Abaloparatide 3 mg

▎ Abaloparatide Structure

▎ Abaloparatide Kev Tshawb Fawb

Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm abaloparatide?

Osteoporosis yog ib hom kab mob ntau yam kab mob uas tshwm sim los ntawm cov pob txha qis thiab microarchitectural deterioration ntawm cov pob txha. Qhov no ua rau cov pob txha muaj zog ntxiv thiab muaj kev cuam tshuam rau pob txha, nrog rau lub duav thiab txha caj qaum yog qhov tshwm sim. Nws cuam tshuam rau cov neeg mob lub neej zoo thiab ua rau muaj kev tsis taus thiab kev tuag ntau ntxiv. Nrog rau kev nrawm thoob ntiaj teb cov neeg laus, qhov xwm txheej ntawm osteoporosis tseem nce ntxiv. Nws kwv yees tias 42% -56% ntawm cov poj niam thiab 27% -29% ntawm cov txiv neej hnub nyoog tshaj 50 xyoo yuav ntsib cov pob txha pob txha, ua rau muaj teeb meem kev noj qab haus huv ceev ceev. Kev kho mob osteoporosis ib txwm muaj, xws li bisphosphonates thiab xaiv cov tshuaj estrogen receptor modulators (SERMs), feem ntau tswj cov pob txha ceev los ntawm inhibiting osteoclast-mediated pob txha resorption. Txawm li cas los xij, lawv qhov kev ua tau zoo tsuas yog txwv rau cov neeg mob uas txo cov pob txha loj thiab muaj feem cuam tshuam rau pob txha. Although parathyroid hormone (PTH) 1-34 fragment (teriparatide) was the first anabolic agent approved by the US Food and Drug Administration (FDA), effectively increasing bone density and reducing fracture risk, its long-term use carries limitations including enhanced bone resorption, hypercalcemia, and a potential increased risk of osteosarcoma.

Tawm tsam qhov teeb meem no, tsim cov tshuaj tshiab uas ua ke muaj zog anabolic cuam tshuam thaum zam cov teeb meem no yog qhov tseem ceeb. Raws li parathyroid hormone-related peptide (PTHrP) analog, abaloparatide khaws cov kev ua haujlwm anabolic muaj zog thaum txo cov kev cuam tshuam ntawm cov pob txha resorption thiab txo qis cov tshuaj calcium hauv cov ntshav, ua rau nws muaj txiaj ntsig zoo rau pob txha.

Dab tsi yog cov txheej txheem ntawm kev txiav txim rau abaloparatide?

Kev sib tham nrog Parathyroid Hormone Receptor 1 (PTH1R)

Receptor Selective Activation: Abaloparatide yog ib qho kev xaiv agonist ntawm parathyroid hormone receptor 1 (PTH1R). PTH1R tau nthuav dav dav rau ntawm cov hlwb hauv cov ntaub so ntswg xws li pob txha thiab lub raum, ua lub luag haujlwm tseem ceeb hauv kev tswj cov pob txha metabolism. Abaloparatide tshwj xeeb khi rau PTH1R, pib ua ntau txoj hauv kev hauv lub cev kom tswj cov pob txha metabolism. Thaum khi, nws ua kom adenylate cyclase, nce intracellular cyclic AMP (cAMP) ntau lawm los hloov kho cellular muaj nuj nqi thiab metabolism ^[1,2].

