What is the role of systemic conditions and options for manipulation of bone formation and bone resorption in rotator cuff tendon healing and repair?

Rotator cuff pathology is a significant cause of shoulder pain. Operative repair of rotator cuff is an established standard of care for these patient, however, failure of the procedure is common. Systemic conditions such as diabetes mellitus, hypocholesteremia, thyroid disease, and smoking significantly affect the outcomes of rotator cuff repair and have significant implications for the management of these patients. Diabetes mellitus has been proposed to damage tendons through non-enzymatic glycosylation of collagen with advanced glycation end product formation and impaired microcirculation. Hypocholesteremia may lead to fatty infiltration and subsequent pro-inflammatory degenerative enzymatic degeneration. Thyroid disease may disrupt tendon homeostasis through the alteration of collagen production and the accumulation of glycosaminoglycans. Lastly, smoking inhibits tendon healing through the induction of hypovascularity and hypoperfusion. Understanding of the implications these systemic conditions have on the outcomes is important in the management of rotator cuff disease.

[1]  N. Maffulli,et al.  Thyroid hormones and tendon: current views and future perspectives. , 2019, Muscle Ligaments and Tendons Journal.

[2]  J. Oh,et al.  Effect of hypercholesterolemia on fatty infiltration and the quality of tendon-to-bone healing in a rabbit model of a chronic rotator cuff tear: Electrophysiological, biomechanical, and histological analyses , 2016 .

[3]  C. Cho,et al.  Serial Comparison of Clinical Outcomes After Arthroscopic Capsular Release for Refractory Frozen Shoulder With and Without Diabetes. , 2016, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[4]  Min-Wook Kim,et al.  Influence of Hyperlipidemia on the Treatment of Supraspinatus Tendinopathy With or Without Tear , 2016, Annals of rehabilitation medicine.

[5]  L. Soslowsky,et al.  Effect of simvastatin on rat supraspinatus tendon mechanical and histological properties in a diet‐induced hypercholesterolemia model , 2016, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[6]  N. Roupas,et al.  Spontaneous rupture of the long head of the biceps tendon in a woman with hypothyroidism: a case report , 2016, Journal of Medical Case Reports.

[7]  L. Soslowsky,et al.  Tendon Homeostasis in Hypercholesterolemia. , 2016, Advances in experimental medicine and biology.

[8]  R. Rossi,et al.  Subclinical hypothyroidism and diabetes as risk factors for postoperative stiff shoulder , 2017, Knee Surgery, Sports Traumatology, Arthroscopy.

[9]  Jill L Cook,et al.  Is there an association between tendinopathy and diabetes mellitus? A systematic review with meta-analysis , 2015, British Journal of Sports Medicine.

[10]  W. Sheu,et al.  The Effect of Diabetes, Hyperlipidemia, and Statins on the Development of Rotator Cuff Disease , 2015, The American journal of sports medicine.

[11]  E. Pimentel,et al.  Structural and biomechanical changes in the Achilles tendon after chronic treatment with statins. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[12]  A. Saripalli,et al.  Simvastatin reduces fibrosis and protects against muscle weakness after massive rotator cuff tear. , 2015, Journal of shoulder and elbow surgery.

[13]  Y. Rhee,et al.  The Influence of Diabetes Mellitus on Clinical and Structural Outcomes After Arthroscopic Rotator Cuff Repair , 2015, The American journal of sports medicine.

[14]  A. Bedi,et al.  Reduced muscle fiber force production and disrupted myofibril architecture in patients with chronic rotator cuff tears. , 2015, Journal of shoulder and elbow surgery.

[15]  N. Maffulli,et al.  Epidemiology of the rotator cuff tears: a new incidence related to thyroid disease. , 2014, Muscles, ligaments and tendons journal.

[16]  Jess G Snedeker,et al.  The role of collagen crosslinks in ageing and diabetes - the good, the bad, and the ugly. , 2014, Muscles, ligaments and tendons journal.

