Abaloparatide 3 mg

▎ Abaloparatide Structure

▎ Abaloparatide Nyocha

Kedu ihe ndabere nyocha nke abaloparatide?

Osteoporosis bụ ọrịa skeletal sistemu nke ọtụtụ ihe na-emekarị nke ọkpụkpụ ọkpụkpụ dị ala na mmebi microarchitectural nke ọkpụkpụ ọkpụkpụ. Nke a na-eduga n'ịba ụba nke ọkpụkpụ na ike ịdaba na mgbaji, na mgbaji úkwù na ọkpụkpụ azụ bụ ihe a na-emekarị. Ọ na-emetụta ndụ ndị ọrịa nke ukwuu ma na-abawanye nkwarụ na ọnụ ọgụgụ ọnwụ. Site na ọnụ ọgụgụ ndị na-eme agadi n'ụwa na-arị elu, ọnụ ọgụgụ osteoporosis na-aga n'ihu na-arị elu. A na-eme atụmatụ na 42%-56% nke ụmụ nwanyị na 27%-29% nke ndị ikom karịrị afọ 50 ga-enweta mgbaji ọkpụkpụ osteoporotic, na-eme ka ọ bụrụ nsogbu ahụike ọha na eze ngwa ngwa. Ọgwụgwọ osteoporosis ọdịnala, dị ka bisphosphonates na nhọrọ ndị na-anabata estrogen receptor modulators (SERMs), bụ isi na-edobe njupụta nke ọkpụkpụ site n'igbochi ọkpụkpụ osteoclast-mediated resorption. Otú ọ dị, arụmọrụ ha dị oke maka ndị ọrịa nwere oke ọkpụkpụ na-ebelata nke ukwuu na ihe ize ndụ mgbaji. Ọ bụ ezie na parathyroid hormone (PTH) 1-34 iberibe (teriparatide) bụ onye ọrụ anabolic mbụ kwadoro site na US Food and Drug Administration (FDA), na-amụba njupụta ọkpụkpụ n'ụzọ dị irè ma na-ebelata ihe ize ndụ mgbaji, iji ya ogologo oge na-ebu njedebe gụnyere mmụba ọkpụkpụ, hypercalcemia, na ihe ize ndụ dị ukwuu nke osteosarcoma.

N'ime ihe ndabere a, ịmepụta ọgwụ ọhụrụ na-ejikọta mmetụta anabolic dị ike ma na-ezere ihe ndọghachi azụ ndị a dị mkpa. Dị ka peptide hormone metụtara parathyroid (PTHrP), abaloparatide na-ejigide ọrụ anabolic siri ike ma na-ebelata mmetụta na resorption ọkpụkpụ ma na-ebelata mgbanwe calcium serum, na-eme ka ọ baa uru maka osteoporosis.

Kedu usoro eji eme abaloparatide?

Mmekọrịta na Parathyroid Hormone Receptor 1 (PTH1R)

Nrụ ọrụ Nhọrọ nke Nnabata: Abaloparatide bụ agonist nhọrọ nke parathyroid hormone receptor 1 (PTH1R). PTH1R na-egosipụta nke ọma n'elu sel dị na anụ ahụ dị ka ọkpụkpụ na akụrụ, na-arụ ọrụ dị mkpa n'ịhazi metabolism ọkpụkpụ. Abaloparatide na-ejikọta kpọmkwem na PTH1R, na-amalite usoro nke ụzọ mgbaàmà intracellular iji mezie metabolism ọkpụkpụ. Mgbe ejikọtara ya, ọ na-arụ ọrụ adenylate cyclase, na-abawanye mmepụta intracellular cyclic AMP (cAMP) iji gbanwee ọrụ cellular na metabolism ^[1,2]..

