Rest-inserted loading rapidly amplifies the response of bone to small increases in strain and load cycles

2007 ◽  
Vol 102 (5) ◽  
pp. 1945-1952 ◽  
Author(s):  
Sundar Srinivasan ◽  
Brandon J. Ausk ◽  
Sandra L. Poliachik ◽  
Sarah E. Warner ◽  
Thomas S. Richardson ◽  
...  
Keyword(s):  
Bone Formation ◽  
Mechanical Loading ◽  
Formation Rate ◽  
Load Cycle ◽  
Rest Interval ◽  
Bone Formation Rate ◽  
Dynamic Histomorphometry ◽  
Cyclical Loading ◽  
Strain Magnitude ◽  
The Right

We hypothesized that a 10-s rest interval (at zero load) inserted between each load cycle would increase the osteogenic effects of mechanical loading near previously identified thresholds for strain magnitude and cycle numbers. We tested our hypothesis by subjecting the right tibiae of female C57BL/6J mice (16 wk, n = 70) to exogenous mechanical loading within a peri-threshold physiological range of strain magnitudes and load cycle numbers using a noninvasive murine tibia loading device. Bone responses to mechanical loading were determined via dynamic histomorphometry. More specifically, we contrasted bone formation induced by cyclic vs. rest-inserted loading (10-s rest at zero load inserted between each load cycle) by first varying peak strains (1,000, 1,250, or 1,600 με) at fixed cycle numbers (50 cycles/day, 3 days/wk for 3 wk) and then varying cycle numbers (10, 50, or 250 cycles/day) at a fixed strain magnitude (1,250 με). Within the range of strain magnitudes tested, the slope of periosteal bone formation rate (p.BFR/BS) with increasing strain magnitudes was significantly increased by rest-inserted compared with cyclical loading. Within the range of load cycles tested, the slope of p.BFR/BS with increasing load cycles of rest-inserted loading was also significantly increased by rest-inserted compared with cyclical loading. In sum, the data of this study indicate that inserting a 10-s rest interval between each load cycle amplifies bone's response to mechanical loading, even within a peri-threshold range of strain magnitudes and cycle numbers.

A SHORT-TERM FREE-FALL LANDING ENHANCES BONE FORMATION AND BONE MATERIAL PROPERTIES

2011 ◽  
Vol 11 (05) ◽  
pp. 1125-1139 ◽  
Author(s):  
HSIN-SHIH LIN ◽  
TSANG-HAI HUANG ◽  
SHIH-WEI MAO ◽  
YUH-SHIOU TAI ◽  
HUNG-TA CHIU ◽  
...  
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Free Fall ◽  
Tissue Level ◽  
Young Female ◽  
Female Rats ◽  
Short Term ◽  
Bone Formation Rate ◽  
Local Bone ◽  
Dynamic Histomorphometry

To investigate the effects of a short-term free-fall landing course on local bone metabolism and biomaterial properties, 32 female Wistar rats (7 week old) were randomly assigned to three groups: L30 (n = 11), L10 (n = 11) and CON (n = 10). Animals in the L30 and L10 groups were subjected to 30 and 10 free-fall landings per day, respectively, from a height of 40 cm for five consecutive days. Animals' ulnae were studied using methods of dynamic histomorphometry, tissue geometry, biomaterial measurements and collagen fiber orientation (CFO) analysis. In dynamic histomorphometry analysis, periosteal as well as endosteal mineral apposition rates (MAR, μm/day) were significantly higher in L30 group than in the CON group (p < 0.05). In addition, the periosteal bone formation rate (BFR/BS, μm2/μm3/year) was significantly higher in the L10 and L30 groups (p < 0.05). The ulnae of the animals in the two landing groups were higher in post-yield energy without significant changes in CFO, tissue size or tissue weight measurements. In conclusion, a short-term free-fall landing training produced a slight, but significant, higher bone formation in the ulnae of young female rats. Enhanced tissue biomaterial properties did not accompany size-related changes, suggesting that bone adapting to mechanical loading begins with changes in tissue-level properties.

scholarly journals Bone-loading response varies with strain magnitude and cycle number

2001 ◽  
Vol 91 (5) ◽  
pp. 1971-1976 ◽  
Author(s):  
D. M. Cullen ◽  
R. T. Smith ◽  
M. P. Akhter
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Low Frequency ◽  
Constant Frequency ◽  
Bone Formation Rate ◽  
Cycle Number ◽  
Adult Rat ◽  
Early Loading ◽  
Bone Response ◽  
Strain Magnitude

