Osteoarthritis and Cartilage 19 (2011) 58e64

Osteoathitis and Catilage 19 (2011) 58e64 Does measuement of the anatomic axis consistently pedict hip-knee-ankle angle (HKA) fo knee alignment studies in osteoathitis? Analysis of long limb adiogaphs fom the multicente osteoathitis (MOST) study L. Sheehy y *, D. Felson z a, Y. Zhang z a, J. Niu z a, Y.-M. Lam x, N. Segal k a, J. Lynch { a, T.D.V. Cooke y y School of Rehabilitation Theapy, Queen s Univesity, Kingston, Ontaio, Canada z Boston Univesity School of Medicine, Boston, MA, USA x Community Health and Epidemiology, Mathematics and Statistics, Queen s Univesity, Kingston, Ontaio, Canada k Depatment of Othopaedics & Rehabilitation, Univesity of Iowa, Iowa City, IA, USA { Depatment of Epidemiology & Biostatistics, Univesity of Califonia at San Fancisco, San Fancisco, CA, USA aticle info summay Aticle histoy: Received 10 June 2010 Accepted 24 Septembe 2010 Keywods: Knee osteoathitis Alignment Radiogaphy Anatomic axis Mechanical axis Defomity Objective: Reseaches commonly use the femoal shaftetibial shaft angle (FSeTS) fom knee adiogaphs to estimate the hip-knee-ankle angle (HKA) in studies examining isk factos fo knee osteoathitis (OA) incidence and pogession. The objective of this study was to detemine the elationship between HKA and FSeTS, depending on the method of calculating FSeTS and the diection and degee of knee defomity. Methods: 120 full-length digital adiogaphs wee assigned, with 30 in each of fou alignment goups (0.0 e4.9, and 5.0 of vaus and valgus), fom a lage cohot of pesons with and at isk of knee OA. HKA and five measues of FSeTS (using pogessively shote shaft lengths) wee obtained using Hoizons Analysis Softwae, Othopaedic Alignment & Imaging Systems Inc. (OAISYS). The offsets between HKA and the diffeent vesions of FSeTS wee calculated, with 95% confidence intevals (CIs). Peason coelations wee calculated. Results: In vaus limbs use of a shote shaft length inceased the offset between HKA and FSeTS fom 5.1 to 7.0. The opposite occued with valgus limbs (fom 5.0 to 3.7 ). Coelations between HKA and FSeTS fo the whole sample of 120 individuals wee excellent ( ange 1.00e0.88). Howeve, coelations fo individual alignment goups wee low to modeate, especially fo the shotest-shaft FSeTS ( ange 0.41e0.66). Conclusions: The offsets obtained using the shote FSeTS measuements vay depending on diection and degee of knee defomity, and theefoe may not povide eliable pedictions fo HKA We ecommend that full-length adiogaphs be used wheneve an accuate estimation of HKA is equied, although boad categoies of alignment can be estimated with FSeTS. Ó 2010 Osteoathitis Reseach Society Intenational. Published by Elsevie Ltd. All ights eseved. Symptomatic knee osteoathitis (OA) with adiogaphic changes was estimated to affect between 6.7% and 16.7% of individuals ove 45 yeas old in a 2005 eview of studies pefomed in the United States 1. This ate is inceasing, pimaily due to demogaphic factos such as aging of the population, inceasing ates of obesity and an inceasing pevalence of taumatic OA 2. Vaus o valgus alignment of the lowe limb has been shown to incease the isk of pogession of knee OA 3e8. Moe specifically, the odds atio (OR) of OA pogession in the * Addess coespondence and epint equests to: Lisa Sheehy, School of Rehabilitation Theapy, Queen s Univesity, Louise D. Acton Building, 31 Geoge Steet, Kingston, Ontaio, K7L 3N6, Canada. Tel: 1-613-744-6517. E-mail addess: lisasheehy@sympatico.ca (L. Sheehy). a Fo the Multicente Osteoathitis Goup. medial tibiofemoal compatment fo those with vaus defomity has been calculated to be between 2.90 and 10.96 3,4,6,7. Fo pogession of lateal compatment OA in individuals with valgus defomity the OR is between 1.39 and 10.44 