Ọdịiche dị na njikọ ndị ọzọ: Parathyroid hormone (PTH) na protein parathyroid metụtara hormone (PTHrP) na-ejikọta na PTH1R. Ọ bụ ezie na PTH, PTHrP, na Abaloparatide niile na-egosi site na PTH1R, ụzọ mgbama ala ha dị iche. PTH na PTHrP na-egosipụta ụdị mmekọ ahụ maka steeti R^G (GTPγS-sensitive) nke PTH1R. Teriparatid (TPTD, ntụgharị, 1-34 PTH) nwere njikọ dị elu okpukpu anọ maka steeti R^0 (GTPγS-enweghị mmetụta) karịa PTHrP, na-ebute akara CAMP ogologo oge nke TPTD kpatara. N'ụzọ dị iche, abaloparatide, nke sitere na PTHrP (1-34), emebere ya maka nkwụsi ike na-eme ka ọ dịkwuo elu ma merie nsogbu ndị dị ka mfu nke windo anabolic na hypercalcemia jikọtara ya na iji TPTD. N'ihi na ọnụ ọgụgụ dissociation nke PTHrP-PTH1R mgbagwoju dị ngwa ngwa karịa nke PTH-PTH1R mgbagwoju, mmetụta osteogenic nke PTHrP na-esonyere obere absorption na hypercalcemia karịa TPTD. Abaloparatide ketara uru nke a ^[1,2,3].

Iwu nke Ọkpụkpụ Metabolism

Nkwalite nke Osteogenesis: Abaloparatide na-akpali ọrụ osteoblast, na-amụba njikọ na ntinye nke ọkpụkpụ ọkpụkpụ iji kwalite ọkpụkpụ ọkpụkpụ. Osteoblasts na-emepụta ma na-ezobe ihe mejupụtara matriks ọkpụkpụ dị ka collagen na osteocalcin, nke na-eji nwayọọ nwayọọ mee ka ọkpụkpụ ọkpụkpụ dị ọhụrụ. Nnyocha na-egosi na n'ịgwọ ọrịa osteoporosis postmenopausal, abaloparatide na-abawanye ụba nke ịnweta ọkpụkpụ (BMD) na saịtị gụnyere mkpokọta hip, olu femoral, na spine lumbar. Site n'ịkwalite okwu nke mkpụrụ ndụ ihe nketa metụtara osteoblast, ọ na-emezi njikọ nke protein ndị dị mkpa dị ka osteocalcin na ụdị m collagen. Nke a na-akwalite mkpụkọ trabecular na ike cortical, na-eme ka ike na ịdị mma skeletal dịkwuo elu ma na-ebelata ihe ize ndụ mgbaji ^[1,2,3].

Mgbochi nke ọkpụkpụ ọkpụkpụ: Ọ bụ ezie na Abaloparatide na-arụ ọrụ dị ka onye na-ahụ maka anabolic, ọ na-egosipụtakwa ụfọdụ mmetụta mgbochi na ọkpụkpụ ọkpụkpụ. Ọ na-agbanwe ọdịiche na ọrụ nke osteoclasts-sel ndị na-ahụ maka resorption ọkpụkpụ nke na-agbaze mineral ọkpụkpụ na matrix organic site na ịhapụ ihe acidic na proteolytic enzymes. Abaloparatide nwere ike ibelata ọnụego resorption ọkpụkpụ site na ibelata ọdịiche nke sel precursor osteoclast n'ime osteoclasts tozuru oke ma ọ bụ na-ebelata ndụ nke osteoclasts tozuru oke. N'otu oge ahụ, ọ na-agbanwe akara n'etiti osteoblasts na osteoclasts, na-ejigide nha anya dị ike n'etiti nhazi ọkpụkpụ na resorption. Dịka ọmụmaatụ, ọ na-ebelata ọrụ osteoclast na ọrụ resorptive site na ibelata osteoblast nzuzo receptor activator nke κB ligand (RANKL). N'adịghị ka teriparatide, abaloparatide anaghị abawanye mmepụta RANKL nke ukwuu, si otú a na-egbochi mfu nke windo anabolic nke na-eme mgbe resorption gafere n'usoro n'ikpeazụ ^[1,2,3].

Ọgụgụ 1 Ụdị nke hormone parathyroid (PTH) / teriparatide na peptide metụtara PTH (PTHrP / abaloparatide activation nke parathyroid hormone ụdị 1 receptor (PTH1R)) ^[4].

