikendeeza ku bulabe bw’okumenya. Mu bakyala abava mu nsonga, okukozesa teriparatide buli lunaku kwongera ku bungi bw’amagumba, ekikendeeza ku bulabe bw’okumenya omugongo ebitundu 65% n’okumenya okumenya omugongo okutali kwa maanyi ebitundu 53% bw’ogeraageranya ne placebo. Okwekenenya (meta-analysis of individual patient-level data) kwalaga okukendeera kwa 56% mu bulabe bw’okumenya ekisambi bw’ogeraageranya n’abafuga. Ekirala, bw’ogeraageranya ne risedronate, Teriparatid yakendeeza ku bulabe bw’okumenya omugongo omupya n’okumenya mu bujjanjabi ebitundu 56% ne 52%, mu bakyala abalina obulwadde bw’amagumba obw’amaanyi ^[3,6,7]..

Obulwadde bw’amagumba bw’abasajja: Bukkirizibwa n’okujjanjaba obulwadde bw’amagumba bw’abasajja. Quattrocchi E ne banne. yalaga nti mu balwadde b’amagumba abasajja, Teriparatid (empiso 20μg ne 40μg buli lunaku) yaleeta okweyongera okw’amaanyi mu bibalo mu density y’amagumba g’omugongo ogw’omugongo: 5.9% mu kibinja kya 20μg ne 9.0% mu kibinja kya 40μg (bombi P < 0.001). Ku bulago bw’ekisambi, density y’amagumba yeeyongera ebitundu 1.5% mu kibinja kya 20μg (P = 0.021) ne 0.9% mu kibinja kya 40μg (P < 0.001) ^[7]..

Glucocorticoid-Associated Osteoporosis: Teriparatid era ekozesebwa okujjanjaba obulwadde bw’amagumba obuva ku glucocorticoid mu balwadde abasajja n’abakazi abamenyese, okuyamba abalwadde bano okwongera ku bunene bw’amagumba n’okukendeeza ku kufiirwa amagumba n’obulabe bw’okumenya obukwatagana n’okukozesa glucocorticoid ^[8]..

Obuwagizi mu kuwonya okumenya: Ku balwadde abamenyese, okwongera okutondebwa kw’amagumba okumala akaseera katono mu kifo we bamenyese kikulu nnyo mu kuddaabiriza, omulimu teriparatide gw’esobola okutuukiriza. Kibadde kinoonyezebwa mu bikolwa by’ebisolo n’abalwadde ng’ekiyinza okutumbula okuwona kw’okumenya. Wadde nga kyetaagisa okwongera okunoonyereza, okunoonyereza okuliwo kulaga obusobozi bwayo mu kutumbula okuwona kw’okumenya ^[3]..

Okuzzaawo amagumba g’omu nnyindo: Okunoonyereza okukwatagana kulaga nti Teriparatid eyinza okukozesebwa mu kuzzaawo amagumba g’amagumba mu mbeera nga okufa kw’amagumba g’amagumba, obulwadde bw’amagumba obutawona, okugatta amagumba g’amannyo agateekebwamu amannyo, n’okutambula kw’amannyo mu kulongoosa amannyo, gy’eyongera okutondebwa kw’amagumba g’amagumba. Wabula, okugezesebwa okulala okw’obujjanjabi kw’abantu kwetaagibwa okukakasa okukozesebwa kwayo n’ebizibu ebivaamu mu ndwadde ez’enjawulo ez’amagumba g’omu kamwa ^[9]..

Obulwadde bw’amagumba obukwatagana n’olubuto n’okuyonsa: Mu balwadde abalina obulwadde bw’amagumba obuva ku lubuto n’okuyonsa (PLO), okujjanjabwa ne Teriparatid (20μg/day) nga kugatta wamu ne kalisiyamu ne vitamiini D kyavaamu okweyongera ennyo mu bungi bw’amagumba g’omugongo mu myezi 12 ne 24 bw’ogeraageranya ne kalisiyamu ne vitamiini D yokka. Ku myezi 12, okweyongera kwa wakati mu lumbar spine bone mineral density kwali 20.9 ± 11.9% mu kibinja kya teriparatide okusinziira ku 6.2 ± 4.8% mu kibinja ekifuga (P < 0.001). Ku myezi 24, okweyongera kwa wakati mu lumbar spine bone mineral density kwali 32.9 ± 13.4% mu balwadde 7 abajjanjabwa ne Teriparatid ne 12.2 ± 4.2% mu balwadde 6 abafuga (P = 0.001). Tewali kumenya kwa bujjanjabi kupya kwaliwo mu kiseera ky’obujjanjabi ^[10]..

Okukozesebwa okw’enjawulo: Teriparatid ebadde etegeezebwa mu kunoonyereza ku mbeera z’amagumba ezenjawulo, gamba nga hypoparathyroidism-associated osteodystrophy (ABD) n’obulwadde bwa hypercalcemia. Omukyala ow’emyaka 51 eyeesigama ku dialysis yafuna hypercalcemia post-parathyroidectomy, ekyakakasibwa okukebera amagumba nti ABD. Oluvannyuma lw’emyezi 12 egy’obujjanjabi bwa Teriparatid, emiwendo gya calcium mu musaayi gyatuuka mu mbeera eya bulijjo, ekikiikirira omusango ogwasooka ogwawandiikibwa ogwa Teriparatid okugonjoola obulwadde bwa ABD-related hypercalcemia ^[11]..

