Full text of DOI:10.1359/jbmr.2000.15.12.2305

JOURNAL OF BONE AND MINERAL RESEARCH
Volume 15, Number 12, 2000
©
2000 American Society for Bone and Mineral Research
Perspective
Biomechanics of Fracture: Is Bone Mineral Density
Sufficient to Assess Risk?
BARBARA R. McCREADIE and STEVEN A. GOLDSTEIN
HIS ISSUE of the Journal includes an article by Beck et al.
entitled “Structural Trends in the Aging Femoral Neck
than that of serum cholesterol for cardiovascular dis-
ease.”
(4)
T
and Proximal Shaft: Analysis of the NHANES III DCS
● “ . . . the osteoporosis model proposed by the World
Health Organization (WHO), which assumes that fra-
gility depends only on a single mean value of bone
mineral density (BMD) for a patient, is over-simplistic
and requires upgrading to include indices representing
(1)
Data.” The authors show a change in the geometry of
femurs with age, which appears to maintain the mechanical
integrity of the femoral neck. Furthermore, the authors
suggest that a loss in bone mass in the proximal femur may
not be indicative of an increase in fracture risk, because of
this geometric compensatory factor. These results, as well
as others in the literature, encourage us to “step back” and
review what we understand about fractures of the aging
skeleton and what factors seem to be associated most with
an increase in fracture risk.
(5)
the distribution of bone mineral.”
● “Risk factors not related to bone mass contribute sig-
(6)
nificantly to hip fracture risk.”
● “Recent studies have shown that factors related to fall
biomechanics may play as important a role in the
(7)
etiology of hip fracture as age-related bone loss.”
Popular conventional wisdom suggests that the most
dominant factor related to skeletal fragility due to aging or
osteoporosis is reduced bone mass. However, on further
questioning, many experts would caution that measures of
bone mass or density alone cannot reliably predict fracture
risk in patients. Given this controversy and the fact that
hundreds of studies have been conducted to examine the
factors associated with osteoporotic fractures, it seems ap-
propriate to revisit current perspectives. The following
statements were excerpted directly from the literature and
illustrate the continuing disagreements about fracture risk
factors.
● “ . . . there is no doubt that deterioration of trabecular
architecture is a contributor factor to the bone fragility
(8)
in osteoporosis . . . ”
● “Measurements of bone mineral density can predict
fracture risk but cannot identify individuals who will
have a fracture. We do not recommend a programme of
screening menopausal women for osteoporosis by mea-
(4)
suring bone density.”
How has the community arrived at such opposing view-
points about a single condition? Is it a single condition?
Osteoporosis and skeletal fragility in general are extremely
complex, cross many hierarchical levels, and may be impacted
by many physiological variables. From a biomechanical
perspective, there are a variety of factors to consider:
●
The recent interim report from the World Health Or-
ganization (WHO) Task Force for Osteoporosis, al-
though briefly mentioning microstructure, recommends
using only bone mineral density (BMD) for determin- (1) The loss of bone mass or BMD is an extremely impor-
ing fracture risk, and their research recommendations
focus on methods to assess and alter BMD and bone
turnover.
tant feature related to osteoporotic fractures. BMD ex-
plains a significant portion of the risk of osteoporotic
(2)
(9–11)
fractures
strength.
and correlates significantly with bone
The risk of fracture increases by 50–
(12–16)
●
●
“Mechanically, osteoporosis is rather simple: there is
not enough bone tissue, and therefore the bone struc-
ture is weak and fractures occur. The complexity is in
the bone remodeling biology that leads to diminished
150% with each SD decrease in bone mass as measured
(4)
by dual-energy X-ray absorptiometry (DXA). In fact,
the performance of BMD in predicting fracture is at
least as good as that of blood pressure in predicting
stroke and better than the use of serum cholesterol in
(3)
bone structure.”
“ . . . the predictive ability of bone mass was . . . better
Orthopedic Research Laboratories, University of Michigan, Ann Arbor, Michigan, USA.
