The upward classification of hip, knee and shoulder joint replacements renders them subject to a more burdensome set of regulatory requirements, most importantly, requiring direct scrutiny of clinical data used to support performance claims.

The primary difference between Class IIB and Class III devices lies in the requirements of Annex II, point four, of Council Directive 93/42/EEC, the Medical Devices Directive. The Annexes to that directive delineate the various routes to obtaining a CE mark, depending on the risk classification for a particular medical device. Point four, “Examination of the design of the product,” is applicable to Class III products, but not Class IIB products. It requires a manufacturer to prepare the documentation needed for examination of the intended product’s design dossier and to describe the design, manufacture and performance of the product.

In practice, point four requires companies to provide their EU conformity assessment bodies (“notified bodies”) with full clinical data to support their medical device applications. Pursuant to point four, a notified body will assess the manufacturer’s clinical data, the manufacturer’s evaluation of the data, and the validity of the manufacturer’s conclusions. For Class IIB devices, a notified body need only assess the manufacturer’s procedures for evaluating its clinical data. Although the notified body could request the underlying clinical data for a Class IIB device in an audit, review of the clinical data is not required.

EU Member States have until March 1st, 2007 to adopt regulations implementing the Reclassification Directive, which will be enforceable beginning September 1st, 2007. Already approved products have varying deadlines to meet the new requirements, depending on the regulatory pathway that a product initally took to market. Products that had been subject to the Annex III EC type examination coupled with Annex IV EC verification or Annex V declaration of conformity procedures are unaffected by the Directive, owing to the identical requirements for Class IIb and Class III devices under these Annexes.

Joint replacements will come under even closer scrutiny under new EC laws

Joint replacements subject to Annex III EC requirements coupled with Annex VI declaration of conformity procedures may be subject to conformity assessment as Class III devices by September 1st, 2010. Joint replacements that have followed the requirements of Annex II to market, minus the requirements of point four, as noted above, will be subject to a complementary conformity assessment under point four, leading to an EC design examination certificate before September 1st, 2009. The Reclassification Directive does not apply to ancillary components (screew, wedges, plates and instruments) used with affected joint replacements.

The Reclassification Directive responds to a November 2002 request for reclassification of total joint replacements by the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) and the French Agence Francais de Securité Sanitaire des Produits de Sante (AFSSAPS). A number of high-profile issues involving joint replacements prompted the request. Some have argued that the reclassification is simply a political exercise in the wake of the negative reports concerning joint failures, rather than a response grounded in objective scientific data.

In adopting the Reclassification Directive, the Commission cited a number of factors, including:

1. the complexity of the replacements in question;
2. the weight-bearing role of hip and knee replacements, which leads to a significantly greater risk of revision surgery;
3. the recency of shoulder implants and the dynamic forces to which they are subjected;
4. the increasing frequency with which replacement surgery is conducted on young people with long life expectancies, resulting in the need to ensure the implants function over this longer life span; and
5. the observation that total joint replacements are potentially subject to many different design modifications following their introduction into the market, and that these modifications can result in early failure and other safety concerns.

The major medical device industry associations, most notably Advamed and Eucomed, had opposed the reclassification request. Eucomed commissioned an independent report to examine the proposed reclassification. That study concluded that the chances of detecting manufacturing flaws likely to cause an unacceptable level of failure, through review of clinical data in a design dossier, would be “very small.”

In short, the proposed scrutiny of clinical data via the design dossier would not enhance safety. In fact, the report also concluded that a reclassification may have the opposite intended effect on public opinion by negatively colouring the public’s perception of the safety of these devices, who may lump joint replacements in with other, more risk-prone devices.

In the United States, joint replacements generally are Class II medical devices. It has been argued that the EU reclassification of hip, knee and shoulder joint replacements is just one more example of an increasingly burdensome EU medical device process that is sapping the ability of the medical device industry to flourish in the EU market, by raising costs and lengthening the time it takes to bring products to market.

Regardless of the impact on companies that manufacture hip, knee and shoulder joint replacements, the Reclassification Directive presents significant new requirements that affected companies must consider carefully.

References

1. D.F. Williams, The Classification of Total Joint Replacements in The European Union: An Independent Report on the European Commission Proposed Directive for Reclassification of Certain Total Joint Replacement Prostheses, at 44 (October 2003).
2. Id. at 43.

