Teriparatid 750 mg

▎ Teriparatid Ọdịdị

▎ Teriparatid Nchọpụta

Gịnị bụ nkọwa nke Teriparatid?

Teriparatid bụ homonụ parathyroid mmadụ recombinant (PTH) nke mejupụtara amino acid 34 mbụ nke homonụ parathyroid mmadụ. Ọ na-achịkwa metabolism nke ọkpụkpụ site na iṅomi omume physiological nke hormone parathyroid endogenous. Teriparatid bụ ọgwụ anabolic sịntetị nke mbụ akwadoro maka osteoporosis siri ike. Ọdịdị ya na-egosipụta homology dị elu na PTH endogenous, na-eme ka onye na-anabata PTH rụọ ọrụ iji gbanwee ọrụ metabolic osteoclast.

Kedu ihe bụ usoro ọgwụgwọ maka Teriparatid?

Mmetụta na osteoblasts:

Na-akwalite mgbasawanye osteoblast: Teriparatid na-akpali mgbasa nke osteoblasst precursor cell, na-amụba ọnụ ọgụgụ osteoblast. N'ime ọmụmụ anụmanụ, nchịkwa na-adịte aka nke teriparatide mere ka mmụba nke mkpụrụ ndụ sel mesenchymal nwere ike ịdị iche na osteoblasts na ụmị ọkpụkpụ. Nke a mere ka ọtụtụ mkpụrụ ndụ nwee ike ịmata ọdịiche dị n'ime osteoblasts tozuru okè, na-enye oke cellular maka nhazi ọkpụkpụ. Nnwale ọdịnala nke mkpụrụ ndụ in vitro gosipụtara na ọnụego nkewa nke mkpụrụ ndụ precursor osteoblast na otu Teriparatid a na-agwọ dị elu nke ukwuu karịa na otu njikwa, na-egosi na Teriparatid na-akwalite mgbasa nke sel osteoblast precursor ^[1,2]..

Ọrụ Osteoblast emelitere: Teriparatid abụghị naanị na-abawanye ọnụọgụ osteoblast kamakwa na-ebuli ọrụ ha elu. Ọ na-edozi okwu nke mkpụrụ ndụ ihe nketa jikọtara ya na njikọ nke matrix ọkpụkpụ na osteoblasts, dị ka ụdị ntinye koodu nke m collagen na osteocalcin, nke na-egosi mmụba nke ọkwa okwu. Ụdị m collagen, bụ isi ihe na-emepụta ihe na-emepụta ihe nke ọkpụkpụ ọkpụkpụ, na-enye aka n'ịmepụta usoro matrix siri ike karị site na ụbara njikọ. Osteocalcin na-arụ ọrụ dị mkpa n'ịmepụta ọkpụkpụ site n'ịkwalite ntinye calcium ion n'ime matriks, si otú ahụ na-eme ka ọkpụkpụ ọkpụkpụ dịkwuo elu. Site na usoro ndị a, osteoblasts na-emepụta ma na-ezobe matrix ọkpụkpụ nke ọma, na-eme ka ọkpụkpụ ọhụrụ dị ọhụrụ ^[2,3]..

Mgbochi nke osteocyte apoptosis: N'okpuru ọnọdụ physiological nkịtị, osteocytes na-enweta apoptosis mgbe ha rụchara ọrụ nhazi ọkpụkpụ. Teriparatid na-egbochi usoro apoptotic a, na-agbatị ndụ osteocyte ogologo. Teriparatid na-eme ka ụzọ mgbaàmà ekwentị dị mkpa, dị ka ụzọ PI3K/Akt. Mgbe a na-arụ ọrụ, ụzọ a na-egbochi nkwupụta nke protein ndị metụtara apoptosis, na-enyere osteoblasts aka ịkwado ọrụ ọkpụkpụ ha ma nọgide na-aga n'ihu na nkwụsi ike nke ọkpụkpụ ọkpụkpụ ^[1,3]..

