Reference data and calculators for second-generation HR-pQCT measures of the radius and tibia at anatomically standardized regions in White adults.

High-resolution peripheral quantitative computed tomography (HR-pQCT) is a powerful tool to assess bone health. To determine how an individual's or population of interest's HR-pQCT outcomes compare to expected, reference data are required. This study provides reference data for HR-pQCT measures acquired in a population of White adults. PURPOSE: To provide age- and sex-specific reference data for high-resolution peripheral quantitative computed tomography (HR-pQCT) measures of the distal and diaphyseal radius and tibia acquired using a second-generation scanner and percent-of-length offsets proximal from the end of the bone. METHODS: Data were acquired in White adults (aged 18-80 years) living in the Midwest region of the USA. HR-pQCT scans were performed at the 4% distal radius, 30% diaphyseal radius, 7.3% distal tibia, and 30% diaphyseal tibia. Centile curves were fit to the data using the LMS approach. RESULTS: Scans of 867 females and 317 males were included. The fitted centile curves reveal HR-pQCT differences between ages, sexes, and sites. They also indicate differences when compared to data obtained by others using fixed length offsets. Excel-based calculators based on the current data were developed and are provided to enable computation of subject-specific percentiles, z-scores, and t-scores and to plot an individual's outcomes on the fitted curves. In addition, regression equations are provided to convert estimated failure load acquired with the conventional criteria utilized with first-generation scanners and those specifically developed for second-generation scanners. CONCLUSION: The current study provides unique data and resources. The combination of the reference data and calculators provide clinicians and investigators an ability to assess HR-pQCT outcomes in an individual or population of interest, when using the described scanning and analysis procedure. Ultimately, the expectation is these data will be expanded over time so the wealth of information HR-pQCT provides becomes increasingly interpretable and utilized.

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 (<-2, -2 to 2, 2 to 4, 4 to 10, and >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.

Activated leukocyte cell adhesion molecule (ALCAM or CD166) modulates bone phenotype and hematopoiesis.

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166), is expressed on osteoblasts (OB) and hematopoietic stem cells (HSC) residing in the hematopoietic niche, and may have important regulatory roles in bone formation. Because HSC numbers are reduced 77% in CD166(-/-) mice, we hypothesized that changes in bone phenotype and consequently the endosteal niche may partially be responsible for this alteration. Therefore, we investigated bone phenotype and OB function in CD166(-/-) mice. Although osteoclastic measures were not affected by loss of CD166, CD166(-/-) mice exhibited a modest increase in trabecular bone fraction (42%), and increases in osteoid deposition (72%), OB number (60%), and bone formation rate (152%). Cortical bone geometry was altered in CD166(-/-) mice resulting in up to 81% and 49% increases in stiffness and ultimate force, respectively. CD166(-/-) OB displayed elevated alkaline phosphatase (ALP) activity and mineralization, and increased mRNA expression of Fra 1, ALP, and osteocalcin. Overall, CD166(-/-) mice displayed modestly elevated trabecular bone volume fraction with increased OB numbers and deposition of osteoid, and increased OB differentiation in vitro, possibly suggesting more mature OB are secreting more osteoid. This may explain the decline in HSC number in vivo because immature OB are mainly responsible for hematopoiesis enhancing activity.

Age-related changes in proximal humerus bone health in healthy, white males.

UNLABELLED: The proximal humerus is a common site for osteoporotic fracture. The current study demonstrates the rate of age-related decline in proximal humerus bone health. The data suggest aging is associated with considerable loss of bone mass, structural deterioration and reduced bone strength at the proximal humerus. INTRODUCTION: The proximal humerus is relatively under investigated despite being the fourth most common site for osteoporotic fracture. METHODS: A cross-sectional study was performed to assess age-related changes in dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) properties of the proximal humerus in a cohort of 170 healthy, white males. RESULTS: Regression models estimated considerable age-related loss of DXA measured bone quantity at the proximal humerus, with areal bone mineral density modeled to decline by 29% (95% confidence interval [CI], 17.5-35.0%) in the 50 years between ages 30 and 80 years (p < 0.001). pQCT measures indicated aging was associated with progressive periosteal and endosteal expansion, with the later occurring more rapidly as indicated by age-related declines in cortical bone mass, area and thickness (all p < 0.01). The net result of the density, mass and structural changes was a 26% (95% CI, 13.5-38.0%) decline in pQCT estimated proximal humerus bone strength in the 50 years between ages 30 and 80 years (p < 0.001). CONCLUSION: Aging is associated with considerable declines in proximal humeral bone health which, when coupled with a traumatic event such as a fall, may contribute to osteoporotic fracture at this site.

Strontium ranelate does not stimulate bone formation in ovariectomized rats.

INTRODUCTION: Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium. METHODS: Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, mu-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed. RESULTS: SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca. CONCLUSION: These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.

Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats.

