Download PDF
Osteologie 2024; 33(03): 185-195
DOI: 10.1055/a-2315-9880
Review

Abaloparatid – eine neue osteoanabole Therapieoption für die Osteoporose bei postmenopausalen Frauen

Abaloparatide – A new osteoanabolic Therapeutic Option for Osteoporosis in Postmenopausal Women
Peter Herbert Kann
1   Deutsches Endokrinologisches Versorgungszentrum, Frankfurt am Main, Germany
2   Fachbereich Medizin, Philipps-Universität, Marburg, Germany
,
Peyman Hadji
3   Frankfurter Hormon- und Osteoporosezentrum, Frankfurt am Main, Germany
,
Andreas Kurth
4   Orthopädisches Institut Dr. Baron und Kollegen, Frankfurt am Main, Germany
5   Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
,
Ralf Schmidmaier
6   Medizinische Klinik und Poliklinik IV, LMU Klinikum der Ludwig-Maximilians-Universität, München, Germany
,
Friederike Thomasius
3   Frankfurter Hormon- und Osteoporosezentrum, Frankfurt am Main, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Zusammenfassung

Abaloparatid ist ein synthetisches Strukturanalogon des Parathormon-verwandten Peptids (PTHrP). Durch Bindung an Parathormon-1-Rezeptor stimuliert es Osteoblasten zum Knochenaufbau, dies bei einer geringeren begleitenden Osteoklastenstimulation, so dass in der Summe ein größerer osteoanaboler Nettoeffekt im Vergleich zu Teriparatid resultiert. Auch klinisch ist es mindestens so stark wirksam wie Teriparatid, möglicherweise diesem sogar überlegen, wobei hier unmittelbare head-to-head Studien derzeit nicht vorliegen. Abaloparatid reduziert effektiv das Auftreten vertebraler und peripherer osteoporotischer Frakturen mit auch entsprechenden günstigen Effekten auf die Knochendichte und die Knochenumbaumarker. Zu beachten ist, dass nach der subcutanen Injektion ein moderater Anstieg der Herzfrequenz beobachtet werden kann, wobei es aber keine Anhaltspunkte dafür gibt, dass dies mit schwerwiegenderen kardiovaskulären Komplikationen zu assoziieren wäre. Abaloparatid (Eladynos) wurde in Europa zur Behandlung der Osteoporose bei postmenopausalen Frauen mit erhöhtem Frakturrisiko für eine Therapiedauer von 18 Monaten zugelassen. Nachfolgend ist die Durchführung einer osteoklasteninhibierenden Bisphosphonattherapie als Sequenz zu empfehlen.

Abstract

Abaloparatide is a synthetic structural analogue of the parathyroid hormone related peptide (PTHrP). It stimulates osteoblasts to synthesize bone by binding to the parathyroid hormone 1 receptor, which is accompanied by just a slight osteoclast activation. Thus, compared to teriparatide, the resulting osteoanabolic net effect is more pronounced. Clinically, its therapeutic effect is at least equal, perhaps superior to teriparatide. However, direct head-to-head studies are not available yet. Abaloparatide reduces effectively the risk for vertebral and peripheral osteoporotic fractures accompanied by positive effects on bone density and bone turnover markers. Following subcutaneous injection, a moderate increase of the heart rate may be observed. However, there are no indications that this might be correlated to serious cardiovascular events. Abaloparatide (Eladynos) has been approved in Europe for the treatment of osteoporosis in postmenopausal women with an increased fracture risk for a therapy duration of 18 months. Thereafter, an osteoclast inhibiting bisphosphonate sequential treatment is needed.

