Knee pain is a common complaint, especially in the over 50’s.  Studies have shown that almost half of over 50’s complain of pain in the knee, and in about 25% it lasts for a prolonged period, being termed chronic (Urquhart et al 2015).  Chronic knee pain can lead to a significant reduction in quality of life (QOL) and difficulty carrying out common activities of daily living.  Although the condition can progress, many risk factors of progression are modifiable.  Exercise therapy can improve muscle strength and control of movement, and increase range of motion.  Strength exercise may increase muscle mass and muscle recruitment providing the overload on the muscle tissue is great enough.  Strength increase to the knee musculature may lessen internal knee forces, modify biomechanics, decrease rate of joint loading and reduce articular cartilage stress (Fransen et al 2015).  Overload during strength exercise may be reduced where pain is a barrier to exercise performance leading to exercise under dosage, often making pain management early on in the condition especially important.  Exercise in general may improve QOL increasing the number and variety of daily living tasks and improving physical function, these factors in turn having positive psychological benefits.

 

What is Arthritis?

The term arthritis tends to be used to describe any chronic inflammatory reaction affecting a joint. However, the term simply means ‘joint inflammation’, and as such must be qualified by a description of the cause of inflammation.  Acute joint injury which causes swelling within the joint may be termed ‘traumatic arthritis’ for example. True osteoarthritis (OA) involves cartilage degeneration, initially with little inflammation, so the term osteoarthrosis is often used nowadays. This condition must be differentiated from inflammatory states affecting multiple joints such as rheumatoid arthritis (RA).

The initial changes in OA are usually painless and show no gross joint swelling. The tissue affected first appears to be the joint cartilage, which shows an increased water content resulting from degrading (proteolysis) of the cartilage proteins.  Mild fraying or flaking of superficial collagen fibres within the hyaline cartilage occurs. This happens first at the periphery of the joint in the non-weight-bearing region. Later, damage (fibrillation) is to the deeper cartilage layers in the weight-bearing areas of the joint, extending down to one-third of the cartilage thickness. Small cavities form (blistering) between the cartilage fibres which gradually extend to become vertical clefts. If cartilage fragments break off, they may float free in the joint fluid as loose bodies, giving sudden twinges of pain and sometimes the joint feels as if it has locked. The presence of a loose body and the by-products of cartilage destruction causes the synovium (deep joint membrane) to inflame, and it is only now that many patients become aware that a problem exists.  At this stage medication to reduce pain and  inflammation can give some temporary relief.

Cartilage degeneration of the femoral condyle

Cartilage degeneration of the femoral condyle

Turnover of proteoglycan and collagen within the cartilage ground substance is increased, and the proteoglycan molecules near the fibrillated cartilage are smaller than normal. Mechanically, this altered cartilage is weaker to both compression and tension stresses, but it is still resistant to gliding. As the cartilage thins the joint space is reduced, a change visible on X-ray.

The bone beneath the fibrillated cartilage (subchondral bone) becomes shiny and smooth, an appearance called eburnation.   Below the eburnated region the area becomes osteoporotic and local avascular necrosis causes cyst formation where there is complete bone loss. Osteophytes (bone slivers) covered with fibrocartilage form at the periphery of the joint, and may protrude into the joint space or more frequently into surrounding soft tissue.

The synovial membrane becomes thickened and its vascularity increases in line with an inflammatory response . The joint capsule demonstrates small tears filled with fibrous tissue, causing thickening and stiffening, often most noticeable first thing in the morning or on rising from prolonged sitting.  Contracture usually alters both physiological and accessory movements, the first representing normal joint movement, the second joint play.  Synovial proliferation alters the consistency of the synovial fluid, giving it a lower viscosity.  Injections of hyaluronic acid (HA) are designed to slow this process. Increased growth of blood vessels (angiogenesis or neovascularization) occurs in OA in bone, synovial membrane and joint capsule. In addition new vessels may also grow across the subchondral barrier dragging nerve fibres with them (Jones, 2007).

From Norris (2011)

From Norris (2011)

It is important to realise that the knee joint is adapting.  Just as muscles get stronger when you go to a gym and do more with them, they can get weaker if a joint is painful meaning you move it less.  Joints become stiff if they are not moved regularly – ‘motion is lotion’ is an old adage, but very true! OA is a condition which has mechanical factors driving it.  Alteration to joint loading as a result of training or injury will cause the joint to react and repair, and an equilibrium must exist between stimulus (joint loading) and response (bone change).