Mmetụta na Osteoclasts: Mmetụta Teriparatid na osteoclasts dị mgbagwoju anya. N'oge doses na-adịte aka, ọ na-emetụta osteoclasts site na usoro na-apụtaghị ìhè. Ọ na-akwalite nzuzo osteoblast nke osteoprotegerin (OPG), cytokine nke na-ejikọta ya na onye na-anabata ihe na-eme ihe nuklia κB ligand (RANKL). RANKL bụ isi ihe na-achịkwa ọdịiche osteoclast na ịgbalite. Mgbe OPG jikọtara ya na RANKL, RANKL enweghị ike ijikọ na onye na-anabata RANK n'elu sel osteoclast precursor, si otú a na-egbochi ọdịiche osteoclast na maturation na ibelata resorption ọkpụkpụ. N'ime ndị ọrịa osteoporosis, ebe resorption ọkpụkpụ karịrị nhazi nke na-eduga n'ọkpụkpụ ọkpụkpụ, teriparatide na-ebelata ọrụ osteoclast site na usoro a. Nke a na-eweghachi nguzozi n'etiti resorption na nhazi, na-akwalite uru ọkpụkpụ ^[2,3].

Ọgụgụ 1 Ebe a na-eme ihe maka ọgwụgwọ osteoporosis nke mbụ. Teriparatid, akụkụ recombinant nke hormone parathyroid, na-akpali ọkpụkpụ site n'ịbawanye ọrụ osteoblast na, n'ókè dị nta, na-egbochi ọrụ osteoclast ^[4]..

Mgbanwe nke ụzọ mgbama metụtara metabolism nke ọkpụkpụ:

Ụzọ nrịbama Wnt / β-Catenin: Ụzọ akara Wnt / β-catenin na-arụ ọrụ dị mkpa na mmepe ọkpụkpụ na nhazi nke homeostasis ọkpụkpụ. Teriparatid na-eme ka ụzọ a rụọ ọrụ, na-akwalite mkpokọta intracellular na ntụgharị nuklia nke β-catenin. Nuclear β-catenin na-ejikọta ya na ihe odide ederede, na-amalite nsụgharị nke mkpụrụ ndụ ihe nketa metụtara ọkpụkpụ na ịkwalite nkwupụta nke osteoblast-specific transcription factor Runx2. Runx2 na-achịkwa ọdịiche na ọrụ osteoblast, si otú ahụ na-akwalite nhazi ọkpụkpụ. Ịgbalite ụzọ a na-egbochikwa ọdịiche osteoblast n'ebe adipocytes nọ, na-eme ka ọdịiche dị ukwuu nke ụmị ọkpụkpụ mesenchymal sel na-aga n'usoro osteoblast, si otú ahụ na-amụba ọkpụkpụ ^[1,3]..

Ụzọ nrịbama nke PTH/PTHrP: Teriparatid, ihe analog nke hormone parathyroid (PTH), na-arụ ọrụ ya site na ijikọta onye na-anabata PTH/PTHrP. Mgbe ejikọtara ya, Teriparatid na-arụ ọrụ ụzọ mgbaama mgbada dị ka ụzọ cAMP/PKA na ụzọ PLC/PKC. Ịkwalite ụzọ ndị a na-achịkwa osteoblast na ọrụ osteoclast, na-akwalite nhazi ọkpụkpụ. Ụzọ cAMP/PKA na-akwalite nkwupụta nke mkpụrụ ndụ ihe nketa metụtara osteoblast site n'ịgbanwe ọrụ ihe odide ederede, ebe ụzọ PLC/PKC na-emetụta nhazigharị cytoskeletal na motility cell, na-emetụta njem na ọrụ osteoblast ^[2,5].

Kedu ihe bụ ngwa Teriparatid?

Ọgwụgwọ Osteoporosis

Osteoporosis postmenopausal: Teriparatid bụ onye na-ahụ maka anabolic synthetic nke mbụ kwadoro maka ịgwọ ụmụ nwanyị postmenopausal nwere osteoporosis siri ike. Site n'ịkwalite ọkpụkpụ ọkpụkpụ, ọ na-abawanye ọkpụkpụ ọkpụkpụ, si otú a na-ebelata ihe ize ndụ mgbaji. N'ime ụmụ nwanyị postmenopausal, iji teriparatide kwa ụbọchị na-abawanye njupụta ịnweta ọkpụkpụ, na-ebelata ihe ize ndụ nke ọkpụkpụ vertebral site na 65% na fragility fragility na-abụghị vertebral site na 53% ma e jiri ya tụnyere placebo. Nnyocha meta nke data ọkwa onye ọrịa gosipụtara mbelata 56% na ihe egwu mgbaji hip ma e jiri ya tụnyere njikwa. Ọzọkwa, ma e jiri ya tụnyere risedronate, Teriparatid belatara ohere nke mgbaji vertebral ọhụrụ na ụlọ ọgwụ site na 56% na 52%, n'otu n'otu, n'ime ụmụ nwanyị nwere osteoporosis siri ike ^[3,6,7]..