However, few foods naturally contain vitamin D. Only a small number (oily fish, eggs, butter, liver and certain types of meat) contain significant amounts of vitamin D and average daily intakes are too small to influence vitamin D status substantively, unless fortified foods are eaten regularly, e.g. margarine, milk and cereal.¹

Food 9	Serving 9	Vitamin D (µg) 9	No. of servings required to achieve RDA1 in persons aged over 65yrs
Margarine	10 g	0.8	12.5
Eggs	1	1.1	9
Cheese	60 g	0.2	50
Milk	0.15 litres	0.05	200
Butter	10 g	0.1	100
Herrings	100 g	16.5	0.61
Tuna	100 g	4	2.5
Mackerel	100 g	8	1.25
Kippers	100 g	13.5	0.74
Sardines	100 g	7.5	1.33

Age	Dietary intake
50-64 years	731 mg/day
65-74 years (in community)	682 mg/day
75-84 years (in community)	631 mg/day
65-86 years (in institutions)	856 mg/day

There is considerable conflicting evidence on whether supplementation with vitamin D and/or calcium supplementation alone is an effective osteoporosis therapy. An initial French study among a nursing home population showed that supplementation with vitamin D and calcium significantly reduced the risk of hip and vertebral fractures in frail elderly women with insufficient levels of vitamin D.¹⁴

Some subsequent studies have shown similar results in different patient populations. Dawson-Hughes et al found vitamin D supplementation significantly improved bone mass density (BMD) measured at the hip, spine and across the entire body and fewer non-vertebral fractures occurred in those patients taking supplementation.¹²

Trivedi et al. investigated vitamin D supplementation alone in 2,686 men and women between the ages of 65 and 85. The study showed an overall reduction in first fracture risk by 22%.¹⁵

A three year study¹⁶ of 9,605 men and women aged over 65 taking daily supplementation of vitamin D and calcium showed a 16% decrease in fracture incidence.

A recent Cochrane review concluded that vitamin D and calcium supplementation may lead to fewer hip and other non-vertebral fractures in frail and older people confined to institutions.¹⁷

Two more recent studies^18,19 reported no reduced fracture risk with vitamin D and calcium supplements alone for secondary prevention of fractures. In the RECORD study¹⁸ of 5,292 men and women who had suffered previous fracture(s), no significant difference in low trauma fractures was reported between different study groups, i.e. those taking vitamin D plus placebo, calcium plus placebo, vitamin D plus calcium or double placebo. However, there was no assessment to establish how vitamin D inadequate these patients were at the start of the trial. It is also worth noting that these patients were not receiving any other treatment for osteoporosis.

Porthouse et al¹⁹ recorded no significant difference in fracture risk between patients receiving vitamin D plus calcium and those receiving placebo in three randomized controlled trials. These results may be partly explained by the study design which was statistically limited and could not reliably exclude a reduction in fractures of <30%. In addition, the baseline vitamin D status was not assessed and some patients may have started the study with higher levels of vitamin D than others.

Patients in the control group were given dietary information that may have increased their vitamin D and calcium intake, and thus nullified their “control status”.

SIGN (Scottish Intercollegiate Guidelines Network) recommends that everyone over the age of 65 should aim to take vitamin D (400 IU daily), but suggests that the recommended intake may only be achieved through the use of supplements.²¹

The Royal College of Physicians and Bone and Tooth Society of Great Britain’s clinical guidelines for osteoporosis (2003) state that there is evidence to support the use of vitamin D and calcium in elderly osteoporotic women and that there is also evidence of anti-fracture efficacy in the frail elderly. The report recommends prescribing vitamin D (800 IU) and calcium (0.5-1g) for those who are frail, housebound or have an increased risk of fracture.¹³

The Scientific Committee for Food at the European Commission recommends that all women aged over 65 years should have a daily intake of vitamin D 400 IU (10ug).1 A daily intake of 700mg calcium is recommended by the UK’s Food Standards Agency.¹⁰

For some however, shoulder function is severely affected. The unstable joint produces symptoms of pain, fatigue and the inability to lift with that limb. Occasionally traction on the brachial plexus causes neuralgic pain as well.

For those with significant symptoms a number of surgical solutions have been proposed. Operative repair of the disrupted ACJ seems to gain little when compared to conservative treatment. Various methods of securing a fixation of the clavicle to the coracoid process combined with excision of the lateral end of the clavicle have been suggested but complications of implant breakage, bone fracture, graft failure or need to remove the implant means that surgery seldom provides the reliable restoration of function that is desired.

‘Surgilig’ was developed by the Nottingham Shoulder Unit and was first introduced in November 2001 as a method of addressing the failed ACJ surgery but has gained popularity in the last three years as a primary method of stabilizing the disrupted ACJ. This artificial ligament provides a strong, flexible and permanent solution to the torn coracoclavicular ligaments with few complications to date.

With the patient in the beach chair position a vertical incision is made over the lateral clavicle to approach the AC joint and the coracoid.