 

Where does the pain come from?

The pain of OA knee comes from a number of sources, other than the bone changes seen on X-ray (see below).  Irritation and swelling to the bone beneath the joint cartilage, swelling within the joint, and overuse and irritation of the soft tissues (capsule, ligaments, muscles) supporting the joint may all be local causes.  However, these will only generate electrical signals in the nerves which supply them.  The same signals would be generated by movement or simply touching your knee.  As the intensity of these signals increases – a little like turning up the volume on a radio, there comes a point where the body choses to interpret the signals not as normal, but as threatening damage to the body.  When this happens, we would term the sensation we feel as painful, and the point at which this occurs is hugely variable between individuals.

The severity of pain which a person with OA feels will be influenced by a number of psychological factors such as fear of the condition getting worse, and the effect it might have on their lifestyle (home, work, sport) for example.  Changes in pain processing are also important.  This is the way in which the electrical signals are viewed as painful or not.  If you are a builder, used to heavy work on your knees, you are less likely to view a mild change in feeling of your knee as pain.  If you are a professional ballerina the day before an important performance, any change in the way your knee feels may be interpreted as pain.  In both cases, the electrical signals from the nerves to the brain are the same, but the brains interpretation (what the feeling means to you) is very different.

When the electrical stimuli from your knee due to irritation (noxious stimuli) have been present for some time, the structures involved in feeling them become hypersensitive.  This process is called central sensitisation and may explain why 20% of individuals with severe knee OA who have their knee joints replaced, still complain of long term pain afterwards (Wylde et al 2016).

 

Do X-rays & scans show knee pain?

X-rays and scans will often look for two essential signs in the presence of OA in the knee, osteophytes and joint space narrowing.  Some individuals who show marked changes on x-ray report very little pain, while others with obvious pain show few radiographic changes (Bedson & Croft 2008).  The changes on an x-ray which together indicate the presence of OA sometimes explain less than 20% of the pain (Wylde et al 2016).  A positive x-ray does not indicate that the condition cannot be treated, and usually patients can expect significant improvement in their symptoms with treatment such as muscle strengthening, active general exercise, and weight loss.

From totalknee.com

From totalknee.com

Normally your doctor or therapist will be looking for a number of features on your x-ray to guide treatment.  Firstly they will look at the alignment of the bones themselves.  Sometimes, an excessive angulation can occur called Valgus or knock knee.  Although this is not necessarily a  problem, if altering the angle by using a shoe insert reduces your pain, this may be used as a temporary measure.

From AAOP.org

From AAOP.org

Secondly the gap between the bones is assessed.  This gap is filled with cartilage which does not show up on x-ray, and where the joint space is reduced, either between the knee bones themselves, or between the thigh bone and the kneecap (Patella) this is an indication that the cartilage has thinned.   When looking for OA in the knee, a number of X-ray views are normally taken, including one to show the condition of the kneecap under surface (Patello-femoral joint).  The front to back (Antero-posterior or AP) view looks straight on to the knee, while the lateral view looks from the side, both of these may be taken weightbearing or with weight off the knee.  A skyline view (infer superior) looks between the thighbone and the kneecap.   Cartilage has a number of functions, one of which is to absorb and redistribute shock.  If the cartilage has worn, your physiotherapist may recommend using shock absorbing heel pads or springy shoes to compensate.

The x-ray will also show if another injury co-exists (co-morbidity) such as a hairline fracture if you have had a fall, and if there is swelling (effusion) within the knee which will take time to settle.  If you have slipped and fallen heavily, this fluid may also contain a small amount of blood (Haemarthrosis) which acts as an irritant causing sensory signals to go to the brain.  The health of the knee joint bones is also important and the bone density can be assessed from a x-ray.  If it is poor, a condition called Osteoporosis may be present which can require further tests (Dexa bone scan) to assess this.

From yoursurgery.com

From yoursurgery.com

Looking more closely at the x-ray you may see bone spurs or osteophytes at the edge of the joint, and sometimes bone cysts which appear almost as pockets within the bone.  Where the cartilage has worn, the bone beneath becomes stronger and shows up as white indicating bone sclerosis.  Remember though that the x-ray appearance does not mean your condition will stay as it is, because the x-ray does not accurately assess pain, muscle strength or your confidence in the knee all of which can improve significantly with rehabilitation.

