Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

Yan Chen , Yong-Can Huang , Chun Hoi Yan , Kwong Yuen Chiu , Qingjun Wei , Jingmin Zhao , X Edward Guo , Frankie Leung , William W Lu

Bone Research ›› 2017, Vol. 5 ›› Issue (1) : 17034

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Bone Research ›› 2017, Vol. 5 ›› Issue (1) : 17034 DOI: 10.1038/boneres.2017.34
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Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients

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Abstract

Type 2 diabetes (T2D) is associated with systemic abnormal bone remodeling and bone loss. Meanwhile, abnormal subchondral bone remodeling induces cartilage degradation, resulting in osteoarthritis (OA). Accordingly, we investigated alterations in subchondral bone remodeling, microstructure and strength in knees from T2D patients and their association with cartilage degradation. Tibial plateaus were collected from knee OA patients undergoing total knee arthroplasty and divided into non-diabetic (n=70) and diabetes (n=51) groups. Tibial plateaus were also collected from cadaver donors (n=20) and used as controls. Subchondral bone microstructure was assessed using micro-computed tomography. Bone strength was evaluated by micro-finite-element analysis. Cartilage degradation was estimated using histology. The expression of tartrate-resistant acidic phosphatase (TRAP), osterix, and osteocalcin were calculated using immunohistochemistry. Osteoarthritis Research Society International (OARSI) scores of lateral tibial plateau did not differ between non-diabetic and diabetes groups, while higher OARSI scores on medial side were detected in diabetes group. Lower bone volume fraction and trabecular number and higher structure model index were found on both sides in diabetes group. These microstructural alterations translated into lower elastic modulus in diabetes group. Moreover, diabetes group had a larger number of TRAP+ osteoclasts and lower number of Osterix+ osteoprogenitors and Osteocalcin+ osteoblasts. T2D knees are characterized by abnormal subchondral bone remodeling and microstructural and mechanical impairments, which were associated with exacerbated cartilage degradation. In regions with intact cartilage the underlying bone still had abnormal remodeling in diabetes group, suggesting that abnormal bone remodeling may contribute to the early pathogenesis of T2D-associated knee OA.

Osteoarthritis: Diabetic knees show bone and cartilage deficiencies

Abnormal bone remodeling may contribute to the early development of knee osteoarthritis associated with type 2 diabetes (T2D). A group headed by William Lu at the University of Hong Kong investigated changes in subchondral bone remodeling (metabolism of bone below the cartilage in a joint), microstructure, and strength in knees from T2D patients. The authors collected the upper surfaces of shin bones from diabetic and non-diabetic patients undergoing total knee replacement. They found that the knees of diabetic patients showed abnormal bone remodeling as well as microstructural and mechanical deficiencies, which were associated with cartilage deterioration. In these patients, regions with intact cartilage displayed abnormal remodeling of the underlying bone. The authors concluded that T2D patients undergo abnormal subchondral bone remodeling, which may facilitate the development of knee osteoarthritis.

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Yan Chen, Yong-Can Huang, Chun Hoi Yan, Kwong Yuen Chiu, Qingjun Wei, Jingmin Zhao, X Edward Guo, Frankie Leung, William W Lu. Abnormal subchondral bone remodeling and its association with articular cartilage degradation in knees of type 2 diabetes patients. Bone Research, 2017, 5(1): 17034 DOI:10.1038/boneres.2017.34

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References

[1]

Rubin MR, Patsch JM. Assessment of bone turnover and bone quality in type 2 diabetic bone disease: current concepts and future directions. Bone Res, 2016, 4: 16001

[2]

Schwartz AV. Epidemiology of fractures in type 2 diabetes. Bone, 2016, 82: 2-8

[3]

Napoli N, Strotmeyer ES, Ensrud KE et al. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia, 2014, 57: 2057-2065

[4]

Patsch JM, Burghardt AJ, Yap SP et al. Increased cortical porosity in type 2 diabetic postmenopausal women with fragility fractures. J Bone Miner Res, 2013, 28: 313-324

[5]

Farr JN, Drake MT, Amin S et al. In vivo assessment of bone quality in postmenopausal women with type 2 diabetes. J Bone Miner Res, 2014, 29: 787-795

