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How to treat
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Diagnosis &
investigation
Established and
new therapies
Issues for debate
Case studies
The author
DR RODERICK
J CLIFTON-BLIGH,
staff specialist in endocrinology,
Royal North Shore Hospital, St
Leonards; and senior lecturer in
medicine, University of Sydney,
NSW.
OSTEOPOROSIS
Background
OSTEOPOROSIS is defined as a
metabolic bone disease characterised
by low bone mass and deterioration
in the architecture of bone tissue,
which in combination leads to bone
fragility and fracture. It is one of the
leading diseases affecting our ageing
population. Its genesis is mostly
explained either by failure to achieve
normal peak bone mass during
growth and young adulthood, or by
excessive bone loss caused by agerelated factors in both genders, and
more particularly after menopause
in women.
Normally, at a cellular level, new
bone is formed by osteoblasts as
older bone is resorbed by osteoclasts,
with these two processes coupled
together to ensure maintenance of
skeletal integrity. Disruption of this
balance causes bone loss and skeletal
fragility. For example, oestrogen
deficiency after menopause causes
excessive osteoclastic activity
unmatched by commensurate
osteoblastic reformation.
Successful osteoporosis therapy
therefore targets either the overactive osteoclast (anti-resorptive) or the
www.australiandoctor.com.au
underperforming osteoblast (anabolic), or both (figure 1, page 39).
Osteoporotic fractures
The clinical expression of osteoporosis is fracture. Of course, any
bone will break under sufficient
force, so that osteoporotic fractures
are limited to those occurring with
cont’d page 39
11 July 2008 | Australian Doctor |
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from page 37
so-called minimal trauma such
as falling from standing height.
Classic osteoporotic fractures
occur at the hip, spine or forearm, although fragility fracture
of any bone (except the skull)
might be due to osteoporosis.
In 2001 an estimated two million Australians had osteoporosis, with fractures occurring every
8.1 minutes and costing $1.9 billion in direct care. About one in
two women, and one in three
men over 60 will have a fracture
in their remaining lifetime.
Between 10% and 20% of those
with hip fracture will die within a
year of the event and 20-30%
will require nursing home care.
Vertebral fractures (figure 2) are
also associated with significant
morbidity and increased mortality.
Osteoporosis is an increasing
global problem, and the
number of hip fractures worldwide is expected to increase
from 1.7 million in 1990 to 6.3
million in 2050.
Osteoporosis is a
major problem for
the individual and
community alike.
Figure 1: Bone biology and cellular targets of osteoporosis therapies.
Osteoblasts form new bone whereas osteoclasts resorb bone.
Osteoporosis develops from an imbalance between these two
processes. Osteoblasts stimulate osteoclastic activation via a protein
called RANK ligand (RANKL, shown as
). PTH = parathyroid
hormone, SERMs = selective oestrogen-receptor modulators.
(RANKL inhibitors)
teriparatide
(PTH 1-34)
osteoblasts
osteoclast
Figure 2: A thoracic vertebral wedge fracture in a
patient with postmenopausal osteoporosis. Note the
30% reduction of anterior vertebral body height
relative to the posterior vertebral height. A vertebral
fracture is defined as a *20% reduction in height of
the anterior or mid-portion of a vertebral body
relative to the posterior height of that body, or a
*20% reduction in any of these heights compared
with the vertebral body above or below the affected
vertebral body.
bisphosphonates
oestrogen
osteoid
SERMs
bone
strontium
Most osteoporotic fractures
occur in people over 60. Osteoporosis can also occur in children and young adults, but discussion of this is beyond the
scope of this review and should
probably be managed in a specialist setting.
Preventing the consequences
of osteoporosis relies on three
strategies:
■ Identifying those who need
treatment.
■ Choosing from a range of
effective therapies.
■ Maintaining adherence to
treatment, and monitoring for
treatment response.
Diagnosis
Who needs to be treated?
Stratifying fracture risk
GENERALLY speaking, a
postmenopausal woman (or
man over 50) with a fragility
fracture will be at sufficiently high risk of a further
fracture to warrant specific
treatment. They have
already failed their skeletal
stress test. Investigations
(such as bone mineral density [BMD] measurement —
see below) may help ensure
compliance with therapy,
and can be used to monitor
progress.
On some occasions the
history of fracture is not
immediately obvious, such
as the woman with progres-
sive height loss and chronic
back pain due to as yet
unrecognised vertebral fracture. After the diagnosis has
been established by plain
radiography of the lateral
spine, this patient also needs
specific therapy to prevent
further fractures.
For those without a preexisting clinical fracture, the
decision to treat relies on
stratifying fracture risk and
determining which elements
of that risk are amenable to
treatment. These factors are
summarised below.
Bone strength
At present, BMD is most conveniently and accurately esti-
mated by dual-energy X-ray
absorptiometry (DEXA). This
technique actually measures
so-called ‘areal’ bone density
2
(g/cm ), which is bone mass
normalised to the size of the
projected bone area. A wealth
of data associates reduced
BMD measured by DEXA
with increased fracture risk.
Each standard deviation
reduction in femoral neck
BMD increases age-adjusted
risk of hip fracture 2-3.5-fold,
and the risk of any fracture
1.7-2.4-fold.
Lumbar spine BMD is a
slightly better predictor of vertebral fracture (1.9-2.8-fold
risk per SD) although the presence of degenerative spine dis-
ease or aortic calcification can
spuriously elevate BMD at
this site.
Precision of DEXA is excellent (1-2%) but because usual
rates of change in BMD either
with age or treatment are usually no more than 1-2% per
year, an interval of two years
is typically required to detect a
significant change in the measurement.
The BMD result is usually
interpreted as a T-score,
which is the number of standard deviations from young
normal mean BMD. The
WHO defines:
■ Normal bone density as a Tscore of > –1.
■ Osteopenia as a T-score
between –1 and –2.5.
Osteoporosis as a T-score of
) –2.5.
The nationwide introduction of a standardised Australian reference range based
on data from the Geelong
Osteoporosis Study is now in
progress.1
Whereas BMD in the osteoporotic range was previously
regarded as a threshold for
offering treatment, more
recently there have been
moves towards developing
gradient-of-risk models that
incorporate other clinical risk
factors (figure 3, page 41).
Two cardinal factors in
addition to BMD are age and
presence of fracture. The
■
decrease in bone strength that
occurs with age is not fully
captured by BMD alone. Fracture risk increases with age for
any given BMD, which is also
partly related to the increased
risk of falls with age.2
A history of previous
fragility fracture (after age 50)
increases the risk of another
fracture between 2- and 5fold. Sometimes vertebral fractures may not be clinically
apparent. Particularly in older
patients or patients with lower
BMD (eg, T-scores <–2.0), lateral spine radiographs may be
useful in identifying asymptomatic vertebral deformities.
