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ABSTRACT: This study aimed to understand the role of Cav1.3, one of the four L-type voltage sensitive calcium channels (VSCC) alpha(1) subunits, in the skeletal response to mechanical loading and intermittent PTH treatment. The Cav1.3 mRNA is expressed in osteoblasts. The Cav1.3 mRNA level in male wild type mice is higher than those in female. Loss of Cav1.3 resulted in a smaller skeleton in male mice as indicated by significantly lower body weight, less bone mineral content and smaller cross-sectional area of femoral midshaft. However, the osteogenic response to mechanical loading of the ulna was normal in Cav1.3(-/-) compared to the normal control mice. Male mice Cav1.3(-/-) were then treated daily with PTH at a dose of 40 microg/kg. A 6-week course of intermittent PTH treatment enhanced bone mineral content and mechanical strength equally in wild type control and Cav1.3 null mice. We also found that Cav1.2 subunit significantly increases in the absence of Cav1.3 gene. In conclusion, Cav1.3 is involved in bone metabolism, especially in male mice. Cav1.3 does not mediate osteoblast response to mechanical loading and PTH. Our data suggest that Cav1.1 and Cav1.2 subunits may substitute for Cav1.3 to maintain bone response to mechanical loading.
Journal of musculoskeletal & neuronal interactions 06/2010; 10(2):180-7. · 2.00 Impact Factor
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ABSTRACT: Genetic effects on mechanical properties have been demonstrated in rodents, but not confirmed in primates. Our aim was to quantify the proportion of variation in vertebral trabecular bone mechanical properties that is due to the effects of genes. L3 vertebrae were collected from 110 females and 46 male baboons (6-32 years old) from a single extended pedigree. Cranio-caudally oriented trabecular bone cores were scanned with microCT then tested in monotonic compression to determine apparent ultimate stress, modulus, and toughness. Age and sex effects and heritability (h(2)) were assessed using maximum likelihood-based variance components methods. Additive effects of genes on residual trait variance were significant for ultimate stress (h(2)=0.58), toughness (h(2)=0.64), and BV/TV (h(2)=0.55). When BV/TV was accounted for, the residual variance in ultimate stress accounted for by the additive effects of genes was no longer significant. Toughness, however, showed evidence of a non-BV/TV-related genetic effect. Overall, maximum stress and modulus show strong genetic effects that are nearly entirely due to bone volume. Toughness shows strong genetic effects related to bone volume and shows additional genetic effects (accounting for 10% of the total trait variance) that are independent of bone volume. These results support continued use of bone volume as a focal trait to identify genes related to skeletal fragility, but also show that other focal traits related to toughness and variation in the organic component of bone matrix will enhance our ability to find additional genes that are particularly relevant to fatigue-related fractures.
Bone 11/2009; 46(3):835-40. · 4.02 Impact Factor
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ABSTRACT: The osteo-anabolic effects of intermittent parathyroid hormone (PTH) treatment require insulin-like growth factor (IGF) signaling through the IGF-I receptor. A major downstream target of the IGF-I receptor (via Akt) is the mammalian target of rapamycin (mTOR), a kinase involved in protein synthesis. We investigated whether the bone-building effects of intermittent PTH require functional mTOR signaling. Mice were treated with daily PTH 1-34 (0, 10, 30, or 90 microg/kg) for 6 weeks in the presence or absence of rapamycin, a selective inhibitor of mTOR. We found that all PTH doses were effective in enhancing bone mass, whether rapamycin was present or not. Rapamycin had little to no effect on the anabolic response at low (10 microg) PTH doses, small effects in a minority of anabolic measures at moderate doses (30 microg), but the anabolic effects of high-dose PTH (90 microg) were consistently and significantly suppressed by rapamycin ( approximately 4-36% reduction). Serum levels of Trap5b, a marker of resorption, were significantly enhanced by rapamycin, but these effects were observed whether PTH was absent or present. Our data suggest that intermittent PTH, particularly at lower doses, is effective in building bone mass in the presence of rapamycin. However, the full anabolic effects of higher doses of PTH are significantly suppressed by rapamycin, suggesting that PTH might normally activate additional pathways (including mTOR) for its enhanced high-dose anabolic effects. Clinical doses of intermittent PTH could be an effective treatment for maintaining or increasing bone mass among patients taking rapamycin analogs for unrelated health issues.
