Knee osteoarthrosis and total knee arthroplasty (TKA)

2.1.1 Biomechanics

The knee joint is located between femur and tibia, which are the two longest bones of the human skeleton. It is the largest weight-bearing joint in human body. There-fore, there are high mechanical forces transferred through the joint especially dur-ing walkdur-ing, kneeldur-ing and climbdur-ing stairs. The patella is responsible in transmittdur-ing the tensile force of the extensor apparatus across the knee. Gait analysis has shown that in normally aligned knees during walking, approximately 70% of the total load is transmitted through the medial compartment (Hurwitz, et al. 1998), causing 2.5-fold load to the medial joint surface compared with the lateral one (Baliunas, et al.

2002). The forces from the femoral condyles to the tibial plateau during normal walking have been estimated to be 2-4 times the body weight. At 45 degrees of knee flexion, the tensile force in the surface of patella reaches the maximum, which can be 7-8 times the body weight during deep knee bends such as kneeling (Taylor, et al. 2004).

The lower limb mechanical axis is regarded as the most important biomechani-cal mechanism of the knee joint. The mechanibiomechani-cal axis is a combination of the femo-ral and tibial axis. The femofemo-ral axis is measured from the center of the femofemo-ral head to the center of the knee joint. The tibial axis is measured from the center of the knee to the center of the ankle joint (or center of the talus). The angle between the femoral and tibial axis demonstrates the degree of the aberration from the straight mechanical axis. Varus alignment means that the mechanical axis deviates medially from the center of the knee and valgus alignment laterally, respectively (Figure 1).

A proper mechanical axis is considered to provide optimal and equal loading con-ditions of the tibial condyles (Hvid, et al. 1988, Miyazaki, et al. 2002). A major pur-pose of the joint replacement surgery is to restore a normal axis, and a postopera-tive aberration of 3 degrees to valgus or varus is still considered to be acceptable.

The varus malalignment caused by knee OA further increases the normally greater load of the medial tibial condyle. Valgus malalignment, on the other hand, dimin-ishes the load-bearing forces of the medial condyle and more weight is transferred through the lateral compartment of the joint. Force-analysis calculations and dy-namic analysis of forces around the knee during gait have also shown that the me-dial compartment bears the entire load in knees with varus malalignment, and that the lateral compartment bears increased load only in instances of more advanced valgus malalignment (Li and Nilsson. 2001). Deviation of alignment is also

associat-ed with the progression of knee OA (Sharma, et al. 2001, Felson, et al. 2005, Sharma.

2007, Eckstein, et al. 2009, Khamaisy, et al. 2015).

Figure 1. Varus alignment (A) and valgus alignment (B) of the knee.

(A) The lower limb mechanical axis is in 21 degrees of varus. (B) The lower limb mechanical axis

is in 10 degrees of valgus.

During the knee flexion, there is a complex pattern movement between the articular facets of the distal femur and proximal tibia. The medial condyle of the femur can be viewed as a sphere, which rotates to produce a combination of flexion, longitu-dinal rotation and minimal varus. There is only a minimal translation of approxi-mately ±1,5mm between the medial femoral condyle and medial tibial facet. On the lateral side, there is a rolling and sliding movement, which allows a 15mm posterior translation of the lateral femoral condyle. As a consequence, the tibia rotates inter-nally approximately 30 degrees between 10 and 120 degrees of flexion (Pinskerova, et al. 2000, Pinskerova, et al. 2003, Freeman and Pinskerova. 2003, Freeman and Pinskerova. 2005).

