The coupling of bone and cartilage turnover in osteoarthritis: Opportunities for bone antiresorptives and anabolics as potential treatments?

Annals of the Rheumatic Diseases

Volumn 73, Issue 2, 2014, Pages 336-348

  Karsdal, M A ^a   Bay Jensen, A C ^a   Lories, R J ^b,c   Abramson, S ^d   Spector, T ^e   Pastoureau, P ^f   Christiansen, C ^a   Attur, M ^d   Henriksen, K ^a   Goldring, S R ^g   Kraus, V ^h  

^a NORDIC BIOSCIENCE A S   (Denmark)

^b SKELETAL BIOLOGY AND ENGINEERING RESEARCH CENTER   (Belgium)

^c UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^d NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e KING'S COLLEGE LONDON   (United Kingdom)

^f INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

^g HOSPITAL FOR SPECIAL SURGERY   (United States)

^h DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGENTS AFFECTING METABOLISM; ALENDRONIC ACID; ANABOLIC AGENT; ANTIRESORPTIVE AGENT; BISPHOSPHONIC ACID DERIVATIVE; CALCITONIN; CATHEPSIN K; CATHEPSIN K INHIBITOR; CENTCHROMAN; DENOSUMAB; ESTROGEN; PARATHYROID HORMONE; PARATHYROID HORMONE RELATED PROTEIN; PLACEBO; RALOXIFENE; RISEDRONIC ACID; SALCATONIN; SELECTIVE ESTROGEN RECEPTOR MODULATOR; STRONTIUM RANELATE; TIBOLONE; UNCLASSIFIED DRUG; ZOLEDRONIC ACID;

ARTICULAR CARTILAGE; BONE STRUCTURE; BONE TURNOVER; CARTILAGE TURNOVER; CELL ACTIVITY; DRUG MECHANISM; ESTROGEN THERAPY; HUMAN; IMMUNE SYSTEM; INFLAMMATION; MUSCULOSKELETAL FUNCTION; NONHUMAN; OSTEOARTHRITIS; OSTEOBLAST; OSTEOCLAST; OSTEOCYTE; OSTEOLYSIS; OSTEOPOROSIS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SUBCHONDRAL BONE PLATE; SYSTEMATIC REVIEW;

EID: 84891747397     PISSN: 00034967     EISSN: 14682060     Source Type: Journal    
DOI: 10.1136/annrheumdis-2013-204111     Document Type: Review

References (264)

1. Abramson SB, Attur M, Yazici Y. Prospects for disease modification in osteoarthritis. Nat Clin Pract Rheumatol 2006;2:304-12. (Pubitemid 43842259)
2. Bijlsma JW, Berenbaum F, Lafeber FP. Osteoarthritis: an update with relevance for clinical practice. Lancet 2011;377:2115-26.
3. Felson DT, Neogi T. Osteoarthritis: is it a disease of cartilage or of bone? Arthritis Rheum 2004;50:341-4. (Pubitemid 38198815)
4. Hayami T, Pickarski M, Wesolowski GA, 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. Arthritis Rheum 2004;50:1193-206. (Pubitemid 38480830)
5. Bellido M, Lugo L, Roman-Blas JA, et al. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Arthritis Res Ther 2010;12:R152.
6. Bellido M, Lugo L, Roman-Blas JA, et al. Improving subchondral bone integrity reduces progression of cartilage damage in experimental osteoarthritis preceded by osteoporosis. Osteoarthritis Cartilage 2011;19:1228-36.
7. Castaneda S, Roman-Blas JA, Largo R, et al. Subchondral bone as a key target for osteoarthritis treatment. Biochem Pharmacol 2012;83:315-23.
8. Calvo E, Castaneda S, Largo R, et al. Osteoporosis increases the severity of cartilage damage in an experimental model of osteoarthritis in rabbits. Osteoarthritis Cartilage 2007;15:69-77. (Pubitemid 46117909)
9. Bay-Jensen AC, Hoegh-Madsen S, Dam E, et al. Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis? Rheumatol Int 2010;30:435-42.
10. Sandell LJ. Etiology of osteoarthritis: genetics and synovial joint development. Nat Rev Rheumatol 2012;8:77-89.
11. Chapman K, Valdes AM. Genetic factors in OA pathogenesis. Bone 2012;51:258-64.
12. Noble BS, Peet N, Stevens HY, et al. Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol 2003;284:C934-43. (Pubitemid 36336949)
13. Rodan GA. Mechanical loading, estrogen deficiency, and the coupling of bone formation to bone resorption. J Bone Miner Res 1991;6:527-30.
14. Richette P, Bardin T. Structure-modifying agents for osteoarthritis: an update. Joint Bone Spine 2004;71:18-23. (Pubitemid 38183282)
15. Richette P, Corvol M, Bardin T. Estrogens, cartilage, and osteoarthritis. Joint Bone Spine 2003;70:257-62. (Pubitemid 37064580)
16. Gelber AC, Hochberg MC, Mead LA, et al. Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med 2000;133:321-8.
17. Gelber AC, Hochberg MC, Mead LA, et al. Body mass index in young men and the risk of subsequent knee and hip osteoarthritis. Am J Med 1999;107:542-8.
18. Bijlsma JW, Knahr K. Strategies for the prevention and management of osteoarthritis of the hip and knee. Best Pract Res Clin Rheumatol 2007;21:59-76. (Pubitemid 46351947)
19. Mouritzen U, Christgau S, Lehmann HJ, 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. Ann Rheum Dis 2003;62:332-6. (Pubitemid 36363439)
20. Ma HL, Blanchet TJ, Peluso D, et al. Osteoarthritis severity is sex dependent in a surgical mouse model. Osteoarthritis Cartilage 2007;15:695-700. (Pubitemid 46760614)
21. Hoegh-Andersen P, Tanko LB, Andersen TL, et al. Ovariectomized rats as a model of postmenopausal osteoarthritis: validation and application. Arthritis Res Ther 2004;6:R169-80.
22. Christgau S, Tanko LB, Cloos PA, et al. Suppression of elevated cartilage turnover in postmenopausal women and in ovariectomized rats by estrogen and a selective estrogen-receptor modulator (SERM). Menopause 2004;11:508-18. (Pubitemid 40362149)
23. Mansell JP, Collins C, Bailey AJ. Bone, not cartilage, should be the major focus in osteoarthritis. Nat Clin Pract Rheumatol 2007;3:306-7. (Pubitemid 46864879)
24. Bailey AJ, Mansell JP, Sims TJ, et al. Biochemical and mechanical properties of subchondral bone in osteoarthritis. Biorheology 2004;41:349-58. (Pubitemid 39277092)
25. Mansell JP, Bailey AJ. Increased metabolism of bone collagen in post-menopausal female osteoporotic femoral heads. Int J Biochem Cell Biol 2003;35:522-9. (Pubitemid 36140072)
26. Bailey AJ, Mansell JP. Do subchondral bone changes exacerbate or precede articular cartilage destruction in osteoarthritis of the elderly? Gerontology 1997;43:296-304. (Pubitemid 27390311)
27. Mansell JP, Tarlton JF, Bailey AJ. Biochemical evidence for altered subchondral bone collagen metabolism in osteoarthritis of the hip. Br J Rheumatol 1997;36:16-19.
