Musculoskeletal adaptations to weightlessness and development of effective countermeasures.

A Research Roundtable, organized by the American College of Sports Medicine with sponsorship from the National Aeronautics and Space Administration, met in November 1995 to define research strategies for effective exercise countermeasures to weightlessness. Exercise was considered both independently of, and in conjunction with, other therapeutic modalities (e.g., pharmacological nutritional, hormonal, and growth-related factors) that could prevent or minimize the structural and functional deficits involving skeletal muscle and bone in response to chronic exposure to weightlessness, as well as return to Earth baseline function if a degree of loss is inevitable. Musculoskeletal deficits and countermeasures are described with respect to: 1) muscle and connective tissue atrophy and localized bone loss, 2) reductions in motor performance, 3) potential proneness to injury of hard and soft tissues, and 4) probable interaction between muscle atrophy and cardiovascular alterations that contribute to the postural hypotension observed immediately upon return from space flight. In spite of a variety of countermeasure protocols utilized previously involving largely endurance types of exercise, there is presently no activity-specific countermeasure(s) that adequately prevent or reduce musculoskeletal deficiencies. It seems apparent that countermeasure exercises that have a greater resistance element, as compared to endurance activities, may prove beneficial to the musculoskeletal system. Many questions remain for scientific investigation to identify efficacious countermeasure protocols, which will be imperative with the emerging era of long-term space flight.

Mechanical loading stimulates rapid changes in periosteal gene expression.

Although mechanical forces regulate bone mass and morphology, little is known about the signals involved in that regulation. External force application increases periosteal bone formation by increasing surface activation and formation rate. In this study, the early tibial periosteal response to external loads was compared between loaded and nonloaded contralateral tibia by examining the results of blot hybridization analyses of total RNA. To study the impact of external load on gene expression, RNA blots were sequentially hybridized to cDNAs encoding the protooncogene c-fos, cytoskeletal protein beta-actin, bone matrix proteins alkaline phosphatase (ALP), osteopontin (Op), and osteocalcin (Oc), and growth factors insulin-like growth factor I (IGF-I) and transforming growth factor-beta (TGF-beta). The rapid yet transient increase in levels of c-fos mRNA seen within 2 hours after load application indirectly suggests that the initial periosteal response to mechanical loading is cell proliferation. This is also supported by the concomitant decline in levels of mRNAs encoding bone matrix proteins ALP, Op, and Oc, which are typically produced by mature osteoblasts. Another early periosteal response to mechanical load appeared to be the rapid induction of growth factor synthesis as TGF-beta and IGF-I mRNA levels were increased in the loaded limb with peak levels being observed 4 hours after loading. These data indicate that the acute periosteal response to external mechanical loading was a change in the pattern of gene expression which may signal cell proliferation. The altered pattern of gene expression observed in the present study supports previous evidence of increased periosteal cell proliferation seen both in vivo and in vitro following mechanical loading.

Periosteal bone formation stimulated by externally induced bending strains.

The rat tibia four-point bending model is a new mechanical loading model in which force is applied through external pads to the rat lower limb. The advantages of the model are controlled force application to a well-defined bone, noninvasive external loading, and the addition of loads to normal daily activity. A disadvantage of the model is that the pads create local pressure on the leg at the contact sites. This study examined the differences in tibial response to bending strains and to local pressure under the pads. A total of 30 adult Sprague-Dawley rats were randomized into three external loading groups: bending, cyclic pressure, and static pressure. The right leg of each rat was externally loaded to create either bending or local pressure without bending; the left leg served as a control. Strains on the lateral surface averaged 1200 mu epsilon in compression during bending load application and < 200 mu epsilon in compression during pressure loading. Histomorphometric data were collected from three regions: the maximal bending region, under the loading pads, and outside the maximal bending region. In the maximal bending region, bending loads created greater mineral apposition rate (MAR) on the lateral surface and greater MAR and formation surface on the medial surface of loaded than control tibiae. The region under the bending pad was exposed to similar bending strains and showed the same pattern of increased MAR as sections from the maximal bending region. Cyclic pressure had no effect on periosteal MAR or formation surface. Static pressure increased MAR only on the lateral tibial surface. Bending stimulates bone formation in regions with the highest bending strains. Similar forces applied only in the form of pressure loading do not stimulate tibial formation either at the contact site or between loading pads. These results suggest that externally applied forces of moderate magnitude stimulate bone formation primarily as a result of increased bending strains, not local pressure at the contact site.

Bone response to alternate-day mechanical loading of the rat tibia.

Mechanical loading of the living skeleton influences bone formation, mass, and strength. The primary purpose of the present study was to examine the influence of different loading schedules (days/week) on the bone response to external loading using an in vivo rat tibia four-point bending model. Three studies were conducted to (1) characterize the loaded region, (2) examine the variation of the response within the loaded region, and (3) test the response to different loading schedules. In all studies adult female retired breeder Sprague-Dawley rats were used (6 months, 285 g). First, the location of the loaded region during four-point bending was determined by radiogrammetry of 7 rats. Second, 5 rats were externally loaded for 8 of 10 days at 31 N, 36 cycles, and 2 Hz (1349 +/- 244 mu epsilon). The extent of labeled (forming) periosteal and endocortical surface in the loaded region was compared both among four serial sections from the same tibia and between the loaded and the contralateral tibiae. Finally, 50 rats were randomized into five groups: two nonloaded, control and sham, and three loaded, alternate day, Monday, Wednesday, and Friday, and daily. The rats were externally loaded for 3 weeks at 35 N, 36 cycles, and 2 Hz (1533 +/- 308 mu epsilon). The tibia and fibula were studied for labeled surfaces and mineral apposition rate. For adult female rats with tibial length 39 mm, the loaded region was located 3.5-14 (+/- 0.7) mm proximal to the tibia-fibula junction (TFJ).(ABSTRACT TRUNCATED AT 250 WORDS)