Mmetụta na Metabolism Cartilage (na ọmụmụ metụtara ọrịa ogbu na nkwonkwo)

Na-akwalite Synthesis Cartilage Matrix Synthesis: Nnyocha na ọrịa ogbu na nkwonkwo (OA) egosila na abaloparatide na-arụ ọrụ nchebe na cartilage. Chondrocytes articular na-egosipụta PTH1R, na Abaloparatide na-eme ka onye na-anabata ya rụọ ọrụ, na-akpali chondrocytes iji mepụta akụkụ nke matrix cartilage. Dịka ọmụmaatụ, ọmụmụ na-egosi Abaloparatide na-abawanye okwu lubricin (Prg4), protein dị mkpa nke matrix extracellular na cartilage nke dị oke mkpa maka idowe mmanu nkwonkwo na ibelata esemokwu. Ọ na-akwalitekwa njikọ nke ụdị II collagen, bụ isi akụkụ nke cartilage matrix, nke na-enyere aka ịnọgide na-enwe nguzozi nke cartilage na arụ ọrụ. Site n'ịbawanye njikọ nke akụrụngwa matrix cartilage ndị a, Abaloparatide na-enyere aka n'ịrụzi na ichekwa anụ ahụ mebiri emebi, na-ebelata ọganihu osteoarthritis ^[5]..

Na-egbochi hypertrophy chondrocyte na degeneration: Abaloparatide nwere ike igbochi usoro ọdịiche hypertrophic nke chondrocytes. N'oge osteoarthritis na-aga n'ihu, chondrocytes na-enweta ọdịiche hypertrophic, nke a na-eji ụda cell na-abawanye na nkwupụta dị elu nke ihe nrịbama hypertrophy dị ka ụdị X collagen (Col10). Usoro a na-eduga na mmebi nke matrix cartilage na cartilage degeneration. Nnyocha na-egosi na ọgwụgwọ Abaloparatide na-ebelata nkwalite okwu Col10 na anụ ahụ cartilage ma na-ebelata ọnụ ọgụgụ nke nnukwu hypertrophic-dị ka sel. Nke a na-egosi na ọ nwere ike belata ọdịiche hypertrophic chondrocyte, na-edobe phenotype chondrocyte nkịtị, si otú ahụ chebe cartilage na igbu oge ọganihu osteoarthritis ^[5].

Kedu ihe bụ ngwa Abaloparatide?

Ọgwụgwọ Osteoporosis

Postmenopausal Osteoporosis: Abaloparatide, onye na-ahọrọ agonist nke parathyroid hormone receptor 1 (PTHR1), ka egosiri maka ịgwọ ọrịa ọkpụkpụ azụ, karịsịa na ụmụ nwanyị postmenopausal na-enwe mgbagwoju anya ma ọ bụ na-anabataghị ọgwụgwọ ndị ọzọ. Ọ na-abawanye njupụta ịnweta ọkpụkpụ ma na-ebelata ihe omume na ihe ize ndụ nke ọkpụkpụ vertebral ọhụrụ na ndị na-abụghị vertebral na ụmụ nwanyị postmenopausal.

Osteoporosis nwoke: Na nyocha Chandler H na osteoporosis nwoke na-eji oke orchidectomized (oke ORX, ụdị osteoporosis nwoke), ọgwụgwọ Abaloparatide mere ka mmụba dị ukwuu na BMD tụrụ site na ọnụọgụ X-ray absorptiometry (DXA) na peripheral quantitative gụnyere mkpokọta, nke gụnyere mkpokọta spine. femur, na tibia. Ọ kwalitere nguzobe trabecular nke ọma, olu ọkpụkpụ, na microarchitecture na-enweghị ụbara ọnụọgụ osteoclast. Nke a na-egosi na Abaloparatide na-ejide uru ọgwụgwọ maka osteoporosis nwoke ^[6].