Journal of Cellular Physiology 08/2009; 221(3):579-85. · 3.87 Impact Factor
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ABSTRACT: The benefits of impact exercise and dietary calcium on bone development are controversial. We used inbred rats under highly controlled conditions to test the independent and combined effects of impact exercise and physiological levels of calcium intakes on the growing skeleton. Forty growing F-344 female rats were fed diets containing either 100% (Ca+; 0.5% Ca) or 40% (Ca(-); 0.2% Ca) of their calcium requirements. Half of each dietary group was subjected to either 10 impacts per day from 45 cm freefall drops (Impact+), or no impact (Impact(-)). All rats received a free choice of physical activity period daily. After 8 weeks, the mechanical strength, volumetric density, geometry, and microarchitecture of their ulnae were measured. Body weight and bone length did not differ among groups. On both diets, freefall impact resulted in greater bone strength, cross-sectional moments of inertia, and endosteal and periosteal circumferences in the shaft. Only Ca+ resulted in greater shaft volumetric bone mineral density (vBMD) but that did not affect shaft breaking strength. In the bone ends, both Impact+ and Ca+ positively affected density and structure of both cortical and trabecular bone but the effects of Impact+ were more pervasive. In the proximal end, Impact+ resulted in greater bone volume fraction (BV/TV) in the trabecular bone due to greater trabecular thickness, and cortical thickness was greater due to a smaller endosteal circumference. Impact+ exerted a compensatory effect on vBMD and BV/TV in Ca(-) rats at the proximal site. In Impact(-) rats only, Ca+ resulted in greater total and cortical vBMD and BV/TV in the proximal ulna. Impact+ and Ca+ exerted additive effects on cortical bone area (BA) in the proximal ulna and on total BA, periosteal circumference, and trabecular vBMD in the distal ulna. In conclusion, impact exercise was more beneficial than adequate dietary calcium to growing bones, although sufficient dietary calcium was beneficial in rats not subjected to impact exercise.
Bone 05/2008; 42(4):660-8. · 4.02 Impact Factor
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ABSTRACT: The relationship between bone quality and strength was studied in 11 BXH recombinant inbred (RI) strains of mice. The bone quality parameters studied were bone mineralization, microhardness, architecture, and connectivity. Previous studies have demonstrated considerable variability in bone density, biomechanical properties, and microstructure among inbred strains of mice. In particular, C3H/HeJ (C3H) mice exhibit thicker femoral and vertebral cortices and fewer trabeculae in the vertebral body compared with C57BL/6J (B6) mice, despite having similar vertebral bone strength. A set of RI mouse strains has been generated from B6 and C3H (denoted BXH) in an attempt to isolate genetic regulation of numerous traits, including bone. The objective of this study was to investigate relationships among bone quality and bone strength in femurs and vertebrae among BXH RI mice. The study involved 11 BXH RI strains of female mice (n = 5-7) as well as the B6 and C3H progenitor strains. Parameters contributing to bone quality were evaluated, including BMD, bone mineralization, microhardness, architecture, and connectivity. There was a strong correlation between femoral and vertebral BMD in all strains (P < 0.001) except in BXH-9 and -10 (P < 0.001). Within the vertebrae, cortical bone was more mineralized than trabecular bone, and a strong correlation existed between the two (P < 0.001). However, cortical microhardness did not differ from trabecular microhardness. Cortical bone was more mineralized in the femur than in the vertebrae and significantly harder, by 30%. There was a wide range in trabecular connectivity, architecture, and femur geometry among BXH RI strains. BMD explained 43% of vertebral bone strength but only 11% of femoral bone strength. Trabecular connectivity explained an additional 8% of vertebral strength, while mineralization and femur geometry explained 7% and 50% of femoral strength, respectively. Different bone quality parameters had varying influences on bone mechanical properties, depending on bone site. BMD may play a larger role in explaining bone strength in the vertebrae than in the femur. Moreover, cortical bone in the femur is harder than in vertebrae. The control of cortical bone material properties may be site-dependent.