28. Davis MA, Ettinger WH, Neuhaus JM, et al. Knee osteoarthritis and physical functioning: evidence from the NHANES I Epidemiologic Followup Study. J Rheumatol 1991;18:591-8.
29. Davis MA, Ettinger WH, Neuhaus JM. Obesity and osteoarthritis of the knee: evidence from the National Health and Nutrition Examination Survey (NHANES I). Semin Arthritis Rheum 1990;20(3 Suppl 1):34-41.
30. Suri S, Gill SE, Massena de CS, et al. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis 2007;66:1423-8. (Pubitemid 350032647)
31. Dequeker J, Tobing L, Rutten V, et al. Relative risk factors for osteoporotic fracture: a pilot study of the MEDOS questionnaire. Clin Rheumatol 1991;10:49-53.
32. Dequeker J, Johnell O. Osteoarthritis protects against femoral neck fracture: the MEDOS study experience. Bone 1993;14(Suppl 1):S51-6. (Pubitemid 23361518)
33. Dequeker J, Aerssens J, Luyten FP. Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship. Aging Clin Exp Res 2003;15:426-39. (Pubitemid 37509168)
34. bdin-Mohamed M, Jameson K, Dennison EM, et al. Volumetric bone mineral density of the tibia is not increased in subjects with radiographic knee osteoarthritis. Osteoarthritis Cartilage 2009;17:174-7.
35. Arden NK, Nevitt MC, Lane NE, et al. Osteoarthritis and risk of falls, rates of bone loss, and osteoporotic fractures. Study of Osteoporotic Fractures Research Group. Arthritis Rheum 1999;42:1378-85. (Pubitemid 30265595)
36. Arden NK, Griffiths GO, Hart DJ, et al. The association between osteoarthritis and osteoporotic fracture: the Chingford Study. Br J Rheumatol 1996;35:1299-304.
37. Hassett G, Hart DJ, Manek NJ, et al. Risk factors for progression of lumbar spine disc degeneration: the Chingford Study. Arthritis Rheum 2003;48:3112-17. (Pubitemid 37409322)
38. Dolan AL, Hart DJ, Doyle DV, et al. The relationship of joint hypermobility, bone mineral density, and osteoarthritis in the general population: the Chingford Study. J Rheumatol 2003;30:799-803. (Pubitemid 36402775)
39. Bettica P, Cline G, Hart DJ, et al. Evidence for increased bone resorption in patients with progressive knee osteoarthritis: longitudinal results from the Chingford study. Arthritis Rheum 2002;46:3178-84. (Pubitemid 35453526)
40. Hannan MT, Anderson JJ, Zhang Y, et al. Bone mineral density and knee osteoarthritis in elderly men and women. The Framingham Study. Arthritis Rheum 1993;36:1671-80. (Pubitemid 23360006)
41. Hunter DJ, Hart D, Snieder H, et al. Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins. Rheumatology (Oxford) 2003;42:1311-16. (Pubitemid 37407022)
42. Hunter DJ, Spector TD. The role of bone metabolism in osteoarthritis. Curr Rheumatol Rep 2003;5:15-19.
43. Dieppe P, Cushnaghan J, Young P, et al. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. Ann Rheum Dis 1993;52:557-63. (Pubitemid 23246656)
44. Rogers J, Shepstone L, Dieppe P. Is osteoarthritis a systemic disorder of bone? Arthritis Rheum 2004;50:452-7. (Pubitemid 38198829)
45. Nelson F, Dahlberg L, Laverty S, et al. Evidence for altered synthesis of type II collagen in patients with osteoarthritis. J Clin Invest 1998;102:2115-25. (Pubitemid 29018818)
46. McCrae F, Shouls J, Dieppe P, et al. Scintigraphic assessment of osteoarthritis of the knee joint. Ann Rheum Dis 1992;51:938-42.
47. McCarthy C, Cushnaghan J, Dieppe P. The predictive role of scintigraphy in radiographic osteoarthritis of the hand. Osteoarthritis Cartilage 1994;2:25-8. (Pubitemid 24159677)
48. Hamilton-Wood C, Hollingworth P, Dieppe P, et al. The painful swollen sterno-clavicular joint. Br J Radiol 1985;58:941-5. (Pubitemid 16215275)
49. Dieppe P. Subchondral bone should be the main target for the treatment of pain and disease progression in osteoarthritis. Osteoarthritis Cartilage 1999;7:325-6. (Pubitemid 29244113)
50. Arden N, Nevitt MC. Osteoarthritis: epidemiology. Best Pract Res Clin Rheumatol 2006;20:3-25. (Pubitemid 43230460)
51. Kraus VB, Feng S, Wang S, et al. Trabecular morphometry by fractal signature analysis is a novel marker of osteoarthritis progression. Arthritis Rheum 2009;60:3711-22.
52. Goldring MB, Goldring SR. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann N Y Acad Sci 2010;1192:230-7.
53. Garnero P, Peterfy C, Zaim S, et al. Bone marrow abnormalities on magnetic resonance imaging are associated with type II collagen degradation in knee osteoarthritis: a three-month longitudinal study. Arthritis Rheum 2005;52:2822-9. (Pubitemid 41369112)
54. Taljanovic MS, Graham AR, Benjamin JB, et al. Bone marrow edema pattern in advanced hip osteoarthritis: quantitative assessment with magnetic resonance imaging and correlation with clinical examination, radiographic findings, and histopathology. Skeletal Radiol 2008;37:423-31.
55. Hunter DJ, Gerstenfeld L, Bishop G, et al. Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized. Arthritis Res Ther 2009;11:R11.
56. Driban JB, Lo GH, Lee JY, et al. Quantitative bone marrow lesion size in osteoarthritic knees correlates with cartilage damage and predicts longitudinal cartilage loss. BMC Musculoskelet Disord 2011;12:217.
