Cindy Boer

Hand Osteoarthritis Phenotypes | 95 2.2 Introduction Osteoarthritis (OA) is a serious destructive joint disorder and the third most rapidly rising condition associated with disability[1]. Despite this, no effective treatments that target OA are available. Current treatments only manage pain, not the underlying mech- anisms of disease etiology. An estimated 5% of the world population is affected by OA, with hand OA as one of its most prevalent forms. Given the high prevalence with age and high estimated lifetime risk rates for symptomatic hand OA (39.8%), the number of individuals affected will only continue to increase[2, 3]. Hand OA has a high clinical burden, involving considerable pain, deformity, and impaired function[4-6]. In addition, hand joints are non-weight bearing, and therefore may reflect the systemic aspects of the disease more than knee and/or hip OA, where mechanical loading is a dominant risk factor[7]. A better understanding of hand OA, its causes and pathophysiological mecha- nisms is therefore urgently needed. Hand OA is a complex multifactorial disorder. It shares risk factors, such as re- petitive movements and obesity, with OA at other joint sites[8, 9]. Hand OA also has a strong genetic component, with heritability estimates ranging from 39%–84% depend- ing on the hand joint affected[10, 11]. Recently, major advances were made in elucidat- ing the genetic background of hip and knee OA, using large (n>400,000 individuals) genome-wide association studies (GWAS)[12-14]. Yet, for hand OA only two common genetic loci have been found near the MGP and ALDH1A2 genes[15, 16]. The lack of findings for hand OA may be attributed to the modest samples sizes (n<9,000 individu- als) in previous GWAS and disease heterogeneity[17], which is known to reduce power to robustly detect genetic loci[18]. Osteoarthritis in the handmay be present in any joint, but is most prevalent in the distal interphalangeal joints (DIP), first carpometacarpal (CMC1) and trapezioscaphoid (TS) joints, followed by the proximal interphalangeal joints (PIP). Osteoarthritis is least prevalent in metacarpophalangeal joints (MCP)(19, 20). Diverse definitions of hand OA have been used including nodal hand OA (interphalangeal (IP) joints), thumb base OA (CMC1/TS), and generalized hand OA (DIP/PIP/CMC1)[19, 20] with varying results, suggesting that disease etiology may differ between the joints. Moreover, OA affects multiple tissues within the joint including cartilage and bone. This further contributes to disease heterogeneity and warrants the assessment of hand OA by endophenotypes such as joint space narrowing (JSN) and osteophytes (OST) that may capture separate biological processes underlying OA pathology. The use of endophenotypes, quantifiable biological phenotypes intermediate to the genes and the disease, has been successfully used in OA for the detection of novel genetic loci[16, 21, 22] in knee and hip OA, and