NSAIDs

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NSAIDs Musculoskeletal Injuries?

• Major Crystal Hnatko, USAF, MC
• Spangdahlem AFB, Germany

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Objectives

• When to use NSAIDs ?
• When NOT to use NSAIDs?
• Food for Thought
• Should NSAIDs be common place in the treatment of
  musculoskeletal injuries?
• What duration of treatment?
• 
  
• 
  COX2s

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NSAIDs

• Analgesic properties
• Anti-Inflammatory properties
• Proven efficacy in inflammatory arthropathies
• -Why wouldnt we use them in musculoskeletal
  injuries?

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Biomechanical Call for Help
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Biochemical Call For Help
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Initial Tissue Response to Injury

• Inflammatory Phase
• Arachidonic acid cascade
• ? PGs, cytokines, growth factors
• ? influx of inflammatory cells
• ? Sensitize nocioceptors PAIN
• ? Vascular effects SWELLING
• CLEAN UP!

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Tissue Response to Injury

• Inflammatory/Destruction phase
• -- Clean up
• Proliferative/Repair/Resorption phase
• New extracellular matrix being formed
• Maturation/Remodeling/Formation phase
• Functional tissue created
• Can take up to 1 year

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The NSAID/Injury Controversy

• If Inflammation is part of healing
• How do NSAIDs impact tissue level healing?

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Pro-NSAID Group

• Reduces the secondary tissue damage from
  excessive inflammation
• Less pain/inflammation
• leads to early remobilization
• reducing disuse-related physiological changes
• Allows earlier resumption of normal activity
• Effective in other muscskeletal d/os
• RA, OA, gouty arthropathies etc.

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NSAID Skeptics

• Without inflammation tissue healing is bound to
  be impaired
• Masking the bodys natural alarm system
• Early return risks re-injury
• Alternatives analgesics are readily available
• Other side effects make NSAIDs risky in many
  populations

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Who do you believe?What is the evidence?
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Musculoskeletal Injuries

• Bone
• Fractures
• Ligament
• Ankle sprain
• Muscle
• Acute/chronic strain, contusion, eccentric injury
• Tendon
• Tendinopathies

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FRACTURES
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Bone NSAIDs--Fractures--

• Animal studies
• Delayed healing and increased non-union
• Human studies
• Suggest negative impact on fracture healing
• Impact most pronounced in early stages
• Studies of various quality
• No evidence exists in regards to stress fractures

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Bone NSAIDs --C Recommendation--

• Fractures
• Judicious use of NSAIDs
• Especially if risk for non-union
• Especially in 1st two weeks

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Ligaments NSAIDs --Sprains--

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Ligaments NSAIDs --Sprains--

• Animal studies
• variable findings among animal models
• Human studies
• Primarily ankle sprain

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Ligaments NSAIDs --Ankle Sprains--

• Randomized controlled trial - 1997
• Outcome
• Effective at decreasing pain
• Allowed a faster return to duty (5.7days)
• Other observations Treatment arm
• Greater joint instability
• More swelling
• Less ROM

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Ligament NSAIDs--B Recommendation--

• Ankle Sprain
• Short course NSAIDs (3-7 days)
• Analgesic benefit
• Return to function sooner
• Return to full duty sooner!!

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Muscle NSAIDs
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Muscle NSAIDs--Acute Strain--

• Sparse literature
• Conflicting outcomes in human and animal studies
• No conclusions can be drawn
• Clinical Judgment

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Muscle NSAIDs--Chronic Injury--

• Evidence suggests a compromise of the structure
  function
• Paradoxical late impairment
• Studies are dated limited quality
• Consideration of adverse systemic side effects
  with chronic use
• RiskgtgtBenefits

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Muscle NSAIDs --Heterotopic Ossification--

• Post Operative
• Decrease ectopic bone formation
• Muscle Contusion
• Decrease myositis ossificans