The geometry of the distal femur and proximal tibia are intimately linked with the kinematics of the tibiofemoral and patellofemoral joints. Therefore, it is necessary to define the anatomical landmarks, especially in TKA surgery, since any misplacement will affect the loads and ligament tensions, leading to aberrant kinematics of the prosthesis (Victor. 2009). The generalized use of CT has given possibilities to assess the rotational alignments (Berger, et al. 1993). The rotation of the femur is typically determined by the angle comparing the surgical epicondylar axis with the posterior condylar axis, which is a line connecting the surfaces of the

2 REVIEW OF THE LITERATURE

2.1 KNEE OSTEOARTHROSIS AND TOTAL KNEE ARTHRO-PLASTY (TKA)

2.1.1 Biomechanics

The knee joint is located between femur and tibia, which are the two longest bones of the human skeleton. It is the largest weight-bearing joint in human body. There-fore, there are high mechanical forces transferred through the joint especially dur-ing walkdur-ing, kneeldur-ing and climbdur-ing stairs. The patella is responsible in transmittdur-ing the tensile force of the extensor apparatus across the knee. Gait analysis has shown that in normally aligned knees during walking, approximately 70% of the total load is transmitted through the medial compartment (Hurwitz, et al. 1998), causing 2.5-fold load to the medial joint surface compared with the lateral one (Baliunas, et al.

2002). The forces from the femoral condyles to the tibial plateau during normal walking have been estimated to be 2-4 times the body weight. At 45 degrees of knee flexion, the tensile force in the surface of patella reaches the maximum, which can be 7-8 times the body weight during deep knee bends such as kneeling (Taylor, et al. 2004).

The lower limb mechanical axis is regarded as the most important biomechani-cal mechanism of the knee joint. The mechanibiomechani-cal axis is a combination of the femo-ral and tibial axis. The femofemo-ral axis is measured from the center of the femofemo-ral head to the center of the knee joint. The tibial axis is measured from the center of the knee to the center of the ankle joint (or center of the talus). The angle between the femoral and tibial axis demonstrates the degree of the aberration from the straight mechanical axis. Varus alignment means that the mechanical axis deviates medially from the center of the knee and valgus alignment laterally, respectively (Figure 1).

A proper mechanical axis is considered to provide optimal and equal loading con-ditions of the tibial condyles (Hvid, et al. 1988, Miyazaki, et al. 2002). A major pur-pose of the joint replacement surgery is to restore a normal axis, and a postopera-tive aberration of 3 degrees to valgus or varus is still considered to be acceptable.

The varus malalignment caused by knee OA further increases the normally greater load of the medial tibial condyle. Valgus malalignment, on the other hand, dimin-ishes the load-bearing forces of the medial condyle and more weight is transferred through the lateral compartment of the joint. Force-analysis calculations and dy-namic analysis of forces around the knee during gait have also shown that the me-dial compartment bears the entire load in knees with varus malalignment, and that the lateral compartment bears increased load only in instances of more advanced valgus malalignment (Li and Nilsson. 2001). Deviation of alignment is also

associat-ed with the progression of knee OA (Sharma, et al. 2001, Felson, et al. 2005, Sharma.

2007, Eckstein, et al. 2009, Khamaisy, et al. 2015).

Figure 1. Varus alignment (A) and valgus alignment (B) of the knee.

(A) The lower limb mechanical axis is in 21 degrees of varus.

(B) The lower limb mechanical axis is in 10 degrees of valgus.

During the knee flexion, there is a complex pattern movement between the articular facets of the distal femur and proximal tibia. The medial condyle of the femur can be viewed as a sphere, which rotates to produce a combination of flexion, longitu-dinal rotation and minimal varus. There is only a minimal translation of approxi-mately ±1,5mm between the medial femoral condyle and medial tibial facet. On the lateral side, there is a rolling and sliding movement, which allows a 15mm posterior translation of the lateral femoral condyle. As a consequence, the tibia rotates inter-nally approximately 30 degrees between 10 and 120 degrees of flexion (Pinskerova, et al. 2000, Pinskerova, et al. 2003, Freeman and Pinskerova. 2003, Freeman and Pinskerova. 2005).

