1 low-energy bone fractures david pienkowski, phd, mba and hartmut malluche, md university of...
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Low-Energy Bone Fractures
David Pienkowski, PhD, MBAand
Hartmut Malluche, MD
University of KentuckyDepartments of Biomedical Engineering,
Orthopaedic Surgery, and Internal MedicineLexington, KY
presented at the American Academy of Forensic Sciences
Seattle, WA20 February 2014
copyright © 2014
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Recently, at our institution…
• increasing incidence of “atraumatic“ bone fractures─ i.e., fractures without high-energy cause
─ a.k.a. “low-energy” fractures
• “low-energy” bone fractures also reported in the literature─ etiology unknown
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Low-Energy Fractures
a.k.a. fragility or atraumatic fractures
1. qualitative definition (as per the literature):
a) due to fall from standing height or less*
b) accompanying Activities of Daily Living
c) occurring from unknown non-trauma causes
2. no quantitative definition exists a) unlike: blood pressure, height, weight – all have
well-defined normal, low & high values
*Mackey C., Dawn. “High-Trauma Fractures and Low Bone Mineral Density in Older Women and Men. “J Am Med Assoc 28 November 2007
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Problem
• forces accompanying the fracture-related event• disproportionately small compared to those
causing “typical” fractures• creates uncertainty for the forensic investigator:
─ were all pertinent facts collected?
─ was the reconstruction valid?
─ what’s wrong with _____?
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Learning Objectives
1. increase awareness of low-energy fractures
2. define “bone quality” & its parameters
3. add to our understanding why injury may occur from low-energy events
Bone Quality…
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• the term used to expressing bone’s biomechanical competence
• quantified by many parameters…
Bone Quality
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Bone
Material
&
Structure
Bone
Stiffness,
Strength
& Fx Tough-
ness
Material ParametersRelative Mineralization
Crystal Size
Crystal Composition
Crystal Purity
Matrix Crosslinking
Microdamage
Structural Parameters
Trabecular Bone Volume
Trabecular Thickness
Trabecular Separation
Cortical thickness
Cortical porosity
Strategy
• identify subjects with low-energy fractures• quantify bone density & bone quality parameters• compare to control population• test for statistically significant bone quality
abnormalities• try “easiest & least expensive” tests firsts
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First Potential Cause
• Potential Cause #1: low bone mass attributable to undiagnosed osteoporosis
• Procedure:─ interview subjects for history of surgical or natural
loss of estrogen production
─ perform Dual Energy X-ray Absorptiometry test
─ quantify Bone Mineral Density
─ compare BMD values with large population-based “normal” values
─ do low-energy fracture subjects meet osteoporosis criteria?
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Osteoporosis* is Well-Defined
•qualitatively:─ thinner cortices & thinner trabeculae─ greater cortical porosity─ fewer trabecular connections─ less mineralized*
•quantitatively:─BMD t-score < 2.5 s
*Type I Osteoporosis accompanying cessation of estrogen production
** hypothesis based on findings from: Malluche HH, Porter DS, Monier-Faugere MC, Mawad H, Pienkowski D. Differences in Bone Quality between High versus Low Turnover Renal Osteodystrophy. Journal of the American Society of Nephrology 23(3):525-32, 2012
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Prevalence of Osteoporosis
• 10% of Americans > 50 years of age have osteoporosis─ 16% women─ 4% men*
• 49 million Americans now have, or are at high risk of, low bone mass due to osteoporosis**
• CDC Report: Scientific American, 4/26/12
• **NIH Osteoporosis and Related Bone Diseases National Resource Center, November 2011
Results
• all low fracture subjects had DEXA t-scores > -2.5
─no subjects were osteoporotic*
• Bottom line: low bone strength due to osteoporosis was not the explanation
• Next…
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*also, no subjects were > 50 years of age, nor were any of these women pre/post/perimenopausal
Second Potential Cause• Potential Cause #2: bone microstructural
abnormality─ same amount of bone, but abnormal microstructure
• Procedures:─ DEXA unable to determine microstructural differences
─ need invasive bone (iliac crest of hip) biopsy
─ sample staining, mounting, histological processing, & histomorphometric examination for quantification of established bone micro architectural parameters
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Bone Histomorphometry
Bell KL et al. Bone. 2000;27:297–304.Figure reprinted from Bone, Vol. 27, Bell KL, et al. A novel mechanism for induction of increased cortical porosity in cases of intracapsular hip fracture; p 297–304, Copyright 2000, with permission from Elsevier.
