Bone Quality

Induction of Osteoporotic
Fractures

Prof. Dr. Hazem Abd El-Azeem

Professor of Orthopaedic Surgery
Cairo University
 Traditional (Old) Definition of
Osteoporosis
1. Pathological :
– A disease characterized by low bone
mass leading to bone fragility and
increased risk of fractures.
2. Denstiometry
– T-score <- 2.5 8D = osteoporosis .
– (> -1= normal , -1:-2.5 = osteopenia )
 Staging of osteoporosis based on BMD (DEXA)
and vertebral fracture

 Clinical Stage  Criteria

 0 osteopenia
(preclinical osteoporosis)
 1 Osteoporosis without
fractures
 2 Established osteoporosis
 - lowered BMD
(T score: —1 to —2.5 SD)
 reduced BMD, no fractures
(T score: <—2.5 SD)
 - reduced BMD -trauma, vertebral fractures

( T score : > —2.5 )

(with fractures)
 - reduced BMD, multiple
 3 Advanced vertebral fractures, often non-
osteoporosis vertebral fractures
 Fluoride
 sodium fluoride, BMD at the
lumbar spine increased by 35%.
but there was no decrease in
fracture incidence.
 Bone Quantity vs Bone Quality:
Evolution of the Paradox
Positive bone former/ Increase in % Decrease in vertebral
antiresorptive agent vertebral BMD fracture risk
35 0
Fluoride1
1-1.5 36
Calcltonin-salmon2
2-3 30
Raioxifene3
3-5 41
Risedronate4
6-8 47
Alendronate5
1. Riggs BL et al. N Engi J Med 1990;322:802-9.
2. Chesnut C III et al. Am J Med. 2000;109:267-76.
3. Ettinger B et al. JAMA. 1999;282:637-45.
4. Harris ST et al. JAMA. 1999;282:1344-52
 BMD increase is not proportional to reduction of
relative risk of vertebral fracture

Tested Change in BMD versus % reduction of vertebra

Studies
Product control (%) fracture risk over 3 year

PROOF
(Chesnut et al., Calcitonin 0.5 36
Am.J.Med.2000)

MORE
(Ettinger et al., JAMA 1999) Raloxifen 2.6 30
FIT2
(Cummings et al., JAMA Alendronate 6.8 44
1998)

VERT-MN
(Reginster et al. ,
Osteoporosis Int 2000)
Risedronate 5.9 49
 Bone Mechanics
 Bone mechanics can be
used to define the material
properties of bone such as
strength, resilience and
toughness.

The mechanics of bone can

be illustrated using a stress-
strain curve.
 Bone Strength is the
Function
of Multiple Factors!

Bone Quality
Bone Quantity
-Micro-Architecture
Mass
Connectivity
Bone Mineral Density
Mineralization
Size
Micro-damage
Collagen cross-linking

Chesnut et al. JBMR 2001; 16: 2163-72.

 The Basic Bone Quality
Concept
 Because osteoporosis is associated with
low bone mass, BM D measurements are
used to assess the efficacy of treatment
for the disease. However, there is
growing evidence that bone mass is just
one of many factors that contribute to
bone strength. The concept of bone
quality has been introduced to
incorporate these other factors.
What is Bone Quality?
 Architecture
 Mineralization
 Organic matrix
 Damage state
 Rapid Deterioration of Microarchitecture
parameters
Amount of Bone
Bone volume

Trabecula
r Status
Trabecular
number
Trabecular
separation

Porosity
Marrow Star 1 Year
Baseline
Volume
Control Patients
Borah
, et al. OI 2002 World Congress on Osteoporosis
Dufre
e,
snet al. OI 2002 World Congress on Osteoporosis
 Osteoporotic Changes in the
Trabecular Architecture
Normal Female, 54 yr
of Vertebrae
Osteoporotic Female (with vert. Fx), 82
yr.

Loss of bone mass and horizontal trabeculae connectivity

3-D computer tomography, human cadaver vertebral bone Borah, et al. Anat. Rec. 2001
 Why Is It Important to Examine
Trabecular Connectivity ?
 Decrease in trabecular thickness is
Normal
more pronounced for non load-
bearing horizontal trabeculae.

