Skeletal muscle disuse atrophy – pathophysiology, prognosis and treatment

Skeletal muscle disuse atrophy – pathophysiology, prognosis and treatment

Dr KS Dhillon MBBS, FRCS, LLM

Introduction

Skeletal muscular atrophy can result from disuse or neurological injury/disease. Atrophy can also occur due to ageing (sarcopenia) and it is believed to be due to neural degeneration. Disuse atrophy results from limb immobilisation, bed rest, physical inactivity, joint dysfunction and elimination of gravity (space flights). In the past disuse atrophy of muscles was not given much attention because it was believed to resolve spontaneous with return to normal activities. However with the advent of space flights there has been renewed interest in disuse skeletal muscle atrophy. In recent years there have been more animal and human studies to understand the pathophysiology and prognosis of disuse skeletal muscle atrophy.

Disuse skeletal muscle atrophy

Disuse skeletal muscle atrophy as the name suggests is due to inactivity of the muscle brought about by limb immobilisation, bed rest, physical inactivity, joint dysfunction or elimination of gravity (space flights). It results in loss of muscle bulk and strength. The atrophy starts within a few days and the severity of the atrophy is proportionally more with increase in the duration of disuse of the muscle. Loss of muscle bulk and strength can also result from neurological injury, neurological disease and ageing. Loss of muscle bulk and strength that results from ageing is known as sarcopenia which starts after the age of 40 years and progresses as we age. It is believed to result from neurodegeneration and age related hormonal changes (1).

Pathophysiology

The cellular mechanisms responsible for muscle atrophy have been studied in animals by hind limb suspension or limb immobilisation by cast or external fixation (2). Zarzheveky et al showed that immobilisation of the hind limb of rats with an external fixator for 4 weeks produced about 50% weight loss of the gastrocnemius, quadriceps, plantaris and the soleus. Histological and ultrastructure examination showed marked myopathy changes in the muscles with distortion of the sarcomeres and loss of myofibrils. The acid phosphate activity increased by about 85% and the creatine phosphokinase activity was reduced by about 40% reflecting a significant decrease in protein synthesis in the muscles. The biochemical values and muscle morphology returned to near normal after 4 weeks of mobilisation of the limb in the rats. (2).

Although protein synthesis reduces there is no change in protein degradation in humans which results in the loss of the muscle bulk. However there is no decrease in the number of muscle fibres (3).

Prognosis

Snijders et al studied muscle disuse atrophy in 12 young (24 +/- 1 year old) adults who were subjected to a 2 weeks immobilisation of one lower limb in full length cast. They tested muscle strength; muscle cross sectional area (CT scan) and muscle fibre type characteristic (muscle biopsies), before and after immobilisation as well at 6 weeks after natural rehabilitation. They found that there was considerable loss in skeletal muscle mass and strength after 2 weeks of immobilisation and that the muscle mass and strength returned to the baseline values within 6 weeks of recovery without any specific rehabilitative programme. The loss of muscle mass was attributed to both type I and type II muscle fibre atrophy but there was no decline in satellite cell content (4).

Rittweger and Felsenberg studied the recovery of muscle atrophy and bone loss from 90 days of strict bed rest with -6 degrees head down tilt in 25 young healthy participants. The participants were followed up at 90,180 and 360 days and they were advised to return to their normal activities as soon as possible. No specific post immobilisation rehabilitation was instituted. The study found that the calf cross section as measure with a CT scan recovered rapidly after re-ambulation with the largest part of losses restored within 14 days and full recovery was seen within 90 days. The functional recovery however lagged behind morphological recovery. The vertical jump performance was completely recovered in 180 days. Even the diaphyseal bone losses fully recovered within a year of follow up in all subjects (5).

The loss of muscle mass and strength due to disuse appears to be different in different muscle groups and loss of muscle strength is not proportional to the loss of muscle mass. LeBlanc et al studied the loss of muscle area and strength changes associated with 5 weeks of horizontal bed rest in 9 male volunteers. The subjects underwent a 10 weeks of metabolic study in which they underwent 5 weeks of ambulatory control and 5 weeks of complete horizontal bed rest. They measured the leg muscle area with an MRI before and after bed rest and the strength was measured with a dynamometer. They found that the muscle area of the ankle plantarflexors (gastrocnemius and soleus) decreased by 12% whereas the muscle area of the ankle dorsiflexors did not reduce significantly after 5 weeks of disuse. Similarly the muscle strength of the plantarflexors reduced 26% but there was no significant reduction in the strength of the dorsiflexors. The study showed that there was a differential loss in muscle mass and strength in different muscle groups and the loss of strength was more than the loss of muscle bulk in the same group of muscles (6).

LeBlanc et al in an another study involving 8 male volunteers who underwent 17 weeks of continuous bed rest and another 8 weeks of reambulation found significant loss of muscle volume as measured with MRI scans of the back and the lower limbs. There was a decreased muscle volume of 30% in ankle planterflexors, 21% in ankle dorsiflexors, 16 to 18 % in the quadriceps and hamstrings and 9% in the low back intrinsic muscles (7).

Restoration of Skeletal Muscle after Disuse Atrophy

When the cause of the muscle atrophy is disuse, it is logical that the best way to restore the muscle’s previous function would be a return to normal physical activities. Applying mechanical load would be the most effective method to restore the muscle mass. An isolated bout of concentric or eccentric resistance exercise in young adults can produce a 112% increase in protein fractional synthesis rate at 3 hrs, 65% at 24 hrs and a 35% rate at 48 hrs post exercise. Exercise leads to an increase in muscle net protein balance that persists up to 2 days after an exercise bout and this increase is unrelated to the type of muscle contraction performed (8).  Low volume (140 contractions in 14 days) resistance exercise has been found to prevent immobilisation induced atrophy in the quadriceps muscle (9). During bed rest exercise alone can reduce a loss in muscle mass (10).

 Most often the muscle atrophy from disuse, recovers completely within 6 weeks, with return to normal activities and without specific rehabilitative exercises (4). In some cases it may take up 90 days for complete recovery from disuse atrophy without specific rehabilitation (5). 

Muscle atrophy due to joint dysfunction

There is paucity of literature on muscle atrophy after uncomplicated skeletal injuries, probably due to the fact that the muscle atrophy that occurs due to disuse after fractures recovers spontaneously with fracture healing and after the patient returns to normal activities and whatever residual atrophy that remains does not produce functional disability. On the other hand when musculoskeletal injures produce joint dysfunction some amount of muscle atrophy and loss of muscle strength always does persists. This has been extensively studied in patients with anterior cruciate ligament laxity (ACL).

In assessing muscle bulk of the thigh it has to be remembered that there is a side to side difference in the muscle bulk due limb dominance with the bulk on the right being more than the left. Strandberg et al studied 60 patients who were scheduled for anterior cruciate ligament reconstruction. They performed CT scan of the thigh to measure the cross sectional area (CSA) of the thigh muscles. They found that the quadriceps CSA was 5 % smaller on the injured side and that the difference between the injured and non-injured side was larger for the right side as compared to the left which is suggestive of a larger muscle bulk on the right side (11). 

