The effects of a 7-month high impact jumping intervention on bone mass in pre-pubescent boys and girls

High impact loading activities such as jumping, performed during childhood is advocated as one preventive method for increasing peak bone mass. Thus, we conducted a randomized intervention to examine the effect of high impact loading on bone mass in 34 pre-pubescent boys and girl over a seven month period. Participants meeting all inclusion criteria were randomized into either a jumping (n=18) or stretching group (n=16), both of which exercised three times per week for 15 minutes. The jumping group completed 100 jumps off 24-inch boxes each session, while the stretching group performed low impact flexibility exercises. Attrition was 85% (6 drop outs), with an overall attendance rate of 95%. Bone area and bone mineral content (BMC) was assessed using dual energy x-ray absorptiometery (Ho logic QDR 1000/W) for the left hip (femoral neck, greater trochanter, total hip), and lumbar spine (L[subscript 2-4]). Other measures were body composition (Lang skinfold calipers); physical activity (self-report questionnaire); and calcium intake (food survey). All measurements were assessed at baseline and 7 months. Significance is denoted as p.05); however, gender differences were found for FN BMC at baseline (p.05). No group by gender interactions were found at baseline or at the completion of the seven month intervention. No significant differences between groups were identified for body composition, physical activity, or calcium intake in repeated measures ANOVA analyses (p>.05). In conclusion, 100 jumps performed 3 times per week at approximately 8x body weight were sufficient to stimulate an osteogenic response at the femoral neck in pre-pubescent boys and girls. Implementing jumping exercises into regular physical activity programs during pre-pubescent growing years may increase peak bone mass and potentially reduce the onset of osteoporosis

Concise Review: Plasma and Nuclear Membranes Convey Mechanical Information to Regulate Mesenchymal Stem Cell Lineage

Numerous factors including chemical, hormonal, spatial, and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well-characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on “outside-in” signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell uses integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these outside-in connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the biochemical signals generated at the cell membrane and the nucleus, and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis

Exercise Completed When Young Provides Lifelong Benefit to Cortical Bone Structure and Estimated Strength

poster abstractExercise induces greatest bone gains during growth, yet reduced bone strength is an age-related phenomenon. This raises the question of whether exercise-induced bone changes when young persist into adulthood. The current studies used Major/Minor League Baseball (MLB/MiLB) players to explore whether exercise-induced gains in humeral bone structure and strength accrued when young persist lifelong. MLB/MiLB players are a unique model as the unilateral upper extremity loading associated with throwing enables the contralateral side to serve as an internal control site and former MLB/MiLB players were consistently exposed to extreme loading reducing secular variations in exercise levels between generations. Dominant-to-nondominant (D-to-ND) differences in humeral cross-sectional properties in MLB/MiLB players were normalized to matched controls to correct for side-to-side differences due to elevated habitual loading associated with arm dominance. Exercise when young induced significant skeletal benefits, with active MLB/MiLB players having nearly double the estimated ability to resist torsion (polar moment of inertia, IP) in the humerus of their dominant arm. The cortical bone mass and area benefits of exercise observed in active MLB/MiLB players were lost in former MLB players following 40-49 years of detraining as a result of elevated medullary expansion and endocortical trabecularization. However, 42% of the total bone area benefit persisted following 50+ years of detraining and contributed to the maintenance of 24% of the benefit on IP. In MLB players who continued to exercise during aging, medullary expansion and endocortical trabecularization were reduced and there was maintenance of the cortical bone mass and area benefits of exercise. These cumulative data indicate: 1) the extreme plasticity of the growing skeleton to exercise; 2) that exercise when young has lifelong benefits on cortical bone size and estimated strength, but not bone mass, and; 3) exercise continued during aging maintains the bone mass benefits of exercise

Baseball and softball pitchers are distinct within-subject controlled models for exploring proximal femur adaptation to physical activity

Purpose: Within-subject controlled models in individuals who preferentially load one side of the body enable efficient exploration of the skeletal benefits of physical activity. There is no established model of physical activity-induced side-to-side differences (i.e., asymmetry) at the proximal femur. Methods: Proximal femur asymmetry was assessed via dual-energy x-ray absorptiometry in male jumping athletes (JMP, n=16), male baseball pitchers (BB, n=21), female fast-pitch softball pitchers (SB, n=22), and controls (CON, n=42). The jumping leg was the dominant leg in JMP, whereas in BB, SB and CON the dominant leg was contralateral to the dominant/throwing arm. Results: BB and SB had 5.5% (95%CI, 3.9 to 7.0%) and 6.5% (95%CI, 4.8 to 8.2%) dominant-to-nondominant leg differences for total hip areal bone mineral density (aBMD), with the asymmetry being greater than both CON and JMP (p8%) dominant-to-nondominant leg differences in cross-sectional area, cross-sectional moment of inertia and section modulus, which were larger than any other group (p≤0.02). Conclusion: Male baseball and female softball pitchers are distinct within-subject controlled models for exploring adaptation of the proximal femur to physical activity. They exhibit adaptation in their dominant/landing leg (i.e., leg contralateral to the throwing arm), but the pattern differs with softball pitchers exhibiting greater femoral neck adaptation