The geometry of the distal femur and proximal tibia are intimately linked with the kinematics of the tibiofemoral and patellofemoral joints. Therefore, it is necessary to define the anatomical landmarks, especially in TKA surgery, since any misplacement will affect the loads and ligament tensions, leading to aberrant kinematics of the prosthesis (Victor. 2009). The generalized use of CT has given possibilities to assess the rotational alignments (Berger, et al. 1993). The rotation of the femur is typically determined by the angle comparing the surgical epicondylar axis with the posterior condylar axis, which is a line connecting the surfaces of the

medial and lateral posterior femoral condyles. The rotation from the posterior condylar angle is 0.3° (± 1.2°) internal rotation for females and 3.5° (± 1.2°) internal rotation for males relative to the surgical epicondylar axis, which connects the medial epicondylar sulcus with the lateral epicondyle (Berger, et al. 1993, Berger, et al. 1998, Victor. 2009). To assess the tibial rotation, the geometric center (G.C.) of the tibial plateau is located and axially transposed to the level of the tibial tubercle. The line connecting the tip of the tubercle to the G.S. is the tibial anatomic axis. The AP tibial axis is drawn perpendicular to the posterior surface of the tibia. The angle between tibial anatomic axis and AP tibial axis is then measured to determine the rotation. Normal rotation using this method is 18° (± 2.6°) of internal rotation (Berger, et al. 1998).

2.1.2 Development of osteoarthrosis and effect on bone mineral density Knee OA is a very common degenerative joint disease (Sharma. 2016). According to the Mini-Finland health survey, the prevalence of knee OA in the population over 30 years of age was 6.1% in men and 8.0% in women (Toivanen, et al. 2010). There are many known risk factors for incident knee OA: Female gender, aging, obesity, traumatic knee injury, physically demanding work and heredity (Toivanen, et al.

2010, Sharma. 2016). However, OA is not only a disease of the cartilage. It can be defined as a disorder characterized by cell stress and extracellular matrix degrada-tion initiated by micro- and macro-injury that activates maladaptive repair respons-es including pro-inflammatory pathways of innate immunity (oarsi.org. 2015, Sharma. 2016). The disease manifests first as abnormal joint tissue metabolism fol-lowed by damage to the cartilage, bone remodeling, osteophyte formation, joint inflammation and loss of normal joint function. Nevertheless, the basic reason for OA remains unknown.

There has been a continuous debate of the relationship between high BMD and OA. The Chingford study over 20 years ago suggested that small increases in BMD are present in middle aged women with early radiological OA of the hands, knees and lumbar spine (Hart, et al. 1994). The Framingham study 17 years ago suggest-ed, that high BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee OA (Zhang, et al. 2000). A more recent data suggests that higher BMD could even reduce the risk of radiological hip OA, while intermediate levels may increase the risk of symptomatic knee OA (Barbour, et al. 2017). However, there are studies suggesting, that OA could be associated with high BMD and high bone mass phenotype (Burg-er, et al. 1996, Hardcastle, et al. 2015), and OA and osteoporosis rarely develop sim-ultaneously (Hannan, et al. 2000). In fact, there is evidence of an inverse relation-ship between these two disorders (Dequeker, et al. 2003, Multanen, et al. 2015),

which could be explained by differences in bone metabolism (Jiang, et al. 2008) or genetic factors (Logar, et al. 2007, Valdes and Spector. 2011).

2.1.3 Total knee arthroplasty

Total knee replacement is an established treatment method to reduce pain and dis-ability caused by end-stage OA. In this indication, it has been proved to be more effective than non-surgical treatment in a recent randomized controlled trial (Skou, et al. 2015) with a good survivorship of 90% or more up to fifteen years of follow-up (Robertsson, et al. 2000, Roberts, et al. 2007, Niinimaki, et al. 2014). Whereas the studies from previous decades mostly measured surgeon-driven objective scales or survivorship data, the recent focus been more on patient-reported outcome measures (PROMs) (Ethgen, et al. 2004, Jones, et al. 2014). These studies reveal that the proportion of patients satisfied after undergoing primary TKA ranges from 81.8% in a register study of England and Wales (Baker, et al. 2007) with similar re-sults in the Ontario Joint Replacement Registry (Bourne, et al. 2010), up to 90% in prospective study settings (Klit, et al. 2014, Parvizi, et al. 2014). However, the knees of many dissatisfied patients are not revised. The recent focus of TKA research has been on perioperative and implant-related factors. The influence of computer-assisted navigation on the alignment of the prosthesis components and functional outcome measures has been a major topic, even though the clinical long-term bene-fits are still controversial (Burnett and Barrack. 2013, van der List, J P, et al. 2016).