Lorentzon et al also found an average of 5.1% decrease in quadriceps CSA in patients with chronic ACL laxity. The isokinetic mechanical output was on the average 21% less on the injured side. However the isokinetic performance did not correlate with the amount of muscle atrophy and the authors believe that non-optimal activation of the muscles is probably involved in the poorer isokinetic performance (12).

Even after ACL reconstruction some amount of lingering Quadriceps atrophy and weakness persists even after adequate rehabilitation (13) (14). A 20% Quadriceps strength deficit has been found in patients at 1year follow up after reconstruction of the ACL (15).

Conclusion

Skeletal muscle atrophy sets in rapidly within days after immobilisation or disuse. Two weeks of immobilisation can cause considerable loss of muscle mass and strength. Immobilisation produces morphological changes in the muscle as well as alteration of biochemical markers that are indicative of significant decrease in protein synthesis. However no loss of muscle fibres occurs with disuse of muscles.

With mobilisation a rapid change in the level of biochemical markers occurs within hours which is suggestive of a significant increase of protein synthesis. Most of the atrophy from immobilisation returns to normal after mobilisation within 6 weeks and in others it may take up to 180 days depending on the severity of the atrophy. Mechanical loading appears to be the best way to restore the muscle mass and strength. In most instances when no joint dysfunction exists no specific rehabilitative exercises are needed. However when joint dysfunction is present, even intensive rehabilitation may fail to fully restore the muscle strength despite a complete recovery of muscle mass.

References

1. Kim TN, Choi KM. Sarcopenia: Definition, Epidemiology, and Pathophysiology. J Bone Metab 2013; 20:1-10.

2. Zarzhevsky N, Coleman R, Volpin G, Fuchs D, Stein H, Reznick AZ. Muscle recovery after immobilisation by external fixation. J Bone Joint Surg Br. 1999 Sep; 81(5):896-901.

3. Ferrando AA, Lane HW, Stuart CA, Davis-Street J, Wolfe RR. Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am J Physiol 1996; 270(4 Pt 1):E627–33.

4. Snijders T, Wall BT, Dirks ML, Senden JMG, Hartgens F, Dolmans J et al. Muscle disuse atrophy is not accompanied by changes in skeletal muscle satellite cell content. Clinical Science (2014) 126, (557–566).

5. Rittweger J, Felsenberg D. Recovery of muscle atrophy and bone loss from 90 days bed rest: results from a one-year follow-up. Bone. 2009 Feb; 44(2):214-24.

6. LeBlanc A, Gogia P, Schneider V, Krebs J, Schonfeld E, Evans H. Calf muscle area and strength changes after five weeks of horizontal bed rest. Am J Sports Med December 1988; 16: 624-629.

7. Leblanc A, Schneider V, Evans H, Pientok C, Rowe R and Spector E. Regional changes in muscle mass following 17 weeks of bed rest. J. Appl. Physiol. 1992; 73:2172-2178.

8. Phillips SM, Tipton KD, Aarsland A, Wolf SE and Wolfe RR. Mixed muscle protein synthesis and breakdown after resistance exercise in humans. Am J Physiol. 1997 Jul; 273(1 Pt 1):E99-107.

9. Oates BR, Glover EI, West DW, Fry JL, Tarnopolsky MA and Phillips SM. (2010). Low-volume resistance exercise attenuates the decline in strength and muscle mass associated with immobilization. Muscle Nerve 2010; 42 : 539–546.

10. Ferrando AA, Lane HW, Stuart CS, Davis-Street J, and Wolfe RR. (1996). Prolonged bed rest decreases skeletal muscle and whole body protein synthesis. Am. J. Physiol. 1996; 270: E627–E633.

11. Strandberg S, Lindström M, Wretling ML, Aspelin P and Shalabi A. Muscle morphometric effect of anterior cruciate ligament injury measured by computed tomography: aspects on using non-injured leg as control. BMC Musculoskeletal Disorders 2013, 14:150. 

12. Lorentzon R, Elmqvist LG, Sjöström M, Fagerlund M, Fuglmeyer AR. Thigh musculature in relation to chronic anterior cruciate ligament tear: muscle size, morphology, and mechanical output before reconstruction. Am J Sports Med. 1989 May-Jun; 17(3):423-9.

13. Lindström M1, Strandberg S, Wredmark T, Felländer-Tsai L, Henriksson M. Functional and muscle morphometric effects of ACL reconstruction. A prospective CT study with 1 year follow-up. Scand J Med Sci Sports. 2013 Aug; 23(4):431-42. 

14. Karanikas K1, Arampatzis A, Brüggemann GP. Motor task and muscle strength followed different adaptation patterns after anterior cruciate ligament reconstruction. Eur J Phys Rehabil Med. 2009 Mar;45(1):37-45.

15. de Jong SN, van Caspel DR, van Haeff MJ, Saris DB. Functional assessment and muscle strength before and after reconstruction of chronic anterior cruciate ligament lesions. Arthroscopy. 2007 Jan; 23(1):21-8, 28.e1-3.

Surgery for removal of metallic implants after fracture union: Is it necessary?

Surgery for removal of metallic implants after fracture union: Is it necessary?

                          Dr KS Dhillon, MBBS, FRCS, LLM

Introduction

After fracture union metallic implants used for stabilization of the fracture serves no purpose, hence in the past it was advocated that all such implants should be removed. This was partly due fears of corrosion associated with the commonly used stainless steel alloy implants. However subsequent research found such claims to be unfounded.

There are two broad class of fixation devices used in orthopaedic surgery for fixation of limb bones. The first group consists of wire or pins and the other includes screws, plates and nails. In the past most of the implants were made of stainless steel alloy, however now titanium alloy implants are now becoming more popular.

There are no clear guidelines in the medical literature on indications for removal of metallic internal fixation devices after fracture union. Surgeons have been making decisions about implant removal arbitrarily because of lack of evidence based literature to guide them. The general rule has been that all wires should be removed while plates, nails and screws may or may not be removed depending on prevailing circumstances.

The presence of metallic implants in the body usually does not produce any symptoms. However under some circumstance they can be a source of pain and or limitation of movement of the joints. In such circumstances doctors are often compelled to remove the implants although not all such patients will be relieved of their symptoms after the surgery. Surgery for removal implants is not as innocuous as we often assume.

This review will probe what the current state of knowledge is regarding the need for implant removal after fracture union.