Age-Related Changes in Proximal Humerus Bone Health in White Males

poster abstractThe proximal humerus is a common site for osteoporotic fracture during aging, accounting for up to 5% of fractures to the appendicular skeleton. While falls onto an outstretched hand are usually physically responsible for proximal humerus fractures, the ability of the underlying bone to resist applied loads must also play a role. Few studies have assessed proximal humerus bone health with aging. The aim of the current study was to explore age-related bone changes at the proximal humerus in men. A cross-sectional study design was used to assess peripheral quantitative computed tomography (pQCT)-derived bone properties of the proximal humerus in a cohort of 112 white males (age range = 30-85 yrs). A tomographic slice of the non-dominant upper extremity was acquired at 80% of humeral length proximal from its distal end—a location corresponding to the surgical neck of the humerus. Images were assessed for cortical (Ct.BMC) and trabecular (Tb.BMC) BMC, total (Tt.Ar), cortical (Ct.Ar) and medullary (Me.Ar) area, periosteal (Ps.Pm) and endosteal (Es.Pm) perimeter, cortical thickness (Ct.Th), and bone strength index for compression (BSIc). BSIc was calculated as the product of Tt.Ar and the square of total volumetric BMD. Data were plotted against age and linear regression lines assessed for their slope. Slopes were subsequently converted to percent change in the bone property per year. During aging, the proximal humerus expanded with Tt.Ar and Ps.Pm increasing at rates of 0.40%/yr and 0.19%/yr, respectively. However, Me.Ar (0.62%/yr) and Es.Pm (0.34%/yr) expanded at faster rates such that there was net loss of both Ct.BMC (-0.23%/yr) and Tb.BMC (-1.08%/yr). Also, the more rapid expansion of Me.Ar relative to Tt.Ar meant that Ct.Ar (-0.15%/yr) and Ct.Th (-0.34%/yr) both decreased with age. The net result of these mass and structural changes was progressive loss of bone strength with age, as indicated by a 0.44%/yr decline in BSIc. These data provide a picture of bone changes at the proximal humerus during aging. They suggest that between age 30 and 80 yrs, approximately 54% and 11% of Tb.BMC and Ct.BMC at the proximal humerus is lost, respectively. They also suggest that compressive strength of the proximal humerus declines by 22% between age 30 and 80 years. These declines in proximal humerus bone health have implications for fracture risk at this location during aging

Hand1 phosphoregulation within the distal arch neural crest is essential for craniofacial morphogenesis

In this study we examine the consequences of altering Hand1 phosphoregulation in the developing neural crest cells (NCCs) of mice. Whereas Hand1 deletion in NCCs reveals a nonessential role for Hand1 in craniofacial development and embryonic survival, altering Hand1 phosphoregulation, and consequently Hand1 dimerization affinities, in NCCs results in severe mid-facial clefting and neonatal death. Hand1 phosphorylation mutants exhibit a non-cell-autonomous increase in pharyngeal arch cell death accompanied by alterations in Fgf8 and Shh pathway expression. Together, our data indicate that the extreme distal pharyngeal arch expression domain of Hand1 defines a novel bHLH-dependent activity, and that disruption of established Hand1 dimer phosphoregulation within this domain disrupts normal craniofacial patterning

Bone Microarchitecture and Strength Adaptation to Physical Activity: A Within-Subject Controlled, HRpQCT Study

Purpose Physical activity benefits bone mass and cortical bone size. The current study assessed the impact of chronic (≥10 years) physical activity on trabecular microarchitectural properties and micro-finite element (μFE) analyses of estimated bone strength. Methods Female collegiate-level tennis players (n=15; age=20.3±0.9 yrs) were used as a within-subject controlled model of chronic unilateral upper-extremity physical activity. Racquet-to-nonracquet arm differences at the distal radius and radial diaphysis were assessed using high-resolution peripheral computed tomography (HRpQCT). The distal tibia and tibial diaphysis in both legs were also assessed, and cross-country runners (n=15; age=20.8±1.2 yrs) included as controls. Results The distal radius of the racquet arm had 11.8% (95% confidence interval [CI], 7.9 to 15.7%) greater trabecular bone volume/tissue volume, with trabeculae that were greater in number, thickness, connectivity, and proximity to each other than in the nonracquet arm (all p<0.01). Combined with enhanced cortical bone properties, the microarchitectural advantages at the distal radius contributed a 18.7% (95% CI, 13.0 to 24.4%) racquet-to-nonracquet arm difference in predicted load before failure. At the radial diaphysis, predicted load to failure was 9.6% (95% CI, 6.7 to 12.6%) greater in the racquet vs. nonracquet arm. There were fewer and smaller side-to-side differences at the distal tibia; however, the tibial diaphysis in the leg opposite the racquet arm was larger with a thicker cortex and had 4.4% (95% CI, 1.7 to 7.1%) greater strength than the contralateral leg. Conclusion Chronically elevated physical activity enhances trabecular microarchitecture and μFE estimated strength, furthering observations from short-term longitudinal studies. The data also demonstrate tennis players exhibit crossed symmetry wherein the leg opposite the racquet arm possesses enhanced tibial properties compared to in the contralateral leg

