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Jeremy M LaMothe

Publications and source records attributed to Jeremy M LaMothe.

3 recordsLinked to original sources

Strain rate influences periosteal adaptation in mature bone.

Mechanical forces influence bone form and function. Although the adaptive capabilities of bone are well known, the nuances of the mechanical stimuli regulating adaptation remain elusive. Recently, it was suggested that strain rate influences bone adaptation, and impact exercises with high strain rates during growth may be more osteogenic than low impact aerobic exercises. Building on those findings, we hypothesized that higher rates of mechanical loading would evoke greater adaptive responses than lower rates of loading in mature bone. To test that hypothesis, skeletally mature (16 weeks) female C57BL/6 mice underwent non-invasive exogenous cantilever bending of the right tibia with a 1 Hz trapezoidal waveform for 60 s, 5 days per week, for 4 weeks. Loading was calibrated (strain gauge) to induce peak magnitudes of 1000 microepsilon on the lateral tibial middiaphysis. Mice were randomly assigned to three groups based on strain rate of the applied load: low (0.004 s(-1); n = 14), medium (0.020 s(-1); n = 15), and high (0.100 s(-1); n = 14). Calcein injections (i.p., 10 mg kg(-1)) permitted histomorphometric analyses of bone formation. Loading significantly enhanced periosteal mineral apposition rate (MAR), mineralizing surface (MS), and bone formation rate (BFR BS(-1)) in all three strain rate groups, relative to control tibiae. Furthermore, a graded dose-response relation was observed between the applied strain rate and periosteal BFR BS(-1). These increases in MAR, MS, and BFR BS(-1) were not seen on the endosteal surface. Endosteal adaptation was not statistically different between loaded and control tibiae in most endosteal indices of bone adaptation. Moreover, endosteal adaptation did not increase with strain rate. Understanding the nature of the stimuli to which bone cells respond to may underpin the development of non-pharmacological treatments devised to enhance bone mass.

Adaptation, Physiological↗

Rest insertion combined with high-frequency loading enhances osteogenesis.

Mechanical loading can significantly affect skeletal adaptation. High-frequency loading can be a potent osteogenic stimulus. Additionally, insertion of rest periods between consecutive loading bouts can be a potent osteogenic stimulus. Thus we investigated whether the insertion of rest-periods between short-term high-frequency loading bouts would augment adaptation in the mature murine skeleton. Right tibiae of skeletally mature (16 wk) female C57BL/6 mice were loaded in cantilever bending at peak of 800 microepsilon, 30 Hz, 5 days/wk for 3 wk. Left tibiae were the contralateral control condition. Mice were randomly assigned into one of two groups: continuous high-frequency (CT) stimulation for 100 s (n = 9), or 1-s pulses of high-frequency stimuli followed by 10 s of rest (RI) for 100 s (n = 9). Calcein labels were administered on days 1 and 21; label incorporation was used to histomorphometrically assess periosteal and endosteal indexes of adaptation. Periosteal surface referent bone formation rate (pBFR/BS) was significantly enhanced in CT (>88%) and RI (>126%) loaded tibiae, relative to control tibiae. Furthermore, RI tibiae had significantly greater pBFR/BS, relative to CT tibiae (>72%). The endosteal surface was not as sensitive to mechanical loading as the periosteal surface. Thus short-term high-frequency loading significantly elevated pBFR/BS, relative to control tibiae. Furthermore, despite the 10-fold reduction in cycle number, the insertion of rest periods between bouts of high-frequency stimuli significantly augmented pBFR/BS, relative to tibiae loaded continually. Optimization of osteogenesis in response to mechanical loading may underpin the development of nonpharmacological regiments designed to increase bone strength in individuals with compromised bone structures.

Adaptation, Physiological↗

Selected contribution: Bone adaptation with aging and long-term caloric restriction in Fischer 344 x Brown-Norway F1-hybrid rats.

Rodents are commonly used as models for human aging because of their relatively short life span, the ease of obtaining age-specific tissue samples, and lower cost. However, age-associated disease may confound inbred animal studies. For example, numerous physiologically significant lesions, such as chronic nephropathy, are more common in aged Fischer 344 (F344) rats than in other strains (Bronson RT, Genetic Effects of Aging, 1990). Conversely, F344 x Brown-Norway F1-hybrid (F344BN) rats, developed by the National Institute on Aging for aging research, live considerably longer and have fewer pathologies at any given age vs. inbred strains (Lipman RD, Chrisp CE, Hazzard DG, and Bronson RT, J Gerontol A Biol Sci Med Sci 51: 54-59, 1996). To our knowledge, there are no data regarding the effect of age on bone geometry and mechanics in this strain of rat. Furthermore, caloric restriction (CR) extends the mean and maximal life span of animals and significantly reduces age-associated disease but may have adverse consequences for bone growth and mechanics. Thus we investigated the effects of age and CR on bone geometry and mechanics in the axial and appendicular skeleton of F344 Brown-Norway rats. Ad libitum fed rats were assessed at 8 mo (young adult; n = 6), 28 mo (late middle age; n = 5), and 36 mo (senescence; n = 6). CR rats were assessed at 28 mo (n = 6). Tibiae and the sixth lumbar vertebrae (L6) were dissected, scanned (micro-computed tomography) to determine geometry, and tested mechanically. From 8 to 36 mo, there were no significant changes in L6 geometry, and only the cross-sectional moment of inertia changed (increased) with the tibia. CR-induced body mass reductions accounted for changes in L6 load at proportional limit, maximal load, and stiffness (structural properties), but altered tibial structural properties were independent of body mass. In tibiae, geometric changes dominated alterations in structural properties. Those data demonstrated that, whereas aging in ad libitum-fed animals induced minor changes in bone mechanics, axial and appendicular bones were adversely influenced by CR in late-middle-aged animals in different manners.

Adaptation, Physiological↗