Osteoporosis nwoke: A kwadoro ya maka ịgwọ ọkpụkpụ ọkpụkpụ nwoke. Quattrocchi E et al. gosipụtara na n'ime ndị ọrịa osteoporosis nwoke, Teriparatid (20μg na 40μg injections kwa ụbọchị) na-emepụta mmụba dị ịrịba ama na njupụta ịnweta ọkpụkpụ lumbar: 5.9% na 20μg otu na 9.0% na 40μg otu (ma P <0.001). N'olu femoral, njupụta ọkpụkpụ mụbara site na 1.5% na otu 20μg (P = 0.021) na site na 0.9% na otu 40μg (P <0.001) ^[7].

Glucocorticoid-Associated Osteoporosis: A na-ejikwa Teriparatid na-agwọ ọrịa osteoporosis nke glucocorticoid na ndị nwoke na ndị nwanyị nwere mgbawa, na-enyere ndị ọrịa a aka ịbawanye ọkpụkpụ ọkpụkpụ ma belata ọkpụkpụ ọkpụkpụ na ihe ize ndụ nke na-ejikọta na glucocorticoid iji ^[8]..

Nkwado ọgwụgwọ mgbaji agbaji: Maka ndị ọrịa gbajiri agbaji, ọkpụkpụ na-abawanye n'oge na-adịghị anya na saịtị mgbawa dị oke mkpa maka ịrụzi ọrụ, ọrụ teriparatide nwere ike ịrụzu. A mụọla ya n'ụdị anụmanụ na ndị ọrịa dịka onye nwere ike ime ka ọgwụgwọ mgbaji dị elu. Ọ bụ ezie na achọrọ nyocha ọzọ, nyocha ndị dị adị na-egosipụta ikike ọ nwere n'ịkwalite ọgwụgwọ mgbaji ^[3].

Ọkpụkpụ ọkpụkpụ Alveolar: Nnyocha ndị metụtara ya na-egosi na Teriparatid nwere ike ịdị na-emetụta maka ọkpụkpụ ọkpụkpụ alveolar na ọnọdụ ndị dị ka necrosis agba agba, periodontitis na-adịghị ala ala, osseointegration nke eze na-etinye eze, na ọkpụkpụ ezé nke orthodontic, ebe ọ na-eme ka ọkpụkpụ alveolar dịkwuo elu. Otú ọ dị, a ga-achọkwu ule ụlọ ọgwụ mmadụ iji kwado ngwa ya na mmetụta ọjọọ n'ofe ọrịa ọkpụkpụ dị iche iche ^[9].

Osteoporosis metụtara ime ime na ịmụ nwa: Na ndị ọrịa nwere afọ ime na osteoporosis metụtara lactation (PLO), ọgwụgwọ na Teriparatid (20μg / ụbọchị) jikọtara ya na calcium na vitamin D mere ka mmụba dị ukwuu na njupụta ịnweta ọkpụkpụ lumbar na 12 na 24 ọnwa tụnyere calcium na vitamin D naanị. Na ọnwa 12, mmụba pụtara na njupụta ịnweta ọkpụkpụ lumbar bụ 20.9 ± 11.9% na otu teriparatide na 6.2 ± 4.8% na otu njikwa (P <0.001). Na ọnwa 24, mmụba pụtara na njupụta ịnweta ọkpụkpụ lumbar bụ 32.9 ± 13.4% na ndị ọrịa 7 na-emeso Teriparatid na 12.2 ± 4.2% na ndị ọrịa nchịkwa 6 (P = 0.001). Ọ nweghị mgbawa ụlọ ọgwụ ọhụrụ mere n'oge ọgwụgwọ ^[10].

Ngwa pụrụ iche: A kọwala Teriparatid n'ọmụmụ ihe gbasara ọrịa ọkpụkpụ, dị ka hypoparathyroidism metụtara osteodystrophy (ABD) na hypercalcemia. Otu nwanyị dị afọ 51 na-adabere na dialysis mepụtara hypercalcemia post-parathyroidectomy, nke ọkpụkpụ biopsy kwadoro dị ka ABD. Mgbe ọnwa 12 nke ọgwụgwọ Teriparatid gasịrị, ọkwa calcium serum na-edozi, na-anọchite anya ikpe mbụ edere nke Teriparatid na-edozi hypercalcemia metụtara ABD ^[11]..