Schlüsselwörter

Osteoporose - Abaloparatid - postmenopausal - Fraktur - Knochen

Keywords

osteoporosis - abaloparatide - postmenpausal - fracture - bone


Publication History

Received: 25 January 2024

Accepted: 26 April 2024

Article published online:
10 July 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Pöss J, Link A, Böhm M. Akute und chronische Herzinsuffizienz im Spiegel der neuen ESC-Leitlinie. Herz 2013; 38: 812-820
    CrossrefPubMedSearch in Google Scholar
  • 2 Flu H, van der Hage JH, Knippenberg B. et al. Treatment for peripheral arterial obstructive disease: An appraisal of the economic outcome of complications. J Vasc Surg 2008; 48: 368-376
    CrossrefPubMedSearch in Google Scholar
  • 3 Amso Z, Cornish J, Brimble MA. Short anabolic peptides for bone growth. Med Res Rev 2016; 36: 579-640
    CrossrefPubMedSearch in Google Scholar
  • 4 Hosking DJ. Calcium homeostasis in pregnancy. Clin Endocrinol (Oxf.) 1996; 56: 1-6
    CrossrefSearch in Google Scholar
  • 5 Horseman ND, Hernandez LL. New concepts of breast cell communication to bone. Trends Endocrinol Metab 2014; 25: 34-41
    CrossrefPubMedSearch in Google Scholar
  • 6 Nagata M, Ono N, Ono W. Mesenchymal progenitor regulation of tooth eruption: A view from PTHrP. J Dent Res 2020; 99: 133-142
    CrossrefPubMedSearch in Google Scholar
  • 7 Grunbaum A, Kremer R. Parathyroid hormone-related protein (PTHrP) and malignancy. Vitam Horm 2022; 120: 133-177
    CrossrefPubMedSearch in Google Scholar
  • 8 Sutkeviciute I, Clark LJ, White AD. et al. PTH/PTHrP receptor signaling, allostery, and structures. Trends Endocrinol Metab 2019; 30: 860-874
    CrossrefPubMedSearch in Google Scholar
  • 9 Jilka RL. Molecular and cellular mechanisms of the anabolic effect of intermittent PTH. Bone 2007; 40: 1434-1446
    CrossrefPubMedSearch in Google Scholar
  • 10 Tella SH, Kommalapati A, Correa R. Profile of abaloparatide and its potential in the treatment of postmenopausal osteoporosis. Cureus 2017; 9: e1300
    PubMedSearch in Google Scholar
  • 11 Hattersley G, Dean T, Corbin BA. et al. Binding selectivity of abaloparatide for PTH-type-1-receptor conformations and effects on downstream signaling. Endocrinology 2016; 157: 141-149
    CrossrefPubMedSearch in Google Scholar
  • 12 Brent MB. Abaloparatide: A review of preclinical and clinical studies. Eur J Pharmacol 2021; 909: 174409
    CrossrefPubMedSearch in Google Scholar
  • 13 Ricarde FR, Le Henaff C, Kolupaeva VG. et al. Parathyroid hormone(1-34) and its analogs differently modulate osteoblastic Rankl expression via PKA/SIK2/SIK3 and PP1/PP2A-CRT3 signaling. J Biol Chem 2018; 293: 20200-20213
    CrossrefPubMedSearch in Google Scholar
  • 14 Miller PD, Troy S, Weiss RJ. et al. Phase 1b evaluation of abaloparatide solid microstructured transdermal system (Abaloparatide-sMTS) in postmenopausal women with low bone mineral density. Clin Drug Invest 2021; 41: 277-285
    CrossrefPubMedSearch in Google Scholar
  • 15 Lewiecki ME, Czerwinski E, Recknor C. et al. Efficacy and safety of transdermal abaloparatide in postmenopausal women with osteoporosis: A randomized study. J Bone Miner Res 2023; 38: 1404-1414
    CrossrefPubMedSearch in Google Scholar
  • 16 Sahbani K, Cardozo CP, Bauman WA, Tawfeek HA. Abaloparatide exhibits greater osteoanabolic response and higher cAMP stimulation and β-arrestin recruitment than teriparatide. Physiol Rep 2019; 7: e14225
    CrossrefPubMedSearch in Google Scholar
  • 17 Le Henaff C, Ricarte F, Finnie B. et al. Abaloparatide at the same dose has the same effects on bone as PTH (1-34) in mice. J Bone Miner Res 2020; 35: 714-724
    CrossrefPubMedSearch in Google Scholar
  • 18 Arlt H, Mullarkey T, Hu D. et al. Effects of abaloparatide and teriparatide on bone resorption and bone formation in female mice. BoneKEy Rep 2020; 13: 100291
    CrossrefPubMedSearch in Google Scholar
  • 19 Makino A, Hasegawa T, Takagi H. et al. Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: a comparison with teriparatide. Bone 2021; 142: 115651
    CrossrefPubMedSearch in Google Scholar
  • 20 Makino A, Takagi H, Takahashi Y. et al. Abaloparatide exerts bone anabolic effects with less stimulation of bone resorption-related factors: a comparison with teriparatide. Calcif. Tissue Int 2018; 103: 289-297