Ọgwụgwọ Osteoarthritis Post-Traumatic (PTOA): Na-esote ntinye PTOA ikpere site na medial meniscus destabilization (DMM) ịwa ahụ na ụmụ oke C57BL / 6 dị izu 16, injections subcutaneous kwa ụbọchị nke 40 μg / kg Abaloparatide (ma ọ bụ saline dị ka njikwa) ka a na-enye izu 6 tupu izu 2 gachara. A na-eme nyocha anụ ahụ na izu 8. Nsonaazụ gosiri na ma e jiri ya tụnyere ìgwè a na-agwọ saline, ndị otu Abaloparatide na-agwọ ọrịa gosipụtara mbelata nke cartilage articular nke DMM na-ebute ma chekwaa anụ ahụ tibial elu cartilage. Nyocha nke immunohistochemical gosiri na ọgwụgwọ Abaloparatide na-ebelata mmepụta nke ụdị X collagen (Col10) na cartilage, ụbara lubricin (Prg4) okwu na mpaghara cartilage na-enweghị calcified, ma belata ọnụ ọgụgụ nke nnukwu hypertrophic sel. na-atụ aro na Abaloparatide na-ebelata ọdịiche hypertrophic ma na-arụ ọrụ chondroprotective na òké PTOA, na-enye usoro ọgwụgwọ ọhụrụ maka PTOA ^[5].

Ọkpụkpụ Alveolar Mweghachi: Mwepụta nke ọkpụkpụ alveolar na-egbochi mmegharị ezé orthodontic na-esote (OTM) ma ọ bụ ntinye ntinye. Tan B synthesized biodegradable, bifunctional bioactive calcium phosphate nanoblossoms (NFs) jupụtara na Abaloparatide (ABL), nke akpọrọ ABL@NFs. Ihe a na-egosiputa ihe owuwu nwere oghere nwere oghere, arụmọrụ mkpuchi ọgwụ dị elu, yana ezigbo bioacompatibility. A tọhapụrụ ABL na mbụ ka ọ were sel stem, sochiri ntọhapụ nke Ca⊃2;⁺ na PO₄⊃3;⁻ n'ihi na n'ime situ interfacial mineralization. Nke a weghachiri nke ọma na ọkpụkpụ alveolar na-arụ ọrụ nke ọma n'emebighị OTM ^[7].

Refractory Hypoparathyroidism (HPT): Chamseddin R kọrọ otu nwanyị dị afọ 39 nwere HPT iatrogenic nke na-emezughị ọkwa calcium serum nkịtị n'agbanyeghị nnukwu vitamin D, ihe mgbakwunye calcium, na ntinye PTH (rPTH) recombinant. N'ịgbaso nchịkwa subcutaneous nke abaloparatide site na patch dị mfe site na nleba anya na usoro ọgwụgwọ ahaziri onwe ya, calcium serum ya kwụsiri ike na 9 mg/dL mgbe ọnwa 2 gachara. N'ime ọnwa anọ, ọ na-edobe calcium serum nkịtị na-enweghị usoro hypocalcemia ebe ọ na-eji nwayọọ nwayọọ na-ebelata calcium ọnụ na ntinye vitamin D ^[3].

Ịkwalite Spinal Fusion: Na cervical-thoracic revision ịwa ahụ, a na-eji abaloparatide mee ihe iji kwalite njikọ ọkpụkpụ azụ na ndị ọrịa nwere akụkọ ihe mere eme nke cervical cervical na ọtụtụ ịwa ahụ cervical dara. Parikh S et al. kọrọ otu nwanyị nwanyị dị afọ 66 nke malitere ọgwụgwọ 80 mcg Abaloparatide kwa ụbọchị n'izu abụọ ka emechara ya maka usoro izu iri na abụọ ezubere. Nyocha cervical CT na ọnwa 3 na 6 gosipụtara njikọ cervical-thoracic gwọọ nke ọma na-enweghị akara nke enweghị njikọ ^[8].

Mmechi

Ngwa ụlọ ọgwụ Abaloparatide gbadoro ụkwụ na ọgwụgwọ osteoporosis. A na-egosi ya maka ụmụ nwanyị postmenopausal nwere osteoporosis n'ihe ize ndụ dị elu ma ọ bụ na-anabataghị ọgwụgwọ ndị ọzọ, na-abawanye ụba ịnweta ọkpụkpụ (BMD) ma na-ebelata ihe ize ndụ nke ọkpụkpụ vertebral na ndị na-abụghị vertebral. Maka osteoporosis nwoke, ihe ọmụmụ anụmanụ na-egosi mmụba BMD na saịtị dị iche iche na microarchitecture ọkpụkpụ ka mma, na-egosi uru ọgwụgwọ nwere ike. Na post-traumatic osteoarthritis, ọ na-ebelata mfu cartilage ma na-egbochi hypertrophy chondrocyte iji chebe cartilage. Na ọkpụkpụ ọkpụkpụ alveolar, ABL @ NF ihe ejiri ọgwụ a na-akwalite ọkpụkpụ ọkpụkpụ, na-enye ngwọta maka nrụzi ọkpụkpụ post-orthodontic. Nchọpụta na-akwadokwa ojiji ya na hypoparathyroidism refractory na nkwalite njikọ ọkpụkpụ azụ.

