Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future.

[1]  M. Karsdal,et al.  KBP-042 improves bodyweight and glucose homeostasis with indices of increased insulin sensitivity irrespective of route of administration. , 2015, European journal of pharmacology.

[2]  Raveendhara R. Bannuru,et al.  Effectiveness and Implications of Alternative Placebo Treatments , 2015, Annals of Internal Medicine.

[3]  R. Matico,et al.  Translational development of an ADAMTS-5 antibody for osteoarthritis disease modification. , 2015, Osteoarthritis and cartilage.

[4]  M. Karsdal,et al.  Call for standardized definitions of osteoarthritis and risk stratification for clinical trials and clinical use. , 2015, Osteoarthritis and cartilage.

[5]  F. Berenbaum,et al.  Emerging targets in osteoarthritis therapy. , 2015, Current opinion in pharmacology.

[6]  M. Karsdal,et al.  Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials. , 2015, Osteoarthritis and cartilage.

[7]  M. Karsdal,et al.  OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA. , 2015, Osteoarthritis and cartilage.

[8]  T. Ghayur,et al.  Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-IgTM) molecule that specifically and potently neutralizes both IL-1α and IL-1β , 2015, mAbs.

[9]  F. Eckstein,et al.  Intraarticular Sprifermin (Recombinant Human Fibroblast Growth Factor 18) in Knee Osteoarthritis: A Randomized, Double‐Blind, Placebo‐Controlled Trial , 2014, Arthritis & rheumatology.

[10]  L. Reynard,et al.  CpG methylation regulates allelic expression of GDF5 by modulating binding of SP1 and SP3 repressor proteins to the osteoarthritis susceptibility SNP rs143383 , 2014, Human Genetics.

[11]  C. Edenius,et al.  MIV-711, a highly selective cathepsin K inhibitor: safety, pharmacokinetics and pharmacodynamics of multiple oral doses in healthy postmenopausal women , 2014 .

[12]  E. Hohenester,et al.  Normal Activation of Discoidin Domain Receptor 1 Mutants with Disulfide Cross-links, Insertions, or Deletions in the Extracellular Juxtamembrane Region , 2014, The Journal of Biological Chemistry.

[13]  C. Christiansen,et al.  The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments? , 2013, Annals of the rheumatic diseases.

[14]  F. Flamigni,et al.  IKKα/CHUK Regulates Extracellular Matrix Remodeling Independent of Its Kinase Activity to Facilitate Articular Chondrocyte Differentiation , 2013, PloS one.

[15]  P. Low,et al.  Direct in vivo evidence of activated macrophages in human osteoarthritis. , 2013, Osteoarthritis and cartilage.

[16]  Scott A. Mercer,et al.  Growth factor regulation of growth factor production by multiple gene transfer to chondrocytes , 2013, Growth factors.

[17]  C. Cooper,et al.  Extended report: Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial , 2013 .

[18]  M. Karsdal,et al.  Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis , 2012, Menopause.

[19]  Peter Jüni,et al.  Doxycycline for osteoarthritis of the knee or hip. , 2012, The Cochrane database of systematic reviews.

[20]  C. Hayes,et al.  A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee , 2012, Annals of the rheumatic diseases.

[21]  M. Beekman,et al.  Metabolic health in families enriched for longevity is associated with low prevalence of hand osteoarthritis and influences OA biomarker profiles , 2012, Annals of the rheumatic diseases.

[22]  M. Karsdal,et al.  The Pathogenesis of Osteoarthritis Involves Bone, Cartilage and Synovial Inflammation: May Estrogen Be a Magic Bullet? , 2012, Menopause international.

[23]  C. Laurencin,et al.  Studies of bone morphogenetic protein-based surgical repair. , 2012, Advanced drug delivery reviews.

[24]  S. Goldring,et al.  The role of synovitis in osteoarthritis pathogenesis. , 2012, Bone.

[25]  M. Nevitt,et al.  Progression of osteoarthritis as a state of inertia , 2012, Annals of the rheumatic diseases.

[26]  L. Duong,et al.  Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. , 2012, Bone.

[27]  C. Benhamou,et al.  Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib. , 2012, Journal of the American Academy of Dermatology.

[28]  Xiaojuan Li,et al.  Imaging longitudinal changes in articular cartilage and bone following doxycycline treatment in a rabbit anterior cruciate ligament transection model of osteoarthritis. , 2012, Magnetic resonance imaging.

[29]  G. Verbruggen,et al.  Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification , 2011, Annals of the rheumatic diseases.

[30]  D. Burstein,et al.  A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. , 2011, Arthritis research & therapy.

[31]  Peggy H. Wong,et al.  Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. , 2011, Pharmacogenomics.

[32]  F. Berenbaum,et al.  Osteoarthritis: an update with relevance for clinical practice , 2011, The Lancet.

[33]  A R Poole,et al.  Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis OARSI FDA Osteoarthritis Biomarkers Working Group , 2011 .

[34]  S. Reichenbach,et al.  All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study , 2011, BMJ : British Medical Journal.

[35]  I. Sekiya,et al.  Intra‐articular injections of bone morphogenetic protein‐7 retard progression of existing cartilage degeneration , 2010, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[36]  D. Hunter,et al.  Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis , 2010, BMC musculoskeletal disorders.

[37]  J. McDougall,et al.  Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig model of spontaneous osteoarthritis. , 2010, Osteoarthritis and cartilage.

[38]  L. Leventhal,et al.  Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease. , 2010, Osteoarthritis and cartilage.

[39]  M. Karsdal,et al.  Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis - the effect of sex, Kellgren-Lawrence (KL) score, Body Mass Index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation , 2010, BMC musculoskeletal disorders.