57. Felson DT, Chaisson CE, Hill CL, et al. The association of bone marrow lesions with pain in knee osteoarthritis. Ann Intern Med 2001;134:541-9. (Pubitemid 32245315)
58. Wohl GR, Shymkiw RC, Matyas JR, et al. Periarticular cancellous bone changes following anterior cruciate ligament injury. J Appl Physiol 2001;91:336-42. (Pubitemid 32574743)
59. Hayami T, Pickarski M, Zhuo Y, et al. Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis. Bone 2006;38:234-43. (Pubitemid 43165790)
60. Boyd SK, Matyas JR, Wohl GR, et al. Early regional adaptation of periarticular bone mineral density after anterior cruciate ligament injury. J Appl Physiol 2000;89:2359-64.
61. Ham KD, Carlson CS. Effects of estrogen replacement therapy on bone turnover in subchondral bone and epiphyseal metaphyseal cancellous bone of ovariectomized cynomolgus monkeys. J Bone Miner Res 2004;19:823-9. (Pubitemid 41094394)
62. Boyd SK, Muller R, Zernicke RF. Mechanical and architectural bone adaptation in early stage experimental osteoarthritis. J Bone Miner Res 2002;17:687-94. (Pubitemid 34246644)
63. Mansell JP, Bailey AJ. Abnormal cancellous bone collagen metabolism in osteoarthritis. J Clin Invest 1998;101:1596-603. (Pubitemid 28198488)
64. Ham KD, Loeser RF, Lindgren BR, et al. Effects of long-term estrogen replacement therapy on osteoarthritis severity in cynomolgus monkeys. Arthritis Rheum 2002;46:1956-64. (Pubitemid 34774529)
65. Carbone LD, Nevitt MC, Wildy K, et al. The relationship of antiresorptive drug use to structural findings and symptoms of knee osteoarthritis. Arthritis Rheum 2004;50:3516-25. (Pubitemid 39488676)
66. Stok KS, Pelled G, Zilberman Y, et al. Revealing the interplay of bone and cartilage in osteoarthritis through multimodal imaging of murine joints. Bone 2009;45:414-22.
67. Pastoureau PC, Chomel AC, Bonnet J. Evidence of early subchondral bone changes in the meniscectomized guinea pig. A densitometric study using dual-energy X-ray absorptiometry subregional analysis. Osteoarthritis Cartilage 1999;7:466-73. (Pubitemid 29468741)
68. Sassi ML, Eriksen H, Risteli L, et al. Immunochemical characterization of assay for carboxyterminal telopeptide of human type I collagen: loss of antigenicity by treatment with cathepsin K. Bone 2000;26:367-73. (Pubitemid 30136127)
69. Quasnichka HL, Anderson-MacKenzie JM, Bailey AJ. Subchondral bone and ligament changes precede cartilage degradation in guinea pig osteoarthritis. Biorheology 2006;43:389-97. (Pubitemid 44221920)
70. Anderson-MacKenzie JM, Quasnichka HL, Starr RL, et al. Fundamental subchondral bone changes in spontaneous knee osteoarthritis. Int J Biochem Cell Biol 2005;37:224-36. (Pubitemid 39286038)
71. Huebner JL, Hanes MA, Beekman B, et al. A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis. Osteoarthritis Cartilage 2002;10:758-67. (Pubitemid 35153716)
72. Huebner JL, Williams JM, Deberg M, et al. Collagen fibril disruption occurs early in primary guinea pig knee osteoarthritis. Osteoarthritis Cartilage 2010;18:397-405.
73. Diarra D, Stolina M, Polzer K, et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 2007;13:156-63.
74. Oh H, Chun CH, Chun JS. Dkk-1 expression in chondrocytes inhibits experimental osteoarthritic cartilage destruction in mice. Arthritis Rheum 2012;64:2568-78.
75. Daoussis D, Andonopoulos AP. The emerging role of Dickkopf-1 in bone biology: is it the main switch controlling bone and joint remodeling? Semin Arthritis Rheum 2011;41:170-7.
76. Honsawek S, Tanavalee A, Yuktanandana P, et al. Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients. BMC Musculoskelet Disord 2010;11:257.
77. Weng LH, Wang CJ, Ko JY, et al. Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic knees. Arthritis Rheum 2010;62:1393-402.
78. Voorzanger-Rousselot N, Ben-Tabassi NC, Garnero P. Opposite relationships between circulating Dkk-1 and cartilage breakdown in patients with rheumatoid arthritis and knee osteoarthritis. Ann Rheum Dis 2009;68:1513-14.
79. Lane NE, Nevitt MC, Lui LY, et al. Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women. Arthritis Rheum 2007;56:3319-25. (Pubitemid 47585426)
80. Goldring MB. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis. Ther Adv Musculoskelet Dis 2012;4:269-85.
81. Goldring SR. Alterations in periarticular bone and cross talk between subchondral bone and articular cartilage in osteoarthritis. Ther Adv Musculoskelet Dis 2012;4:249-58.
82. Goldring S, Lane N, Sandell L. Foreword: osteoarthritis. Bone 2012;51:189.
83. Goldring SR, Goldring MB. Bone and cartilage in osteoarthritis: is what's best for one good or bad for the other? Arthritis Res Ther 2010;12:143.
84. Goldring SR. Role of bone in osteoarthritis pathogenesis. Med Clin North Am 2009;93:25-35, xv.
85. Karsdal MA, Martin TJ, Bollerslev J, et al. Are nonresorbing osteoclasts sources of bone anabolic activity? J Bone Miner Res 2007;22:487-94. (Pubitemid 47457424)
86. Couchourel D, Aubry I, Delalandre A, et al. Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production. Arthritis Rheum 2009;60:1438-50.
87. Amiable N, Tat SK, Lajeunesse D, et al. Proteinase-activated receptor (PAR)-2 activation impacts bone resorptive properties of human osteoarthritic subchondral bone osteoblasts. Bone 2009;44:1143-50.
88. Kwan TS, Pelletier JP, Amiable N, et al. Activation of the receptor EphB4 by its specific ligand ephrin B2 in human osteoarthritic subchondral bone osteoblasts. Arthritis Rheum 2008;58:3820-30.
89. Boileau C, Tat SK, Pelletier JP, et al. Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling. Arthritis Res Ther 2008;10:R71.
90. Kwan TS, Pelletier JP, Lajeunesse D, et al. The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin Exp Rheumatol 2008;26:295-304. (Pubitemid 351659137)
91. Tat SK, Pelletier JP, Lajeunesse D, et al. Differential modulation of RANKL isoforms by human osteoarthritic subchondral bone osteoblasts: influence of osteotropic factors. Bone 2008;43:284-91.
92. Tat SK, Pelletier JP, Verges J, et al. Chondroitin and glucosamine sulfate in combination decrease the pro-resorptive properties of human osteoarthritis subchondral bone osteoblasts: a basic science study. Arthritis Res Ther 2007;9:R117.