[6]

Jiajue R, Jiang Y, Wang O et al. Suppressed bone turnover was associated with increased osteoporotic fracture risks in non-obese postmenopausal Chinese women with type 2 diabetes mellitus. Osteoporos Int, 2014, 25: 1999-2005

[7]

Li J, He W, Liao B et al. FFA-ROS-P53-mediated mitochondrial apoptosis contributes to reduction of osteoblastogenesis and bone mass in type 2 diabetes mellitus. Sci Rep, 2015, 5: 12724

[8]

King KB, Rosenthal AK. The adverse effects of diabetes on osteoarthritis: update on clinical evidence and molecular mechanisms. Osteoarthritis Cartilage, 2015, 23: 841-850

[9]

Schett G, Kleyer A, Perricone C et al. Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care, 2013, 36: 403-409

[10]

Laiguillon MC, Courties A, Houard X et al. Characterization of diabetic osteoarthritic cartilage and role of high glucose environment on chondrocyte activation: toward pathophysiological delineation of diabetes mellitus-related osteoarthritis. Osteoarthritis Cartilage, 2015, 23: 1513-1522

[11]

Ribeiro M, Lopez de Figueroa P, Blanco FJ et al. Insulin decreases autophagy and leads to cartilage degradation. Osteoarthritis Cartilage, 2016, 24: 731-739

[12]

Onur T, Wu R, Metz L et al. Characterisation of osteoarthritis in a small animal model of type 2 diabetes mellitus. Bone Joint Res, 2014, 3: 203-211

[13]

Rosa SC, Rufino AT, Judas FM et al. Role of glucose as a modulator of anabolic and catabolic gene expression in normal and osteoarthritic human chondrocytes. J Cell Biochem, 2011, 112: 2813-2824

[14]

Zhen G, Wen C, Jia X et al. Inhibition of TGF-beta signaling in mesenchymal stem cells of subchondral bone attenuates osteoarthritis. Nat Med, 2013, 19: 704-712

[15]

Lories RJ, Luyten FP. The bone-cartilage unit in osteoarthritis. Nat Rev Rheumatol, 2011, 7: 43-49

[16]

Kazakia GJ, Kuo D, Schooler J et al. Bone and cartilage demonstrate changes localized to bone marrow edema-like lesions within osteoarthritic knees. Osteoarthritis Cartilage, 2013, 21: 94-101

[17]

Chen Y, Wang T, Guan M et al. Bone turnover and articular cartilage differences localized to subchondral cysts in knees with advanced osteoarthritis. Osteoarthritis Cartilage, 2015, 23: 2174-2183

[18]

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: 1193-1206

[19]

Crema MD, Cibere J, Sayre EC et al. The relationship between subchondral sclerosis detected with MRI and cartilage loss in a cohort of subjects with knee pain: the knee osteoarthritis progression (KOAP) study. Osteoarthritis Cartilage, 2014, 22: 540-546

[20]

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

[21]

Herrero-Beaumont G, Roman-Blas JA. Osteoarthritis: osteoporotic OA: a reasonable target for bone-acting agents. Nat Rev Rheumatol, 2013, 9: 448-450

[22]

Altman R, Asch E, Bloch D et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum, 1986, 29: 1039-1049

[23]

American Diabetes Association Executive summary: standards of medical care in diabetes--2014. Diabetes Care, 2014, 37: S5-S13

[24]

Wen CY, Chen Y, Tang HL et al. Bone loss at subchondral plate in knee osteoarthritis patients with hypertension and type 2 diabetes mellitus. Osteoarthritis Cartilage, 2013, 21: 1716-1723

[25]

Kellgren JH, Lawrence JS. Radiological assessment of osteo-arthrosis. Ann Rheum Dis, 1957, 16: 494-502

[26]

Sharma L, Chmiel JS, Almagor O et al. The role of varus and valgus alignment in the initial development of knee cartilage damage by MRI: the MOST study. Ann Rheum Dis, 2013, 72: 235-240

[27]

Insall JN, Dorr LD, Scott RD et al. Rationale of the Knee Society clinical rating system. Clin Orthop Relat Res, 1989, 248: 13-14

[28]

