Increased muscle mass with myostatin deficiency improves gains in bone strength

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J Bone Miner Res. 2006 Mar;21(3):477-83.

Increased muscle mass with myostatin deficiency improves gains in

bone strength with exercise.

Hamrick MW, Samaddar T, Pennington C, McCormick J.

Department of Cellular Biology and Anatomy Medical College of

Georgia, Augusta, Georgia, USA.

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.

INTRODUCTION: 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.

MATERIALS AND 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.