Increased muscle mass with myostatin deficiency improves gains in bone strength with exercise.
We tested the hypothesis that increased muscle mass augments increases in bone strength normally observed with exercise. Myostatin-deficient mice, which show increased muscle mass, were exercised along with wildtype mice. Results indicate that increases in bone strength with exercise are greater in myostatin-deficient mice than in wildtype mice, suggesting that the combination of increased muscle mass and physical activity has a greater effect on bone strength than either increased muscle mass or intense exercise alone.


BACKGROUND
Muscle (lean) mass is known to be a significant predictor of peak BMD in young people, and exercise is also found to increase bone mass in growing humans and laboratory animals. We sought to determine if increased muscle mass resulting from myostatin deficiency would enhance gains in bone strength that usually accompany exercise.


METHODS
Male mice lacking myostatin (GDF-8) were used as an animal model showing increased muscle mass. Wildtype and myostatin-deficient mice (n = 10-12 per genotype) were exercised on a treadmill for 30 minutes/day, 5 days/week, for 4 weeks starting at 12 weeks of age. Caged wildtype and myostatin-deficient mice (n = 10-12 per genotype) were included as sedentary controls. Structural and biomechanical parameters were measured from the radius.


RESULTS
Ultimate force (F(u)), displacement (D(u)), toughness (energy-to-fracture; U), and ultimate strain (epsilon(u)) increased significantly with exercise in myostatin-deficient mice but not in normal mice. When F(u) is normalized by body mass, exercised myostatin-deficient mice show an increase in relative bone strength of 30% compared with caged controls, whereas exercised wildtype mice do not show a significant increase in ultimate force relative to caged controls. Relative to body weight, the radii of exercised myostatin-deficient mice are >25% stronger than those of exercised normal mice.


CONCLUSIONS
Increased muscle mass resulting from inhibition of myostatin function improves the positive effects of exercise on bone strength.
Hamrick
Mark W
MW
Department of Cellular Biology and Anatomy Medical College of Georgia, Augusta, Georgia 30912, USA. mhamrick@mail.mcg.edu
Samaddar
Ted
T
Pennington
Catherine
C
McCormick
John
J
D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D005080:Exercise Test; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D055435:Myostatin; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011859:Radiography; D011884:Radius / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta