BONE DISORDERS
Prevention and
management of
osteoporosis
Richard Eastell
Abstract
Fractures resulting from osteoporosis are a major public health prob-
lem. Physicians should be aware of the chief risk factors for osteopo-
rosis and refer appropriately for bone densitometry. Risk factors
include previous fracture, family history of fracture, slender habitus,
early menopause, treatment with drugs known to affect bone (gluco-
corticoids) and diseases known to affect bone (rheumatoid arthritis).
The diagnosis of osteoporosis can be made if the bone density T-
score is 2.5 or below. This information can be used with other risk
factors to estimate the 10-year risk of fractures. Patients at the highest
risk for fracture benet from many licensed treatments. These can be
given orally (alendronic acid, disodium etidronate, risedronate sodium,
ibandronic acid, calcitriol, raloxifene, hormone replacement therapy),
subcutaneously (parathyroid hormone, denosumab) or intravenously
(ibandronic acid, zoledronic acid) and usually result in an increase in
bone mineral density and a reduction in fracture risk. Osteoporosis
can be prevented by careful attention to exercise and diet.
Keywords Bone mineral density; kyphoplasty; MRCP; osteoporosis;
treatment; vertebroplasty
Introduction
Osteoporosis is a systemic skeletal disease characterized by low
bone mass and microarchitectural deterioration, with a conse-
quent increase in bone fragility and susceptibility to fracture,
particularly of the vertebral body, distal forearm and proximal
femur in postmenopausal women.1 A more practical definition of
osteoporosis is based on bone mineral density (BMD). The BMD
of the older person is compared with the average BMD of a
person of the same gender at age 30 years, and the results
expressed in standard deviation units, the so-called T-score. If
the T-score is equal to or less than 2.5, osteoporosis may be
diagnosed.
Fractures that result from osteoporosis cause considerable
morbidity and mortality. Their incidence is increasing in
Richard Eastell FRCP (London, Edinburgh, Ireland) FRCPath FMedSci is
Professor of Bone Metabolism at the University of Shefeld and
Honorary Consultant Physician at the Shefeld Teaching Hospitals
NHS Foundation Trust, Shefeld, UK. Competing interests: Professor
Eastell receives consulting fees from Amgen, AstraZeneca, Chronos,
GSK, Immunodiagnostic Systems, Fonterra Brands, Ono Pharma,
Lilly, Bayer, Janssen Research, Alere, CL Biosystems, Teijin Pharma,
D-Star, Roche Diagnostics and Inverness Medical, and grant support
from Amgen, Alexion, Immunodiagnostic Systems, Roche and
AstraZeneca.
MEDICINE --:-
Please cite this article in press as: Eastell R, Prevention and management of osteoporosis, Medicine (2017), http://dx.doi.org/10.1016/
j.mpmed.2017.06.004
Key points
C It is worthwhile measuring bone mineral density (BMD) in
patients with strong risk factors (e.g. those taking long-term
corticosteroids, older patients with low-trauma fractures)
C There is good evidence that treatment prevents fractures in
women with vertebral fractures or with BMD T-scores of 2.5
or less
C It is usual to give a 5-year course of oral bisphosphonates (or
a 3-year course of intravenous bisphosphonates) and then a
drug holiday; in more severe cases, it is usual to give a 10-year
course of oral bisphosphonates (or a 6-year course of intra-
venous bisphosphonate)
C Denosumab should be given every 6 months, punctually, and
treatment should not be stopped without considering alter-
native therapy
C Hip fracture can be prevented in frail, elderly patients by cal-
cium and vitamin D supplements
developed countries as a result of the increase in the proportion
of elderly people in the population, and an increase in the inci-
dence of fracture within the elderly population resulting,
perhaps, from a more sedentary lifestyle.
It is now possible to determine an individuals risk of osteo-
porosis and fracture accurately, and to monitor their response to
treatment by bone densitometry. The prediction algorithm
FRAX allows estimation of 10-year risk,2 and treatment guid-
ance can be based on this. Many cases of osteoporosis are pre-
ventable, and treatment is effective in reducing the number of
further fractures in patients with established osteoporosis.
Diagnostic testing
Investigations
Patients with an osteoporosis-related low-trauma fracture should
undergo systematic investigation to identify underlying causes
(or secondary osteoporosis) (Tables 1 and 2).1 Identification of a
low-trauma fracture (a fall from standing height or less) of the hip
or distal forearm is straightforward. However, identification of
vertebral fracture can be difficult because it may not be painful.
Radiology
The most reliable finding on a spine radiograph to support the
diagnosis of osteoporosis is the presence of a deformed vertebra.
Vertebral fracture is characterized by depression of the endplate
and can appear as:
 a wedge deformity (loss of anterior height)
 an endplate deformity (loss of middle height)
 a compression deformity (loss of anterior, posterior and
middle height).
Subtle changes of osteoporosis may be identified on spine
radiographs (e.g. low density compared with soft tissue, promi-
nence of vertical trabeculae), but these changes are unreliable,
1 2017 Published by Elsevier Ltd.
 BONE DISORDERS

Dual-energy X-ray absorptiometry (DXA) is precise and accu-

Factors affecting rate of bone loss rate, involves exposure to only low doses of X-rays and allows
Nutrition Body weight Lifestyle Genetic the measurement of bones of clinical interest (lumbar spine,
proximal femur). In DXA, two energy peaks of X-rays are
Increase Sodium Thinness Alcohol abuse Family history absorbed to different extents by bone and soft tissue, and the
bone loss Caffeine Cigarette Female sex density of bone is calculated, in g/cm2, using simultaneous
smoking equations. The measurement is compared with two reference
Bed rest ranges: one for young adults (aged 30 years; giving a T-score)
Decrease Calcium Obesity High activity Race (black) and one for age-matched adults (giving a Z-score). These BMD
bone loss measurements have several uses (Table 3).
Unknown Phosphate Normal activity
effect on Bone turnover
bone loss Bone biopsy can be useful in unusual forms of osteoporosis (e.g.
idiopathic osteoporosis in young adults). It provides information
Sex hormones Diseases Drug therapy
about the rate of bone turnover and the presence of secondary
Increase Early Cushings syndrome Glucocorticoids forms of osteoporosis (e.g. systemic mastocytosis). Patients with
bone loss menopause high bone turnover usually respond better to antiresorptive drugs
Oophorectomy Hyperthyroidism Thyroxine (e.g. oestrogen, bisphosphonates, calcium).
Postmenopause Hyperparathyroidism Heparin
Amenorrhoea Diuretics Biochemical markers of bone turnover (Table 4) reflect the
(furosemide) processes of bone resorption and bone formation (see Bone
Aromatase structure and metabolism on pages xxx of this issue). Markers
inhibitors that are specific to bone (e.g. osteocalcin, N-terminal telopep-
Decrease Hormone tides) are useful in predicting individuals at risk of osteoporosis
bone loss replacement (fast bone-losers) or in monitoring the effect of drugs used in
therapy treatment.
Markers of bone resorption can be particularly useful, as
Table 1 changes in their concentration reflect the reduction in risk of
fracture following treatment with bisphosphonates more closely
than do changes in measured BMD. The changes in bone
Diagnostic evaluation of osteoporosis resorption markers are usually maximal after 6 months of
treatment. This makes them more suitable for treatment moni-
Establish presence of low-trauma fracture toring than bone density as changes in density are often not
C Spine radiography apparent for 2 years. Also, access to bone density facilities can be
Evaluate degree of osteopenia limited.
C Bone densitometry
Exclude secondary osteoporosis
Management and prevention
C Primary hyperparathyroidism (serum calcium)
C Thyrotoxicosis (plasma thyroid-stimulating hormone) Treating established osteoporosis
C Multiple myeloma (erythrocyte sedimentation rate, protein elec- The aims of treatment of established osteoporosis are alleviation
trophoresis, urinary Bence Jones protein) of symptoms and reduction of the risk of further fractures.
C Osteomalacia (serum 25-hydroxyvitamin D, plasma parathyroid Currently available drugs can prevent further bone loss and
hormone, serum calcium, phosphate, alkaline phosphatase, 24- reduce the risk of further fractures by up to 50%. Drug treat-
hour urinary calcium and creatinine) ments should be monitored by BMD or bone turnover marker
C Malabsorption syndrome (full blood count) measurements as some patients fail to respond to certain drugs.
C Hypogonadism in men (testosterone) The rate of bone loss can be accelerated once treatment is
Evaluate bone turnover stopped; it therefore remains important to measure BMD or bone
C Biochemical markers turnover markers after stopping treatment.
C Bone histomorphometry
Pain relief: this is provided by analgesic drugs or physical
Table 2 measures (e.g. lumbar support for a limited period of time,
transcutaneous nerve stimulator). Fracture pain usually resolves
and the apparent low bone density seen on a radiograph may be within 3 months, but patients with vertebral fractures can require
a technical artefact introduced by overexposure. Osteoporosis long-term analgesia because of secondary degenerative disease.
must therefore be confirmed by BMD measurement. During the early phase (6 weeks), some patients can benefit from
percutaneous vertebroplasty (injection of bone cement into a
Bone mineral density measurement collapsed or fractured vertebra) or balloon kyphoplasty (inflation
BMD measurement has become more reliable and more widely of a balloon within the collapsed vertebral body before stabili-
available. zation with bone cement). During the later phase (after 6

