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Use of Finger Length Ratio As a Marker for Knee Osteoarthritis: a Case-Control Study of 2,456 Patients

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Use of Finger Length Ratio As a Marker for Knee Osteoarthritis: a Case-Control Study of 2,456 Patients medRxiv preprint doi: https://doi.org/10.1101/2020.07.22.20159681; this version posted July 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Title: Use of finger length ratio as a marker for knee osteoarthritis: A case-control study of 2,456 patients Running/Short Title: Can finger lengths be used as a marker for knee osteoarthritis? Article category: Qualitative research Dukhum Magua; Aditya Aggarwalb; Prateek Beherac; Ankit Khuranad* aDepartment of Orthpaedics, District Hospital Tawang, Tawang, India, bDepartment of Orthopaedics, PGIMER, Chandigarh, India, cDepartment of Orthopaedics, AIIMS, Bhopal, India, dDepartment of Orthopaedics, Dr BSA Medical college and Hospital, Delhi, India *Correspondence to Dr A Khurana, Department of Orthopaedics, Dr BSA Medical college and Hospital, Rohini Sector 6, Delhi-110009; E-mail: [email protected] KEY MESSAGES Evaluation of finger patterns reveals an association with osteoartritis knee (KOA) Low 2D:4D ratio and Type 3 finger pattern is associated with increased KOA risk Low 2D:4D ratio has as positive correlation to radiographic severity of KOA Preventive interventons can be initiated for those with at risk finger pattern Abstract Background: In the human hand, the index and ring finger present a considerable variation in their relative lengths and the ratio of their lengths (2D:4D ratio). This ratio is associated with a variety of behavioral and physiological traits possibly linked to variation in sex hormones levels. Previous studies have revealed inconsistent results while assessing the association of 2D:4D ratio as a risk factor for occurrence of knee osteoarthritis (KOA). This study was designed as a prospective observational study to analyze this association using a better methodology. Methods: Patients were enrolled into KOA group (1396 patients) and non-KOA group (1060 patients) based on ACR criteria for OA knee. Knee and hand radiographs of all patients enrolled were assessed. The 2D:4D length ratio was calculated for phalanges, metacarpal bones and for the combined (metacarpal & phalanx) finger lengths on radiographs and visual finger lengths. The finger patterns were classified and assessment was done between these ratios and finger pattern types for occurrence and severity of KOA.NOTE: This Results: preprint reportsA lower new research2D:4D that ratio has notin beenan individualcertified by peer was review associated and should not with be used an to increased guide clinical chancepractice. of KOA and a dose response relationship was found between radiographic grading of KOA and 2D:4D medRxiv preprint doi: https://doi.org/10.1101/2020.07.22.20159681; this version posted July 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . ratio. Conclusion: Based on the findings of this study one can predict the risk of developing KOA using this simple technique which can be used as a screening tool whereby preventive intervention can be started if someone presents early with a low 2D:4D finger length ratio. Keywords: Fingers; Geriatrics; Odds ratio; Osteoarthritis, Knee; Risk assessment; Risk medRxiv preprint doi: https://doi.org/10.1101/2020.07.22.20159681; this version posted July 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Introduction Osteoarthritis (OA) is among the most prevalent diseases in the world.(1) It is one of the leading causes of disability among elderly. Numerous risk factors are suspected to play a role in the causation of primary OA. They can be broadly classified as non-modifiable and modifiable. While the non-modifiable risk factors for OA are age, sex, genetic influences and race; modifiable risk factors include occupation, nutrition, muscle weakness, knee instability, malalignment and abnormal joint loading (including obesity).(2,3) It has been suggested that estrogen depletion plays a role in the onset and progression of OA. Men are known to have a higher prevalence of OA than women before the age of 50 (4), but after this age the prevalence is higher in women.