Curr Osteoporos Rep (2011) 9:129–140
DOI 10.1007/s11914-011-0060-5
A Review of Osteoporosis Diagnosis and Treatment Options
in New and Recently Updated Guidelines on Case Finding
Around the World
William D. Leslie & John T. Schousboe
Published online: 8 June 2011
# Springer Science+Business Media, LLC 2011
Abstract Fracture rates are known to vary by more than an
order of magnitude worldwide; therefore, a single approach
cannot be universally applied to all countries. National
considerations must reflect the burden of osteoporosis,
available resources, the disease costs to the individual and
society, and how these relate to competing health and other
societal priorities. Recent developments in terms of diag-
nosis, fracture risk prediction, and therapeutic options have
prompted many countries to review and update their
clinical practice guidelines (CPGs) for the prevention and
management of osteoporosis intended for use in primary
care in the general adult population. This paper reviews
recently updated CPGs from the following countries:
Australia, Belgium, Canada, Germany, the United Kingdom,
and the United States.
Keywords Osteoporosis . Fracture . Clinical practice
guidelines . Bone mineral density . Diagnosis . Treatment
W. D. Leslie
University of Manitoba,
Winnipeg, MB, Canada
J. T. Schousboe
University of Minnesota,
Minneapolis, MN, USA
e-mail: scho0600@umn.edu
W. D. Leslie (*)
Department of Medicine (C5121), St. Boniface General Hospital,
409 Tache Avenue,
Winnipeg, MB, Canada R2H 2A6
e-mail: bleslie@sbgh.mb.ca
Introduction
Osteoporosis is characterized by low bone mass and
increased risk of fractures [1]. In the absence of a defining
fracture, the diagnosis of osteoporosis is based on the
measurement of bone mineral density (BMD) by dual x-ray
absorptiometry (DXA). The World Health Organization
(WHO) has provided an operational definition of osteopo-
rosis given as a BMD that lies 2.5 standard deviations (SD)
or more below the average mean value for young healthy
women (T-score ≤−2.5 SD) based upon a standardized
reference site (the femoral neck) and a standard reference
range for both men and women (the NHANES III [third
National Health and Nutrition Examination Survey] data for
white women ages 20–29 years) [2–4].
Worldwide, the number of people who have suffered a prior
osteoporotic fracture was estimated to be 56 million in 2000
with approximately 9 million new osteoporotic fractures each
year [5]. As the prevalence of osteoporosis increases with
age, the global burden of osteoporosis is projected to rise
markedly over the next few decades as the number of elderly
individuals increases [6]. The presence of osteoporosis is a
major risk factor for the development of fractures of the hip,
proximal humerus, vertebra, and forearm but all skeletal sites
(other than craniofacial) are at increased risk of fracture [7].
The consequences of fracture include increased mortality,
morbidity, institutionalization, and economic costs [8, 9]. An
individual with a hip fracture has a markedly increased risk
of death within the first 6 months that is partly attributable to
the fracture itself. Both hip and vertebral fractures are
associated with an excess risk of death beyond the first year
[10–12], and are largely attributed to underlying comorbidity
[13, 14]. Moreover, all osteoporosis-related fractures can
lead to significant long-term disability and decreased quality
of life [15, 16].
130
Fracture rates are known to vary by more than an order
of magnitude worldwide [17]; therefore, a single approach
cannot be universally applied to all countries. National
considerations must reflect the burden of osteoporosis,
available resources, the disease costs to the individual and
society, and how these relate to competing health and other
societal priorities. As a result, different countries have
evolved their own unique approaches to case finding and
treatment that are responsive to their particular circum-
stances. Recent developments in terms of diagnosis,
fracture risk prediction, and therapeutic options have
prompted many countries to review and update their
clinical practice guidelines (CPGs) for the prevention and
management of osteoporosis.
Although reduced bone mass is an important and easily
quantifiable measurement, studies have shown that most
fractures occur in individuals with a BMD T-score above
the operational threshold for osteoporosis [18]. Recently,
the use of new fracture risk prediction systems that
integrate multiple clinical risk factors (CRFs) has been
shown to enhance the performance of BMD in the
prediction of hip and other major osteoporotic fractures
[19]. This has initiated a paradigm shift in the field of
osteoporosis. One such example, the fracture risk assess-
ment tool (FRAX®), was developed by the WHO Collab-
orating Centre for Metabolic Bone Diseases for estimation
of individual 10-year osteoporotic and hip fracture proba-
bility [20••]. In addition to a prior fragility fracture, age,
sex, body mass index, and additional risk factors for
fractures were identified including the prior use of
glucocorticoids, secondary osteoporosis, rheumatoid arthri-
tis, a parental history of hip fracture, current cigarette
smoking, and alcohol intake of 3 or more units/day.
Population-specific FRAX tools can be customized to the
fracture and mortality epidemiology in that specific region
[20••]. At present more than 35 FRAX models are
available, and others are being developed. The FRAX
system been endorsed and integrated into CPGs by several
national bodies [21–29]. Adaptations of the FRAX algo-
rithm and completely separate algorithms have also been
developed for estimating fracture probability.
In light of the above, it is timely and instructive to review
how different countries have approached the development of
CPGs for the prevention and management of osteoporosis.
This review focuses on recently updated CPGs from the
following countries: Australia, Belgium, Canada, Germany,
the United Kingdom (UK), and the United States (US). In
two cases (UK and US), more than one national organization
had produced a CPG and two from each of these countries
are reviewed. We acknowledge that additional countries have
or will soon be updating their national osteoporosis guide-
lines (eg, the Netherlands) and therefore our review should
be considered illustrative rather than exhaustive.