 Stages of Osteoarthritis

Osteoarthritis is normally categorised (stages or grades) as  1-4 in terms of severity, with 0 being a normal joint.

stages-of-osteoarthritis

Stage 1 is often asymptomatic, but on x-ray mild cartilage changes may be detected, often as a result of an x-ray being taken for another condition such as a ligament injury.  Osteophytes may be seen but do not affect joint function.  Stage 2 pathology shows more changes on x-ray with greater osteophyte formation and  change in sub chondral bone density.  Bone will often appear whiter on x-ray (sclerosis) and bone cysts may sometimes be seen, and occasional  cartilage thinning may be noted.  Symptoms may occur on severe joint loading and muscle wasting may be noted where mild pain has encouraged reduced activity.  Stage 3 injury will show more severe osteophyte formation and joint space narrowing.  Overall bone shape may change and cartilage erosion is noted, in patches down to sub-chondral bone.  Muscle wasting and joint stiffness are common, and should be addressed by rehabilitation.  Joint stiffness is seen following prolonged rest (on rising from a chair or waking).  Stage 4 OA is severe, and can often show complete loss of joint space with severe bone end deformity.  Pain is common following rest and joint loading.  Movement range is severely limited and muscle wasting marked.

stages of knee

(from medicalgrapevineasia.com)

Arthritis and exercise

Joint cartilage is continually subjected to impact stress in sport. For example when running a marathon an athlete is said to take 38 000 steps and each time to subject the knee joint to between 4 and 8 times their bodyweight, which equates to almost 5000 tons force.  After a 20 km run cartilage volume is seen to reduce by 8% in the patella, 10% in the meniscus and 6% on the tibial plateau, with all cartilage volumes returning to normal within 1 hour of cessation of exercise (Hohmann, 2006). Joint cartilage is open to continuous micro-damage. However, providing the cartilage repair mechanisms outweigh the damage process, the joint will remain healthy.

Animal studies have failed to show a direct link between exercise and arthritis. Radin, Eyre and Schiller (1979) found no evidence of cartilage deterioration in sheep forced to walk for 4 hours daily on concrete for 12 and 30 months. Videman (1982) found that running did not affect the development of OA in rabbits. Experimentally induced OA was not increased when the animals were forced to run over 2000 m per week for 14 consecutive weeks.  Studies on runners have also failed to show any significant difference from non-runners.   Puranen et al. (1975) found less hip OA in Finnish distance runners than in non-runners of a similar age. Panush et al. (1987) found no greater clinical or radiological evidence of OA in male runners of average age 55 years, and Lane, Oehlert and Block (1998) concluded that runners and non-runners showed similar evidence of hip and knee OA.

Although chronic mechanical loading may be detrimental to the knee, evidence suggests that recreational running is not a cause of knee OA (leech et al 2015) and may even be used therapeutically in OA patients (Lo et al 2014).  Chronic knee stress which may be imposed by elite level running is less clear cut.  A systematic review of 19 studies looked at MRI scans of knees of distance runners and found no irreversible effects other than temporary proteoglycan depletion which took more than 3  months to recover to baseline.  The authors were unable to conclude if this represented permanent structural damage (Hoessly and Wildi 2015)

Maintaining the normal mobility and strength of a joint throughout life, and maintaining a healthy BMI (body mass index)  could help maintain the health of the joint structures and perhaps delay the onset of OA, and many forms of exercise including running are helpful in doing.   Certainly obese individuals have been shown to be more likely to develop OA, the increased risk being 4.8-fold in men and 4.0-fold in women (Felson, 1997).

 

Physiotherapy treatment of OA knee

Treatment of OA knee may be invasive (techniques are used which enter the knee joint such as  injections or operations) or non-invasive (techniques are used outside the knee such as physiotherapy).  Unless a severe injury has occurred such as a car accident, non-invasive techniques should always be used first as they have less risk.  In addition physiotherapy plays a vital role after invasive techniques for OA knee such as joint replacement.

Exercise therapy plays the primary pivotal role in the management of OA in the knee, with hands on techniques and pain relieving modalities such as acupuncture and electrotherapy having secondary supporting roles.

In the acute (reactive) stage of the condition the knee may be too painful to exercise.  The aim in the short term is to allow the joint to settle and relive pain so exercise can be used as soon as possible as this gives the longer term benefit.  Small joint movements (joint mobilisation) and gentle sustained lengthening (joint distraction) can often be very relieving.   Joint mobilisation involves the physiotherapist performing small rhythmic movements on your knee.  Normally when you move your knee, bending and straightening it you are performing physiological movements.  These are movements over which you have some control, but the joint can also move in other directions such as side to side and forwards and backwards.  These joint-play movements are called accessory movements because the joint is capable of performing them, but you cannot use them yourself.  Accessory movements usually occur as part of general exercise, but when your knee has been painful or stiff these movements can reduce.  The aim of the joint mobilisation techniques that your physiotherapist will use is to regain the accessory movements to reduce (modulate) pain and help give your knee its normal springy movement.  Two accessory movements are especially useful, and you may be able to use these yourself working with a partner.

