
ABSTRACT
It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that ex-tremely low-magnitude (<10 microstrain) mechanical signals readily stimulate bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control ( 97%). Disuse alone reduced BFR ( 92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing( 61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized
BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.-Rubin, C., Xu, G., Judex, S. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical
MATERIALS AND METHODS
Experimental design Adult female Sprague-Dawley rats (6- to 8-month-old retired breeders, Charles River Laboratory, ilmington, MA) were assigned to baseline controls (BLC, n 15), long-term (age matched) normal weight-bearing controls (LTC, n 30), normal weight-bearing animals subject to 10 min day 190 Hz mechanical stimulation at 0.25 g peak to peak (MS, n 21),animals subject to 24 h day 1 disuse via hind limb suspension, animals subject to disuse interrupted by 10 min day 1 of normal weight bearing (Dis WB, n 7), and disuse interrupted by 10 min day 1 of 90 Hz stimulation at 0.25 g (Dis MS, n 19). All protocols ran for 28 days; animals were weighed at the beginning and end of the study. Baseline control rats were killed 1 day before the protocols commenced. Rats were individually housed at 24°C with free
access to food and water. To measure indices of bone formation, all rats (except baseline controls) were given injections of demeclocycline [25 mg kg 1, intraperitoneal(i.p.)] before the beginning of the study and calcein (15i.p.) on day 18 of the protocol. Rats were killed by carbon dioxide inhalation, and right and left tibiae harvested. All procedures were reviewed and approved by the Animal Care Committee of SUNY Stony Brook, and met all guidelines for the health and welfare of the animals.Suspension model and daily loading of animals All disuse animals were subject to hind limb suspension for 28 days according to the Morey-Holton tail suspension model of disuse osteopenia (14). For those animals receiving mechanical intervention (MS, Dis MS), this stimulus was provided by a platform that oscillated at 90 Hz, giving rise to a vertical accelerations of 0.25 g (9.8 m sEarth's gravitational field). When a human stands on a plate providing a 0.25 g mechanical stimulus, the vibration is barely perceptible. The apparatus uses a small, low-force (18N) but highly linear moving coil actuator (15). During the mechanical stimulation, each rat was placed in regular plastic cage where it was allowed to move freely. Once a day, 5 days/wk, each animal in a loading protocol was subjected to 10 min day
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