Connective Tissue Response to Immobility

Connective Tissue Response to Immobility: Correlative Study of Biomechanical and Biochemical Measurements of Normal and Immobilized Rabbit Knees

Arthritis and Rheumatism

May-June 1975; Vol. 18, No. 3; pp. 257-264

Savio Woo, John Matthews, Wayne Akeson, David Amiel, Richard Convery: from the University of California, San Diego, Division of Orthopedics and Rehabilitation.

The authors documented the biomechanical changes in 20 rabbit knees after 9 weeks of immobilization and compared them to the opposite knee that was not immobilized.

These tissue changes from immobilization are the problem as they affect the repair responses to trauma. [Important]

GAG = glycosaminoglycan: mucopolysaccharides that attract water to function as lubricants and shock absorbers.

Proteoglycans: a protein-sugar matrix that fills in the spaces of connective tissue.

KEY POINTS FROM THIS ARTICLE:

1) There is significant knee contracture after 9 weeks of immobilization.

2) This study shows that fibrous connective tissue loses significant amounts of glycosaminoglycan (GAG) and water after periods of immobilization.

• “The biochemical results indicate that in the contracture joint, periarticular connective tissue loses a significant amount of water and glycosaminoglycan.”
• “Loss of these components was relatively uniform in tendon, capsule, ligament, and fascia.”
• The loss of total GAG correlates significantly with joint stiffness. [Important]
  • The stiffness was mainly due to changes in knee ligaments and capsules.
• The loss of glycosaminoglycans in immobilized joints correlated significantly with reduced motion.
• There was a 20% reduction in collagen on the immobilized side: “statistically, this reduction is highly significant.” [Important]

3) All connective tissues distend easily with very little stress because its collagen fibers are not straight in the relaxed state but are loosely oriented in various directions.

• “With higher applied stress, collagen fibers begin to align in the direction of load and to straighten.”

4) “Newly synthesized collagen, although less in quantity, is laid down haphazardly and thus interferes with joint mechanics.” [Key Point]

• “[The] loss of GAG may permit crosslinking between existing collagen fibers.”

5) “Physical forces of stress and motion modulate synthesis of proteoglycans and collagen in normal joints by fibroblasts.”

• “The proteoglycans, which loosely bind and entrap water, lubricate the connective tissue fiber interface and minimize the number of anomalous cross-linkings of fibers by maintaining a critical inter-fiber distance.”
• “Flexibility is preserved, the joint moves easily, and the applied physical forces further stimulate cellular synthesis.”
• “At the same time, stress and motion influence the disposition of newly synthesized collagen fibers in such a manner as to resist tensile stresses.”
• “Furthermore, motion of fiber precludes the development of anomalous crosslinks.” [Important]

6) Motion of the connective tissue matrix inhibit the contracture process through these mechanisms:

• Stimulation of proteoglycan synthesis, thereby lubricating and maintaining a critical distance between existing fibers.
• “Ordering (rather than randomizing) the disposition of new collagen fibers so as to resist tensile stresses.”
• “Prevention of anomalous cross-links in the matrix.”

7) During healing, inflammation and scar formation must be avoided.

COMMENTS FROM DAN MURPHY:

The healing of injured soft tissues requires early and persistent controlled motion into the damaged tissues. Immobilization results in “haphazard” healing with an increase in “anomalous” cross-links. This results in long-term alterations in joint biomechanical function and residual weaknesses to future loads.

This study supports these articles we have reviewed on related topics:

Article Review 9-00:
Immobilization or Early Mobilization After an Acute Soft-Tissue Injury?

Article Review 36-04:
Acute Soft Tissue Injuries-A Review of the Literature

Article Review 23-13:
A Theoretical Basis for Maintenance Spinal Manipulative Therapy for the Chiropractic Profession

Article Review 18-14
Ligament Injury and Healing:

Article Review 25-16:
Findings and Outcome in Whiplash-Type Neck Distortions

Article Review 50-21:
Injury and Repair of Ligaments and Tendons

When this study was conducted at the University of California, San Diego, I was an undergraduate student there, majoring in biochemistry.