Curr Osteoporos Rep (2011) 9:129–140
Methods
We considered CPGs that were intended for use in primary
care in the general adult population. Specifically, we did not
consider CPGs that were intended for specialists or
secondary osteoporosis (eg, glucocorticoid-induced osteo-
porosis). Furthermore, we selected guidelines that were
developed by national organizations for countrywide
application and that included diagnostic, risk assessment,
and therapeutic components. In addition to a narrative
review, we also identified seven specific criteria for
categorizing guidelines as good, moderate, or poor quality
based upon the Appraisal of Guidelines, Research, and
Evaluation (AGREE) instrument [30••]. Scott et al. [31••]
identified 7 of the 23 AGREE criteria as “essential” and
provided a scoring system (maximum possible of 28 [7×
4]). The quality assessments were performed independently
by the two coauthors and then averaged, except in the case
of the Canadian CPGs in which only a single individual
performed the scoring due to the fact that one of the authors
(WDL) was a coauthor on this CPG (Table 1). Individual
elements that differed by more than a single point were
resolved through discussion. Specific content elements
from each CPG are summarized in Table 2.
Guidelines Overviews
Australia
The CPG for Australia was commissioned by the Royal
College of Australian General Practitioners and the
Australian Government Department of Health and Aging,
and approved by the Australian National Health and
Medical Research Council (NHMRC) of the Australian
Government in 2010 [32•, 33]. The target audience of this
CPG is specifically primary care general practitioners in
Australia, and its use is intended to assist general
practitioners’ management of osteoporosis in clinical
practice. The guideline focused on postmenopausal women
and men over age 50 years at risk of developing
osteoporosis, those diagnosed with osteoporosis by bone
density criteria, and those age 60 years and older who had
one or more fractures with minor trauma. The guideline is
not intended to apply to those on prolonged glucocorticoid
therapy, those with osteoporosis secondary to other morbid
conditions, men with hypogonadism, or women with
hypogonadism due to conditions other than natural
menopause.
A multidisciplinary guideline working group (including
physician specialists, general practitioners, patient/health
care consumer advocates) selected the German guidelines
as a basis after review of various recent guidelines using the
Curr Osteoporos Rep (2011) 9:129–140 131

Table 1 Quality assessment of clinical practice guidelines

Australia Belgium Canada Germany UK- UK- US- US-

NICE NOGG AACE PSTF

Systematic search conducted 3.5 2 4 4 4 2.5 2 4

Methods used to formulate recommendations described 2.5 2 4 4 3 2.5 2.5 4
Link between recommendations and evidence 3 2 4 4 3 2.5 3.5 3
External review by experts 3.5 1 3 4 4 3.5 3 4
Specific, unambiguous recommendations 4 2.5 3 4 4 3.5 3.5 3.5
Editorially independent from funder 4 1.5 3 2.5 4 3 1.5 4
Conflicts of interest reported 4 3.5 4 4 4 2 3.5 4
Total 24.5 14.5 25 26.5 26 19.5 19.5 26.5

Quality assessments scores were averaged for the two co-authors, except in the case of the Canadian clinical practice guidelines, which are based
on a single scoring
US-AACE United States Association of Clinical Endocrinologists; UK-NICE United Kingdom National Institute for Health and Clinical
Excellence; UK-NOGG United Kingdom National Osteoporosis Guideline Group; US-PSTF United States Preventive Services Task Force

Scottish Intercollegiate Guidelines Network (SIGN) meth-
odology (http://www.sign.ac.uk/guidelines/fulltext/50/
checklist1.html) Additional references were added from
the time of those guidelines. In addition a comprehensive
literature search was carried out using OVID Medline,
Cochrane review databases, the Health Technology Assess-
ment database, and the National Health Service (NHS)
economic database. A total of 2500 articles were reviewed
and graded by two or more working group members to
ensure no relevant information was excluded from the
guidelines. Twenty-eight consensus recommendations
were formulated by the group based on unanimous
agreement. These recommendations were graded A (ex-
cellent) to D (poor), and were sent to 14 outside experts
(Australian and non-Australian) for review and released
for public comment. The working group then revised the
document based on stakeholder comments and sent it to
NHMRC for review and approval.
Bone densitometry using DXA was recommended for
those men and women age 70 years and older, and for
women age ≥50 years and older and men age ≥60 years
and older with additional risk factors. For postmenopausal
women and men suffering a fragility fracture at any
skeletal site, bone densitometry is recommended but not
considered essential before starting pharmacologic fracture
prevention therapy. Follow-up bone densitometry was
judged to be appropriate 2 years after starting pharmaco-
logic therapy. Recommendations were also made for
additional investigations including lateral spine imaging
for suspected vertebral fracture, indications for specialist
referral, calcium, vitamin D, lifestyle interventions, exer-
cise, and intervention to reduce of falls risk. Use of
pharmacologic agents (bisphosphonates, hormone therapy,
selective estrogen receptor modulator therapy, parathyroid
hormone, and strontium ranelate) to reduce the risk of
fragility fractures were recommended for consideration in
light of a person’s absolute fracture risk (once bone
densitometry and other BMD fracture risk factors are
assessed). Nomograms for the Garvan fracture risk
calculator are provided in the guideline to aid absolute
fracture risk assessment. In line with current Australian
pharmaceutical benefits treatment availability, no specific
cutpoints of bone density or absolute fracture risk are
offered as an indication for fracture prevention therapy.
