DOI: 10.1111/j.1744-4667.2012.00135.

x 2012;14:251–6
The Obstetrician & Gynaecologist
Review
http://onlinetog.org

Prevention and treatment of postmenopausal osteoporosis

a b c,
Sunna Kwun MD, Marc J Laufgraben MD MBA FACE FACP, Geetha Gopalakrishnan MD *
a
Endocrine Fellow, Division of Endocrinology, Alpert Medical School of Brown University, Hallett Center for Diabetes and Endocrinology, 900
Warren Ave, East Providence, RI 02914, USA
b
Division Head, Division of Endocrinology, Diabetes, and Metabolism, Cooper Medical School of Rowan University, Cooper University Hospital,
Cooper Plaza, Suite 220, Camden, NJ 08103, USA
c
Associate Professor of Medicine, Alpert Medical School of Brown University Medicine, 900 Warren Ave, East Providence, RI 02914, USA
*Correspondence: Geetha Gopalakrishnan. Email: ggopala@lifespan.org

Key content  Make the diagnosis of osteoporosis.

 Osteoporotic fractures are associated with increased morbidity and  Decide appropriate treatment for the prevention or treatment of
mortality. osteoporosis.
 Clinical history and bone densitometry can identify individuals at
Ethical issues
risk for osteoporotic fractures. 
 Treatment is available to prevent and treat osteoporosis.
Maximising health benefit while minimising financial implications.
Key words: menopause / osteoporosis / bone density / calcium /
Learning objectives

vitamin D / bisphosphonates
Identify populations at risk for osteoporotic fractures.

Please cite this paper as: Kwun S, Laufgraben MJ, Gopalakrishnan G. Prevention and treatment of postmenopausal osteoporosis. The Obstetrician & Gynaecologist
2012;14:251–6.

to reach a peak level by the third decade of life.

Introduction
Osteoporosis is the most common skeletal disorder affecting
postmenopausal women. It is characterised by a decrease in
bone mass resulting in fragility fractures. It is estimated that
one-third of adult women will have an osteoporosis-related
fracture in their lifetime.1 Osteoporosis-related fractures
typically involve the spine, hip, humerus and forearm.
Colles’ (forearm) fractures are more common in younger
postmenopausal women while hip fractures peak in the
seventh to eighth decade of life.2
Most vertebral fractures are asymptomatic. However, they
can cause back pain, height loss and kyphosis. Vertebral
deformities may result in decreased lung capacity, impaired
balance and gastrointestinal symptoms.2 The consequences
of a hip fracture are often debilitating. It is estimated
that 50% of patients with a hip fracture will no longer be
able to live independently and 20% will die in the year
following the fracture.1 Therefore, various organisations
have recommended screening strategies to identify those at
high risk of osteoporotic fractures.1,3–5
Risk factor assessments and bone mineral density
(BMD) measurements can identify patients at risk of
osteoporotic fractures. A decrease in bone density is
associated with an increased risk of fractures. In general,
bone mass increases during childhood and adolescence
Subsequently, a steady rate of decline is noted with age
in both sexes. In women, the decline of estrogen at
menopause leads to increased bone resorption and a rapid
decline in bone density in the early postmenopausal
years.6,7 Furthermore, certain lifestyle factors, medical
conditions and medications can also impact peak
bone mass, rate of bone loss and fracture risk. Since
pharmacological treatments can substantially reduce
fracture rates, identifying high-risk individuals is the
cornerstone of osteoporosis management.
Susceptible populations
The presence of one or more risk factors increases the risk of
osteoporosis (Box 1). Modification of these factors can
reduce fracture rates. Therefore, osteoporosis risk
assessment is recommended in all postmenopausal
women. Bone density screening can identify individuals at
risk for osteoporotic fractures. Independent of bone
density, risk factors for an osteoporosis-related fracture
include: age, female gender, current smoking, high alcohol
intake (>3 units/day), history of hip fracture in a parent, prior
fragility fracture, low body mass index, rheumatoid arthritis
and use of glucocorticoids (prednisolone >5 mg for more
than 3 months).8