[17]  N. Maffulli,et al.  Thyroid hormones increase collagen I and cartilage oligomeric matrix protein (COMP) expression in vitro human tenocytes. , 2014, Muscles, ligaments and tendons journal.

[18]  G. Boivin,et al.  Biomechanical properties and histology of db/db diabetic mouse Achilles tendon. , 2014, Muscles, ligaments and tendons journal.

[19]  T. Brosh,et al.  Statins Enhance Rotator Cuff Healing by Stimulating the COX2/PGE2/EP4 Pathway , 2014, The American journal of sports medicine.

[20]  Sally R. Hinchliffe,et al.  Comorbidities in rotator cuff disease: a case-control study. , 2014, Journal of shoulder and elbow surgery.

[21]  L. Engebretsen,et al.  Rotator cuff tear degeneration and cell apoptosis in smokers versus nonsmokers. , 2014, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[22]  D. P. Beason,et al.  Rat rotator cuff tendon-to-bone healing properties are adversely affected by hypercholesterolemia. , 2014, Journal of shoulder and elbow surgery.

[23]  Joon Yub Kim,et al.  2013 Neer Award: Effect of the adipose-derived stem cell for the improvement of fatty degeneration and rotator cuff healing in rabbit model. , 2014, Journal of shoulder and elbow surgery.

[24]  T. Davis,et al.  Incidence and predictors of hospitalization for tendon rupture in Type 2 diabetes: the Fremantle Diabetes Study , 2014, Diabetic medicine : a journal of the British Diabetic Association.

[25]  A. Saripalli,et al.  Aging-associated exacerbation in fatty degeneration and infiltration after rotator cuff tear. , 2014, Journal of shoulder and elbow surgery.

[26]  N. Maffulli,et al.  Thyroid hormones and tendon: current views and future perspectives. Concise review. , 2013, Muscles, ligaments and tendons journal.

[27]  L. Galatz,et al.  The effect of unloading on gene expression of healthy and injured rotator cuffs , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  N. Maffulli,et al.  Thyroid hormones enhance growth and counteract apoptosis in human tenocytes isolated from rotator cuff tendons , 2013, Cell Death and Disease.

[29]  Rakesh D. Patel,et al.  The musculoskeletal effects of cigarette smoking. , 2013, The Journal of bone and joint surgery. American volume.

[30]  D. P. Beason,et al.  Hypercholesterolemia increases supraspinatus tendon stiffness and elastic modulus across multiple species. , 2013, Journal of shoulder and elbow surgery.

[31]  J. Snedeker,et al.  Advanced glycation end-products diminish tendon collagen fiber sliding. , 2013, Matrix biology : journal of the International Society for Matrix Biology.

[32]  S. L. Lozano Calderón,et al.  Arthroscopic Rotator Cuff Repair: Impact of Diabetes Mellitus on Patient Outcomes , 2013, The Physician and sportsmedicine.

[33]  L. Nové-Josserand,et al.  Arthroscopic suture-bridge repair for small to medium size supraspinatus tear: healing rate and retear pattern. , 2013, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[34]  Joshua D. Harris,et al.  The Effect of Smoking on Ligament and Cartilage Surgery in the Knee , 2012, The American journal of sports medicine.

[35]  R. Tashjian Epidemiology, natural history, and indications for treatment of rotator cuff tears. , 2012, Clinics in sports medicine.

[36]  L. Sørensen Wound Healing and Infection in Surgery: The Pathophysiological Impact of Smoking, Smoking Cessation, and Nicotine Replacement Therapy A Systematic Review , 2012, Annals of surgery.

[37]  C. Fagnani,et al.  The impact of preoperative smoking habit on rotator cuff tear: cigarette smoking influences rotator cuff tear sizes. , 2012, Journal of shoulder and elbow surgery.

[38]  N. Maffulli,et al.  Calcific Tendinopathy of the Rotator Cuff Tendons , 2011, Sports medicine and arthroscopy review.