Qhov sib txawv ntawm lwm cov ligands: Parathyroid hormone (PTH) thiab parathyroid hormone-related protein (PTHrP) kuj khi rau PTH1R. Txawm hais tias PTH, PTHrP, thiab Abaloparatide tag nrho cov teeb liab los ntawm PTH1R, lawv cov kev taw qhia qis qis sib txawv. PTH thiab PTHrP nthuav tawm qhov sib xws rau R^G (GTPγS-sensitive) lub xeev ntawm PTH1R. Teriparatid (TPTD, piv txwv li, 1-34 PTH) muaj plaub zaug ntau dua affinity rau R^0 (GTPγS-insensitive) xeev tshaj PTHrP, ua rau lub sij hawm ntev cAMP signaling induced los ntawm TPTD. Hauv qhov sib piv, abaloparatide, muab los ntawm PTHrP(1–34), yog tsim los txhim kho kev ruaj ntseg thiab kov yeej cov teeb meem xws li poob ntawm qhov rais anabolic thiab hypercalcemia cuam tshuam nrog TPTD siv. Vim tias qhov sib txawv ntawm PTHrP-PTH1R complex yog sai dua li ntawm PTH-PTH1R complex, cov teebmeem osteogenic ntawm PTHrP tau nrog tsawg nqus thiab hypercalcemia dua li TPTD. Abaloparatide tau txais txiaj ntsig zoo sib xws ^[1,2,3].

Kev tswj cov pob txha metabolism

Txhawb nqa Osteogenesis: Abaloparatide txhawb nqa kev ua haujlwm ntawm osteoblast, nce kev sib txuas thiab tso cov pob txha matrix los txhawb kev tsim cov pob txha. Osteoblasts synthesize thiab secrete pob txha matrix Cheebtsam xws li collagen thiab osteocalcin, uas maj mam mineralize los tsim cov pob txha tshiab. Cov kev tshawb fawb qhia tias hauv kev kho mob osteoporosis postmenopausal, abaloparatide ua rau cov pob txha pob txha pob txha ntom ntom (BMD) ntawm cov chaw suav nrog tag nrho lub duav, femoral caj dab, thiab lumbar qaum. Los ntawm stimulating cov kev qhia ntawm osteoblast-txog cov noob, nws upregulates cov synthesis ntawm cov proteins tseem ceeb xws li osteocalcin thiab hom I collagen. Qhov no txhawb nqa trabecular thickening thiab ntxiv dag zog rau cortical, txhim kho pob txha lub zog thiab zoo thaum txo kev pheej hmoo ntawm pob txha ^[1,2,3].

Inhibition ntawm Pob Txha Resorption: Thaum Abaloparatide feem ntau ua raws li tus neeg sawv cev anabolic, nws kuj nthuav tawm qee qhov cuam tshuam rau pob txha resorption. Nws hloov pauv qhov sib txawv thiab kev ua haujlwm ntawm osteoclasts - cov cell ua lub luag haujlwm rau cov pob txha resorption uas yaj cov pob txha ntxhia thiab cov organic matrix los ntawm kev tso cov kua qaub thiab cov enzymes proteolytic. Abaloparatide tuaj yeem txo cov pob txha resorption tus nqi los ntawm kev txo qis qhov sib txawv ntawm osteoclast precursor cells rau hauv osteoclasts paub tab lossis ua rau lub neej luv ntawm cov laus osteoclasts. Concurrently, nws modulates signaling ntawm osteoblasts thiab osteoclasts, tswj lub dynamic equilibrium ntawm pob txha tsim thiab resorption. Piv txwv li, nws txo osteoclast activation thiab resorptive kev ua si los ntawm kev txo qis osteoblast-secreted receptor activator ntawm nuclear factor κB ligand (RANKL). Tsis zoo li teriparatide, abaloparatide tsis dhau ua rau RANKL ntau lawm, yog li tiv thaiv qhov poob ntawm lub qhov rais anabolic uas tshwm sim thaum resorption overtakes tsim nyob rau tom qab theem ^[1,2,3].

Daim duab 1 Tus qauv ntawm parathyroid hormone (PTH) / teriparatide thiab PTH-txog peptide (PTHrP / abaloparatide activation ntawm parathyroid hormone type 1 receptor (PTH1R)) ^[4].