93. Massicotte F, Aubry I, Martel-Pelletier J, et al. Abnormal insulin-like growth factor 1 signaling in human osteoarthritic subchondral bone osteoblasts. Arthritis Res Ther 2006;8:R177.
94. Lajeunesse D, Delalandre A, Martel-Pelletier J, et al. Hyaluronic acid reverses the abnormal synthetic activity of human osteoarthritic subchondral bone osteoblasts. Bone 2003;33:703-10. (Pubitemid 37222397)
95. Hilal G, Massicotte F, Martel-Pelletier J, et al. Endogenous prostaglandin E2 and insulin-like growth factor 1 can modulate the levels of parathyroid hormone receptor in human osteoarthritic osteoblasts. J Bone Miner Res 2001;16:713-21. (Pubitemid 32230600)
96. Hilal G, Martel-Pelletier J, Pelletier JP, et al. Abnormal regulation of urokinase plasminogen activator by insulin-like growth factor 1 in human osteoarthritic subchondral osteoblasts. Arthritis Rheum 1999;42:2112-22. (Pubitemid 30263594)
97. Hilal G, Martel-Pelletier J, Pelletier JP, et al. Osteoblast-like cells from human subchondral osteoarthritic bone demonstrate an altered phenotype in vitro: possible role in subchondral bone sclerosis. Arthritis Rheum 1998;41:891-9. (Pubitemid 28225790)
98. Henrotin Y, Pesesse L, Sanchez C. Subchondral bone and osteoarthritis: biological and cellular aspects. Osteoporos Int 2012;23(Suppl 8):847-51.
99. Sanchez C, Pesesse L, Gabay O, et al. Regulation of subchondral bone osteoblast metabolism by cyclic compression. Arthritis Rheum 2012;64:1193-203.
100. Sanchez C, Gabay O, Henrotin YE, et al. Osteoblast: a cell under compression. Biomed Mater Eng 2008;18:221-4.
101. Sanchez C, Gabay O, Salvat C, et al. Mechanical loading highly increases IL-6 production and decreases OPG expression by osteoblasts. Osteoarthritis Cartilage 2009;17:473-81.
102. Sanchez C, Deberg MA, Bellahcene A, et al. Phenotypic characterization of osteoblasts from the sclerotic zones of osteoarthritic subchondral bone. Arthritis Rheum 2008;58:442-55. (Pubitemid 351294879)
103. Lamour V, Detry C, Sanchez C, et al. Runx2- and histone deacetylase 3-mediated repression is relieved in differentiating human osteoblast cells to allow high bone sialoprotein expression. J Biol Chem 2007;282:36240-9.
104. Sanchez C, Deberg MA, Piccardi N, et al. Osteoblasts from the sclerotic subchondral bone downregulate aggrecan but upregulate metalloproteinases expression by chondrocytes. This effect is mimicked by interleukin-6, -1beta and oncostatin M pre-treated non-sclerotic osteoblasts. Osteoarthritis Cartilage 2005;13:979-87. (Pubitemid 41536130)
105. Sanchez C, Deberg MA, Piccardi N, et al. Subchondral bone osteoblasts induce phenotypic changes in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 2005;13:988-97. (Pubitemid 41536131)
106. Chou CH, Lee CH, Lu LS, et al. Direct assessment of articular cartilage and underlying subchondral bone reveals a progressive gene expression change in human osteoarthritic knees. Osteoarthritis Cartilage 2013;21:450-61.
107. Kumarasinghe DD, Sullivan T, Kuliwaba JS, et al. Evidence for the dysregulated expression of TWIST1, TGFbeta1 and SMAD3 in differentiating osteoblasts from primary hip osteoarthritis patients. Osteoarthritis Cartilage 2012;20:1357-66.
108. Chan TF, Couchourel D, Abed E, et al. Elevated Dickkopf-2 levels contribute to the abnormal phenotype of human osteoarthritic osteoblasts. J Bone Miner Res 2011;26:1399-410.
109. Corrado A, Neve A, Cantatore FP. Expression of vascular endothelial growth factor in normal, osteoarthritic and osteoporotic osteoblasts. Clin Exp Med 2013;13:81-4.
110. Henriksen K, Karsdal M, Delaisse JM, et al. RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism. J Biol Chem 2003;278:48745-53. (Pubitemid 41079516)
111. Jaiprakash A, Prasadam I, Feng JQ, et al. Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones: a possible pathological role in subchondral bone sclerosis. Int J Biol Sci 2012;8:406-17.
112. Westacott CI, Webb GR, Warnock MG, et al. Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum 1997;40:1282-91. (Pubitemid 27430140)
113. Pritzker KP, Gay S, Jimenez SA, et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage 2006;14:13-29. (Pubitemid 43034086)
114. Fazzalari NL, Kuliwaba JS, Atkins GJ, et al. The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis. J Bone Miner Res 2001;16:1015-27. (Pubitemid 32467145)
115. Lacey DL, Timms E, Tan HL, et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-76. (Pubitemid 28180851)
116. Boyle WJ, Simonet WS, Lacey DL. Osteoclast differentiation and activation. Nature 2003;423:337-42. (Pubitemid 40852708)
117. Appel H, Ruiz-Heiland G, Listing J, et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 2009;60:3257-62.
118. Chan BY, Fuller ES, Russell AK, et al. Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. Osteoarthritis Cartilage 2011;19:874-85.
119. Schett G, Hayer S, Zwerina J, et al. Mechanisms of Disease: the link between RANKL and arthritic bone disease. Nat Clin Pract Rheumatol 2005;1:47-54.
120. Schett G, Stolina M, Bolon B, et al. Analysis of the kinetics of osteoclastogenesis in arthritic rats. Arthritis Rheum 2005;52:3192-201. (Pubitemid 41447102)
121. Stolina M, Adamu S, Ominsky M, et al. RANKL is a marker and mediator of local and systemic bone loss in two rat models of inflammatory arthritis. J Bone Miner Res 2005;20:1756-65. (Pubitemid 41361876)
122. Blaney Davidson EN, Vitters EL, van der Kraan PM, et al. Expression of transforming growth factor-beta (TGFbeta) and the TGFbeta signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation. Ann Rheum Dis 2006;65:1414-21. (Pubitemid 44629115)
123. Andersson MK, Lundberg P, Ohlin A, et al. Effects on osteoclast and osteoblast activities in cultured mouse calvarial bones by synovial fluids from patients with a loose joint prosthesis and from osteoarthritis patients. Arthritis Res Ther 2007;9:R18.