The lateral 1cm of clavicle is resected and then the base of the coracoid exposed on its lateral side. Initially a wire ended loop is threaded around the coracoid using the curved hollow ligament passer.

Figure 3

Figure 4

Figure 5

This allows accurate measurement and is then used to pull the definitive implant around the base of the coracoid. The “hard” loop end is then passed through the “soft” loop to provide a fixation on the coracoid and the hard loop taken around and over the posterior of the clavicle before screw fixation on the dorsal surface.

Postoperatively the arm is managed in a sling for three weeks with gentle movements below shoulder height. After three weeks the sling is removed and movement increased. Heavy loads in the hand are not permitted for eight weeks. In the small numbers to date complications include: shoulder stiffness, some remaining clavicular prominence, screw prominence and infection.

The implant is made from polyester and was originally developed from the braiding technology used to produce the ABC, the ARD and the Soffix ligaments, which have been extensively used in the knee. At each end there is a loop. A “soft” loop is used around the base of the coracoid to provide a broad based fixation less likely to cut through the bone and a “hard” loop at the clavicular end allows screw fixation to the bone. The material is of a sufficiently open weave to permit fibrous ingrowth and in the few patients who have required screw removal there has been no failure of the reduction.

• A Cadaveric Study examining Acromioclavicular joint congruity after different methods of coracoclavicular loop repair Baker JE, Nicandri GT JSES 2003: Dec, 595-598
• Grade 1 and 2 Acromioclavicular dislocations: Results of conservative treatment Mouhsine E, Garofolo R JSES 2003: Dec, 599-Stabilization of acute, complete acromioclavicular joint dislocations with a new C hook implant Ryhanen J, Niemela E JSES 2003; Oct, 442-5
• The Management of Acute Acromioclavicular Dislocation Bannister GC, Wallace WA JBJS 1989; 71-B:848-50
• Operation for Acromioclavicular Dislocation Warren-Smith CD, Ward MW JBJS 1987; 69-B 5: 715-718 602
• The Conservative Treatment of Acromioclavicular Dislocation Dias JJ, Steingold RF JBJS 1987; 69-B:719-722
• Acromioclavicular Joint Injuries & Distal Clavicle Fractures Nuber GW, Bowen MK Am Acad of Orth Surgery 1997; 5:1 11-18
• A comparative Analysis of Operative Vs Nonoperative Treatment of Grade 3 Acromioclavicular Separations Galpin RD, Hawkins RJ CORR 1985; 193: 150-155
• Treatment of Acromioclavicular Injuries Weaver JK, Dunn HK JBJS 54-A :6, 1972 1187-1194

We reserve the Nottingham Surgilig as a treatment for severe acute (Rockwood Type 5) ACJ injuries and chronic ACJ separations (Rockwood Type 3 & 5), but particularly for revision reconstruction when the coracoacromial ligament is no longer available.

Acromio-clavicular injuries are common sequelae of falls on to the point of the shoulder and comprise 3-5% of all shoulder girdle injuries¹. Such trauma may tear the acromioclavicular ligaments as well as result in apparent superior subluxation of the clavicle (in fact it is the acromion which displaces downwards).

The forces from the fall can lead to rupture of the coracoclavicular ligaments leading to complete dislocation of the joint. The latter injuries may be classified by severity with a view to guiding treatment, both operative and non-operative. We use Rockwood’s classification to facilitate understanding of the indications for surgical treatment ². This classification can be applied to both the acute dislocations and those which are old and chronically unreduced ³.

The original classification of ACJ injury severity proposed by Tossy et al ⁴ comprised grades I-III as determined by the individual structures damaged. Rockwood’s classification (Type I-VI) expanded on the latter by further sub-classifying Grade III injuries into types III-VI (See Figure 1).

Type I injuries result from minor strains of the acromioclavicular ligament and joint capsule with minimal displacement. These produce minimal pain and joint stability is preserved. Larger forces may cause a Type II injury involving rupture of the acromioclavicular ligament and joint capsule thereby compromising joint stability predominantly in the anteroposterior plane.

Type I	Type II	Type III
Type IV	Type V	Type VI
Fig. 1: The Rockwood Classification of Acromioclavicular Injuries (Drawings adapted from Campbell’s Operative Orthopaedics 4)

As illustrated in Figure 1, Type II injuries are essentially limited to subluxation of the ACJ – about half its vertical height and may be apparent radiologically with a stress view being the investigation of choice (see Figure 2). The latter injuries are most often treated conservatively with analgesia, immobilisation in a broad arm sling followed by early mobilisation.