Cov teebmeem ntawm pob txha mos Metabolism (hauv Osteoarthritis-Related Studies)

Txhawb nqa pob txha mos Matrix Synthesis: Kev tshawb fawb hauv osteoarthritis (OA) tau pom tias abaloparatide ua rau muaj kev tiv thaiv ntawm pob txha mos. Articular chondrocytes nthuav qhia PTH1R, thiab Abaloparatide activates no receptor, stimulating chondrocytes rau synthesize Cheebtsam ntawm pob txha mos matrix. Piv txwv li, cov kev tshawb fawb qhia Abaloparatide nce lubricin (Prg4) qhia, ib qho tseem ceeb extracellular matrix protein nyob rau hauv pob txha mos uas yog ib qho tseem ceeb rau kev tuav lub lubrication thiab txo kev sib txhuam. Nws kuj tseem txhawb kev sib txuas ntawm hom II collagen, lub hauv paus tseem ceeb ntawm pob txha mos matrix, uas pab tswj cov pob txha mos thiab kev ua haujlwm zoo. Los ntawm kev nce synthesis ntawm cov pob txha mos matrix Cheebtsam, Abaloparatide pab kho thiab tiv thaiv cov pob txha mos uas puas lawm, ua rau qeeb ntawm kev mob osteoarthritis ^[5].

Inhibiting chondrocyte hypertrophy thiab degeneration: Abaloparatide tuaj yeem cuam tshuam cov txheej txheem hypertrophic sib txawv ntawm chondrocytes. Thaum lub sij hawm osteoarthritis kev loj hlob, chondrocytes undergo hypertrophic sib txawv, tus cwj pwm los ntawm kev nce cell ntim thiab siab qhia txog cov cim hypertrophy xws li hom X collagen (Col10). Cov txheej txheem no ua rau degradation ntawm pob txha mos matrix thiab pob txha mos degeneration. Cov kev tshawb fawb qhia tias kev kho Abaloparatide alleviates lub upregulation ntawm Col10 qhia nyob rau hauv cov pob txha mos thaum txo tus naj npawb ntawm loj hypertrophic-zoo li hlwb. Qhov no qhia tias nws tuaj yeem ua rau qeeb chondrocyte hypertrophic sib txawv, tswj cov chondrocyte phenotype ib txwm, yog li tiv thaiv pob txha mos thiab ncua kev mob osteoarthritis ^[5].

Dab tsi yog kev siv ntawm Abaloparatide?

Kev Kho Mob Osteoporosis

Postmenopausal Osteoporosis: Abaloparatide, ib qho kev xaiv agonist ntawm parathyroid hormone receptor 1 (PTHR1), yog qhia rau kev kho mob pob txha, tshwj xeeb tshaj yog nyob rau hauv cov poj niam postmenopausal ntawm kev pheej hmoo ntawm pob txha los yog tsis teb rau lwm yam kev kho mob. It significantly increases bone mineral density and reduces the incidence and risk of new vertebral and non-vertebral fractures in postmenopausal women.

Txiv neej Osteoporosis: Hauv Chandler H txoj kev tshawb fawb ntawm txiv neej osteoporosis siv cov nas orchidectomized (ORX nas, tus txiv neej osteoporosis qauv), kev kho Abaloparatide ua rau muaj kev nce ntxiv hauv BMD ntsuas los ntawm dual-zog X-ray absorptiometry (DXA) thiab peripheral compatibility tom qab ntawm lub cev (tom qab tag nrho ntawm qhov chaw) lumbar qaum, femur, thiab tibia. Nws tau txhim kho trabecular tsim, pob txha ntim, thiab microarchitecture yam tsis tau nce tus lej osteoclast. Qhov no qhia tias Abaloparatide tuav cov txiaj ntsig kho mob rau txiv neej osteoporosis ^[6].