Mechanical loading stimulates bone formation and regulates bone size, shape, and strength. It is recognized that strain magnitude, strain rate, and frequency are variables that explain bone stimulation. Early loading studies have shown that a low number (36) of cycles/day (cyc) induced maximal bone formation when strains were high (2,000 με) (Rubin CT and Lanyon LE. J Bone Joint Surg Am 66: 397–402, 1984). This study examines whether cycle number directly affects the bone response to loading and whether cycle number for activation of formation varies with load magnitude at low frequency. The adult rat tibiae were loaded in four-point bending at 25 (−800 με) or 30 N (−1,000 με) for 0, 40, 120, or 400 cyc at 2 Hz for 3 wk. Differences in periosteal and endocortical formation were examined by histomorphometry. Loading did not stimulate bone formation at 40 cyc. Compared with control tibiae, tibiae loaded at −800 με showed 2.8-fold greater periosteal bone formation rate at 400 cyc but no differences in endocortical formation. Tibiae loaded at −1,000 με and 120 or 400 cyc had 8- to 10-fold greater periosteal formation rate, 2- to 3-fold greater formation surface, and 1-fold greater endocortical formation surface than control. As applied load or strain magnitude decreased, the number of cyc required for activation of formation increased. We conclude that, at constant frequency, the number of cyc required to activate formation is dependent on strain and that, as number of cyc increases, the bone response increases.

scholarly journals The TrkA agonist gambogic amide augments skeletal adaptation to mechanical loading through actions on sensory nerves and osteoblasts

2020 ◽  
Author(s):  
Gabriella Fioravanti ◽  
Phuong Q. Hua ◽  
Ryan E. Tomlinson
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Thermal Hyperalgesia ◽  
Osteoblastic Differentiation ◽  
Sensory Nerves ◽  
Thermal Stimulus ◽  
Differentiation Markers ◽  
Bone Formation Rate ◽  
Dynamic Histomorphometry ◽  
Skeletal Adaptation

ABSTRACTThe periosteal and endosteal surfaces of mature bone are densely innervated by sensory nerves expressing TrkA, the high-affinity receptor for nerve growth factor (NGF). In previous work, we demonstrated that administration of exogenous NGF significantly increased load-induced bone formation through the activation of Wnt signaling. However, the translational potential of NGF is limited by the induction of substantial mechanical and thermal hyperalgesia in mice and humans. Here, we tested the effect of gambogic amide (GA), a recently identified robust small molecule agonist for TrkA, on hyperalgesia and load-induced bone formation. Behavioral analysis was used to assess pain up to one week after axial forelimb compression. Contrary to our expectations, GA treatment was not associated with diminished use of the loaded forelimb or sensitivity to thermal stimulus. Furthermore, dynamic histomorphometry revealed a significant increase in relative periosteal bone formation rate as compared to vehicle treatment. Additionally, we found that GA treatment was associated with an increase in the number of osteoblasts per bone surface in loaded limbs as well as a significant upregulation of Wnt1, Wnt7b, and Ngf in loaded bones. To determine if these effects were exclusively mediated by NGF-TrkA signaling in sensory nerves, we cultured MC3T3-E1 cells for 7 or 14 days in osteogenic differentiation media containing NGF (50 ng/mL), GA (5, 50, or 500 nM), or vehicle (DMSO). After 7 days of culture, we observed increases in osteoblastic differentiation markers Runx2, Bglap2, and Sp7 in response to GA, whereas treatment with NGF was not different than vehicle. Only cells treated with the highest dose of GA (500 nM) had significantly impaired cell proliferation. In conclusion, our study indicates GA may be useful for augmenting skeletal adaptation to mechanical forces without inducing hyperalgesia through actions on both sensory nerves and osteoblasts.

The skeletal responsiveness to mechanical loading is enhanced in mice with a null mutation in estrogen receptor-β

2007 ◽  
Vol 293 (2) ◽  
pp. E484-E491 ◽  
Author(s):  
L. K. Saxon ◽  
A. G. Robling ◽  
A. B. Castillo ◽  
S. Mohan ◽  
C. H. Turner
Keyword(s):  
Bone Formation ◽  
Mechanical Loading ◽  
Internal Control ◽  
Bone Cells ◽  
Mechanical Load ◽  
Formation Rate ◽  
Estrogen Signaling ◽  
Bone Formation Rate ◽  
Female Mice ◽  
Periosteal Surface

