The n e w e ng l a n d j o u r na l of
clinical practice
From the Department of Medicine
(K.E.E., J.T.S.) and the Division of Epide-
miology and Community Health (K.E.E.),
University of Minnesota; the Department
of Medicine, Veterans Affairs Medical
Center (K.E.E.); and Park Nicollet Insti-
tute (J.T.S.) — all in Minneapolis. Ad-
dress reprint requests to Dr. Ensrud at
1 Veterans Dr. (111-0), Minneapolis, MN
55417, or at ensru001@umn.edu.
N Engl J Med 2011;364:1634-42.
Copyright © 2011 Massachusetts Medical Society.
An audio version
of this article
is available at
NEJM.org
1634
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Copyright © 2011 Massachusetts Medical Society. All rights reserved.
m e dic i n e
Vertebral Fractures
Kristine E. Ensrud, M.D., M.P.H., and John T. Schousboe, M.D., Ph.D.
This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors’ clinical recommendations.
A 72-year-old woman presents with a 2-month history of increasing pain in her lower
back, which has not improved with ibuprofen and is causing difficulty with walking
and dressing. On questioning, she reports having lost about 5 cm (2 in.) of height since
she was a young woman. On examination, there is mild kyphosis in her lower thoracic
spine but no point tenderness. A lateral spine radiograph reveals that the L2 vertebra is
biconcave in appearance, a finding that is consistent with a vertebral fracture (Fig. 1).
How should this case be managed?
The Cl inic a l Probl em
Vertebral fractures — deformities of the vertebral bodies identified with imaging of
the lateral spine and characterized according to shape — are the most common
manifestation of osteoporosis. Vertebral fractures of the thoracic and lumbar spine
account for an estimated 700,000 of the 1.5 million osteoporotic fractures occur-
ring annually in the United States.1 These fractures are usually identified clinically
when a patient presents with back pain, and a spinal radiograph is interpreted as
showing a fracture of a vertebral body, most commonly in the thoracolumbar tran-
sition zone or midthoracic region.2 However, in contrast with other fracture types,
most vertebral fractures do not come to medical attention at the time of their
­occurrence. Only one fourth to one third of incident radiographically identified
vertebral fractures are clinically diagnosed.2,3
Prevalent radiographic vertebral fractures are modestly associated with back pain
and health-related quality of life4,5; the likelihood of back pain, reduced health-
related quality of life, and a clinical diagnosis increase with the severity and num-
ber of fractures.3-5 New radiographic vertebral fractures (e.g., not present on prior
radiographs) are associated with increased risks of back pain and back-related dis-
ability; the strength of these associations is greater among persons with clinically
recognized vertebral fractures.6,7 Fracture-related disability may also be greater
among patients with lumbar fractures than among those with thoracic fractures.5,6
Vertebral fractures in older adults are associated with an increased risk of death,8
but this increased risk is due in large part to underlying conditions (e.g., frailty) as-
sociated with both vertebral fracture and death. Both prevalent radiographic ver-
tebral fractures and clinical vertebral fractures are also associated with a higher risk
of subsequent hip and other fractures9; this increase in risk is only partially ex-
plained by the lower bone mineral density among patients with vertebral fractures.
Thus, the presence of a vertebral fracture has a substantial effect on the risk of
subsequent fracture and should influence decisions regarding therapies intended to
reduce that risk.
n engl j med 364;17  nejm.org  april 28, 2011
The New England Journal of Medicine
 clinical pr actice