 Decrease in connections between

Moderate
Osteoporosis horizontal trabeculae

 Decrease in trabecular strength

Severe
Osteoporosis
and increased susceptibility to
fracture from gravity and physical
activity.
Mosekilde L. Calcified Tissue Inter. 53(Suppl 1): S121-S126. 1993
 Architecture
 Similarly in
osteoporosis a small
increase in the mass
of structurally
important trabeculae
would have little
effect on total BUD,
but would improve
bone strength
greatly.
 Architecture
 The supportive
strength of a series of
columns can be±
enhanced greatly, but
with minimal effect
on mass, by adding a
few, relatively small
cross‑struts.
 Mineralization
 Changes in the mineral density or
organic matrix of bone may effect
bone strength..
 Organic Matrix
 The organic matrix is composed
mostly of type l collagen and
provides the plasticity of bone.
 Collagen-deficient bone are less
tough than bone with normal
collagen, although the difference
in BMD was minor .(shown in
animal studies on mice )
 Damage State
 The extent of fatigue or micro-
damage affects the mechanics of
any material, and particularly its
strength
 The number of micro-cracks
increases exponentially with age
and cannot be assessed by BMD
measurements.
Preservation of horizontal Trabecular
struts
Osteoporosis Normal
Bone remodeling
Bone Remodelling
Cycle

• Initiated by:
—Unknown signal:
? Hormonal
? Stress
???
 Bone Remodelling
Cycle
 First : - Erosion phase (resorption)
- Cell: Osteoclast
- Span: From 2-4 weeks
- Loss: Erosion of 40-60 hm
Bone remodelling
cycle

 Second :- Lag
phase..
 7 to 10 days
 Bone Remodelling
Cycle
 Third : reversal phase:
- Cell : Osteoblast
- Span :Variable
- Gain : Variable - depending
on several factors: Up to 22 years of age
22 years to menopause
After menopause
 Bone Remodelling
Is it Reparative or Damaging ?
 The main functions of bone remodelling
are mineral homeostasis and the
maintenance of strength,
 A high resorption rate is 'coupled with a
significantly increased fracture risk.
 Resorption affects bone strength by
mechanisms that are independent of
bone density.
Excessive repairs weaken structures
 Bone Remodelling

 Possible theoretical explanations:

1. increased resorption results. in a
greater number of bone remodelling.
cavities, which may severely weaken, or
possibly breach, crucial trabeculae.
Bone quality would be impaired, but
with only a minimal change in BMD.
 Bone Remodelling

 Possible theoretical explanations:

2. Excessive remodelling at micro-
damaged sties may occur, weakening
the bone even further and possibly
leading to increased micro-damage.
 Bone Remodelling
 Possible theoretical explanations:
3. A high resorption rate may prevent
complete mineralization of new bone
before the remodelling process begins
again. This will impact on bone trength,
but also affects BMD.
 Bone Quality Concept
 That is why some newly added
words to the definition of
osteoporosis emphasize the
importance of the bone micro-
architecture.
 Bone Quality Concept
 High resorption rate associated
with osteoporosis reduces bone
strength without necessarily
reducing bone mass.
 Bone strength can be improved
without increasing bone mass.
 New defintion
Bone Strength replacing BMD as the key

Before endpoint for proof of efficacy

Now

Definition of Osteoporosis
1993 consensus conference
“osteoporosis is a “Osteoporosis is a skeletal disorder characterized by compromised
bone strength predisposing a person to an increased risk of fracture.”
systemic skeletal disease
characterized by
low bone mass and micro
-architectural deterioration
of bone tissue with a resultant
increase in fragility and
risk of fracture
Normal Osteoporosis
1. Consenses Development Conference, JAMA 2001; 285: 785-95.
 Bone Strength is the
Function
of Multiple Factors!

Bone Quality
Bone Quantity
-Micro-Architecture
Mass
Connectivity
Bone Mineral Density
Mineralization
Size
Micro-damage
Collagen cross-linking

Chesnut et al. JBMR 2001; 16: 2163-72.

 How to Assess Bone
Quality?
 Bone quality could not be assessed
clinically.
 New imaging techniques (e.g. scanning
electron microscopy) assessing bone
architecture and micro-damage.
 Bone remodelling markers e.g.
dexoxy‑pyridinoline ( bone resorption )
and alkaline phosphates ( bone
formation
Micro-Computed Tomography
 Proposed Hypothesis:
Actions of Antiresorptive Therapies in
Reducing Osteoporotic Fracture Risk1-4

1. Riggs BL and Melton LJ. J Bone Miner Res. 2002;17:11-4

2. Chesnut CH III et al AMJ Med. 2000; 109:267-76.
3. Chesnut CH III and Rosen CJ. J Bone Miner Res. 20001;16:2163-72.
 Conclusion
 Fracture incidence can be reduced
significantly with only a small increase
in bone mass, and that improvements
in bone quality may explain the
increase in bone strength,
 Risk of osteoporotic fractures is
minimised by combined effect of :
1. Increase of BMD
2. Improvement of micro-architecture by
induction of slow remodelling