    CrossrefPubMedSearch in Google Scholar
  • 21 Doyle N, Varela A, Haile S. et al. Abaloparatide, a novel PTH receptor agonist, increased bone mass and strength in ovariectomized cynomolgus monkeys by increasing bone formation without increasing bone resorption. Osteoporos Int 2018; 29: 685-697
    CrossrefPubMedSearch in Google Scholar
  • 22 Chandler H, Brooks DJ, Hattersley G. et al. Abaloparatide increases bone mineral density and bone strength in ovariectomized rabbits with glucocorticoid-induced osteopenia. Osteoporos Int 2019; 30: 1607-1616
    CrossrefPubMedSearch in Google Scholar
  • 23 Besschetnova T, Brooks DJ, Hu D. et al. Abaloparatide improves cortical geometry and trabecular microarchitecture and increases vertebral and femoral neck strength in a rat model of male osteoporosis. Bone 2019; 124: 148-157
    CrossrefPubMedSearch in Google Scholar
  • 24 Brent MB, Thomsen S, Brüel A. Short-term glucocorticoid excess blunts abaloparatide-induced increase in femoral bone mass and strength in mice. Sci Rep 2021; 11: 12258
    CrossrefPubMedSearch in Google Scholar
  • 25 Teguh DA, Nustad JL, Craven AE. et al. Abaloparatide treatment increases bone formation, bone density and bone strength without increasing bone resorption in a rat model of hindlimb unloading. Bone 2021; 144: 10.1016
    CrossrefPubMedSearch in Google Scholar
  • 26 Sahbani K, Pan J, Zaidi M. et al. Abaloparatide prevents immobilization-induced cortical but not trabecular bone loss after spinal cord injury. FASEB J 2023; 37: e22984
    CrossrefPubMedSearch in Google Scholar
  • 27 Makino A, Hasegawa T, Takagi H. et al. Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: a comparison with teriparatide. Bone 2021; 142: 115651
    CrossrefPubMedSearch in Google Scholar
  • 28 Dempster DW, Zhou H, Rao SD. et al. Early effects of abaloparatide on bone formation and resorption indices in postmenopausal women with osteoporosis. J Bone Miner. Res 2021; 10: 1002
    Search in Google Scholar
  • 29 Moreira CA, Fitzpatrick LA, Wang Y, Recker RR. Effects of abaloparatide-SC (BA058) on bone histology and histomorphometry: the ACTIVE phase 3 trial. Bone 2017; 97: 314-319
    CrossrefPubMedSearch in Google Scholar
  • 30 Leder BZ, O’Dea LSL, Zanchetta JR. et al. Effects of abaloparatide, a human parathyroid hormone-related peptide analog, on bone mineral density in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2015; 100: 697-706
    CrossrefPubMedSearch in Google Scholar
  • 31 Matsumoto T, Sone T, Yamashita A, Inoue T. Abaloparatide dose-dependently increases bone mineral density in postmenopausal women with osteoporosis: a phase 2 study. J Bone Miner Metab 2023; 41: 807-816
    CrossrefPubMedSearch in Google Scholar
  • 32 Sackett D. Evidence-based medicine. Lancet 1995; 346: 1171
    CrossrefPubMedSearch in Google Scholar
  • 33 Miller PD, Hattersley G, Riis BJ. et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis a randomized clinical trial. J Am Med Assoc 2016; 316: 722-733
    CrossrefPubMedSearch in Google Scholar
  • 34 Reginster JY, Hattersley G, Williams GC, Hu M-y, Fitzpatrick LA, Lewicki EM. Abaloparatide is an effective treatment option for postmenopausal osteoporosis: review of the number needed to treat compared with teriparatide. Calcif Tissue Int 2018; 103: 540-545
    CrossrefPubMedSearch in Google Scholar
  • 35 McClung MR, Harvey NC, Fitzpatrick LA. et al. Effects of abaloparatide on bone mineral density and risk of fracture in postmenopausal women aged 80 years or older with osteoporosis. Menopause 2018; 25: 767-771
    CrossrefPubMedSearch in Google Scholar
  • 36 Saag KG, Williams SA, Wang Y. et al. Effect of abaloparatide on bone mineral density and fracture incidence in a subset of younger postmenopausal women with osteoporosis at high risk for fracture. Clin Ther 2020; 42: 1099-1107
    CrossrefPubMedSearch in Google Scholar
  • 37 Cosman F, Hattersley G, Hu MY. et al. Effects of abaloparatide-SC on fractures and bone mineral density in subgroups of postmenopausal women with osteoporosis and varying baseline risk factors. J Bone Miner Res 2017; 32: 17-23
    CrossrefPubMedSearch in Google Scholar