Vertebral fracture assessment
cont’d next page
One Australian life is lost
to heart disease every 20 minutes1,2
1 in 7 patients with a history of CAD* will suffer a major event
(heart attack, stroke or CV death) or hospitalisation within 1 year. 3
*CAD refers to coronary artery disease.
For PBS Information refer to primary advertisement.
BEFORE PRESCRIBING PLEASE REVIEW PRODUCT INFORMATION IN THE PRIMARY ADVERTISEMENT IN THIS PUBLICATION. Plavix (clopidogrel 75 mg). References: 1. www.heartfoundation.com.au (accessed
Nov 2007), media release date 14/9/07. 2. The Shifting Burden of Cardiovascular Disease in Australia. Access Economics; 2005. Downloaded from www.heartfoundation.org.au; 1 April 2008. 3. Steg PG, et al. JAMA 2007;
297(11):1197-1206. sanofi-aventis australia pty ltd ABN 31 008 558 807, Talavera Corporate Centre, Building D, 12-24 Talavera Road, Macquarie Park, NSW 2113. Plavix is a registered trademark of sanofi-aventis. HSX0364/AD/1
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How to treat – osteoporosis
from previous page
by DEXA is a potentially more costeffective alternative that also involves
less ionising radiation. However, this
technique requires an appropriate
densitometer and software, which are
not yet widely available.
Operation of these three key factors is illustrated by considering the
following individuals with about
equal fracture risk in the next 5-10
years (assuming no difference in
other risk factors or risk of falling):
■ A 60-year-old woman with one
existing vertebral fracture and
BMD T-score of –2.5.
■ A 75-year-old woman with no
prior history of fracture and BMD
T-score of –2.5
■ A 60-year-old woman without previous fracture and BMD T-score of
–3.5.
Other important clinical risk factors that are at least semi-independent of age and BMD include:
■ Low body weight (<58kg).
■ Maternal history of hip fracture.
■ Current smoking.
■ Inability to stand up from a chair
without using arms.
However, it is less certain whether
the presence of these latter factors
confers risk that alters with treatment. Another important category
The principal
determinant of bone
strength is its mineral
density, but clinical
risk factors (in
particular age and the
presence of fracture)
provide important
additive information
for calculating
individual fracture
risk.
of risk involves iatrogenic factors,
most particularly the use of systemic
corticosteroids, which are dealt with
separately below.
So who should have a BMD measurement? The MBS criteria for
rebate of a BMD scan now include
those aged *70, and younger individuals with either fracture or
selected clinical conditions associated with osteoporosis.
Falls risk
Most hip and peripheral fractures
result from a fall. The risk of falling
increases with age, such that 50% of
those aged *85 will fall each year
and 50% have had a previous fall. A
history of falling in the previous 12
months has been shown to be an
independent risk for fracture (after
accounting for age, BMD, etc) in several studies.
Identifying falls risk is therefore an
important adjunct when considering
management to prevent fracture.
Note that this is bi-directional: a
patient with low bone mass should
be assessed for risk of falling, and
the patient with frequent falls should
have their bone density measured.
Falls risk factors may be either
environmental (such as home hazards or unsuitable footwear) or
intrinsic, including a wide range of
medical conditions such as impaired
vision or cognition, previous stroke,
Parkinson’s disease or use of sedative medications.
Clinical examination should
include an assessment of postural sta-
bility. One simple screening tool is
the timed up-and-go test, in which
the patient is asked to rise from a
chair, walk 3m at normal pace (and
with usual walking aids), return to
the chair and sit down. A time of
*15 seconds to complete this is
regarded as abnormal. More complex and comprehensive assessment
tools are available that more accurately determine falls risk and identify
key impairments that might respond
to targeted intervention.3
Although it is reasonable to
assume that preventing falls would
reduce the burden of fractures in the
elderly, there is little published evidence yet to confirm this.
Iatrogenic osteoporosis
Use of systemic corticosteroids is
associated with rapid bone loss via a
combination of negative calcium balance and direct effects on bone tissue.
Increased fracture risk is particularly
evident in postmenopausal women
and older men.
Fracture risk is influenced by daily
corticosteroid dose and duration of
use. For example, taking at least
7.5mg prednisone daily for longer
than two months increases the risk of
vertebral fractures 2.8-fold and hip
fractures 2.2-fold. The risk of verte-
bral fracture is increased by up to
14-fold in those taking *30mg prednisone daily for a cumulative exposure of *5g. Fracture risk decreases
after corticosteroid therapy is discontinued.
Fracture risk with corticosteroid
use appears to increase when BMD
T-score falls below –1.5, so intervention may be appropriate at higher
BMD values than typically used to
consider treatment for postmenopausal osteoporosis.
Several other medications can
adversely affect fracture risk. Aromatase inhibitors are now increasingly used in the treatment of breast
cancer, and the risk of fracture
(mostly vertebral fractures) with
these agents may be increased by up
to 60%. Bone turnover increases
after an aromatase inhibitor is
started, which suggests that even the
small residual oestradiol levels present in postmenopausal women are
important for bone health. A woman
starting an aromatase inhibitor
should have her bone density measured and be offered treatment if it is
low (figure 3, page 41).
A similar effect on fracture risk is
seen in men having medical or surgical orchidectomy for treatment of
prostate cancer.
Investigations
IF low bone mass has been
discovered, the purpose of
further investigations is to
exclude potentially treatable
secondary causes (table 1).
Although a long list of medical conditions is associated
with osteoporosis (including
rheumatoid arthritis, chronic
kidney or liver diseases,
inflammatory bowel disease,
and Cushing’s syndrome),
most of these are readily evident before a BMD test.
Other secondary causes
of accelerated bone loss are
important because they may
be clinically silent, and specific treatment may improve
Table 1: Investigations for secondary causes of
bone loss
Serum 25-hydroxyvitamin D (and serum parathyroid hormone
[PTH] if the 25(OH)D level is low)
■ Serum calcium (and PTH if calcium level is elevated)
■ Serum TSH (and free T4/T3 if TSH level is abnormal)
■ Anti-transglutaminase IgA antibody (total IgA levels may need
to be checked in case of IgA deficiency)
■ FBC
■ Creatinine, liver function
■ Testosterone in men
■ Serum and urinary electrophoretogram/ immunoelectrophoretogram if there is rapid bone loss, osteoporosis
or multiple fractures
■ 24-hour urinary free cortisol if Cushing’s syndrome is clinically
suspected
■
bone strength.