3,4,6,7. The hip-knee-ankle angle (HKA) is a measue of lowe-limb alignment, defined as the angle between the mechanical axes of the femu and the tibia (Fig. 1). HKA is measued fom a full-length lowe-limb adiogaph. In healthy adults with a neutal alignment, HKA is between 1.0 and 1.5 of vaus 9,10. The femoal shaftetibial shaft angle (FSeTS) is the angle between the anatomic axes of the femu and the tibia (Fig. 1). Many advocate the use of FSeTS taken fom adiogaphs of the knee to estimate HKA, with o without an offset, which is the diffeence between HKA and FSeTS 11e13. They ague that thee is a high coelation ( ¼ 0.65e0.88) between HKA and FSeTS, and that thee ae seveal advantages of a knee 1063-4584/$ e see font matte Ó 2010 Osteoathitis Reseach Society Intenational. Published by Elsevie Ltd. All ights eseved. doi:10.1016/j.joca.2010.09.011

L. Sheehy et al. / Osteoathitis and Catilage 19 (2011) 58e64 59 adiogaph ove a full-length one. Howeve, othes ague that in ode to obtain the best estimate of mechanical alignment, HKA must be diectly measued fom full-limb adiogaphs, because using a knee adiogaph limits the accuacy of the measuement 14,15. Defomities of shafts of the long bones might alte the elationship between HKA and FSeTS, as may subluxation at the knee 15e17. One facto which might influence the ability of FSeTS to accuately estimate HKA is the method used to calculate FSeTS. Statistically significant diffeences in FSeTS measuements have been found depending on how the anatomic axes wee measued 10,18. FSeTS is commonly measued on knee adiogaphs using lines dawn fom the knee to a point 10 cm along the shafts of the long bones 11,13,14. Howeve, the use of othe locations fo the shaft points might change the elationship of FSeTS to HKA. Theefoe, we wished to compae seveal diffeent vesions of FSeTS, using diffeent points of oigin, to estimate HKA. An impotant consideation is that fo the esults to be useful the shaft points must be visible on commonly acquied adiogaphs. It is also possible that the elationship between HKA and FSeTS might vay with espect to the natue (vaus o valgus) and seveity of defomity. We wee unable to find any pio studies that evaluated this question. Theefoe, we wished to study this elationship in cohots of individuals with mild and sevee vaus and valgus defomities. Thus, the aim of the cuent study was to detemine the elationship between HKA and FSeTS in subjects with o at high isk of knee OA. We asked thee eseach questions. Does the elationship between FSeTS and HKA diffe depending on diection and magnitude of knee defomity? Does the shaft length used to detemine FSeTS affect its ability to accuately estimate HKA? What popotions of the femoal and tibial shafts ae seen on a typical knee adiogaph? The esults of this study will infom eseaches who pefom clinical and epidemiological studies which method of measuing lowe-limb alignment best suits thei needs. Patients and methods Fig. 1. Diagam of a full-length lowe-limb adiogaph with a vaus alignment. Mechanical and anatomic axes as well as the vaious angles ae epesented. The points maked on the adiogaph in ode to calculate the HKA and the vaious FSeTSs ae numbeed 1e13. 1 e cente of head of femu, 2 e femoal intetochanteic point, 3 e 2/3 femoal shaft point, 4 e 1/2 femoal shaft point, 5 e 1/3 femoal shaft point, 6 e 10 cm femoal shaft point, 7 e femoal intecondyla point, 8 e tibial intespinous point, 9 e 10 cm tibial shaft point, 10 e 1/3 tibial shaft point, 11 e 1/2 tibial shaft point, 12 e 2/3 tibial shaft point, 13 e tibial mid-plafond point. FS e femoal shaft (femoal anatomic axis), FM e femoal mechanical axis, TS e tibial shaft (tibial anatomic axis), TM e tibial mechanical axis, HKA hip-knee-ankle angle, FS-TSefemoal shaft-tibial