Disuse muscle atrophy inhibited by nutritional supplement

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During periods of immobilization and restricted activity, muscles atrophy as a result of increased myostatin. Myostatin is a protein that triggers muscle breakdown and hinders muscle protein synthesis and muscle cell differentiation.¹ This phenomenon especially reveals itself during the requisite 8 to 12 weeks of postsurgical “down time” following repair of cranial cruciate ligament (CCL) rupture, the most common stifle injury in medium- and large-breed dogs.²

The commercial supplement Fortetropin (MYOS Rens Technology), a freeze-dried, fertilized chicken egg yolk product, reduces myostatin. Human studies have shown that Fortetropin abates serum myostatin levels by 18% to 22% and increases muscle thickness and lean body mass; Fortetropin has similar effects on serum myostatin in rats.³ In both healthy dogs and golden retrievers with muscular dystrophy, reduction of serum myostatin boosts muscle mass.⁴

In a prospective, double-blinded study,_⁵ researchers at Kansas State University’s Veterinary Health Center investigated the effects of Fortetropin supplementation on disuse muscle atrophy. A total of 100 client-owned dogs with naturally occurring CCL ruptures were randomized into two groups: a Fortetropin treatment group and a placebo-control group.

All dogs in the study weighed between about 39 and 165 lb (18-75 kg); had a diagnosis of naturally occurring CCL rupture; had no surgical correction of the contralateral CCL within the six months prior to enrollment; and had no concurrent disease.

One-third of the enrolled dogs were purebred or mixed Labrador retrievers. Golden retrievers, boxers, Rottweilers, American bulldogs and American Staffordshire terriers were also highly represented. Seventy-one of the dogs were female and 29 were male; the average age was 5.5 years. Bilateral CCL ruptures were present in 16 dogs.

Study methods

Each patient underwent tibial plateau leveling osteotomy (TPLO), the most common surgical repair technique for CCL rupture.⁶ The Fortetropin group, composed of 52 dogs, was dosed at 300 mg/kg of the powdered supplement mixed with canned food once daily for 12 weeks. The placebo group, made up of 48 dogs, received a cheese powder.

The following assessments were performed preoperatively on each dog, and then at 8 and 12 weeks postoperatively:

• Thigh circumference, measured with a retractable tape measure at the midpoint of the femur for both the affected and unaffected legs
• Muscle thickness, assessed by B-mode ultrasonography cranial and lateral to the mid-femur of both the affected and contralateral hindlimbs; and dorsal to ventral transverse thickness of the epaxial muscles at the level of the 13th rib for both the affected and unaffected sides
• Stance analysis, or the percentage body weight placed on each limb at a static stance
• Serum myostatin measurement

Some dogs did not finish all evaluations. Complete data sets were obtained for 77 dogs for muscle measurements and stance analysis, and for 69 dogs for serum myostatin measurement.

Dogs that received Fortetropin experienced no significant change in thigh circumference for either hindlimb over any time periods, while dogs receiving placebo had a significant reduction from weeks 0 to 8. For ultrasound muscle measurements, however, there was a significant decrease in the Fortetropin group from weeks 0 to 8, but not from weeks 8 to 12 or weeks 0 to 12. Dogs given placebo had no significant changes in muscle thickness over any time periods.

Stance analysis for the Fortetropin group showed a 7.0% climb in weight supported by the affected hindlimb from weeks 0 to 12, compared with 4.9% for the placebo group. The corresponding drop in weight supported by the contralateral hindlimb from weeks 0 to 12 was 6.5% for the dogs receiving Fortetropin, compared with 5.8% for the placebo group.

Serum myostatin levels did not change significantly over any time period (0-8, 8-12 and 0-12 weeks) in the Fortetropin group. But in the placebo group, serum myostatin rose significantly from weeks 0 to 8, although not from weeks 8 to 12 or 0 to 12.

Study conclusions

The addition of Fortetropin to the diet following TPLO surgery seemed to have a protective effect on thigh circumference compared with placebo, yet this benefit was not substantiated in the ultrasound measurements of muscle thickness. These measurements dropped significantly from weeks 0 to 8 in the Fortetropin group, and insignificantly in the placebo group. Investigators attributed this contradiction to inconsistency in the personnel performing the ultrasonographic measurements and to differing degrees of transducer force applied by the examiners. They also raised the possibility that thigh circumference measurements may have been impacted by variations in hair coat thickness and postoperative hair regrowth rates.

Nonetheless, compared with placebo, Fortetropin supplementation appeared to hasten weight-bearing capacity for the affected limb. Serum myostatin increased significantly in the placebo group during the period of exercise restriction but did not change significantly in the Fortetropin group. Preventing a rise in serum myostatin during periods of exercise restriction is key to curtailing disuse atrophy.

Fortetropin is an established agent for increasing lean body mass and cutting myostatin levels in people.³ But for dogs undergoing orthopedic surgery, the study described herein is the first published report on the protective effect of Fortetropin. When comparing Fortetropin with placebo administered during the postoperative exercise-restricted period, Fortetropin seems to prevent rise in myostatin and corresponding loss of muscle mass.

Dr. Capuzzi is a small animal veterinarian and journalist based in the Philadelphia area.

References

1. Elliott B, Renshaw D, Getting S, et al. The central role of myostatin in skeletal muscle and whole body homeostasis. Acta Physiol (Oxf). 2012;205(3):324–40.

2. Johnston S, Tobias K. Veterinary Surgery: Small Animal Expert Consult, 2nd ed. Saunders; 2017.

3. Sharp MH, Lowery RP, Mobley CB, et al. The effects of Fortetropin supplementation on body composition, strength, and power in humans and mechanism of action in a rodent model. J Am Coll Nutr. 2016;35(8):679-691.

4. Freeman LM, Rush JE, Cunningham SM, et al. Pilot study of a myostatin antagonist in dogs with cardiac cachexia. J Vet Cardiol. 2015;17(3):210-215.

5. White DA, Harkin KR, Roush JK, et al. Fortetropin inhibits disuse muscle atrophy in dogs after tibial plateau leveling osteotomy. PLOS One. 2020;15(4).

6. Reif U, Hulse DA, Hauptman JG. Effect of tibial plateau leveling on stability of the canine cranial cruciate-deficient stifle joint: an in vitro study. Vet Surg. 2002;31(2):147-154.