MEDICINE --:- 2 2017 Published by Elsevier Ltd.

Please cite this article in press as: Eastell R, Prevention and management of osteoporosis, Medicine (2017), http://dx.doi.org/10.1016/
j.mpmed.2017.06.004
 BONE DISORDERS
Uses of bone density measurements
To establish current fracture risk by comparison with young adult
reference range
C A decrease in spine density of one standard deviation (or 12%) is
associated with a doubling of fracture risk
To establish future fracture risk by comparison with age-matched
adults
C This is particularly useful in perimenopausal women; assuming
that bone loss proceeds at the average rate, those who will be at
high risk of fracture by 70 years of age can be detected
To monitor the effect of treatment
C Measurements are made every 2 years
C A difference of >3% can be detected by DXA of the lumbar spine
(the average rate of bone loss in untreated osteoporosis is about
2% per year; the average rate of bone gain in osteoporosis
treated with antiresorptive agents is 3% per year)
Table 3
Biochemical markers of bone turnover
Bone resorption Bone formation
C Pyridinium C Osteocalcin
cross-links of collagen C Bone-specific alkaline
 Pyridinoline phosphatase
 Deoxypyridinoline C Procollagen type
C Cross-linking I C-terminal (PICP)
telopeptides of and N-terminal
type I collagen (PINP) propeptides
 N-terminal (NTX)
 C-terminal (CTX)
C Tartrate-resistant
acid phosphatase
The International Osteoporosis Foundation has recommended the use of CTX
as a marker of bone resorption and PINP as the reference for bone turnover
markers (see Further reading).
Table 4
months), some patients benefit from injection of local anaes-
thetic into the facet joints of the spine.
Drugs to increase or maintain bone mass: drugs either inhibit
bone resorption or stimulate bone formation. Most drugs
approved for use in osteoporosis inhibit bone resorption, but some
of these (e.g. hormone replacement therapy (HRT), bisphospho-
nates) increase BMD by 5e10% over the first 2 years of treatment.
We can try to prevent osteoporosis in people who have
osteoporosis but not yet a fracture (primary prevention) and
people who have already had a fracture (secondary prevention).
These treatments are usually given for secondary prevention and
treatment according to the National Institute of Health and Care
Excellence guidance.3,4 It is usual to consider treating patients
who have low-trauma fractures of the hip and spine. It is usual to
treat people who have a BMD T-score at the lumbar spine or total
hip of e2.5 or less (osteoporosis). The National Osteoporosis
Guideline Group recommends the FRAXTM tool to guide the use
MEDICINE --:-
Please cite this article in press as: Eastell R, Prevention and management of osteoporosis, Medicine (2017), http://dx.doi.org/10.1016/
j.mpmed.2017.06.004
of BMD testing and preventive drugs according to clinical vari-
ables including the patients age.5
Antiresorptive drugs: in the UK, seven agents are currently
approved for use in osteoporosis: disodium etidronate, alen-
dronic acid, risedronate sodium, ibandronic acid, zoledronic acid
(all bisphosphonates), denosumab (a human monoclonal anti-