shaft angle. Modified fom Cooke et al. J Rheumatol 2007;34:1796e1801, with pemission. The database of full-length lowe-limb adiogaphs fom the Multicente Osteoathitis (MOST) Study was used to select images fo this study. The MOST study was appoved by institutional eview boads at the Univesity of Iowa, Univesity of Alabama, Bimingham, Univesity of Califonia, San Fancisco and Boston Univesity Medical Campus and paticipants povided witten infomed consent. All of the paticipants in the MOSTstudy eithe had knee OA o wee at high isk fo developing knee OA. This included individuals who wee oveweight o obese and those with cuent knee pain o a histoy of knee injuy o sugey 6. Individuals wee excluded if they had heumatoid athitis, ankylosing spondylitis, psoiatic athitis, Reite s syndome, significant kidney disease, cance, bilateal knee eplacements, wee unable to walk without assistance o wee planning to move out of the study aea in the next 3 yeas 6. Fulllength films wee obtained fom 1598 subjects, accoding to the method of Shama et al. 7, with both ight and left limbs viewed. Vaious joint angles (including HKA) and limb lengths had peviously been detemined as descibed by Cooke et al. 19 The eliability of this technique has been confimed [inte-eade eliability fo HKA: Intaclass coelation coefficient (ICC) ¼ 0.995 [95% confidence inteval (CI), 0.994e1]; inta-eade eliability fo HKA: ICC ¼ 0.998 (95% CI, 0.998e1); inte-eade eliabilities fo othe angles between the femu and tibia: ICCs between 0.839 and 0.993; inta-eade eliabilities fo othe angles between the femu and tibia: ICCs between 0.908 and 0.998] 20. To avoid selecting both limbs fom the same subject only ight limbs wee selected. Limbs that showed factues, pins o plates and hip o knee eplacements wee excluded,

60 L. Sheehy et al. / Osteoathitis and Catilage 19 (2011) 58e64 as wee those whee full analysis was not possible because of poo image quality o because some of the limb was not visible on the image. Finally, chosen images must have had a ule to allow fo scaling. Thus 1240 limb images wee available fo analysis. Fom these, 30 ight limbs wee andomly selected fo each of fou categoies, based on HKA; goup 1: HKA of 5.0 vaus o geate, goup 2: HKA fom 0.0 up to and including 4.9 vaus, goup 3: HKA fom 0.1 up to and including 4.9 valgus, and goup 4: HKA of 5.0 valgus o geate. Goup 1 was chosen fom 181 individuals (14.6% of the available limb images), goup 2 fom 598 individuals (48.2%), goup 3 fom 406 individuals (32.7%) and goup 4 fom 55 individuals (4.4%). We attempted to select each goup so that it would contain balanced epesentation of the sexes. While equal numbes of adiogaph images wee selected fo each sex fo thee of the fou HKA-based alignment goups, only two male subjects had valgus defomities of geate than 5. Both wee included in goup 4. The goups wee compaed with espect to demogaphic vaiables [age, weight, height, body mass index (BMI) and KellgeneLawence gade (K/L)] using t-tests fo continuous vaiables and Chi-squae fo odinal vaiables (Table I). K/L gade was significantly associated with goup (c 2 ¼ 55.8, P < 0.0001). Subjects with geate defomity (vaus and valgus) moe often had OA, based on K/L gade. A custom vesion of Suveyo 2.0 softwae fom Othopaedic Alignment & Imaging Systems Inc. (OAISYS) was used to detemine HKA and seveal vaiations of FSeTS on the full-length adiogaphs (Fig. 1). Points wee placed on the images with digital tools (centeline, cicle, ule), using stict citeia to minimize bias. Fo measuements of HKA, points placed at the cente of the femoal head, the femoal intecondyla notch, the tibial intespinous goove and at the cente of the tibial plafond wee used. The fist two points defined the femoal mechanical axis and the second two points defined the tibial mechanical axis. The angle at the intesection of the two lines was HKA, with negative numbes indicating vaus alignment and positive numbes indicating valgus alignment. Fo full-length FSeTS, the points wee located at the intetochanteic point between the geate and lesse femoal tochantes in line with the femoal neck axis and at the femoal intecondyla notch (femoal anatomic axis), as well as at the tibial intespinous goove and at the cente of the tibial plafond (tibial anatomic axis). The angle between these axes defined the full-length FSeTS. Thee additional points wee located on the mid-shaft of the femu, twothids, one-half and one-thid of the length of the femoal shaft fom the knee. Coesponding points wee located on the mid-shaft of the tibia. Finally, points wee located on the femoal and tibial shafts 10 cm fom the knee points. The shaft points wee used to calculate fou diffeent FSeTS angles, descibed as 2/3 FSeTS, 1/2 FSeTS, 1/3 FSeTS and 10 cm FSeTS. To minimize bias, the points wee maked in poximal to distal ode, and the esulting angles wee not eviewed until afte all points wee maked. The images wee analysed in ode of acquisition athe than by goup. Mean offset was defined as the mean HKA minus the mean FSeTS. Mean offsets and 95% CIs between HKA and the diffeent methods of calculating FSeTS wee detemined fo the complete sample of 120 limbs and fo each alignment goup. Peason coelation coefficients (CC) wee used to compae HKA and the diffeent methods of calculating FSeTS, fo the complete sample and sepaately fo each alignment goup. To detemine if the elationship between FSeTS and HKA diffeed depending on diection and magnitude of knee defomity, the size of the mean offsets was examined between alignment goups and compaed to that of the complete sample. CIs and CCs wee used to study the ability of the vaious FSeTS measuements to accuately estimate HKA. To detemine any effect of sex on the esults we caied out a twoway analysis of vaiance (ANOVA) to compae sex diffeences with goup, sex and goupsex as factos, fo all of the alignment angles and mean offsets. Post-hoc Tukey analyses wee pefomed as needed. Goup 4 was not included due to insufficient numbes of male subjects. Fo goups 1e3 thee wee no goupsex inteactions o sex main effects fo the angles and offsets, with two exceptions. Sex had a main effect fo the angle 10 cm FSeTS and the offset HKA e 10 cm FSeTS (Table II). Howeve, we did not find significant offset sex diffeences in the offsets among alignment goups. All statistical analyses wee pefomed using MinitabÔ statistical softwae (Release 15.1.30, Minitab Inc., State College, Pennsylvania). Statistical significance was set at a ¼ 0.05 (two-sided) fo all tests. Finally, the popotion of the femoal and tibial shafts visible on a typical knee adiogaph was detemined. Typical adiogaph cassettes and digital adiogaph systems have an exposue aea that is 16.5 o 17.0 inches (419 o 432 mm) long. All 120 ight limbs wee eviewed to detemine what popotion of the shaft lengths would be visible on a 419 mm long image. Results To investigate the elationship between HKAeFS-TS offset, FSeTS shaft length and alignment goup, mean offsets and 95% CIs wee calculated and plotted (Fig. 2). The aveage offset between the mechanical and anatomic axes (full-length FSeTS) fo the entie dataset was 5.0 (95% CI, 5.1, 4.9). Howeve, when the sample was boken down into alignment goups, substantial vaiability was evident. Fo limbs with a vaus defomity the magnitude of the Table I Demogaphic data, with mean and standad deviation, fo each alignment goup Goup HKA Sex % of women Complete dataset 61% 63.0 8.4 1 5.0 50% 62.4 Vaus 9.5 2 Between 50% 61.5 0.0 and 4.9 8.0 Vaus 3 Between 0.1 and 4.9 Valgus 4 5.0 Valgus Significant diffeences (P < 0.05) 50% 63.9 9.1 Age mean (yeas) SD (yeas) Weight mean (kg) SD (kg) 89.3 16.0 93.7 15.6 88.8 18.3 86.8 13.1 Height mean (mm) SD (mm) 1682 91 1674 109 1683 85 1722 94 BMI mean (kg/m 2 ) SD (kg/m 2 ) 31.6 5.8 33.8 6.8 31.4 6.0 93% 64.2 87.8 1652 32.2 7.0 16.4 61 5.9 None None 3 & 4 P ¼ 0.025 1 & 3 P ¼ 0.022 29.2 3.3 K/L Gade % gade 2 o geate 51% 70% 33% 20% 80%