S t r ategie s a nd E v idence
Evaluation
A woman’s first vertebral fracture usually occurs
well past menopause. The prevalence and inci-
dence of radiographic vertebral fractures increase
with age, with the prevalence among white wom-
en rising from 5% to 10% between the ages of 50
and 59 years and to 30% or more at 80 years of age
or older.10 Reported prevalence rates are lower
among black women,11 Asian women,12 and men.13
Among older white women without a prevalent
vertebral fracture, there is a 0.9% annual risk of
incident vertebral fracture among those 65 years
of age or older; among those 80 years of age or
older, the annual risk is 1.7%.14 In addition to
older age, clinical risk factors for incident verte-
bral fractures include prior fracture, history of one
or more falls, inactivity, current smoking, use of
systemic glucocorticoids (the risk increases with
increasing cumulative exposure), certain chronic
medical conditions (e.g., chronic obstructive pul-
monary disease, seropositive rheumatoid arthritis,
and Crohn’s disease), and a low body-mass in-
dex.14,15 In populations not selected for osteopo-
rosis or fracture risk, height loss (e.g., a loss ≥4 cm
since the age of 25 years) has a low sensitivity (31
to 56%) and a positive predictive value (14 to 26%)
for the presence of radiographic vertebral fracture
but a high negative predictive value (≥86%).14,16
Physical examination may reveal excess sagit-
tal convexity of the thoracic spine (hyperkyphosis,
or dowager’s hump), especially among patients
with multiple anterior wedge fractures of the tho-
racic spine. However, severe kyphosis is frequent-
ly present in older adults without prevalent radio-
graphic vertebral fractures.17
Bone Mineral Density
Low bone mineral density, as measured with the
use of dual-energy x-ray absorptiometry (DEXA),
is associated with higher odds of prevalent radio-
graphic vertebral fractures and an increased risk
of incident radiographic fractures (odds ratio or
hazard ratio for each 1-SD decrease in bone min-
eral density at the spine or hip, 1.5 to 2.0).11,14 Al-
though the prevalence of radiographic vertebral
fractures is highest among persons with osteo-
porosis (defined by a T score at the spine or hip of
−2.5 or lower [≥2.5 SD below the mean bone min-
eral density for healthy young adults]), more than
Figure 1. Lateral Radiograph of the Spine.
The radiograph shows a biconcave fracture, grade 2, in
the L2 vertebra.
one third of postmenopausal women with preva-
lent radiographic vertebral fractures have T scores
at the spine and hip that are higher than −2.5.18
The prevalence of radiographic vertebral fractures
among women 60 years of age or older with low
bone mass (T score at the hip or spine, −1.5 to −2.4)
has been reported to range from 14 to 18%.19
Diagnosis
Although a medical history and an examination
may suggest the possibility of a clinical vertebral
fracture, the diagnosis must be confirmed with a
spinal imaging study.20 In many cases, lateral chest
radiographs ordered for other indications reveal
radiographic vertebral fractures, but frequently,
such incidental findings are not reported by the
radiologist or, if reported, are not acted on by the
clinicians responsible for the patient’s care.21
Lateral thoracic and lumbar spinal radiographs
continue to be the standard for assessment.22
There is no consensus on the definition of a ver-
tebral fracture, but several qualitative and quan-
titative methods of adjudication have been devel-
oped.16 The semiquantitative method developed
by Genant et al.23 is widely accepted and is prac-
tical for use in the clinical setting.16 The method
uses the qualitative features of vertebral shape
and degree of reduction in vertebral height in the
anterior, middle, or posterior vertical dimension