[39]  R. Warren,et al.  Diabetes mellitus alters the mechanical properties of the native tendon in an experimental rat model , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[40]  Ana Paula Agostini,et al.  Análise comparativa do resultado da sutura artroscópica da lesão do manguito rotador em pacientes fumantes e não fumantes , 2011 .

[41]  Alexandre Almeida,et al.  COMPARATIVE ANALYSIS ON THE RESULT FOR ARTHROSCOPIC ROTATOR CUFF SUTURE BETWEEN SMOKING AND NON-SMOKING PATIENTS , 2011, Revista brasileira de ortopedia.

[42]  K. Yamaguchi,et al.  Factors Affecting Healing Rates after Arthroscopic Double-Row Rotator Cuff Repair , 2010, The American journal of sports medicine.

[43]  A. Gibofsky,et al.  Musculoskeletal manifestations of thyroid disease. , 2010, Rheumatic diseases clinics of North America.

[44]  E. Itoi,et al.  Alteration of the material properties of the normal supraspinatus tendon by nicotine treatment in a rat model , 2010, Acta orthopaedica.

[45]  R. Warren,et al.  Diabetes mellitus impairs tendon-bone healing after rotator cuff repair. , 2010, Journal of shoulder and elbow surgery.

[46]  R. Warren,et al.  Massive tears of the rotator cuff. , 2010, The Journal of bone and joint surgery. American volume.

[47]  D. Macdonald,et al.  Does diabetes affect outcome after arthroscopic repair of the rotator cuff? , 2010, The Journal of bone and joint surgery. British volume.

[48]  E. Viikari-Juntura,et al.  Lifestyle and metabolic factors in relation to shoulder pain and rotator cuff tendinitis: A population-based study , 2010, BMC musculoskeletal disorders.

[49]  S. Chillag,et al.  Perioperative Management of Diabetes and Hyperglycemia in Patients Undergoing Orthopaedic Surgery , 2010, The Journal of the American Academy of Orthopaedic Surgeons.

[50]  K. Yamaguchi,et al.  Cigarette Smoking Increases the Risk for Rotator Cuff Tears , 2010, Clinical orthopaedics and related research.

[51]  J. Abboud,et al.  The Effect of Hypercholesterolemia on Rotator Cuff Disease , 2010, Clinical orthopaedics and related research.

[52]  S. Namdari,et al.  Range of motion limitation after rotator cuff repair. , 2010, Journal of shoulder and elbow surgery.

[53]  Roger Holder,et al.  Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. , 2010, The American journal of medicine.

[54]  B. Morrey Do Outcomes Differ after Rotator Cuff Repair for Patients Receiving Workers' Compensation? , 2010 .

[55]  Q. Fatima,et al.  Musculoskeletal manifestations of diabetes mellitus. , 2009, Journal of the Indian Medical Association.

[56]  G. Hofmann,et al.  Advanced glycation end products induce cell cycle arrest and proinflammatory changes in osteoarthritic fibroblast-like synovial cells. , 2009, Arthritis research & therapy.

[57]  V. Denaro,et al.  Triglycerides and total serum cholesterol in rotator cuff tears: do they matter? , 2009, British Journal of Sports Medicine.

[58]  G. Melino,et al.  Transglutaminases expression in human supraspinatus tendon ruptures and in mouse tendons. , 2009, Biochemical and biophysical research communications.

[59]  R. Adler,et al.  Prospective analysis of arthroscopic rotator cuff repair: prognostic factors affecting clinical and ultrasound outcome. , 2009, Journal of shoulder and elbow surgery.

[60]  L. Beaupre,et al.  Do Outcomes Differ after Rotator Cuff Repair for Patients Receiving Workers’ Compensation? , 2008, Clinical orthopaedics and related research.

[61]  V. Novack,et al.  Risk factors for idiopathic frozen shoulder. , 2008, The Israel Medical Association journal : IMAJ.

[62]  J. Cook,et al.  Adiposity and tendinopathy , 2008, Disability and rehabilitation.