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 Prevention and treatment of postmenopausal osteoporosis

Box 1. Risk factors for osteoporosis and fractures3 osteoporosis-related fracture is estimated. Depending on the
patient’s age, body mass index and fracture probability, a
General
recommendation is made to reassure the patient without
Female gender, older age, Caucasian race
further evaluation, pursue DXA for further refinement of
Fractures
fracture risk, or, in some cases, begin pharmacological
Previous fragility fracture
therapy without DXA testing.1
Family history
In contrast, US guidelines recommend DXA for all women
Heredity is the greatest influence on peak bone mass: history of
65 or older, or for younger postmenopausal women with major
fracture in a first-degree relative can double fracture risk
osteoporotic fracture risk greater than 9.3% by FRAX®.3,10
Body habitus
Generally, bone density testing is not recommended in
Low weight (commonly approximated as <57 kg), recent weight loss
healthy premenopausal women. However, adult women with
of 4.5 kg or more, kyphosis
certain medical conditions such as a history of fragility
Hormones
fractures, rheumatoid arthritis or glucocorticoid treatment
Delayed menarche (>15 years of age), early menopause (estrogen
can be considered for bone density testing. Testing should
deficiency before 45 years), other causes of hypoestrogenism
also be considered for women with premature ovarian
Lifestyle factors
insufficiency who are not using estrogen.3
Cigarette smoking, poor nutrition, heavy alcohol consumption (3 or
more units of alcohol per day), insufficient physical activity
Risk factors for falls Interpreting DXA results
Inadequate lighting, loose rugs, poor vision, orthostatic hypotension,
DXA reports usually include assessment of the hip (total hip
weak muscles, problems with balance
and femoral neck), lumbar spine or both. The National
Underlying medical issues
Osteoporosis Guideline Group (NOGG) recommends
Rheumatoid arthritis, chronic renal disease, organ transplantation,
assessment of a single site with emphasis on the femoral
hyperparathyroidism, Cushing’s syndrome, hyperthyroidism,
neck, particularly in older people.1 A forearm BMD may be
malabsorption, multiple myeloma, HIV, type 1 diabetes
useful in patients with hyperparathyroidism.11 The BMD result
Medications
is then compared with the mean BMD of a normal, young,
Chemotherapeutic drugs, aromatase inhibitors, gonadotrophin-
gender-matched adult population (T-score) and to the mean
releasing hormone agonists, depo-medroxyprogesterone
BMD of an age, race and gender-matched population
contraceptives, antiepileptic drugs, glucocorticoids, lithium
(Z-score). Osteoporosis is defined by a T-score <2.5 standard
deviation (Box 2). In postmenopausal women, the Z-score
may used to characterise BMD well outside the expected range
Options for bone density screening for age, race and gender (Box 3), often indicating an individual
with higher risk for secondary causes of osteoporosis.6,7
Central dual-energy X-ray absorptiometry (DXA) is the
standard method used to evaluate BMD of the spine, hip Box 2. World Health Organization (WHO) bone
and forearm. The resulting BMD correlates with bone mineral density (BMD) diagnostic criteria
strength and predicts fracture risk.3 Therefore, DXA can be
used to diagnose osteoporosis and to monitor patients on Bone density category WHO BMD diagnostic criteria4
or off therapy.9
Normal T-score  –1
Alternative screening tools, such as computed tomography-
Osteopenia T score <–1 but >–2.5
based absorptiometry, peripheral DXA and ultrasonography Osteoporosis T score  –2.5
are not routinely recommended to diagnose osteoporosis or Established osteoporosis denotes patients who meet BMD criteria for
to monitor changes in bone density.9 diagnosis who have already experienced fragility fracture

Recommendations for screening

Box 3. International Society for Clinical
Osteoporosis risk factors should be assessed in all Densitometry (ISCD) bone density diagnostic criteria
postmenopausal women. The National Osteoporosis
Guideline Group recommends using the FRAX® (Fracture Bone density category ISCD diagnostic criteria9
Risk Assessment) calculator (available online at www.shef.ac.
Within the expected range for age Z-score >–2.0
uk/FRAX) to identify individuals at sufficient risk for fracture Below the expected range for age Z-score  –2.0
to warrant treatment or further evaluation by DXA. Using
clinical risk factors, an individual’s 10-year risk of major

252 ª 2012 Royal College of Obstetricians and Gynaecologists

 Kwun et al.