Hypogonadism is of
course the principal cause
of postmenopausal osteoporosis, but hypogonadism
should also be routinely
excluded in men with low
bone mass. Other conditions include vitamin D
deficiency, hyperthyroidism,
coeliac disease and primary
hyperparathyroidism. Multiple myeloma is rarely diagnosed (<1%) in otherwise
asymptomatic patients with
osteoporosis.
Diagnosis of monoclonal
gammopathy of uncertain
significance (MGUS) is not
uncommon but there are no
data on fracture risk that
would otherwise guide
treatment decisions for low
bone mass in this condition.
Patients with MGUS should
be periodically monitored to
exclude progression to
myeloma.
Several markers of
dynamic bone turnover are
now available that reflect
either bone formation (eg,
serum bone-specific ALP,
osteocalcin, and aminoterminal propeptide of type I
collagen [PINP]) or bone
resorption (eg, urinary Nterminal telopeptides of
type 1 collagen [NTX] or
urinary deoxypyridinoline
[DPD]).
At present these markers
have a biological variability
such that a single measurement has low predictive
value for individual fracture
risk. However, an elevated
bone resorption marker in
addition to low BMD may
strengthen the argument for
treatment of that individual.
Moreover, demonstrating a
reduced resorption measurement after three months
of therapy generally indicates adequate treatment
response.
Management
)THE goal of therapy is to prevent
fracture. Several therapies are now
available that have been shown to
reduce fractures in selected high-risk
populations. The choice of therapy
will depend on the nature of fracture
risk (spine or non-spine), the presence of contraindications to specific
therapies, and patient preference.
Therapies differ with respect to
their mechanism of action (figure 1,
page 39), but all target the skeleton to
improve bone strength. Fractures may
not be prevented with these therapies
in patients at high risk of falling
unless their bone density is also
demonstrably low.
Oral bisphosphonates
(Level 1 evidence for prevention of vertebral and non-vertebral fractures)
These drugs are analogues of
pyrophosphate and bind tightly to
skeletal hydroxyapatite. They are
potent inhibitors of osteoclastic bone
resorption. Further bone loss is
thereby prevented and mineral density is increased, but little if any new
bone is formed. Orally administered
40
| Australian Doctor | 11 July 2008
bisphosphonates have low bioavailability (<1%), which is further
reduced if taken with food, calcium
or iron.
Three oral bisphosphonates are
available in Australia for osteoporosis
treatment: alendronate, risedronate
and etidronate. In the case of alendronate and risedronate, multiple
studies confirm efficacy in treating
osteoporosis. Both reduce the relative
risk of vertebral (by 40-50%) and
non-vertebral fracture (by 20-40%)
in patients with osteoporosis and at
least one pre-existing vertebral fracture. Hip fractures are reduced by 3050% by these two oral bisphosphonates in similarly high-risk patients.
There are also data showing that
these two oral bisphosphonates prevent spine fractures (by about 50%)
in patients with low BMD even without pre-existing fracture. Overall, the
effect on fracture risk is seen within
12 months after starting these agents.
In the only two head-to-head studies, alendronate was associated with
significantly greater increases in hip
and spine BMD, and greater reduc-
sis and may still have some role in
those patients intolerant of other
agents.
Selective oestrogen-receptor
modulators
(Level 1 evidence for vertebral
fracture prevention)
Hip fractures may be reduced by
30-50% by use of alendronate or
risedronate in high-risk patients.
tion in bone turnover, than risedronate over 12 months.4,5 However,
it is important to emphasise that no
difference in anti-fracture efficacy has
been demonstrated between the two
agents.
There are much fewer data to support the utility of etidronate. Improvement in BMD is less than that seen
with either alendronate or risedronate, and fracture prevention has
only been shown for spinal fractures.
Nevertheless, etidronate is available
on the PBS (authority required) for
treatment of established osteoporowww.australiandoctor.com.au
Selective oestrogen-receptor modulators (SERMs) are non-hormonal analogues of oestrogen that activate the
oestrogen receptor in bone but antagonise it in other tissues such as uterus
and breast. Raloxifene is the only
SERM registered for use in osteoporosis.
Raloxifene reduces the relative risk
of vertebral fracture by 36% in postmenopausal women with osteoporosis.6 Recent data have also demonstrated reduced risk of clinical
vertebral fractures in women not otherwise selected on the basis of osteoporosis risk factors such as low BMD.
Raloxifene does not appear to prevent non-vertebral fractures.
The effect on bone density with
raloxifene is typically less than that
seen with the use of bisphosphonates,
despite broadly comparable reduction in vertebral fracture risk with
either class of agent.
Raloxifene has also been associated with a 55-70% reduction in the
relative risk of oestrogen-receptorpositive breast cancer, equivalent to
1.2 fewer invasive breast cancers per
1000 women treated for one year.6,7
Raloxifene increases relative risk
of venous thromboembolism by
44%, equivalent to 1.2 more events
per 1000 women-years of treatment.6
In a recent trial involving women
with an already high risk for coronary heart disease there was an excess
relative risk of fatal stroke with raloxifene (increased by 49%) equivalent
to 0.7 extra events per 1000 womenyears.7 Raloxifene use may also exacerbate hot flushes, leg cramps and
peripheral oedema.
Strontium
(Evidence for prevention of vertebral
[level 1] and non-vertebral [level 2]
fractures)
Strontium is a naturally occurring
trace element, a divalent cation like
AD_041___JUL11_08 Page 4 3/7/08 3:47 PM
calcium but with greater molecular weight. It is given as
ranelate salt to improve its
palatability. While its exact
mechanism of action is
unknown, strontium stimulates bone formation via
increased pre-osteoblast cell
number and bone formation
rate, while at the same time
inhibiting osteoclast resorption
activity (although its antiresorptive activity is less than
that of bisphosphonates).
Two multinational phase III
studies have now reported a
significant relative reduction in
risk of vertebral (by 41%)8
and non-vertebral fractures (by
16%) 9 in postmenopausal
women with osteoporosis
given strontium ranelate. In
these studies, relative risk of
vertebral fractures was also
significantly reduced in
women with osteopenia10 and
in women aged >80 years.11
Relative hip fracture risk was
reduced by 36% in a post-hoc
analysis of women aged *74
years with BMD T-scores
) –2.4.9
Strontium ranelate significantly increases bone density
at both spine and hip,
although about 50% of the
observed change is due to a
small interchange of strontium
for skeletal calcium. Its use is
associated with an increased
incidence of GI side effects
such as diarrhoea, and a small
increased risk of venous
thromboembolism (0.9%
compared with 0.6% in the
placebo group).9 Drug rash
with eosinophilia and systemic
symptoms has been recently
reported as a very rare reaction.