Capsular stretching is a technique which uses a pivot (therapist forearm or rolled towel) at the back of the knee.  The knee is gently bent (flexed) against the pivot in a ‘nutcracker’ action and a comfortable stretch is held for 5-15 seconds and repeated 3-5 times. The aim is to feel pain reducing and stiffness easing.

20161116-p1030432-2

Joint distraction aims to gently draw the knee bones apart.  Although  little movement is likely as the knee is a very strong joint, patients who find their pain is worse with prolonged standing (joint compression) may often get relief from distraction.  Your physiotherapist will fix your shin beneath their arm and gently lead backwards.  As they do so your knee undergoes a longitudinal glide mobilisation.  They may oscillate this action over a 30-60 second period.  If you are trying this with your partner at home, the force must be quite small and put on, and taken off, slowly to avoid jarring the knee.

20161116-p1030432-1

Exercise therapy may also be used early on for pain reduction.  Sitting on the end of a table or bench, you can gently bend and straighten your knee to move the fluids within the joint and increase circulation to the tissues.  This action, called pendular swinging can help to ease pain and stiffness and is a useful method of targeting non acute (cold) swelling, where your knee has been stiff and puffy for some time.  Perform the action for able 3-5 minutes morning and evening until pain has eased sufficiently to begin walking and using more challenging exercise.  Even early on, walking itself is an excellent form of pain management with OA knee.  People often say that walking makes their pain worse.  However, when we look closely at this it is normally prolonged walking, often carrying heavy shopping bags for instance.  A short walk in springy shock absorbing shoes will often help to ease stiffness.  Your knees may ache to begin but this should ease with time.  Pace yourself and only walk up to the point of pain.  If you find your knees ache if you walk for 15 minutes, next day just try 10 minutes.  Do this for 3-5 days and then try to increase the time.  This approach is called graded exposure and it is a little like building reps and sets up in the gym.  The aim is to progress as your knee get stronger.

Acupuncture is often used by physiotherapists in the early treatment of the osteoarthritic knee, and the results are generally quite good. In a systematic review of seven trials (393 patients) Ezzo et al. (2001) concluded that acupuncture was effective for both pain relief and restoration of function, and that real acupuncture was better than sham acupuncture. In a later systematic review of 13 RCTs (1334 patients) White et al. (2007) concluded that acupuncture was superior to sham acupuncture for improving pain and function with chronic knee pain. Some patients find acupuncture enables them to reduce the number of pain killers they take and lets them begin exercise early.  Once they can exercise, this takes over from the acupuncture.

 

Simple knee strengthening.

Your physiotherapist will assess your knee and guide you through a personalised programme which suits your particular knee condition.  Here are some simple knee exercises which you can do at home.  In all cases you are looking to make your knee better, but a little discomfort is a good thing as it shows you are targeting the right tissues.  In the same way as if you went to a gym you would expect to react to exercise (ache and be stiff the next morning perhaps) you should feel a reaction in your knee.  The  joint may ache, the muscles feel stiff and tight, and the leg feel tired.  This is a sign that the tissues are adapting and becoming more resilient.  If you think you have done too much, don’t panic – just have a day off.  Rest, allow things to settle and then start again.

To be effective, exercise must be progressive.  This means that an exercise challenges your knee and the tissues adapt.  Muscle strength increases and joint stiffness reduces, and as it does so the exercise becomes easier.  When this occurs the exercise must increase to continue to challenge your body.  If you keep using the same exercise at the same intensity, you will not make progress (you will plateaux).  It may take 6 months to fully strengthen your knee.  Begin with the simple exercises below, but as you progress there will probably come a time when you need to go to a gym to be able to strengthen further.  By doing this, your knee could end up a lot better than when you first had pain!