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Muscle NSAIDs--Eccentric Injuries--

• Delayed Onset Muscle Soreness
• Running down hill
• Negative Repetitions
• Conflicting results animal human studies
• No conclusions can be drawn
• Clinical Judgment

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Muscle NSAIDs

• --A Recommendations--
• Heterotopic Ossification gt 7 days
• High Risk Contusions
• --C Recommendations--
• Acute Strain 3 to 7 days
• Chronic Strain Not Recommended
• Eccentric Injury 3 to 7 days

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Tendons NSAIDS

• 
  

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Tendon NSAIDs

• Tendon Rupture
• Surgical treatment
• Same 3 phases of tissue response
• Tendonopathy
• TendonITIS or TendonOSIS (histological dx)
• No traditional inflammatory cells
• acute tendonopathy or failed healing response

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Tendon NSAIDs-- Tendonopathy--

• Animal studies
• Suggest variable effects
• Accelerate cross-link collagen fiber
• Human studies
• Demonstrate possible benefit
• Small and short duration trials
• ? delaying definitive healing

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Tendon NSAIDsB Recommendations

• Achilles TendonOPATHY
• Consider 3-7 day course
• Analgesic benefits
• PatelloFemoral Syndrome
• Consider short course
• Inconclusive for/against

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Tendon NSAIDsB Recommendations

• Lateral Elbow Pain
• Some support for topical
• Inconclusive for/against oral
• Rotator Cuff d/os
• Prescribe NSAIDS with caution
• Simple analgesic alternatives

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Safety Considerations--Patients at risk--
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Safety Considerations

• AHA Guidelines
• Avoid NSAIDs in all pts at risk for
  Cardiovascular disease
• (Tylenol ? ASA ? tramadol ? opiods ? salsalate
• Then NSAID (naprosyn). Then Cox II).
• FDA advises use the drugs at the lowest
  effective dose and for the shortest possible
  time.

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Safety Considerations

• Minimize Cardiovascular Risk
• Naproxen
• Minimize Renal Dysfunction
• Celecoxib
• Minimize GI Side Effects
• COX2
• Non specific PPI

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Other Safety Considerations

• Prolonged Bleeding Time
• Hepatic and Bone Marrow toxicity
• Hypersensitivity Reaction (SCARs)

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Summary
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Review

• When to use NSAIDs?
• When NOT to use NSAIDs?
  
• 
  

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When to use NSAIDs

• Acute Ankle Sprain 3 to 7 days
• Prevent Heterotopic Ossification
• High Risk Contusions gt 7 days
• Achilles Tendonopathy 3 to 7 days

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When not to use NSAIDs

• Fracture _at_ risk for non-union
• Especially the 1st two weeks
• (No data re stress fractures)
• Chronic Muscle Strains
• Risks outweigh benefits

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When to consider an NSAID

• Acute Muscle Strain
• Eccentric Muscle Injury
• PatelloFemoral Syndrome
• Other Musculoskeletal d/os
• All short course 3-7 days suggested
• Primarily for analgesic benefit
• Inconclusive evidence

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Summary of Evidence
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Food for thought?

• Should NSAIDs be common place in the treatment of
  musculoskeletal injuries?
• What duration of treatment?
• 3-7 days??
• FDA boxed warning Use the lowest effective
  dose for the shortest duration of time

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Questions?
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General References

• Buckwalter J. Pharmacological Treatment of
  Soft-Tissue Injuries. J Bone Joint Surg 1995
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• Hertal J. The Role of Nonsteroidal
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  Treatment of Acute Soft Tissue Injuries. J Athl
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• Mehallo C, Drezner J, Bytomski J. Practical
  Management Nonsteroidal Anti-inflammatory Drug
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• Pearsall A, Kovaleski. Update on COX-2 Inhibitors
  and Non-Selective NSAIDS Safety and Patient
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• Radi Z, Khan N. Effects of Cyclooxygenase
  Inhibition on Bone, Tendon, and Ligament Healing.
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• Stanley K, Weaver J. Pharmacologic Management of
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• Stovitz S, Johnson R. NSAIDs and Musculoskeletal
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• Warden S. Cyclo-oxygenase-2 inhibitors
  Beneficial or Detrimental for Athletes with Acute
  Musculoskeletal Injuries. Sport Med 2005
  35271-83.

