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CCEB. Whole Body Vibration as an Anabolic Bone Therapy in Children. Mary B. Leonard, MD, MSCE The Children’s Hospital of Philadelphia Center for Clinical Epidemiology and Biostatistics. 2000 NIH Osteoporosis Consensus Conference Statement.

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Whole Body Vibration as an Anabolic Bone Therapy in Children

Mary B. Leonard, MD, MSCE

The Children’s Hospital of Philadelphia

Center for Clinical Epidemiology and Biostatistics

2000 nih osteoporosis consensus conference statement
2000 NIH Osteoporosis Consensus Conference Statement

  • Peak Bone Mass is a critical determinant of life-long skeletal health

  • Maximizing peak bone mass is a priority

  • The NIH called for research strategies to identify and intervene in disorders that compromise attainment of peak bone mass in children with chronic disease

    • Especially corticosteroid therapy

Rethinking osteoporosis
Rethinking Osteoporosis

  • Bone strength is a function of bone density (g/cm3) and bone quality

  • Bone quality refers to geometry, micro-architecture, turnover, micro-damage repair, and mineralization

Osteoporosis Prevention, Diagnosis & Therapy

NIH Consensus Conference 2000

Cortical dimensions strength
Cortical Dimensions & Strength

Cross-Sectional Moment of Inertia

p(RP4 - RE4)

Remove 30 mm2

Add 100 mm2

D. Burr and C. Turner. ASBMR Primer

Skeletal remodeling
Skeletal Remodeling

Skeletal modeling during growth
Skeletal Modeling during Growth

W.S. Jee

Changes in cortical trabecular bone with growth
Changes in Cortical & Trabecular Bone with Growth

  • Trabecular Bone Volume Fraction

    • Increases during Tanner stages III – V

    • Increases are greater in blacks than whites

    •  trabecular thickness and material density

  • Cortical Density and Dimensions

    • Density increases with age, F > M

    • During puberty boys develop greater periosteal radius and girls develop relatively smaller endosteal radius

    • CSMI greater in blacks than whites

Gilsanz V, et al. NEJM 1991, J Clin Endo Metab 1997, J Clin Endo Metab 1998.

Seeman E. Lancet 2002. Rauch and Schoenau JBMR 2001.

Threats to bone health in children with crohn diseases
Threats to Bone Health in Children with Crohn Diseases

  • Decreased muscle forces / loading

  • Malnutrition

    • Calcium, Vitamin D, Vitamin K, Zinc

  • Delayed puberty

  • Alternations in GH / IGF axis

  • Medications

    • Glucocorticoids

  • Inflammatory Cytokines

    • IL-6, TNF-a

Glucocorticoid induced osteoporosis
Glucocorticoid-Induced Osteoporosis

  • Glucocorticoids are widely used in pediatrics

  • Glucocorticoids

    •   Bone formation

    •  Bone resorption then ?  Bone resorption

  • Glucocorticoids are associated with increased fracture rates in children

  • Assessment of GC effects may be confounded by

    • effects of the underlying disease

    • altered growth, maturation and body composition

    • limitations of DXA techniques


Glucocorticoid & Cytokine Effects

on Bone Cells

  • Glucocorticoid Effects

  • Decrease Bone Formation

  • Shift cellular differentiation of stem cells away from osteoblasts

  • Inhibit osteoblast production of bone matrix

  • Promote osteoblast apoptosis

  • Impair osteocytes

    Increase Bone Resorption

  • Promote osteoclastogenesis by  RANKL and  OPG expression in osteoblasts

  • TNF-a Effects

  • Decrease Bone Formation

  • Shift cellular differentiation of stem cells away from osteoblasts

  • Inhibit collagen synthesis by osteoblasts

  • Promote osteoblast apoptosis

  • Impair osteocytes

    Increase Bone Resorption

  • Promote osteoclastogenesis by  RANKL and  OPG expression in osteoblasts

Models of glucocorticoid induced osteoporosis in children
Models of Glucocorticoid-Induced Osteoporosis in Children