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Copyright © 2011 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l
to grade a vertebral body as normal, uncertain
regarding fracture, or characterized by a mild,
moderate, or severe fracture (see the figure in the
Supplementary Appendix, available with the full
text of this article at NEJM.org). Appropriate use
of this method requires knowledge of develop-
mental deformities (e.g., Scheuermann’s disease
[osteochondrosis of vertebral end plates]) and ac-
quired deformities (e.g., osteoarthritis) that do not
represent fractures and recognition of features that
suggest causes of fractures other than osteopo-
rosis (e.g., expansion of the cortex or lysis of tra-
beculae or any part of the cortex, findings that are
suggestive of cancer). Studies have indicated that
the Genant semiquantitative method has good
interobserver reliability, concurrent validity (e.g.,
prevalent fractures are associated with low bone
mineral density), and predictive validity (e.g., prev-
alent fractures predict the risk of incident frac-
tures independently of bone mineral density).16
Assessment for asymptomatic prevalent verte-
bral fractures can be performed at the time of
bone-mineral-density testing with the use of lat-
eral spinal images generated with fan-beam DEXA
and appropriate software. The term vertebral-
fracture assessment (VFA) denotes densitometric
spine imaging from T4 to L4 for the purpose of
identifying prevalent vertebral fractures.24 As com-
pared with spinal radiographs, VFA images (Fig.
2) are more likely to produce results that cannot
be evaluated (especially when used to assess ver-
tebrae superior to T7)16 but entail much less ra-
diation exposure (3 µSv for VFA vs. 600 µSv for
a radiograph of the lateral lumbar spine), substan-
tially reduce the parallax (e.g., projection distor-
tion) often present in vertebrae on radiographs
taken with standard cone-beam x-rays, and are
more convenient for patients, since imaging can be
performed at the same time that bone mineral
density is tested. When the Genant semiquantita-
tive method is used with both imaging methods
to identify prevalent vertebral fractures, VFA and
spinal radiographs have similar intraobserver
and interobserver reliability and concurrent valid-
ity.19,25 VFA images have a sensitivity and speci-
ficity of about 90% for detecting moderate and
severe fractures; they are inferior to standard ra-
diographs for detecting mild fractures,19,25 but
mild fractures are not as strongly predictive of
subsequent fractures as are moderate-to-severe
fractures.26
Standard spinal radiographs and VFA are not
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Copyright © 2011 Massachusetts Medical Society. All rights reserved.
of m e dic i n e
usually indicated in patients with T scores for bone
mineral density that are very low (−2.5 or lower) or
high (higher than −1.5), since documentation of
vertebral fractures is unlikely to influence manage-
ment of patient care. However, among postmeno-
pausal women with T scores between −1.5 and
−2.4 for whom the benefit of pharmacologic treat-
ment is uncertain, identification of prevalent verte-
bral fractures may alter management. According
to a cost-effectiveness analysis, the use of either
spinal radiography or VFA to assess the vertebrae
in these women — with bisphosphonates pre-
scribed to those having at least one vertebral
fracture — is expected to result in a reduction in
the number of fractures for an additional cost
(<$50,000 per quality-adjusted life-year gained).27
Other methods of spinal imaging (e.g., com-
puted tomography and magnetic resonance imag-
ing) and radionuclide bone scanning are typically
reserved for patients in whom additional infor-
mation is needed to evaluate the acuity of frac-
tures or to differentiate osteoporotic fractures
from pathologic fractures.28
Treatment
Pain Management
Clinical vertebral fractures may cause pain severe
enough to require hospitalization.29 Data from ran-
domized, controlled trials evaluating the efficacy
of pain medications in patients with acute vertebral
fracture are lacking, but in practice, nonsteroidal
antiinflammatory drugs, analgesics (including nar-
cotics and tramadol), transdermal lidocaine, and
agents used to relieve neuropathic pain (e.g., tricy-
clic antidepressants) are commonly used. Although
the pain of acute vertebral fracture typically sub-
sides over the course of several weeks, narcotics
are often required temporarily to facilitate mobil-
ity and avoid prolonged bed rest.30 Small, random-
ized, placebo-controlled trials suggest that calci-
tonin (administered by intramuscular injection or
as a nasal spray) may modestly reduce pain associ-
ated with acute vertebral fracture.31 Teriparatide
and bisphosphonates may reduce back pain by
preventing new vertebral fractures, but their ef-
fectiveness in reducing pain from acute vertebral
fractures has not been tested in randomized trials.
Rehabilitation
Limited evidence from small, randomized, con-
trolled trials involving patients with clinical verte-
bral fractures supports the use of therapeutic exer-
 clinical pr actice

A B C

Figure 2. Comparison of Densitometric Vertical Fracture Assessment (VFA) with Standard Radiographic Images
of the Lateral Thoracic and Lumbar Spine.
As compared with radiographic images, those obtained with the use of VFA have a lower resolution (the vertebral
cortices and end plates are less distinct) and do not capture the thoracic spine well at a level superior to T7 (Panel
A, arrow). However, in standard lateral spinal radiographs, projection distortion (parallax) is common (Panels B
and C, arrows).