Types of implants used for internal fixation of limb fractures

1.      Kirschner wires- These are non-malleable stainless steel wires which come in different sizes and usually vary in diameter from between 0.7 mm to about 1.6 mm and in lengths of between 4 to 12 inches. There are usually used to fix small bone fragments which are not suitable for fixation with other devices such as screws, plates and nails. Wires are frequently used to fix peri-articular fractures in children and also in adults, where non-invasive close reduction of the fracture can be carried out and the fracture stabilized with percutaneous wires. The frequent sites where wires are used for fixation of fractures include the elbow, wrist, hand, fingers, foot and the toes.

2.      Cerclage wires- These are malleable stainless steel wires which can twisted around bones and tied in a knot. They are often used to fix fractures of the patella and the olecranon. They can also be used at other sites to complement fixation of bones with other devices. 

3.      Plates, screws and nails

Various designs of plates, screws and nails are available for internal fixation of fractures. These are usually made of stainless steel alloy or titanium alloy. The stainless steel implants are iron-carbon alloys with some element of chromium, molybdenum and manganese. The titanium implants are alloys of titanium, aluminium and niobium.

Indications of implant removal

There is usually no disagreement among surgeons that K-wires that are used for temporary fixation of fractures should be removed after fracture union. K-wires protruding under the skin can cause skin irritation and pain. They can also migrate, if they are not securely fixed across two bone cortices, causing damage to other body structures. Cerclage wires can also cause skin irritation and pain if they are not buried in deep tissues and under such circumstance they should be removed. Screws that are subcutaneous and causing skin irritation should be removed.

Deep implants such as plates, nails and screws may or may not be symptomatic and the removal such implants has been an area of debate and controversy. The questions that arise are whether the implants will cause harm if left in the body and do they cause any functional disability.

Do implants cause harm?

Biocompatibility of metallic implants has always been a concern because of release of biologically active small particles due to oxidation of metal and the possibility of toxicity of these particles to the human body. Stainless steel alloys do corrode in the body but the implants become covered with a layer of fibrous tissue often as thick as 2mm depending on the amount of corrosive material released and the amount of movement between the implant and the surrounding tissues. Titanium alloys on the other do not corrode but they release ions which diffuse into the surrounding tissues [1]. It was believed in the 1970’s and 1980’s that these corrosive materials and metallic ions may be carcinogenic and predispose patients to cancers. However, experimental studies have not revealed any association between metallic implants and the development of any cancers [2]. Presently the possibility of corrosion and cancer are no longer considered to be an indication for removal of implant [2]. Allergic reactions to metals in the body are rare and data substantiating implant related allergic reactions is scarce [2].

Another reason why plate removal was recommended in the past was due to the widely held believe that the presence of plates on the bone leads to bone atrophy. However, more recent studies have showed that if the plates are left in the body long enough the density of the bone returns to normal. Rosson et al studied the bone density in patients with forearm fractures and found that the bone density returns to normal after 21 months [3]. Similarly studies of tibia after plate removal have failed to show significant bone atrophy [4]. Hence plates can be left in the body without fear of plates causing bone atrophy or stress protection.

Essentially implants left behind after fracture healing do not cause any bodily harm. The next question that needs to be answered is whether implant produces symptoms or functional disability.

Do implants cause symptoms and when should they be removed?

There are very few circumstances under which implants would definitely need to be removed (absolute indications). K-wires can migrate and cause harm to other body structures and K-wires that are under the skin can produce pain, hence removal of K-wire would be indicated. Screws that perforate the joint should be removed because they can damage the joint when the joint is mobilised. Cerclage wires whose sharp ends are not properly buried under deep tissues can protrude under the skin leading to pain. Such wires obviously need to be removed. Implants such as plates adjacent to joints which are imperfectly positioned can obstruct joint motion and it would be necessary to remove them to improve joint function. Implants that are loose can migrate or produce irritation of adjoining soft tissues and such implants would also need to be removed.

Indication for removal of implants under most other circumstances is controversial and debateable. Some patients complain of pain or discomfort in the limb even when the implants are securely fixed and well positioned. The cause of such pain remains unclear and it is difficult determine whether the implant is the cause of the pain or it is due the injury itself [2]. In patients with such pain the results of implant removal are ‘unpredictable and depend on both the implant type and its anatomic location’ [5].Minkowitz in a study of 57 patients who had implant removal because of complains of pain found that only 53% of the patients had complete resolution of pain at one year follow up[6]. Brown et al studied 126 patients who complained of lateral ankle pain in the region of the implants. Only 50% (11 out of 22 patients) had improvement of pain after implant removal. The functional scores were no different in patient who had and did not have implant removal [7]. The unpredictability of outcome has to be kept in mind when removal of implants for pain is contemplated.

Removal of implants involves another surgery which is accompanied with the risk of anaesthesia related complications as well as complications associated with the surgery itself. Cost of the surgery and hospitalization as well as time off work has to be borne in mind. Not only is the results of the surgery unpredictable, the surgery itself can sometimes be difficult and frustrating, resulting in broken implants and retrieval instruments. Surgical complications include bleeding, wound infections, neurovascular injury, refractures, recurrence of deformity, incomplete removal of hardware and sometimes poor cosmetic results because incisions for removal of minimally invasive plate and nails are not so ‘minimal’.

Sanderson et al in a study of 188 patients who had implant removal found an overall complication rate of 20% and for forearm implant removal the complication rate was 42%. The nerve injuries that occurred were all permanent and were produced by junior doctors [8]. Richards et al in a smaller series of 86 adult patients who had a routine removal of implants in both symptomatic and asymptomatic patients reported a much lower rate of complications (3%) which included a nerve injury, a refracture and a haematoma. However the authors recommended that it would be appropriate to leave asymptomatic implants in situ [9].

Removals of implants from forearm bones appear to a have high complication rate. Langkamer et al [10] reported a 40% complication rate after forearm implant removal. Chia et al [11] reported a 27% and Bednar et al [12] reported a 10% complication rate following removal implants from the forearm.

Brown et al reported a 19% rate of significant complications in patients who had implant removal. They also found that patients who did not have their implants removed had no ‘appreciable problems’ and the authors recommended that implants should only be removed if there is a clear indication for the removal [13].

Karladani et al in a study of 71 patients who had removal of the tibial nail for pain found that only 39 of the 71 patients had improvement of pain and they were not totally pain free after the surgery. In 14 patients the pain was the same and in 18 patients the pain was worse after the removal of the nail. Four of the 6 patients who had a previous fasciotomy were unhappy with the outcome of the surgery to remove the nail. The authors concluded that the outcome of tibial nail removal for pain is poor and that the nail should not be removed unless there are convincing reasons to do so [14].

There have been concerns that athletes with implants in situ, who participate in contact sports run the risk of a refracture because the implant can act as a ‘stress riser’. Evans and Evans did a retrospective study of 15 elite rugby players who returned to competitive sports while having implants in situ. Two of the players’ sustained implant related complications and the other 13 continued playing for up to 6 years without any symptoms. One of the players needed removal of wires which produced pain after the tension band wiring for a fracture of the patella while another player sustained an undisplaced fracture of the radius and had to be treated in a cast for one month. The authors concluded that an early return to sports after fracture union is feasible and it is not necessary to remove the implants which would further delay return to sports [15].