Laboratory assessments
Box 4. Calcium-rich foods3
The NOGG recommends the following in all people with
Dairy products
osteoporosis: complete blood count, sedimentation rate,
Yoghurt
serum calcium, albumin, creatinine, phosphate, liver enzymes
Cheese
and thyroid function tests.1 Other guidance recommends
Milk
routine measurement of 25-hydroxy vitamin D and 24-hour
Fish
urinary calcium excretion. Tests such as serum protein
Salmon
electrophoresis, 24-hour urine free cortisol, tissue
Sardines
transglutaminase antibody and intact parathyroid hormone
Nuts
(PTH) can also be considered if clinically indicated.3
Almonds
Bone turnover markers such as urinary N-telopeptide have
Walnuts
limited use in monitoring therapy. In large clinical trials
Sesame seeds
suppression of bone turnover markers was noted after
Fruit
3–6 months.3 When testing, a second urine collection in
Figs
the early morning after an overnight fast, is recommended.1,3
Oranges
Vegetables
General recommendations Broccoli
Spinach
Lifestyle changes Cabbage
Therapeutic lifestyle changes should focus not only on
Miscellaneous
improving bone density but also on falls prevention. Nearly
Calcium-fortified foods
30% of older adults fall each year and 5% of these falls result
Tofu
in fractures or hospitalisation.12 Therefore, alleviating home
Estimating calcium intake: Total calcium intake + 250 mg from a
hazards, modifying psychotropic medications, correcting
general non-dairy diet = total daily calcium intake. Note: 1 serving of
vision and hearing impairment, and addressing
dairy = ~300 mg calcium
neurological deficits can reduce falls and prevent
fractures.13 Furthermore, regular physical activity improves
agility, strength, posture and balance, and thus reduces falls. Vitamin D is necessary for calcium absorption and bone
Although the optimal exercise is unknown, weight-bearing health. Vitamin D can be formed by exposure of the skin to
exercises have been shown to improve bone density and UV rays from the sun; however, formation is decreased by
reduce fracture rates.14,15 Immobilisation, on the other hand, age, geographic location away from the equator, sunscreen,
precipitates bone loss and therefore should be avoided darker skin tones, time of day and season. Thus, most women
whenever possible.3 will depend on dietary intake and supplements to maintain
Women should be advised to avoid smoking and restrict adequate levels. A vitamin D intake of 800 IU daily is
alcohol intake to no more than 2 units per day.1 Smokers recommended for all postmenopausal women.1 If serum 25-
have low bone mass and lose bone more rapidly than non- hydroxyvitamin D concentration is measured, most experts
smokers.16 Excessive alcohol intake can affect nutrition as recommend a goal of at least 75 nmol/L.3
well as balance, leading to low bone density, falls and
fractures.17 Hip protectors can reduce the impact of a fall
and therefore may reduce hip fracture in older nursing
Pharmacological treatment options
home patients.18 Pharmacological therapy is recommended for
postmenopausal women who have a history of fragility
Calcium and vitamin D fracture or who meet NOGG-designated thresholds for
Adequate intake of calcium and vitamin D is recommended treatment based on FRAX®.1 NOGG emphasises that the
for all postmenopausal women. The NOGG recommends threshold for diagnosing osteoporosis may be different from
at least 1000 mg calcium daily.1 Dietary intake of calcium the threshold for pharmacological treatment of osteoporosis.1
should be emphasised in light of recent data suggesting Furthermore, it is important to keep in mind that the FRAX®
a possible increase in cardiovascular events with tool should not be used in premenopausal women, women
calcium supplementation.19 under 40 years or on pharmacological therapy.1,3

