Denosumab: mechanism of action and clinical outcomes

Aims:  To describe the mechanisms of action of denosumab, a novel antiresorptive agent, contrasting it with other antiresorptive and anabolic osteoporosis treatments.

[1]  R. Dore.  Data from Extension Trials: Denosumab and Zoledronic Acid , 2012, Current Osteoporosis Reports.

[2]  P. Marie,et al.  Osteoblasts in osteoporosis: past, emerging, and future anabolic targets. , 2011, European journal of endocrinology.

[3]  R. Baron,et al.  Denosumab and bisphosphonates: different mechanisms of action and effects. , 2011, Bone.

[4]  J. S. San Martin,et al.  Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. , 2011, The Journal of clinical endocrinology and metabolism.

[5]  Aliya A. Khan,et al.  Primary hyperparathyroidism: Update on presentation, diagnosis, and management in primary care. , 2011, Canadian family physician Medecin de famille canadien.

[6]  David A Hanley,et al.  2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary , 2010, Canadian Medical Association Journal.

[7]  D. Hussar,et al.  New drugs: Denosumab, dienogest/estradiol valerate, and polidocanol. , 2010, Journal of the American Pharmacists Association : JAPhA.

[8]  A. LaCroix,et al.  Impact of prevalent fractures on quality of life: baseline results from the global longitudinal study of osteoporosis in women. , 2010, Mayo Clinic proceedings.

[9]  Sharmila Majumdar,et al.  Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[10]  W. Leslie,et al.  Population-based Canadian hip fracture rates with international comparisons , 2010, Osteoporosis International.

[11]  E. Michael Lewiecki.  Treatment of osteoporosis with denosumab. , 2010, Maturitas.

[12]  I. Reid,et al.  Effect of osteoporosis treatment on mortality: a meta-analysis. , 2010, The Journal of clinical endocrinology and metabolism.

[13]  Eve Donnelly,et al.  The assessment of fracture risk. , 2010, The Journal of bone and joint surgery. American volume.

[14]  Jian-min Liu,et al.  Raloxifene inhibits bone loss and improves bone strength through an Opg-independent mechanism , 2010, Endocrine.

[15]  Jacques P. Brown,et al.  Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  Claus Christiansen,et al.  Denosumab for prevention of fractures in postmenopausal women with osteoporosis. , 2009, The New England journal of medicine.

[17]  C. Deal,et al.  Clinical update on teriparatide , 2009, Current rheumatology reports.

[18]  M. Hiligsmann,et al.  The clinical and economic burden of non-adherence with oral bisphosphonates in osteoporotic patients. , 2009, Health policy.

[19]  G. Ioannidis,et al.  The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study , 2009, Osteoporosis International.

[20]  R. O’Keefe,et al.  Activation of β‐Catenin Signaling in Articular Chondrocytes Leads to Osteoarthritis‐Like Phenotype in Adult β‐Catenin Conditional Activation Mice , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[21]  J. S. San Martin,et al.  Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. , 2008, Bone.

[22]  N. Watts,et al.  Mechanisms of action of bisphosphonates: similarities and differences and their potential influence on clinical efficacy , 2008, Osteoporosis International.

[23]  M. Maglione,et al.  Comparative Effectiveness of Treatments To Prevent Fractures in Men and Women With Low Bone Density or Osteoporosis , 2007 .

[24]  F. Pérez-López.  Vitamin D and its implications for musculoskeletal health in women: an update. , 2007, Maturitas.

[25]  S. Cummings,et al.  Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. , 2007, The New England journal of medicine.

[26]  Roberto Pacifici,et al.  Estrogen deficiency and bone loss: an inflammatory tale. , 2006, The Journal of clinical investigation.

[27]  Jacques P. Brown,et al.  Canadian Consensus Conference on osteoporosis, 2006 update. , 2006, Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC.

[28]  Jacques P. Brown,et al.  Risk factors associated with incident clinical vertebral and nonvertebral fractures in postmenopausal women: the Canadian Multicentre Osteoporosis Study (CaMos) , 2005, Osteoporosis International.

[29]  David Greenblatt,et al.  Treatment of Postmenopausal Osteoporosis , 2005, Pharmacotherapy.

[30]  J. Bilezikian.  Anabolic Therapy for Osteoporosis , 2005, Women's health.

[31]  E. Seeman.  Reduced bone formation and increased bone resorption: rational targets for the treatment of osteoporosis , 2003, Osteoporosis International.

[32]  D. Goltzman,et al.  Discoveries, drugs and skeletal disorders , 2002, Nature Reviews Drug Discovery.

[33]  G. Guyatt,et al.  Meta-analyses of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. , 2002, Endocrine reviews.

[34]  C. Kooperberg,et al.  Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. , 2002, JAMA.

[35]  J. Reginster,et al.  Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. , 2001, The New England journal of medicine.

[36]  P Geusens,et al.  Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group. , 2001, The New England journal of medicine.

[37]  S. Manolagas,et al.  Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. , 2000, Endocrine reviews.

[38]  H K Genant,et al.  Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. , 1999, JAMA.

[39]  C C Glüer,et al.  Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. , 1999, JAMA.

[40]  M. Rogers,et al.  Bisphosphonates: from the laboratory to the clinic and back again. , 1999, Bone.

[41]  A. LaCroix,et al.  Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. , 1998, JAMA.

[42]  S. Cummings,et al.  Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures , 1996, The Lancet.

[43]  B. Clarke,et al.  Five Years of Denosumab Exposure in Women With Postmenopausal Osteoporosis: Results From the First Two Years of the FREEDOM Extension , 2012 .

[44]  S. Keam,et al.  Denosumab: a review of its use in the treatment of postmenopausal osteoporosis. , 2011, Drugs & aging.

[45]  Jennifer M. Belavic.  Denosumab (Prolia): A new option in the treatment of osteoporosis. , 2011, The Nurse practitioner.

[46]  A. Lipton,et al.  Clinical development of anti-RANKL therapies for treatment and prevention of bone metastasis. , 2011, Bone.

[47]  C. Lebrun.  2010 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada: summary , 2011 .

[48]  B. Clarke,et al.  Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis , 2010 .

[49]  D. Dempster,et al.  Pharmacological Mechanisms of Therapeutics: Parathyroid Hormone , 2008 .

[50]  J. Brown,et al.  The care gap in diagnosis and treatment of women with a fragility fracture , 2007, Osteoporosis International.

[51]  Jacques P. Brown,et al.  clinical practice guidelines for the diagnosis and management of osteoporosis in Canada , 2002 .

[52]  R. Goodman,et al.  The effect of risedronate on the risk of hip fracture in elderly women. , 2001, The New England journal of medicine.

[53]  Product Monograph,et al.  PRODUCT MONOGRAPH , 2000 .

[54]  Effects of hormone therapy on bone mineral density: results from the postmenopausal estrogen/progestin interventions (PEPI) trial. The Writing Group for the PEPI. , 1996, JAMA.

[55]  John P. Bilezikian,et al.  Principles of Bone Biology , 1996 .