Calcified Tissue International 10/2007; 81(3):215-23. · 2.38 Impact Factor
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ABSTRACT: 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-beta, influences the responsiveness of bone to mechanical loads. To test our hypothesis, 16-wk-old male and female mice with null mutations in ER-beta (ER-beta(-/-)) 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-beta(-/-) and wild-type (WT) mice. The ulnar responsiveness to loading was similar in male ER-beta(-/-) vs. WT mice, but for female mice bone formation was stimulated more effectively in ER-beta(-/-) mice (P < 0.001). We conclude that estrogen signaling through ER-beta suppresses the mechanical loading response on the periosteal surface of long bones.
AJP Endocrinology and Metabolism 08/2007; 293(2):E484-91. · 4.75 Impact Factor
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ABSTRACT: Risk factors for osteoporotic hip fracture include reduced bone mineral density and poor structure of the femoral neck, both of which are heritable traits. Previously, we showed that despite similar body size, Fischer 344 (F344) rats have significantly different skeletal traits compared with Lewis (LEW) rats. To identify a gene or genes regulating fracture risk at the femoral neck, we mapped quantitative trait loci (QTL) for femoral neck density and structure phenotypes using a 595 F2 progeny derived from the inbred F344 and LEW strains of rats. Femoral neck phenotypes included volumetric bone mineral density (vBMD), neck width, femoral neck cross-sectional area and polar moment of inertia (Ip). A 20-cM genome-wide scan was performed using 118 microsatellite markers and linkage analysis was conducted to identify chromosomal regions harbor QTL for femoral neck phenotypes. Strong evidence of linkage (P<0.01) to femoral neck vBMD was observed on chromosomes (Chrs) 1, 2, 4, 5, 7, 10 and 15. QTL affecting femoral neck structure and biomechanical properties were detected only on Chr 4 where the F344 alleles were shown to improve femoral neck structure, whereas these alleles had no effect on bone measurements at the lumbar spine and only modest effects at the femoral midshaft. In contrast, QTL on Chrs 1, 2 and 10 affected multiple skeletal sites. Several QTL regions in this study are homologous to human chromosomal regions, where linkage to femoral neck and related phenotypes has been reported previously. These findings represent an important first step in localizing and identifying genes that influence hip fragility.
Bone 07/2006; 39(1):93-9. · 4.02 Impact Factor
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ABSTRACT: We previously demonstrated that suppression of bone remodeling allows microdamage to accumulate, thereby leading to reduced bone toughness in dog bone. In this study we evaluated the relationships between bone remodeling at the iliac crest and skeletal activation frequency, microdamage accumulation, or biomechanical properties of lumbar vertebrae using the same dogs to determine whether bone remodeling at the iliac crest can predict damage accumulation and mechanical parameters of the lumbar spine following treatment with antiresorptive agents. Thirty-six female beagles, 1 to 2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with oral risedronate at a dose of 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day orally. The doses of these bisphosphonates were 5 to 6 times the clinical doses approved for treatment of osteoporosis in humans. After sacrifice, the right ilium and L2 vertebra were assigned to histomorphometry. The left ilium and L3 vertebra were used for microdamage analysis. The L4 vertebra was mechanically tested to failure in compression, and bone toughness calculated from the stress-strain curve. There was a strong positive relationship for activation frequency (Ac.f) between ilium and lumbar vertebrae (r2 = 0.82; P < 0.0001). Iliac crest Ac.f underestimates Ac.f in L2, but L2 Ac.f reaches a minimum threshold and does not decline further when iliac crest Ac.f is below 0.10/yr. Microdamage (Cr.S.Dn) accumulation at the ilium was significantly associated with increased microdamage accumulation in the L3 lumbar vertebra (r2 = 0.43, P < 0.0001). The data also show that bisphosphonate treatment increased Cr.S.Dn at a faster rate in L3 than in the iliac crest. Although bisphosphonate treatment decreased bone toughness in L4, this decrease demonstrated no relationship to decreased Ac.f in the ilium. These results clearly indicate that bone remodeling data obtained from iliac crest biopsy could be used to estimate the activation frequency and microdamage burden in the vertebral column.