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Bone References

• Ankarath S, Raman R, Giammoudis V. Nonsteroidal
  Anti-inflammatory Drugs in Orthopaedic Practice
  An Update. Current Orthop 2003 17 144-149.
• Harder A, Yuehuei H. The Mechanisms of the
  Inhibitory Effects of Nonsteroidal
  Anti-Inflammatory Drugs on Healing A Concise
  Review. J Clin Pharmacol. 200343807-15
• Murnaghan M, Li G, Marsh D. Nonsteroidal
  Anti-inflammatory Drug-induced Fracture Nonunion
  An Inhibition of Angiogenesis? J Bone Joint Surg
  Am 2006 88-A (S3)140-7.
• Simon A, OConnor P. Dose and Tims-Dependant
  Effects of Cyclooxygenase-2 Inhibition on
  Fracture-Healing. J Bone Joint Surg. 2007
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• Vuolteenaho K, Moilanen T, Moilanen E.
  Non-Steroidal Anti-Inflammatory Drugs,
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  Basic Clin Pharmacol Tox. 2007 10210-14.

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Ligament References

• Hanson C, Weinhold O, Afshari H, Dahners. Am J
  Sports Med. The Effects of Analgesic Agents on
  the Healing Rat Medial Collateral Ligament.
  200533674-9.
• Institute for Clinical Systems Improvement
  (ICSI). Ankle Sprain. Bloomington (MN)
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• Slatyer M, Hensley M, Lopert R. A Randomized
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• Warden S, Avin K, Yeck E DeWolf M, Hagemeier,
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  Accelerates and a Nonsteroidal Anti-inflammatory
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Muscle References

• Mishra D, Friden J, Schmitz M, Lieber R.
  Anti-inflammatory Medication after Muscle Injury.
  A Treatment Resulting in Short-term Improvement
  but Subsequent Loss of Muscle Function. J Bone
  Joint Surg. 1995 77-A(10) 1510-1519.
• Orchard J, Best T. The Management of Muscle
  Strain Injuries An Early Return versus the Risk
  of Recurrence. Clin J Sport Med. 2002 123-5.
• Rahusen F, Weinhold P, Almekinders L.
  Nonsteroidal Anti-inflammatory Drugs and
  Acetaminophen in the Treatment of an Acute Muscle
  Injury. Am J Sports Med 2004 321856-59.

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Tendon References

• Almekinders L, Temple J. Etiology, diagnosis, and
  treatment of tendonitis an analysis of the
  literature. Med Sci Sports Exerc. 1998
  301183-1190.
• Green s, Buchbinder R, Barnsley L, Hall S, White
  M, SmidtN, Assendelft W. Non-steroidal
  anti-inflammatory drugs for treating lateral
  elbow pain in adults. Cochrane Database of Syst
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• Magra M, Maffulli N. Nonsteroidal
  Anti-inflammatory Drugs in Tendinopathy Friend
  or Foe? Clin J Sport Med. 2006 16815-8.
• Mazzone M, Mccue T. Common Conditions of the
  Achilles Tendon. Am Fam Phys. 2002 651805-1810.
• McLauchlan G, Handoll H. Interventions for
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• New Zealand Guidelines (NZGG). The diagnosis and
  management of soft tissue shoulder injuries and
  related disorders. Wellington (NZ) NZGG 2004.
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• Sharma P, Maffulli N. Tendon Injury and
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• Warden S. Brukner P. Patellar Tendinopathy. Clin
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