2
305

2
306
McCREADIE AND GOLDSTEIN
(
4)
predicting cardiovascular disease. However, BMD by
itself does not determine if an individual will sustain a
erage mineral content) in hip fracture patients compared
with controls.
(51)
(4,17)
fracture.
normal and osteoporotic populations.
ship between BMD and fracture risk is less consistent
There is substantial overlap between the (7) Genetics, body size, and environmental factors may
(18)
The relation-
influence fracture risk through expression of many of
the factors described previously. For example, it has
been reported that up to 80–85% of BMD is determined
(14)
for vertebral fractures than for hip fractures.
2) The geometry of the bones and the distribution of bone
mass play an important role in determining bone (8) Currently approved therapies are able, at best, to in-
(52,53)
(
by genetics.
(54)
strength and appear to differ in ways that parallel the
crease bone density by up to 10%,
of fracture decreases by a much larger extent.
has been found to be correlated with the risk of hip (9) Recent experiments investigating biomechanics at the
although the risk
(
19,20)
(14)
risk of osteoporotic fracture.
The hip axis length
(9,21)
fracture,
ferences in hip fracture
increasing hip fracture since the 1950s.
and may be an explanation for racial dif-
level of the cell have found no evidence of factors at this
scale that appear to contribute to increased fracture risk. It
has been suggested that degradation in the ability of os-
teocytes to sense strain could be responsible for the loss of
bone associated with osteoporosis. This change in the
ability of the cell to sense strain could be caused by
changes in the geometry of the osteocyte and its lacuna,
changes within the cell, changes in the fluid flow surround-
ing the cell, etc. It has been shown that there are no
differences in the shape of the osteocyte lacunae in osteo-
(22)
and the secular trends for
(23)
The accom-
(24)
panying article and others have shown aging trends
in the geometry of the aging femur. Sandor, Cody,
(5)
(25)
(26)
and McCubbrey
have shown that the distribution
patterns of bone mass, not just its quantity, are impor-
tant in predicting whole bone strength. Likewise, the
cross-sectional area of vertebrae is important in deter-
(27–31)
mining their strength.
has been shown to decrease with age,
changes, particularly periosteal expansion,
Although cortical thickness
(
17)
geometric
porotic individuals compared with those without frac-
(
32–35)
(51)
may
ture.
Other experimental measurements of potential
more than compensate for this loss by increasing the
structural resistance to load.
biomechanical changes at this level are technically diffi-
cult and to our knowledge have not been attempted to date.
(
3) The force applied to each bone must be greater than its (10) Achieving effective and efficient experimental designs
(36)
strength in order for a fracture to occur. Hayes et al.
in the study of osteoporosis is extremely difficult.
First, it is difficult to define and then find a true
control. Should the control be a young adult, age-
matched without a fracture, or age-matched and BMD-
matched without a fracture? Is tissue from a cadaver
without fracture “normal”? Would a fracture have
occurred within a few days had the individual lived
longer? Second, it is often difficult to obtain experi-
mental samples for in vitro research. Fractured verte-
brae are not removed after fracture, and hip fractures
are most often fixed without the need for arthroplasty.
Tissue, which is obtained after fracture, therefore is
not representative of all osteoporotic fractures. Pro-
spective clinical trials are difficult and expensive be-
cause of the long follow-up times and the large num-
ber of individuals required to provide statistically
significant and meaningful data. A further complica-
tion arises with the variations across different fracture
sites. These variations have been hypothesized to be
have clearly described that there are two factors that
determine whether a bone fractures, the applied load
and the fracture load. They incorporate these into a
fraction, applied load/fracture load, which describes the
risk of fracture. The force applied to the bone is influ-
enced by padding (artificial or body fat), the distribution
of mass (including any carried weight), and the direc-
(7,37)
tion of the fall.
These are particularly important
relative to hip fractures. Loading rate also has been
(38)
shown to influence fracture strength,
the strength of the bone.
by modifying
(
4) Trabecular bone microarchitecture, separate from den-
sity or bone volume fraction, is another important de-
(8)
terminant of bone strength and appears to differ be-
tween osteoporotic and normal individuals and with
(19,32,33)
age.