[63]  T. Trappe,et al.  Collagen, cross-linking, and advanced glycation end products in aging human skeletal muscle. , 2007, Journal of applied physiology.

[64]  M. Fisher,et al.  Prevalence of symptoms and signs of shoulder problems in people with diabetes mellitus. , 2007, Journal of shoulder and elbow surgery.

[65]  Evan L. Flatow,et al.  Fatty Infiltration and Atrophy of the Rotator Cuff do not Improve after Rotator Cuff Repair and Correlate with Poor Functional Outcome , 2007, The American journal of sports medicine.

[66]  M. Cohenford,et al.  Non-enzymatic interactions of glyoxylate with lysine, arginine, and glucosamine: a study of advanced non-enzymatic glycation like compounds. , 2007, Bioorganic chemistry.

[67]  A. Carr,et al.  Calcific tendinitis: natural history and association with endocrine disorders. , 2005, Journal of shoulder and elbow surgery.

[68]  W. Chou,et al.  Surgical results in rotator cuff tears with shoulder stiffness. , 2007, Journal of the Formosan Medical Association = Taiwan yi zhi.

[69]  Matthew J. Silva,et al.  Nicotine delays tendon-to-bone healing in a rat shoulder model. , 2006, The Journal of bone and joint surgery. American volume.

[70]  P. Durrington,et al.  Familial hypercholesterolaemia commonly presents with Achilles tenosynovitis , 2005, Annals of the rheumatic diseases.

[71]  J. Bécue,et al.  Anatomic study of the tendinous rotator cuff of the shoulder , 2006, Surgical and Radiologic Anatomy.

[72]  N. Prasad,et al.  Outcome of open rotator cuff repair. An analysis of risk factors. , 2005, Acta orthopaedica Belgica.

[73]  S. Ling,et al.  A study on the vascular supply of the supraspinatus tendon , 2005, Surgical and Radiologic Anatomy.

[74]  C. Gerber,et al.  Effect of tendon release and delayed repair on the structure of the muscles of the rotator cuff: an experimental study in sheep. , 2004, The Journal of bone and joint surgery. American volume.

[75]  M. Engelgau,et al.  The Evolving Diabetes Burden in the United States , 2004, Annals of Internal Medicine.

[76]  J. Frenette,et al.  Insulin-dependent diabetes impairs the inflammatory response and delays angiogenesis following Achilles tendon injury. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[77]  G. Reddy Cross-Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon , 2004, Experimental diabesity research.

[78]  K. Tanigawa,et al.  Embryonic growth impaired by maternal hypoglycemia during early organogenesis in normal and diabetic rats , 1994, Acta Diabetologica.

[79]  T. Hughes,et al.  Advanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics. , 2004, Analytical biochemistry.

[80]  L. Józsa,et al.  The pathogenesis of tendolipomatosis; an electron microscopical study , 2004, International Orthopaedics.

[81]  J. Bassett,et al.  Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions , 2003, Molecular and Cellular Endocrinology.

[82]  P. Gleyze,et al.  Influence of cuff muscle fatty degeneration on anatomic and functional outcomes after simple suture of full-thickness tears. , 2003, Journal of shoulder and elbow surgery.

[83]  Masato Nakamura,et al.  Vascular endothelial growth factor 121 and 165 in the subacromial bursa are involved in shoulder joint contracture in type II diabetics with rotator cuff disease , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[84]  J. Zuckerman,et al.  Rotator cuff repair in patients with type I diabetes mellitus. , 2003, Journal of shoulder and elbow surgery.

[85]  M. Serdar,et al.  Is high concentration of serum lipids a risk factor for Achilles tendon rupture? , 2003, Clinica chimica acta; international journal of clinical chemistry.

[86]  J. Samarut,et al.  Thyroid hormone receptors: lessons from knockout and knock-in mutant mice , 2003, Trends in Endocrinology & Metabolism.