Post-Traumatic Osteoarthritis (PTOA) Kev Kho Mob: Tom qab lub hauv caug PTOA induction ntawm medial meniscus destabilization (DMM) kev phais hauv 16-lub lim tiam-laus txiv neej C57BL / 6 nas, niaj hnub txhaj tshuaj subcutaneous ntawm 40 μg / kg Abaloparatide (los yog saline raws li kev tswj) tau noj 6 lub lis piam pib. Kev tshuaj xyuas cov ntaub so ntswg tau ua tiav ntawm 8 lub lis piam. Cov txiaj ntsig tau pom tias piv rau pab pawg kho cov ntsev, cov pab pawg kho mob Abaloparatide tau nthuav tawm txo DMM-vim cov pob txha mos pob txha poob thiab khaws cia tibial pob txha pob txha pob txha. Immunohistochemical tsom xam tau qhia tias kev kho Abaloparatide txo qis kev txhim kho ntawm hom X collagen (Col10) hauv pob txha mos, nce lubricin (Prg4) qhia hauv cov pob txha mos uas tsis yog calcified, thiab txo cov cell hypertrophic loj. qhia tias Abaloparatide slows hypertrophic sib txawv thiab exerts chondroprotective nyhuv nyob rau hauv nas PTOA, muab ib tug tshiab kho tswv yim rau PTOA ^[5].

Alveolar Bone Regeneration: Post-extraction alveolar pob txha resorption hnyav heev impedes tom qab orthodontic hniav txav (OTM) los yog implant placement. Tan B synthesized biodegradable, bifunctional bioactive calcium phosphate nanoblossoms (NFs) loaded nrog Abaloparatide (ABL), hu ua ABL@NFs. Cov khoom no nthuav tawm cov txheej txheem ntxeem tau, cov tshuaj encapsulation siab, thiab biocompatibility zoo heev. ABL tau pib tso tawm los nrhiav cov qia hlwb, ua raws li kev tso tawm ntawm Ca⊃2;⁺ thiab PO₄⊃3;⁻ rau hauv qhov chaw interfacial mineralization. Qhov no tau ua tiav rov qab ua tiav morphologically thiab ua haujlwm zoo ntawm cov pob txha alveolar yam tsis muaj kev cuam tshuam OTM ^[7].

Refractory Hypoparathyroidism (HPT): Chamseddin R qhia txog 39-xyoo-laus poj niam nrog iatrogenic HPT uas ua tsis tau raws li cov tshuaj calcium hauv cov ntshav txawm tias muaj cov tshuaj vitamin D ntau, cov tshuaj calcium, thiab cov tshuaj PTH (rPTH) rov ua dua. Tom qab kev tswj hwm subcutaneous ntawm abaloparatide los ntawm Simplicity thaj nrog kev saib xyuas thiab kev siv tus kheej, nws cov calcium hauv cov ntshav tseem nyob ruaj khov ntawm 9 mg / dL tom qab 2 lub hlis. Los ntawm 4 lub hlis, nws khaws cov tshuaj calcium uas tsis muaj cov tshuaj hypocalcemia thaum maj mam txo qhov ncauj calcium thiab vitamin D supplementation ^[3].

Txhawb nqa Spinal Fusion: Hauv kev phais lub ncauj tsev menyuam-thoracic, abaloparatide tau siv los txhawb kev txha caj qaum hauv cov neeg mob uas muaj keeb kwm ntawm ncauj tsev menyuam tsis muaj zog thiab ntau yam kev phais ncauj tsev menyuam ua tsis tiav. Parik S et al. tshaj tawm ib tus poj niam hnub nyoog 66 xyoo uas tau pib kho txhua hnub 80 mcg Abaloparatide ob lub lis piam tom qab kev phais rau kev npaj 12 lub lis piam. Cervical CT scans ntawm 3 thiab 6 lub hlis qhia tau hais tias kho tau zoo ntawm ncauj tsev menyuam-thoracic fusion uas tsis muaj cov cim qhia ntawm nonunion ^[8].