cise programs to reduce pain and improve strength,
balance, functional status, and quality of life, but
the findings are not consistent across studies.32
Back braces (i.e., spinal orthoses) have been
used to treat patients with acute vertebral frac-
tures, but their benefits and harms have not been
rigorously evaluated. The results of small, ran-
domized, unblinded trials suggest that use of a
rigid back brace during waking hours for 6 weeks
or use of a nonrigid back brace for 2 hours per day
for 24 weeks may reduce self-reported pain and
disability after a clinical vertebral fracture.33,34
Vertebroplasty and Kyphoplasty
Vertebral augmentation procedures (vertebroplas-
ty or kyphoplasty) are being performed with in-
creasing frequency in the United States; in 2005,
86 of every 100,000 fee-for-service Medicare ben-
eficiaries underwent vertebroplasty.35 Observa-
tional studies have reported reductions in pain,
disability, and length of hospital stay among pa-
tients with acute vertebral fracture who undergo
these procedures as compared with those who do
not,36 but these studies are susceptible to sub-
stantial biases.
Two randomized, open-label trials conducted
with women who had acute, painful vertebral frac-
tures (mean duration of back pain, 4 to 6 weeks)
showed reduced pain and improved physical func-
tion among those undergoing kyphoplasty37 or
vertebroplasty,38 but the comparison in each of
these trials was usual care rather than a sham
procedure. Thus, the observed benefit may have
been due to a placebo effect. Another small, ran-
domized trial showed no differences in pain or
functional status with vertebroplasty as compared
with conservative treatment in patients with pain-
ful vertebral fractures that had occurred within
the preceding 8 weeks.39 Moreover, in two ran-
domized, double-blind trials40,41 comparing verte-
broplasty with a sham procedure, patients with
painful vertebral fractures that had been identi-
fied within the preceding 12 months had no
benefit from vertebroplasty with respect to pain,

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Copyright © 2011 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l
functional disability, or quality of life. The mean
duration of symptoms before performance of the
procedure was 12 to 13 weeks in one trial40 and
16 to 20 weeks in the other.41 Since vertebroplasty
and kyphoplasty have been proposed to be most
effective for acute fracture pain, analyses were
performed in these trials within the subgroup of
patients whose pain was of shorter duration, but
these analyses did not indicate that vertebroplasty
was more beneficial than the sham procedure.
However, the power to detect between-group dif-
ferences was limited.
Vertebroplasty and kyphoplasty are invasive
procedures that carry small risks of symptomatic
epidural cement leakage, causing nerve-root inju-
ry (in 0.4 to 4% of patients),42-44 and symptomatic
cement pulmonary embolism (in approximately
0.1% of patients).44,45 More worrisome is the pos-
sibility that the procedures may increase the risk
of subsequent vertebral fractures by increasing
mechanical load on the vertebrae adjacent to
those being treated.46,47 No excess risk of subse-
quent vertebral fractures with vertebroplasty or
kyphoplasty has been documented in the ran-
domized trials conducted to date, but these trials
were not powered for this outcome.
Calcium and Vitamin D
All current guidelines for the management of os-
teoporosis recommend adequate intake of calcium
(≥1000 mg per day) and vitamin D (≥600 IU per
day). However, no placebo-controlled, randomized
trial has shown that there is a reduced risk of
incident radiographic or clinical vertebral frac-
tures with the use of calcium alone, vitamin D
alone, or calcium combined with vitamin D.48,49
Pharmacotherapy
Pharmacologic therapy is indicated to reduce the
risk of subsequent fractures in persons with ra-
diographic or clinical vertebral fractures that are
not the result of major trauma or cancer, irre-
spective of the presence or absence of associated
symptoms or the bone mineral density T score.
Large, randomized, placebo-controlled, double-
blind trials conducted in women with postmeno-
pausal osteoporosis (entry criteria included ei-
ther low bone mineral density or a prevalent
radiographic vertebral fracture) have shown the
efficacy of several pharmacotherapies in reduc-
ing the risk of incident clinical or radiographic
vertebral fractures (Table 1). The agents studied
1638 n engl j med 364;17  nejm.org  april 28, 2011
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Copyright © 2011 Massachusetts Medical Society. All rights reserved.
of m e dic i n e
included oral bisphosphonates (alendronate, iban­
dronate, and risedronate),50,51 intravenous bisphos­
phonates (zoledronic acid),50 selective estrogen-
receptor modulators (bazedoxifene,52 lasofoxifene,53
and raloxifene50,51), parathyroid hormone,50,51,54
denosumab,55 strontium ranelate,56,57 and calci-
tonin,50 although the reported efficacy of calcito-
nin in reducing new vertebral fractures is ques-
tionable. Treatment with bisphosphonates (except
ibandronate, for which no data are available), laso­
foxifene, strontium, denosumab, or teriparatide
has also been shown to reduce the risk of nonver-
tebral fracture, and there is evidence that alen-
dronate, risedronate, zoledronic acid, or deno-
sumab reduce the risk of hip fracture. Generic
alendronate is frequently used as a first-line treat-
ment because of its efficacy in reducing nonver-
tebral (including hip) and vertebral fractures, its
safety profile during 10 years of use, and its rela-
tive cost.
A r e a s of Uncer ta in t y
The value of spinal imaging is uncertain in pa-
tients for whom pharmacologic treatment is rec-
ommended on the basis of an indication other
than vertebral fracture (e.g., bone-mineral-density
T score of −2.5 or lower). Information about status
with respect to prevalent vertebral fractures may
improve the prediction of new vertebral fractures
beyond that provided by existing risk-assessment
tools, such as the Fracture Risk Assessment Tool
(FRAX) from the World Health Organization,58
but it is unknown whether this is the case for
prediction of incident fractures at other skeletal
sites and to what extent this information would
alter the management of patient care. Among pa-
tients with prevalent vertebral fractures or those
with osteoporosis, the efficacy of pharmacologic
treatment in preventing fractures over a period
longer than 3 to 5 years is uncertain, and the risks
and benefits of discontinuing treatment for a
given period of time are unknown. Additional data
from randomized, blinded, well-controlled trials
are needed to determine whether vertebral aug-
mentation procedures performed within the first
6 weeks after a disabling vertebral fracture are
efficacious and safe. Trials are also warranted
for patients with clinical vertebral fractures to
determine the effect of spinal orthoses and exer-
cise programs on long-term pain, mobility, func-
tional status, and quality of life.
 Table 1. Medications for Reducing the Risk of Fracture in Postmenopausal Women with Prevalent Vertebral Fractures.*

