Osteoarthritis (OA) is a debilitating disease that results in pain and physical disability. Currently, more than 250 million people worldwide are affected by this disease and its prevalence will continue to rise as the population ages, contributing to a substantial health burden. There is new evidence to suggest that OA may be due to inflammatory processes associated with alarmins. Alarmins such as S100, high mobility group protein B1 (HMGB1) and heat shock proteins (HSP), are endogenous molecules released during tissue damage, Alarmins have been found abundantly within synovial tissues and have been implicated in proinflammatory responses such as synovial inflammation, cartilage degeneration and osteophyte formation. Our specific aim is to compare the spatial topography of alarmins (specifically, S100, HMGB1 and HSP), chondrocytes and M1/M2 macrophages in the subchondral bone and synovium of an arthritic knee, using tissue samples retrieved from total knee arthroplasty (TKA).
In collaboration with SKH and SGH's Department of Rheumatology, the team conducts radiographic and MRI evaluation of patients with knee osteoarthritis in early and late stages. Serum and synovial fluid analysis of a panel of biomarkers related to innate immunity were also conducted. Associations between inflammatory biomarkers and various MRI features in early-stage osteoarthritis were observed. Follow-up studies to establish temporal relationship between progression of osteoarthritis and changes in biomarker activity are in progress.
Demographic and functional outcome data using validated orthopaedic scoring systems will be recorded for each patient. Radiological data including anteroposterior, lateral, skyline and long-leg X-rays of both knees will be taken preoperatively. Patients will also undergo a 3.0-T MRI of the knee, which will be scored using the Whole Organ Magnetic Resonance Imaging Score (WORMS). The anterior/central/posterior regions of the medial and lateral tibial plateaus will be scored separately for cartilage morphology, subchondral bone cysts, bone marrow lesions (BML), subchondral bone attrition and osteophytes.
Rajandran SN, Ma CA, Tan JR, Liu J, Wong SBS, Leung YY. Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis. Front Med (Lausanne). 2020 Nov 12;7:554669. doi: 10.3389/fmed.2020.554669.
Atypical femoral fractures are fractures of the femur involving the subtrochanteric region and shaft which are often related to bisphosphonate therapy, used to treat osteoporosis and prevent osteoporotic fractures. It is an effective anti-resorptive agent but is associated with complications which include atypical femoral fractures. Atypical femoral fractures are rare but more frequent in Asians and Orientals than Caucasian populations, resulting in a fair number of these cases being reported in Singapore. Orthopaedists at SGH were one of the first to publish a series of these cases. Dr P Chandra Mohan and Dr Png Meng Ai, from Department of Diagnostics Radiology, have been collaborating with SGH Department of Orthopaedic Surgery on this project.
With greater awareness, this condition is being detected at the stress fracture or incomplete fracture stage. Clinical management aims to prevent progression to displaced fractures with their associated surgical challenges and complications. Investigation into management of incomplete atypical femoral fractures has been research focus area of Dr Png. Some authors advocate routine prophylactic fixation for this group of patients while others have promoted the use of synthetic parathormone or teriparatide in addition to stopping bisphosphonates to improve healing of incomplete fractures. Nevertheless, further research is needed to clarify how to best manage this group of patients.
Please contact Drs Png Meng Ai, Lim Chee Yeong, Tan Eu Jin, Tan Jin Rong for more information.
Dr Png Meng Ai – png.meng.ai@singhealth.com.sg
Dr Lim Chee Yeong – lim.chee.yeong@singhealth.com.sg
Dr Tan Eu Jin – tan.eu.jin@singhealth.com.sg
Dr Tan Jin Rong – tan.jin.rong@singhealth.com.sg
Mohan PC, Howe TS, Koh JS, Png MA. Radiographic features of multifocal endosteal thickening of the femur in patients on long-term bisphosphonate therapy. Eur Radiol. 2013 Jan;23(1):222-7. doi: 10.1007/s00330-012-2587-y. Epub 2012 Jul 20.
Ng AC, Png MA, Mohan PC, Koh JS, Howe TS. Atypical femoral fractures: transverse morphology at lateral cortex is a critical feature. J Bone Miner Res. 2014 Mar;29(3):639-43. doi: 10.1002/jbmr.2078.
Png MA, Mohan PC, Koh JSB, Howe CY, Howe TS. Natural history of incomplete atypical femoral fractures in patients after a prolonged and variable course of bisphosphonate therapy-a long-term radiological follow-up. Osteoporos Int. 2019 Dec;30(12):2417-2428. doi: 10.1007/s00198-019-05067-7. Epub 2019 Aug 21.
Png MA, Koh JS, Goh SK, Fook-Chong S, Howe TS. Bisphosphonate-related femoral periosteal stress reactions: scoring system based on radiographic and MRI findings. AJR Am J Roentgenol. 2012 Apr;198(4):869-77. doi: 10.2214/AJR.11.6794.
Schilcher J, Howe TS, Png MA, Aspenberg P, Koh JS. Atypical Fractures are Mainly Subtrochanteric in Singapore and Diaphyseal in Sweden: A Cross-Sectional Study. J Bone Miner Res. 2015 Nov;30(11):2127-32. doi: 10.1002/jbmr.2547. Epub 2015 Jun 15.
Chou AC, Ng AC, Png MA, Chua DT, Ng DC, Howe TS, Koh JS. Bone cross-sectional geometry is not associated with atypical femoral fractures in Asian female chronic bisphosphonate users. Bone. 2015 Oct;79:170-5. doi: 10.1016/j.bone.2015.06.003. Epub 2015 Jun 9.
Kwek EB, Goh SK, Koh JS, Png MA, Howe TS. An emerging pattern of subtrochanteric stress fractures: a long-term complication of alendronate therapy? Injury. 2008 Feb;39(2):224-31. doi: 10.1016/j.injury.2007.08.036. Epub 2008 Jan 28.
Koh JS, Goh SK, Png MA, Kwek EB, Howe TS. Femoral cortical stress lesions in long-term bisphosphonate therapy: a herald of impending fracture? J Orthop Trauma. 2010 Feb;24(2):75-81. doi: 10.1097/BOT.0b013e3181b6499b.
Koh JS, Goh SK, Png MA, Ng AC, Howe TS. Distribution of atypical fractures and cortical stress lesions in the femur: implications on pathophysiology. Singapore Med J. 2011 Feb;52(2):77-80.