Calcified Tissue International 09/2005; 77(3):180-5. · 2.38 Impact Factor
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ABSTRACT: We previously demonstrated that suppression of bone remodeling allows microdamage to accumulate, thereby leading to reduced
bone toughness in dog bone. In this study we evaluated the relationships between bone remodeling at the iliac crest and skeletal
activation frequency, microdamage accumulation, or biomechanical properties of lumbar vertebrae using the same dogs to determine
whether bone remodeling at the iliac crest can predict damage accumulation and mechanical parameters of the lumbar spine following
treatment with antiresorptive agents. Thirty-six female beagles, 1 to 2 years old, were divided into three groups. The control
group was treated daily for 12 months with saline vehicle. The remaining two groups were treated daily with oral risedronate
at a dose of 0.5 mg/kg/day, or alendronate at 1.0 mg/kg/day orally. The doses of these bisphosphonates were 5 to 6 times the
clinical doses approved for treatment of osteoporosis in humans. After sacrifice, the right ilium and L2 vertebra were assigned
to histomorphometry. The left ilium and L3 vertebra were used for microdamage analysis. The L4 vertebra was mechanically tested
to failure in compression, and bone toughness calculated from the stress–strain curve. There was a strong positive relationship
for activation frequency (Ac.f) between ilium and lumbar vertebrae (r2 = 0.82; P < 0.0001). Iliac crest Ac.f underestimates Ac.f in L2, but L2 Ac.f reaches a minimum threshold and does not decline further
when iliac crest Ac.f is below 0.10/yr. Microdamage (Cr.S.Dn) accumulation at the ilium was significantly associated with
increased microdamage accumulation in the L3 lumbar vertebra (r2 = 0.43, P < 0.0001). The data also show that bisphosphonate treatment increased Cr.S.Dn at a faster rate in L3 than in the iliac crest.
Although bisphosphonate treatment decreased bone toughness in L4, this decrease demonstrated no relationship to decreased
Ac.f in the ilium. These results clearly indicate that bone remodeling data obtained from iliac crest biopsy could be used
to estimate the activation frequency and microdamage burden in the vertebral column.
Calcified Tissue International 08/2005; 77(3):180-185. · 2.38 Impact Factor
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British journal of sports medicine 05/2005; 39(4):188-9. · 2.55 Impact Factor
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ABSTRACT: We have known for sometime that sex hormones influence the growth, preservation, and loss of bone tissue in the skeleton. However, we are only beginning to recognize how estrogen influences the responsiveness of the skeleton to exercise. Frost's mechanostat theory proposes that estrogen reduces the mechanical strain required to initiate an osteogenic response, but this may only occur at the endocortical and trabecular bone surfaces. The discovery of estrogen receptors alpha and beta may help us to understand the bone surface-specific effects of exercise. Findings from estrogen receptor knockout mice suggest that the activity of ERalpha may explain the positive interaction between estrogen and exercise on bone formation near marrow, that is, endocortical and trabecular bone surfaces. Estrogen inhibits the anabolic exercise response at the periosteal surface, and this we propose is due to the activation of ERbeta. Signaling through this receptor retards periosteal bone formation and suppresses gains in bone size and bone strength, and for these reasons it behaves as an antimechanostat.