Mu bufunzi

Teriparatid ekola bulungi ku bulwadde bw’amagumba obw’amaanyi nga bulina akabi ak’okumenya. Kilagibwa eri abalwadde abalina ebyafaayo by’okumenya amagumba emirundi mingi, abalina eby’obugagga by’amagumba ebitono ennyo, n’okuddamu okutono ku bujjanjabi obw’amagumba obwa bulijjo.

Ebikwata ku Muwandiisi

Ebintu ebyogeddwako waggulu byonna binoonyerezeddwako, birongooseddwa era ne bikung’aanyizibwa kkampuni ya Cocer Peptides.

Omuwandiisi wa Scientific Journal

Susan V. Bukata munoonyereza mu yunivasite y’e Rochester School of Medicine and Dentistry, ng’akuguse mu by’amagumba n’endwadde z’ebinywa n’amagumba. Abadde omu ku bawandiisi ebitabo bingi ebissa essira ku biramu by’amagumba, okuwonya okumenya, n’okukozesa eddagala eriweweeza ku bulwadde nga teriparatide mu nkola y’amagumba. Omulimu gwe guyambye okutegeera enkola z’obujjanjabi ez’okutumbula okuddaabiriza n’okuzza obuggya amagumba. Susan V. Bukata awandiikiddwa mu kiwandiiko ekijuliziddwa [1].

▎ Ebiwandiiko Ebikwatagana

[1] Bukata S. V., Puzas J. E., ne bannaabwe. Enkozesa y’amagumba eya teriparatide. Alipoota z’obulwadde bw’amagumba mu kiseera kino 2010; 8(1): 28-33.DOI: 10.1007/s11914-010-0006-3.

[2] Hasegawa T, Miyamoto Y, Yamamoto T, Amizuka N. [Ekikolwa kya anabolic ekya teriparatide eri abalwadde b’amagumba]. Nihon Yakurigaku Zasshi 2019, omuyimbi wa Uganda. 153(1): 16-21.DOI: 10.1254/fpj.153.16.

[3] Marin F, Ma YL, era nga bano. Osteoporotic Fracture and Systemic Skeletal Disorders: Enkola, Okukebera, n’Obujjanjabi. Mu: Takahashi H. E., Burr D. B., Yamamoto N, abawandiisi. Ebiwuka ebiyitibwa Teriparatid. Singapore: Springer Singapore, Omuwandiisi w’ebitabo; 2022: 339-359.DOI: 10.1007/978-981-16-5613-2_22.

[4] Hanley D, Adachi J, Bell A, Brown V. Denosumab: Enkola y’okukola n’ebiva mu bujjanjabi. Ekitabo ky’ensi yonna eky’enkola y’obujjanjabi 2012; 66.DOI: 10.1111/ijcp.12022.

[5] Kim S. Enkola n’obulungi bw’obusimu bwa parathyroid mu bulwadde bw’amagumba. Journal of ekibiina ekigatta abasawo mu Korea 2022; 65: 361-365.DOI: 10.5124/jkma.2022.65.6.361.

[6] Stroup JS, Kane MP, Abu-Baker A. Teriparatid mu kujjanjaba obulwadde bw’amagumba. American Journal of Health-System Pharmacy : Ajhp : Ekitabo ekitongole eky’ekibiina ky’Amerika eky’abakugu mu by’eddagala mu nkola y’ebyobulamu 2008; 65 6: 532-539. https://api.semanticscholar.org/CorpusID:207290777. Enkola y’okukuuma obutonde bw’ensi.

[7] Quattrocchi E, Kourlas H. Ebiwuka ebiyitibwa Teriparatid: okwekenneenya. Enzijanjaba y’obujjanjabi 2004; 26 6: 841-854. https://api.semanticscholar.org/CorpusID:20011673. Enkola y’okutumbula eby’obulamu mu ggwanga.

[8] Minisola S, Cipriani C, Grotta GD, n’abalala. Ebipya ku bulamu n’obulungi bwa teriparatide mu kujjanjaba obulwadde bw’amagumba. Enkulaakulana mu bujjanjabi mu bulwadde bw’ebinywa n’amagumba 2019;DOI: 10.1177/1759720X19877994.

[9] Agnihotri R, Gaur S. Enkozesa ya Teriparatid mu kuzzaawo amagumba g’omu nnyindo: Okuddamu okwetegereza okutegekeddwa. Journal of International Society of Okuziyiza n’okujjanjaba amannyo mu kitundu 2021; 11 (6): 639-643.DOI: 10.4103 / jispcd.JISPCD_169_21.

[10] Lampropoulou-Adamidou K, Trovas G, Triantafyllopoulos I. K., n’abalala. Obujjanjabi bwa Teriparatid mu balwadde abalina obulwadde bw’amagumba obukwatagana n’olubuto n’okuyonsa. Ebitundu ebiyitibwa Calcified Tissue International 2021; 109(5): 554-562.DOI: 10.1007/s00223-021-00871-y.

[11] Peugh J, Khalil A, Chan M. R., Hansen KE., ne bannaabwe abalala. Obujjanjabi bwa Teriparatid ku Hypercalcemia ekwatagana n’obulwadde bw’amagumba obutakyukakyuka. Jbmr Plus 2019; 3(7): e10176.DOI: 10.1002/jbm4.10176.

EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA BYOKKA.  

Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu kisenge (in vitro research) (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.