  • 38 McCloskey EV, Fitzpatrick LA, Hu MY. et al. Effect of abaloparatide on vertebral, nonvertebral, major osteoporotic, and clinical fractures in a subset of postmenopausal women at increased risk of fracture by FRAX probability. Arch Osteoporos 2019; 14: 15
    CrossrefPubMedSearch in Google Scholar
  • 39 Bilezikian JP, Hattersley G, Mitlak BH. et al. Abaloparatide in patients with mild or moderate renal impairment: results from the ACTIVE phase 3 trial. Curr Med Res Opin 2019; 35: 2097-2102
    CrossrefPubMedSearch in Google Scholar
  • 40 McClung MR, Williams GC, Hattersley G. et al. Geography of fracture incidence in postmenopausal women with osteoporosis treated with abaloparatide. Calcif Tissue Int 2018; 102: 627-633
    CrossrefPubMedSearch in Google Scholar
  • 41 Miller PD, Hattersley G, Lau E. et al. Bone mineral density response rates are greater in patients treated with abaloparatide compared with those treated with placebo or teriparatide: Results from the ACTIVE phase 3 trial. Bone 2019; 120: 137-140
    CrossrefPubMedSearch in Google Scholar
  • 42 Winzenrieth R, Humbert L, Boxberger JI. et al. Abaloparatide effects on cortical volumetric BMD and estimated strength indices of hip subregions by 3D-DXA in women with postmenopausal osteoporosis. J Clin Densitom 2022; 25: 293-400
    CrossrefPubMedSearch in Google Scholar
  • 43 Leder BZ, Neer RM, Wyland JJ. et al. Effects of teriparatide treatment and discontinuation in postmenopausal women and eugonadal men with osteoporosis. J Clin Endocrinol Metab 2009; 94: 2915-2921
    CrossrefPubMedSearch in Google Scholar
  • 44 Bone HG, Cosman F, Miller PD. et al. ACTIVExtend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis. J Clin Endocrinol Metab 2018; 103: 2949-2957
    CrossrefPubMedSearch in Google Scholar
  • 45 Matsumoto T, Sone T, Soen S. et al. Abaloparatide increases lumbar spine and hip BMD in Japanese patients with osteoporosis: The phase 3 ACTIVE-J study. J Clin Endocrinol Metab 2022; 107: e4222-e4231
    CrossrefPubMedSearch in Google Scholar
  • 46 Czerwinski E, Cardona J, Plebanski R. et al. The efficacy and safety of abaloparatide-SC in men with osteoporosis: A randomized clinical trial. J Bone Miner Res 2022; 37: 2435-2442
    CrossrefPubMedSearch in Google Scholar
  • 47 Tabacco G, Bilezikian JP. Osteoanabolic and dual action drugs. Br J Clin Pharmacol 2019; 85: 1084-1094
    CrossrefPubMedSearch in Google Scholar
  • 48 Jolette J, Attalla B, Varela A. et al. Comparing the incidence of bone tumors in rats chronic ally exposed to the selective PTH type 1 receptor agonist abaloparatide or PTH(1–34). Regul Toxicol Pharmacol 2017; 86: 356-365
    CrossrefPubMedSearch in Google Scholar
  • 49 Gilsenan A, Midkiff K, Harris D, Kellier-Steele N. et al. Teriparatide did not increase adult osteosarcoma incidence in a 15-year US postmarketing surveillance study. J Bone Miner Res 2021; 36: 244-251
    CrossrefPubMedSearch in Google Scholar
  • 50 McDonald CL, Johnson K, Alsoof D. et al. Treatment of osteoporosis with anabolic agents and the risk of primary bone cancers: A study of 44,728 patients treated with teriparatide and abaloparatide. J Am Acad Orthop Surg 2023; 31: 520-528
    CrossrefPubMedSearch in Google Scholar
  • 51 Cosman F, Peterson LR, Towler DA. et al. Cardiovascular safety of abaloparatide in postmenopausal women with osteoporosis: analysis from the ACTIVE phase 3 trial. J Clin Endocrinol Metab 2020; 105: 1-12
    CrossrefPubMedSearch in Google Scholar
  • 52 Cosman F, Cooper C, Wang Y. et al. Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database study. Osteoporos Int 2022; 33: 1703-1714
    CrossrefPubMedSearch in Google Scholar
  • 53 Hong P, Liu R, Rai S. et al. Is abaloparatide more efficacious on increasing bone mineral density than teriparatide for women with postmenopausal osteoporosis? An updated meta-analysis. J Orthop Surg Res 2023; 18: 116
    CrossrefPubMedSearch in Google Scholar
  • 54 Gold DT, Weiss R, Beckett T. et al. Abaloparatide real-world patient experience study. JBMR Plus 2021; 5: e10457
    CrossrefPubMedSearch in Google Scholar
  • 55 Brent MB, Thomsen JS, Brüel A. The efficacy of PTH and abaloparatide to counteract immobilization-induced osteopenia is in general similar. Front Endocrinol (Lausanne) 2020; 11: 588773
    CrossrefPubMedSearch in Google Scholar