Drug Administration Fracture Risk Reduction Side Effects or Risks

Bisphosphonates50,51
Alendronate† 70 mg orally, once per wk Vertebral, nonvertebral, hip Upper gastrointestinal irritation is common, esophageal ulcer and bone pain
are uncommon, and osteonecrosis of the jaw and atypical fractures of the
femoral shaft are rare
Ibandronate† 150 mg orally, once per mo Vertebral with oral administration, With oral administration, upper gastrointestinal irritation is common, esoph-
3 mg intravenous, every but no benefit demonstrated ageal ulcer and bone pain are uncommon, and osteonecrosis of the jaw
3 mo with intravenous administration and atypical fractures of the femoral shaft are rare; with intravenous ad-
ministration, ­influenza-like symptoms are common, hypo­calcemia is
­uncommon, and osteonecrosis of the jaw and atypical ­fractures of the
femoral shaft are rare
Risedronate† 35 mg orally, once per wk, Vertebral, nonvertebral, hip Upper gastrointestinal irritation is common, esophageal ulcer and bone pain
or 150 mg orally, once are uncommon, and osteonecrosis of the jaw and atypical fractures of the
per mo femoral shaft are rare
Zoledronic acid† 5 mg intravenously, once Vertebral, nonvertebral, hip Bone pain with first dose and influenza-like symptoms are common, hypocal-
per year cemia is uncommon, and osteonecrosis of the jaw and atypical fractures
of the femoral shaft are rare
SERMs
Bazedoxifene52‡ 20 mg orally, once per day Vertebral Leg cramps and hot flashes are common; uterine polyps and deep-vein throm-
bosis are uncommon
Lasofoxifene53‡ 0.5 mg orally, once per day Vertebral, nonvertebral Leg cramps and hot flashes are common; uterine polyps and deep-vein throm-
bosis are uncommon
clinical pr actice

Raloxifene50,51† 60 mg orally, once per day Vertebral Leg cramps and hot flashes are common; uterine polyps and deep-vein throm-
bosis are uncommon
PTH