  • Crohn Disease

  • Steroid Dependent Nephrotic Syndrome

  • Juvenile Idiopathic Arthritis

  • Renal Transplant

Crohn disease
Crohn Disease

  • Chronic inflammatory bowel disease

  • Insidious onset

  • May result in abscesses, granulomas or fistulas

  • 85% of children present with weight loss

  • Growth failure and pubertal delay are common

  • Treated with systemic glucocorticoids, steroid enemas, 5-ASA, methotrexate and other immunomodulators

  • Associated with fractures in children and adults

Crohn disease bone mineral content
Crohn Disease & Bone Mineral Content

  • DXA Scans in 104 children and young adults with CD

  • Age: 4 – 25 yr

  • CD duration: 4.0 + 3.4 yr

  • Median cumulative glucocorticoid exposure: 10,300 mg

Ln (Height)

Burnham, et al. J Bone Miner Res 2004

Whole body bone mineral content in crohn disease compared with controls
Whole Body Bone Mineral Content in Crohn Disease Compared with Controls

Burnham, et al. J Bone Miner Res 2004

Inflammatory cachexia
Inflammatory Cachexia with Controls

  • Lean mass deficits without fat mass deficits

  • Muscle active cytokines (TNF-a, IL-6, IL-1b)

    • inhibit myogenic differentiation

    • stimulate muscle protein degradation

    • induce myoblast apoptosis

  • Note: Glucocorticoids increase myostatin, a negative regulator of muscle mass

Burnham, et al. AJCN 2005

Thayu, et al IBD 2007

Hip structural analysis
Hip Structural Analysis with Controls

T. Beck

Femoral shaft z scores in crohn disease and nephrotic syndrome

1.00 with Controls





Group differences eliminated after adjustment for lean mass for height z-score



Z Scores













Femoral Shaft Z-Scores in Crohn Disease and Nephrotic Syndrome

Burnham, et al. JBMR 2007


Peripheral Quantitative CT with Controls

Muscle CSA

Cortical Dimensions

Trabecular Density

Treatment options
Treatment Options with Controls

  • Treat the underlying disease!

  • Calcium and Vitamin D supplements

  • Osteoporosis medications?

    • Antiresorptive agents

    • Anabolic agents

  • Weight bearing physical activity


High Impact Physical Activity in Childhood with Controls

Increases Bone Density and Dimensions

Athlete studies
Athlete Studies with Controls


Triple Jumper


Area +30%


Density +67%

Rachel Wetzsteon Heinonen et al. Bone, 2003

Is there a window of opportunity
Is there a “Window of Opportunity?” with Controls



BMC % Side-to-Side Diff




Slide prepared by Rachel Wetzsteon Kannus et al., 1995.

Bone strain
Bone Strain with Controls

  • Osteocytes sense bone strain

  • Bone strain is the percentage change in length in response to a load.

  • If bone is deformed by 0.1%, its strain is 0.001, or 1000 mstrain.

  • In humans, peak strains are generally less than 2000-3000 mstrain, even during vigorous activities


anabolic with Controls



Bone can be maintained with a few large loading cycles, or thousands of extremely small ones

Qin et. al., 1998


control with Controls


45% increase in trabecular bone volume

12% increase in stiffness

27% increase in strength

Rubin et. al.,Nature 2001

But wait there s more to the story
But, wait! with ControlsThere’s more to the story….


Control with Controls

  • Adipogenesis

  • Mesenchymal stem cell differentiation into adipocytes


Acknowledgements with Controls

  • Project Staff

    • Krista Howard and Kristin Frino

  • NIH


  • CHOP IBD Center and GI Division

    • Robert Baldassano and Meena Thayu

    • Meena Thayu, MD

  • CHOP Nutrition and Growth Lab

    • Babette S. Zemel, PhD

  • SUNY and Juvent, Inc

    • Clint Rubin, PhD