Thomas G. Travison, Ph.D.

1
Body Composition, Sex Steroids and Proximal
Femur Geometry in Men

• Thomas G. Travison, Ph.D.

New England Research Institutes, Watertown, MA
02472 ttravison_at_neriscience.com Supported by
the NIH (DK56842, AG20727) and GlaxoSmithKline,
USA
2
Introduction

• Osteoporosis is an emerging public health concern
  for aging men
• United States 2 million men1
• Unexpectedly high mortality following
  osteoporotic fracture2
• Elevated bone mineral content (BMC) and bone
  mineral density (BMD) protect against fracture
• Body Mass Index (BMI) and circulating estradiol
  (E2) and testosterone (T) associated with
  increased BMD
• BMI cannot differentiate between lean and fat
  mass
• BMD not a direct measure of bone strength
• Material (captured by BMC/BMI)
• Architectural Arrangement

1Looker et al. Osteoporos Int 8(5) 46889.
2Seeman E. Rev Endocr Metab Disord 2(1) 25-64.
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Role of Lean vs. Fat Mass Lack of Consensus

• Many authors Fat mass of primary importance1
• Others Lean mass of
• greater importance in women2,
• men3, or both4

(2) Aloia et al. Am J Clin Nutr 1995. Li S et al.
Maturitas 2004. Wang MC et al. Bone 2005.
(1) Stewart et al. J Intern Med 2002. Reid et
al. J Clin Endocrinol Metab 1992. Reid et al. J
Clin Endocrinol Metab 1992. Khosla et al. J Bone
Miner Res 1996. Ravn et al. J Bone Miner Res
1999. Pluijm et al. J Bone Miner Res 2001. Wu et
al. Clin Endocrinol (Oxf) 2002. Reid. Bone
2002. Lim et al. Bone 2004. Wang MC et al. Bone
2005.
(3) Reid et al. J Clin Endocrinol Metab
1992. Taaffe et al. J Bone Miner Res 2001. Van
Langendonck et al. Am J Hum Biol 2002. Lim et al.
Bone 2004.
(4) Ferretti JL et al. Bone 1998. Bakker et al. J
Clin Endocrinol Metab 2003. Capozza et al. Bone
2004. Hsu et al. Am J Clin Nutr 2006. Zhao et al.
J Clin Endocrinol Metab 2007.
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Objective

• Using measures of bone material and architectural
  arrangement, assess competing influences of
• Body Composition (lean and fat mass)
• Circulating Sex Hormones (T and E2)
• on bone strength at the proximal femur.

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Methods

• Boston Area Community Health/Bone Study
  (BACH/Bone)
• Randomly-selected, community-dwelling subjects
• N 1,219
• BMC, Body Composition by DXA
• B.U. School of Medicine (Michael Holick, MD, PhD)
• Lean mass Nonfat mass bone mass
• Total T and SHBG by competitive
  electrochemiluminescence immunoassay. Total E2 by
  liquid chromatography-tandem mass spectrometry.
• Calculated Free T and E2 by mass action
  equations1,2
• Hip geometry by Hip Structural Analysis (HSA)3

1Sodergard, J Steroid Biochem 1982 2Vermeulen, J
Clin Endocrinol Metab 1999 3 Beck Curr
Osteoporos Rep 2007
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Methods HSA

• Use engineering principles1 to understand
  proximal femurs capacity to resist failure

• From DXA Images, obtain
• BMD
• Material
• Cross-Sectional Area (CSA)
• Width
• Outer Diameter (OD)
• Bending Strength
• Section Modulus (Z)
• Resistance to Buckling
• Average Buckling Ratio (ABR)

• Measurement Johns Hopkins School of Medicine
  (Thomas Beck, ScD)

1Martin RB, Burr DB J Biomech 17(3)195-201
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Threshold association
Results BMI and BMC
BMC (g)
Corr BMI, LM .62
Corr BMI, LM .20
Association driven by LM?
Travison et al, Osteoporos Int. 2008
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Results Threshold Models1
Positive associations between fat mass / BMI and
BMC removed by control for lean mass
1 Multiple linear regression, controlling for
age, race/ethnicity, physical activity, and
height (for models excluding BMI).
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Results Hip Structural Analysis

• Control for lean mass removes fat mass
  associations

• Control for fat mass does not affect lean mass
  associations

Travison et al, J Bone Miner Res 2008
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Summary Results Body Composition

• In BACH/Bone, Lean Mass accounts for
  cross-sectional associations between
• BMI or Fat Mass and
• bone material, architectural strength at the hip

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Exploratory Results Circulating Sex Hormones
E2, but not T, demonstrates age-adjusted
association with BMC and BMD
Results similar for HSA measures of geometric
strength
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Results Body Comp Accounts for E2 Effect at
Most Sites
Significant Age-Adjusted Associations
Removed by Control for Body Composition
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Results Summary

• Control for total body lean mass removes Positive
  association between BMI / fat and conventional
  BMD, or HSA measures
• 2. Control for age removes T ? BMD/HSA
  association, but not E2 ? BMD/HSA association
• Results suggest that body composition can account
  for influence of E2

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Implications

• It is likely that elevated lean mass accompanying
  elevated BMI accounts for protective influence of
  obesity for fracture risk
• Maintenance of proportionate lean mass (and not
  only weight) is a promising strategy for
  maintaining bone strength
• Aspects of body composition may mediate the
  protective influence of circulating E2 on male
  bone strength
• Future Longitudinal Data, Path / Causal Modeling