In Type III injuries there is additionally rupture of the coraco-clavicular ligament and minor disruption of the distal clavicular attachment of the deltoid. Here the ACJ is dislocated, with the distal clavicle displaced superiorly relative to the acromion by at least the height of the ACJ, thought to be secondary to depression of the acromion ¹. Here, there is more tenderness over the joint and a prominent ‘step’ in the contour of the clavicle clinically.

Fig. 2: An AP stress view of the acromioclavicular joint illustrating a Rockwood Type II injury involving subluxation 5

Injuries meeting Type IV criterion must include posterior displacement of the clavicle toward or through the trapezius muscle. In this injury the AP radiograph may be remarkably normal but the patient can be very disabled with an inability to raise the arm above shoulder level. More severe trauma may lead to a Type V injury comprising extensive displacement of the clavicle from the acromion together with detachment of both the trapezius and deltoid attachments at the distal half of the clavicle and resulting in the lateral end of the clavicle lying subcutaneously and easily palpable clinically.

Finally, the rarely seen type VI injuries produce gross inferior displacement of the clavicle, which subsequently resides under the coracoid and deep to the conjoined tendons of biceps and coracobrachialis (See Figure 1).

Treatment of the ACJ dislocation present in Rockwood Type III injuries has been a contentious issue and practice varies across centres and individuals. Increasingly, injuries tend to be treated conservatively in the first instance with late reconstruction if required ⁴. This method is favoured in our department. Conversely, there is a general consensus that type IV-VI injuries have a poor outcome if managed conservatively and open reduction and internal fixation are required.

Surgical intervention is favoured as it allows an anatomical reduction of the joint and secure fixation permitting earlier shoulder mobilisation over closed techniques. Recognised operative techniques in use can be categorised into several groups and here we list examples within each (See Table 1).

Table 1: Operative techniques for ACJ reduction with examples

Group	Example
ACJ reduction and fixation	Modified Phemister 6 Internal fixation with unthreaded Kirschner-wires followed by mobilisation at 2 weeks. Carries risk of wire loosening and migration until removed ~8 weeks post-operatively when sufficient time for healing has passed
ACJ reduction, coraco-clavicular ligament repair/reconstruction and coraco-clavicular fixation	Modified Bosworth 4 Fixation achieved by drilling a Bosworth screw from clavicle, inferiorly into base of coracoid followed by coraco-clavicular ligament repair with sutures. Again there is risk of migration and the necessity of a second procedure to remove the screw. Gentle mobilisation after 1 week and screw removal at 8 weeks comprise aftercare.
Distal clavicular excision	Mumford & Gurd 3 Indicated for symptomatic unreduced type II unreduced subluxations. The acromion is sutured to raw end of the clavicle followed by prompt mobilisation after 1 week.
Distal clavicular excision with coraco-clavicular ligament reconstruction	Weaver-Dunn 4 Coraco-acromial ligament is freed from the acromion and sutured to the remaining end of the clavicle through its intramedullary canal to achieve reduction. This procedure relies on a viable coraco-acromial ligament and unavoidably disrupts the coraco-acromial arch. Patient may mobilise after one week in a sling.
Muscle transfers	Coraco-clavicular ligament reconstruction using various soft tissue e.g. free tendon grafts, long head of biceps tendon, fascial grafts 4
Coraco-clavicular ligament reconstruction with prosthetic ligament	The Nottingham Surgilig – Reconstruction achieved using a braided polyester ligament indicated for Rockwood Type V injuries and some Type 3 injuries. With a loop at each end, the prosthetic ligament is looped around the coracoid process, threaded through itself, then passed through around the posterior aspect of the clavicle and anchored with a cortical screw. Immobilisation in a sling for 10-14 days then mobilise as tolerated.

Figure 3: The Nottingham Surgilig

All eleven patients were followed up post-operatively for a mean interval of 55 months. In addition to clinical and radiological assessment, functional outcome was quantitatively assessed via use of the Constant 8 and Imatani 9 scoring systems. This cohort yielded a mean Constant scores of 92.3 (Range 64-100). Using the Imatani Score, seven patients were graded seven as excellent, three good and only one as poor. Pain was only an issue in this one “poor” patient who suffered a coracoid fracture associated with “cheese-wiring” of one of the early ligaments. This was sustained during the early recovery phase when, against medical advice, he undertook heavy lifting. This complication has been avoided subsequently by modifying the design of the loop at the coracoid end from a “hard” loop to a “soft” loop.

A completely normal range of motion was restored in nine of the 11 patients, with ten being able to return to their pre-morbid level of activity and employment at a mean time of five weeks. Nine of the 11 patients were completely satisfied with the post-operative improvement in strength and desire to undergo the same operation should a similar problem occur. Radiological assessment revealed minor subluxation in ten patients and moderate in the remaining one (with the coracoid fracture).