[40]  R. Rizzoli,et al.  Odanacatib in the treatment of postmenopausal women with low bone mineral density: Three‐year continued therapy and resolution of effect , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[41]  M. Karsdal,et al.  The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study. , 2010, Osteoarthritis and cartilage.

[42]  J. Eisman,et al.  Odanacatib, a cathepsin‐K inhibitor for osteoporosis: A two‐year study in postmenopausal women with low bone density , 2009, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[43]  Gwo‐Jaw Wang,et al.  Parathyroid hormone 1-34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in rats. , 2009, Arthritis and rheumatism.

[44]  S. Kumar,et al.  Protective effects of a cathepsin K inhibitor, SB-553484, in the canine partial medial meniscectomy model of osteoarthritis. , 2009, Osteoarthritis and cartilage.

[45]  C. Christiansen,et al.  Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation , 2008, BMC musculoskeletal disorders.

[46]  R. Coleman,et al.  Association of bone scintigraphic abnormalities with knee malalignment and pain , 2008, Annals of the rheumatic diseases.

[47]  M. Hochberg,et al.  Mortality in osteoarthritis. , 2008, Clinical and experimental rheumatology.

[48]  K Henriksen,et al.  Should subchondral bone turnover be targeted when treating osteoarthritis? , 2008, Osteoarthritis and cartilage.

[49]  Gillian Murphy,et al.  Reappraising metalloproteinases in rheumatoid arthritis and osteoarthritis: destruction or repair? , 2008, Nature Clinical Practice Rheumatology.

[50]  Y. Yoo,et al.  Cilostazol protects rat chondrocytes against nitric oxide-induced apoptosis in vitro and prevents cartilage destruction in a rat model of osteoarthritis. , 2008, Arthritis and rheumatism.

[51]  T. Spector,et al.  Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebo-controlled study , 2007, Arthritis research & therapy.

[52]  A. Tsykin,et al.  Microarray gene expression profiling of osteoarthritic bone suggests altered bone remodelling, WNT and transforming growth factor-β/bone morphogenic protein signalling , 2007, Arthritis research & therapy.

[53]  M. Karsdal,et al.  The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model. , 2007, Arthritis and rheumatism.

[54]  E. Thonar,et al.  Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis. , 2006, Arthritis and rheumatism.

[55]  R. Wallace,et al.  Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative. , 2006, Arthritis and rheumatism.

[56]  D J Hunter,et al.  Classification of osteoarthritis biomarkers: a proposed approach. , 2006, Osteoarthritis and cartilage.

[57]  Claus Christiansen,et al.  Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation. , 2006, Arthritis and rheumatism.

[58]  C. Bingham,et al.  A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. , 2006, Rheumatology.

[59]  M. Karsdal,et al.  Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA? , 2006, Osteoarthritis and cartilage.

[60]  S. Abramson,et al.  Prospects for disease modification in osteoarthritis , 2006, Nature Clinical Practice Rheumatology.

[61]  L. Sharma,et al.  Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. , 2005, Arthritis and rheumatism.

[62]  D. Thompson,et al.  Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. , 2005, Osteoarthritis and cartilage.

[63]  T. Spector,et al.  Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173] , 2005, Arthritis Research & Therapy.

[64]  D. Chappard,et al.  Effects of Calcitonin on Subchondral Trabecular Bone Changes and on Osteoarthritic Cartilage Lesions After Acute Anterior Cruciate Ligament Deficiency , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[65]  C. Christiansen,et al.  Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM) , 2004, Menopause.

[66]  L. Duong,et al.  The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model. , 2004, Arthritis and rheumatism.

[67]  K. Jordan,et al.  Clinical comorbidity in patients with osteoarthritis: a case-control study of general practice consulters in England and Wales , 2004, Annals of the rheumatic diseases.

[68]  D. Felson,et al.  Osteoarthritis: is it a disease of cartilage or of bone? , 2004, Arthritis and rheumatism.

[69]  T. Spector,et al.  Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies , 2004, The New England journal of medicine.

[70]  C. Christiansen,et al.  Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index , 2003, Annals of the rheumatic diseases.

[71]  A. Reiner,et al.  Molecular changes in human osteoarthritic cartilage after 3 weeks of oral administration of BAY 12-9566, a matrix metalloproteinase inhibitor. , 2003, The Journal of rheumatology.

[72]  B. Lindgren,et al.  Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys. , 2002, Arthritis and rheumatism.

[73]  R. Wynn,et al.  Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins. , 1999, Science.

[74]  B. Lanske,et al.  Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development. , 1996, Endocrinology.

[75]  D. Felson,et al.  The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. , 1995, Arthritis and rheumatism.

[76]  G. Panayi,et al.  Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. , 1993, Annals of the rheumatic diseases.

[77]  C. Christiansen,et al.  Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. , 2014, Osteoarthritis and cartilage.

[78]  K Henriksen,et al.  Osteoarthritis--a case for personalized health care? , 2014, Osteoarthritis and cartilage.

[79]  F. Berenbaum,et al.  Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). , 2013, Osteoarthritis and cartilage.

[80]  M. Karsdal,et al.  Calcitonin — A Drug of the Past or for the Future? , 2012, BioDrugs.

[81]  R. Panush.  Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis , 2012 .

[82]  K A Athanasiou,et al.  Systematic assessment of growth factor treatment on biochemical and biomechanical properties of engineered articular cartilage constructs. , 2009, Osteoarthritis and cartilage.

[83]  M. Karsdal,et al.  Strontium ranelate reduces the urinary level of cartilage degradation biomarker CTX-II in postmenopausal women. , 2007, Bone.

[84]  H. Ma,et al.  Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis , 2007, Nature.

[85]  M. Karsdal,et al.  Call for standardized de fi nitions of osteoarthritis and risk strati fi cation for clinical trials and clinical use , 2022 .