(5,6) The prevalence increases with age in both men and women, but in women, it increases dramatically after the age of 50 (7), which coincides with menopause. In the human hand, the 2nd (index finger) and the 4th (ring finger) digits present a pattern of approximate symmetry around the central axis of the 3rd (Middle finger) digit. However, there is considerable variation in the ratio of the lengths of the 2nd to the 4th digit (2D:4D). Many individuals have a longer 2nd digit (2D:4D>1) while many have a longer 4th digit (2D:4D<1). The former is usually more common in females and the latter in males. (8) The index to ring finger length ratio (2D:4D) is believed to be associated with a wide variety of behavioral and physiological traits. (8– 12) Finger length patterns have been studied in relation to several diseases and physiologic traits and have been linked to the levels of sex hormones. Associations have been described with coronary artery disease, autism, infertility, and age at menarche. Based on the 2D:4D ratio, the hand has been classified into three types - index finger longer than ring finger (type 1), equal to the ring finger (type 2), or shorter than the ring finger (type 3). (8–12) Men are over 2.5 times more likely than women to have a type 3 pattern. Type 3 finger pattern was also associated with a female estrogen deficiency and could be considered a surrogate marker of earlier onset of menopause. (13) The association of 2D:4D ratio has been assessed as an independent risk factor to occurrence and severity of knee osteoarthritis (KOA) in few previous studies.(13–16) However, the results are inconsistent among them. Their reported inconsistencies are probably related to ethnicity of their study population or are from a difference in the case definition of osteoarthritis considered by them. Our aim was thus to assess whether predicting the possibility of developing a future knee osteoarthritis could be based on this association using a better methodology. This has the advantage of early initiation of preventive strategies thereby reducing the burden of this morbid disease. Methods medRxiv preprint doi: https://doi.org/10.1101/2020.07.22.20159681; this version posted July 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . This prospective observational study was performed at a tertiary care teaching hospital in Northern India. Institutional ethical committee approval was obtained prior to initiation of the study. All the patients reporting to the out-patient clinic of the Department of Orthopedics over a 2 years period (2014-2016) were considered and those who consented were included. Two groups of patients were enrolled – those with KOA (KOA group) and those without (non-KOA group). Inclusion criteria for the KOA group were age more than 25 years and a diagnosis of primary KOA based on American college of Rheumatology criteria (ACR criteria) (17) irrespective of the grade of OA (Kellgren - Lawrence grade). Patients were excluded if they had KOA secondary to trauma, inflammatory diseases (rheumatoid arthritis, ankylosing spondylitis etc.) or as a sequelae of infective diseases like septic arthritis. Patients with crystal arthropathy and with any injury or deformity of the hand not from primary OA were also excluded. The non-KOA patients were also >25 years of age and had presented to the clinic with complaints other than OA. Demographic characteristics with a potential to cause or contribute to KOA were recorded in a pre- defined format and included weight, height, waist circumference (WC), blood pressure and history of other risk factors like smoking, alcohol intake, diabetes mellitus and hypertension. Postero- anterior (PA) radiographs of the hands were obtained. Finger length measurements were obtained for participants of both the groups by two methods – visual and radiographic. For visual finger length the soft tissue outlines of the index and ring finger were measured from the base of a digit to its tip using a Vernier caliper. The Vernier caliper is an extremely precise measuring instrument; the reading error is 1/20 mm = 0.05 mm. The radiographic method involved measuring the lengths of 2nd (2D) & 4th metacarpal (4D) and 2nd (2D) & 4th phalanx (4D) with on 100% magnification X- rays of the hand by an independent observer and the 2D:4D length ratio was calculated. (Figure 1) The radiographic phalanx length is the length from the midpoint of the base of the proximal phalanx to the midpoint of the tip of the distal phalanx, and the radiographic metacarpal length (cm) is measured from the midpoint of the base of the metacarpal to the midpoint of the tip of the metacarpal bone. The 2D:4D length ratio was calculated separately for phalanges and metacarpal bones, as well as for the combined (metacarpal & phalanx) finger lengths. This has been described in Table 1. The values for left and right hand were averaged out. Average finger length was classified into 3 types based on relative length of the index finger with respect to ring finger and index finger was either longer (type 1), equal to (type 2), or shorter than the ring finger (type 3).
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