Exercise and bisphosphonate therapies increase bone strength by primarily increasing bone formation and reducing resorption, respectively. Based on these different mechanisms of action, it is possible that combined introduction of exercise and bisphosphonate therapies generates greater improvements in bone mass and strength than either intervention alone. The aim of this study was to examine the individual and combined effects of exercise (treadmill running) and bisphosphonate therapy (alendronate [ALN]) on bone mass and strength in ovariectomized (OVX) rats. Seven-month-old virgin female rats were randomly assigned to either a sham-OVX group (n=13) or one of four OVX groups: vehicle-treated cage-control (VEH-CON, n=10); ALN-treated cage-control (ALN-CON, n=13); vehicle-treated plus treadmill running (VEH-RUN, n=13); and ALN-treated plus treadmill running (ALN-RUN, n=13). ALN-treated groups received twice-weekly ALN (0.015 mg/kg), and exercise groups ran on a motorized treadmill at a 5% incline for 60 min/day, 22-24 m/min, 5 days/week. In vivo measurements included dual-energy X-ray absorptiometry (DXA) of whole-body bone mineral content (BMC), and ex vivo measurements included DXA, micro-computed tomography (muCT), and mechanical testing of the femur and L4 vertebrae. After 14 weeks of intervention, exercise and ALN had additive benefits on whole body and proximal femur BMC, cross-sectional area of the L4 vertebrae, and mechanical properties of the mid-shaft femur. In comparison, for total and mid-shaft femur BMC, L4 vertebrae BMC, and mid-shaft femur cortical thickness and area, there were significant exercise and ALN interactions indicating that the two interventions worked in synergy to enhance bone properties. Supporting the contention that ALN and exercise function via distinct mechanisms of action, ALN successfully reduced medullary canal area suggesting it reduced endocortical bone resorption, whereas exercise augmented periosteal perimeter suggesting it stimulated periosteal bone formation. In summary, we found combined treadmill running and ALN to be more beneficial in preventing declines in bone mass and strength following OVX than the introduction of either intervention alone. These data suggest that a comprehensive program of bisphosphonate therapy and weight-bearing exercise may be an effective method for preventing and treating osteoporosis in post-menopausal women.

Steps for targeting exercise towards the skeleton to increase bone strength.

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.

Bone gains and losses follow seasonal training and detraining in gymnasts.

The response of the human skeleton to high magnitude loading and unloading is poorly understood. Our aim was to evaluate changes in bone mineral density (BMD) in a group of intercollegiate gymnasts (n = 8, age = 18.6+/-0.8 years) over 24 months that included two 8-month competitive seasons and two 4-month offseasons. BMD of the hip, spine, and whole body was evaluated by DXA (Hologic QDR-1000/W) at baseline, 8, 12, 20, and 24 months. Results indicated significant seasonal trends in BMD of the femoral neck, trochanter, total hip, lumbar spine, and whole body. Specifically, there was a strikingly consistent pattern of bone density increases over the training seasons followed by clear declines in the offseasons. Increases at the spine were 3.5% and 3.7% followed by declines of 1.5% and 1.3% in the offseasons. Total hip BMD increased 2.3% and 1.9% during the competitive seasons followed by decreases of 1.5% and 1.2% in the offseasons. We observed a significant 24-month increase of 4.3% in spine BMD but no significant overall change at the hip. In conclusion, the human skeleton demonstrated a measurable response to high magnitude loading and unloading that was consistent across bone sites over 24 months of observation.

Jumping improves hip and lumbar spine bone mass in prepubescent children: a randomized controlled trial.

Physical activity during childhood is advocated as one strategy for enhancing peak bone mass (bone mineral content [BMC]) as a means to reduce osteoporosis-related fractures. Thus, we investigated the effects of high-intensity jumping on hip and lumbar spine bone mass in children. Eighty-nine prepubescent children between the ages of 5.9 and 9.8 years were randomized into a jumping (n = 25 boys and n = 20 girls) or control group (n = 26 boys and n = 18 girls). Both groups participated in the 7-month exercise intervention during the school day three times per week. The jumping group performed 100, two-footed jumps off 61-cm boxes each session, while the control group performed nonimpact stretching exercises. BMC (g), bone area (BA; cm2), and bone mineral density (BMD; g/cm2) of the left proximal femoral neck and lumbar spine (L1-L4) were assessed by dual-energy X-ray absorptiometry (DXA; Hologic QDR/4500-A). Peak ground reaction forces were calculated across 100, two-footed jumps from a 61-cm box. In addition, anthropometric characteristics (height, weight, and body fat), physical activity, and dietary calcium intake were assessed. At baseline there were no differences between groups for anthropometric characteristics, dietary calcium intake, or bone variables. After 7 months, jumpers and controls had similar increases in height, weight, and body fat. Using repeated measures analysis of covariance (ANCOVA; covariates, initial age and bone values, and changes in height and weight) for BMC, the primary outcome variable, jumpers had significantly greater 7-month changes at the femoral neck and lumbar spine than controls (4.5% and 3.1%, respectively). In repeated measures ANCOVA of secondary outcomes (BMD and BA), BMD at the lumbar spine was significantly greater in jumpers than in controls (2.0%) and approached statistical significance at the femoral neck (1.4%; p = 0.085). For BA, jumpers had significantly greater increases at the femoral neck area than controls (2.9%) but were not different at the spine. Our data indicate that jumping at ground reaction forces of eight times body weight is a safe, effective, and simple method of improving bone mass at the hip and spine in children. This program could be easily incorporated into physical education classes.