On the contrary, there is a evidence from register data showing that cross-linked polyethylene (PE) inserts have a statistically lower revision rate at 10 years than conventional PE inserts (Civinini, et al. 2017). Since it is assumed that PE wear is a major contributor to implant loosening following TKA, cross-linked PE inserts may reduce wear-related loosening (Civinini, et al. 2017). Nevertheless, clear evidence of better clinical outcome or longevity of one prosthesis design over the others is un-convincing (Jo, et al. 2014, Hofstede, et al. 2015, Jiang, et al. 2016), and any benefits of patient-specific (PSI) or gender-specific instrumentations have not yet been prov-en in clinical use (Xie, et al. 2014, Sassoon, et al. 2015). The importance of compo-nent positioning and alignment (coronal and rotational) for longevity of the pros-thesis and patient satisfaction is quite incontrovertible (Gromov, et al. 2014).

TKA operations are nowadays performed also on younger patients (even under 50 years of age) with satisfactory results and improvements in their quality of life at rates similar to those of older populations (Goh, et al. 2017). Because primary knee replacements are conducted in such patients with ever increasing life expectancy, it seems quite obvious that the revision burden will also increase, since these younger patients are more likely to outlive their implants than older patients (Lavernia, et al.

2006, Inacio, et al. 2017, Goh, et al. 2017).

medial and lateral posterior femoral condyles. The rotation from the posterior condylar angle is 0.3° (± 1.2°) internal rotation for females and 3.5° (± 1.2°) internal rotation for males relative to the surgical epicondylar axis, which connects the medial epicondylar sulcus with the lateral epicondyle (Berger, et al. 1993, Berger, et al. 1998, Victor. 2009). To assess the tibial rotation, the geometric center (G.C.) of the tibial plateau is located and axially transposed to the level of the tibial tubercle. The line connecting the tip of the tubercle to the G.S. is the tibial anatomic axis. The AP tibial axis is drawn perpendicular to the posterior surface of the tibia. The angle between tibial anatomic axis and AP tibial axis is then measured to determine the rotation. Normal rotation using this method is 18° (± 2.6°) of internal rotation (Berger, et al. 1998).

2.1.2 Development of osteoarthrosis and effect on bone mineral density Knee OA is a very common degenerative joint disease (Sharma. 2016). According to the Mini-Finland health survey, the prevalence of knee OA in the population over 30 years of age was 6.1% in men and 8.0% in women (Toivanen, et al. 2010). There are many known risk factors for incident knee OA: Female gender, aging, obesity, traumatic knee injury, physically demanding work and heredity (Toivanen, et al.

2010, Sharma. 2016). However, OA is not only a disease of the cartilage. It can be defined as a disorder characterized by cell stress and extracellular matrix degrada-tion initiated by micro- and macro-injury that activates maladaptive repair respons-es including pro-inflammatory pathways of innate immunity (oarsi.org. 2015, Sharma. 2016). The disease manifests first as abnormal joint tissue metabolism fol-lowed by damage to the cartilage, bone remodeling, osteophyte formation, joint inflammation and loss of normal joint function. Nevertheless, the basic reason for OA remains unknown.

There has been a continuous debate of the relationship between high BMD and OA. The Chingford study over 20 years ago suggested that small increases in BMD are present in middle aged women with early radiological OA of the hands, knees and lumbar spine (Hart, et al. 1994). The Framingham study 17 years ago suggest-ed, that high BMD and BMD gain decreased the risk of progression of radiographic knee OA, but may be associated with an increased risk of incident knee OA (Zhang, et al. 2000). A more recent data suggests that higher BMD could even reduce the risk of radiological hip OA, while intermediate levels may increase the risk of symptomatic knee OA (Barbour, et al. 2017). However, there are studies suggesting, that OA could be associated with high BMD and high bone mass phenotype (Burg-er, et al. 1996, Hardcastle, et al. 2015), and OA and osteoporosis rarely develop sim-ultaneously (Hannan, et al. 2000). In fact, there is evidence of an inverse relation-ship between these two disorders (Dequeker, et al. 2003, Multanen, et al. 2015),

which could be explained by differences in bone metabolism (Jiang, et al. 2008) or genetic factors (Logar, et al. 2007, Valdes and Spector. 2011).

