Bruce Hamilton

Growth factor delivery methods in the management of sports injuries: the state of play

In recent years there have been rapid developments in the use of growth factors for accelerated healing of injury. Growth factors have been used in maxillo-facial and plastic surgery with success and the technology is now being developed for orthopaedics and sports medicine applications. Growth factors mediate the biological processes necessary for repair of soft tissues such as muscle, tendon and ligament following acute traumatic or overuse injury, and animal studies have demonstrated clear benefits in terms of accelerated healing. There are various ways of delivering higher doses of growth factors to injured tissue, but each has in common a reliance on release of growth factors from blood platelets. Platelets contain growth factors in their α-granules (insulin-like growth factor-1, basic fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, vascular endothelial growth factor, transforming growth factor-β1) and these are released upon injection at the site of an injury. Three commonly utilised techniques are known as platelet-rich plasma, autologous blood injections and autologous conditioned serum. Each of these techniques has been studied clinically in humans to a very limited degree so far, but results are promising in terms of earlier return to play following muscle and particularly tendon injury. The use of growth factors in sports medicine is restricted under the terms of the World Anti-Doping Agency (WADA) anti-doping code, particularly because of concerns regarding the insulin-like growth factor-1 content of such preparations, and the potential for abuse as performance-enhancing agents. The basic science and clinical trials related to the technology are reviewed, and the use of such agents in relation to the WADA code is discussed.

Platelet-rich plasma treatment for ligament and tendon injuries.

Platelet-rich plasma (PRP) is derived from centrifuging whole blood, has a platelet concentration higher than that of the whole blood, is the cellular component of plasma that settles after centrifugation, and contains numerous growth factors. There is increasing interest in the sports medicine and athletic community about providing endogenous growth factors directly to the injury site, using autologous blood products such as PRP, to potentially facilitate healing and earlier return to sport after musculoskeletal injury. Despite this interest, and apparent widespread use, there is a lack of high-level evidence regarding randomized clinical trials assessing the efficacy of PRP in treating ligament and tendon injuries. Basic science and animal studies and small case series reports on PRP injections for ligament or tendon injuries, but few randomized controlled clinical trials have assessed the efficacy of PRP injections and none have demonstrated scientific evidence of efficacy. Scientific studies should be performed to assess clinical indications, efficacy, and safety of PRP, and this will require appropriately powered randomized controlled trials with adequate and validated clinical and functional outcome measures and sound statistical analysis. Other aspects of PRP use that need to be determined are (1) volume of injection/application, (2) most effective preparation, (3) buffering/activation, (4) injection technique (1 depot vs multiple depots), (5) timing of injection to injury, (6) single application versus series of injections, and (7) the most effective rehabilitation protocol to use after PRP injection. With all proposed treatments, the doctor and the patient should weigh up potential benefits of treatment, potential risks, and costs. Based on the limited publications to date and theoretical considerations, the potential risks involved with PRP are fortunately very low. However, benefits remain unproven to date, particularly when comparing PRP with other injections for ligament and tendon injuries.

Vitamin D deficiency is endemic in Middle Eastern sportsmen.

OBJECTIVE While vitamin D deficiency is well recognized in Middle Eastern women as a result of cultural norms of remaining covered, Middle Eastern men are an under-reported group. Vitamin D is now known to have multiple effects, including an impact on muscle function, thereby increasing the relevance for sportsmen. The aim of the present study was to evaluate serum 25-hydroxyvitamin D (25(OH)D) levels in young male Middle Eastern athletes. DESIGN Cross-sectional study. SETTING Qatar Orthopaedic and Sports Medicine Hospital, Doha, Qatar. SUBJECTS Ninety-three Middle Eastern men presenting to hospital for an annual screening undertook a blood test to evaluate their vitamin D status. RESULTS Ninety-one per cent of athletes were found to be deficient in 25(OH)D (serum concentration <20 ng/ml). Athletes with severe deficiencies were significantly younger than those with less marked deficiency. A subset of athletes underwent bone mineral density assessment and 59 % were shown to have at least one Z-score less than -1; despite this, however, no athletes reported a stress fracture. There was no correlation between 25(OH)D concentration and sunlight exposure, skin coverage and skin colouring. CONCLUSIONS The study revealed that 25(OH)D deficiency is very common among otherwise healthy Middle Eastern male athletes. Given the potentially significant long- and short-term effects of 25(OH)D deficiency, serum 25(OH)D evaluation should be part of the routine assessment in this region.

The early management of muscle strains in the elite athlete: best practice in a world with a limited evidence basis.