[87]  Guy Trudel,et al.  Early reattachment does not reverse atrophy and fat accumulation of the supraspinatus—an experimental study in rabbits , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[88]  L. Bigliani,et al.  Infection after mini-open rotator cuff repair. , 2002, Journal of shoulder and elbow surgery.

[89]  I. Björkhem,et al.  Mechanism of Accumulation of Cholesterol and Cholestanol in Tendons and the Role of Sterol 27-hydroxylase (CYP27A1) , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[90]  D. Nathan,et al.  Musculoskeletal disorders of the hand and shoulder in patients with diabetes mellitus. , 2002, The American journal of medicine.

[91]  H. Uhthoff,et al.  Delayed tendon reattachment does not reverse atrophy and fat accumulation of the supraspinatus — an experimental study in rabbits , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[92]  S. Karaahmetoğlu,et al.  Thickness of the supraspinatus and biceps tendons in diabetic patients. , 2002, Diabetes care.

[93]  P. Yen,et al.  Physiological and molecular basis of thyroid hormone action. , 2001, Physiological reviews.

[94]  J. Deisenhofer,et al.  Structural Mechanism for Statin Inhibition of HMG-CoA Reductase , 2001, Science.

[95]  J. E. Hale,et al.  Alterations of Cartilage and Collagen Expression during Fracture Healing in Experimental Diabetes , 2000, Connective tissue research.

[96]  M. Balci,et al.  Shoulder adhesive capsulitis and shoulder range of motion in type II diabetes mellitus: association with diabetic complications. , 1999, Journal of diabetes and its complications.

[97]  L. Jørgensen,et al.  Less collagen production in smokers. , 1998, Surgery.

[98]  A. Vinik,et al.  Electron microscopic investigation of the effects of diabetes mellitus on the Achilles tendon. , 1997, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[99]  K H Jungbluth,et al.  [Rotator cuff rupture. Vascular supply and collagen fiber processes as pathogenetic factors]. , 1997, Unfallchirurgie.

[100]  F. Blevins,et al.  Biology of the rotator cuff tendon. , 1997, The Orthopedic clinics of North America.

[101]  W. Knopp,et al.  Hypothyroidism presenting as tendinitis. , 1997, The Physician and sportsmedicine.

[102]  J. Viikari,et al.  Shoulder capsulitis in type I and II diabetic patients: association with diabetic complications and related diseases. , 1996, Annals of the Rheumatic Diseases.

[103]  J. Viikari,et al.  Limited Joint Mobility is Associated with the Presence but Does Not Predict the Development of Microvascular Complications in Type 1 Diabetes , 1996, Diabetic medicine : a journal of the British Diabetic Association.

[104]  J. Bernhagen,et al.  An agent cleaving glucose-derived protein crosslinks in vitro and in vivo , 1996, Nature.

[105]  W. Hutton,et al.  Nicotine on the Revascularization of Bone Graft: An Experimental Study in Rabbits , 1994, Spine.

[106]  R. Spanheimer,et al.  Correlation between decreased collagen production in diabetic animals and in cells exposed to diabetic serum: response to insulin. , 1992, Matrix.

[107]  Ling Sc,et al.  A study on the vascular supply of the supraspinatus tendon. , 1990 .

[108]  M. Mavrikakis,et al.  Calcific shoulder periarthritis (tendinitis) in adult onset diabetes mellitus: a controlled study. , 1989, Annals of the rheumatic diseases.

[109]  M. Marsh,et al.  Abnormalities of Granulation Tissue and Collagen Formation in Experimental Diabetes, Uraemia and Malnutrition , 1986, Diabetic medicine : a journal of the British Diabetic Association.

[110]  R. Ross,et al.  Studies of Hypercholesterolemia in the Nonhuman Primate: I. Changes that Lead to Fatty Streak Formation , 1984, Arteriosclerosis.

[111]  D. Daly,et al.  Carpal-tunnel syndrome associated with myxedema. , 1961, Archives of internal medicine.