Biological Mechanisms Underlying Tendon Injuries: Why it is Clinically Relevant? Diabetes, cholesterol & statins James Gaida B.Physio(Hons), PhD

Monash University School of Primary Health Care Department of Physiotherapy



[email protected]

Tendinopathy 101 • Tendinopathy is the culmination of numerous intrinsic and extrinsic risk factors • Exists on a continuum1

Reactive tendinopathy, tendon dysrepair, degenerative tendinopathy • Relative tendon overload is a dominant clinical finding2,3 • Load-based rehabilitation (mechanotransduction) is first line treatment4,5

1. Cook and Purdam. Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy. British Journal of Sports Medicine (2009) vol. 43 (6) pp. 409-16 2. Hägglund et al. Epidemiology of Patellar Tendinopathy in Elite Male Soccer Players. The American journal of sports medicine (2011) pp. 3. Visnes and Bahr. Training volume and body composition as risk factors for developing jumper's knee among young elite volleyball players. Scandinavian Journal of Medicine & Science in Sports (2012) pp. 4. Scott et al. Conservative treatment of chronic Achilles tendinopathy. CMAJ (2011) vol. 183 (10) pp. 1159-65 5. Gaida and Cook. Treament Options for patellar tendinopathy: a critical review. Current sports medicine reports (2011) vol. 10 (5) pp. 255-270

How much is too much?

Tendon capacity

✔

Tendon loading

☺ Tendon capacity

✘

☹

Tendon loading

Clinical presentation of reduced tendon capacity • Detailed interview fails to identify convincing overload ✘ Work duties ✘ Handyman work ✘ Resumption of sport following

injury ✘ Inefficient running mechanics ✘ Recent change or increase in

training or sport ✘ High level sport

• History of multiple connective tissue presentations - Plantar fasciitis - Tibialis anterior reconstruction - Tibialis posterior tendinopathy - Hip bursitis (?glut med) - Tennis elbow - Rotator cuff tear

Reduced tendon capacity: Type 2 diabetes

7.5%

% 15

%

Achilles tendinopathy

10

Tendon strain inversely

correlated with T2DM

duration

Dutch population

5%

•

Biomechanics2:

3.3%

0%

• Clinical1:

7.5% of patients with Achilles

tendinopathy have T2DM

Diabetes prevalence

• Mechanism3:

Tendon collagen from T2DM

“apparent age” ~2.5x actual

age

1. de Jonge et al. Incidence of midportion Achilles tendinopathy in the general population. British Journal of Sports Medicine (2011) vol. 45 (13) pp. 1026-8 2. Cronin et al. Achilles tendon length changes during walking in long-term diabetes patients. Clinical biomechanics (Bristol, Avon) (2010) vol. 25 (5) pp. 476-82 3. Hamlin et al. Apparent accelerated aging of human collagen in diabetes mellitus. Diabetes (1975) vol. 24 (10) pp. 902-4

Reduced tendon capacity: clinical implications • Address contributing factors - Educate patient - Tendinopathy may be

symptom of underlying

insulin resistance1 • Optimal management of diabetes2 • Slower progression • Build muscle bulk3

1. Gaida et al. Dyslipidemia in Achilles tendinopathy is characteristic of insulin resistance. Medicine and Science in Sports and Exercise (2009) vol. 41 (6) pp. 1194-7 2. Hider et al. Resolution of diabetic cheiroarthropathy after pancreatic transplantation. Diabetes Care (2004) vol. 27 (9) pp. 2279-80 3. Holten et al. Strength training increases insulinmediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes. Diabetes (2004) vol. 53 (2) pp. 294-305

Reduced tendon capacity: Diabetes screening? • Patients with flexor tenosynovitis should be screened for diabetes1

- Abnormal OGTT

trigger finger: 1 in 4

control: 1 in 20 • Thick tendons

Definitely: Achilles2-5

Likely: Biceps brachii6,7

Not affected: patellar8

1. Leden et al. Flexor tenosynovitis (FTS): a risk indicator of abnormal glucose tolerance. Scandinavian Journal of Rheumatology (1985) vol. 14 (3) pp. 293-7 2. Akturk et al. Evaluation of Achilles tendon thickening in type 2 diabetes mellitus. Experimental and Clinical Endocrinology and Diabetes (2007) vol. 115 (2) pp. 92-6 3. Papanas et al. Achilles tendon volume in type 2 diabetic patients with or without peripheral neuropathy: MRI study. Experimental and Clinical Endocrinology and Diabetes (2009) vol. 117 (10) pp. 645-8 4. Abate et al. Achilles tendon and plantar fascia in recently diagnosed type II diabetes: role of body mass index. Clin Rheumatol (2012) pp. 5. Giacomozzi et al. Does the thickening of Achilles tendon and plantar fascia contribute to the alteration of diabetic foot loading?. Clinical biomechanics (Bristol, Avon) (2005) vol. 20 (5) pp. 532-9 6. Akturk et al. Thickness of the supraspinatus and biceps tendons in diabetic patients. Diabetes Care (2002) vol. 25 (2) pp. 408 7. Abate et al. Sonographic evaluation of the shoulder in asymptomatic elderly subjects with diabetes. BMC musculoskeletal disorders (2010) vol. 11 pp. 278 8. Altinel et al. The midterm effects of diabetes mellitus on quadriceps and patellar tendons in patients with knee arthrosis: a comparative radiological study. J Diabetes Complicat (2007) vol. 21 (6) pp. 392-6

