Download Osteoporosis

Osteoporosis
 Osteoporosis is a progressive skeletal
disease that is characterised by low bone
mass, skeletal fragility and susceptibility to
fracture.
Facts and figures
 1 in 3 women and 1 in 12 men in the UK will have
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osteoporosis over the age of 50
Every 3 minutes someone has a fracture due to
osteoporosis
An estimated 3 million people in the UK suffer from
osteoporosis
 Each year the numbers of people with osteoporosis
include over
 70,000 hip fractures
 50,000 wrist fractures
40,000 spinal fractures
Osteoporosis costs the NHS and government over £1.7
billion each year, that's £5 million each day!
Risk factors
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For women:
a lack of oestrogen, caused by
early menopause (before age 45)
early hysterectomy (before the age of 45),
particularly when both ovaries are removed
(oophorectomy)
 missing periods for six months or more
(excluding pregnancy) as a result of overexercising or over-dieting
Risk factors
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For men:
low levels of the male hormone, testosterone (hypogonadism)
For men and women:
long-term use of high dose corticosteroid tablets (for conditions
such as arthritis and asthma)
close family history of osteoporosis (mother or father),
particularly if your mother suffered a hip fracture
other medical conditions such as Cushing's syndrome and liver
and thyroid problems
malabsorption problems (coeliac disease, Crohn's disease,
gastric surgery)
long-term immobility
heavy drinking
smoking
Diagnosis
 normal x-ray of bone cannot reliably measure
bone density but is useful to identify spinal
factures, explains back pain, height loss or
kyphosis.
 A bone density scan, called a dual energy xray absorptiometry (DXA) scan, is used to
measure the density of bones and compare
this to a normal range. This test is currently
the most accurate and reliable means of
assessing the strength of bones and your risk
or fracture.
Treatments
 For people who have been diagnosed with osteoporosis there are a
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range of treatments available. The most common treatments include:
Bisphosphonates are non hormonal drugs, which help maintain bone
density and reduce fracture rates.
Calcium and vitamin D supplements can be of benefit for older people
to reduce the risk of hip fracture.
Hormone replacement therapy (HRT) is oestrogen replacement for
women at the menopause, which help maintain bone density and
reduce fracture rates for the duration of therapy.
Selective Estrogen Receptor Modulators (SERMs) are drugs which
act in a similar way to oestrogen on the bone, helping to maintain bone
density and reduce fracture rates specifically at the spine.
Testosterone therapy is testosterone placement for men with low
testosterone levels to help maintain bone density.
Osteoporosis Defn
 The definition of osteoporosis is centred on the level of bone mass,
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measured as BMD.
For diagnostic purposes, two thresholds of BMD have been defined by
the World Health Organization, on the basis of the relationship of
fracture risk to BMD.
The first threshold- defines the majority of individuals who will sustain
a fracture in the future (osteoporosis), and
The second a higher threshold more appropriate to the prevention of
bone loss in women at the time of the menopause (low bone mass or
osteopenia).
Osteoporosis’ denotes a value for BMD or bone mineral content that is
2.5 standard deviations (SDs) or more below the young adult mean
value (T-score less than –2.5).
‘Low bone mass’ means a T-score that lies between –1 and –2.5.
‘Severe’ or ‘established’ osteoporosis denotes osteoporosis as defined
above in the presence of one or more documented fragility fractures.
Key points
 The NOS endorses the Royal College of Physicians’ guidelines, which
currently provide the most up-to-date recommendations about
treatment for physicians.
 The bisphosphonates (alendronate, etidronate and risedronate),
 calcium andVitamin D, HRT and raloxifene are the licensed
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treatments generally prescribedfor the prevention and treatment of
osteoporosis, all of which have evidence to support their anti-fracture
efficacy.
Several other drugs are also under development.
There is currently no concrete evidence that, as an intervention,
exercise reduces the risk of fracture.
Falls prevention strategies, including fitness training and use of hip
protectors, may protect against fracture risk in older women.
To date there have been very few studies that have directly compared
the antifracture efficacy of the different treatment approaches.
