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Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury.

Sandberg O, Eliasson P, Andersson T, Agholme F, Aspenberg P - Acta Orthop (2012)

Bottom Line: Likewise, screw pull-out force was not significantly influenced.More than 25% decrease or 18% increase could be excluded with 95% confidence.Etanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

View Article: PubMed Central - PubMed

Affiliation: Orthopedics Division, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden. olof.sandberg@liu.se

ABSTRACT

Background and purpose: Should blockade of TNF-α be avoided after orthopedic surgery? Healing of injuries in soft tissues and bone starts with a brief inflammatory phase. Modulation of inflammatory signaling might therefore interfere with healing. For example, Cox inhibitors impair healing in animal models of tendon, ligament, and bone injury, as well as in fracture patients. TNF-α is expressed locally at increased levels during early healing of these tissues. We therefore investigated whether blocking of TNF-α with etanercept influences the healing process in established rat models of injury of tendons and metaphyseal bone.

Methods: Rats were injected with etanercept, 3.5 mg/kg 3 times a week. Healing of transected Achilles tendons and bone healing around screws implanted in the tibial metaphysis were estimated by mechanical testing. Tendons were allowed to heal either with or without mechanical loading. Ectopic bone induction following intramuscular BMP-2 implants has previously been shown to be stimulated by etanercept in rodents. This was now tested as a positive control.

Results: Tendon peak force after 10 days was not significantly influenced by etanercept. Changes exceeding 29% could be excluded with 95% confidence. Likewise, screw pull-out force was not significantly influenced. More than 25% decrease or 18% increase could be excluded with 95% confidence. However, etanercept treatment increased the amount of bone induced by intramuscular BMP-2 implants, as estimated by blind histological scoring.

Interpretation: Etanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

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Related in: MedlinePlus

Ossicles induced by BMP-2 in a collagen scaffold. Row A: control. Row B: continuously etanercept-treated. Column I: raw image. Column II: low threshold (ossicle size). Column III: high threshold (estimate of bone density).
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Figure 3: Ossicles induced by BMP-2 in a collagen scaffold. Row A: control. Row B: continuously etanercept-treated. Column I: raw image. Column II: low threshold (ossicle size). Column III: high threshold (estimate of bone density).

Mentions: The total area of the formed ossicle on the radiographs was not significantly different in the 3 treatment groups, as shown by one-way ANOVA (p = 0.06) (Figure 3). Therefore, to increase power, the etanercept groups were pooled and compared with the controls by a t-test, which showed a larger total area with etanercept treatment, compared to the controls (p = 0.02) (Figure 4 and Table 3). However, no statistically significant effect was seen on the amount of bone within the ossicle, as estimated by radiodensity with a higher threshold (Figure 3 and Table 3).


Etanercept does not impair healing in rat models of tendon or metaphyseal bone injury.

Sandberg O, Eliasson P, Andersson T, Agholme F, Aspenberg P - Acta Orthop (2012)

Ossicles induced by BMP-2 in a collagen scaffold. Row A: control. Row B: continuously etanercept-treated. Column I: raw image. Column II: low threshold (ossicle size). Column III: high threshold (estimate of bone density).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369160&req=5

Figure 3: Ossicles induced by BMP-2 in a collagen scaffold. Row A: control. Row B: continuously etanercept-treated. Column I: raw image. Column II: low threshold (ossicle size). Column III: high threshold (estimate of bone density).
Mentions: The total area of the formed ossicle on the radiographs was not significantly different in the 3 treatment groups, as shown by one-way ANOVA (p = 0.06) (Figure 3). Therefore, to increase power, the etanercept groups were pooled and compared with the controls by a t-test, which showed a larger total area with etanercept treatment, compared to the controls (p = 0.02) (Figure 4 and Table 3). However, no statistically significant effect was seen on the amount of bone within the ossicle, as estimated by radiodensity with a higher threshold (Figure 3 and Table 3).

Bottom Line: Likewise, screw pull-out force was not significantly influenced.More than 25% decrease or 18% increase could be excluded with 95% confidence.Etanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

View Article: PubMed Central - PubMed

Affiliation: Orthopedics Division, Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden. olof.sandberg@liu.se

ABSTRACT

Background and purpose: Should blockade of TNF-α be avoided after orthopedic surgery? Healing of injuries in soft tissues and bone starts with a brief inflammatory phase. Modulation of inflammatory signaling might therefore interfere with healing. For example, Cox inhibitors impair healing in animal models of tendon, ligament, and bone injury, as well as in fracture patients. TNF-α is expressed locally at increased levels during early healing of these tissues. We therefore investigated whether blocking of TNF-α with etanercept influences the healing process in established rat models of injury of tendons and metaphyseal bone.

Methods: Rats were injected with etanercept, 3.5 mg/kg 3 times a week. Healing of transected Achilles tendons and bone healing around screws implanted in the tibial metaphysis were estimated by mechanical testing. Tendons were allowed to heal either with or without mechanical loading. Ectopic bone induction following intramuscular BMP-2 implants has previously been shown to be stimulated by etanercept in rodents. This was now tested as a positive control.

Results: Tendon peak force after 10 days was not significantly influenced by etanercept. Changes exceeding 29% could be excluded with 95% confidence. Likewise, screw pull-out force was not significantly influenced. More than 25% decrease or 18% increase could be excluded with 95% confidence. However, etanercept treatment increased the amount of bone induced by intramuscular BMP-2 implants, as estimated by blind histological scoring.

Interpretation: Etanercept does not appear to impair tendon or metaphyseal bone healing to any substantial degree.

Show MeSH
Related in: MedlinePlus