Belgium
In 2010, the Belgian Bone Club updated their guidelines
from 2005 regarding screening and treatment of osteopo-
rosis [34•, 35]. The target audience was clinicians in
Belgium, both generalist and specialist, involved in the
care of those at risk of osteoporosis and fragility
fractures. The scope of the guideline was limited to
postmenopausal women; osteoporosis due to glucocorti-
coid therapy, to other secondary medical conditions, and
osteoporosis in men were considered to be outside the
scope of the guideline. The Belgian Bone Club has
previously published a guideline regarding management
of glucocorticoid-induced osteoporosis [36].
Systematic literature reviews from Medline and the
Cochrane databases were done, and grading of the evidence
was done by consensus of a committee of experts in the
field. The precise criteria by which articles were selected
from the literature search, were graded for quality of
evidence, and the method by which consensus was
achieved were not described. The evidence regarding the
fracture prevention efficacy of calcium and vitamin D
supplementation was extensively reviewed, and daily
intakes of 1000 to 1200 mg of calcium and 800 IU of
vitamin D recommended.
132 Curr Osteoporos Rep (2011) 9:129–140

Table 2 Summary of clinical practice guidelines Table 2 (continued)

Australia [32•, 33] Germany and the Dachverband Osteologie [38•]

Patient Postmenopausal women and older men Patient All adult women and men
population population
Scope Screening, prevention, treatment (nonpharmacologic Scope Prevention, diagnosis, and therapy of primary
and pharmacologic) osteoporosis; common forms of secondary osteoporosis
BMD testing Women and men age ≥70 y (younger with additional BMD testing Women age ≥70 y and men age ≥80 y (younger with
CRFs) additional CRFs)
Risk Garvan fracture risk calculator Risk 10-y risk morphometric vertebral or hip fracture
assessment assessment
Calcium 1200 mg/d Calcium 1000 mg/d
Vitamin D > 800–1000 IU/d (target serum 25(OH)D ≥60 nmol/L) Vitamin D 800–2000 IU/d (target 25(OH)D ≥50 mol/L)
Drug •BMD T-score ≤−2.5 Drug •10-y risk clinical or radiologic vertebral or hip
treatment •Hip or spine fracture treatment fracture ≥30% with T-score ≤−2.0
•BMD −1.0 to −2.5 plus low trauma fracture •Single grade 2+ or multiple grade 1+ vertebral
fractures with minimum T-score −2.0
•Consider absolute fracture risk but no treatment
thresholds recommended •Prednisolone, 7.5 mg/d, for >3 mo with ≤ T-score −1.5
BMD •Consider at 1 y after change in osteoporosis Rx BMD •On treatment 2–5 y
monitoring monitoring •High-dosage glucocorticoids 1 y or less
•Consider at 1 y if on glucocorticoid Rx ≥7.5 mg/d of
prednisone
UK National Institute for Health and Clinical
•Consider if BMD T-score is likely to be approaching −2.5
Excellence [40•, 41–43]
(at intervals no more frequent than once every 2 y)

Belgium [34•] Patient Postmenopausal women

population
Patient Postmenopausal women Scope Treatment for primary and secondary fracture prevention
population BMD testing No specific recommendation
Scope Treatment (calcium, vitamin D, and pharmacologic Risk T-score (spine and/or hip), age, number of independent
therapies) assessment CRFs for fracture, and indicators of low BMD
BMD testing Beyond scope of guidelines Calcium No specific recommendations. Assumes that women
Risk BMD plus vertebral fracture history who receive treatment have an adequate calcium
assessment intake and are vitamin D replete. Unless clinicians
Calcium 1000–1200 mg/d are confident that women who receive treatment
Vitamin D 800–1000 IU/d (target serum 25(OH)D ≥50 nmol/L) meet these criteria, calcium and/or vitamin D
Drug BMD spine or hip T-score ≤−2.5 plus prevalent supplementation should be considered
treatment vertebral fracture Vitamin D No specific recommendations
BMD Beyond scope of guidelines Drug •Based upon incremental cost-effectiveness ratio
monitoring treatment •T-score intervention criteria vary by agent (base case
generic alendronate), age, fracture status, number of
Canada [29•] independent CRFs for fracture, and indicators of low
BMD
Patient Adult women and men age ≥50 y
population BMD No specific recommendations
Scope Screening and treatment monitoring
BMD testing Women and men age ≥65 y (younger with additional UK National Osteoporosis Guideline Group [44•]
CRFs)
Risk FRAX or CAROC Patient Adult women and men age ≥50 y
assessment population
Calcium 1200 mg/d Scope Assessment, diagnosis, and treatment
Vitamin D 800–1000 IU/d (target serum 25(OH)D ≥75 nmol/L) BMD testing Case-finding strategy based upon age-specific fracture
Drug •10-y major fracture risk ≥20% probability thresholds
treatment •Hip fracture Risk FRAX
assessment
• Spine fracture Calcium 500–1000 mg/d (1000–1200 mg/d for housebound
•Multiple (>1) fragility fractures elderly or nursing home residents)
BMD •High risk or on treatment: initial repeat BMD 1–3 y, Vitamin D 800 IU/d
monitoring less once treatment shown to be effective Drug •Prior fragility fracture
•Moderate risk: initial repeat BMD 1–3 y treatment •FRAX major fracture risk (without BMD) above the
•Low risk: 5–10 y age-specific upper assessment threshold
Curr Osteoporos Rep (2011) 9:129–140 133

Table 2 (continued) explicitly offered, although the relative efficacy of the

•FRAX major fracture risk (with BMD) above the agents in prevention of hip and other nonvertebral fractures,
age-specific intervention threshold and the underlying risk of breast cancer (because raloxifene
BMD No specific recommendations has been shown to prevent invasive breast cancer) were
monitoring stated to be reasonable considerations when choosing a
US American Academy of Clinical Endocrinology [45•]
specific therapeutic agent. Hormone therapy (estrogen) was
recommended only for those with symptoms of estrogen
Patient Postmenopausal women deficiency for short periods of time. Teriparatide was
population recommended only for those with both very low bone
Scope Prevention, diagnosis, and treatment (pharmacologic
and nonpharmacologic)
density (T-score ≤−2.5) and a prevalent vertebral fracture.
