Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass
Tony M. Keaveny,Daria B. Crittenden,Michael A. Bolognese,Harry K. Genant,Klaus Engelke,Beatriz Oliveri,Jacques P. Brown,Bente L. Langdahl,Chris Yan,Andreas Grauer,Cesar Libanati +10 more
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TLDR
It is suggested that romosozumab may offer patients with osteoporosis a new bone‐forming therapeutic option that increases both vertebral and femoral strength within 12 months.Abstract:
Romosozumab is a monoclonal antibody that inhibits sclerostin and has been shown to reduce the risk of fractures within 12 months. In a phase II, randomized, placebo-controlled clinical trial of treatment-naive postmenopausal women with low bone mass, romosozumab increased bone mineral density (BMD) at the hip and spine by the dual effect of increasing bone formation and decreasing bone resorption. In a substudy of that trial, which included placebo and teriparatide arms, here we investigated whether those observed increases in BMD also resulted in improvements in estimated strength, as assessed by finite element analysis. Participants received blinded romosozumab s.c. (210 mg monthly) or placebo, or open-label teriparatide (20 μg daily) for 12 months. CT scans, obtained at the lumbar spine (n = 82) and proximal femur (n = 46) at baseline and month 12, were analyzed with finite element software (VirtuOst, O.N. Diagnostics) to estimate strength for a simulated compression overload for the spine (L1 vertebral body) and a sideways fall for the proximal femur, all blinded to treatment assignment. We found that, at month 12, vertebral strength increased more for romosozumab compared with both teriparatide (27.3% versus 18.5%; p = 0.005) and placebo (27.3% versus -3.9%; p < 0.0001); changes in femoral strength for romosozumab showed similar but smaller changes, increasing more with romosozumab versus teriparatide (3.6% versus -0.7%; p = 0.027), and trending higher versus placebo (3.6% versus -0.1%; p = 0.059). Compartmental analysis revealed that the bone-strengthening effects for romosozumab were associated with positive contributions from both the cortical and trabecular bone compartments at both the lumbar spine and hip. Taken together, these findings suggest that romosozumab may offer patients with osteoporosis a new bone-forming therapeutic option that increases both vertebral and femoral strength within 12 months. © 2017 American Society for Bone and Mineral Research.read more
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Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis
Kenneth G. Saag,Jeffrey Petersen,Maria Luisa Brandi,Andrew C. Karaplis,Mattias Lorentzon,Thierry Thomas,Judy Maddox,Michelle Fan,Paul D Meisner,Andreas Grauer +9 more
TL;DR: In postmenopausal women with osteoporosis who were at high risk for fracture, romosozumab treatment for 12 months followed by alendronsate resulted in a significantly lower risk of fracture than alendronate alone.
Journal ArticleDOI
Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment
TL;DR: Recent advances in understanding the molecular mechanisms regulating osteoblast differentiation and adipocyte differentiation of Mesenchymal stem cells are reviewed and the therapeutic application studies of MSCs in osteoporosis treatment are highlighted.
Journal ArticleDOI
A Phase III Randomized Placebo-Controlled Trial to Evaluate Efficacy and Safety of Romosozumab in Men With Osteoporosis
E. Michael Lewiecki,Tomasz Blicharski,Stefan Goemaere,Kurt Lippuner,Paul D Meisner,Paul D. Miller,Akimitsu Miyauchi,Judy Maddox,Li Chen,Stéphane Horlait +9 more
TL;DR: Treatment with romosozumab for 12 months increased the spine and hip BMD compared with placebo and was well tolerated in men with osteoporosis.
Journal ArticleDOI
One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study.
E. Michael Lewiecki,Rajani Dinavahi,Marise Lazaretti-Castro,Peter R. Ebeling,Jonathan D. Adachi,Akimitsu Miyauchi,Evelien Gielen,Cassandra E Milmont,Cesar Libanati,Andreas Grauer +9 more
TL;DR: In postmenopausal women with osteoporosis, 12 months of romosozumab led to persistent fracture reduction benefit and ongoing BMD gains when followed by 24 months of denosumab.
Journal ArticleDOI
The clinician’s guide to prevention and treatment of osteoporosis
Meryl S. LeBoff,Susan L. Greenspan,Karl L. Insogna,E. Michael Lewiecki,Kenneth G. Saag,Andrea Singer,E. S. Siris +6 more
TL;DR: Osteoporosis is the most common metabolic bone disease in the USA and the world and it is a subclinical condition until complicated by fracture(s). These fractures place an enormous medical and personal burden on individuals who suffer from them and take a significant economic toll as mentioned in this paper .
References
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Clinician’s Guide to Prevention and Treatment of Osteoporosis
Felicia Cosman,S. J. de Beur,Meryl S. LeBoff,E. M. Lewiecki,B. Tanner,S. Randall,Robert Lindsay +6 more
TL;DR: The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteiporosis Foundation in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF.
Journal ArticleDOI
Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling
Xiaofeng Li,Yazhou Zhang,Heeseog Kang,Wenzhong Liu,Peng Liu,Jianghong Zhang,Stephen E. Harris,Dianqing Wu +7 more
TL;DR: It is found that sclerostin could antagonize canonical Wnt signaling in human embryonic kidney A293T cells and mouse osteoblastic MC3T3 cells and that s clergyostin bound to LRP5 as well as LRP6 and the first two YWTD-EGF repeat domains of L RP5 as being responsible for the binding.
Journal ArticleDOI
Romosozumab Treatment in Postmenopausal Women with Osteoporosis.
Felicia Cosman,Daria B. Crittenden,Jonathan D. Adachi,Neil Binkley,Edward Czerwiński,Serge Ferrari,Lorenz C. Hofbauer,E. Lau,E. M. Lewiecki,Akimitsu Miyauchi,C. A. F. Zerbini,C. E. Milmont,L. Chen,Judy Maddox,Paul D Meisner,Cesar Libanati,Andreas Grauer +16 more
TL;DR: In postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months.
Journal ArticleDOI
Romosozumab in Postmenopausal Women with Low Bone Mineral Density
Michael R. McClung,Andreas Grauer,Steven Boonen,Michael A. Bolognese,Jacques P. Brown,Adolfo Diez-Perez,Bente L. Langdahl,Jean-Yves Reginster,Jose R. Zanchetta,Scott M. Wasserman,Leonid Katz,Judy Maddox,Y.-C. Yang,Cesar Libanati,Henry G. Bone +14 more
TL;DR: In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption.
Journal ArticleDOI
Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation
Kenneth E. S. Poole,Rutger L. van Bezooijen,Nigel Loveridge,Herman Hamersma,Socrates E. Papapoulos,Clemens W.G.M. Löwik,Jonathan Reeve +6 more
TL;DR: In vivo evidence is provided for the first time to support the concept that osteocytes secrete sclerostin after they become embedded in a mineralized matrix to limit further bone formation by osteoblasts and propose that sclerOSTin production by osteocytes may regulate the linear extent of formation and the induction or maintenance of a lining cell phenotype on bone surfaces.