body that inhibits osteoclast formation, function and survival)
and raloxifene (a selective oestrogen receptor modulator).
Bisphosphonates are considered to be the treatment of choice.1e5
Calcium 1000 mg/day and vitamin D 800 IU/day given
together have been shown to prevent hip fracture in house-
bound, elderly patients. This treatment is safe and inexpensive,
and does not require monitoring. It is commonly given with other
treatments for osteoporosis. There has been some concern about
an increased risk of cardiovascular disease with calcium sup-
plementation, so it is wise to encourage obtaining adequate cal-
cium from the diet, if possible.1
Disodium etidronate is less potent than other oral bisphosph-
onates and is now rarely used. It is given in a cyclical regimen at a
dose of 400 mg/day for 2 weeks, followed by elemental calcium,
500 mg daily for 11 weeks. The effects on spine BMD are similar
to those of HRT. Adverse effects are uncommon.
Alendronic acid is given in a dose of 10 mg/day continuously
or 70 mg once weekly. It must be taken at least 30 minutes before
breakfast (to help absorption) with a full glass of water, and the
patient must not lie down for at least 30 minutes after taking the
tablet (to avoid oesophagitis). Alendronic acid is equally effective
for the hip, forearm and spine, and has been shown to prevent
fracture at all these sites.
Risedronate sodium is given in a dose of 5 mg/day continu-
ously or 35 mg once weekly. Risedronate can be taken at least 30
minutes before breakfast or 2 hours after a meal. It has been
shown to prevent spine, hip and other fractures.
Ibandronic acid is given in a dose of 150 mg once monthly. It
reduces the risk of vertebral fracture (and other fractures, if the
BMD T-score is less than 3). It can also be given by intravenous
injection (3 mg) every 3 months.
Zoledronic acid is given by intravenous infusion (5 mg over 15
minutes) every 12 months. It reduces fractures of the spine and
hip and all other fracture sites; it has also been shown to reduce
further fractures in patients presenting with hip fractures.
Denosumab is given at a dose of 60 mg every 6 months by
subcutaneous injection. It has been shown to reduce the risk of
spine, hip and non-spine fractures. After stopping treatment,
there is a rebound increase in bone turnover markers; therefore it
should be given at intervals of no less than 6 months, and
another drug should be started as soon as it is withdrawn to
prevent this increase in bone turnover and a likely increase in the
risk of vertebral fractures.
Raloxifene is given in a dose of 60 mg/day continuously.
Raloxifene has been shown to reduce the risk of spine (but not
other) fracture, and can reduce the risk of breast cancer. How-
ever, it can increase the risk of deep vein thrombosis and does
not prevent hot flushes.
HRT is an effective treatment for osteoporosis even in elderly
women. However, compliance and acceptability are often low in
older patients, and the observation that HRT is associated with
increased risk of stroke and ischaemic heart disease means that it
3 2017 Published by Elsevier Ltd.
 BONE DISORDERS