L. Sheehy et al. / Osteoathitis and Catilage 19 (2011) 58e64 61 Table II Means and 95% CIs fo lowe-limb angles and (HKA e FSeTS) offsets, divided by sex. Goup 4 was not included in the ANOVA to compae goup and sex due to insufficient male subjects (a) Lowe-limb angles Goup Sex HKA FSeTS 2/3 FSeTS 1/2 FSeTS 1/3 FSeTS 10 cm FSeTS Complete dataset 73 \ 1.4 (0.0, 2.8) 6.4 (5.1, 7.8) 7.3 (6.0, 8.5) 6.8 (5.6, 7.9) 6.2 (5.1, 7.3) 6.0* (4.9, 7.1) 47 _ 2.0 ( 3.4, 0.5) 3.0 (1.6, 4.5) 4.2 (2.8, 5.5) 4.1 (2.8, 5.4) 4.0 (2.8, 5.3) 4.6* (3.3, 5.8) 1 5.0 Vaus 15 \ 7.0 ( 7.6, 6.3) 1.5 ( 2.3, 0.7) 0.1 ( 0.7, 1.0) 0.3 ( 0.6, 1.2) 0.2 ( 0.9, 1.3) 0.3 ( 0.9, 1.5) 15 _ 7.7 ( 8.7, 6.7) 2.6 ( 3.5, 1.7) 1.2 ( 2.0, 0.3) 0.9 ( 2.1, 0.2) 0.7 ( 2.0, 0.6) 0.2 ( 1.7, 1.4) 2 Between 0.0 and 15 \ 2.6 ( 3.4, 1.8) 2.3 (1.5, 3.1) 3.8 (2.8, 4.7) 3.9 (2.9, 4.8) 3.6 (2.3, 4.9) 3.5 (2.1, 4.9) 4.9 Vaus 15 _ 2.0 ( 2.6, 1.4) 2.9 (2.3, 3.5) 4.3 (3.6, 5.0) 4.5 (3.7, 5.3) 4.6 (3.8, 5.3) 5.2 (4.4, 6.1) 3 Between 0.1 and 15 \ 2.0 (1.2, 2.7) 7.1 (6.4, 7.8) 7.4 (6.6, 8.2) 6.6 (5.6, 7.5) 5.7 (4.7, 6.7) 5.4 (4.3, 6.6) 4.9 Valgus 15 _ 2.0 (1.4, 2.6) 6.9 (6.3, 7.5) 7.6 (6.8, 8.3) 7.2 (6.4, 8.0) 6.9 (6.1, 7.7) 7.4 (6.4, 8.4) 4 5.0 Valgus 28 \ 7.7 (7.0, 8.5) 12.6 (11.8, 13.4) 12.9 (12.0, 13.8) 11.9 (11.0, 12.9) 11.0 (10.0, 12.0) 10.7 (9.6, 11.8) 2 _ 12.0 (9.9, 14.0) 17.3 (15.0, 19.7) 17.3 (16.2, 18.3) 15.6 (15.0, 16.2) 14.4 (14.0, 14.8) 13.7 (12.6, 14.7) (b) Lowe limb (HKA e FSeTS) offsets Goup Sex HKA e FSeTS HKA e 2/3 FSeTS HKA e 1/2 FSeTS HKA e 1/3 FSeTS HKA e 10 cm FSeTS Complete dataset 73 \ 5.0 ( 5.2, 4.9) 5.9 ( 6.2, 5.6) 5.4 ( 5.8, 5.0) 4.7 ( 5.3, 4.2) 4.6* ( 5.2, 4.0) 47 _ 5.0 ( 5.2, 4.8) 6.1 ( 6.4, 5.8) 6.1 ( 6.5, 5.6) 6.0 ( 6.6, 5.4) 6.5* ( 7.3, 5.8) 1 5.0 Vaus 15 \ 5.4 ( 5.7, 5.1) 7.1 ( 7.5, 6.7) 7.3 ( 7.8, 6.7) 7.2 ( 8.0, 6.3) 7.2 ( 8.2, 6.2) 15 _ 5.1 ( 5.4, 4.8) 6.5 ( 7.1, 6.0) 6.8 ( 7.7, 5.9) 7.0 ( 8.2, 5.7) 7.5 ( 9.1, 6.0) 2 Between 0.0 and 15 \ 4.9 ( 5.3, 4.6) 6.4 ( 7.0, 5.8) 6.5 ( 7.2, 5.7) 6.2 ( 7.3, 5.1) 6.2 ( 7.4, 4.9) 4.9 Vaus 15 _ 4.9 ( 5.2, 4.6) 6.3 ( 6.8, 5.8) 6.5 ( 7.1, 5.8) 6.5 ( 7.3, 5.8) 7.2 ( 8.1, 6.4) 3 Between 0.1 and 15 \ 5.1 ( 5.4, 4.9) 5.4 ( 5.9, 5.0) 4.6 ( 5.2, 4.0) 3.8 ( 4.6, 3.0) 3.5 ( 4.4, 2.6) 4.9 Valgus 15 _ 4.9 ( 5.3, 4.5) 5.6 ( 6.3, 5.0) 5.3 ( 6.0, 4.5) 4.9 ( 5.7, 4.1) 5.5 ( 6.4, 4.6) 4 5.0 Valgus 28 \ 4.9 ( 5.0, 4.7) 5.2 ( 5.6, 4.8) 4.2 ( 4.8, 3.7) 3.2 ( 4.0, 2.5) 2.9 ( 3.8, 2.1) 2 _ 5.4 ( 5.6, 5.1) 5.3 ( 6.3, 4.3) 3.7 ( 5.1, 2.2) 2.5 ( 4.9, 0.0) 1.7 ( 4.8, 1.4) * Sex main effect, P < 0.05. offset inceased as the shaft length fo the FSeTS calculation deceased. But fo limbs with a valgus defomity, the magnitude of this offset deceased. Similaly, the data fo the individual alignment goups evealed much weake coelations. Linea egession equations fo 10 cm FSeTS wee as follows: goup 1 (sevee vaus) HKA ¼ 7.34 þ 0.266 10 cm FSeTS; goup 2 (mild vaus) HKA ¼ 3.47 þ 0.267 10 cm FSTS; goup 3 (mild valgus) HKA ¼ 0.039 þ 0.298 10 cm FSTS; and goup 4 (sevee valgus) HKA ¼ 2.67 þ 0.491 10 cm FSTS. FSeTS shaft length appeas to influence the ability to estimate HKA. When we examined the coelation between HKA and FSeTS, we found that coelations fo the entie sample wee high ( > 0.88) (Table III). Howeve the coelations wee much weake fo shoteshaft FSeTS measuements. Despite the sex main effect fo HKA e 10 cm FSeTS the coelations fo the entie sample divided into males ( ¼ 0.87) and females ( ¼ 0.89) wee vey simila. Finally, we investigated how much of the femoal and tibial shafts ae visible on a typical knee adiogaph. Pesuming that the knee was centeed pefectly on the image, a 419 mm long adiogaph image showed appoximately 208 mm above and 208 mm below the joint line. One-thid of the tibial and femoal shafts wee seen on all images, as wee the 10 cm points. One-half of the femoal shaft was seen on the shotest limbs (23% of the 120 limbs in the sample) and one-half of the tibial shaft was seen on most of the limbs (92% of the limbs). The two-thids femoal and two-thids tibial shaft points wee not seen on limbs of any length. Discussion Seveal studies have investigated the elationship between HKA and FSeTS. 11e14,21 The cuent study, to ou knowledge, is the fist to suggest that the elationship between HKA and FSeTS diffes Table III Peason coelations () between HKA and the diffeent methods of measuing FSeTS. P < 0.05 in each case Fig. 2. Mean offsets (with 95% CIs) between HKA and the diffeent methods of detemining FSeTS, fo each alignment goup. Goup FSeTS 2/3 FSeTS 1/2 FSeTS 1/3 FSeTS 10 cm FSeTS Complete 1.0 0.98 0.96 0.92 0.88 dataset 1 5.0 Vaus 0.95 0.85 0.71 0.52 0.41 2 Between 0.0 0.90 0.74 0.62 0.51 0.45 and 4.9 Vaus 3 Between 0.1 0.87 0.73 0.60 0.50 0.50 and 4.9 Valgus 4 5.0 Valgus 0.98 0.91 0.82 0.72 0.66

62 L. Sheehy et al. / Osteoathitis and Catilage 19 (2011) 58e64 depending on the diection and degee of defomity of the lowe limb. Also, we found that using shote FSeTS shaft lengths to estimate HKA modestly weakened the elationship of anatomic axis with mechanical axis in the oveall sample. The elationship of these two measues was especially attenuated when both shote-shaft lengths wee used and subcategoies of alignment wee studied. The fou alignment goups demogaphics did not diffe significantly, with a few exceptions. Only two males in the entie MOST database had HKA angles of geate than 5 valgus. The aity of valgus defomity in males has been noted befoe 9,11,22 and patly explains the diffeence in height between goups 3 and 4. Those with geate defomities (vaus o valgus) had highe K/L gades and tended to have highe BMIs. With only two exceptions no significant diffeences wee found between the sexes with espect to the vaious angles and offsets, simila to pio esults fom adults with 11 and without knee OA 16,18 Howeve, in contast to the cuent study, a diffeence has peviously been found in HKA and (HKA e FSeTS) offsets between the sexes 11,12,17. The offset fo females has been epoted to be between 3.0 and 3.5 while that fo males was between 4.7 and 6.4 11,12. Chang et al. 17 epoted the opposite tend, with females having a lage offset than males (7.3 vs 6.0,FSeTS measued with 15 cm shaft lengths), at least fo individuals with knee OA. Futhe compaisons of males and females need to be pefomed to confim if eal diffeences exist and in what diection. Reseach question 1 asked whethe the elationship between FSeTS and HKA diffes depending on the diection and magnitude of knee defomity. Ou aveage offset between HKA and full-length FSeTS of 5.0 is simila to findings fom othe studies whee 4 e6 is typically consideed as the diffeence 10,11,21,23. Howeve, ou data show that the HKA e FSeTS offset vaied as a function of the degee of defomity, especially fo FSeTS measues made using shote shaft lengths. Specifically, fo vaus limbs the offset inceased and fo valgus limbs, it deceased. Theefoe when dealing with individuals with significant vaus o valgus defomity, it would be inaccuate to use 5.0 as the diffeence between HKA and the shote-shaft vesions of FSeTS, as FSeTS measuements vay widely fom HKA. Reseach question 2 asked whethe the shaft length used to detemine FSeTS affects its