124. Logar DB, Komadina R, Prezelj J, et al. Expression of bone resorption genes in osteoarthritis and in osteoporosis. J Bone Miner Metab 2007;25:219-25. (Pubitemid 47012479)
125. Karsdal MA, Leeming DJ, Dam EB, et al. Should subchondral bone turnover be targeted when treating osteoarthritis? Osteoarthritis Cartilage 2008;16:638-46.
126. Goldring MB, Marcu KB. Epigenomic and microRNA-mediated regulation in cartilage development, homeostasis, and osteoarthritis. Trends Mol Med 2012;18:109-18.
127. Pettit AR, Ji H, von SD, et al. TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 2001;159:1689-99. (Pubitemid 33062512)
128. Gravallese EM, Harada Y, Wang JT, et al. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol 1998;152:943-51. (Pubitemid 28173356)
129. Durand M, Komarova SV, Bhargava A, et al. Monocytes from patients with osteoarthritis display increased osteoclastogenesis and bone resorption: the In Vitro osteoclast differentiation in arthritis (IODA) study. Arthritis Rheum 2013;65:148-58.
130. Engsig MT, Chen QJ, Vu TH, et al. Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones. J Cell Biol 2000;151:879-89.
131. Ortega N, Behonick D, Stickens D, et al. How proteases regulate bone morphogenesis. Ann N Y Acad Sci 2003;995:109-16. (Pubitemid 36706618)
132. Henriksen K, Bollerslev J, Everts V, et al. Osteoclast activity and subtypes as a function of physiology and pathology-implications for future treatments of osteoporosis. Endocr Rev 2011;32:31-63.
133. Ota N, Takaishi H, Kosaki N, et al. Accelerated cartilage resorption by chondroclasts during bone fracture healing in osteoprotegerin-deficient mice. Endocrinology 2009;150:4823-34.
134. Henriksen K, Flores C, Thomsen JS, et al. Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength. PLoS ONE 2011;6:e27482.
135. Henriksen K, Bollerslev J, Everts V, et al. Osteoclast activity and subtypes as a function of physiology and pathology-implications for future treatments of osteoporosis. Endocr Rev 2011;32:31-63.
136. Casden AM, Jaffe FF, Kastenbaum DM, et al. Osteoarthritis associated with osteopetrosis treated by total knee arthroplasty. Report of a case. Clin Orthop Relat Res 1989; (247): 202-7. (Pubitemid 19253010)
137. Bollerslev J, Andersen PE Jr. Radiological, biochemical and hereditary evidence of two types of autosomal dominant osteopetrosis. Bone 1988;9:7-13.
138. Karsdal MA, Schett G, Emery P, et al. IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522). Semin Arthritis Rheum 2012;42:131-9.
139. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage 2013;21:16-21.
140. Attur M, Krasnokutsky-Samuels S, Samuels J, et al. Prognostic biomarkers in osteoarthritis. Curr Opin Rheumatol 2013;25:136-44.
141. Kyostio-Moore S, Nambiar B, Hutto E, et al. STR/ort mice, a model for spontaneous osteoarthritis, exhibit elevated levels of both local and systemic inflammatory markers. Comp Med 2011;61:346-55.
142. Attur M, Belitskaya-Levy I, Oh C, et al. Increased interleukin-1beta gene expression in peripheral blood leukocytes is associated with increased pain and predicts risk for progression of symptomatic knee osteoarthritis. Arthritis Rheum 2011;63:1908-17.
143. Attur M, Wang HY, Kraus VB, et al. Radiographic severity of knee osteoarthritis is conditional on interleukin 1 receptor antagonist gene variations. Ann Rheum Dis 2010;69:856-61.
144. Gyorgy B, Szabo TG, Turiak L, et al. Improved flow cytometric assessment reveals distinct microvesicle (cell-derived microparticle) signatures in joint diseases. PLoS ONE 2012;7:e49726.
145. de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, et al. Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage 2012;20:1484-99.
146. Scanzello CR, Plaas A, Crow MK. Innate immune system activation in osteoarthritis: is osteoarthritis a chronic wound? Curr Opin Rheumatol 2008;20:565-72.
147. Lisignoli G, Toneguzzi S, Grassi F, et al. Different chemokines are expressed in human arthritic bone biopsies: IFN-gamma and IL-6 differently modulate IL-8, MCP-1 and rantes production by arthritic osteoblasts. Cytokine 2002;20:231-8. (Pubitemid 37163476)
148. Schett G, Firestein GS. Mr Outside and Mr Inside: classic and alternative views on the pathogenesis of rheumatoid arthritis. Ann Rheum Dis 2010;69:787-9.
149. Ritchlin CT, Haas-Smith SA, Li P, et al. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest 2003;111:821-31. (Pubitemid 37074957)
150. Appel H, Kuhne M, Spiekermann S, et al. Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthritis Rheum 2006;54:1805-13. (Pubitemid 43877930)
151. Stoch SA, Zajic S, Stone J, et al. Effect of the cathepsin K inhibitor odanacatib on bone resorption biomarkers in healthy postmenopausal women: two double-blind, randomized, placebo-controlled phase I studies. Clin Pharmacol Ther 2009;86:175-82.
152. Hayami T, Zhuo Y, Wesolowski GA, et al. Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. Bone 2012;50:1250-9.
153. Zhu S, Chen K, Lan Y, et al. Alendronate protects against articular cartilage erosion by inhibiting subchondral bone loss in ovariectomized rats. Bone 2013;53:340-9.
154. Strassle BW, Mark L, Leventhal L, et al. Inhibition of osteoclasts prevents cartilage loss and pain in a rat model of degenerative joint disease. Osteoarthritis Cartilage 2010;18:1319-28.
155. Yu DG, Yu B, Mao YQ, et al. Efficacy of zoledronic acid in treatment of osteoarthritis is dependent on the disease progression stage in rat medial meniscal tear model. Acta Pharmacol Sin 2012;33:924-34.
156. Funck-Brentano T, Lin H, Hay E, et al. Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism. PLoS ONE 2012;7:e33543.
157. Moreau M, Rialland P, Pelletier JP, et al. Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model. Arthritis Res Ther 2011;13:R98.
158. Shirai T, Kobayashi M, Nishitani K, et al. Chondroprotective effect of alendronate in a rabbit model of osteoarthritis. J Orthop Res 2011;29:1572-7.
159. Prieto-Alhambra D, Javaid MK, Judge A, et al. Fracture risk before and after total hip replacement in patients with osteoarthritis: potential benefits of bisphosphonate use. Arthritis Rheum 2011;63:992-1001.
160. Zhang L, Hu H, Tian F, et al. Enhancement of subchondral bone quality by alendronate administration for the reduction of cartilage degeneration in the early phase of experimental osteoarthritis. Clin Exp Med 2011;11:235-43.