There is still much to learn
about the potential uses of
strontium in osteoporosis
management. There are no
data yet to confirm its efficacy
in patients who have previ-
Figure 3: Managing osteoporosis: gradient-of-risk model incorporating other clinical risk factors
besides BMD.
Clinical fragility fracture
No
Yes
Clinical suspicion
BMD
(to monitor
treatment)
Treat
(PBS authority)
Offer treatment
BMD
T-score ) –3
Aged * 70
T-score ) –2
or ) –1 with
clinical risk
factors*
T-score
) –1 and
> –2 and
no clinical
risk factors
T-score
> –1
VFA or spine
X-ray
Monitor
(BMD in
2 years)
Reassure
Fracture
No fracture
*Clinical risk factors for fragility fracture include older age, family history, smoking, weight < 58kg, frequent falls
and drugs (corticosteroids, aromatase inhibitors, GnRH agonists). VFA = vertebral fracture assessment.
ously been treated with other
agents (such as bisphosphonates), nor whether its effects
might be additive to those of
purely anti-resorptive agents.
Studies in men, or in patients
with glucocorticoid-induced
bone loss, are also awaited.
Oestrogen
(Level 1 evidence for prevention
of vertebral and non-vertebral
fractures)
Many studies have shown
oestrogen therapy is effective
at preventing menopausal
bone loss. The utility of
HRT in preventing osteoporotic fractures was conclusively demonstrated in the
Women’s Health Initiative
trial.12 Women randomised
to combined HRT had 24%
fewer fractures, including
34% fewer hip fractures
(absolute risk decrease of
0.05% per annum) over the
seven years of that study.
However, the skeletal benefits of HRT in that trial were
outweighed by an excess risk
of breast cancer, stroke, pulmonary embolism and coronary events, even though the
absolute risk for each was
increased by less than 0.1%
per annum.12 In women who
had previously undergone hysterectomy and were randomised to oestrogen alone,
there was a comparable reduction in fracture risk, which was
again counterbalanced by an
excess number of strokes and
venous thromboembolic
events.
The main indication for
HRT continues to be the
control of menopausal
symptoms. At this stage, it
is unclear whether there is a
particular subgroup of otherwise asymptomatic postmenopausal women for
whom the skeletal benefits
of HRT outweigh the risks.
General measures
should be avoided in patients
with a history of renal calculi
in the presence of hypercalciuria.
A recent trial conducted in
New Zealand has raised a cautionary note regarding use of
calcium citrate as monotherapy
for treating osteoporosis, particularly in older women.14 This
study found that postmenopausal women aged 74 ± 4.2
years given 1000mg calcium
citrate daily for five years had
significantly more vascular
events (relative risk of MI 2.12).
When interpreting these
findings we should bear in
mind that vascular risk was
not a primary endpoint of this
study but rather a safety endpoint analysed in secondary
analyses. Further studies are
therefore needed before a firm
conclusion can be drawn
regarding any adverse vascular effect, or whether there is a
risk with calcium carbonate.
Indeed, the Women’s Health
Initiative reported that calcium carbonate was not associated with excess cardiovascular event rates.
Calcium
Dietary intake of 1200mg of
calcium per day (equivalent to
three or more servings of dairy
products) is generally recommended, although there is still
controversy regarding any primary anti-fracture efficacy of
calcium monotherapy. A
recent meta-analysis showed
that calcium supplementation
prevented menopausal bone
loss, with a trend towards
fewer vertebral fractures but
no effect on non-vertebral
fractures.13
It is important to emphasise
that trials of the effective antiosteoporosis agents discussed
above have generally included
calcium as adjunctive therapy
in both treatment and control
groups. Calcium supplements
Vitamin D
Vitamin D is important for
skeletal health across all ages.
Most vitamin D is obtained
from UV-B action in the skin.
Exposure of hands, face and
arms to adequate sunlight
(about 5-8 minutes daily in
summer and 20-30 minutes in
winter, although these times
vary by latitude) should produce about 1000 units of vitamin D daily.
Elderly skin or increased
cutaneous melanin is associated with less vitamin D production. The major risk factors for vitamin D deficiency
are therefore older age, dark
skin pigment and sun avoidance (including residential
care, religious veiling, certain
medical conditions).
Some but not all studies
show that supplemental vitamin D reduces the risk of
osteoporotic fractures, with a
more obvious effect seen in vitamin D-deficient populations.
Vitamin D supplementation
with cholecalciferol is recommended to achieve a target
serum 25-hydroxyvitamin D
(25[OH]D) of at least
50nmol/L.
There is only weak (level 3)
evidence to support the use of
calcitriol (Rocaltrol) in osteoporosis treatment. There is
some evidence to support its
use in preventing glucocorticoid-induced osteoporosis. It
may still have some role in
treating patients with osteoporosis who are intolerant of
the more effective therapies
discussed above. It is PBS listed
(authority required) for the
treatment of osteoporosis in
patients with a pre-existing
minimal trauma fracture.
Exercise and other nonpharmacological therapies
Weight-bearing exercise is usually recommended for preventing osteoporosis (level 3
evidence). Meta-analyses of
short-term trials have shown
that resistance training (3-5
times a week) or regular walking (90-280 minutes a week)
produces a small increase in
spinal BMD without any consistent effect on hip BMD. As
noted above, specific programs
for muscle strengthening and
balance training can reduce
falls in high-risk groups. However, there is no evidence yet
that any of these interventions
protect against fractures.
Hip protectors have been
shown in some studies to
reduce hip fractures in
patients at high risk of falls.
However, their use is limited
by compliance.
Plavix + aspirin gives ACS
patients added protection
†
against future CV events1–3 *
†ACS refers to acute coronary syndrome: UA/NSTEMI/STEMI. *Compared to aspirin alone.
For PBS Information refer to primary advertisement.
BEFORE PRESCRIBING PLEASE REVIEW PRODUCT INFORMATION IN THE PRIMARY ADVERTISEMENT IN THIS PUBLICATION. Plavix (clopidogrel 75 mg). References: 1. CURE Trial Investigators. N Engl J Med
2001;345(7): 494-502. 2. Sabatine MS, et al, for the CLARITY-TIMI 28 Investigators. N Engl J Med 2005; 352:1179-1189. 3. COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Lancet 2005;
366:1607-1621. sanofi-aventis australia pty ltd ABN 31 008 558 807, Talavera Corporate Centre, Building D, 12-24 Talavera Road, Macquarie Park, NSW 2113. Plavix is a registered trademark of sanofi-aventis.HSX0364/AD/2
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11 July 2008 | Australian Doctor |
41
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How to treat – osteoporosis
Issues for debate
Non-responders
A KEY unresolved issue in osteoporosis management is identifying
patients who do not respond to a
given therapy. Although BMD assessment is clearly useful in identifying
those at increased risk of fracture,
change in BMD with treatment only
explains a small proportion of antifracture efficacy.