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 Prevention and treatment of postmenopausal osteoporosis
By contrast, US guidelines suggest treatment of all
postmenopausal women with fragility fracture or T-score at
any site <–2.5. For US patients with osteopenia, FRAX® is
used to identify patients with sufficient fracture risk to merit
preventive treatment.3 It is important to identify these
patients since a majority of osteoporotic fractures occur in
patients with T-scores better than –2.5.20 Pharmacological
therapy is recommended in patients with osteopenia if the
10-year risk of a hip fracture is greater than 3% or major
osteoporosis-related fracture risk is greater than 20%.3
Antiresorptive agents
Bisphosphonates inhibit osteoclast-mediated bone
resorption. By slowing the bone remodelling cycle,
bisphosphonates increase BMD in postmenopausal women
and reduce the risk of osteoporotic fractures. Although all
bisphosphonates approved for osteoporosis treatment have
been shown to reduce vertebral fractures, only certain agents,
such as alendronate, risedronate and zoledronic acid, reduce
the rate of hip fractures (Table 1). Furthermore, the
acquisition costs of these agents can vary. In general,
alendronate is fairly inexpensive and is the preferred agent
for postmenopausal osteoporosis.21–25
In clinical trials, BMD remains stable or decreases slowly
after discontinuation of bisphosphonates. Although long-
term fracture benefit is unknown, fracture protection seems
to persist for up to 5 years after drug discontinuation in low-
risk patients treated with bisphosphonates for 5 years.26
Therefore, a drug holiday can be considered after 5 years of
treatment in some patients. The drug can be restarted if there
is evidence of bone loss on serial BMD measurements.
The most common side effect of bisphosphonates is
oesophageal irritation. Therefore, individuals with
oesophageal abnormalities who delay oesophageal emptying
and those who cannot stand or sit upright for at least 30 to
60 minutes after dosing should not receive bisphosphonates.
Additionally, women with hypocalcaemia and those with
glomerular filtrate rate lower than 30–35 ml/min should not
receive bisphosphonates.1,3
Bisphosphonates are poorly absorbed from the
gastrointestinal tract, so for maximal absorption they must
be taken on an empty stomach with water, with no further
oral intake for 30 to 60 minutes. Parenteral bisphosphonates
Table 1. Bisphosphonates associated with a reduction in hip and vertebral fractures
Bisphosphonate7 Decrease in hip fractures Decrease in vertebral fractures
Alendronate + +
Etidronate – +
Ibandronate – +
Risedronate + +
Zolendronic acid + +
254
are generally reserved for those with documented
oesophageal disorders or gastrointestinal intolerance to
bisphosphonates. Rarely, transient flu-like illness can occur
with oral or intravenously administered bisphosphonates.
This is considered an acute phase reaction that can be
treated symptomatically.1,3
There is a theoretical concern regarding oversuppression of
bone turnover with long-term bisphosphonate use. Several
hundred case reports of atypical hip fractures involving the
subtrochanteric region have been reported in patients treated
with long-term bisphosphonates, that is, for more than
3 years.27 In addition, osteonecrosis of the jaw (ONJ) has
been observed in patients receiving bisphosphonates. While
the vast majority of ONJ cases have occurred in cancer
patients receiving intravenous bisphosphonates, there have
been some cases of ONJ occurring in patients with
osteoporosis taking oral bisphosphonates.28 Incidence of
both phenomena is unknown and there are no data to
support discontinuation of bisphosphonate treatment based
on the theoretical risk.
Strontium ranelate decreases bone resorption and
maintains bone formation. Although the mechanism of
action is unknown, it reduces the risk of both vertebral and
hip fractures. It has been approved for the treatment of
postmenopausal osteoporosis in the UK but not in the USA.
It is administered orally at least 2 hours after a meal. It is not
recommended in individuals with renal impairment and
should be used with caution in patients at risk of venous
thromboembolism. Other side effects include hypersensitivity
reaction, diarrhoea, headache and dermatitis.1
Nasal calcitonin is approved for treatment of
postmenopausal osteoporosis. It inhibits osteoclastic bone
resorption but is less effective than other pharmacological
therapies. It has been shown to reduce the risk of vertebral
fractures but not non-vertebral or hip fractures in
postmenopausal women. Calcitonin is generally reserved
as an alternative for women who cannot take other
osteoporosis agents. Side effects include rhinitis and nasal
discomfort. It is contraindicated in patients with
hypocalcaemia and nasal ulcerations.1,3
Denosumab inhibits bone resorption by interfering with
the proliferation and differentiation of osteoclasts.
Denosumab is a monoclonal antibody directed to RANKL
Oral formulation IV formulation
+ –
+ –
+ +
+ –
– +
ª 2012 Royal College of Obstetricians and Gynaecologists