ability to accuately estimate HKA. As the FSeTS shaft length deceased, the confidence limits aound ou offsets inceased and the coelations fo the individual alignment goups deceased fom geate than ¼ 0.87 (fo HKA e full-length FSeTS) to less than ¼ 0.66 (fo HKA e 10 cm FSeTS) (Table III), contibuting to a poo estimate fo HKA. Pio studies, using 10 cm shaft lengths and the same knee points as in the cuent study, have found poo to excellent coelations between HKA and FSeTS ( ¼ 0.27e0.88 fo FSeTS obtained with standing adiogaphs 11,13,14,17 and ¼ 0.66e0.75 fo FSeTS obtain with fixedflexion adiogaphs 11,21 ). Some of these studies had a wide vaiety of subjects with vaus, valgus and neutal lowe-limb alignments ( ¼ 0.27e0.80) 11,17,21 while othes only used subjects with medial compatment OA, which is associated with vaus alignment ( ¼ 0.34e0.88) 13,14. When ou subject sample was boken down into alignment stata the coelations become much weake, especially fo the 1/3 and 10 cm FSeTS calculations. One limitation of pefoming coelations on subgoups of a dataset is that because each goup is limited to individuals within a small ange of HKA values, the coelations will be attenuated. Howeve, we also found that the coelations became weake as the FSeTS shaft lengths deceased. Confidence limits aound the HKAs imputed wee wide enough to suggest caution when using 1/3 FSeTS and 10 cm FSeTS measuements to estimate HKA. Seveal authos have epoted esults simila to ous when compaing diffeent methods of calculating FSeTS, including geate vaiation between the mechanical axis and distal femoal anatomic axis than the full-length anatomic axis, and a highe coelation ( ¼ 0.65, P < 0.0001) between HKA and FSeTS calculated using the mid-diaphyseal lines of the femu and tibia than 10 cm FSeTS ( ¼ 0.34, P ¼ 0.005) 14,18. As well, FSeTS measuements taken using a 15 cm shaft length ( ¼ 0.81 fo males, ¼ 0.88 fo females) had geate coelations to HKA than those taken using a 10 cm shaft length ( ¼ 0.69 fo males, ¼ 0.80 fo females) 17. These studies lend suppot to ou contention that shot-shaft FSeTS measuements incease uncetainty if used to estimate HKA. HKA measuements allow the oppotunity to study the contibution of vaious pats of the limb to alignment 9,24. Geometic changes in the shafts of the bones may cause some of the discodance between HKA and FSeTS 9,17. These changes might pedispose individuals to knee OA o may be bought on by bone emodelling that occus with OA development 9,17. Reseach question 3 asked what popotions of the femoal and tibial shafts ae seen on a typical knee adiogaph. Much of the pio eseach compaing HKA and FSeTS uses FSeTS measuements calculated using a 10 cm shaft length 11,13,14. The esults show that one-thid of the femoal and tibial shafts ae visible on the aveage cassette, even fo the tallest subjects. Unfotunately, the coelations ae similaly poo fo the 10 cm and 1/3 FSeTS compaisons to HKA. One limitation to this study is that the vaious FSeTS measuements wee detemined fom full-length adiogaphs athe than anteoposteio knee adiogaphs which ae commonly used in eseach investigating the incidence and pogession of knee OA. FSeTS calculated fom full-length adiogaphs and anteoposteio knee adiogaphs have neve been compaed, howeve Kaus et al. 11 found a good coelation ( ¼ 0.73, P < 0.0001) between FSeTS measued fom semiflexed knee adiogaphs and FSeTS measued fom full-length adiogaphs. This study has pactical implications with espect to the measuement of lowe-limb alignment fo eseach puposes. Thee ae significant limitations to using FSeTS to pedict lowe-limb alignment, especially when an accuate measuement of mechanical alignment is equied and we ecommend that HKA be used to detemine lowe-limb alignment. Howeve, fo samples