For example, raloxifene reduces the
relative risk of vertebral fracture by
30-60%, yet observed change in
spinal BMD with this treatment is
only 2-3% in three years — that is,
only 4% of fracture reduction is
explained by the change in BMD.
The proportion of fracture risk
reduction explained by change in
BMD seen with oral bisphosphonate
treatment is only 16-18%. Conversely, significant reduction in fracture risk is observed within 3-6
months of starting bisphosphonate
therapy — well before maximum
BMD gains with these treatments.
Therefore there is reasonable evidence
to suggest that anti-resorptive therapy is efficacious, provided BMD
remains at least stable.
Recurrence of multiple fractures,
and/or loss of BMD after starting
anti-resorptive therapy, places the
patient and clinician in a difficult situation without adequate evidence to
guide decision-making. Compliance
with treatment should be carefully
reviewed, particularly in the case of
bisphosphonates, when contemporaneous ingestion of food, calcium or
iron will impair absorption.
Calcium supplementation (and
repletion of vitamin D) should be
checked, and other secondary
causes of accelerated bone loss
should be re-evaluated (table 1,
page 40). After these factors have
been corrected or excluded, changing to another anti-osteoporosis
therapy might be considered. An
IV bisphosphonate is an attractive
option because this overcomes the
problem of poor GI absorption and
variable compliance, but osteoporosis is not yet a registered indication for these agents in Australia.
In patients at very high risk of
In cases of
non-response to
therapy, calcium
supplementation
(and repletion of
vitamin D) should be
checked, and other
secondary causes
of accelerated bone
loss should be reevaluated.
recurrent fracture, use of subcutaneous teriparatide (parathyroid hormone [PTH]; see below) might be
considered but this is costly (and not
PBS listed) and may not be as effective after prolonged initial therapy
with bisphosphonates.
Combining two anti-resorptive
therapies has not been shown to additively reduce fracture risk, but does
increase the risk of side effects. There
are no data as yet on switching to
strontium ranelate in patients who
have previously taken other osteoporosis therapies.
Treatment duration
A connected theme in this discussion is the issue of how long treatment should continue. The primary
aim of treatment ideally should be
to achieve adequate bone strength
to resist fracture and, secondarily,
to restore bone turnover to a physiological range such that ongoing
bone loss does not occur. There
have been some fears that oversuppression of bone turnover might
predispose to microdamage accumulation. The little evidence there
is to support this hypothesis comes
from animal models.
Discontinuing oestrogen or raloxifene results in a return of postmenopausal bone loss and decreases
in BMD within 12 months. Bisphos-
phonates have a longer skeletal retention time, and BMD gains are preserved for some time after their discontinuation. Recent data from the
Fracture Intervention Trial Long-term
Extension Trial showed that women
who stopped alendronate after five
years of treatment had stable lumbar
spine BMD over the subsequent five
years, but a significant decrease in hip
BMD occurred within 1-2 years.15
Continuing alendronate in this trial
resulted in fewer clinical vertebral
fractures, but no further reduction
in incidence of non-vertebral fractures. Even after 10 years of alendronate treatment, there was no evidence on transiliac bone biopsy that
bone remodelling was over-suppressed.15
Therefore, women who have taken
alendronate for up to five years
might elect to suspend therapy for
1-2 years if their vertebral fracture
risk is low; but for women at high
risk of recurrent fracture, therapy
should not be discontinued. Other
bisphosphonates differ in their affinity for bone, so the alendronate data
cannot be extrapolated to risedronate
or etidronate.
Osteonecrosis of the jaw
Osteonecrosis of the jaw (ONJ) is a
potential complication of bisphosphonate therapy that deserves partic-
ular mention. First recognised in
2003, it has since been mainly
reported in patients with cancer
receiving higher total doses of bisphosphonates.
Bisphosphonate-associated ONJ is
defined as ‘confirmed’ when an area
of exposed bone in the maxillofacial
region does not heal within eight
weeks after identification in a patient
receiving a bisphosphonate who has
not had radiation therapy to the area.
Exposed alveolar bone present for
less than eight weeks is termed a ‘suspected’ ONJ case.
The defect may be accompanied
by pain, swelling, paraesthesia and
infection. The pathophysiology of
the condition is not well understood but may initially relate to
soft tissue inflammation causing a
persistent ulcer with or without
oral super-infection.
The incidence of ONJ is still
unclear. An Australian study that
surveyed oral and maxillofacial surgeons and the Commonwealth
Adverse Drug Reaction Committee
identified 158 cases, including 26
patients with osteoporosis.16 Comparing these data with estimates of
bisphosphonate exposure in the population generated risks of between one
in 2260 and one in 8470 (0.010.04%) patients treated with oral bisphosphonates for osteoporosis.16
Most cases had occurred after
dental extraction. The risk was
higher for patients receiving IV bisphosphonates for treatment of malignancy (0.88-1.15%) and the condition may be more severe in these
patients. The median time to onset of
ONJ was 12 months for zoledronic
acid, and 24 months for alendronate.
German registry data presented in
abstract form have estimated a lower
risk of ONJ in osteoporosis patients
(<1 in 100,000 patient-treatment
years).17
Other risk factors for ONJ
appear to include pre-existing
dental or periodontal disease, alcohol or tobacco abuse and glucocorticoid treatment.
Patients must be properly
informed about the risk of ONJ
before starting a bisphosphonate,
and advised to inform their dentist
of the treatment. Patients should
be encouraged to maintain good
oral hygiene and, ideally, have regular dental visits. Periodontal disease should be non-surgically
treated if possible.
Endodontic treatment is preferable to extraction. If a dental
extraction has to be performed,
some experts recommend temporary discontinuation of bisphosphonates for a period before and
after the procedure, although there
are no data to support improved
dental outcomes by doing so. Current information suggests that
taking bisphosphonates is not a
contraindication to dental
implants.
Management of established ONJ
should be by dental specialists, and
guidelines include appropriate use
of analgesia, oral microbial rinses,
and systemic antibiotics if infection
is evident. Surgical treatment
should be conservative, and
delayed if possible. Osteoporosis
patients may be less prone to severe
ONJ than cancer patients receiving higher bisphosphonate doses.
At least temporary withdrawal of
bisphosphonate therapy is recommended when ONJ has developed,
until healing has occurred.