(receptor activator of nuclear factor-kappa B ligand)
receptor. In contrast to bisphosphonates, denosumab may
be used in women with renal insufficiency. In
postmenopausal women with osteoporosis, denosumab
reduces vertebral, non-vertebral and hip fractures. Adverse
side effects include increased incidence of skin infections,
osteonecrosis of the jaw and hypocalcaemia.1,3
Hormone therapies
Estrogen slows bone resorption, improves bone density and
reduces hip and vertebral fractures. However, the benefits of
estrogen dissipate quickly after drug discontinuation.1,3
Estrogen replacement therapy in older postmenopausal
women is associated with multiple nonskeletal risks
including venous thromboembolism, breast cancer,
cardiovascular events and dementia.29 Since there are
alternative treatment options for osteoporosis, the primary
indication for systemic hormonal therapy is limited to
individuals with moderate-to-severe menopausal symptoms.
However, in women with premature ovarian failure or early
menopause, estrogen replacement therapy should be
considered for bone and other health benefits.30
Raloxifene is a selective estrogen receptor modulator
that inhibits bone resorption. It has been shown to
improve bone mineral density and reduced vertebral
fractures.1,31 However, a reduction in non-vertebral or hip
fractures has not been adequately evaluated.1 Side effects
include venous thromboembolism, vasomotor symptoms
and leg cramps.1,3
Anabolic therapy
Two PTH peptides – teriparatide (recombinant human
PTH 1–34) and recombinant human PTH (1–84) – are
approved for use in the UK. PTH peptides stimulate bone
formation by osteoblasts. Teriparatide has been shown to
reduce vertebral and non-vertebral fractures but not hip
fractures, while recombinant human PTH (1–84) has only
been shown to reduce vertebral fractures.3 Treatment
duration is limited to 24 months. These agents are
contraindicated in patients with hypercalcaemia, renal or
liver impairment, skeletal radiation exposure, malignancy
involving the bone and other metabolic bone disease.1,3
Treatment considerations
Cost-effectiveness analysis guides treatment strategies
recommended by various organisations in both the US and
UK. The choice of agent is determined by anti-fracture data,
side effect profile and acquisition costs. Alendronate is used
for firstline treatment of osteoporosis in most
postmenopausal women. Other bisphosphonates can be
considered in patients who cannot tolerate alendronate.
Estrogen replacement therapy can be prescribed to younger
ª 2012 Royal College of Obstetricians and Gynaecologists
Kwun et al.
postmenopausal women with menopausal symptoms.
Strontium ranelate, denosumab and raloxifene are options
for bisphosphonate-intolerant patients who have a high risk
of fracture based on age, BMD and clinical risk factors.
Because of the high cost of therapy, teriparatide is reserved
for very high-risk patients who are intolerant of other agents
or who have had an unsatisfactory response to initial
treatment, that is, fragility fracture and declining BMD
while adherent to therapy.1,3,21–25
Conclusions
Prevention of osteoporotic fractures is a major public
health issue, which will continue to grow in importance
as the population ages. Attention to appropriate
screening by FRAX®, selective use of DXA, and treatment
decisions based on age and fracture risk will help to
maximise the cost–benefit ratio of osteoporosis prevention
and treatment.
Conflict of interest
None declared.
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