Routine removal of implants in the paediatric patients is a common practice among many orthopaedic surgeons [16]. Kahle in arguing against routine removal of implants in children did a retrospective survey of 138 patients who had removal of implants and found a complication rate of 13%. Seven percent of the patients had an incomplete removal of the implant and 1.4% had a refracture. The study showed no evidence to support the policy of routine removal of implants [17].

Davids et al in a retrospective survey of 801 children with 1223 implants removed over a 17 years period reported a 12.5% complication rate of which 6% were major and 6.5% minor complications [18].

There appears to be no compelling reason to remove implants in children as is the case in adults after fracture union when the patient is asymptomatic.

Routine implant removal after fracture surgery consumes a remarkable portion of resources allocated for elective orthopaedic surgery and is a potentially reducible consumer of hospital resources in trauma units [19].

The medical literature provides only level IV or level V evidence regarding removal of implants after fracture healing. Vos DI et al [20] have carried out a prospective multicentre clinical cohort study to evaluate the outcome of implant removal after fracture healing. The study included 288 adult patients, 146 patients had removal of upper limb implants and 142 patients had removal of lower limb implants. Removal of implants of the clavicle, humerus, radius/ulna, tibia and femur was included.

The most frequent indication for implant removal was pain (63%) and limitation of joint motion (56%).

For removal of femoral nails, extension of the scar was necessary in 62% of the patients and for tibial nails in 35% of the patients. For removal of upper limb implants the estimated blood loss was between 0 to 300 ml and the operating time varied between 3 mins to 90 mins. For removal of lower limb implants the blood loss was between 0 ml to 500 ml and the operating time was between 13 mins to 120 mins.

Thirty percent of the patients had one or more surgery related complications. The complications included post-operative bleeding (11%), refractures (1%), nerve injuries (6) other complication in 9% of the patients. The complication rate for upper limb procedures was 22% while for the lower limbs it was 37%.

The number of patients with pre-operative complaints who had complete follow up was 214 (88%) and 6 months after the surgery the number of patients with complaints was reduced to 49% (P<0.0005). Despite the significant number of patients (39%) who had improved after implant removal there were 8 patients, who had no pre-operative complaints but developed 25 new post-operative complaints such as paraesthesia, pain, loss of strength and limited joint motion.

There appears to be no indication for removal of implant in patients, both adults and children, when there are no symptoms. In symptomatic patients the outcome of implant removal is unpredictable and the patient should be advised accordingly if implant removable is contemplated. In about half the patients the symptoms will not improve after the surgery. Furthermore the surgery is not innocuous and between 3% to over 40% of the patients can develop complications depending on the type and location of the implant.

Conclusion

In the past routine removal of implants after fracture union was a common practice. This was because the metallic implants used for stabilization of the fracture served no purpose after the fracture had united and there were fears of carcinogenic toxicity of ions release form oxidative corrosion of the stainless steel alloy implants that were commonly used for fracture stabilisation. However subsequent research has found that such claims are unfounded. Fears of bone atrophy and stress shielding related to the implants have also been found to be unfounded provided the implants are left in situ long enough. Hence implants need not be removed for these reasons.

However under some circumstances there are definite indications for removal of implants. There is no controversy or debate about removing K-wires, Cerclage wires, implants that penetrate joints and those that are imperfectly position and obstruct joint motion.

 In most other situations the indications for removal of implants are relative. Even stable infected implants, before fracture union occurs, are often left in situ but infected implants after fracture union should be removed to control infection. Implants that are loose which can sometimes migrate and cause symptom may have to be removed.

Deep seated stable implants are usually asymptomatic and most authors recommend that they should be left in situ even in children. Removal of implants is not as innocuous as is often believed. Besides anaesthesia related complications there are surgery related complications in 3% to over 40% of the patients. Implant removal is also associated with increased cost and time off work.

In many patients who complain of pain around the site of the implant the actual cause of the pain is often not known and it could be due to effect of the injury rather than the implant itself. In symptomatic patients removal of implants resolve the symptoms in only about 50 % of the patients.

Before undertaking surgery to remove implants, it is imperative that the surgeon informs the patient about complications that can arise from the surgery. The patient also needs to be made aware about the unpredictability of the outcome of such surgery. Most authors are of the opinion that asymptomatic implants should not be removed and in other situations the implants should only be removed if there is a definite compelling reason to do so.

 References

1.      Gotman I. Characteristics of metals used in implants. J Endourol. 1997; 11(6):383-9.

2.       Vos DI, Verhofstad MHJ. Indications for implant removal after fracture healing: a review of the literature. European Journal of Trauma and Emergency Surgery. August 2013, Volume 39, Issue 4, pp 327-337.

3.      Rosson JW, Petley GW, Shearer JB. Bone structure after removal of internal fixation plates. J Bone Joint Surg [Br] 1991 ; 73-B :65-7.

4.      Terjesen T, Nordby A, Arnulf V. The extent of stress-protection after plate osteosynthesis in the human tibia. Clin Orthop 1986; 207: 108-12.

5.      Busam ML, Esther RJ, Obremskey WT. Hardware removal: indications and expectations. J Am Acad Orthop Surg. 2006 Feb;14(2):113-20.

6.      Minkowitz RB, Bhadsavle S, Walsh M, Egol KA Removal of painful orthopaedic implants after fracture union. J Bone Joint Surg Am. 2007 Sep; 89(9):1906-12.

7.      Brown OL, Dirschl DR, Obremskey WT. Incidence of hardware-related pain and its effect on functional outcomes after open reduction and internal fixation of ankle fractures. J Orthop Trauma. 2001 May; 15(4):271-4.

8.      Sanderson PL, Ryan W, Turner PG. Complications of metalwork removal. Injury. 1992; 23:29-30.

9.      Richards RH, Palmer JD, Clarke NM. Observations on removal of metal implants. Injury. 1992; 23:25-8.

10.   Langkamer VG, Ackroyd CE. Removal of forearm plates. A review of the complications. JBJS (Br) 1990 Jul;72(4):601-4.

11.   Chia J, Soh CR, Wong HP, et al. Complications following metal removal: a follow-up of surgically treated forearm fractures. Singapore Med J. 1996 Jun;37(3):268-9.

12.  Bednar DA, Grandwilewski W. Complications of forearm-plate removal. Can J Surg. 1993 Feb;36(1):16.

13.  Brown RM, Wheelwright EF, Chalmers J. Removal of metal implants after fracture surgery: indications and complications. J R Coll Surg Edinb 1993;38:96-100.

14.  Karladani AH, Ericsson PA, Granhed H, Karlsson L, Nyberg P. Tibial intramedullary nails -- should they be removed? A retrospective study of 71 patients. Acta Orthop. 2007 Oct;78(5):668-71.

