Osteologie 2019; 28(01): 29-33
DOI: 10.1055/a-0800-0860
Originalarbeit
© Georg Thieme Verlag KG Stuttgart · New York

Sclerostin-Antikörper als neue Therapieoption der Osteoporose

Sclerostin antibody as a new treatment option for osteoporosis
Simon Sebastian
1   Barmherzige Schwestern Krankenhaus Wien, II. Medizinische Abteilung, Akademisches Lehrkrankenhaus der Medizinischen Universität Wien, VINforce Study Group
,
Heinrich Resch
1   Barmherzige Schwestern Krankenhaus Wien, II. Medizinische Abteilung, Akademisches Lehrkrankenhaus der Medizinischen Universität Wien, VINforce Study Group
2   Lehrstuhl für klinische Osteologie, Medizinische Fakultät, Sigmund Freud Privatuniversität, Wien
› Author Affiliations
Further Information

Publication History

11/07/2018

11/15/2018

Publication Date:
05 March 2019 (online)

Zusammenfassung

Romosozumab ist ein humanisierter monoklonaler Antikörper gegen Sclerostin, der inhibierend auf die Osteogenese in Osteoblasten wirkt. Der Antikörper hat sowohl anabole als auch antiresorptive Eigenschaften. Bei postmenopausalen Frauen mit Osteoporose senkt Romosozumab die Inzidenz sowohl von vertebralen, als auch von non-vertebralen Frakturen und erhöht nicht nur die Knochenmineraldichte und die Parameter der Knochenneubildung, sondern senkt ebenfalls die Parameter der Knochenresorption. Auch bei Männern kann biochemisch eine gesteigerte Knochenneubildung und eine Zunahme der Knochenmineraldichte beobachtet werden. Obwohl in rezenten Publikationen Romosozumab gut toleriert wird, sollte das Risikoprofil und die Einsetzbarkeit in weiteren Studien diskutiert werden.

Abstract

Romosozumab is a monoclonal antibody that binds to sclerostin and prevents sclerostin from exerting his inhibitory effect on osteoblasts, producing an osteoanabolic response. This antibody increases bone formation on the one hand and decreases bone resorption on the other hand and shows in addition a significant gain in the bone-mineral-density. In women with postmenopausal osteoporosis, Romosozumab decreases the risk of vertebral and non-vertebral fractures compared to other anabolic and antiresorptive treatment option like bisphosphonate or Teriparatide. Moreover, Romosozumab increases bone-mineral-density and has effects on the bone metabolism also in men with osteoporosis. Although, Romosozumab is well tolerated in general with no major safety signals reported. At present, more studies are needed to determine the ideal setting of Romosozumab treatment and its potential risk.

 
  • Literatur

  • 1 Cosman F, Crittenden DB, Adachi JD. et al. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. The New England journal of medicine 2016; 375 (16) 1532-1543
  • 2 Saag KG, Petersen J, Brandi ML. et al. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. The New England journal of medicine 2017; 377 (15) 1417-1427
  • 3 Nguyen ND, Ahlborg HG, Center JR. et al. Residual lifetime risk of fractures in women and men. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2007; 22 (06) 781-788
  • 4 Haas AV, LeBoff MS. Osteoanabolic Agents for Osteoporosis. Journal of the Endocrine Society 2018; 2 (08) 922-932
  • 5 Langdahl BL, Libanati C, Crittenden DB. et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet 2017; 390 (10102): 1585-1594
  • 6 McClung MR, Grauer A, Boonen S. et al. Romosozumab in postmenopausal women with low bone mineral density. The New England journal of medicine 2014; 370 (05) 412-420
  • 7 Li X, Ominsky MS, Niu QT. et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2008; 23 (06) 860-869
  • 8 McClung MR, Brown JP, Diez-Perez A. et al. Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2018; 33 (08) 1397-1406
  • 9 Lewiecki EM, Blicharski T, Goemaere S. et al. A Phase 3 Randomized Placebo-controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis. The Journal of clinical endocrinology and metabolism. 2018
  • 10 Li X, Ominsky MS, Warmington KS. et al. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2009; 24 (04) 578-588
  • 11 Ominsky MS, Vlasseros F, Jolette J. et al. Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2010; 25 (05) 948-959
  • 12 Padhi D, Jang G, Stouch B. et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2011; 26 (01) 19-26
  • 13 Lim SY, Bolster MB. Profile of romosozumab and its potential in the management of osteoporosis. Drug design, development and therapy 2017; 11: 1221-1231
  • 14 Canalis E. Wnt signalling in osteoporosis: mechanisms and novel therapeutic approaches. Nature reviews Endocrinology 2013; 9 (10) 575-583
  • 15 Krause C, Korchynskyi O, de Rooij K. et al. Distinct modes of inhibition by sclerostin on bone morphogenetic protein and Wnt signaling pathways. The Journal of biological chemistry 2010; 285 (53) 41614-4126
  • 16 Genant HK, Engelke K, Bolognese MA. et al. Effects of Romosozumab Compared With Teriparatide on Bone Density and Mass at the Spine and Hip in Postmenopausal Women With Low Bone Mass. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2017; 32 (01) 181-187
  • 17 Cosman F, Crittenden DB, Ferrari S. et al. Romosozumab FRAME Study: A Post Hoc Analysis of the Role of Regional Background Fracture Risk on Nonvertebral Fracture Outcome. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2018; 33 (08) 1407-1416
  • 18 Glorieux FH, Devogelaer JP, Durigova M. et al. BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 2017; 32 (07) 1496-1504
  • 19 Simon S, Resch H, Klaushofer K. et al. Hypophosphatasia: From Diagnosis to Treatment. Current rheumatology reports 2018; 20 (11) 69
  • 20 Seefried L, Baumann J, Hemsley S. et al. Efficacy of anti-sclerostin monoclonal antibody BPS804 in adult patients with hypophosphatasia. The Journal of clinical investigation 2017; 127 (06) 2148-2158