is no longer routinely used for the treatment of osteoporosis. It is

still used up to the age of 50 years in women with early or pre- Prevention of osteoporosis
mature menopause. Optimize peak bone mass
Testosterone therapy is effective in men with hypogonadism. C Exercise must be regular and weight-bearing (e.g. walking,
Three other agents can be useful in special circumstances, for aerobics); exercise that results in amenorrhoea can lead to bone
example intolerance of other agents: loss
 Strontium ranelate works by mechanisms that are not yet C Dietary calcium can be important, particularly during growth
fully elucidated. It reduces the risk of spine and non-spine Reduce rate of bone loss
fracture and is given in a dose of 2 g/day in water. How- C Regular exercise
ever, it increases the risk of cardiovascular disease so C Maintain calcium intake
should not be given to patients at risk of this. Following C Moderate alcohol intake
these cardiovascular concerns, strontium ranelate will no C Stop smoking
longer be available in the UK after August 2017.
 Calcitonin intranasally has recently been withdrawn by the Table 5
Medicines and Healthcare products Regulatory Agency for
Preventing osteoporosis
use in osteoporosis. Its use has been associated with an
Preventive treatments aim to increase peak bone mass and
increased risk of cancer.
reduce the subsequent rate of bone loss (Table 5).
 Calcitriol stimulates calcium absorption and may stimulate
Prophylactic treatment against bone loss can be considered in
osteoblasts directly. It appears to be effective in
postmenopausal women whose BMD at the lumbar spine or hip
corticosteroid-induced osteoporosis, in which it can be
is more than one standard deviation below the mean for their
considered an alternative to HRT or bisphosphonates,
age. However, this approach has not gained general acceptance
particularly in younger patients. Regular monitoring of
because it is not cost-effective.
serum calcium is required because hypercalcaemia is a
Women with BMD above the mean for young adults probably
common adverse effect.
do not require treatment for prevention of osteoporosis.
Women with intermediate BMD may benefit from these
Formation-stimulating drugs: have recently been licensed for
treatments if they lose bone at a faster than average rate; this can
osteoporosis.3 Use of a recombinant fragment of parathyroid
be determined from a repeat measurement of BMD after 2 years.
hormone (teriparatide) may be advised for patients with severe
In future, it may be possible to predict who will lose bone quickly
osteoporosis (very low T-score, vertebral fractures) who have
using biochemical markers of bone turnover.
failed to respond to or are intolerant of antiresorptive therapy.
Teriparatide treatment increases the thickness of cortical bone
Case report
and the connectivity of trabecular bone. These improvements
A 62-year-old woman developed acute-onset, low-back pain after
in bone quality and quantity are particularly associated with
lifting. Radiography showed superior end-plate deformity of
reductions in fractures of the spine. It is given by daily subcu-
vertebra L1. She developed abdominal distension. The major risk
taneous injection (20 micrograms/day), with calcium supple-
factor present was bilateral oophorectomy at the age of 38 years.
mentation for a 2-year course; it no longer works if given for
Biochemical tests to exclude secondary osteoporosis were normal.
longer, and there has been concern (from studies on rats) that
The results of bone densitometry of her lumbar spine are shown
long-term therapy might result in osteosarcoma.
below. The BMD of the proximal femur was also measured.

Long-term treatment with bisphosphonates: the bisphospho-

Spine Femoral neck
nates have an excellent safety record. However, there have been
case reports of osteonecrosis of the jaw (particularly after tooth Bone mineral density (g/cm2) 0.65 0.72
extraction) and atypical femur fractures (subtrochanteric or Young normal (standard deviation units) 4.2 2.4
femoral shaft stress fractures) that might be caused by long-term Age-matched (%) 65 91
use. Experts1,5 have proposed that oral bisphosphonate therapy
be continued for up to 5 years and intravenous therapy up to 3 SD, standard deviation.
years; if bone density of the femoral neck is then above 2.5,
treatment is stopped and bone density (or bone turnover markers)
measured every 2 years until bone loss resumes. If the bone This patient is at high risk of future fracture of the spine
density is 2.5 or lower, the bisphosphonate should be continued (about 16-fold) and proximal femur (about eightfold). She was
up to 10 years and then stopped. Bisphosphonates such as alen- treated with alendronic acid, vitamin D (800 IU/day) and calcium
dronic acid and zoledronic acid suppress bone turnover and supplements, 1000 mg/day, and BMD increased at both the
prevent bone loss for several years after they have been stopped. lumbar spine and the femoral neck. The increase at the lumbar
spine showed the pattern typical for antiresorptive drugs such as
Treating secondary osteoporosis often leads to partial recovery oestrogen and bisphosphonates (an increase in BMD over 3 years
of bone mass. followed by a plateau), although the increase was greater than
that usually seen. She sustained a further fracture after 2 years
Preventing falls treatment; therapy reduces the incidence of fractures by 50%,
(see Falls in Medicine 2017; 45(1): 28e33). but does not prevent them completely. A

MEDICINE --:- 4 2017 Published by Elsevier Ltd.