Mmechi

Teriparatid dị irè maka osteoporosis siri ike nke nwere nnukwu ihe egwu mgbaji. A na-egosi ya maka ndị ọrịa nwere akụkọ ihe mere eme nke ọtụtụ mgbaji ọkpụkpụ osteoporotic, njupụta ịnweta ọkpụkpụ dị oke ala, yana nzaghachi dị nta maka ọgwụgwọ ọkpụkpụ ọkpụkpụ.

Banyere Onye dere ya

Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.

Onye ode akwụkwọ akụkọ sayensị

Susan V. Bukata bụ onye nyocha na Mahadum Rochester School of Medicine and Dentistry, ọkachamara na orthopedics na ọrịa anụ ahụ. O meela ọtụtụ akwụkwọ na-elekwasị anya na usoro ihe ọmụmụ ọkpụkpụ, ọgwụgwọ mgbaji, na ngwa ụlọ ọgwụ nke ndị ọrụ anabolic dị ka teriparatide na orthopedic omume. Ọrụ ya enyela aka n'ịghọta usoro ọgwụgwọ maka ịkwalite nrụzi ọkpụkpụ na ịmaliteghachi. Susan V. Bukata depụtara n'akwụkwọ ntụaka [1].

▎ Okwu ndị dị mkpa

[1] Bukata SV, Puzas JE. Orthopedic eji teriparatide eme ihe. Akụkọ Osteoporosis dị ugbu a 2010; 8(1): 28-33.DOI: 10.1007/s11914-010-0006-3.

[2] Hasegawa T, Miyamoto Y, Yamamoto T, Amizuka N. [Arụ ọrụ anabolic nke teriparatide nye ndị ọrịa osteoporotic]. Nihon Yakurigaku Zasshi 2019; 153(1): 16-21.DOI: 10.1254/fpj.153.16.

[3] Marin F, Ma YL. Ọkpụkpụ Osteoporotic na Ọgbaghara Skeletal System: Mechanism, Ntụle, na Ọgwụgwọ. Na: 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, Bell A, Brown V. Denosumab: Usoro nke ime ihe na nsonaazụ ụlọ ọgwụ. Akwụkwọ akụkọ International nke Clinical Practice 2012; 66.DOI: 10.1111/ijcp.12022.

[5] Kim S. Mechanism na nrụpụta nke homonụ parathyroid na osteoporosis. Akwụkwọ akụkọ nke Òtù Ahụ Ike Korea 2022; 65: 361-365.DOI: 10.5124/jkma.2022.65.6.361.

[6] Stroup JS, Kane MP, Abu-Baker A. Teriparatid na ọgwụgwọ osteoporosis. American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists 2008; 65 6: 532-539 . https://api.semanticcholar.org/CorpusID:207290777.

[7] Quattrocchi E, Kourlas H. Teriparatid: nyocha. Clinical Therapeutics 2004; 26 6: 841-854. https://api.semanticcholar.org/CorpusID:20011673.

[8] Minisola S, Cipriani C, Grotta GD, et al. Mmelite na nchekwa na ịdị irè nke teriparatide na ọgwụgwọ osteoporosis. Ọganihu ọgwụgwọ na Ọrịa Musculoskeletal 2019; DOI: 10.1177/1759720X19877994.

[9] Agnihotri R, Gaur S. Ngwa nke Teriparatid maka Mweghachi Ọkpụkpụ Alveolar: Nyochaa Usoro. Akwụkwọ akụkọ nke International Society of Preventive and Community Dentistry 2021; 11 (6): 639-643.DOI: 10.4103/jispcd.JISPCD_169_21.

[10] Lampropulou-Adamidou K, Trovas G, Triantafyllopoulos IK, et al. Ọgwụgwọ Teriparatid na ndị ọrịa nwere ime ime na 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. Ọgwụgwọ Teriparatid maka Hypercalcemia jikọtara ya na Ọrịa Ọkpụkpụ Adynamic. Jbmr gbakwunyere 2019; 3(7): e10176.DOI: 10.1002/jbm4.10176.

Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.  

Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.