Banyere Onye dere ya

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Onye ode akwụkwọ akụkọ sayensị

Bin T bụ onye nyocha na Ngalaba Chemistry, Mahadum Peking, ọkachamara na nanomaterials na ngwa ha na injinia biomedical. Ọrụ ya na-elekwasị anya na nhazi na njikọ nke nanostructures na-arụ ọrụ maka nnyefe ọgwụ ezubere iche na ịmaliteghachi anụ ahụ. Tan ejikọtala ọtụtụ akwụkwọ na akwụkwọ akụkọ sayensị na-eduga, na-enye aka na ọganihu na nanomedicine na usoro ọgwụgwọ na-emegharị ahụ. A na-edepụta Bin T n'akwụkwọ ntụaka [7].

▎ Okwu ndị dị mkpa

[1] Shirley M. Abaloparatide: Nkwado zuru ụwa ọnụ nke mbụ. Ọgwụ 2017; 77 (12): 1363-1368.DOI: 10.1007/s40265-017-0780-7.

[2] Sleeman A, Clements JN. Abaloparatide: Nhọrọ ọgwụ ọhụrụ maka osteoporosis. Akwụkwọ akụkọ America nke Health-System Pharmacy 2019; 76: 130-135.https://api.semanticscholar.org/CorpusID:59338650.

[3] Chamseddin R, Mathew A, Alzohaili O. Abstract #1407986: Nlekọta Abaloparatide Site na Mfe Mfe: Nhọrọ ọgwụgwọ maka Refractory Hypoparathyroidism Post-thyroidectomy. Omume Endocrine 2023; 29: S57-S58.DOI: 10.1016/j.eprac.2023.03.131.

[4] Thompson JC, Wanderman N, Anderson PA, Freedman BA. Abaloparatide na ọkpụkpụ azụ: Nyocha akụkọ. Ntinye aka ụlọ ọgwụ na ịka nká 2020; 15: 1023-1033. DOI:10.2147/CIA.S227611.

[5] Landgrave S, Ishii T, Maynard R, et al. 302 Abaloparatide dị ka ọgwụgwọ ọhụụ maka osteoarthritis posttraumatic. Akwụkwọ akụkọ nke Clinical and Translational Science 2022; 6: 53. DOI:10.1017/cts.2022.166.

[6] Chandler H, Lanske B, Varela A, et al. Abaloparatide, akwụkwọ akụkọ osteoanabolic PTHrP analọg, na-eme ka ọkpụkpụ cortical na trabecular na-eme ka ọkpụkpụ na-arụ ọrụ n'ime oke oke orchiectomized site n'ịbawanye ọkpụkpụ ọkpụkpụ na-enweghị mmụba ọkpụkpụ. Ọkpụkpụ 2019; 120: 148-155.DOI: 10.1016/j.ọkpụkpụ.2018.10.012.

[7] Tan B, Wu Y, Wang R, et al. Nanoflowers na-emebi emebi nwere Abaloparatide Spatiotemporal Management of Functional Alveolar Bone Regeneration. Akwụkwọ ozi Nano 2024. https://api.semanticscholar.org/CorpusID:267655299.

[8] Parikh S, Lubitz SE, Sharma A. MON-365 Akwụkwọ akụkọ iji Abaloparatide na-abawanye n'ọkpụkpụ azụ azụ n'ime onye ọrịa na-aga ịwa ahụ nyocha nke Cervicothoracic. Akwụkwọ akụkọ nke Endocrine Society 2020; 4 (Mgbakwunye_1): 365.DOI: 10.1210/jendso/bvaa046.108.

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) akwadobeghị 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.