Bone 03/2005; 36(2):185-92. · 4.02 Impact Factor
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ABSTRACT: After the initial adaptation to large mechanical loads, it appears as though the skeleton's responsiveness to exercise begins to wane. To counteract the waning effects of long-term mechanical loading, "time off" may be needed to improve the responsiveness of bone cells to future mechanical signals and reinitiate bone formation. The aim of this study was to determine whether bone becomes less sensitive to long-term mechanical loading and whether time off is needed to improve mechanosensitivity. Fifty-seven female Sprague-Dawley rats (7-8 months of age) were randomized to one of following groups: Group 1 loading was applied for 5 weeks followed by 10 weeks of time off (1 x 5); Group 2 loading was applied for 5 weeks, followed by time off for 5 weeks and loading again for 5 weeks (2 x 5); Group 3 loading was applied continuously for 15 weeks (3 x 5); Group 4 age-matched control group; and Group 5 baseline control group. An axial load was applied to the right ulna for 360 cycles/day, at 2 Hz, 3 days/week at 15 N. At the end of the intervention, all three loaded groups showed similar increases in bone mass, cortical area, and I(MIN) in response to mechanical loading(.) Bone formation rate of the loaded ulna was increased in the first 5 weeks of loading for all three loaded groups; however, during the last 5 weeks, it was only significantly increased in the group that had time off (2 x 5) (P < 0.05). The group that had time off (2 x 5) also showed greater improvements in work to failure compared to the group loaded for 5 weeks (1 x 5) and the entire 15 weeks (3 x 5). A second experiment showed that the waning effect of long-term loading on the skeleton is not a result of aging. In conclusion, mechanical loading of the rat ulna results in large improvements in bone formation during the first 5 weeks of loading, but continual loading decreases the osteogenic response. Having time off increases bone formation and improves the resistance to fracture.
Bone 03/2005; 36(3):454-64. · 4.02 Impact Factor
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C H Turner
Journal of musculoskeletal & neuronal interactions 01/2005; 4(4):402-3. · 2.00 Impact Factor
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ABSTRACT: Impact exercise can have beneficial effects on the growing skeleton. To understand what changes it promotes in the shafts and ends of weight-bearing bones, we measured the effects of impact from repetitive free falls in growing rats. Fischer 344 female rats, 6.5 wk old, were assigned to one of three groups (n = 10 each). Controls were not dropped, whereas those subjected to impact were dropped from 30 or 60 cm. Rats in both free-fall groups were dropped 10 times per day for 8 wk. Leg bones were mechanically tested, and their cross-sectional area (CSA), cross-sectional moments of inertia, and volumetric bone mineral density (BMD) were measured by peripheral quantitative computed tomography. In the shafts of the forelimbs, but not the hindlimbs, free-fall impact resulted in greater ultimate breaking force, minimum and maximum second moments of area, and CSA but not BMD. In the bone ends of the forelimb and tibial bones, trabecular BMD increased but CSA did not. Landing from 30 and 60 cm produced peak impact forces of 12.0 and 16.7 times the standing forefoot weight for each front leg and of 4.5 and 7.7 times the standing hind foot weight for each hind foot. Overall, free-fall impact affected the forelimbs by increasing trabecular bone density in the bone ends and improving the strength at the shaft as a result of geometric improvements. These results indicate that adaptation to impact may occur by different mechanisms in bone end and shaft regions.
Journal of Applied Physiology 12/2004; 97(5):1859-65. · 3.75 Impact Factor
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ABSTRACT: Osteoporosis is a disease of bone fragility resulting mostly from low bone mass and a concomitant increase in the risk for fracture. Exercise is a commonly prescribed intervention for osteoporosis because bone tissue is mechanosensitive. The ability of mechanical stimuli to influence bone biology has been known for over a century, but it has been only in the past several decades that great gains have been made in terms of understanding factors that influence this response. By understanding these factors, steps can be developed to maximize the osteogenic effects of exercise on the skeleton and potentially reduce the incidence of bone fractures. This paper outlines these steps. They include: 1) starting exercise when young while the skeleton is most responsive to mechanical stimuli; 2) selecting exercises that are dynamic and high-impact to maximize osteogenic responses, such as jumping for the lower extremity and racquet sports for the upper extremity; 3) exercising the specific skeletal regions you want to strengthen as the bone response to mechanical loading is highly site-specific; 4) exercising briefly, yet often to offset the desensitization of skeletal mechanotransduction pathways; and 5) continuing to exercise as you age to prevent bone loss and reduce the risk of falls. Following these steps will help to promote skeletal health at all ages and may reduce an individuals risk for fracture by augmenting bone mass and size during youth, while reducing age-related bone loss and the risk for falls in adulthood.