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The New England Journal of Medicine

Recombinant human 100 μg subcutaneously, Vertebral Nausea, arthralgia, leg cramps, hypercalcemia, and hypercal­ciuria are com-
PTH(1–84)54‡ once per day mon; hyperuricemia and hypotension are ­uncommon
Teriparatide (PTH[1–34])50,51† 20 μg subcutaneously, once Vertebral, nonvertebral Nausea, arthralgia, leg cramps, hypercalcemia, and hypercal­ciuria are com-
per day mon; hyperuricemia and hypotension are ­uncommon
RANKL inhibitor

Copyright © 2011 Massachusetts Medical Society. All rights reserved.

Denosumab55† 60 mg subcutaneously, — Vertebral, nonvertebral, hip Eczema, nausea, and injection-site reactions are common; osteo­necrosis of
every 6 mo the jaw is rare
Calcitonin50† 100–200 IU nasally or Vertebral With nasal administration, nasal stuffiness is common and nausea is uncom-
subcu­taneously, once mon; with subcutaneous administration, nausea, injection site-reactions,
per day and flushing of hands or face are common

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Other
Strontium ranelate56,57‡ 2 g orally, once per day Vertebral, nonvertebral Diarrhea, nausea, eczema, and headache are common; elevated serum ­levels
of creatine kinase are uncommon

* All agents have been evaluated in randomized, placebo-controlled trials with a fracture outcome as the primary end point. The proportion of participants with prevalent vertebral fractures in
these trials ranged from 19 to 100%. All participants in these trials, including those in the placebo group, received supplemental calcium and vitamin D. PTH denotes parathyroid hormone,
RANKL receptor activator of nuclear factor κB ligand, and SERM selective estrogen-receptor modulator.
† This agent was approved by the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis.
‡ This drug has not been approved by the FDA but has been approved for use in the European Union.

1639
 The n e w e ng l a n d j o u r na l of m e dic i n e

mobility should be immediate goals that may re-

Guidel ine s from Profe ssiona l
So cie t ie s
The International Society for Clinical Densitom-
etry has published guidelines for the assessment
of vertebral fractures.16 Several organizations, in-
cluding the National Osteoporosis Foundation, the
European Society for Clinical and Economic Eval-
uation of Osteoporosis and Osteoarthritis, and
the American College of Physicians,59-61 have
published guidelines for the diagnosis and treat-
ment of osteoporosis that address the manage-
ment implications of identifying vertebral frac-
tures and the effectiveness of pharmacologic
agents in fracture prevention. The recommenda-
tions in this article are generally concordant with
these guidelines.
C onclusions a nd
R ec om mendat ions
The history and examination of the patient in the
vignette suggest a clinical vertebral fracture, but
the diagnosis must be confirmed with an imag-
ing study of the spine. The identification of a
vertebral fracture indicates a diagnosis of osteo-
porosis, regardless of the patient’s bone-mineral-
density T score. Relieving pain and preserving
quire short-term narcotic therapy. Although there
are uncertainties about the effect of therapeutic
exercise, we would recommend a targeted physi-
cal therapy program that incorporates postural
retraining and exercises to improve the strength
of back extensor musculature and mobility.
Since vertebral fractures are associated with
an increased risk of future fractures, the longer-
term goal should be reducing the risk of subse-
quent fractures. We recommend a calcium in-
take of 1000 to 1200 mg per day and a vitamin
D intake of 600 to 800 IU per day (through diet,
supplements, or both), although the benefit of
this approach in reducing the risk of subsequent
vertebral fractures is uncertain. Although sev-
eral medications reduce the risk of new verte-
bral fractures, we recommend the initiation of
treatment with generic alendronate, considering
its efficacy in reducing incident fractures, includ-
ing hip fracture, and its safety and relatively
low cost.
Dr. Ensrud reports receiving travel support from Pfizer, Merck,
and the Croatian Osteoporosis Society; and Dr. Schousboe, receiv-
ing consulting fees from Roche and grant support from Hologic
and Eli Lilly. No other potential conflict of interest relevant to this
article was reported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.

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