BMD testing Women age ≥65 y, men age ≥70 y, younger ages with
Combinations of antiresorptive medications and alendronate
CRFs combined with teriparatide were specifically discouraged.
Risk FRAX plus DXA of hip, spine, and/or forearm Fall prevention strategies were recommended, but the
assessment specific content of these strategies or their specific indica-
Calcium 1200 mg/d tions were not explicated. No recommendations were made
Vitamin D No amount specified; adjust dose to achieve 25(OH)D regarding indications for bone densitometry, use of other
level 75–150 nmol/L
screening tools such as fracture risk calculators, workup for
Drug •Hip or vertebral fracture
secondary causes of bone loss, or regarding monitoring of
treatment •BMD T-score ≤−2.5 individuals on pharmacologic fracture prevention therapy.
•BMD T-score −1.0 to −2.5 plus 10-y hip fracture risk
≥3%
Canada
•BMD T-score −1.0 to −2.5 plus 10-y major osteopo-
rotic fracture risk ≥20%
BMD •Not on Rx, near treatment threshold: test every 1–2 y The CPGs for Canada was released in 2010 and updated the
monitoring •Not on Rx, BMD borderline low: test every 3–5 y
2002 guidelines [29•, 37]. The CPG development followed
•Not on Rx, well above treatment threshold: test every
the AGREE process. Systematic reviews were performed in
5–10 y or longer two key areas, one related to absolute fracture risk
•On Rx: baseline DXA plus DXA every 1–2 y until assessment and the other related to the benefits and harms
BMD is stable of osteoporosis therapies. A level of evidence was assigned
to each abstracted paper, and graded recommendations were
US Preventive Services Task Force [47•]
developed. An expert panel provided feedback on the CPG
Patient Postmenopausal women and older men using a modified RAND/UCLA Delphi method, the
population considerable “care gap” that exists in patients at highest
Scope Screening for osteoporosis risk of fractures, namely those who have already sustained a
BMD testing Women age ≥65 y, postmenopausal women younger fragility fracture.
than age 65 y with absolute (by US FRAX) 10-y major
BMD testing is recommended as part of the risk
osteoporotic fracture risk ≥9.3%No recommendations
for men: available data judged to be insufficient assessment process in all individuals over age 65 years,
Risk FRAX plus DXA of hip, spine, and/or forearm and in younger individuals with additional risk factors for
assessment fracture or rapid BMD loss. A FRAX tool for Canada was
Calcium Beyond scope of guidelines developed, based upon national hip fracture and mortality
Vitamin D Beyond scope of guidelines data, and the accuracy of the fracture predictions was
Drug No criteria for drug therapy specified validated in two large, independent cohorts. Therefore, the
treatment FRAX tool, and the Canadian Association of Radiologists
BMD Beyond scope of guidelines
monitoring and Osteoporosis Canada tool (a simplified, semiquantita-
tive version of FRAX) are recommended for prediction of
BMD bone mineral density; CAROC Canadian Association of fracture risk. Major osteoporotic fracture probability is
Radiologists and Osteoporosis Canada; CRFs clinical risk factors; categorized as low (<10%), moderate (10–20%), or high
DXA dual x-ray absorptiometry; Rx medication.
(>20%). Individuals who have already sustained fragility
fractures affecting the vertebra or hip, or those with more
Oral and intravenous bisphosphonates, raloxifene, and than one fragility fracture, are also designated at high risk,
strontium ranelate were recommended as first-line therapies regardless of BMD value. Pharmacotherapy, in addition to
for fracture prevention in those with either osteoporosis regular weight-bearing exercise, appropriate calcium
(lumbar spine or hip T-score ≤−2.5) or a prevalent vertebral (1200 mg daily) and vitamin D supplementation (800–
fracture. Criteria for choosing among these agents were not 1000 IU daily to achieve a serum level of at least 75 nmol/
134
L), and fall prevention strategies, are recommended for
high-risk individuals. In those at low risk, there is little
evidence for benefit from pharmacotherapy and basic bone
health measures are recommended with periodic risk re-
evaluation (5 years following the initial evaluation).
The Canadian CPGs recognize that the largest number of
osteoporotic fractures occurs in those at moderate risk, just
as the majority of osteoporotic fractures occurs in individ-
uals with a T-score between −1 and −2.5. For those at
moderate risk of fracture, patient preference and additional
risk factors are outlined for identifying moderate-risk
individuals who may benefit from pharmacotherapy. These
include spinal imaging to look for clinically silent vertebral
fractures, features that indicate greater fracture risk (eg,
lumbar spine T-score much lower then femoral neck T-
score, wrist fracture with T-score −2.5 or lower, recurrent
falls in the last year), or risk factors for rapid BMD loss (eg,
women undergoing aromatase inhibitor therapy for breast
cancer, men undergoing androgen deprivation therapy for
prostate cancer).