Several studies measuring microarchitec-
ture in two and three dimensions have correlated mea-
sures of density and architectural organization with
(39–41)
(55)
trabecular bone stiffness and strength.
In addi-
caused by two types of osteoporosis
and also may
tion, changes in architectural features with age and
differences between males and females have been doc-
be a function of further site-specific factors.
11) The etiologies of osteoporosis, whether biomechani-
cal, molecular, cellular, environmental, or otherwise,
are still relatively unknown.
(
(42,43)
umented.
In a recent, more direct study, trabecular
bone from hip fracture patients was found to be more
anisotropic than a matched cohort of female subjects
(44)
who died without fracture.
What is the “take-home” message? What does this say
(
5) Microdamage and/or increased remodeling density may about the best methods of screening for fracture risk and the
play roles in weakening bone tissue, predisposing to future of biomechanics research in osteoporosis?
(45–47)
fracture.
For robust fracture risk screening, it appears that we can
(
6) Changes in the bone tissue properties may be associated do better than BMD alone with current knowledge and
with osteoporotic fracture. Shifts in the mineral content technology. BMD by itself can predict fractures with a
(48)
of the tissue will influence its stiffness
and have been related to bone fragility.
and strength, detection rate of 30–50% and a false positive rate of about
Recent 15%, using a cut-off of 1 SD below the mean BMD and
(17,49,50)
(4,56)
data suggest that there may be greater variability in actual hip fracture and BMD data.
Using a 0.5 SD
local mineral content (even without differences in av- difference in BMD between individuals who will and will

BIOMECHANICS OF FRACTURE
2307
(
56)
not develop fracture, Law et al. show a 6% detection rate
and 2% false positive rate with a cut-off of 2 SD below the
mean. Looking at the numbers from a different perspective,
Analysis of the Third National Health and Nutrition Exami-
nation Survey dual-energy X-ray absorptiometry data. J Bone
Miner Res Int 15:2297–2304.
2
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8
5–95% of white women who fracture have BMD measure-
ments less than 2.5 SD below normal.
BMD and some “geometric” factors, either by looking at the
size and shape of a bone or further describing the BMD by
location within the bone, we can likely identify more accu-
rately those who have or will sustain a fracture. For exam-
(57)
By combining
(5)
ple, Sandor et al. claim an accuracy of 90% by including
the distribution of BMD. It is inappropriate to expect to
achieve perfect identification of individuals who will frac-
ture, because there is a varying amount of risk that is
attributable to the chance of sufficient loading to fracture the
bone (i.e., a significant fall). Although technology appears to
be available to improve on BMD alone, clinical trials have not
been completed that will enable its acceptance and general use.
There is a need for prospective clinical trials to verify previous
results in large populations and determine what geometry/
location information provides the best fracture prediction.
However, once it is indicated, it should require little work to
incorporate into current screening protocols.
There are several characteristics of bone that have a
potential to further improve our ability to identify those at
risk of fracture. Tissue material properties may provide
additional information about fracture risk, but it is unlikely
that it will become routine in screening for osteoporosis
because of its invasive nature. Genetic analysis may, in the
future, provide additional methods of screening, and with
3
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8
9
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progress may begin to accelerate. In addition, noninvasive
means of measuring trabecular bone architecture may soon
provide an additional level of insight for screening, although
the resolution is currently insufficient. There are likely to be
additional attributes that are discovered from ongoing basic
science research that correlate with fracture risk. However,
it is unclear whether these methods provide improved risk
estimates beyond that from BMD and geometry/location.
Biomechanics teaches us that the risk of fracture is de-
pendent on the geometry of the bone, its architecture (at all
scales of hierarchy), its material properties and the distri-
bution of material properties, and the character of the im-
posed load (magnitude, rate, and direction). Genetics can
influence the geometry, material properties, architecture, or
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Address reprint requests to:
Steven A. Goldstein, Ph.D.
Orthopedic Research Laboratories
Room G161, 400 North Ingalls
Ann Arbor, MI 48109-0486, USA
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