In summary, we have used a braided polyester ligament with loops on both ends that confer favourable prosthetic qualities such as mechanical strength and minimal tissue reaction. Reassuringly, independent biological testing has been proved that our ligament could endure enough mechanical strain to permit early postoperative mobilisation ¹¹.

Among the multiple operative techniques in use for reducing ACJ dislocation, the Weaver-Dunn technique is widely used and efficacious since the position of the distal clavicle is usually well maintained by the coraco-acromial ligament transfer. Drawbacks however, include the delay in performing resistive shoulder exercises until soft tissue healing is sufficiently advanced at 10-12 weeks. Conversely, using the Nottingham Surgilig, patients are able to resume normal activities from 2 weeks without the need for medium term protection. Indeed, the functional outcome of our technique, 92/100 for the Constant score and 90% excellent or good results ⁹, is comparable to other reports ^{1, 10}.

We conclude that insertion of the Nottingham Surgilig is a useful alternative for the treatment of chronic acromio-clavicular separation especially in revision reconstruction when the coraco-acromial ligament is no longer available. In addition, there may be a role for the technique in acute injuries with wide separation at the ACJ. Finally the Nottingham Surgilig was used to provide lateral stability in the world’s first ever artificial Clavicle Replacement (Claviculoplasty) performed in Nottingham with a near perfect result at follow-up over two years later.

1. Rockwood Jr CA, Young DC. Disorders of the Acromioclavicular Joint. In Rockwood Jr CA, Matsen III FA (eds). The Shoulder. Philadelphia: WB Saunders, 1990: 413-468
2. Rockwood Jr CA. Injuries to the Acromioclavicular Joint. In Rockwood Jr CA, Green DP (eds). Fractures in Adults. Philadelphia: JB Lippincott, 1984: 860-910
3. Freeman B. Old unreduced dislocations. In: Canale JT. Campbell’s Operative Orthopaedics. Mosby, 1998: 2657-2677
4. Tossy JD, Mead NC, Sigmond HM. Acromio-claviculare separations: useful and practicazl classification for treatment. Clinical Orthopaedics and Related Research 1963; 28: 111
5. Harris JH. Shoulder, including clavicle and scapula. In: Harris JH, et al. The Radiology of Emergency Medicine (3rd Ed). Baltimore: Williams & Wilkins, 1993: 283-290
6. Phemister DB: The treatment of dislocation of acromioclavicular joint by open reduction and threaded-wire fixation, J Bone Joint Surg. 1942; 24:166
7. Weaver JK, Dunn HK. Treatment of acromioclavicular injuries, especially complete acromioclavicular separation. J Bone Joint Surg Am. 1972 ; 54A:1187-94
8. Constant CR, Murley AG. A clinical method of functional assessment of the shoulder. Clin Orthop 1987; 214:160-4
9. Imatani RJ, Hanlon JJ, Cady GW. Acute, complete acromioclavicular separation. J Bone Joint Surg Am. 1975; 57A: 328-32
10. Guy DK, Wirth MA, Griffin JL, Rockwood CA Jr. Reconstruction of chronic and complete dislocations of the acromioclavicular joint. Clin Orthop. 1998 ;347:138-49.
11. Field JR, Hearn TC, Costi JJ, McGee M, Costi K, Adachi N, Ochi M. Ultimate tensile strength of a Leeds-Keio/autograft ACL reconstruction utilizing PLLA tibial staple fixation. Injury. 2003; 34: 334-42

These autografts encourage new bone growth in the region of the graft. The disadvantages of autografts are their limited availability and the need for a second surgical procedure at the donor site, the latter being associated with donor site morbidity, nerve and vascular injury, post-operative discomfort, increased surgical time, healing time and significant cost implications.

Furthermore, alternatives such as xenografts of bovine bone, demineralised bone matrix, bovine collagen or synthetic ceramic biomaterials show poor levels of osteoinductivity. A breakthrough in the field of regenerative bone repair could be achieved by the use of bone morphogenetic proteins (BMPs). The first recombinant BMP (rhBMP) products have been used in combination with collagen, and although they are effective in inducing bone growth, one crucial point is that very high doses of rhBMP are required due to the soft biomechanic properties of the collagen carrier beside an increased risk for uncontrolled bone formation.

Here we present a new approach that combines a ceramic biomaterial of proven strength with a bone morphogenetic protein. This new biomaterial is homogeneously coated with an osteoinductive growth factor, displays compression resistant mechanical properties and results in a controlled and consistent bone formation across the site of application.

In its most advanced stages, disc degeneration may be followed by ultimate collapse, producing excruciating pain. In cases of degeneration leading to collapse, most frequently in the cervical or lumbar region, patients suffer from debilitating pain, and impairment of neurological function.

