Risk factors for the progression of finger interphalangeal joint osteoarthritis: a systematic review

Osteoarthritis is one of the leading causes of worldwide disability [1], and, in the USA alone, carries a cost of $10 billion just from economic loss [2]. Hand osteoarthritis is one of the most common types of radiographic osteoarthritis [1]. Hand osteoarthritis also presents in a younger population than osteoarthritis at other joints, with a prevalence of 3% in men and 8% in women aged 45–64 years [3, 4]. It is considered a chronic disease, with some cases progressing and the prevalence increasing to 5% in men and 9% in women aged 65–74 years [5]. Symptomatic treatment for progressive hand osteoarthritis is limited, with patients often requiring surgical management, such as arthrodesis or arthroplasty [6].

Measuring progressive hand osteoarthritis is difficult, with no consensus for defining or quantifying worsening of disease [7]. The Osteoarthritis Research Society International (OARSI) 2006 Task Force described hand osteoarthritis progression as being joint specific, whereby osteoarthritis in one hand joint evolves independently from other hand joints [8]. However, analysis from a large cohort study suggests there are patterns of symmetry, osteoarthritis clustering by row (across distal interphalangeal joints (DIPJs) or across proximal interphalangeal joints (PIPJs)), and clustering by ray (within a finger) also exist [9]. There is also poor correlation between radiographic and symptomatic disease [10, 11].

The aetiology for the progression of hand osteoarthritis is also poorly understood, and therefore identifying patients at highest risk for needing surgical management is limited. When managing hip and knee osteoarthritis surgically, shared decision making between clinicians and patients has been shown to be beneficial [12]. In the hand, a better understanding of whether a patient is at increased risk of progressive disease would help to inform shared decision making. In particular, it would enable earlier investigations, more personalised treatment pathways, and targeted interventions for prevention and treatment. These priorities have been highlighted by the recent Commission on the Future of Surgery [13]. Similarly, being able to identify patients with osteoarthritis who will not progress will prevent the over-investigation and excessive medical treatment of these patients. A review has found that abnormal scintigraphy scans, higher Australian/Canadian Hand Osteoarthritis Index (AUSCAN) scores, number of osteoarthritis joints at baseline, more pain, and nodal osteoarthritis were risk factors for the progression of radiographic or clinical hand osteoarthritis [14]. However, this review combined interphalangeal joint (IPJ) and base of thumb [first carpometacarpal joint (CMCJ)] osteoarthritis under the umbrella of ‘hand osteoarthritis.’ Finger IPJ and first CMCJ osteoarthritis are now thought to be different subsets of the disease, with different risk factors, pathophysiology and patterns of progression [15].

Therefore, the primary aim of this systematic review is to identify risk factors for the progression of finger IPJ osteoarthritis. The secondary aim is to describe the measurements used to define the progression of IPJ osteoarthritis.

The reporting of this systematic review followed the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement [16]. The protocol was prospectively registered on PROSPERO [17] (CRD42019121034).

Marshall et al. assessed diabetes type 2/IFG compared to not having these conditions in a total of 474 participants [42] (effect measures shown in Electronic Supplementary Material 3). In a complete case analysis, these conditions were associated with an increase by ≥ 1 grade in a cumulative KL [47] sum score for all IPJs [adjusted mean difference (95% confidence interval) 7.78 (1.13–14.43)] [42]. However, there was no association following multiple imputation [4.50 (− 0.26 to 9.25)] [42]. Diabetes type 2/IFG was associated with an increase in the number of IPJs with KL [47] grade ≥ 2 following multiple imputation and complete case analysis [2.06 (0.25–3.87) and 3.35 (1.08–5.62), respectively] [42].

Kalichman et al. investigated larger EI in 177 participants [44] (Electronic Supplementary Material 3). A positive association was found in both males (multiple regression coefficient, β = 0.202; 95% CI not reported) and females (β = 0.325; 95% CI not reported), between larger EI and IPJ osteoarthritis progression (measured as an increase by ≥ 1 grade in a cumulative KL [38] sum score for PIPJs in the assessed digits).

Osteoarthritis is one of the largest health-care burdens, and radiographic hand osteoarthritis is highly prevalent, affecting more than one out of five adult Americans [48]. Osteoarthritis is considered to be progressive in some cases. However, there is no unified method to measure the progression of hand osteoarthritis, and IPJ osteoarthritis is now considered to be a different disease subset from first CMCJ osteoarthritis. As IPJ osteoarthritis progresses, it can be treated surgically, and there are currently no disease-modifying drugs. Risk factors which increase the chance of IPJ osteoarthritis progression in patients have been studied in the literature. We identified eight studies (seven high risk of bias) investigating potential risk factors for the progression of finger IPJ osteoarthritis [37‐44]. All studies measured osteoarthritis progression radiographically, using a version of the KL classification system [45, 46]. Our review found that patients with diabetes/IFG [42], and both male and females with a larger finger EI [44], are at increased risk of IPJ osteoarthritis progression (limited evidence), whilst older age in men [37‐39, 43] and in women [43] showed mixed evidence. Results were largely similar when DIPJ and PIPJ osteoarthritis when assessed separately.