New therapies
Teriparatide
STUDIES over many years
had uncovered a curious
paradox about PTH:
whereas continuous exposure to PTH (such as in primary hyperparathyroidism)
causes bone loss, intermittent dosing with PTH actually stimulates osteoblastic
activity and new bone formation.
In 2001, daily SC administration of a synthetic fragment of PTH (teriparatide)
was reported to reduce vertebral fractures by 65% and
non-vertebral fractures by
53% in postmenopausal
women with osteoporosis.18
This trial was stopped prematurely after 20 months
because of concerns that
rodents developed osteosarcomas during high-dose and
long-term administration of
the drug.
42
Only one human case of
osteosarcoma has been
reported after teriparatide
treatment in more than
550,000 treated patients
worldwide — an incidence
that approximates the
expected occurrence of this
rare bone malignancy. Current recommendations are
that:
■ PTH therapy should be
limited to patients at high
risk of osteoporotic fracture.
■ Treatment duration should
not exceed 18 months.
■ Teriparatide should be
avoided in patients at
increased risk of osteosarcoma (eg, Paget’s disease
of bone or previous chest
wall radiotherapy).
The major limitations of
teriparatide are its cost and
the need for daily SC injections. Otherwise it is gener-
| Australian Doctor | 11 July 2008
ally well tolerated.
The hope that concurrent
therapy with teriparatide
and anti-resorptive therapies
would be of additive benefit
was not borne out in recent
studies; indeed, previous
treatment with bisphosphonates appeared to blunt the
anabolic effect of teriparatide. Conversely, new
bone formed by teriparatide
is quickly lost unless followed by sequential antiresorptive treatment.
IV bisphosphonates:
zoledronate
In a recent osteoporosis trial,
patients randomised to
receive an annual 15-minute
infusion of zoledronate
(5mg) for three years had an
impressive reduction in risk
of clinical vertebral fractures
(by 70%), hip fractures
(41%) and overall non-ver-
Evidence-based practice
The strongest risk factors for osteoporotic fractures are older age, low bone density and the
presence of a fragility fracture (level 1).
■ Fracture risk is reduced by treatment in patients who have already had a fracture and who have
low bone density (T-score at spine or hip <–2) (level 1).
■ Oral bisphosphonates (alendronate, risedronate) reduce vertebral and non-vertebral fractures in
patients with osteoporosis (level 1).
■ Strontium ranelate reduces vertebral (level 1) and non-vertebral fractures (level 2) in patients with
osteoporosis.
■ Raloxifene reduces vertebral fractures and also reduces risk of oestrogen-receptor-positive
breast cancer (level 1).
■ Oestrogen replacement reduces fracture risk in postmenopausal women (level 1) but benefit may
be outweighed by risk of venous thromboembolism and stroke (and breast cancer with
combined HRT).
■ Oral bisphosphonates prevent glucocorticoid-induced bone loss (level 2).
■ Falls-prevention strategies reduce falls in high-risk patients (level 2).
■
tebral fractures (25%) compared with those taking
placebo.19 Zoledronate was
also
associated
with
increases of 6.7% and 4%
in lumbar spine and femoral
neck BMD, respectively.19
First-dose reactions, including fever, myalgias and
www.australiandoctor.com.au
arthralgias and headaches,
were common (32%) but
transient (usually less than
three days). Serious AF
occurred more frequently in
the zoledronate group (1.3%
vs 0.5%) but there was no
excess risk of stroke. ONJ was
reported in one patient in the
zoledronate group and in one
case in the placebo group.
A parallel trial studied
2127 patients after hip fracture and demonstrated that
an annual zoledronate infusion was associated with a
28% relative reduction in
mortality compared with
AD_ 0 4 3 _ _ _ J UL 1 1 _ 0 8 . PDF
placebo. 20 Zoledronate
(Aclasta) is now registered
for use in post-menopausal
osteoporosis, or in women
or men aged >50 with a
prior low trauma hip fracture. At this stage, treatment
should be restricted to three
annual doses.
RANK ligand inhibitors
An anti-resorptive drug in
late clinical development is
denosumab, a monoclonal
antibody that binds and
inhibits RANK ligand (the
osteoblast signal that triggers
osteoclast activation [figure
1, page 39]). Phase II evaluation of denosumab showed
similar increases in BMD at
spine and hip, and suppression of bone resorption
markers, compared with
alendronate.
Future challenges
At this point in time, the
major obstacle in successful
osteoporosis management
continues to be getting
appropriate patients to start
and adhere to available therapies, rather than the effi-
Pa ge
1
7 / 3 / 0 8 ,
cacy of these therapies per
se. Modelling suggests that,
if all women aged over 60
with osteoporosis were prescribed, and complied with,
appropriate treatment, the
population burden of fractures could be reduced by as
much as 28%. Nevertheless,
new strategies are needed for
preventing the remaining
72% of fragility fractures.
A key deficiency is being
able to reliably identify
patients with osteopenia who
will fracture. Several studies
have examined various combinations of clinical risk factors, BMD measurements and
markers of bone turnover to
find a cost-effective algorithm
that identifies patients who
would benefit from treatment.
One such ‘risk calculator’ has
been created by researchers at
the Garvan Institute in
Sydney, using data from the
Dubbo Osteoporosis Epidemiology Study 21 and is
available online (see Online
resources, below). Utility of
this and other risk calculators
requires validation in prospective intervention studies.
4 : 0 9
PM
Summary and recommendations
Osteoporosis is a major public health burden: one in two women, and one in three men, over 60
will have a fracture in their remaining lifetime.
■ Measurement of BMD by DEXA identifies patients at risk of fracture; each standard deviation
reduction in femoral neck BMD increases age-adjusted risk of hip fracture about threefold, and
the risk of any fracture about twofold.
■ Clinical risk factors (in particular, age and previous fracture, but also maternal fracture, current
smoking and glucocorticoid use) also identify patients at risk.
■ A postmenopausal woman (or man over 50) with a fragility fracture will generally be at sufficiently
high risk to warrant therapy to prevent further fractures; measurement of BMD in this situation
may improve compliance and help monitor therapeutic response.
■ The presence of a vertebral fracture should be considered in patients with progressive height
loss and/or chronic back pain.
■ Most hip and peripheral fractures result from a fall; a patient with low bone mass should be
assessed for risk of falling, and the patient with frequent falls should ideally have their bone
density measured.
■ The timed up-and-go test is a simple screening test for postural instability.
■ Use of systemic corticosteroids is associated with rapid bone loss and increased fracture risk;
aromatase inhibitors and GnRH agonists are also associated with osteoporosis.