 

Knee bracing

Sit on a bed or the floor, with your leg out straight in front of you.  Tighten your thigh muscles and try to brace your leg out straight.  If your knee has been swollen, it might not lock out completely straight (compare it to your other leg).  Tighten your thigh muscles (quadriceps) and hold them tight for 3-5 seconds before relaxing.  Rest and repeat for 5 reps.  Remember to breath as you tighten – don’t hold your breath.  If your muscles are very weak, and you only get a flicker of contraction, grip them with your hand.  This will help send messages to the muscle to remind it to ‘wake up’ (muscle facilitation).  Where your knee does not lock out easily, use your flat hand to gently press down on the thigh to encourage straightening.  Once it has straightened with help from your hand, keep your thigh muscles tight as you remove your hand from your thigh.

20161116-p1030433-3

Leg bracing using tactile (touch) cueing to facilitate muscle action

 

Leg extension

When you are able to brace your thigh muscles, you can use them as you bend and straighten your knee.  Begin with a small movement, placing a block or rolled towel behind your knee.  Press the back of your leg down against the towel as you tighten your thigh muscles to straighten your leg and lift your heel from the floor.  Hold the straight position for 3-5 seconds and then release.  Perform 5-10 reps and then rest.  You can increase the amount of movement by performing the same leg extension action sitting at the edge of a bed or table.  Slowly straighten your knee (concentric action), hold it straight (isometric action) and then bend under control (eccentric action).  Try to use a count of 2 to straightening, 4 to hold and 2-4 to lower.  Don’t just let your leg fall back to the bent position as the lowering phase is important.  Place a small weight on your shin (a weight bag or heavy towel) and perform 10 reps.  Rest and then repeat this (2 sets of 10) and then build to 3 sets of 10 as you feel able.  As the exercise becomes easier remember to increase the weight to keep pace with your strengthening muscles!

Leg extension ensuring full locking

Leg extension ensuring full locking

 

Leg press with band

The first two exercise were performed with your foot free, and we call this type of action ‘open chain’.  The knee joint is free to move, and it is not compressed.  However, eventually you will need to load your knee and we then move to ‘closed chain’ actions.  The leg press with band is a good action to bridge the gap, as you are pressing against something with your foot, but the resistance is light.  Begin sitting on the floor with your back against a wall.  Bend your knee and hook an exercise band over your foot and hold it with both hands (turn you head away from the band for safety – in case is flicks off your foot!).  Straighten your leg by pressing against the band.  Hold for 2-5 seconds in the straight position and then bend your knee under control.  Perform 5- 10 reps and then rest and repeat.  With this type of closed chain action the muscles on the front and back of the thigh (quadriceps and hamstrings) work together to control the knee movement, whereas with an open chain action the muscles on one side of the thigh (quadriceps with the leg extension action) work in isolation.  The closed chain action more accurately mimics the type of action we would perform in our day to day tasks such as pushing, pulling, standing from a chair for example and so are termed ‘functional’.  Using a thicker resistance band increases the work on the muscles, and eventually you will be able to use a gym based leg press machine.

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Supported lunge

Begin this movement standing to the side of a chair, with the chair back towards you.  Hold the back of the chair with one hand and have you feet hip width apart and step forwards by about 1m with one leg – vary the step distance depending on your leg length.  As you step forwards with one leg, lower the knee of your other leg towards the ground.  Your eventual aim is to place your knee on the ground almost level with the heal of your leading leg so that the shin of your leading leg is about vertical.  Begin lowering a small distance and gradually build up as you feel capable.  As you get stronger, gradually release the chair – go from holding it to just touching it lightly and eventually just place you hand over it so you know it is there if you need it.  Reverse the movement putting the other leg forwards.  You are aiming to be able to perform the lunge unsupported (hands behind head) and ultimately holding a weight.

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Mini squat

Patients often find standing from a chair harder when they have had any type of knee pain.  When getting up if the leg muscles are weak they tend to lunge the body forwards, and when sitting down they tend to sit heavily and fall into the seat.  This can be quite dangerous as chairs may slip and people can fall or twist their knee or hip.  Strengthening the leg muscles and improving control and balance is the key, and it can be achieved at any age – you are never too old to improve!  Once you have mastered the leg extension and have begun the lunge exercise, you are ready for the mini squat.  Begin using a firm dining chair with its back against a wall so it does not slip.  Place your feet hip width apart and reach both hands forwards as you bend your knees.  Lower yourself towards the chair seat until you just touch (don’t sit down completely) and then stand up again.  If you find this too hard, have someone hold your hands for balance, and sit towards the seat but don’t quite touch it.  You can even put some solid blocks or books on the seat to raise it up.  As you improve you can go further.  Eventually this action becomes a squat exercise in the gym, and you might think ‘I am 86 so I can’t possibly do that’.  Well, you can – all it takes is practice.  Build up slowly and you will be surprised how much you improve.