The CPGs appreciate that no randomized trials have
directly established the value of BMD monitoring in terms
of clinical outcomes, and that such recommendations are
based upon expert opinion. For patients undergoing
pharmacologic treatment, repeat BMD is initially recom-
mended 1 to 3 years after starting treatment, with a longer
testing interval once therapy is shown to be effective.
Improved or stable BMD is considered to represent an
appropriate response to therapy. For individuals with low
fracture risk and without additional risk factors for rapid
BMD loss, a testing interval of 5 to 10 years is considered
sufficient. Combination therapy and “drug holidays” are not
recommended, based upon currently available evidence.
Criteria for referral to a specialist are provided. There is
also a discussion of approaches that can be used to enhance
the use of appropriate treatment, such as case managers and
point-of-care tools.
Germany and the Dachverband Osteologie
The Dachverband Osteologie (DVO) is the osteology
umbrella organization of the scientific societies for Germany,
Austria, and Switzerland. The 2009 update of the (DVO)
CPGs for the prevention, diagnosis, and therapy of osteopo-
rosis in adults updated the earlier 2006 DVO CPGs, with the
next regular update planned for 2012 [38•]. The guidelines,
approved in Germany, target primary care and specialist
physicians who are clinically involved in the care of persons
with osteoporosis, and provide recommendations on both
primary osteoporosis and common forms of secondary
osteoporosis. A systematic literature search was performed
until December 31, 2008, and followed a multidisciplinary
internal and external consensus process.
Curr Osteoporos Rep (2011) 9:129–140
The guideline highlights that diagnosis and treatment of
patient’s at risk, especially the elderly and those who have
already sustained an osteoporotic fracture, are insufficient.
Prevention focuses on regular physical activity, an annual
fall history after age 70 years, correction of vitamin D
deficiency (<50 nmol/L), and a nutritional intake of
1000 mg of calcium. Daily sun exposure of at least 30
min, or vitamin D3 supplementation 800 to 2000 IU, is
recommended to avoid vitamin D deficiency (defined as
<50 nmol/L). Supplementation with vitamin B12 and folic
acid, as well as avoidance of smoking, are recommended. A
detailed list of CRFs and medications associated with
osteoporotic fractures and/or falls is used in the risk
assessment and treatment algorithm. Although FRAX tools
exist for the DVO countries (Germany, Austria, and
Switzerland), the CPGs recommend an alternative absolute
10-year fracture risk approach developed by the DVO in
2003. It was felt that changing to FRAX would not offer
substantial advantages, and that the FRAX model was still
in development and could change.
The DVO risk assessment system is based upon clinical
or radiologic vertebral and/or hip fracture risk over the
following 10 years, with 20% or higher considered to be the
cutoff for diagnostic investigation. Specific drug treatment
is recommended for an estimated 10-year risk of vertebral
and hip fracture greater than 30% if accompanied by a
minimum T-score (lumbar spine, total hip, or femoral neck)
of −2.0 or lower. Pharmacotherapy for a T-score above −2.0
is not recommended. Age- and sex-specific T-score cutoffs
for initiation of treatment are provided. In the absence of
additional risk factors, a 65- to 70-year-old woman or 75- to
80-year-old man with minimum T-score of −3.0 or lower
would be recommended for treatment; prior to age 60 years
in women or age 70 years in men a T-score of −4.0 or lower
is the threshold for treatment. The T-score intervention
threshold is adjusted upward (0.5 T-score adjustment per
risk factor up to a maximum T-score of −2.0) for additional
CRFs (9 general risks, 9 diseases, 3 drugs). For example, if
a women age 67 years without additional risks would
qualify for treatment based upon a T-score of −3.0, in the
presence of a peripheral fracture after age 50 years
treatment would be initiated at a T-score of −2.5; if in
addition she also had type 1 diabetes mellitus then
treatment would be initiated below a T-sore of −2.0.
Drug therapy is also recommended for a single vertebral
fracture (Genant grade 2 or 3, >25% height reduction) or
multiple vertebral fractures (Genant grades 1–3, >20% height
reduction) if at the same time the minimum T-score is −2.0 or
lower. For individuals on oral glucocorticoids at daily doses
≥7.5 mg of prednisolone equivalent for 3 months or more then
treatment is also recommended if there is a minimum T-score
of −1.5 or lower. Lower doses of oral glucocorticoids are
considered under the earlier DVO risk assessment system.
Curr Osteoporos Rep (2011) 9:129–140
Combination treatment is not recommended. Continuation
of drug therapy beyond 3 to 5 years is recommended in the
case of persisting high 10-year fracture risk. In the event that
a CRF is eliminated (eg, smoking cessation) then the fracture
risk should be reassessed and if the newly calculated 10-year
fracture risk is less than 30% the specific drug treatment can
be stopped. BMD monitoring of drug therapy is generally not
recommended before a treatment period of 2–5 years except in
the case of high-dosage glucocorticoid treatment. A lack of
increasing BMD when taking antiresorptive drugs does not
mean decreased antifracture benefit. Conversely, the BMD
measurement prior to treatment is recommended to determine
long-term fracture risk. Therapy failure is defined as greater
than 5% BMD decrease in the total hip, or two or more
osteoporotic fractures within 3 years, despite appropriate
treatment. Additional sections of the CPGs discuss treatment
of acute vertebral fracture, kyphoplasty/vertebroplasty, and
chronic pain.