15.   Evans NA, Evans RO- Playing with metal: fracture implants and contact sport. Br J Sports Med 1997;31:319-321.

16.  Jamil W, Allami M, Choudhury MZ, Mann C, Bagga T, Roberts A. Do orthopaedic surgeons need a policy on the removal of metalwork? A descriptive national survey of practicing surgeons in the United Kingdom. Injury. 2008; 39:362-7.

17.  Kahle WK. The case against routine metal removal.  J Pediatr Orthop. 1994 Mar-Apr;14(2):229-37

.

18.  Davids JR, Hydorn C, Dillingham C, Hardin JW, Pugh LI. Removal of deep extremity implants in children. J Bone Joint Surg Br. 2010 Jul;92(7):1006-12.

19.  Böstman O, Pihlajamäki H. Routine implant removal after fracture surgery: a potentially reducible consumer of hospital resources in trauma units. J Trauma. 1996 Nov; 41(5):846-9.

20.  Vos DI, Verhofstad MHJ, Vroemen. JPAM, van Walsum ADP, twigt BA, Mulder PGH, van der Graaf Y, van der Werken. Clinical outcome of implant removal after fracture healing. Results of a prospective multicentre clinical cohort study. Submitted for publication. file:///C:/Users/user/Downloads/vos.pdf.

 

Limb Length Inequality: A Much Discussed but Little Understood Medico-legal Quandary

Limb Length Inequality: A Much Discussed but Little Understood Medico-legal Quandary.

                         Dr K.S. Dhillon. MBBS, FRCS, LLM.




Introduction

In law, a person who is injured, due to the fault of another individual, is entitled to compensation for personal injury. In the assessment of damages resulting from the injury and the assessment of award for damages, the legal fraternity depends on a medical report prepared by doctors. The medical report is required to categorise and identify the severity of the injuries as well as to know the effects/ disabilities produced by the injuries. There is a significant difference between a medical examination for treatment and that for legal purposes. An examination for treatment is aimed at treatment and that for legal purposes is to ascertain damages and compensation. In the assessment for damages the asymmetry of the lower limbs and shortening of the limb is taken into consideration for award of damages. It is common belief that the human body is symmetrical and many doctors as well as many in the legal fraternity are unaware that the human body is inherently asymmetrical.

In a normal population 90% of individuals have a 5.2mm limb length inequality. In 32% of the population there is limb length inequality of between 0.5 to 1.5 cm and in 4% there is inequality of more than 1.5cm. Limb length discrepancy of less than 2 cm does not appear to affect function and there is no need to equalise the limb length discrepancy. For accurate assessment of limb length inequality radiological imaging is required. Clinical assessment of discrepancy is a good screening technique but it is not a good technique for accurate assessment of limb length. The medical examiner has to take these factors into consideration before reaching a conclusion that a fracture has produced anatomical shortening or asymmetry. 

Definition of limb length Inequality

Limb length inequality (anisomelia) could be due to structural asymmetry or functional inequality. In patients with structural asymmetry there can be actual shortening or lengthening of the limb. The actual structural skeletal length discrepancy is between the head of the femur and the ankle mortise and it could be in the femur or the tibia (not fibula). The causes of this discrepancy are varied and can be congenital/inherited or acquired. Congenital/inherited disorders include growth inhibiting conditions such as hypoplastic femur, Perthes disease and fibrous dysplasia and growth stimulating conditions such as vascular malformations, neurofibromatosis and fibrous dysplasia besides other causes.

The acquired causes of limb length discrepancy include growth inhibiting factors such as childhood fractures, infections and neurological damage (Polio, Cerebral Palsy, Head injury) and growth stimulating factors such as childhood fractures, haemangiomas, A-V malformations and infections [1]. In skeletally mature patients a common cause of acquired limb length discrepancy is due to fractures involving the femur or the tibia. However in the majority of patients the cause of the limb length discrepancy is not known even when there is a discrepancy of greater than 1 cm and it could be due to normal asymmetrical bone growth [2]. Genetic and environmental factors appear to influence ontogenesis of a person leading to this asymmetry [3].
Functional adaptation occurs in individuals with structurally short lower limbs which include foot pronation on the longer side and pelvic tilt leading to lower anterior and posterior iliac spine on the shorter side [3]. 

Functional inequality results when limb length discrepancy occurs in the absence of actual bone shortening or lengthening. It could be due to flexion contractures of the hip or knee and varus or valgus deformity of the knee besides other causes such as pelvic torsion and scoliosis. In functional limb lower limb inequality the pelvis rotates. The foot on the apparently short limb rotates externally, the heel goes into valgus and the foot arch collapses. The posterior iliac spine is higher on the apparently short side and the anterior iliac spine is high on the apparently longer side [3].


Classification of limb length discrepancy

The magnitude of limb length discrepancy has been classified into mild, moderate and severe [4].
Mild – difference of less than 3 cm
Moderate – difference of between 3 and 6 cm
Severe – difference of more than 6 cm
The definition of biomechanically significant limb length discrepancy remains controversial among orthopaedic surgeons. While most are convinced that moderate and severe discrepancies are associated with some structural and functional disturbances, mild (less than 3 cm) discrepancies have not been convincingly linked to any structural or functional disturbances [3].
Prevalence and clinical significance of structural/anatomic limb length inequality 

Limb length inequality (LLI) appears to be universal phenomena. Knutson in a review of published data on limb length inequality obtained by accurate and reliable x-ray methods found a prevalence of anatomic inequality in 90% of the subjects studied and the mean magnitude of anatomic inequality was 5.2 mm (SD 4.1). He concluded that anatomic leg-length inequality does not appear to be clinically significant until it reaches a magnitude of 20 mm (3/4 inch) [5]. The shortening is more common on the right side but the difference between the two sides is not statistically significant [5].

The most common effect of this limb length inequality is pelvic torsion on weight bearing with the pelvis rotating anteriorly on the short side and posteriorly on the long side. The clinical impact of these dynamic changes remains unclear [6]. Pelvic torsion is the commonest method of compensation with up to 22mm of inequality. With greater degree of inequality knee flexion on the longer side is used as a compensatory mechanism [7].

Hellsing AL did a prospective study of young men during their military service to assess back function and pain before and after basic military training. Around 600 men were examined three times over a period of four years. The study found LLI of 0.5-1.5 cm in 32% of the subjects and 4% had a difference of more than 1.5cm. However there was no correlation between LLI and back pain or pain provocative tests [8].

Gross RH in 1983 studied the incidence and the degree of limb length discrepancy in 35 marathon runners, 70% of whom were in the 30s and 40s. His hypothesis was that the occurrence of asymmetry would be lower in marathon runners than in general population because of attrition of runners with LLI. However he found that 34 of 35 runners participating in the study had LLI when measured by radiography. Eighteen runners (51%) had LLI of less than 5mm, 10 (28.5%) had a LLI of 5 to 9 mm and 7 (20%) had LLI of 1cm or more. He concluded that ‘runners can function handsomely without equalization’ of asymmetry and ‘that discrepancies of 5 to 25 mm are not necessarily a functional detriment to marathon runners, and no consistent benefits could be attributed to the use of a lift’ [9]. 