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Step up

When you have had knee pain, stairs can also be a problem  Going up is normally a bit of a struggle, but coming down can be even worse.  This is because when we go upstairs we naturally lean forwards to take our weight into the stair, but coming down we lead back slightly taking our weight onto our heels.  The step up is simply using a staircase as an exercise.  Begin facing the bottom step of a staircase or use a step bench in a gym.  Place one foot on the step (whole of the foot not just your toes) and press with your leg to straighten it and step up.  Keep the same foot on the step, pause in the top position and then step down under control.  With this first exercise we are deliberately stepping up with the right and down with the right – using the same leg.  The downwards action must be controlled, don’t fall into the movement.  Practice 3-5 reps keeping one foot on the step and then rest and reverse the action keeping the other foot on (up with the left, down with the left).  Once you are able to perform this unaided, alternate the stepping (up with the right, down with the left).  This action uses a concentric action going up and an eccentric action going down.  To progress the action we turn around and stand on the step.  Now, you step down first, tap your foot onto the floor and then go back up (eccentric and then concentric action).  Because you are facing down the staircase it is slightly harder as your weight is back, but really it is the fear factor which is important.  We all have a fear of falling downstairs, and this is worse following a knee injury.  This exercise is as much about confidence as it is about muscle strength.  Again, we use graded exposure.  Begin with a smaller step, holding onto the banister and looking down at your foot.  You are aiming to use a deeper step, look up and fold your arms!

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References

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Ezzo, J., Hadhazy, V., Birch, S., et al., 2001. Acupuncture for osteoarthritis of the knee: a systematic review. Arthritis and Rheumatism 44 (4), 819–825.

Felson, D.T., 1997. Understanding the relationship between bodyweight and osteoarthritis. Clinical Rheumatology 11, 671–681.

Fransen, M., McConnell, S., Harmer AR et al (2015)  Exercise for osteoarthritis of the knee: a Cochrane systematic review.  Br J Sports Med 49: 1554-1557

Hoessly LH, and Wildi LM (2015)  Magnetic resonance imaging findings in the knee before and after long distance running – documentation of irreversible structural damage?  Am J Sports Med 

Hohmann, E., 2006. Long distance running and arthritis. Sportex Medicine 30, 10–13.

Jones, A. (2007)  The Osteoarthritic knee.  In Touch Journal.  119: 16-21

Lane, N.E., Oehlert, J.W., Bloch, D.A., Freis, J.F., 1998. The relationship of running to osteoarthritis of the knee and hip and bone mineral density of the lumbar spine: a 9 year longitudinal study. Journal of Rheumatology 25, 334–341.

Leech, RD Edwards, KL, and Batt ME (2015) Does running protect against knee osteoarthritis? Or promote it? Assessing the current evidence BJSM 49(21): 1355-6

Lo G, Driban J, Kriska A, et al. (2014) Habitual running any time in life is not detrimental and may be protective of symptomatic knee osteoarthritis: data from the osteoarthritis initiative [Abstract]. Arthritis Rheumatol 66:1265–6.

Norris, CM (2011)  Managing sports injuries.  Churchill Livingstone.

Panush, R.S., Brown, D.G., 1987. Exercise and arthritis. Sports Medicine 4, 54–64.

Puranen, J., Ala-Ketola, L., Peltokalleo, P., Saarela, J., 1975. Running and primary osteoarthritis of the hip. British Medical Journal 1, 424–425.

Radin, E.L., Eyre, D., Schiller, A.L., 1979. Effect of prolonged walking on concrete on the joints of sheep. Abstract. Arthritis and Rheumatism 22, 649.

Urquhart, DM;  Phyomaung, PP;  Dubowitz, J  et al (2015) Are cognitive and behavioural factors associated with knee pain? A systematic review.  Seminars in arthritis and rheumatism          vol. 44 (4) p. 445-55

Videman, T., 1982. The effect of running on the osteoarthritic joint: an experimental matched pair study with rabbits. Rheumatology and Rehabilitation 21, 1–8.

White, A., Foster, N., Cummings, M., Barlas, P., 2007. Acupuncture treatment for chronic knee pain: a systematic review. Rheumatology 46 (3), 384–390.

Wylde A. Sayers A. Odutola R. et al (2016)  Central sensitization as a determinant of patients’ benefit from total hip and knee replacement.  European Journal of Pain 1, 1-8.