UK National Institute for Health and Clinical
Excellence
The National Institute for Health and Clinical Excellence
(NICE) is an NHS organization in the UK set up on April 1,
1999 to provide guidance, set quality standards, and
manage a national database to improve people’s health
and prevent and treat ill health. NICE makes recommenda-
tions to the NHS on new and existing medicines, treat-
ments, and procedures treating and caring for people with
specific diseases and conditions. Topics covered by NICE
guidance range from helping people to stop smoking and
encouraging physical activity through to the treatment of
specific conditions including osteoporosis. The framework
for NICE recommendations follows a detailed review and
analysis of effectiveness and cost-effectiveness based upon
incremental cost-effectiveness ratio for cost per quality
adjusted life year gained [39]. The Appraisal Committees,
one of NICE’s standing advisory committees, contain
members who are appointed for a 3-year term. Each
Appraisal Committee considers its own list of technologies,
and topics are not moved between the branches. Committee
members are asked to declare any interests in the topic to be
appraised. If a conflict of interest is considered, the member
is excluded from participating further in that appraisal.
Experts are invited to attend Appraisal Committee meetings
to observe and to contribute as advisers to the Committee.
NICE has recently issued three guidance documents
relevant to osteoporosis: 1) use of bisphosphonates,
raloxifene, and strontium ranelate for the primary preven-
tion of osteoporotic fragility fractures in postmenopausal
women (issued October 2008, updated January 2011) [40•];
2) use of bisphosphonates, raloxifene, strontium ranelate,
135
and teriparatide for the secondary prevention of osteopo-
rotic fragility fractures in postmenopausal women (issued
October 2008, updated January 2011) [41]; and 3) use of
denosumab for the primary or secondary prevention of
osteoporotic fragility fractures in postmenopausal women
(issued October 2010) [42]. These reports do not consider
primary prevention in those with non-osteoporotic BMD,
glucocorticoid-induced osteoporosis, or other populations
(men, premenopausal women, and children). Separate
guidelines and care pathways have been created for
assessment and prevention of falls in older people (issued
2004) [43]. Clinical guidelines on risk assessment of
patients with osteoporosis and hip fractures are currently
being developed. There are no guidelines on calcium and
vitamin D, although it is stated that the guidance assumes
that women who receive treatment have an adequate
calcium intake and are vitamin D replete.
FRAX was not used as the basis for treatment initiation
by NICE. Justifications included that the use of absolute
fracture risk alone did not accurately predict cost effective-
ness, and therefore would not provide a robust basis for
decision making. Different fracture sites have different
impacts on quality of life, costs, and mortality, and cost
effectiveness is therefore dependent on the contribution
from each fracture site to the total fracture risk. The NICE
guidance recommends using a combination of T-score
(spine and/or hip DXA), age, and number of independent
CRFs for fracture. Independent CRFs for fracture (a subset
of the FRAX risk factors) are parental history of hip
fracture, alcohol intake of 4 or more units per day, and
rheumatoid arthritis. Indicators of low BMD are low body
mass index (<22 kg/m2), medical conditions such as
ankylosing spondylitis, Crohn’s disease, rheumatoid arthri-
tis, conditions that result in prolonged immobility, and
untreated menopause.
Generic alendronate was considered as the base treatment
option. Treatment is recommended for the primary preven-
tion of osteoporotic fragility fractures for: 1) women ages
70 years or older who have an independent CRF for fracture
or an indicator of low BMD (see preceding paragraph) and
confirmed osteoporosis (T-score of −2.5 SD or below); 2)
women ages 75 years or older who have two or more
independent CRFs for fracture or indicators of low BMD
(DXA scan not required); 3) women ages 65 to 69 years
with an independent CRF for fracture and confirmed
osteoporosis (T-score of −2.5 SD or below); and 4) younger
postmenopausal women with an independent CRF for
fracture and at least one additional indicator of low BMD
and confirmed osteoporosis (T-score of −2.5 SD or below).
More severe reductions in T-score are required for treatment
with other bisphosphonates (eg, T-score of −3.5 SD or
below plus one independent risk factor for fracture women
ages 65–69 years), strontium ranelate, or denosumab (eg, T-
136
score of −4.5 SD or below plus one independent risk factor
for fracture women ages 65–69 years).
Alendronate is recommended for the secondary preven-
tion of osteoporotic fragility fractures in postmenopausal
women who have sustained a clinically apparent osteopo-
rotic fragility fracture and have osteoporosis by DXA (in
women ages 75 years or older, a DXA scan is not required).
More severe reductions in T-score and/or independent risk
factors for fracture are required for treatment with other
bisphosphonates, strontium ranelate, or denosumab. Teri-
paratide is an alternative treatment option for secondary
prevention in postmenopausal women with intolerance,
contraindications, or unsatisfactory response to other agents
(unsatisfactory response means another fragility fracture
despite adhering fully to treatment for 1 year plus a decline
in BMD below the pretreatment baseline). In addition,
women ages 65 years or older must have a T-score of −4.0
SD or below, or a T-score of −3.5 SD or below plus more
than two fractures; women ages 55–64 years must have a T-
score of −4 SD or below plus more than two fractures.
UK National Osteoporosis Guideline Group
The UK National Osteoporosis Guideline Group (NOGG),
representing several British organizations and societies,
provided guidance on the prevention and treatment of
osteoporosis in the UK subsequent to dissemination of the
NICE guidelines [44•]. The target population is postmen-
opausal women and men ages over 50 years. The
recommendations contained in the CPGs are intended to
aid management decision making as a framework from
which local management protocols could be developed.