Bisphosphonates
 There are currently three bisphosphonate drugs
licensed for osteoporosis in the UK;
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Alendronate (Fosamax),
Cyclical Etidronate (Didronel PMO)
Risedronate (Actonel)
 all of which have an anti-resorptive effect on bone.
 They are currently available as daily tablets,
 Alendronate can also be taken weekly. Pamidronate,
which is available as an
 infusion, is also prescribed by some consultants (out
of licence) for those patients with severe gastric
problems.
Bisphosphonates
 Large randomised controlled trials have shown
that alendronate and risedronate reduce the
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risk of vertebral fracture by about 50%
the treatments work rapidly, bringing about a
reduction in fracture risk within one year.
 Other studies have shown that
 alendronate and risedronate also reduce the risk of
other fractures, including hip fracture.
 However, this effect is much less marked in those
individuals who do not have low bone density.
Calcium and vitamin D
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Supplementation with 1200mg of calcium and 800iu of vitamin D has been
shown to
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significantly reduce the risk of non-vertebral fractures, including hip
fracture, in older women living in sheltered accomodation.
There is also evidence that calcium and vitamin D taken in similar
doses protects against fractures other than in the spine, in older
women living independently.51
However, it remains uncertain as to whether these benefits are
dueto vitamin D, calcium or a combination of both.
Vitamin D deficiency is common amongstthe institutionalised
elderly
the question as to whether vitamin D alone protects against hip
fracture is currently being examined in multi-centre trials.
There is some new
evidence that it may help to reduce falls by influencing
neuromuscular function.
Calcium and vitamin D
 Except perhaps for frail older people, calcium
and vitamin D supplementation is not
sufficient to treat individuals with
osteoporosis.
 Supplementation is required for those who
are
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housebound,
have restricted exposure to sunlight, or
have an inadequate calcium intake
Hormone Replacement Therapy
(HRT
 HRT is available in many different forms which
provide oestrogen, cyclical oestrogen and
progestogen or both hormones in a continuous
combined product
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daily tablets,
patches,
implants,
Gel
nasal spray,
 A synthetic steroid, tibolone (Livial) is also
available.
(WHI) trial
 The most recent evidence comes from the
Women’s Health Initiative (WHI) trial, which has
confirmed that HRT brings about a significant
reduction in risk for all clinical fractures
 In healthy post-menopausal women. These
results should however be interpreted in context,
as the trial also demonstrated that HRT was
associated with an increased risk of
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breast cancer and deep vein thrombosis,
as well as a small but significant increase in the
risk of heart disease and stroke.
 There is also increasing evidence for loss of the
beneficial effects of HRT after treatment is
withdrawn.
Selective Estrogen Receptor
Modulators (SERMs)
 Raloxifene (Evista) is the only SERM currently
licensed in the UK for the prevention and
treatment of vertebral osteoporosis.
 The SERMs work like oestrogen in a beneficial
way on certain organs of the body (i.e. the
skeleton), remain neutral on the endometrium,
whilst inhibiting the detrimental effects of
oestrogen on the breast.
Selective Estrogen Receptor
Modulators (SERMs)
 A large randomised controlled trial has shown
that raloxifene significantly reduces vertebral
fractures by 30-50% after one year of
treatment.
 However, the study was unable to show any
significant reduction in non-vertebral
fractures, including hip fracture.
 Raloxifene has also been demonstrated to
reduce breast cancer risk and has favourable
effects on heart disease risk.
Licensed treatments used less
frequently
 Both calcitriol and calcitonin are licensed for
osteoporosis
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are effective in reducing the risk of vertebral and nonvertebral fractures in postmenopausal women.
However, the data is not as conclusive as for the other
licensed treatments.
 The anabolic steroid nandrolone deconoate (Deca-
Durabolin) is also licensed for osteoporosis,
although there is currently no clinical evidence that its
use reduces the risk of fracture.
Treatments currently under
development
 Parathyroid hormone (teriparatide) has an
anabolic effect and works by stimulating bone
formation.