Concise Review: Plasma and Nuclear Membranes Convey Mechanical Information to Regulate Mesenchymal Stem Cell Lineage: Role of Nuclear Envelope on MSC Lineage

Numerous factors including chemical, hormonal, spatial and physical cues determine stem cell fate. While the regulation of stem cell differentiation by soluble factors is well characterized, the role of mechanical force in the determination of lineage fate is just beginning to be understood. Investigation of the role of force on cell function has largely focused on “outside-in” signaling, initiated at the plasma membrane. When interfaced with the extracellular matrix, the cell utilizes integral membrane proteins, such as those found in focal adhesion complexes to translate force into biochemical signals. Akin to these “outside-in” connections, the internal cytoskeleton is physically linked to the nucleus, via proteins that span the nuclear membrane. Although structurally and biochemically distinct, these two forms of mechanical coupling influence stem cell lineage fate and, when disrupted, often lead to disease. Here we provide an overview of how mechanical coupling occurs at the plasma and nuclear membranes. We also discuss the role of force on stem cell differentiation, with focus on the bio-chemical signals generated at the cell membrane and the nucleus and how those signals influence various diseases. While the interaction of stem cells with their physical environment and how they respond to force is complex, an understanding of the mechanical regulation of these cells is critical in the design of novel therapeutics to combat diseases associated with aging, cancer, and osteoporosis

Impact Exercise Increases BMC During Growth: An 8-Year Longitudinal Study

Our aim was to assess BMC of the hip over 8 yr in prepubertal children who participated in a 7-mo jumping intervention compared with controls who participated in a stretching program of equal duration. We hypothesized that jumpers would gain more BMC than control subjects. The data reported come from two cohorts of children who participated in separate, but identical, randomized, controlled, school-based impact exercise interventions and reflect those subjects who agreed to long-term follow-up (N = 57; jumpers = 33, controls = 24; 47% of the original participants). BMC was assessed by DXA at baseline, 7 and 19 mo after intervention, and annually thereafter for 5 yr (eight visits over 8 yr). Multilevel random effects models were constructed and used to predict change in BMC from baseline at each measurement occasion. After 7 mo, those children that completed high-impact jumping exercises had 3.6% more BMC at the hip than control subjects whom completed nonimpact stretching activities (p \u3c 0.05) and 1.4% more BMC at the hip after nearly 8 yr (BMC adjusted for change in age, height, weight, and physical activity; p \u3c 0.05). This provides the first evidence of a sustained effect on total hip BMC from short-term high-impact exercise undertaken in early childhood. If the benefits are sustained into young adulthood, effectively increasing peak bone mass, fracture risk in the later years could be reduced

Progressive skeletal benefits of physical activity when young as assessed at the midshaft humerus in male baseball players

Physical activity benefits the skeleton, but there is contrasting evidence regarding whether benefits differ at different stages of growth. The current study demonstrates that physical activity should be encouraged at the earliest age possible and be continued into early adulthood to gain most skeletal benefits. INTRODUCTION: The current study explored physical activity-induced bone adaptation at different stages of somatic maturity by comparing side-to-side differences in midshaft humerus properties between male throwing athletes and controls. Throwers present an internally controlled model, while inclusion of control subjects removes normal arm dominance influences. METHODS: Throwing athletes (n = 90) and controls (n = 51) were categorized into maturity groups (pre, peri, post-early, post-mid, and post-late) based on estimated years from peak height velocity (10 years). Side-to-side percent differences in midshaft humerus cortical volumetric bone mineral density (Ct.vBMD) and bone mineral content (Ct.BMC); total (Tt.Ar), medullary (Me.Ar), and cortical (Ct.Ar) areas; average cortical thickness (Ct.Th); and polar Strength Strain Index (SSIP) were assessed. RESULTS: Significant interactions between physical activity and maturity on side-to-side differences in Ct.BMC, Tt.Ar, Ct.Ar, Me.Ar, Ct.Th, and SSIP resulted from the following: (1) greater throwing-to-nonthrowing arm differences than dominant-to-nondominant arm differences in controls (all p < 0.05) and (2) throwing-to-nonthrowing arm differences in throwers being progressively greater across maturity groups (all p < 0.05). Regional analyses revealed greatest adaptation in medial and lateral sectors, particularly in the three post-maturity groups. Years throwing predicted 59% of the variance of the variance in throwing-to-nonthrowing arm difference in SSIP (p < 0.001). CONCLUSION: These data suggest that physical activity has skeletal benefits beginning prior to and continuing beyond somatic maturation and that a longer duration of exposure to physical activity has cumulative skeletal benefits. Thus, physical activity should be encouraged at the earliest age possible and be continued into early adulthood to optimize skeletal benefits