Figure 1a & 1b: Histology of single-level posterolateral intertransverse spinal fusion by beta-TCP without (a) or with rhBMP-2 variant (b). In contrast to beta-TCP alone, beta-TCP coated with the rhBMP-2 variant lead to strong neobone formation which resulted in osseous bridging between the posterior processes.

The gold standard surgical procedure for spinal fusion involves fusion of the vertebrae using autogeneous cancellous bone harvested from the iliac crest, with or without pedicle screws, plates or cages. In these cases bone grafts provide osteoconductive scaffolds for local natural bone growth and more rapid fusion results.

Bone graft material may be placed posterolaterally or directly into the intervertebral gap formerly occupied by the degenerated disc and might be placed into a titanium fusion cage, allograft bone dowel, or femoral ring allografts to induce bone growth into, around and through the structure replacing the disc¹.

For patients, the use of secondary surgery to harvest bone grafts is mostly combined with additional morbidity and post-operative discomfort. In addition, spinal fusion requires a comparatively large amount of bone (up to 40cc per procedure) and it may not be possible to harvest sufficient quantities and bone quality in elderly patients. Consequently, human allografts, xenografts using bovine bone or synthetic biomaterials are used instead.

Although these approaches can stabilise the spine, osteoinduction is limited and fusion therefore takes a considerable time or might even be incomplete.

However, to ensure it has an appropriate effect, high doses of BMP are required. This has obvious safety implications and the risk of osteoinduction in regions distal to the site of application is greatly enhanced.

Therefore, they are usually administered in combination with titanium cages that provide the necessary support. The sponge is inserted into the cage device, which is implanted between the degenerated vertebrae to keep the vertebrae properly spaced and aligned during the fusion process.

In a number of preclinical and clinical studies these procedures have been shown to be as effective as autogenous bone graft ². However, a major drawback of collagen-based material is that very high doses of growth factor are necessary to induce sufficient bone growth across the site of spinal fusion. The bovine origin of the collagen is also a drawback.

Until recently it had proved difficult to find a way of combining bone morphogenetic proteins with ceramic biomaterials as easily as they are combined with the sponge-like collagen. However, we have developed a proprietary coating technology for the non-covalent association of proteins with the surface of ß-TCP-granules (granule size greater than 0,5 mm).

This proprietary coating technology allows for a homogeneous protein coating on the ß-TCP matrix while maintaining the biological activity of the growth factor, avoiding structural modifications as well as aggregation of the protein.

Scil Technology has already successfully demonstrated in various preclinical models, including dental and orthopaedic applications, that this homogeneous coating technology has a dramatic beneficial impact on the biological efficacy of the growth factor ³. This means that lower concentrations of growth factors can be used than in collagen applications while retaining equivalent or superior efficacy and a reduced side-effect profile.

The growth factor is combined with the granular ß-TCP scaffold, which is compression resistant and displays osteoconductive characteristics allowing for cell infiltration and new bone formation. The ß-TCP scaffold degrades over time and ultimately the biomaterial will entirely be replaced by the patient’s own bone.

At the three-week stage no animal treated with autogenous bone graft or ß-TCP alone showed fusion and both demonstrated only immature callus and little neobone formation in the region of administration.

Table 1:
Posterolateral spinal fusion in rabbits (3 weeks observation period)

	Manual Fused	Histology Fused	X-ray Fused	CT Fused
Autograft	0/6	0/6	0/5	0/3
TCP	0/6	0/5	1/6	0/5
TCP (30mg BMP2)	0/7	1/6	0/6	n.d.
TCP (150mg BMP2)	4/7	6/7	3/5	4/5
Collagen (150mg BMP2)	3/6	3/6	3/5	3/5

This data indicate that the homogenous rhBMP-2 coated ß-TCP appears to be superior to the current gold standard treatment for spinal fusion, autograft, and that fusion can be achieved with a lower dose of BMP-2 than that used in collagen/BMP-2 combinations. The spacial distribution of new bone formation was highly controlled and the product is considered to be safe.

Bone cement is used as a grout in the space between the bone and the implant, allowing the transfer of load across the new joint. When implanted the material must be able to withstand the same large loads as the natural joint. Paul, 1976 showed that during walking the force passing through the hip can be almost 5 times body weight. For a person weighing 12 stone this equates to a force of almost 50 stone passing through the joint. For a person that has undergone a hip or knee replacement this is multiplied out by about 5,000 steps per day (Schmalzried et al 1998) and equates to a large mechanical challenge to a layer of bone cement that is typically only 2-3mm thick.