■ A few simple investigations (serum 25(OH)D, calcium, TSH, transglutaminase IgA antibody) may
be appropriate in patients with osteoporosis, to exclude potentially reversible causes; hypogonadism should be routinely excluded in men with low BMD.
■ A range of different therapies that can reduce fracture risk in people with pre-existing fracture or
low bone density is available (see Evidence-based practice, below).
■ BMD can be remeasured 12-24 months after starting treatment; progressive fall in BMD should
prompt evaluation of adherence to therapy and exclusion of secondary causes of bone loss.
■ Calcium supplementation to achieve daily intake of at least 1000mg is recommended in patients
with osteoporosis; vitamin D supplements should be given when the 25(OH)D level is low
(<50nmol/L).
■ The risk of ONJ is low in patients taking bisphosphonates for the treatment of osteoporosis
(between 1:5000 and 1:100,000 per annum); most cases are associated with dental extraction.
Good oral hygiene is essential, and regular dental reviews desirable, to prevent ONJ.
■
References
Available on request from
julian.mcallan@reedbusiness.
com.au
Online resources
■
Garvan Institute
researchers. Osteoporosis
risk calculator:
www.garvan.org.au/
promotions/bonefracture-risk
■ WHO Fracture Risk
Assessment Tool (FRAX):
www.shef.ac.uk/FRAX/
index.htm
Author’s case study
An unusual cause of
osteoporosis
A 62-YEAR-old woman was found
to have rapid bone loss after discontinuing combined HRT. Menopause
had occurred at age 50 and she had
then taken oral conjugated oestrogen
and medroxyprogesterone acetate for
four years until 2002. She had no history of fracture or back pain.
Her bone density was first measured in 2000 and showed mild
osteopenia of the femoral neck (Tscore –1.40) and normal spine BMD
(T-score –0.2). Bone density was remeasured 12 months after stopping
HRT; spine and hip BMD had both
decreased by 6.8%. She had adequate
calcium intake, which had been supplemented with calcium carbonate
1200mg daily for the past five years.
She was regularly active.
She had had a brief course of oral
corticosteroids to treat an exacerbation of asthma five years before, and
she was on regular low-dose inhaled
corticosteroids. She did not smoke
and there was no known family history of osteoporosis. She weighed
65.7kg and had not lost any height
over the preceding three years. Physical examination was unremarkable.
Her rapid bone loss was above that
expected for age, even considering the
recent cessation of HRT. Serum calcium and TSH measurements were
normal. Serum 25(OH)D was low
at 20nmol/L, and IgA tissue transglutaminase antibodies were
strongly positive.
The patient was referred to a
gastroenterologist, and endoscopy
and small-bowel biopsy confirmed
coeliac disease. Although GI symptoms were not particularly obvious
at the time, she did feel noticeably
better after starting a gluten-free
diet. Bone density was re-measured
12 months later and showed a
10% improvement in spine BMD
and 6% improvement in hip BMD.
Comment
Coeliac disease is diagnosed in
about 3% of patients referred to a
specialist osteoporosis service.
Symptoms may be subtle. Clues to
the diagnosis include rapid bone
loss and/or unexpectedly low
25(OH)D levels or iron deficiency.
Some recovery of bone loss can
occur with a gluten-free diet. Any
bone loss that had occurred during
this patient’s brief course of oral
steroid treatment would most
probably have recovered within a
few months, and inhaled corticosteroid treatment typically has only
minor effects on bone density.
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11 July 2008 | Australian Doctor |
43
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How to treat – osteoporosis
GP’s contribution
DR ROSS WHITE
Beecroft, NSW
Case study
TED, a 47-year old clerk, was
diagnosed with ankylosing
spondylitis at age 28. He takes
diclofenac when his back pain
is severe. He has had two
bouts of iritis, the last about
four years ago.
After a recent fractured
wrist, the doctor in the emer-
gency department recommended BMD testing with
DEXA. The radiologist
reported that, because of
lumbar syndesmophytes from
the ankylosing spondylitis,
lumbar BMD was difficult to
assess, but the femoral neck
BMD T-score was –2.3.
After discussion with Ted,
a once-weekly bisphosphonate
was prescribed. Ted returned
after reading the consumer
medicine information (CMI),
concerned because of the
warning in the CMI that
patients should see their doctor
immediately if blurred vision,
pain or redness of the eyes
occurred — symptoms that he
had with his iritis.
more likely to be associated
with ocular complications
such as conjunctivitis, iritis or
uveitis. It is not clear whether
these reactions occur more
often in patients with a history of iritis. Oral bisphosphonates are rarely reported
to be associated with these
complications.
Questions for the author
What is the risk of a bisphosphonate reactivating Ted’s
iritis, and is any one bisphosphonate less likely to cause
this side effect?
IV bisphosphonates are
How to Treat Quiz
2. Which TWO statements about
investigation of osteoporosis are correct?
a) The gold standard for osteoporosis
diagnosis remains dual-energy X-ray
absorptiometry (DEXA) measurement at
spine and hip
b) Hypogonadism should be routinely
excluded in men with low bone mass
c) Potentially treatable secondary causes of
osteoporosis include hypothyroidism and
primary hypoparathyroidism
d) A single baseline measurement of bone
turnover markers is highly predictive of
individual fracture risk
3. Joan’s bone density measured by DEXA
shows osteoporosis of the hip (T-score
–2.6) and osteopenia of the spine (T-score
–2.0). Simple screening reveals no
secondary cause of her osteoporosis. You
advise Joan that specific therapy for
osteoporosis is recommended and discuss
the options. Which TWO statements about
oral bisphosphonate therapy are correct?
General questions for the
author
For people with chronic
autoimmune diseases stabilised on immunosuppres-
sants, not on regular steroids
and with a normal initial
BMD (and no history of
fracture), how often should
BMD be measured?
There are no clear data to
guide this decision, but I
would consider remeasuring
BMD once more in two
years in a postmenopausal
woman (or man older than
50) and, if stable, then reassuring the patient that fracture risk is low, providing
the inflammatory activity of
the underlying disease is well
controlled. In younger
patients I would reassure
and not repeat BMD unless
corticosteroid treatment is
required.
INSTRUCTIONS
Complete this quiz online and fill in the GP evaluation form to earn 2 CPD or PDP points. We no longer accept quizzes
by post or fax.
The mark required to obtain points is 80%. Please note that some questions have more than one correct
answer.