Early diagnosis: - worth the effort? • Medical costs rise 8-years prior to T2DM diagnosis1 • Lifestyle intervention (IGT)2

Delay: 11-years

Reduce: incidence 20% • Cost-effective2

Lifestyle: $8,800/QALY

Metformin: $29,900/QALY

1. Nichols et al. Type 2 diabetes: incremental medical care costs during the 8 years preceding diagnosis. Diabetes Care (2000) vol. 23 (11) pp. 1654-9 2. Herman et al. The cost-effectiveness of lifestyle modification or metformin in preventing type 2 diabetes in adults with impaired glucose tolerance. Annals of Internal Medicine (2005) vol. 142 (5) pp. 323-32

Early diagnosis: - worth the effort? • YES! Tendinopathy-diabetes link needs to be translated to primary care clinician

Reduced tendon capacity: cholesterol • Heterzygous Familial hypercholesterol (HeFH)1 • Non-genetic causes Achilles tendinopathy2,3 Achilles Rupture4 Rotator cuff tear5,6 Obesity7

... our study shows that an attack of pain in the Achilles tendon region should signal the need for cholesterol measurement to exclude a diagnosis of HeFH. ... it may be appropriate to redefine our concept of tendinopathy to that of a cardiovascular disease (CVD) ...perhaps treating CVD risk factors will improve the treatment of tendinopathy.

1. Beeharry et al. Familial hypercholesterolaemia commonly presents with Achilles tenosynovitis. Annals of the Rheumatic Diseases (2006) vol. 65 (3) pp. 312-5 2. Gaida et al. Dyslipidemia in Achilles tendinopathy is characteristic of insulin resistance. Medicine and Science in Sports and Exercise (2009) vol. 41 (6) pp. 1194-7 3. Klemp et al. Musculoskeletal manifestations in hyperlipidaemia: a controlled study. Annals of the Rheumatic Diseases (1993) vol. 52 (1) pp. 44-8 4. Ozgurtas et al. Is high concentration of serum lipids a risk factor for Achilles tendon rupture?. Clinica Chimica Acta (2003) vol. 331 (1-2) pp. 25-8 5. Abboud and Kim. The effect of hypercholesterolemia on rotator cuff disease. Clinical Orthopaedics and Related Research (2010) vol. 468 (6) pp. 1493-7 6. Longo et al. Triglycerides and total serum cholesterol in rotator cuff tears: do they matter?. British Journal of Sports Medicine (2010) vol. 44 (13) pp. 948-51 7. Gaida et al. Is adiposity an under-recognized risk factor for tendinopathy? A systematic review. Arthritis and Rheumatism (2009) vol. 61 (6) pp. 840-849

Tendon capacity: statins • Regression of Achilles tendon thickness in HeFH with statin (atorvastatin 20mg/d)1 • Increased risk for rupture in women (OR=3.8)2 • Achilles tendon >50% cases3

1. Tsouli et al. Regression of Achilles tendon thickness after statin treatment in patients with familial hypercholesterolemia: an ultrasonographic study. Atherosclerosis (2009) vol. 205 (1) pp. 151-5 2. Beri et al. Association between statin therapy and tendon rupture: a case-control study. Journal of Cardiovascular Pharmacology (2009) vol. 53 (5) pp. 401-4 3. Marie et al. Tendinous disorders attributed to statins: A study on ninety-six spontaneous reports in the period 1990-2005 and review of the literature. Arthritis Rheum (2008) vol. 59 (3) pp. 367-372

Cholesterol: Double edged sword • Very high levels negative effect on tendon • Statins

Increase risk of rupture

Years of preceding exposure

Rapid change in cholesterol

the reported association between statins and tendinopathy may simply be a case of ‘‘the straw that broke the camel’s back.’’

1. Gaida et al. Response. Medicine and Science in Sports and Exercise (2010) vol. 42 (1) pp. 215

Take home message Tendon capacity

T2DM Cholesterol

✘

Tendon loading

☹

Screening

Acknowledgements Prof Jill Cook Prof Håkan Alfredson Dr Zolton S Kiss A/Prof Andrew M Wilson Monash University - Bridging Postdoctoral Fellowship ACSM Annual Meeting 2012