Generation of composite osteonal systems with giant Haversian canal
Simple osteonalsystem
Composite osteonal system
Haversian canal
On.Dm.
H.Ca.Dm.
W.Th.
O.Wi.
Minimum Dimensions Measured Within Osteons
On.Dm. = osteon diameter; H.Ca.Dm. = Haversian canal diameter; W.Th. = wall thickness; O.Wi. = osteoid width.
Results• all cortical and cancellous bone structural
parameters were within normal limits• Bottom line: low energy fractures cannot be
explained by microstructural abnormalities• Next…
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Bone Structure & Material
• bone is a composite material• hydroxyapatite (mineral) crystals in a collagen fiber matrix
• complex hierarchy of structures: macro/micro/nano levels
Third Potential Cause• Potential Cause #3: bone mineral abnormality
─ relative mineralization (more precise than DEXA)
─ crystal size, composition, or purity
• Procedure:─ re-examine patient’s bone biopsy
─ cut thin (4 – 7 micron) slices of bone
─ “sandwich” section between 2 BaF discs
─ pass infra-red light through “sandwich”
─ analyze input – output transmitted light spectra via Fourier Transform Infrared Spectroscopy (FTIR)
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Results• relative mineral content = normal• mineral crystal size, composition, & purity =
normal• Bottom line: bone mineral abnormalities were
not statistically associated with low energy fractures
• Next…
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Fourth Potential Cause• Potential Cause #4: bone matrix abnormality
─ abnormality in bone collagen matrix
• Procedure:─ reanalyze existing FTIR data
─ examine spectra for matrix-related information
─ limited matrix information available from FTIR
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Results• statistically significant abnormal relative amounts of
mature and immature collagen crosslinks • Bottom line: patients with low-energy fractures have
abnormal relative amounts of each type of collagen crosslinking*
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* Malluche HH, Porter DS, Mawad H, Faugere MC, Pienkowski D. Low-energy fractures without low BMD t-scores of osteoporosis: a bone matrix disorder. Journal of Bone and Joint Surgery (Am) 2013 October 2;95 (19)
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Limitations
1. no information linking abnormal bone matrix crosslinking ratio with abnormal bone biomechanics
2. other matrix parameters not studied (require additional & more complex techniques)
3. extent of bone microdamage unstudied – work ongoing
Summary1. normal bone = biomechanically optimal material & structure
2. low-energy fracture?• examine bone quality* parameters
3. abnormalities in one or more of these parameters?
4. bone quality abnormalities linked to abnormal biomechanics• small deviations in some bone quality parameters
• may be linked to large changes in fracture-relevant biomechanical parameters
5. despite normal “appearances” not all bones are normal
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*bone quality = ability to bear load, resist excess deformation, & avoid fracture in response to single and repetitive physiological loads
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Mineralization & Biomechanics
*Wainwright, Biggs, Curry, Gosline. Mechanical Design in Organisms. Halsted Press, New York, 1976
fracture toughness depends critically upon mineralization
bone is 3X tougher at 70% mineralization than at 63% mineralization*
Remarks
1. when injury is disproportionate to energy
a) look closer, there is an explanation
b) study bone quality & compare to normal
2. expect more low-energy bone fractures:
a) societal & demographic factors portend a reduction in bone injury thresholds
b) specifically…
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Bone Quality Alterations due to…• lifestyles
─ diet: high protein/sodium/caffeine; low calcium & water intake
─ smoking (28.3% of Kentuckians**, 18.1% of Americans)*
─ inadequate sunlight & Vitamin D deficiency
─ inactivity & suboptimal bone mass
• medications─ long-term steroid use
─ proton-pump inhibitors
─ long-term osteoporosis drug use
• demographics─ aging of the American & world population
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*CDC Center for Disease Control and Prevention, http://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/accessed 2/15/14 **Kentucky ranks #1 in percentage of smokers
Conclusions
1. “low-energy” does not mean “no injury”
2. there is a reason = bone quality abnormalities were linked to reduced injury thresholds
3. applicable to other tissues & organs?• examine the parameters governing injury
thresholds to reconcile disparities between a low-energy mechanical event and the accompanying biological outcome
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Thank You for Your Attention
Questions?
Additional study details may be found from the following sources:*1. Malluche HH, Porter DS, Mawad H, Faugere MC, Pienkowski D. Low-energy fractures without low BMD t-scores of osteoporosis: a bone matrix disorder. Journal of Bone and Joint Surgery (Am) 2013 October 2;95 (19)
2. Malluche, HH, Porter DS, Pienkowski. Bone Quality. Nature Reviews Nephrology, November 2013