Xaus

Abaloparatide's clinical application centers on osteoporosis kho mob. Nws tau qhia rau cov poj niam postmenopausal nrog osteoporosis ntawm kev pheej hmoo ntawm pob txha tawg lossis tsis teb rau lwm cov kev kho mob, ua kom cov pob txha pob txha pob txha ntom ntom (BMD) thiab txo qis vertebral thiab tsis-vertebral puas ntsoog. Rau cov txiv neej osteoporosis, tsiaj kev tshawb fawb pom tau tias muaj BMD nce ntawm ntau qhov chaw thiab txhim kho cov pob txha microarchitecture, qhia tias muaj peev xwm kho tau tus nqi. Hauv post-traumatic osteoarthritis, nws txo qis pob txha mos thiab inhibits chondrocyte hypertrophy los tiv thaiv pob txha mos. Hauv kev tsim cov pob txha alveolar, ABL@NFs cov ntaub ntawv ntim nrog cov tshuaj no txhawb kev tsim cov pob txha, muab kev daws teeb meem rau kev kho pob txha tom qab pob txha. Kev tshawb fawb kuj tseem txhawb nqa nws txoj kev siv hauv refractory hypoparathyroidism thiab spinal fusion txhawb nqa.

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

Bin T yog tus kws tshawb fawb ntawm Department of Chemistry, Peking University, tshwj xeeb hauv nanomaterials thiab lawv cov ntawv thov hauv biomedical engineering. Nws txoj haujlwm tsom mus rau kev tsim thiab kev sib txuas ntawm kev ua haujlwm nanostructures rau kev xa tshuaj thiab cov ntaub so ntswg rov ua haujlwm. Tan tau sib koom sau ntau cov ntawv tshaj tawm hauv cov ntawv xov xwm tshawb fawb, pab txhawb rau kev nce qib hauv nanomedicine thiab kev kho dua tshiab. Bin T tau teev nyob rau hauv qhov kev siv ntawm cov ntaub ntawv pov thawj [7].

▎ Cov Lus Qhia Tseem Ceeb

[1] Shirley M. Abaloparatide: Thawj Kev Pom Zoo Thoob Ntiaj Teb. Tshuaj 2017; 77(12): 1363-1368.DOI: 10.1007/s40265-017-0780-7.

[2] Sleeman A, Clements JN. Abaloparatide: Ib qho kev xaiv tshuaj tshiab rau kev mob pob txha. American Journal of Health-System Pharmacy 2019; 76: 130-135.https://api.semanticscholar.org/CorpusID:59338650.

[3] Chamseddin R, Mathew A, Alzohaili O. Abstract #1407986: Abaloparatide Administration Los ntawm Simplicity Patch: Ib Txoj Kev Kho Mob rau Refractory Hypoparathyroidism Post-thyroidectomy. Endocrine xyaum 2023; 29: S57-S58.DOI: 10.1016/j.eprac.2023.03.131.

[4] Thompson JC, Wanderman N, Anderson PA, Freedman BA. Abaloparatide thiab tus txha nraub qaum: Kev Tshawb Fawb Txog Kev Tshawb Fawb. Kev Pabcuam Kev Khomob hauv Kev Laus 2020; 15: 1023-1033 . DOI: 10.2147/CIA.S227611.

[5] Landgrave S, Ishii T, Maynard R, et al. 302 Abaloparatide raws li kev kho tshiab rau kev mob caj dab tom qab. Phau ntawv Journal of Clinical and Translational Science 2022; 6: 53. DOI: 10.1017/cts.2022.166.

[6] Chandler H, Lanske B, Varela A, et al. Abaloparatide, ib qho tshiab osteoanabolic PTHrP analog, tsub kom cortical thiab trabecular pob txha loj thiab architecture hauv orchiectomized nas los ntawm kev nce pob txha tsis muaj pob txha resorption. Pob txha 2019; 120: 148-155.DOI: 10.1016/j.bone.2018.10.012.

[7] Tan B, Wu Y, Wang R, et al. Biodegradable Nanoflowers nrog Abaloparatide Spatiotemporal Kev Tswj Xyuas Kev Ua Haujlwm ntawm Alveolar Pob Txha. Nano Letters 2024. https://api.semanticscholar.org/CorpusID:267655299.

[8] Parikh S, Lubitz SE, Sharma A. MON-365 Novel Siv Abaloparatide los txhim kho Spinal Fusion hauv Tus Neeg Mob Cervicothoracic Revision Surgery. Phau ntawv Journal of the Endocrine Society 2020; 4(Supplement_1): 365.DOI: 10.1210/jendso/bvaa046.108.

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.