Ogden CL, Carroll MD, Kit BK et al. Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010. JAMA, 2012, 307: 483-490

[29]

Walker MD, Liu XS, Zhou B et al. Premenopausal and postmenopausal differences in bone microstructure and mechanical competence in Chinese-American and white women. J Bone Miner Res, 2013, 28: 1308-1318

[30]

Wang J, Stein EM, Zhou B et al. Deterioration of trabecular plate-rod and cortical microarchitecture and reduced bone stiffness at distal radius and tibia in postmenopausal women with vertebral fractures. Bone, 2016, 88: 39-46

[31]

Liu XS, Wang J, Zhou B et al. Fast trabecular bone strength predictions of HR-pQCT and individual trabeculae segmentation-based plate and rod finite element model discriminate postmenopausal vertebral fractures. J Bone Miner Res, 2013, 28: 1666-1678

[32]

Pritzker KP, Gay S, Jimenez SA et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage, 2006, 14: 13-29

[33]

Ding M, Odgaard A, Hvid I. Changes in the three-dimensional microstructure of human tibial cancellous bone in early osteoarthritis. J Bone Joint Surg Br, 2003, 85: 906-912

[34]

Loeser RF, Goldring SR, Scanzello CR et al. Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum, 2012, 64: 1697-1707

[35]

Roman-Blas JA, Herrero-Beaumont G. Targeting subchondral bone in osteoporotic osteoarthritis. Arthritis Res Ther, 2014, 16: 494

[36]

Bobinac D, Marinovic M, Bazdulj E et al. Microstructural alterations of femoral head articular cartilage and subchondral bone in osteoarthritis and osteoporosis. Osteoarthritis Cartilage, 2013, 21: 1724-1730

[37]

Cui Z, Xu C, Li X et al. Treatment with recombinant lubricin attenuates osteoarthritis by positive feedback loop between articular cartilage and subchondral bone in ovariectomized rats. Bone, 2015, 74: 37-47

[38]

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: 340-349

[39]

Karsdal MA, Bay-Jensen AC, Lories RJ et al. The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments? Ann Rheum Dis, 2014, 73: 336-348

[40]

Klose-Jensen R, Hartlev LB, Boel LWT et al. Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint. Osteoarthritis Cartilage, 2015, 23: 2167-2173

[41]

Wang J, Zhou B, Liu XS et al. Trabecular plates and rods determine elastic modulus and yield strength of human trabecular bone. Bone, 2015, 72: 71-80

[42]

Guermazi A, Hayashi D, Roemer F et al. Severe radiographic knee osteoarthritis--does Kellgren and Lawrence grade 4 represent end stage disease?--the MOST study. Osteoarthritis Cartilage, 2015, 23: 1499-1505

[43]

Ganz ML, Wintfeld N, Li Q et al. The association of body mass index with the risk of type 2 diabetes: a case-control study nested in an electronic health records system in the United States. Diabetol Metab Syndr, 2014, 6: 50

[44]

Lee DH, Jung KY, Park KS et al. Characterization of Patients with Type 2 Diabetes according to Body Mass Index: Korea National Health and Nutrition Examination Survey from 2007 to 2011. Endocrinol Metab (Seoul), 2015, 30: 514-521

[45]

Yoon KH, Lee JH, Kim JW et al. Epidemic obesity and type 2 diabetes in Asia. Lancet, 2006, 368: 1681-1688

[46]

Huxley R, James WP, Barzi F et al. Ethnic comparisons of the cross-sectional relationships between measures of body size with diabetes and hypertension. Obes Rev, 2008, 9: 53-61

[47]

Fujii H, Hamada Y, Fukagawa M. Bone formation in spontaneously diabetic Torii-newly established model of non-obese type 2 diabetes rats. Bone, 2008, 42: 372-379

[48]

Zhuo Q, Yang W, Chen J et al. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol, 2012, 8: 729-737

[49]

Rubin MR. Bone cells and bone turnover in diabetes mellitus. Curr Osteoporos Rep, 2015, 13: 186-191

[50]

Shu A, Yin MT, Stein E et al. Bone structure and turnover in type 2 diabetes mellitus. Osteoporos Int, 2012, 23: 635-641

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