Gross RH in 1978 in a ‘survey of 74 skeletally mature patients with LLI of 1.5 cm or more found that patients with less than 2.0 cm did not consider their short limb to be a problem in any way’. As the magnitude of discrepancy increased there were problems but there was no critical ‘cutoff’ point. Some subjects functioned well athletically with discrepancies of over 2.5 cm. He concluded that there is little indication for equalisation of discrepancies of less than 2cm and for larger discrepancies clinical judgement has to be used on an individual basis [10].

Kaufman et al studied gait asymmetry in patients with LLI. They investigated 20 subjects (mean age, 9.0 +/- 3.9 years) who had documented limb-length inequalities, to determine what magnitude of discrepancies resulted in gait abnormalities. The study involved dynamic gait analysis which showed that generally, a limb-length inequality > 2.0 cm (3.7%) resulted in gait asymmetry which was greater than that observed in the normal population. This gait asymmetry however varied for each individual [11]. Less than 2cm inequality does not seem to affect the kinematics [12].

A discrepancy in length of 5.5 per cent or more is associated with an increased mechanical work by the longer extremity and a greater vertical displacement of the centre of body mass. Clinically, this degree of discrepancy can be compensated by the use of toe-walking strategy while lesser degree of discrepancy can be overcome by a combination of compensatory strategies which normalize the mechanical work performed by the lower extremities [13]. Equalizing limb length can improve the symmetry of gait [14].

Gait asymmetry can easily be studied in a laboratory but it is more difficult to analyse the effect of limb length inequality on the spine, hip and the knee. The correlation between LLI and back pain, scoliosis, as well as knee and hip arthrosis has not been well established. The most commonly cited paper according to Knutson [5] which claims that LLI contributes to low back pain is that by Friberg [15]. Friberg studied 1,157 subjects from a military hospital who were exposed to extreme and repetitive loading military activities. Of these 1,157 subjects, 798 had chronic low back pain and the control was 359 with no low back pain. In 75.4% percent of those with back pain and 43.5% of controls there was a 5 mm or more of LLI. Friberg’s findings were questioned by other investigators [5] and Friberg defended his results and clarified that ‘LLI of less than 5mm has no relationship to lumbar scoliosis or back pain’ and ‘that even marked LLI per se neither produces LBP or contributes to its development if a person is not continually exposed to prolonged standing or gait, e.g., doing daily work, military training and sporting activities’ [16]. Soukka et al in a survey of 257 statistically matched working aged male and females subjects found that there was no increased risk of back pain with a LLI of 10 to 20 mm and that there was no conclusive evidence of increased risk of back pain with LLI of more than 20mm [17].

Gibson et al studied patients who had acquired LLI after femoral fractures. The study included patients between the age of 15 and 21 years who had sustained a fracture of the femur. There were 40 patients who were examined 10 or more years after the fracture. There were 15 patients with LLI of 1.5 cm or more who were studied further. The average LLI was 3 cm and ranged between 1.5 to 5.5 cm. During the 10 years only one patient wore a shoe raise and that too for a short period. None of the patients complained of low back pain and none had significant back pain over the 10 years. The acquired LLI produced little permanent structural abnormality in the spine and there was no degenerative changes seen in the spine after 10 years of the acquired LLI in skeletally mature individuals [18].

White et al studied 200 patients who had LLI after total hip replacement. They studied the relationship of LLI and functional outcome using the Harris hip score and the SF-36 Health Survey and found that leg lengthening (up to 35 mm) or shortening (up to 21 mm) had no correlation with functional outcome or patient satisfaction at six months after the surgery [19].
The association of LLI and lower limb complaints remains speculative. Tjernstrom and Rehnberg in a survey of 85 patients who had limb lengthening for shortening of between 3 and 14 cm (average 6cm) found that lower limb symptoms were not common in these patients and the effect of limb lengthening on joint symptoms was minor [20].

 There appears to be no good evidence that LLI leads to osteoarthritis of the hip or the knee. In 2007 Golightly et al studied the relationship of LLI and osteoarthritis (OA) of the hip and knee. They examined the relationship of LLI with radiographic hip and knee OA in a community based sample. There were 926 subjects with knee OA and 796 with hip OA, and 210 (6.6%) had LLI of 2 cm or more. They found that there was a significant association between LLI and OA of the knee but there was no significant association with hip OA. The weakness of the study was that limb length measurements were clinical with a tape rather than the more reliable radiological method. Furthermore the authors admitted that LLI in patients with OA could have been contributed by the loss of joint space, disfigurement of the joint and malalignment of the joint that occurs with OA. In additions to these drawbacks, the joints were not examined for contractures which can contribute to LLI. The authors proposed that future research should study the relationship of LLI to OA of the hip and the knee [21].

Harvey et al [22] in a recent large prospective study used radiographs for LLI measurements. Their cohort consisted of 2964 individuals with the age between 50-79, who were with or at high risk for knee osteoarthritis. They found leg length inequality ≥1 cm in 14.5% of the study subjects at baseline. In individuals with LLI of ≥1 cm there was significantly higher  prevalence of radiographic and symptomatic osteoarthritis at baseline. The predicted incidence of symptomatic knee osteoarthritis 30-months later was also higher in those with LLI of ≥1 cm. The shorter limbs were also at higher risk of of x-ray progression.

The authors however admitted that there are several weaknesses in their study. The number of incident radiographic OA cases were too small to effectively evaluate the effects of LLI and the authors were, for the same reason, unable to clearly define the risk associated with longer limbs and whether shorter or longer limbs were at higher risk of OA.

The second limitation of the study was the short duration of exposure due to the design of the study. A 30 month follow up was too short to detect progression of the OA. Furthermore even radiographic measurement limb length can be imperfect due to variation of knee flexion on standing radiographs. Hence there remains the possibility of misclassification and bias.
Gofton and Trueman [23] however stated that the LLI produces a pelvic tilt which leads to greater heel impact and stress on joints of the longer limb as compared with the shorter limb.
Kaj Tallroth et al [24] found that hip or knee arthroplasty due to primary OA was done 3 times more often in the longer lower limb than in the shorter limb.

There were however some limitations in this study. No knee radiographs were taken at baseline examination and neither was information about  comorbidities, height, sporting activities and possible hip and knee problems during follow up, available. The only information available was the number arthroplasties done for primary OA of the hip or knee. In this 29 year follow up there was a surprisingly low incidence of OA [24].

Despite several studies having been published in the literature, the association of LLI and lower limb complaints remains largely speculative in nature.