161. Pelletier JP, Troncy E, Bertaim T, et al. Treatment with tiludronic acid helps reduce the development of experimental osteoarthritis lesions in dogs with anterior cruciate ligament transection followed by reconstructive surgery: a 1-year study with quantitative magnetic resonance imaging. J Rheumatol 2011;38:118-28.
162. Kadri A, Funck-Brentano T, Lin H, et al. Inhibition of bone resorption blunts osteoarthritis in mice with high bone remodelling. Ann Rheum Dis 2010;69:1533-8.
163. Iwamoto J, Takeda T, Sato Y, et al. Effects of risedronate on osteoarthritis of the knee. Yonsei Med J 2010;51:164-70.
164. Spector TD, Conaghan PG, Buckland-Wright JC, et al. Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res Ther 2005;7:R625-33.
165. Garnero P, Bingham C, et al. Treatment with risedronate reduced urinary CTX-II, a specificbiochemical marker of cartilage type II collagen degradation in a 24 month study of knee OA. Osteoarthritis Cartilage 2008;16:660-6.
166. Bingham CO III, Buckland-Wright JC, Garnero P, et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 2006;54:3494-507. (Pubitemid 44737161)
167. Buckland-Wright JC, Messent EA, Bingham CO III, et al. A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients. Rheumatology (Oxford) 2007;46:257-64. (Pubitemid 46189786)
168. Garnero P, Aronstein WS, Cohen SB, et al. Relationships between biochemical markers of bone and cartilage degradation with radiological progression in patients with knee osteoarthritis receiving risedronate: the Knee Osteoarthritis Structural Arthritis randomized clinical trial. Osteoarthritis Cartilage 2008;16:660-6. (Pubitemid 351760798)
169. van Spil WE, Drossaers-Bakker KW, Lafeber FP. Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis. Ann Rheum Dis 2013;72:29-36.
170. Catterall J, Dewitt Parr S, Fagerlund K, et al. CTX-II is a marker of cartilage degradation but not of bone turnover. Osteoarthritis Cartilage Supplement[21], S77. 1-4-2013 BC. Ref Type: Abstract.
171. Dam EB, Byrjalsen I, Karsdal MA, et al. Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 months by MRI. Osteoarthritis Cartilage 2009;17:384-9.
172. Reijman M, Hazes JM, Bierma-Zeinstra SM, et al. A new marker for osteoarthritis: cross-sectional and longitudinal approach. Arthritis Rheum 2004;50:2471-8. (Pubitemid 39062707)
173. Chambers TJ, Moore A. The sensitivity of isolated osteoclasts to morphological transformation by calcitonin. J Clin Endocrinol Metab 1983;57:819-24. (Pubitemid 13013542)
174. Nicholson GC, Moseley JM, Sexton PM, et al. Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest 1986;78:355-60. (Pubitemid 16074070)
175. Murrills RJ, Shane E, Lindsay R, et al. Bone resorption by isolated human osteoclasts in vitro: effects of calcitonin. J Bone Miner Res 1989;4:259-68. (Pubitemid 19121802)
176. Karsdal MA, Henriksen K, Arnold M, et al. Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality. BioDrugs 2008;22:137-44. (Pubitemid 351692844)
177. Chesnut CH III, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study. PROOF Study Group. Am J Med 2000;109:267-76.
178. Behets C, Williams JM, Chappard D, et al. Effects of calcitonin on subchondral trabecular bone changes and on osteoarthritic cartilage lesions after acute anterior cruciate ligament deficiency. J Bone Miner Res 2004;19:1821-6. (Pubitemid 41103433)
179. Manicourt DH, Altman RD, Williams JM, et al. Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions. Arthritis Rheum 1999;42:1159-67. (Pubitemid 29268952)
180. Karsdal MA, Tanko LB, Riis BJ, et al. Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA? Osteoarthritis Cartilage 2006;14:617-24. (Pubitemid 43842738)
181. Segovia-Silvestre T, Bonnefond C, Sondergaard BC, et al. Identification of the calcitonin receptor in osteoarthritic chondrocytes. BMC Res Notes 2011;4:407.
182. Sondergaard BC, Wulf H, Henriksen K, et al. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes. Osteoarthritis Cartilage 2006;14:759-68. (Pubitemid 43986356)
183. DiNino DL, Linsenmayer TF. Positive regulation of endochondral cartilage growth by perichondrial and periosteal calcitonin. Endocrinology 2003;144:1979-83. (Pubitemid 36543337)
184. Hellio MP, Peschard MJ, Cohen C, et al. Calcitonin inhibits phospholipase A2 and collagenase activity of human osteoarthritic chondrocytes. Osteoarthritis Cartilage 1997;5:121-8. (Pubitemid 27141775)
185. Martin TJ, Harris GS, Melick RA, et al. Effect of calcitonin on glycosaminoglycan synthesis by embryo calf bone cells in vitro. Experientia 1969;25:375-6.
186. Nielsen Rh, Bay-Jensen AC, Byrjalsen I, et al. Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover. Osteoarthritis Cartilage 2011;19:466-73.
187. Sondergaard BC, Ostergaard S, Christiansen C, et al. The effect of oral calcitonin on cartilage turnover and surface erosion in the ovariectomized rat model. Arthritis Rheum 2007;56:2674-8. (Pubitemid 47237285)
188. Kyrkos MJ, Papavasiliou KA, Kenanidis E, et al. Calcitonin delays the progress of early-stage mechanically induced osteoarthritis. In vivo, prospective study. Osteoarthritis Cartilage 2013;21:973-80.
189. Ryan SM, McMorrow J, Umerska A, et al. An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis. J Control Release 2013;167:120-9.
190. Sondergaard BC, Catala-Lehnen P, Huebner AK, et al. Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus. Osteoarthritis Cartilage 2012;20:136-43.
191. Karsdal MA, Henriksen K, Bay-Jensen AC, et al. Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials. J Clin Pharmacol 2011;51:460-71.
192. Tanko LB, Bagger YZ, Alexandersen P, et al. Safety and efficacy of a novel salmon calcitonin (sCT) technology-based oral formulation in healthy postmenopausal women: acute and 3-month effects on biomarkers of bone turnover. J Bone Miner Res 2004;19:1531-8. (Pubitemid 41094356)
193. Manicourt DH, Azria M, Mindeholm L, 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. Arthritis Rheum 2006;54:3205-11. (Pubitemid 44622091)
194. Manicourt DH, Azria M, Mindeholm L, et al. Efficacy of calcitonin therapy in patients with knee osteoarthritis: a clinical and biochemical preliminary study. Osteoarthritis Cartilage 2005;13(Suppl A):s88.