Therefore it is imperative that the bone cement is mixed to produce optimum mechanical properties in terms of strength, creep and fatigue resistance. Ensuring a reproducibly high quality result requires not just well designed mixing devices but also that the devices and cement are used correctly. Education and continual training programs are key in ensuring consistently good results.

Most bone cements are provided as a polymer powder in a sachet and a monomer liquid in a glass ampoule. A chemical reaction occurs as the two components are mixed together. It is important that during the early stages of mixing that the powder is completely wet down to prevent unmixed powder occurring in the final mix. This is why some vacuum mixing devices require the powder to be added before the liquid. Gravity helps the liquid to seep down through the powder during the early stages of mixing. In the days of open bowl mixing the liquid component was added first to minimize air entrapment in the powder. However better mechanical results (Fig 1) are achieved with modern vacuum systems which use powder first and a vacuum to draw out air from the mix.

Figure 1, Queens University Belfast, 2001

It is important that training identifies these changes in technique, which have developed with advances in mixing system technology.

The polymerization process of the cement has four distinct phases – mixing time, waiting time, working time and setting time. The length of these phases are dependant on temperature, the brand of cement and to a smaller extent mixing technique. A clear understanding by the perioperative practitioner of the timing, and factors which can influence these phases is critical to achieving optimal results.

Temperature has a key role to play in the polymerization process. Each pack of cement should include a temperature versus time graph, which shows that as temperature increases, the phases of polymerization shorten. Figure 2 shows the temperature time graph for Palacos R cement.

Figure 1

This graph demonstrates that at 25 C the surgeon will have about 1 minute less during the working phase to use the cement compared to cement at 19 C. If the surgeon attempts to insert the cement into the patient when it has entered its setting phase the cement can laminate which can significantly reduce the strength of the cement mantle (Lee, 1979). Also at higher temperatures it becomes more difficult for the powder and liquid to integrate which makes it harder to mix effectively. However a well-informed user can take actions to ensure that these difficulties are overcome by employing correct handling and mixing techniques.

For example storage temperature should be cool, together with theatre temperature where possible. In addition the use of mixing systems that don’t require picking up during use can avoid heat transfer into the mix. Also if temperature is higher on a particular day the surgeon needs to be informed of the changes in working time compared to normal conditions so that insertion timings can be modified. It is therefore vital that training includes information on temperature and timing.

Even if temperature and other variables are consistent bone cements can vary considerably when mixed, for the following reasons:

• Some cements contain not only polymethylmethacrylate (PMMA) but also PMMA co-polymers such as methyl acrylate and styrene in the powder and additional polymers such as butyl methacrylate.
• The ratio of the components and the overall powder to liquid ratio may differ between cements
• The size, shape and weight of the polymer molecules can vary considerably
• Manufacturing processes may differ
• Sterilization methods may differ

The design of the mixing device can also have a significant effect on the quality and reproducibility of the cement produced. It is important that the choice of system is based on sound scientific data as different systems have been proven to give significantly different results. In addition those using the systems need to have a full understanding of how to use them correctly to ensure best results. The focus should be on minimizing the variability caused by different levels of user skill and experience. This variability is dependant on two key areas, mixer design and operator technique.

A key concept that users should be aware of in relation to the performance of different systems is fatigue. Fatigue failure begins with a small crack that develops slowly under cyclical loading leading eventually to sudden failure. The initial crack is likely to start in an area of weakness or at a discontinuity in the material due to stress concentration. Evidence of fatigue cracks have been found when examining retrieved cement from revisions.

Culleton et al (1993) examined a cement mantle microscopically and found evidence of fatigue cracking originating from defects in the cement. Topoleski et al (1990) examined 12 failed cement arthroplasties and identified fatigue crack growth as being the most likely mode of failure of the bone cement. Improving the bone cement to resist fatigue failure is therefore important in ensuring that it survives long-term for the well being of the patient.

Manually mixed bone cement has been shown to be porous and contain small and large voids, which is where fatigue fractures are most likely to occur. Vacuum mixing bone cement removes air from the cement and thus reduces the number of voids, leading to an improvement in the strength and fatigue properties of the cement and a decrease in the number of potential crack initiation sites (Wixson 1992, Lewis 2000).

Figure 3 shows how different mixing systems perform in terms of fatigue life. Hand mixing in an open bowl shows the lowest average fatigue cycles to failure compared to three different vacuum mixing systems. This graph also shows that not all vacuum mixing systems provide the same levels of mix quality.