Please cite this article in press as: Eastell R, Prevention and management of osteoporosis, Medicine (2017), http://dx.doi.org/10.1016/
j.mpmed.2017.06.004
 BONE DISORDERS

2 University of Shefeld. FRAX: fracture risk assessment tool. https://

20 www.shef.ac.uk/FRAX/.
3 National Institute for Health and Care Excellence. Alendronate,
Spine
etidronate, risedronate, raloxifene, strontium ranelate and ter-
Bone mineral density (% change)

iparatide for the secondary prevention of osteoporotic fragility

15
fractures in postmenopausal women. https://www.nice.org.uk/
guidance/TA161.
4 National Institute for Health and Care Excellence: Alendronate,
10
etidronate, risedronate, raloxifene and strontium ranelate for
the primary prevention of osteoporotic fragility fractures in
postmenopausal women. https://www.nice.org.uk/guidance/
5 Hip TA160.
5 Compston J, Bowring C, Cooper A, et al. National Osteoporosis
Guideline Group. Diagnosis and management of osteoporosis
0
in postmenopausal women and older men in the UK: National
0 12 24 36 48 60
Osteoporosis Guideline Group (NOGG) update 2013. Maturitas
2013; 75: 392e6.
Time (months)
FURTHER READING
Figure 1 Vasikaran S, Eastell R, Bruyere O, et al. Markers of bone turnover for
the prediction of fracture risk and monitoring of osteoporosis
KEY REFERENCES treatment: a need for international reference standards. Osteoporos
1 Eastell R, ONeill TW, Hofbauer LC, et al. Postmenopausal osteo- Int 2011; 22: 391e420.
porosis. Nat Rev Dis Primers 2016; 2: 1e16.

TEST YOURSELF
To test your knowledge based on the article you have just read, please complete the questions below. The answers can be found at the
end of the issue or online here.

Question 1 had osteoporosis (T-score e2.6 at the spine and hip), treated
with denosumab for 5 years.
A 71-year-old woman presented with a 3-week history of sudden
onset of lower back pain. On clinical examination, she was ten-
What is the most appropriate advice to give?
der over vertebra L1.
A. After 5 years, it is now safe for her to stop
B. Discuss changing to bisphosphonate treatment
Investigations
C. Advise that denosumab therapy is entirely safe and she
 No evidence of secondary osteoporosis
should never stop it
 X-ray of the spine showed collapse of L1 but preservation
D. Switch to teriparatide
of the disc spaces
E. Switch to strontium ranelate
 Bone densitometry of L2eL4 gave a T-score of e3.5

What is the most appropriate treatment to prevent further
fractures?
A. Teriparatide, as she has severe osteoporosis.
B. Alendronate with supplemental calcium and vitamin D
C. Calcitonin, as it will help relieve the pain and reduce
fracture risk
D. Strontium ranelate
E. No treatment other than pain relief
Question 2
A 65-year-old woman wanted to stop her treatment as she was
fed up with injections and concerned about adverse effects. She
Question 3
A 46-year-old woman had had an early menopause aged 45
years. She also had a family history of osteoporosis. She was
taking hormone replacement therapy (HRT) although she had no
perimenopausal symptoms. She wants to know whether to
continue HRT to prevent fractures.
What is the most appropriate next step in her management?
A. Measure bone density
B. Assess bone turnover markers
C. Continue with HRT but do not undertake investigations
D. Stop HRT and add calcium and vitamin D
E. Stop HRT and advise diet and exercise

MEDICINE --:- 5 2017 Published by Elsevier Ltd.

Please cite this article in press as: Eastell R, Prevention and management of osteoporosis, Medicine (2017), http://dx.doi.org/10.1016/
j.mpmed.2017.06.004