195. Bagger YZ, Tanko LB, Alexandersen P, et al. Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis. Bone 2005;37:425-30. (Pubitemid 41160502)
196. Karsdal MA, Byrjalsen I, Azria M, et al. Influence of food intake on the bioavailability and efficacy of oral calcitonin. Br J Clin Pharmacol 2009;67:413-20.
197. Karsdal MA, Byrjalsen I, Henriksen K, et al. Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy. Eur J Clin Pharmacol 2010;66:29-37.
198. Karsdal MA, Byrjalsen I, Henriksen K, 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. Osteoarthritis Cartilage 2010;18:150-9.
199. Karsdal MA, Byrjalsen I, Bay-Jensen AC, 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. BMC Musculoskelet Disord 2010;11:125.
200. Boonen S, Rosenberg E, Claessens F, et al. Inhibition of cathepsin K for treatment of osteoporosis. Curr Osteoporos Rep 2012;10:73-9.
201. McDougall JJ, Schuelert N, Bowyer J. Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig model of spontaneous osteoarthritis. Osteoarthritis Cartilage 2010;18:1355-7.
202. Takahashi D, Iwasaki N, Kon S, et al. Down-regulation of cathepsin K in synovium leads to progression of osteoarthritis in rabbits. Arthritis Rheum 2009;60:2372-80.
203. Connor JR, LePage C, Swift BA, et al. Protective effects of a cathepsin K inhibitor, SB-553484, in the canine partial medial meniscectomy model of osteoarthritis. Osteoarthritis Cartilage 2009;17:1236-43.
204. Vinardell T, Dejica V, Poole AR, et al. Evidence to suggest that cathepsin K degrades articular cartilage in naturally occurring equine osteoarthritis. Osteoarthritis Cartilage 2009;17:375-83.
205. Schurigt U, Hummel KM, Petrow PK, et al. Cathepsin K deficiency partially inhibits, but does not prevent, bone destruction in human tumor necrosis factor-transgenic mice. Arthritis Rheum 2008;58:422-34. (Pubitemid 351294877)
206. Bone HG, McClung MR, Roux C, et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J Bone Miner Res 2010;25:937-47.
207. Eisman JA, Bone HG, Hosking DJ, et al. Odanacatib in the treatment of postmenopausal women with low bone mineral density: three-year continued therapy and resolution of effect. J Bone Miner Res 2011;26:242-51.
208. Oliveria SA, Felson DT, Reed JI, et al. Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis Rheum 1995;38:1134-41.
209. Cauley JA, Kwoh CK, Egeland G, et al. Serum sex hormones and severity of osteoarthritis of the hand. J Rheumatol 1993;20:1170-5. (Pubitemid 23278170)
210. Spector TD, Perry LA, Jubb RW. Endogenous sex steroid levels in women with generalised osteoarthritis. Clin Rheumatol 1991;10:316-19.
211. Sowers MR, McConnell D, Jannausch M, et al. Estradiol and its metabolites and their association with knee osteoarthritis. Arthritis Rheum 2006;54:2481-7. (Pubitemid 44205008)
212. Felson DT, Zhang Y, Hannan MT, et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 1995;38:1500-5.
213. Felson DT, Nevitt MC. The effects of estrogen on osteoarthritis. Curr Opin Rheumatol 1998;10:269-72. (Pubitemid 28286820)
214. Oestergaard S, Sondergaard BC, Hoegh-Andersen P, 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. Arthritis Rheum 2006;54:2441-51. (Pubitemid 44205004)
215. Carlson CS, Loeser RF, Jayo MJ, et al. Osteoarthritis in cynomolgus macaques: a primate model of naturally occurring disease. J Orthop Res 1994;12:331-9. (Pubitemid 24181136)
216. Bay-Jensen AC, Nielsen Rh, Segovia-Silvestre T, et al. A microarray analysis of full depth knee cartilage of ovariectomized rats. BMC Res Notes 2011;4:63.
217. Claassen H, Schunke M, Kurz B. Estradiol protects cultured articular chondrocytes from oxygen-radical-induced damage. Cell Tissue Res 2005;319:439-45. (Pubitemid 40379414)
218. Cirillo DJ, Wallace RB, Wu L, et al. Effect of hormone therapy on risk of hip and knee joint replacement in the Women's Health Initiative. Arthritis Rheum 2006;54:3194-204. (Pubitemid 44622090)
219. Claassen H, Hassenpflug J, Schunke M, et al. Immunohistochemical detection of estrogen receptor alpha in articular chondrocytes from cows, pigs and humans: in situ and in vitro results. Ann Anat 2001;183:223-7. (Pubitemid 32447738)
220. Richmond RS, Carlson CS, Register TC, et al. Functional estrogen receptors in adult articular cartilage: estrogen replacement therapy increases chondrocyte synthesis of proteoglycans and insulin-like growth factor binding protein 2. Arthritis Rheum 2000;43:2081-90.
221. Ushiyama T, Ueyama H, Inoue K, et al. Expression of genes for estrogen receptors alpha and beta in human articular chondrocytes. Osteoarthritis Cartilage 1999;7:560-6.
222. Karsdal MA, Bay-Jensen AC, Henriksen K, et al. The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet? Menopause Int 2012;18:139-46.
223. Lintermans A, Neven P. Pharmacology of arthralgia with estrogen deprivation. Steroids 2011;76:781-5.
224. Crona N, Samsioe G, Lindberg UB, et al. Treatment of climacteric complaints with Org OD 14: a comparative study with oestradiol valerate and placebo. Maturitas 1988;9:303-8.
225. Kicovic PM, Cortes-Prieto J, Luisi M, et al. Placebo-controlled cross-over study of effects of Org OD 14 in menopausal women. Reproduccion 1982;6:81-91. (Pubitemid 13241388)
226. Punnonen R, Liukko P, Cortes-Prieto J, et al. Multicentre study of effects of Org OD 14 on endometrium, vaginal cytology and cervical mucus in post-menopausal and oophorectomized women. Maturitas 1984;5:281-6. (Pubitemid 14125843)
227. Bjarnason NH, Bjarnason K, Haarbo J, et al. Tibolone: prevention of bone loss in late postmenopausal women. J Clin Endocrinol Metab 1996;81:2419-22. (Pubitemid 26240254)
228. Karsdal MA, Leeming DJ, Byrjalsen I, et al. Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation. BMC Musculoskelet Disord 2008;9:153.
229. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 2004;350:459-68. (Pubitemid 38133766)
230. Delmas PD. Clinical effects of strontium ranelate in women with postmenopausal osteoporosis. Osteoporos Int 2005;16(Suppl 1):S16-19. (Pubitemid 40768191)
231. Reginster JY, Kaufman JM, Goemaere S, et al. Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis. Osteoporos Int 2012;23:1115-22.