The CPGs endorse the WHO definition of osteoporosis
including its operational translation using T-scores. The
CPGs explicitly note that the same diagnostic cutoff values
for BMD be applied to men and women, with femoral neck
DXA designated as the reference technology for the
diagnosis of osteoporosis and a normal reference range in
men and women based upon the NHANES survey for
Caucasian women ages 20–29 years. The CPGs specifically
state that use of additional BMD sites for diagnosis (eg, the
lumbar spine) is not recommended except where hip
measurement is not possible, or in younger postmenopausal
women and men in whom the spine is differentially
affected. Population screening is not recommended; the
NOGG recommends use of BMD testing in the context of a
case-finding strategy based upon age-specific fracture
probability thresholds. In the context of high-risk strategies
(selective case finding), no distinction is made between
prevention and treatment. Recommendations are based on
high levels of evidence (meta-analysis or randomized
controlled trials [RCTs]), with the recommendations graded
and summarized based on systematic literature reviews.
Curr Osteoporos Rep (2011) 9:129–140
The guidelines review global strategies for the prevention
of osteoporosis, but make no recommendations concerning
population-based strategies due to uncertainty over their
causal relationship with osteoporosis and the lack of data
regarding uptake and compliance of such strategies for
osteoporosis prevention in the population at large. Supportive
measures based upon the selective case finding approach are
identified. Positive recommendations are made for the use of
dietary supplements in the housebound elderly and those in
nursing homes (800 IU of vitamin D and 1.0–1.2 g of calcium
daily) or as adjuncts to other treatments in patients with
osteoporosis (800 IU of vitamin D and 500–1000 mg of
calcium daily). Adequate protein intake for maintenance and
function of the musculoskeletal system is also recommended.
A case-finding strategy is recommended in which
patients are identified because of a fragility fracture or by
the presence of CRFs. Under these CPGs, fracture risk
should be assessed in postmenopausal women and men
ages 50 years or more with specific risk factors that have
been associated with increased fracture risk (many of which
operate independently of BMD and are incorporated in the
FRAX algorithm). The NOGG Guideline Group notes that
treatment should not be undertaken without recourse to a
BMD test except in those with prior fragility fractures. The
CPGs acknowledge that the FRAX algorithm does not take
into account prior treatment, dose responses for several risk
factors, or additional risk factors for fracture (eg, recurrent
falls and elevated bone turnover markers), and highlight the
need for clinical judgment in the care of individual patients
in clinical practice.
Fracture probability estimates in the NOGG guidelines
are based upon the UK FRAX tool with major osteoporotic
fracture probability estimated without BMD. In individuals
in which the probability exceeds the age-specific upper
assessment threshold then drug treatment without BMD
testing is recommended. In individuals with the fracture
probability below the lower assessment threshold, no
further testing or treatment is required. For those with
fracture probabilities falling between the lower and upper
assessment thresholds, BMD testing with DXA is recom-
mended to improve the accuracy of the FRAX-derived
probability estimate. Treatment is then recommended for
individuals in whom the fracture probability exceeds the
intervention threshold (based upon the fracture probability
for a woman of the same age with a prior fragility fracture,
without knowledge of BMD). This approach is underpinned
by cost-effective analysis for one specific intervention
(generic alendronate) with the assumption that second-line
intervention (other bisphosphonates, denosumab, raloxi-
fene, or strontium ranelate) would be used in approximately
20% of patients. The proportion of women potentially
eligible for treatment rises with age, from 20% at age
50 years to 40% after age 80 years.
Curr Osteoporos Rep (2011) 9:129–140
General practitioners are encouraged to follow up patients
to monitor their use of medications, to ensure co-prescription
of calcium and vitamin D with bone-protective interventions,
and to encourage adherence to therapy. There is no
recommendation regarding BMD monitoring by the NOGG
guidelines. There is a general statement that BMD measure-
ments may be used to monitor the effects of treatment.
Unique features of the CPGs are recommendations for
training of physicians in osteoporosis and metabolic bone
diseases given the diverse specialties that are implicated, as
well as training in the management of osteoporosis for nursing
and other allied professions. Specific recommendations are
made to health authorities and other commissioners of health
care regarding prevention, diagnosis/investigation, and treat-
ment of osteoporosis, as well as to the Department of Health.
US American Association of Clinical Endocrinologists
The American Academy of Clinical Endocrinology updated
and released guidelines for prevention of and treatment of
osteoporosis and related fractures in 2010 [45•]. A task
force of American Association of Clinical Endocrinologists
(AACE) members was assembled to perform literature
searches and update the previous guidelines of 2004, and a
team of three external reviewers (two of whom are
recognized experts within the field of metabolic bone
disease but are not endocrinologists) independently evalu-
ated the guidelines. The exact processes of how medical
literature was extracted and evaluated, and the precise roles
and interactions of the task force and external review panel
were not explicated. The target audience of the guidelines
was not only endocrinologists but also generalists and other
specialty physicians who care for patients at risk of
osteoporosis and fragility fracture. The scope of the guide-
lines was limited to postmenopausal women; specifically,
these guidelines were not intended to apply to men.
Bone densitometry is recommended in the guidelines for
all women ages 65 years and older, and for postmenopausal
women younger than age 65 years with one or more
additional risk factors for fracture. The diagnosis of osteopo-
rosis by BMD criteria is recommended to be limited to BMD
at the lumbar spine, total hip, femoral neck, and one-third
radius site. Recommendations are also given for workup of
individuals with osteoporosis by bone density criteria or
fragility fractures for causes of secondary osteoporosis,
indications for lateral spine imaging to detect prevalent
vertebral fractures, for calcium and vitamin D intakes, and
for lifestyle interventions to reduce risk of fractures.