The KL classification system [45, 46] was used to measure osteoarthritis progression by all studies [37‐44, 49]. The KL classification system [45, 46] is a sensitive method for measuring the progression of radiographic hand osteoarthritis over a 1-year time frame [20]. All of the studies included in this review were longitudinal studies, and the shortest follow-up period had a mean of 2.28 years [39]. Therefore, all studies would have adequately detected any radiographic IPJ osteoarthritis progression. However, the definitions of each measure of progression varied across studies. Some studies measured an increase in KL grade [37‐40], whilst others measured it as an increase in the number of joints with a particular KL grade [38, 40, 42, 43] and still other studies measured it as an increase in a cumulative KL sum score [41, 42, 44] (which is dependent on either an increase in KL grade of already affected joints, or an increase in the number of joints with a particular KL grade). The sensitivity of the KL classification system [45, 46] in detecting IPJ osteoarthritis progression measured in these different ways has not yet been investigated. Additionally, potential risk factors that occur at a localised joint level (such as joint trauma) could also be risk factors for isolated IPJ osteoarthritis progression. However, localised risk factors were not assessed by studies in this review. Further research is required to understand whether there are any joint-specific risk factors for IPJ osteoarthritis progression, and whether these might cause osteoarthritis to progress at one joint independently of other IPJs.

Diabetes/IFG was found to be a risk factor for IPJ osteoarthritis progression [42]. Marshall et al. suggest diabetes/IFG might be a risk factor for the progression of osteoarthritis due to hyperglycaemia [42]. Hyperglycaemia has been shown to induce reactive oxygen species and the production of cytokines, which result in joint inflammation and in the production of proteolytic enzymes that degrade cartilage [50]. However, in a Delphi study consisting of a panel of hand surgeons, the use of diabetic medication and abnormal fasting glucose were not identified as risk factors for finger IPJ osteoarthritis progression [51]. This suggests that though diabetes/IFG might have a relationship with IPJ osteoarthritis on a molecular level, in a clinical context the effect is not yet well recognised. Our results also found that larger finger EI is a risk factor for IPJ osteoarthritis progression [44]. In hip and knee osteoarthritis, larger cross-sectional areas in the femoral neck and proximal femoral shaft and in the tibial plateau, respectively, have also been described [52, 53]. Additionally, in knee osteoarthritis, a loss of articular cartilage coupled with larger bone epiphyseal area results in a change of loading and force across a joint, further contributing to the progression of osteoarthritis [54]. However, in the hands, and particularly the finger IPJs, the load across the joint is much lower, suggesting that there might be other mechanisms which contribute to the relationship between EI and IPJ osteoarthritis progression. Given the limited evidence reported in our systematic review, further high-quality studies are needed to assess this relationship.

The studies included in this systematic review are limited by their moderate/high risk of bias [37‐39, 41‐44]. This resulted in lower levels of evidence for each potential risk factor assessed. All studies included in this review used radiographic methods to measure osteoarthritis progression. However, there is poor correlation between radiographic and symptomatic osteoarthritis [10, 11], and studies assessing risk factors for the progression of symptomatic IPJ osteoarthritis are required. The time interval between baseline and follow-up measurements of osteoarthritis varied between studies, making it difficult to quantify the exact impact of a potential risk factor on osteoarthritis progression. Similarly, study populations varied with regard to age of participants, which could moderate the effect of other potential risk factors. All studies in this review are Phase 1 or 2 prognostic factor studies. Phase 3 studies are required to more adequately understand the effect of multiple risk factors on the progression of IPJ osteoarthritis and assess prognostic pathways [55, 56]. During data extraction, it became clear that studies used a variety of definitions to measure the progression of IPJ osteoarthritis. Therefore, a secondary aim of this review was established, to describe the criteria used to define the progression of IPJ osteoarthritis. This resulted in deviation from the study protocol registered on PROSPERO [17]. However, performing this analysis showed that there is great heterogeneity in the way IPJ osteoarthritis progression is defined, and further consensus work is needed to establish common criteria for defining disease progression. This review is limited by a small number of studies assessing each potential risk factor and meta-analyses could not be performed. Future work should also focus on standardising definitions of IPJ osteoarthritis progression, enabling harmonisation of datasets and pooling of study data.

Few studies which assess potential risk factors for hand IPJ osteoarthritis progression exist, and most are of high risk of bias. In the literature, the progression of IPJ osteoarthritis is measured radiographically using the KL classification system [45, 46], and no studies on symptomatic osteoarthritis progression were identified. Diabetes/IFG and larger finger EI are risk factors for disease progression, though evidence is limited. A better understanding of risk factors is needed to inform the identification and management of patients with a high risk of IPJ osteoarthritis progression.