 There is also evidence that it improves the structure
of bone, an effect not seen with anti-resorptive drugs.
 Recent studies have demonstrated that teriparatide
significantly reduces the incidence of both vertebral
and non-vertebral fractures, although there is
currently no separate evidence for reduction in hip
fracture risk.
 The effect of teriparatide on vertebral fractures was
particularly marked amongst women with moderate to
severe vertebral deformities.
Other treatments under
development
 Include several bisphosphonates (i.e.
pamidronate, clodronate, ibandronate and
zoledronate) and strontium.
Calcium and Vitamin D
 In all of the above trials calcium and vitamin
D were prescribed in addition to the tested
drug.
 As such, the efficacy of the trials can only be
assumed in women with an adequate intake
of these nutrients and cannot be assumed in
those with low calcium intakes and/or vitamin
D deficiency.
Non-drug approaches for preventing
fracture
 Both clinical trials and observational studies suggest that
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load bearing exercise such as weight training and high
impact exercise, are the most effective at increasing BMD
although the change is not sustained once the exercise is
stopped.
There is currently no concrete evidence that exercise
programmes reduce the risk of fracture
but fitness may indirectly protect an individual from fracture
by improving mobility and muscle function and reducing the
risk of falls.
There is good evidence that falls prevention strategies are
effective in reducing falls, although the effects on fracture
reduction remain unclear.
Non-drug approaches for preventing
fracture
 Hip protector pants, which include a
polypropylene shield that decreases the
impact of a fall, have been shown to reduce
the risk of fracture by as much as 50%.
 They are most appropriate for older, frailer
women who need to be wearing them when
they fall (concordance problems are evident
in the trials).
What is it like to take a treatment
for osteoporosis?
 Key points
 Women are able to gain reassurance that a treatment for
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osteoporosis is working mainly through knowledge that its
efficacy has been demonstrated in clinical trials.
The treatments do not make women feel any different in the
short term but do reduce the risk of fracture and the possibility of
further pain and disability in the future.
Several treatments for osteoporosis are associated with side
effects and risks and some involve complicated treatment
regimens. As a result, concordance can be problematic.
A woman may need to try several different treatments before
she finds one that is both appropriate and tolerable. A choice of
treatments is therefore important.
Clear guidance on prescribing and access to a broad range of
treatments will help health professionals manage a patient’s
condition effectively.
Side effects of treatment
 In general, problems with calcium and vitamin D are rare,
although some women do experience bloating, constipation
and an upset stomach.
 Teriparatide also appears to be well tolerated in the clinical
trials to date, although high doses of the drug were associated
with headaches and nausea in some women.
 Concordance with HRT can be problematic, as demonstrated in
the research studies.
 Postmenopausal women taking HRT may return to monthly or
irregular bleeds, experience premenstrual symptoms and breast
tenderness, and are faced with the difficult decision of
considering the potential benefits of the treatment for
osteoporosis versus the risk of breast cancer, DVT, stroke and
heart disease.
 Women taking raloxifene may experience troublesome hot
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flushes. This makes it an inappropriate treatment for younger
postmenopausal women who are already coping with
menopausal symptoms.
Use of raloxifene is also related to an increase in risk of
DVT,similar to that of HRT.
Alendronate and risedronate are unsuitable for those with
regular heartburn, stomach ulcers or a hiatus hernia that causes
symptoms.
A number of women phoning the NOS helpline have also
reported problems with musculoskeletal pain.
Similarly, etidronate can cause nausea and diarrhoea, as well
as bloating and constipation due to the calcium carbonate
that has to be taken for a period of 76 days following the drug.
 To reduce any potential difficulties bisphosphonates
need to be taken in a very specific way.
 The complicated treatment regimens can be
restrictive for active women with busy lifestyles and
may be off-putting for older women, especially those
who are unable to follow instructions.
 Some women find it difficult to remain upright after
taking the tablets, perhaps because of another
chronic condition, and those who need to eat
regularly or take other medications can find the
fasting times difficult.
 Weekly formulations e.g. for alendronate may help
to make the regimens more acceptable.