From 12 to 14 December 2007 UK Sport held a think tank on “muscle strains” in London. This brought together many of UK Sport’s top sports medicine clinicians along with three invited international experts. Many issues of muscle strains were discussed over the three days, but the aspect that attracted the most attention was the early management of strains in the elite athlete. A consensus summary of conclusions on this specific topic from the think tank is presented here. The international experts were chosen by request of the UK clinicians for different reasons. Drs Best (basic science) and Orchard (epidemiology) are recognised internationally by the peer-review system as experts in their fields. Dr Mueller-Wohlfahrt is also recognised internationally as Europe’s premier clinician in the early management of muscle strains. This recognition was initially bestowed on him by his patients, most notably from the thousands of professional football players he has managed over the past 30 years from every country in Europe. Increasingly this recognition has been accorded by the “mainstream” clinicians in the United Kingdom, hence his invitation to the think tank. With the reserve typical of both the British and the scientific community, a common assessment of Dr Mueller-Wohlfahrt’s methods by delegates was “initially I had to be sceptical, but I have seen and heard of so many good results that I am now curious to know why these good outcomes are occurring”. One session of the think tank involved an assessment of our “expert recommendations” for the early management of muscle strains in the elite athlete and a judgement of the evidence base for making the recommendations. The evidence base part was generally easy: almost all of our so-called knowledge has a basis …

Non-steroidal anti-inflammatory drugs in sports medicine: guidelines for practical but sensible use

Introduction: Non-steroidal anti-inflammatory drugs (NSAID) are commonly used in sports medicine. NSAID have known anti-inflammatory, analgesic, antipyretic and antithrombotic effects, although their in-vivo effects in treating musculoskeletal injuries in humans remain largely unknown. NSAID analgesic action is not significantly greater than paracetamol for musculoskeletal injury but they have a higher risk profile, with side-effects including asthma exacerbation, gastrointestinal and renal side-effects, hypertension and other cardiovascular diseases. Discussion: The authors recommend an approach to NSAID use in sports medicine whereby simple analgesia is preferentially used when analgesia is the primary desired outcome. However, based both on the current pathophysiological understanding of most injury presentations and the frequency that inflammation may actually be a component of the injury complex, it is premature to suppose that NSAID are not useful to the physician managing sports injuries. The prescribing of NSAID should be cautious and both situation and pathology specific. Both dose and duration minimisation should be prioritised and combined with simple principles of protection, rest, ice, compression, elevation (PRICE), which should allow NSAID-sparing. NSAID use should always be coupled with appropriate physical rehabilitation. Conclusion: NSAID are probably most useful for treating nerve and soft-tissue impingements, inflammatory arthropathies and tenosynovitis. They are not generally indicated for isolated chronic tendinopathy, or for fractures. The use of NSAID in treating muscle injury is controversial. Conditions in which NSAID use requires more careful assessment include ligament injury, joint injury, osteoarthritis, haematoma and postoperatively.

Hamstring Injuries: Anatomy, Imaging, and Intervention

Injury to the hamstring muscle complex (HMC) is extremely common in the athletic community. Anatomical and functional aspects of the HMC predispose it to injury, including the fact that the muscles cross two joints and undergo eccentric contraction during the gait cycle. Injury most commonly occurs at the muscle tendon junction but may occur anywhere between the origin and insertion. Complete hamstring avulsions require early surgical repair. The principal indication for imaging is in a triage role to rule out or confirm proximal hamstring avulsion. Acute onset and chronic posterior thigh and buttock pain may relate to pathology at the hamstring origin or muscle tendon junction that can be readily defined on magnetic resonance imaging or, less frequently, ultrasound. Some cases of buttock and thigh pain may relate to spinal pathology. In the elite athlete there is an increasing emphasis on optimizing the rehabilitation process after hamstring injury, to minimize the absence from sports and improve the final outcome. Imaging has a role in confirming the site of injury and characterizing its extent, providing some prognostic information and helping plan treatment. There is increasing interest in the use of growth factors to accelerate healing after muscle and tendon injury. Animal studies have demonstrated clear benefits in terms of accelerated healing. There are various methods of delivery of the growth factors, all involving the release of growth factors from platelets. These include plasma rich in platelets and autologous blood. Clinical studies in humans are very limited at this stage but are promising. At present the World Anti-Doping Authority bans the intramuscular administration of these agents. Other percutaneous injection therapies include the use of Actovegin and Traumeel S and antifibrotic agents.

Traumatic injuries of thigh and calf muscles in athletes: role and clinical relevance of MR imaging and ultrasound

ObjectivesMagnetic resonance (MR) imaging and ultrasound have become valuable tools for evaluation of traumatic muscle injuries in athletes. Common athletic injuries include strain, contusion and avulsion, which are characterised by muscle fibre disruption, intramuscular haemorrhagic dissection, haematoma at the musculotendinous junction, and perifascial blood or haematoma.MethodsMR imaging may allow clinicians to predict the time required before athletes can return to competition and the risk of injury recurrence.ResultsFluid-sensitive MR sequences, e.g., fat-suppressed T2-weighted or proton density-weighted turbo spin echo (TSE), and short-tau inversion recovery (STIR) sequences are suitable for detecting oedematous changes in the musculotendinous unit, and for delineating intramuscular or perifascial fluid collections or haematoma. T1-weighted spin echo sequences are used to visualise atrophy and fatty infiltration and to differentiate between haemorrhage/haematoma and oedema. While ultrasound may play a role as an adjunctive imaging method, it is less accurate than MR images for assessing the extent of the injury and it cannot differentiate between new and old injuries.ConclusionsIn this pictorial review, imaging features of lower extremity muscle injuries including strain, contusion and avulsion are reviewed, focusing on MR and ultrasound imaging findings after initial injury and during follow-up, and their relevance in clinical practice is discussed.Teaching points• MR imaging may allow clinicians to predict time required before athletes can return to competition• Fluid-sensitive MR sequences are suitable for detecting oedematous changes in the muscles• T1-weighted sequences are used to differentiate between haemorrhage/haematoma and oedema.• Ultrasound can also be used but is less accurate than MR imaging for assessing the extent of the injury