Mechanical loading caused by physical activity can stimulate bone formation and strengthen the skeleton. Estrogen receptors (ERs) play some role in the signaling cascade that is initiated in bone cells after a mechanical load is applied. We hypothesized that one of the ERs, ER-β, influences the responsiveness of bone to mechanical loads. To test our hypothesis, 16-wk-old male and female mice with null mutations in ER-β (ER-β−/−) had their right forelimbs subjected to short daily loading bouts. The loading technique used has been shown to increase bone formation in the ulna. Each loading bout consisted of 60 compressive loads within 30 s applied daily for 3 consecutive days. Bone formation was measured by first giving standard fluorochrome bone labels 1 and 6 days after loading and using quantitative histomorphometry to assess bone sections from the midshaft of the ulna. The left nonloaded ulna served as an internal control for the effects of loading. Mechanical loading increased bone formation rate at the periosteal bone surface of the mid-ulna in both ER-β−/− and wild-type (WT) mice. The ulnar responsiveness to loading was similar in male ER-β−/− vs. WT mice, but for female mice bone formation was stimulated more effectively in ER-β−/− mice ( P < 0.001). We conclude that estrogen signaling through ER-β suppresses the mechanical loading response on the periosteal surface of long bones.

Time course for bone formation with long-term external mechanical loading

2000 ◽  
Vol 88 (6) ◽  
pp. 1943-1948 ◽  
Author(s):  
D. M. Cullen ◽  
R. T. Smith ◽  
M. P. Akhter
Keyword(s):  
Bone Formation ◽  
Mechanical Loading ◽  
Time Course ◽  
Formation Rate ◽  
Cell Activity ◽  
Structural Response ◽  
Mineral Apposition Rate ◽  
Bone Formation Rate ◽  
Periosteal Apposition

Increased mechanical loading of bone with the rat tibia four-point bending device stimulates bone formation on periosteal and endocortical surfaces. With long-term loading cell activity diminishes, and it has been reported that early gains in bone size may reverse. This study examined the time course for bone cellular and structural response after 6, 12, and 18 wk of loading at 1,200–1,700 microstrain (με). Bone formation rates, measured by histomorphometry, were compared within groups, between loaded and contralateral nonloaded tibiae, and between weeks. Formation surface, mineral apposition rate, and bone formation rate on periosteal and endocortical surfaces were elevated after 6 wk of loading. By 12 wk of loading, periosteal and endocortical formation surface and endocortical mineral apposition rates were elevated. By 18 wk of loading, periosteal adaptation appeared complete, whereas endocortical mineral apposition rate remained elevated. No periosteal resorption was observed. Average thickness of new bone formed, from baseline to collection, was greater in loaded than nonloaded tibiae by week 6 and was maintained through week 18. Early increases in bone formation result in periosteal apposition of new bone that persists after formation ceases.

Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

2006 ◽  
Vol 76 (3) ◽  
pp. 111-116 ◽  
Author(s):  
Hiroshi Matsuzaki ◽  
Misao Miwa
Keyword(s):  
Bone Formation ◽  
Calcium Supplementation ◽  
Control Diet ◽  
Formation Rate ◽  
Dietary Calcium ◽  
Mineral Apposition Rate ◽  
Control Group ◽  
Deficient Diet ◽  
Bone Formation Rate ◽  
Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

Regulation of bone repletion in rats subjected to varying low-calcium stress

1984 ◽  
Vol 246 (2) ◽  
pp. R190-R196 ◽  
Author(s):  
R. H. Drivdahl ◽  
C. C. Liu ◽  
D. J. Baylink
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Bone Volume ◽  
Strong Positive Correlation ◽  
Sprague Dawley ◽  
Bone Formation Rate ◽  
Osteoblast Activity ◽  
Calcium Stress ◽  
Sprague Dawley Rats ◽  
Very High

Weanling Sprague-Dawley rats subjected to varying degrees of low-Ca dietary stress (depletion) showed graded increases in the rate of endosteal bone formation when normal dietary Ca was restored (repletion). There was a strong positive correlation between the rate of bone resorption in depletion and the rate of bone formation attained after 1 wk of repletion. However, bone formation declined rapidly within the first 4 wk of repletion, despite the persistence of a substantial endosteal bone volume deficit. Furthermore the medullary area (indicative of bone volume) did not by itself determine the bone formation rate. Bone volume in test groups was restored to control levels after 6 mo of repletion, and this result could be predicted by a kinetic analysis. Thus, although very high rates of formation in early repletion decline rapidly, smaller increments relative to controls must be sustained for long periods. Our data indicate that increased formation rats at all stages of repletion are a consequence of elevations in both osteoblast number and osteoblast activity.

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