Figure 3, Testing conducted by RAPRA Technology, Shrewsbury, 2000

The two systems on the right of the graph share a similar design and operate at very high vacuum levels yet have lower average fatigue life results than a system that operates at the lower vacuum level of 550mmHg. This can be explained by the concept of optimal vacuum. During polymerization bone cement heats up and then shrinks. If the shrinkage is large the cement will form micro cracks, which can open up during loading and lead to fatigue failure.

When mixed cement contains air the shrinkage is offset by the air pockets expanding during the temperature increase. However if air pockets are too large a basic mechanical weakness can form in the cement mantle. Test work has identified that the optimal vacuum for mixing bone cement is around 550mmHg (Queens University Belfast, 2001). This provides the optimal balance between basic mechanical strength and excessive shrinkage and the formation of micro-cracks. It is important that users ensure that the vacuum system that they use operates at or around this vacuum level.

Figure 3 also demonstrates that different systems provide different levels of variability in cement quality. The two systems on the right of the graph share a basic common design which requires the user to pull and twist a mixing handle to operate. This requires an element of human skill and the mixing action will be slightly different each time it is used.

The graph is based on test work conducted by one skilled user. It shows that these systems have the potential to generate good results but also very poor results. This contrasts with the second system from the left on the graph, which features a repeatable mechanical action, which only requires the operator to pull and push a handle up and down without twisting. The standard deviation shown on figure 3 shows that variability is lower and the patient should not get the worst case results provided by the other type of design. If users have not received comprehensive training the differences in mixer design are likely to be exaggerated.

The design of the mixing device also has been shown to have an influence on the integration of the liquid and powder. For example Kurdy et al 1986 demonstrated that a fixed axis mixing bowl produced significantly inferior results to a rotational axis design or hand mixing. A fixed axis bowl is one where the blades of the mixer rotate on the same track on each turn, compared to a rotational axis design where the whole paddle moves around the bowl.

Figure 4

These graphs (Figure 4) show that a rotational axis design produces significantly less unmixed powder and lower levels of gross porosity. It is important that users understand the benefits of a rotational axis design over fixed axis bowls in order to achieve optimal results, particularly where some systems appear to be similar.

Most vacuum systems contain a filter to reduce methylmethacrylate fumes expelled into theatre during the mixing process. Devices that contain a charcoal filter have been proven to be very effective. Research carried out by Vapour Management Systems in Plymouth demonstrated that four market leading mixing devices expose the user to fumes levels considerably lower than international health & safety standards (Figure 5).

COSHH EXPOSURE GUIDLINES; 100PPM FOR A 15 MINUTE EXPOSURE

Figure 5

Lowest fume levels were experienced with systems that are not picked up during use. Even though some systems are closed once the powder and liquid have been added the user is exposed to slightly elevated fume levels once the system is picked up as the source of fumes is brought closer to the user’s face and nose. However both bench level and hand held devices operated well within the standards and providing they are used correctly, should not constitute a risk to the user.

In his book – “Bone Cements: Up to date Comparison of Physical and Chemical Properties of Commercial Materials” Klaus-Dieter Kuhn states: “The nurses, (together with the surgeon) have enormous influence on the quality of the cement dough produced; in the end, this will considerably influence the clinical long-term result of a cemented hip, or cemented knee.” For this process to happen, it is important that everyone in the theatre environment is supported with comprehensive training and support.

Mixing device suppliers are becoming increasingly keen to work in partnership with theatre teams to provide comprehensive training to ensure that their products are used correctly and that patient outcomes are maximized. As part of this there has been a recent growth in Train the Trainer programmers, which allow key members of theatre teams to train new members of staff in a consistent and structured way. Liz Green, Director of Marketing at Summit Medical, said: “Train the Trainer programmes have been an invaluable way for new users to get the most out of our mixing systems, which in turn has real benefits for the patients.”

As an example of the training support available from suppliers Summit Medical provide The Principles of Bone Cement Mixing presentation giving key background information on; the role of bone cement, mixer design, benefits of vacuum, mechanical properties of bone cement and health & safety. This presentation is available for theatre staff and also features a CME approved version for surgeons.

In addition a comprehensive Train the Trainer scheme gives detailed training on how to use the Summit product range, as well as competency testing, allowing the trainers to accurately assess the ability of their users in following correct technique. To underpin this a wide range of support material is also available including, instructional videos / CD ROM’s, posters, brochures and perioperative updates covering latest research.

Vacuum mixing on bone cement is now seen as a key element in modern cementation technique. The 2003 Swedish Hip Study Annual Report, issued in May 2004, shows that the national average for 10-year survival has improved from 89.4% to 92.5% between the observation periods 1979-1991 and 1992-2003. This has coincided with the advancements in mixing system design and modern cementation technique. For these survivorship improvements to continue it is important that theatre staff and device suppliers work closely together through ongoing training and education programs.

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