Europa medicophysica 10/2004; 40(3):223-32.
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ABSTRACT: Impact exercise can have beneficial effects on the growing skeleton. To understand what changes it promotes in the shafts and ends of weight-bearing bones, we measured the effects of impact from repetitive free falls in growing rats. Fischer 344 female rats, 6.5 wk old, were assigned to one of three groups (n � 10 each). Controls were not dropped, whereas those subjected to impact were dropped from 30 or 60 cm. Rats in both free-fall groups were dropped 10 times per day for 8 wk. Leg bones were mechanically tested, and their cross-sectional area (CSA), cross-sectional moments of inertia, and volumetric bone mineral density (BMD) were measured by peripheral quantitative computed tomography. In the shafts of the forelimbs, but not the hindlimbs, free-fall impact resulted in greater ultimate breaking force, minimum and maximum second moments of area, and CSA but not BMD. In the bone ends of the forelimb and tibial bones, trabecular BMD increased but CSA did not. Landing from 30 and 60 cm
produced peak impact forces of 12.0 and 16.7 times the standing forefoot weight for each front leg and of 4.5 and 7.7 times the standing hind foot weight for each hind foot. Overall, free-fall impact affected the forelimbs by increasing trabecular bone density in the bone ends and improving the strength at the shaft as a result of geometric improvements. These results indicate that adaptation to impact may occur by different mechanisms in bone end and shaft regions.
J Applied Physiology. 05/2004; 97(5):1859--1865.
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ABSTRACT: A dose-response relationship has been shown between loading frequency and cortical bone adaptation for frequencies of up to 10 Hz, and is presumed to persist with further increases in frequency. Studies herein aimed to investigate cortical bone adaptation to loading frequencies of 1, 5, 10, 20 and 30 Hz. Two studies were performed in adult C57BL/6 mice using the ulna axial compression-loading model. In the first study, the histomorphometric response of the ulna was studied when loaded for 120 cycles day(-1) for 3 days at one of the five frequencies and one of two load magnitudes (1.5 or 2.0 N). In the second study, the changes in ulna geometry and mechanical properties were studied following loading for 5 min day(-1), 3 days week(-1) for 4 weeks at one of the five frequencies and one of two load magnitudes (1.0 or 1.6 N). Preliminary strain gauge measurements showed that frequency had no effect on mechanical strain per unit load. In study 1, loading frequency significantly influenced bone adaptation when loading at 2.0 N, with loading at 10 Hz resulting in significantly greater adaptation than with loading at other frequencies. In study 2, loading frequency significantly influenced the change in geometry when loading at 1.6 N, with loading at 5, 10 or 30 Hz resulting in significantly greater change than with loading at 1 Hz. Loading at 5 Hz also resulted in significantly greater change than with loading at 20 Hz. No frequency effect was found on any of the mechanical properties at either load. Overall, we found cortical bone adaptation to mechanical loading to increase with increasing loading frequency up to 5-10 Hz and to plateau with frequencies beyond 10 Hz. The mechanism for this nonlinear frequency response is not known; however, based on strain gauge measurements, we do not believe it resulted from dampening associated with high frequency loading through the flexed carpal joint. The obtained findings may relate to the mechanism of mechanotransduction within the bone. This requires further investigation.