2.1.3 Total knee arthroplasty

Total knee replacement is an established treatment method to reduce pain and dis-ability caused by end-stage OA. In this indication, it has been proved to be more effective than non-surgical treatment in a recent randomized controlled trial (Skou, et al. 2015) with a good survivorship of 90% or more up to fifteen years of follow-up (Robertsson, et al. 2000, Roberts, et al. 2007, Niinimaki, et al. 2014). Whereas the studies from previous decades mostly measured surgeon-driven objective scales or survivorship data, the recent focus been more on patient-reported outcome measures (PROMs) (Ethgen, et al. 2004, Jones, et al. 2014). These studies reveal that the proportion of patients satisfied after undergoing primary TKA ranges from 81.8% in a register study of England and Wales (Baker, et al. 2007) with similar re-sults in the Ontario Joint Replacement Registry (Bourne, et al. 2010), up to 90% in prospective study settings (Klit, et al. 2014, Parvizi, et al. 2014). However, the knees of many dissatisfied patients are not revised. The recent focus of TKA research has been on perioperative and implant-related factors. The influence of computer-assisted navigation on the alignment of the prosthesis components and functional outcome measures has been a major topic, even though the clinical long-term bene-fits are still controversial (Burnett and Barrack. 2013, van der List, J P, et al. 2016).

On the contrary, there is a evidence from register data showing that cross-linked polyethylene (PE) inserts have a statistically lower revision rate at 10 years than conventional PE inserts (Civinini, et al. 2017). Since it is assumed that PE wear is a major contributor to implant loosening following TKA, cross-linked PE inserts may reduce wear-related loosening (Civinini, et al. 2017). Nevertheless, clear evidence of better clinical outcome or longevity of one prosthesis design over the others is un-convincing (Jo, et al. 2014, Hofstede, et al. 2015, Jiang, et al. 2016), and any benefits of patient-specific (PSI) or gender-specific instrumentations have not yet been prov-en in clinical use (Xie, et al. 2014, Sassoon, et al. 2015). The importance of compo-nent positioning and alignment (coronal and rotational) for longevity of the pros-thesis and patient satisfaction is quite incontrovertible (Gromov, et al. 2014).

TKA operations are nowadays performed also on younger patients (even under 50 years of age) with satisfactory results and improvements in their quality of life at rates similar to those of older populations (Goh, et al. 2017). Because primary knee replacements are conducted in such patients with ever increasing life expectancy, it seems quite obvious that the revision burden will also increase, since these younger patients are more likely to outlive their implants than older patients (Lavernia, et al.

2006, Inacio, et al. 2017, Goh, et al. 2017).

The overall incidence of periprosthetic supracondylar femoral fractures ranges from 0.3% to 2.5% after primary TKA surgery (Parvizi, et al. 2008). Diverse general risk factors for femoral fractures proximal to the implant have been documented. These fractures have been associated with conditions that result in osteopenia of the distal part of the femur (Parvizi, et al. 2008, Hoffmann, et al. 2012). The importance of procedure-related notching of the distal femoral anterior cortex as a risk factor for periprosthetic fracture has been controversial. (Ritter, et al. 2005, Parvizi, et al. 2008,

The overall incidence of periprosthetic supracondylar femoral fractures ranges from 0.3% to 2.5% after primary TKA surgery (Parvizi, et al. 2008). Diverse general risk factors for femoral fractures proximal to the implant have been documented. These fractures have been associated with conditions that result in osteopenia of the distal part of the femur (Parvizi, et al. 2008, Hoffmann, et al. 2012). The importance of procedure-related notching of the distal femoral anterior cortex as a risk factor for periprosthetic fracture has been controversial. (Ritter, et al. 2005, Parvizi, et al. 2008,