Treatment
 Key points
 Decisions about the treatment of osteoporosis are currently
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guided by then recommendations of the Royal College of
Physicians, which highlight a selective case-finding approach to
target treatment in those at highest risk.
Despite this, the NHS is still in need of coherent and authoritative
prescribing practices for osteoporosis.
All women should be offered a choice of treatment so that they
can find one that is both tolerable and appropriate to their
personal needs.
In addition to drug therapy women should also receive advice on
how to make other lifestyle changes to reduce the risk of fracture
i.e. exercise, dietary habits and smoking, as well as referral to a
falls service, if necessary.
The management of osteoporotic fracture should be fully
comprehensive and include strategies, such as hydrotherapy,
physiotherapy and pain management clinics, to help women cope
with pain and disability.
Investigations
 FBC, ESR
 Bone and liver function tests [Ca, P, alk phos, albumin, AST/gGT]
 Serum creatinine
 Serum TSH
 If indicated
 Lateral thoracic and lumbar spine X-rays
 Serum paraproteins and urine Bence Jones protein
 Isotope bone scan
 Serum FSH if hormonal status unclear [women]
 Serum testosterone, LH and SHBG [men]
RCP Algorithm
REYKJAVIK, Iceland, Nov 03, 2003 (United Press
International via COMTEX
 An Icelandic firm has identified a gene linked to osteoporosis, a disease
that is responsible for 1 million U.S. bone fractures a year.
 Decode Genetics, an Icelandic company trying to identify genes that
underlie common human diseases, said the people with any of three
specific variants of the gene for osteoporosis have a threefold risk of
developing the disease, according to the study published in the journal
Public Library of Science.
NEW YORK (Reuters Health) - high cholesterol increases the risk of
heart disease, but new research from Italy suggests that it may also be
bad for the bones.
 In a study of postmenopausal women, those with higher levels
of the "bad" form of cholesterol were much more likely to show
signs of bone thinning than women with normal cholesterol.
 The findings do not prove that high cholesterol is to blame for
bone thinning, but the results do provide a possible explanation
for studies suggesting that cholesterol-lowering drugs called
statins protect bones, researchers report in the journal
Obstetrics and Gynecology.
 Very little is known about how cholesterol levels may affect the
risk of developing the brittle-bone disease osteoporosis. Studies
that have examined the relationship between levels of LDL
cholesterol - the "bad" type of cholesterol - and the risk of bone
thinning have produced mixed results. ]
 In the new study, a team led by Dr. Andrea Poli at the University
of Milan measured bone density and cholesterol levels in 1,303
women ages 45 to 65 who had been through menopause.
PTH and Alendronate: Combining Treatments Shows No Bone
Density Advantage
 Combining the bone-building treatment parathyroid hormone
(PTH) with alendronate, a drug that slows bone loss, produces
no significant improvement in bone mineral density (BMD)
beyond that produced by the individual drugs, according to two
new studies involving postmenopausal women and men with
low BMD.
 The two studies, reported in the September 25 issue of the New
England Journal of Medicine and supported by the National
Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS), one of the National Institutes of Health, both tested
BMD in the spine and hip. BMD, a common indicator of bone
health, is used to diagnose the bone-weakening disease
osteoporosis, detect low bone mass before the disease
develops and help predict the risk of future fractures.
DEXA Scan
 A DEXA scan report compares the patient's
bone mineral density values with those of
young normal patient (T score) and
 with age matched normal patient (Z score).
By comparing a patient's bone density
against their peers, a low score indicates
there may be a reason other than age related
bone loss.
Patients risk factors
 Patients risk factors for osteoporosis that
should play a part in the decision to begin
treatment include:
 a maternal history of a hip fracture,
 any previous fracture after the age of fifty,
 tall height at age of 25,
 poor health,
 some sedatives and anticonvulsant drugs,
 and the inability to rise from a chair without
the use of the arms.
 The current treatment recommendations are
the start of drug therapy to reduce the risk
fracture for all women with a bone mineral
density T score of less than -2 without other
risk factors and for those with a T score of
less than -1.5 if other risk factors are present.