Bone 03/2004; 34(2):261-70. · 4.02 Impact Factor
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ABSTRACT: As muscles become larger and stronger during growth and in response to increased loading, bones should adapt by adding mass, size, and strength. In this unilateral model, we tested the hypothesis that (1) the relationship between muscle size and bone mass and geometry (nonplaying arm) would not change during different stages of puberty and (2) exercise would not alter the relationship between muscle and bone, that is, additional loading would result in a similar unit increment in both muscle and bone mass, bone size, and bending strength during growth. We studied 47 competitive female tennis players aged 8-17 years. Total, cortical, and medullary cross-sectional areas, muscle area, and the polar second moment of area (I(p)) were calculated in the playing and nonplaying arms using magnetic resonance imaging (MRI); BMC was assessed by DXA. Growth effects: In the nonplaying arm in pre-, peri- and post-pubertal players, muscle area was linearly associated BMC, total and cortical area, and I(p) (r = 0.56-0.81, P < 0.09 to < 0.001), independent of age. No detectable differences were found between pubertal groups for the slope of the relationship between muscle and bone traits. Post-pubertal players, however, had a higher BMC and cortical area relative to muscle area (i.e., higher intercept) than pre- and peri-pubertal players (P < 0.05 to < 0.01), independent of age; pre- and peri-pubertal players had a greater medullary area relative to muscle area than post-pubertal players (P < 0.05 to < 0.01). Exercise effects: Comparison of the side-to-side differences revealed that muscle and bone traits were 6-13% greater in the playing arm in pre-pubertal players, and did not increase with advancing maturation. In all players, the percent (and absolute) side-to-side differences in muscle area were positively correlated with the percent (and absolute) differences in BMC, total and cortical area, and I(p) (r = 0.36-0.40, P < 0.05 to < 0.001). However, the side-to-side differences in muscle area only accounted for 11.8-15.9% of the variance of the differences in bone mass, bone size, and bending strength. This suggests that other factors associated with loading distinct from muscle size itself contributed to the bones adaptive response during growth. Therefore, the unifying hypothesis that larger muscles induced by exercise led to a proportional increase in bone mass, bone size, and bending strength appears to be simplistic and denies the influence of other factors in the development of bone mass and bone shape.
Bone 03/2004; 34(2):281-7. · 4.02 Impact Factor
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C H Turner
Journal of musculoskeletal & neuronal interactions 01/2004; 3(4):410; discussion 417. · 2.00 Impact Factor
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ABSTRACT: Genetic linkage studies in C3H/HeJ (C3H) and C57BL/6J (B6) mice identified several chromosomal locations or quantitative trait loci (QTL) linked to femoral volumetric bone mineral density (vBMD). From QTL identified on chromosomes (chr) 1, 4, 6, 13, and 18, five congenic mouse strains were developed. In each of these mice, genomic DNA from the QTL region of the donor C3H strain was transferred into the recipient B6 strain. Here we report the effects of donated C3H QTL on femoral structure, cortical vBMD and bending strength. Femoral structure was quantified by the polar moment of inertia (Ip) at the mid-diaphysis, which reflects the bending or torsional rigidity of the femur. Although the C3H progenitor mice have a smaller Ip than B6 progenitor mice, the congenic mice carrying the C3H segment at Chr 4 had significantly increased Ip in both males and females, giving these mice stronger femora. In female mice from the congenic Chr 1 strain, Ip was increased whereas male mice from the Chr 1 strain had smaller femoral cross-sections and significantly reduced Ip. This sex-specific effect on femoral structure was seen to a lesser extent in Chr 18 congenic mice. In addition, cortical vBMD was measured using peripheral quantitative computed tomography. Cortical vBMD was similar among most congenic strains except in Chr 6 congenic mice, where cortical vBMD was significantly less in females, but not in males. We conclude that (1) chromosomal QTL from C3H mice, which are genetically linked to total femoral vBMD, also regulate femoral structure; (2) the QTL on Chr 4 improves femoral structure and strength; (3) QTL on Chr 1 and 18 impart sex-specific effects on femoral structure; and (4) the QTL on Chr 6 imparts a sex-specific effect on cortical vBMD and femoral strength.
Calcified Tissue International 10/2003; 73(3):297-303. · 2.38 Impact Factor