232. Seeman E, Devogelaer JP, Lorenc R, et al. Strontium ranelate reduces the risk of vertebral fractures in patients with osteopenia. J Bone Miner Res 2008;23:433-8. (Pubitemid 351304674)
233. Roux C, Reginster JY, Fechtenbaum J, et al. Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors. J Bone Miner Res 2006;21:536-42.
234. Atkins GJ, Welldon KJ, Halbout P, et al. Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int 2009;20:653-64.
235. Coulombe J, Faure H, Robin B, et al. In vitro effects of strontium ranelate on the extracellular calcium-sensing receptor. Biochem Biophys Res Commun 2004;323:1184-90. (Pubitemid 39296549)
236. Alexandersen P, Karsdal MA, Qvist P, et al. Strontium ranelate reduces the urinary level of cartilage degradation biomarker CTX-II in postmenopausal women. Bone 2007;40:218-22. (Pubitemid 44848419)
237. Bruyere O, Delferriere D, Roux C, et al. Effects of strontium ranelate on spinal osteoarthritis progression. Ann Rheum Dis 2008;67:335-9. (Pubitemid 351281267)
238. Henrotin Y, Labasse A, Zheng SX, et al. Strontium ranelate increases cartilage matrix formation. J Bone Miner Res 2001;16:299-308. (Pubitemid 32105411)
239. Pelletier JP, Kapoor M, Fahmi H, et al. Strontium ranelate reduces the progression of experimental dog osteoarthritis by inhibiting the expression of key proteases in cartilage and of IL-1beta in the synovium. Ann Rheum Dis 2013;72:250-7.
240. Tat SK, Pelletier JP, Mineau F, et al. Strontium ranelate inhibits key factors affecting bone remodeling in human osteoarthritic subchondral bone osteoblasts. Bone 2011;49:559-67.
241. Reginster JY, Badurski J, Bellamy N, et al. Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial. Ann Rheum Dis 2013;72:179-86.
242. Lajeunesse D. The role of bone in the treatment of osteoarthritis. Osteoarthritis Cartilage 2004;12(Suppl A):S34-8. (Pubitemid 38950275)
243. Buckland-Wright JC, Lynch JA, Dave B. Early radiographic features in patients with anterior cruciate ligament rupture. Ann Rheum Dis 2000;59:641-6. (Pubitemid 30617091)
244. Wachsmuth L, Engelke K. High-resolution imaging of osteoarthritis using microcomputed tomography. Methods Mol Med 2004;101:231-48.
245. Cake MA, Read RA, Guillou B, et al. Modification of articular cartilage and subchondral bone pathology in an ovine meniscectomy model of osteoarthritis by avocado and soya unsaponifiables (ASU). Osteoarthritis Cartilage 2000;8:404-11. (Pubitemid 32000963)
246. Buckland-Wright C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthritis Cartilage 2004;12(Suppl A):S10-19. (Pubitemid 38950272)
247. Hopwood B, Tsykin A, Findlay DM, et al. Microarray gene expression profiling of human osteoarthritic bone suggests altered bone remodelling, WNT and TGF beta/BMP signalling. Arthritis Res Ther 2007;9:R100.
248. Kim YJ, Kim HJ, Im GI. PTHrP promotes chondrogenesis and suppresses hypertrophy from both bone marrow-derived and adipose tissue-derived MSCs. Biochem Biophys Res Commun 2008;373:104-8.
249. Weiss S, Hennig T, Bock R, et al. Impact of growth factors and PTHrP on early and late chondrogenic differentiation of human mesenchymal stem cells. J Cell Physiol 2010;223:84-93.
250. Chen-An P, Andreassen KV, Henriksen K, et al. Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model. Rheumatol Int 2013;33:401-11.
251. Lee JM, Im GI. PTHrP isoforms have differing effect on chondrogenic differentiation and hypertrophy of mesenchymal stem cells. Biochem Biophys Res Commun 2012;421:819-24.
252. Amizuka N, Henderson JE, White JH, et al. Recent studies on the biological action of parathyroid hormone (PTH)-related peptide (PTHrP) and PTH/PTHrP receptor in cartilage and bone. Histol Histopathol 2000;15:957-70. (Pubitemid 30488575)
253. Kronenberg HM. Developmental regulation of the growth plate. Nature 2003;423:332-6. (Pubitemid 40852707)
254. Bahrami S, Plate U, Dreier R, et al. Endochondral ossification of costal cartilage is arrested after chondrocytes have reached hypertrophic stage of late differentiation. Matrix Biol 2001;19:707-15. (Pubitemid 32153829)
255. Suda N, Shibata S, Yamazaki K, et al. Parathyroid hormone-related protein regulates proliferation of condylar hypertrophic chondrocytes. J Bone Miner Res 1999;14:1838-47. (Pubitemid 29521778)
256. Amizuka N, Henderson JE, Hoshi K, et al. Programmed cell death of chondrocytes and aberrant chondrogenesis in mice homozygous for parathyroid hormone-related peptide gene deletion. Endocrinology 1996;137:5055-67. (Pubitemid 26403351)
257. Lee K, Lanske B, Karaplis AC, et al. Parathyroid hormone-related peptide delays terminal differentiation of chondrocytes during endochondral bone development. Endocrinology 1996;137:5109-18. (Pubitemid 26403356)
258. Sampson ER, Hilton MJ, Tian Y, et al. Teriparatide as a chondroregenerative therapy for injury-induced osteoarthritis. Sci Transl Med 2011;3:101ra93.
259. Chang JK, Chang LH, Hung SH, et al. Parathyroid hormone 1-34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in rats. Arthritis Rheum 2009;60:3049-60.
260. Malemud CJ, Papay RS. Stimulation of cyclic AMP in chondrocyte cultures: effects on sulfated-proteoglycan synthesis. FEBS Lett 1984;167:343-51. (Pubitemid 14194893)
261. Karsdal MA, Sumer EU, Wulf H, et al. Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation. Arthritis Rheum 2007;56:1549-58. (Pubitemid 46764084)
262. Mwale F, Yao G, Ouellet JA, et al. Effect of parathyroid hormone on type X and type II collagen expression in mesenchymal stem cells from osteoarthritic patients. Tissue Eng Part A 2010;16:3449-55.
263. Takahata M, Awad HA, O'Keefe RJ, et al. Endogenous tissue engineering: PTH therapy for skeletal repair. Cell Tissue Res 2011.
264. Eastell R, Christiansen C, Grauer A, et al. Effects of denosumab on bone turnover markers in postmenopausal osteoporosis. J Bone Miner Res 2011;26:530-7. 348