Reliability of limb length assessment

Assessment of LLI is essential for appropriate treatment to be instituted. The limb can be measured clinically or by radiographic imaging techniques. Before using a particular technique it would be necessary to know the reliability (inter and intra-observer variation) and the accuracy (variation from actual length) of the technique used.

Clinical technique

The most convenient and commonly used method in clinical practice is the tape measure technique (TMM). The length of the lower limb is measured with a tape from the anterior superior iliac spine (ASIS) at the hip to the distal tip of the medial malleolus (MM) at the ankle.

However this method of measurement has some potential for errors, some of which include:

Limb Girth- The size of the limb may vary between the two sides due to muscle wasting or due to swelling and this can produce an error.
Difficulty in identifying the bony landmarks- The ASIS is difficult to palpate in obese individuals and MM can be difficult to palpate when there is swelling of the ankle. These bony landmarks may be deformed due to previous trauma making identification of the landmarks difficult.
Angular deformities- Presences of angular deformities at the thigh, knee, leg and the ankle can introduce errors. A varus deformity will produce shorting while a valgus deformity will produce lengthening of the limb.
Shortening distal to the ankle- This method does not measure shortening distal to the ankle mortise and can introduce error when there is bone loss distal to the ankle.
Contractures- Contracture at the hip and the knee as well as pelvic obliquity can produce functional shortening when there is no actual structural length discrepancy[25].

The problem of shortening distal to the ankle can be overcome by using an indirect method of measuring LLI. Blocks of known height can be place on the short side to obtain a level pelvis. This method also allows the treatment of LLI in patients with functional shortening.

A Galeazzi test is a quick and simple test which can be used to know whether the shortening is in the femur or the tibia. It is done with the person lying supine with the hip and knee flexed and the asymmetry of the level of the knees will confirm there is shortening and also reveal whether it is in the femur or the tibia. This test also eliminates the error of measurements when flexion contractures of the hip or knee are present. The actual length of the femur can be measured from the ASIS to the medial joint line and that of the tibia from the medial joint line to the MM.

Beattie et al studied the validity of tape measure method (TMM) for determining LLI when compared with a scanogram. They found that TMM derived measurement is a valid indicator of LLI and that the validity of the measurement is improved by taking the mean of two separate tape measurements. However the tape measurements were less reliable in healthy subjects as compared to those with LLI [26]. Cleveland et al on the other hand showed that there is a statistically significant and weak correlation between radiographic measurements and physical examination measurements [27]. With tape measurements the accuracy in identifying the bony landmarks in obese patients, discomfort of the patient during the examination, and correct positioning of the patient by the examiner must be kept in mind.

Harris et al studied LLI in 35 patients with femoral fracture who were treated with nailing. Of these 35 patients, 15 patients (43%) had a measurable LLD. They found that ‘there was a positive correlation between direct leg length measurement and the block test (P = 0.003), and between the block test and patient perception of limp and LLD’ however ‘there was no correlation between CT scanogram and clinical measurement of leg length or between CT scanogram and patient perception of LLD or limp’ [28].

Imaging technique

Imaging techniques commonly used for assessment of LLI include plain radiography and computerised radiography.

Plain radiography

 Techniques for measurement of LLI by plain radiography include:

Orthoroentgenogram- This old technique requires a long cassette (longer than the limb length) with three exposures, each centred on the hip, knee and the ankle [29].

Plain radiographic scanogram- This technique uses 3 ordinary cassettes lined up under the limb with the patient supine and a radio-opaque ruler tape to the table. The cassette is moved with each exposure centred on the hip, knee and the ankle [30].

Teleroentgenogram- This technique involves a full length standing AP of the lower limbs using a long cassette with the X-ray beam at about 6 feet. The technique is similar to an Orthoroentgenogram but here a single exposure is used instead of three exposures. This technique is however subjected to magnification error.

Computed radiography- A full length radiograph of the lower limbs can be obtained by obtaining 3 images on a vertical cassette holder containing 3 cassettes. The images are then transferred to a computer where a good quality full image can be downloaded and measurements done [25].

The inter and intra-observer reliability may vary from about 1.5mm to about 5mm. Up to about 10mm would be a threshold for a meaningful difference when assessing differences in measurements by these techniques [25].

CT scanogram

A CT scan is a very useful tool for assessment of limb length discrepancy. A scout view of both femurs and tibias can be obtained and the length of the femurs and tibias can be easily measured. The length of the femur can be measured from the tip of the femoral head to the distal end of the medial femoral condyle and the length of the tibia from the upper end of the medial tibial condyle to the tibial plafond. This technique appears to be more accurate than the plain radiography techniques [25].

The use of a tape is a cheap, simple and non-invasive screening technique for LLI. However it has potential for errors such as difficulty in palpation of bony landmark, difference in size of the limbs, angular deformities of the limb and contractures of the hips and knees. For more accurate assessment of LLI, radiographic techniques need to be used. The type of radiographic technique used will depend on the resources available. CT scans appear to be more accurate and reliable and will require less training and supervision of radiographers when compared with plain radiographic techniques [25].

Limb shortening/lengthening- Legal perspective

There is a significant difference between a medical examination for treatment and that for legal purposes. An examination for treatment is aimed at treatment and that for legal purposes is to ascertain damages and compensation. 

Limb length inequality in the upper limbs usually does not produce any major functional impairment unless it is substantial and produces a cosmetic disfigurement. For example most fractures of the clavicle are treated conservatively and some degree of shortening is inevitable because the bone heals with overlap of bone fragments. However this shortening does not produce significant functional disability [31]. However lower limb length inequality can produce functional disability depending on the severity of the discrepancy between the two limbs.

Clinical measurements for treatment of the patient are commonly taken from the ASIS to the medial malleolus, irrespective of whether the shortening is in the femur or the tibia, because the goal of treatment is to compensate for the shortening when necessary. However the aim of measurements for medico-legal purposes is to determine whether the fracture of the femur or the tibia has resulted in shortening. Hence for medico-legal reporting it will be logical, persuasive and sensible to measure the length of the femur and the tibia individually. It cannot be assumed that when there is limb shortening it is due to the fracture of the tibia or the femur, because there can be inherent asymmetry between the two sides or there can be functional shortening due to angular deformity at the knee (valgus/varus) and/or flexion contracture at the hip or the knee. The length of the femur can be easily measured from the ASIS to the medial knee joint line and that of the tibia from the medial knee joint line to the medial malleolus.

Clinical limb length measurements are prone to errors due to differences in limb girth, difficulty in palpation of bony landmarks, angular deformities of the limb and contractures of joints. For medico-legal reporting, if initial clinical screening shows the presence of LLI, it would be logical, persuasive and sensible to provide accurate radiological measurements, to prevent conflict and make assessment of award for damages simpler. 