Hamstring and Quadriceps Isokinetic Strength Deficits Are Weak Risk Factors for Hamstring Strain Injuries A 4-Year Cohort Study

Background: A hamstring strain injury (HSI) has become the most common noncontact injury in soccer. Isokinetic muscle strength deficits are considered a risk factor for HSIs. However, underpowered studies with small sample sizes unable to determine small associations have led to inconclusive results regarding the role of isokinetic strength and strength testing in HSIs. Purpose: To examine whether differences in isokinetic strength measures of knee flexion and extension represent risk factors for hamstring injuries in a large cohort of professional soccer players in an adequately powered study design. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 614 professional soccer players from 14 teams underwent isokinetic strength testing during preseason screening. Testing consisted of concentric knee flexion and extension at 60 deg/s and 300 deg/s and eccentric knee extension at 60 deg/s. A clustered multiple logistic regression analysis was used to identify variables associated with the risk of HSIs. Receiver operating characteristic (ROC) curves were calculated to determine sensitivity and specificity. Results: Of the 614 players, 190 suffered an HSI during the 4 seasons. Quadriceps concentric strength at 60 deg/s (odds ratio [OR], 1.41; 95% CI, 1.03-1.92; P = .03) and hamstring eccentric strength at 60 deg/s (OR, 1.37; 95% CI, 1.01-1.85; P = .04) adjusted for bodyweight were independently associated with the risk of injuries. The absolute differences between the injured and uninjured players were 6.9 N·m and 9.1 N·m, with small effect sizes (d < 0.2). The ROC analyses showed an area under the curve of 0.54 and 0.56 for quadriceps concentric strength and hamstring eccentric strength, respectively, indicating a failed combined sensitivity and specificity of the 2 strength variables identified in the logistic regression models. Conclusion: This study identified small absolute strength differences and a wide overlap of the absolute strength measurements at the group level. The small associations between lower hamstring eccentric strength and lower quadriceps concentric strength with HSIs can only be considered as weak risk factors. The identification of these risk factors still does not allow the identification of individual players at risk. The use of isokinetic testing to determine the association between strength differences and HSIs is not supported.

Excellent reliability for MRI grading and prognostic parameters in acute hamstring injuries

Background Categorical grading and other measurable MRI parameters are frequently utilised for predicting the outcome of hamstring injuries. However, the reliability and smallest detectable difference (SDD) have not been previously evaluated. It therefore remains unclear if the variability in previously reported results reflects reporting variation or actual injury status. Methods 25 hamstring injuries were scored by two experienced radiologists using the Peetrons grading and specific prognostic MRI parameters: distance from ischial tuberosity (cm), extent (cranio to caudal, anterior to posterior, medial to lateral; (cm)), maximum cross-sectional area (%), volume (cm3) of the oedema. The interobserver and intraobserver reliability was calculated along with the SDDs for each scale variable. Results There were 3 Grade 0 (12%), 11 grade 1 (44%), 9 grade 2 (36%) and 2 grade 3 (8%) injuries. Cronbachs α values for grading were 1.00 (inter) and 0.96 (intra), respectively. The intraclass correlation coefficients for the prognostic MRI parameters were between 0.77 and 1.0. The SDDs varied between each parameter. Conclusions Excellent interobserver and intraobserver reliability was found for grading and prognostic MRI parameters in acute hamstring injuries. In daily practice and research, we can be confident that scoring hamstring injuries by experienced radiologists is reproducible. The documented SDDs allow meaningful clinical inferences to be made when assessing observed and reported changes in MRI status.

Platelet-enriched plasma and muscle strain injuries: challenges imposed by the burden of proof.

Objective:To review the evidence for the clinical utilization of autologous plasma products in the management of muscle strain injuries. Method:Systematic review using EMBASE and MEDLINE (up to March 2010). Results:There is no level 1, 2, and 3 evidence for the use of autologous plasma products in muscle strain injuries. Furthermore, significant methodological limitations impact on the interpretation of the few published studies in this field. Conclusions:Although basic science and the use of recombinant growth factors in animal models support the concept of applying growth factors to acute muscle injuries, it is unclear if this evidence can be directly translated to reflect outcomes from platelet-enriched plasma. There remain a large number of unanswered questions, including the principle questions regarding safety and efficacy, which require appropriate scientific investigation. It is incumbent on sports physicians wishing to enhance athlete care, together with researchers, to search for these answers.