Osteoporosis — 11 July 2008
1. Joan, 59, asks you if she should have a bone
mineral density (BMD) test. Further history
reveals she fractured her wrist four years ago
when she slipped and fell. Which TWO
statements about risk of osteoporosis and
fractures are correct?
a) Each standard deviation reduction in femoral
neck BMD increases age-adjusted risk of
vertebral fracture about threefold, and the risk
of any fracture about twofold
b) Important clinical risk factors for osteoporosis
include low body weight, maternal history of hip
fracture, smoking and inability to stand up from
a chair without using arms
c) A history of falling in the previous 12 months
has been shown to be an independent risk for
fracture
d) Use of systemic corticosteroids is associated
with bone loss but only if taken in doses of
at least 10mg prednisone daily for longer
than six months
If Ted declines bisphosphonate therapy, which other
measures should be advised to
minimise progression of the
osteopenia?
Ted’s serum testosterone
should be measured and
androgen replacement therapy
might be considered if he were
hypogonadal. Similarly, Ted’s
serum 25(OH)D should be
measured and replaced if low
(<70nmol/L). Calcium supplements should be given so that
Ted’s total daily calcium
intake is 1000mg.
Ted should be encouraged
to keep physically active. Specific physical therapy intervention for his ankylosing
spondylitis may help prevent
deformity. Control of any
inflammatory component of
his disease may also help prevent ongoing bone loss.
ONLINE ONLY
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a) Oral bisphosponates are potent stimulators
of bone formation and, to a lesser degree,
inhibit bone resorption
b) Alendronate and risedronate reduce
vertebral and non-vertebral fractures in
patients with osteoporosis
c) Oral bisphosphonates prevent
glucocorticoid-induced bone loss
d) Although a weaker agent than the other two
oral bisphosphonates, etidronate has been
shown to prevent both vertebral and nonvertebral fractures
4. Which THREE statements about other
agents for the treatment of osteoporosis
are correct?
a) Raloxifene reduces vertebral fractures and
also reduces risk of oestrogen-receptorpositive breast cancer
b) Oestrogen replacement reduces fracture
risk in postmenopausal women but benefit
may be outweighed by risk of venous
thromboembolism and stroke (and breast
cancer with combined HRT)
c) Strontium ranelate reduces vertebral and
non-vertebral fractures in postmenopausal
women with osteoporosis
d) Strontium has been shown to be effective in
patients who have been previously treated
with bisphosphonates
5. Which TWO statements about nonpharmacological management of
osteoporosis are correct?
a) Resistance training or regular walking
produces a small increase in spinal BMD,
without any consistent effect on hip BMD
b) Resistance training or regular walking has
been shown to reduce rates of vertebral
fractures but not non-vertebral fractures
c) Specific programs for muscle strengthening and
balance training have been shown to reduce
fracture rates in high-risk groups
d) Hip protectors have been shown in some
studies to reduce hip fractures in patients at
high risk of falls
6. Which TWO statements about calcium and
vitamin D and osteoporosis are correct?
a) Dietary intake of 1200mg of calcium per day
(equivalent to three or more servings of dairy
products) is generally recommended
b) A recent meta-analysis showed that calcium
supplementation prevented menopausal
bone loss, with a trend towards fewer
vertebral and non-vertebral fractures
c) Vitamin D supplementation with
cholecalciferol is recommended to achieve a
target serum 25-hydroxyvitamin D level of at
least 50nmol/L
d) Studies have consistently shown that
vitamin D supplementation reduces the risk
of both vertebral and non-vertebral
fractures, regardless of patients’ baseline
25-hydroxyvitamin D levels
7. Regina, 62, has been taking an oral
bisphosphonate for two years. Follow-up
shows a progressive fall in BMD. Which
THREE statements about non-response to
therapy are correct?
a) It is important to check that Regina has
been taking her bisphosphonate correctly
b) Regina should be re-assessed regarding
secondary causes of accelerated bone loss
c) Changing to another anti-osteoporosis
therapy might be considered
d) Adding a second anti-resorptive therapy will
additively reduce her fracture risk
8. Martha, 72, has been treated for
osteoporosis with alendronate for the past
seven years. Recent DEXA shows stable
BMD measurements of hip (T-score – 2.5)
and spine (T-score – 2.1) for the past 12
months. Martha says she heard the
medication should be stopped after seven
years. Which TWO statements about
duration of therapy are correct?
a) Data from the Fracture Intervention Trial
Long-term Extension Trial showed that
women who stopped alendronate after five
years had a significant decrease in hip BMD
within 1-2 years
b) Data from the Fracture Intervention Trial
Long-term Extension Trial showed that
continuing alendronate beyond five years
resulted in fewer vertebral and non-vertebral
fractures
c) There was no evidence in the Fracture
Intervention Trial Long-term Extension Trial
that bone remodelling was over-suppressed
even after 10 years of alendronate therapy
d) The alendronate data regarding skeletal
retention time can be extrapolated to both
risedronate and etidronate
9. Which THREE statements about
osteonecrosis of the jaw (ONJ) and
bisphosphonate therapy are correct?
a) Bisphosphonate-associated ONJ is
confirmed when an area of exposed bone in
the maxillofacial region does not heal within
three months
b) The risk of ONJ in patients taking
bisphosphonates for the treatment of
osteoporosis is low (between 1:5000 and
1:100,000 per annum)
c) Most cases of ONJ are associated with
dental extraction
d) Patients must be informed about the risk of
ONJ before starting a bisphosphonate, and
advised to inform their dentist of the treatment
10. Which TWO statements about new
therapies and future challenges for
osteoporosis are correct?
a) Parathyroid hormone (PTH) therapy
(teriparatide) should be limited to patients at
high risk of osteoporotic fracture
b) PTH therapy for osteoporosis can be used
for up to five years
c) Teriparatide should be avoided in patients
who have Paget’s disease of bone, or who
have had previous chest wall radiotherapy
d) Modelling suggests that if all women over
60 with osteoporosis were treated
appropriately, population burden of
fractures could be reduced by 5%
CPD QUIZ UPDATE
The RACGP now requires that a brief GP evaluation form be completed with every quiz to obtain category 2 CPD or PDP points for the 2008-10 triennium. You
can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept the quiz by post
or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
HOW TO TREAT Editor: Dr Wendy Morgan
Co-ordinator: Julian McAllan
Quiz: Dr Wendy Morgan
NEXT WEEK Despite otitis media being documented since the start of recorded history, no international consensus on best practice management has emerged, and Australian Aboriginal children remain the
world’s most vulnerable children in terms of prevalence and severity. The next How to Treat presents the latest on treating otitis media in children. The author is Dr Hasantha Gunasekera, clinical research
fellow and general paediatrician, The Children’s Hospital at Westmead; and clinical lecturer, University of Sydney, NSW.
44
| Australian Doctor | 11 July 2008
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