Conclusion

Anecdotal evidence suggests that limb length inequality is a much discussed but little understood entity in personal injury litigation. It is commonly believed by both the medical as well as the legal fraternity that the human body is symmetrical but clinical evidence shows that the human body is inherently asymmetrical. Ninety percent of individuals in the normal population have a 5.2 mm of lower limb length inequality. In 32% of the population there is LLI of 0.5 to 1.5 cm and 4% have inequality of more than 1.5 cm. Limb length inequality of below 2cm does not appear to affect function and there is no need for compensatory correction of the discrepancy. Some individuals function well athletically even with discrepancies of over 2.5 cm. 
It is commonly believed that limb length inequality leads to back pain, scoliosis, as well as osteoarthritis of the hip and knee but clinical evidence does not support such beliefs. The association between LLI and back pain as well as osteoarthritis of the lower limb joints remains largely speculative.
Clinical measurements of lower limb length are commonly included in medico-legal reporting by orthopaedic surgeons. However such measurements are prone to error. The presence of LLI on clinical screening should be followed with accurate radiological measurements so that conflict can be avoided and the award for damages justified. 






References

1. Coleman NW and Sponseller PD. Limb-length discrepancy: Etiology, effects and evaluation. Orthopedic hyperguide at http://www.ortho.hyperguides.com/index.php?option=com_content&view=article&id=1375:limb-length-discrepancy-etiology-effects-and-evaluation&catid=308:operating_techniques.
2. Veterans Affairs Canada. Discussion Paper- Leg length Inequality (LLI) – Entitlement Eligibility Guidelines. March 2014 at http://www.veterans.gc.ca/eng/services/after-injury/disability-benefits/benefits-determined/entitlement-eligibility-guidelines/legleng
3. McCaw MC and Bates BJ. Biomechanical implications of mild leg length inequality. Br J Sp Med 1991; 25(1):10-13.
4. Reid DC, Smith B. Leg length inequality: a review of etiology and management. Physio Can 1984; 36: 177-82.
5. Knutson GA. Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part I, anatomic leg-length inequality: prevalence, magnitude, effects and clinical significance. Chiropractic & Osteopathy 2005, 13:11 doi: 10.1186/1746-1340-13-11.
6. Cummings G, Scholz JP and Barnes K. The effect of imposed leg length difference on pelvic bone symmetry. Spine 1993; 18(3):368-373.
7. Walsh M, Connolly P, Jenkinson A, O'Brien T: Leg length discrepancy – an experimental study of compensatory changes in three dimensions using gait analysis. Gait Posture 2000, 12(2):156-61.
8. Hellsing AL. Leg length inequality. A prospective study of young men during their military service. Ups J Med Sci. 1988; 93(3):245-53.
9. Gross RH. Leg length discrepancy in marathon runners. Am J Sports Med. 1983 May-Jun;11(3):121-4.
10. Gross RH. Leg length discrepancy: how much is too much? Orthopedics.  1978;1(4):307-10.
11. Kaufman KR, Miller LS, Sutherland DH. Gait asymmetry in patients with limb-length inequality. J Pediatr Orthop. 1996 Mar-Apr; 16(2):144-50.
12. Goel A, Loudon J, Nazare A, et al: Joint moments in minor limb length discrepancy: a pilot study. Am J Orthop 26:852-856, 1997.
13. Song KM, Halliday SE, Little DG: The effect of limb-length discrepancy on gait. J Bone Joint Surg Am 79:1690-1698, 1997.
14. Bhave A, Paley D, Herzenberg JE: Improvement in gait parameters after lengthening for the treatment of limb-length discrepancy. J Bone Joint Surg Am 81:529-534, 1999.
15. Friberg O. Clinical symptoms and biomechanics of lumbar spine and hip joint in leg length inequality. Spine. 1983;8:643–651.
16. Friberg O. Letter-to-the-editor. Spine. 1992;17:458–460.
17. Soukka A, Alaranta H, Tallroth K, Heliovaara M. Leg-length inequality in people of working age. The association between mild inequality and low-back pain is questionable. Spine. 1991;16:429–431.
18. Gibson PH, Papaioannou T, Kenwright J: The influence on the spine of leg-length discrepancy after femoral fracture. J Bone Joint Surg (Br) 1983, 65(5):584-7.
19. White TO, Dougall TW: Arthroplasty of the hip. Leg length is not important. J Bone Joint Surg (Br) 2002, 84-B:335-8.
20. Bjorn Tjernstrom and Lars Rehnberg. Back pain and arthralgia before and after leg Lengthening: 75 patients questioned after 6 (1-1 1) years. Acta Orthop Scand 1994; 65 (3): 328-332.
21.  Golightly YM, Allen KD, and Jordan JM. Relationship of Limb Length Inequality with Radiographic Knee and Hip Osteoarthritis. Osteoarthritis Cartilage. Jul 2007; 15(7): 824–829.
22. Harvey W F, Yang M, Cooke T D, Segal N A, Lane N, Lewis C E, Felson D T. Association of leg-length inequality with knee osteoarthritis: A cohort study. Ann Intern Med 2010; 152 (5): 287–95.
23. Gofton J P, Trueman G E. Studies in osteoarthritis of the hip, II: Osteoarthritis of the hip and leg-length disparity. Can Med Assoc J 1971; 104 (9): 791–9.
24. Kaj Tallroth, Leena Ristolainen & Mikko Manninen. Is a long leg a risk for hip or knee osteoarthritis? Acta Orthopaedica. 2017;88: 512-515.
25.  Sabharwal S, and Kumar A, “Methods for Assessing Leg Length Discrepancy” Clin. Orthop. Relat. Res, vol. 466, no. 12, pp. 2910-2922, Dec. 2008.
26. Beattie P, Isaacson K, Riddle DL, Rothstein JM. Validity of derived measurements of leg-length differences obtained by use of a tape measure. Phys Ther. 1990;70:150–157.
27. Cleveland RH, Kushner DC, Ogden MC, Herman TE, Kermond W, Correia JA. Determination of leg length discrepancy. A comparison of weight-bearing and supine imaging. Invest Radiol. 1988;23:301–304.
28. Harris I, Hatfield A, Walton J. Assessing leg length discrepancy after femoral fracture: clinical examination or computed tomography? ANZ J Surg. 2005;75:319–321.
29. Green WT, Wyatt GM, Anderson M. Orthoroentgenography as a method of measuring the bones of the lower extremities. J Bone Joint Surg Am. 1946;28:60–65.
30. Moseley CF. Leg length discrepancy. In: Morrissy RT, Weinstein SL, eds. Lovell and Winter’s Pediatric Orthopedics. Philadelphia, PA: Lippincott Williams & Wilkins; 2006;1213–1256.
31. Nordqvist A, Redlund-Johnell I, von Scheele A, Petersson CJ. Shortening of clavicle after fracture. Incidence and clinical significance, a 5-year follow-up of 85 patients. Acta Orthop Scand. 1997 Aug;68(4):349-51.