title: Tendon collagen synthesis declines with immobilization in elderly humans: no effect of anti-inflammatory medication.
abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used as pain killers during periods of unloading caused by traumatic occurrences or diseases. However, it is unknown how tendon protein turnover and mechanical properties respond to unloading and subsequent reloading in elderly humans, and whether NSAID treatment would affect the tendon adaptations during such periods. Thus we studied human patellar tendon protein synthesis and mechanical properties during immobilization and subsequent rehabilitating resistance training and the influence of NSAIDs upon these parameters. Nineteen men (range 60-80 yr) were randomly assigned to NSAIDs (ibuprofen 1,200 mg/day; Ibu) or placebo (Plc). One lower limb was immobilized in a cast for 2 wk and retrained for 6 wk. Tendon collagen protein synthesis, mechanical properties, size, expression of genes related to collagen turnover and remodeling, and signal intensity (from magnetic resonance imaging) were investigated. Tendon collagen synthesis decreased (P < 0.001), whereas tendon mechanical properties and size were generally unchanged with immobilization, and NSAIDs did not influence this. Matrix metalloproteinase-2 mRNA tended to increase (P < 0.1) after immobilization in both groups, whereas scleraxis mRNA decreased with inactivity in the Plc group only (P < 0.05). In elderly human tendons, collagen protein synthesis decreased after 2 wk of immobilization, whereas tendon stiffness and modulus were only marginally reduced, and NSAIDs had no influence upon this. This indicates an importance of mechanical loading for maintenance of tendon collagen turnover. However, reduced collagen production induced by short-term unloading may only marginally affect tendon mechanical properties in elderly individuals.
  In elderly humans, 2 wk of inactivity reduces tendon collagen protein synthesis, while tendon stiffness and modulus are only marginally reduced, and NSAID treatment does not affect this. This indicates that mechanical loading is important for maintenance of tendon collagen turnover and that changes in collagen turnover induced by short-term immobilization may only have minor impact on the internal structures that are essential for mechanical properties in elderly tendons.
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; kasperjuel@hotmail.com.
authors.forename: Kasper
authors.initials: K
authors.lastname: Dideriksen
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Anders P
authors.initials: AP
authors.lastname: Boesen
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.|Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; and.
authors.forename: Søren
authors.initials: S
authors.lastname: Reitelseder
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.|Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Couppé
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Rene
authors.initials: R
authors.lastname: Svensson
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0001-7138-3211
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.|Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit, Bispebjerg Hospital, Denmark.
authors.forename: S Peter
authors.initials: SP
authors.lastname: Magnusson
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.|Institute of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; and.
authors.forename: Lars
authors.initials: L
authors.lastname: Holm
authors.affiliation: Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Kjaer
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003094:Collagen / Q000096:biosynthesis* / Q000378:metabolism*; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use; D007103:Immobilization / Q000379:methods; D035002:Lower Extremity / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D055070:Resistance Training / Q000379:methods; D013710:Tendons / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D012333:RNA, Messenger; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D007052:Ibuprofen
keywords: ibuprofen; scleraxis; tendon mechanical properties; tendon reloading; tendon unloading