with a vaiety of vaus and valgus limbs and whee boad categoies of alignment ae equied fo lage numbes of pesons in a study, FSeTS could be used with the coection factos we povide to categoize subjects as vaus o valgus, with the ecognition that limbs close to neutal will be had to accuately classify. Fo subgoup studies, such as those of medial knee OA, categoizing limbs will poduce moe accuate estimates (i.e., all will pobably be vaus), but since thee is uncetainty aound each of the coection factos (see CIs in tables), estimation of HKA fom FSeTS is impefect and using FSeTS to guess the exact HKA in individuals is poblematic. This caution also petains to the use of lowe-limb alignment to estimate joint space naowing in the pogession of knee OA. If FSeTS is used to estimate HKA, which in tun is used to estimate joint space naowing, any eo will be compounded. In individuals with sevee valgus defomity, valgus malalignment seveity would be undeestimated using FSeTS, and thus any joint space change would be undeestimated. Convesely, fo individuals with sevee vaus defomity, the degee of vaus malalignment would be oveestimated using FSeTS and any joint space change would be oveestimated. In conclusion, we ecommend that full-length adiogaphs be used wheneve an accuate estimation of HKA is equied. This is because the offset between HKA and shot-shaft FSeTS measuements is vaiable, and is influenced by the diection and degee of malalignment of the lowe limb. Impecision aound the coection facto would make it challenging to accuately pedict an individual s mechanical axis. Howeve, boad categoies of alignment in goups of pesons can be estimated using shot limb films, especially if the sample includes a vaiety of limbs that ae vaus, neutal and valgus.

L. Sheehy et al. / Osteoathitis and Catilage 19 (2011) 58e64 63 Declaation of authos contibutions Lisa Sheehy takes esponsibility fo the integity of the wok as a whole, fom inception to finished aticle. Lisa Sheehy David Felson Yuqing Zhang Jingbo Niu Yuk-Miu Lam Neil Segal John Lynch T.D.V. Cooke Conception and design U U U Analysis and intepetation of the data U U U U U U Dafting of the aticle U U U Citical evision of the aticle fo impotant U U U U U U U U intellectual content Povision of study mateials o patients U U U Statistical expetise U U U U U Obtaining of funding U U Administative, technical, o logistic suppot U U Collection and assembly of data U U U Final appoval of the aticle U U U U U U U U Declaation of funding and ole of funding souces Funding fo the MOST was obtained though NIH and NIA unde the following gant numbes: AG18820, AB18832, AG18947 and AG19069. Funding fo this Ancillay Poject of the MOST study was obtained fom D. Felson, Boston Univesity School of Medicine. D. Felson is one of the authos of this manuscipt and had a ole in the design of the study, the acquisition and intepetation of data, evising the manuscipt fo impotant intellectual content and final appoval of the manuscipt. Conflict of inteest D. Cooke is Pesident and pinciple shaeholde of OAISYS Inc, a medical device company specializing in the analysis of adiogaphic images. Nothing of commecial value was eceived fom any souce duing the couse of this investigation. Acknowledgements We acknowledge Chis Wale fo modifying the OAISYS Suveyo 2.0 softwae pogam fo this study. Financial suppot was povided by NIH AR47785 and by AR051568. Softwae was povided coutesy of OAISYS, Inc. Refeences 1. Lawence RC, Felson DT, Helmick CG, Anold LM, Choi H, Deyo RA, et al. Estimates of the pevalence of athitis and othe heumatic conditions in the United States. Pat II. Athitis Rheum 2008;58:26e35. 2. Ioio R, Robb WJ, Healy WL, Bey DJ, Hozack WJ, Kyle RF, et al. 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