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338
Annals of the Rheumatic Diseases 1996; 55: 338-339
Clinical usefulness of risk factors for osteoporosis
Osteoporosis is a systemic skeletal disease characterised by
loss of bone mass and microarchitectural integrity that lead
to increased bone fragility and risk of fracture.' Its natural
history is one of slow, progressive bone loss that often
remains asymptomatic and undiagnosed for many years.
Only when a substantial amount of bone has been lost do
the characteristic low trauma fractures occur. Because
osteoporotic fractures are associated with considerable
morbidity, mortality, and cost,2 there is a need for methods
of identifying individuals at risk earlier in the disease
process, in whom preventative measures might be
effective.
Epidemiological studies have identified a wide range of
population risk factors for low bone mass and osteoporotic
fracture. These risk factors may relate to low peak bone
mass, subsequent bone loss, or determinants of fracture
independent of bone mineral density (BMD). Risk factors
for low peak bone mass include low body mass index, low
dietary calcium intake,3 physical inactivity, and smoking.4
Those associated with increased bone loss include many
of those for low peak bone mass (but to varying degrees)
with, in addition, corticosteroid drug treatment,5 previous
low trauma fracture,6 7years elapsed since the menopause,8
and tooth loss.9 Risk factors for osteoporotic fracture
independent of BMD may relate to poor bone quality or
biomechanical determinants, for example a history of
previous fracture'0 or increased hip axis length,'2 or to
an increased risk of falling, for example poor visual acuity,
neuromuscular impairment, lower limb weakness, or long
acting psychotropic drug treatment."
The study of epidemiological risk factors for chronic
diseases such as osteoporosis has several uses-first to
provide insight into the aetiology, second to point the way
towards population based preventative strategies (in this
context, measures such as increasing physical activity and
dietary calcium intake), and third to guide the clinical
management of individual patients. In the case of osteo"
porosis, this third application remains controversial,'4
15
and it is this that we shall discuss in the remainder of this
article. The application of risk factors may prove to be of
value through their modification in order to reduce subsequent fracture incidence, their incorporation into guidelines for clinical decision making, and their use to select
for further investigation those with a high probability of
low BMD.
A number of risk factors for osteoporosis are potentially
modifiable, and can be used to target specific areas for
lifestyle advice. 16 These include smoking, high alcohol
consumption, physical inactivity, low dietary calcium and
vitamin D intake,'7 18 the excessive use of drugs known to
reduce BMD such as corticosteroids or thyroxine, and
factors associated with an increased risk of falls."9 20 However, it is important to distinguish between those modifications which have been shown only to increase BMD, such
as weight bearing exercise,2' and those which reduce
fracture risk, such as supplementation of dietary calcium
and vitamin D intake, which has been shown to reduce the
rate of hip fracture in elderly residents of nursing homes
by 23-43%,'17 and the use of external hip protectors to
reduce the effect of falls, which was found to halve the risk
of hip fracture in a similar nursing home population.20
There is now evidence that a number of factors are
associated with an increased risk of osteoporotic fracture
independent of BMD, and that these risks
may
be addi-
tive.'3 They might be particularly useful in making decisions as to whether preventative treatment might be
indicated in patients who have an intermediate BMD. This
is particularly true of factors such as a history of previous
low trauma fracture, which is associated with an approximate doubling of fracture risk after correction for
BMD.'0 11 22 However, the most appropriate method for
incorporating these factors into treatment regimens is as
yet unclear, and their use remains largely hypothetical.
There is a particular need to identify women during the
perimenopausal or early postmenopausal period who are
at risk of later osteoporotic fracture so that preventative
therapy with hormone replacement or bisphosphonates
can be selectively targeted. Currently, the best available
predictor is bone mineral densitometry, by dual energy
x ray absorptiometry (DXA), which is extremely accurate,
precise, and closely related to fracture risk.23 However, this
technique is expensive, time consuming, and of limited
availability. It is, therefore, necessary to target for further
investigation by DXA only those women at greatest risk of
osteoporosis. Several attempts have been made to design
predictive models based on lifestyle risk factors in order to
identify such women,8 24-28 but unfortunately these have all
met with only limited success. The proportion of the
variation in BMD predicted by lifestyle factors ranges from
17-26-8% at the femoral neck, to 18-4-35% at the lumbar
spine, and 37-47% at the radius (table). This poor predictive capability would not necessarily present a major
problem if, despite a poor correlation with absolute BMD,
these models could indicate reliably whether individuals
had a lower or higher value than normal. Unfortunately,
this has not proved to be the case, and though the presence
of multiple risk factors is associated with a substantially
greater risk that could justify further investigation, their
absence does not exclude osteoporosis.
The weakness of these predictive models may in part
reflect that a considerable proportion of an individual's
BMD is genetically determined,29 and studies of heritability have suggested that as much as 70% of the variation
in BMD in younger women may be of genetic origin.30 A
simple way of incorporating this genetic component into
predictive models would be to include a family history of
osteoporosis or low trauma fracture. Unfortunately, this
simple measure has not been found to correlate well with
the presence of a low BMD in perimenopausal women.24 27
Much recent research has been devoted to identifying
reliable markers of the genetic predisposition to osteoporosis, but unfortunately the results of these studies have
been conflicting.3' -4
Which particular risk factors are most useful as predictors of BMD remains the subject of considerable debate
as a result of conflicting evidence from different studies.
This may be attributable to differences in study design and
subject selection. Whilst almost all agree that previous low
Predictive value of risk factor models for bone mineral density in early
postmenopausal women
Source
No
Lumbar spine
(Mo)
Elders et al 198924
Kleerekoper et al 198921
Slemenda etal 199026
Ribot etal 199227
Kroger etal 199428
Tuppurainenetal 19958
286
417
84
1565
1600
1605
Femoral neck
(Go)
31
_
-
-
35
25
19
18
17
25
27
Radius
(G.)
37
47
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Risk factors in osteoporosis
339
trauma fracture, low body mass index, and increasing age
are associated with lower BMD, the significance of gynaecological risk factors, nutritional deficiency, and family
history of osteoporosis or low trauma fracture are more
controversial, and some previously described risk factors
such as a history of back pain have subsequently been
found to be negatively associated with osteoporosis.27 This
protective effect is probably related to the fact that, though
osteoporotic vertebral fracture is a cause of back pain, this
symptom is more commonly the result of spondylotic
change or degenerative disc disease, which coexist infrequently with osteoporosis.
Although numerous epidemiological risk factors for
osteoporosis have been described, their application to
individual patients remains controversial. If appropriate
circumstances can be identified, they may yet prove to be
useful, but they cannot at present replace bone densitometry as the best method for assessing fracture risk. The
bad news is that the use of combinations of risk factors to
decide who should be investigated by DXA is currently
imprecise, though this may improve with future study. In
the absence of further data, those risk factors proposed by
the Advisory Group on Osteoporosis35 are the best currently available.
S A EARNSHAW
D J HOSKING
City Hospital,
Nottingham NGS 1PB,
United Kingdom
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Clinical usefulness of risk factors for
osteoporosis.
S A Earnshaw and D J Hosking
Ann Rheum Dis 1996 55: 338-339
doi: 10.1136/ard.55.6.338
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