With respect to indications for pharmacologic treatment,
AACE endorsed the US National Osteoporosis Foundation
2008 guidelines, and on these aspects the two guidelines
are identical. Pharmacotherapy (with an oral or intravenous
bisphosphonate, calcitonin, denosumab, raloxifene, or
137
teriparatide) is recommended for those who have had a
hip or vertebral fracture (radiographic or clinical), T-score
≤−2.5 at femoral neck, total hip, or lumbar spine, or T-score
−1.0 to −2.5 with hip or major osteoporotic 10-year fracture
risks, respectively, of ≥3% or ≥20%. These guidelines
recommend pharmacologic therapy for a substantially
wider proportion of the population than other guidelines
(eg, 91% of non-Hispanic white women ages 80 years and
older with T-scores between −1.0 and −2.5 would be offered
drug therapy using these guidelines) [46].
Because of their proven hip fracture reduction efficacy,
alendronate, risedronate, zoledronic acid, and denosumab
are recommended as the first-line agents. Simultaneous use
of two or more agents is not recommended. However,
sequential therapy is stated to be appropriate at times,
especially use of antiresorptive agents after a treatment
course of teriparatide. The duration of drug therapy
considered to be safe is explicated in the guidelines. Drug
holidays after many years of bisphosphonate therapy are
thought to be possibly reasonable so long as BMD is
followed and treatment re-initiated if bone loss occurs.
US Preventive Services Task Force
The US Preventive Services Task Force (USPSTF) in 2011
released updated guidelines for public comment regarding
screening and treatment for osteoporosis [47•], in part to
address screening men and postmenopausal women younger
than age 65 years, and to also address the effect of treatment
of those without any known prior fractures who after
screening are judged to be candidates for osteoporosis.
The target audience is all physicians who care for those who
have or are at risk of osteoporosis. The scope was limited to
postmenopausal women and men who have not had a
fragility fracture, a secondary cause of bone loss, and who
are not already known to have osteoporosis.
The committee based their recommendations on an
updated systematic review of medical literature regarding:
1) risk calculators to predict low bone density or fractures;
2) bone densitometry with DXA and other technologies
such as quantitative ultrasound; 3) and pharmacologic
therapy to prevent fractures [48]. No RCTs were found
directly evaluating the effects of screening on fracture
incidence or fracture-related mortality. With respect to
clinical evidence of pharmacologic therapies, the committee
identified only seven high-quality RCTs of postmenopausal
women that either excluded those with prior clinical
fractures or prevalent radiographic vertebral fractures, or
else limited enrollment of those with prior fractures to no
more than 20% of their study populations. No primary
prevention RCTs of any pharmacologic agent to prevent
fractures have been reported in men. The task force found
“convincing evidence” for significant benefit from treatment
138
(with bisphosphonates, estrogen, raloxifene, or teriparatide)
of women age 65 years and older without prior fracture but
with osteoporosis and for women younger than age 65 years
of comparable fracture risk, with small to modest risk of
harm. They concluded with moderate certainty, therefore,
that screening for osteoporosis with DXA yields moderate
net benefit for women age 65 years with no additional risk
factors, and for postmenopausal women younger than age
65 years of comparable risk. Because according to the US
FRAX calculator a 65-year-old Caucasian woman with no
additional risk factors (and presumably average femoral
neck bone density) and body mass index for her age is
9.3%, they recommend bone densitometry for postmeno-
pausal women younger than age 65 years if their calculated
10-year risk of major osteoporotic fracture is 9.3% or higher
according to the US FRAX calculator (without BMD).
Evidence regarding screening in men was judged to be
insufficient to issue any recommendations regarding screen-
ing of men without prior fracture or secondary causes of
bone loss, or regarding use of pharmacologic agents for
primary prevention of fractures in men.
These guidelines did not address choice among available
pharmacologic agents, duration of therapy, the issues of drug
holidays, combination or sequential therapy, calcium or vitamin
D intakes, or nonpharmacologic therapy such as exercise.
Conclusions
International differences also reflect the burden of osteopo-
rosis, available resources, the disease costs to the individual
and society, and how these relate to competing health and
other societal priorities. Not surprisingly, we found signifi-
cant differences between the updated CPGs from Australia,
Belgium, Canada, Germany, the UK, and the US. Although
each CPG claims to be based upon scientific evidence, the
methods for identifying this evidence, assessing data quality,
and translating this information into specific recommenda-
tions varied considerably. Fundamental differences in “phi-
losophy” were also evident, such that some guidelines will not
issue specific recommendations in which the evidence is
considered very weak. In contrast, as an aide to physicians
responsible for clinical decision making, other guidelines
issue recommendations in areas in which the evidence base is
limited while acknowledging these limitations. Different
approaches to risk assessment and variable incorporation of
absolute fracture risk prediction systems contribute to the very
wide indications for drug therapy.
Disclosures Conflicts of interest: W.D. Leslie: Advisory boards for
Novartis, Amgen, Genzyme; unrestricted research grants from Merck
Frosst, Genzyme, Amgen, Sanofi-Aventis, Warner Chilcott (formerly
Curr Osteoporos Rep (2011) 9:129–140
Procter & Gamble); speaker fees from Merck Frosst and Amgen; and
conference expenses from Genzyme; J.T. Schousboe: has received
grant support from Eli Lilly and Co.
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