|

The Management of Osteoporosis After

Fragility Fracture
The Orthopaedic Perspective

Jonathan Morris, MD Abstract

» The greatest risk factor for fragility fracture is a previous fragility
Alexa J. Karkenny, MD
fracture.
Jose B. Toro, MD
» During post-fracture follow-up, the orthopaedic surgeon has an
opportunity to intervene in the management of osteoporosis.
Investigation performed at the Jacobi
» A novel algorithm for interpreting laboratory values and starting
Medical Center, Bronx, New York
antiresorptive and bone-stimulating agents is presented.

O
steoporosis is the most
common metabolic bone
disease worldwide1. It is a
result of an imbalance in
bone formation and resorption leading to
disruption of bone microarchitecture.
This disruption of normal physiology
ultimately results in increased fracture
risk. The prevalence of osteoporosis and
its associated fragility fractures have been
progressively increasing, and this course
is projected to continue from 2 million
fractures in 2005 to a projected 3 million
fractures in 2025 in the United States.
Annually in the United States, osteopo-
rosis is implicated in approximately
280,000 hip fractures, 540,000 vertebral
fractures, 380,000 wrist fractures, and
.800,000 fractures at other sites2,3.
Fracture is the most common musculo-
skeletal diagnosis requiring hospital
admission among the Medicare popula-
tion4. The lifetime risk of any fragility
fracture approaches 40% in Caucasian
women and 13% for men who are $50
years of age5. In total, 50% of women and
25% of men who are $50 years of age will
have an osteoporosis-related fracture in
their lifetime5.
Fragility fractures are not benign
events. A history of a fragility fracture in-
creases the risk of future fragility fractures.
A prior vertebral compression fracture
results in a 5 times greater risk of future
vertebral compression fracture and a 2
times greater risk of future hip fracture6.
Hip fractures are associated with an overall
mortality of 15% to 30% within 1 year of
fracture7. A majority of the deaths occur
within the first 6 months after the fracture,
with 1 study showing 52.4% of deaths
occurring within 3 months of the fracture
and 72.5% of deaths occurring within
6 months of the fracture8. Less than 25%
of patients who present with fragility
fractures for the first time receive initial
drug therapy to treat the underlying oste-
oporosis9; at 2 years, only 60% of these
patients are compliant with the
medication10.
Despite the high prevalence of oste-
oporosis and the widespread knowledge
of the risk of fragility fractures, the role of
the orthopaedic surgeon who primarily
treats these fractures remains unclear. Pa-
tients are often referred to their primary
care physician for osteoporosis manage-
ment after acute management of the frac-
ture11. However, recently, it has been
demonstrated that when the orthopaedic
surgery team initiates osteoporosis man-
agement, the rate of patients receiving
treatment increases11. Thus, there is a
tremendous opportunity to improve the

COPYRIGHT © 2017 BY THE

JOURNAL OF BONE AND JOINT Disclosure: There was no source of external funding for this study. The Disclosure of Potential Conflicts
SURGERY, INCORPORATED of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSREV/A236).

JBJS REVIEWS 2017;5(8):e4 · http://dx.doi.org/10.2106/JBJS.RVW.16.00098 1

 | The Management of Osteoporosis After Fragility Fracture

rate of patients who receive treatment
for osteoporosis after presenting with a
fragility fracture. The purpose of this
article was to review the current medical
treatments for osteoporosis and to
present a treatment algorithm for the
orthopaedic surgeon managing pa-
tients with fragility fractures.
Medical Screening and Evaluation
The initial management of osteopo-
rosis begins with a complete history,
including the identification of risk
factors. The strongest risk factors are
advanced age and a history of fragility
fracture. Other risk factors include sex,
postmenopausal status, long-term
corticosteroid use, low body weight,
family history of hip fracture, smoking
history, and excessive alcohol use12.
Further evaluation should look to rule
out secondary causes of decreased bone
strength (Table I).
Initial evaluation should include
blood tests to aid in the evaluation of
bone strength. The Joint Commission
recommends a complete blood-cell
count, kidney function tests, liver
function tests, serum calcium, and
25-hydroxy vitamin D level (25-OH
vitamin D)13. A fasting comprehensive
metabolic panel allows for the assess-
ment of renal function, liver function,
and nutritional status. A complete
blood-cell count evaluates the bone
marrow erythropoietic potential. Se-
rum calcium and phosphate represent
nutrient metabolism and dietary con-
sumption. Total protein and albumin
levels represent liver function and nu-
tritional status. Elevated protein levels
may identify neoplastic protein syn-
thesis from multiple myeloma, whereas
decreased levels may be associated with
poor nutritional states such as alcohol-
ism. Bone health can be determined
with serum calcium, phosphate, albu-
min, 25-OH vitamin D, and intact
parathyroid hormone levels. The opti-
mal 25-OH vitamin D level for skeletal
health is controversial, but an Institute
of Medicine systematic review favors
maintaining levels between 20 and
40 ng/mL14. Intact parathyroid hormone
measures parathyroid function. Para-
thyroid hormone levels of .50 pg/mL
suggest hypocalcemia and those of
,20 pg/mL suggest hypercalcemia, but
this is not universally true15. These
values must be carefully interpreted be-
cause there is dysregulation of calcium
homeostasis in hyperparathyroidism.
Bone turnover can be determined by
measuring bone-specific alkaline phos-
phatase (BSAP) and urine N-terminal
telopeptide (NTX). Normal BSAP
values should be ,22 mg/L and should
decrease within 3 to 6 months of anti-
resorptive therapy16. Urine NTX

TABLE I Differential Diagnosis for Decreased Bone Mineral Density and Clinical Evaluation to Assist in
Ruling Out the Secondary Causes of Decreased Bone Strength

Pathology Description Blood Tests

Osteomalacia or rickets
Hypogonadism
Hypophosphatasia
Hyperparathyroidism
Malignancy
Endocrinopathy
Medication-related
Disuse
Decreased mineralization of osteoid, occurs 25-OH vitamin D, serum calcium,
with hypocalcemia or hypophosphatemia phosphorus, intact parathyroid hormone
because of vitamin D deficiency or increased
parathyroid hormone
Low testosterone levels in males Serum testosterone
Autosomal recessive inheritance resulting in 25-OH vitamin D, serum calcium,
impairment of bone mineralization, phosphorus, intact parathyroid hormone
manifests similar to rickets
Increased production of parathyroid Serum calcium, phosphorus, intact
hormone leading to increased bone parathyroid hormone, alkaline phosphatase
resorption, from primary causes (i.e.,
parathyroid adenoma or hyperplasia),
secondary causes (i.e., renal osteodystrophy
or chronic kidney disease), or tertiary causes
(i.e., dysregulated parathyroid glands
secrete parathyroid hormone independent
of calcium levels)
Most common cause is multiple myeloma Serum and urine protein electrophoreses,
complete blood-cell count, creatinine,
calcium, total protein, alkaline phosphatase,
lactate dehydrogenase
Deficiency in the hypothalamic-pituitary Thyroid function tests
axis, such as hypothyroidism
Long-term use of glucocorticoids Serum cortisol levels
Disuse osteopenia 25-OH vitamin D, serum calcium,
phosphorus, intact parathyroid hormone

2 AUGUST 2017 · VOLUME 5, ISSUE 8 · e4


levels should be between 20 and 60
equivalents/mmol. Mild elevation,
,1.5 times the normal, is associated
with osteoporosis and a reduction of
50% is expected within 6 months
of initiation of treatment17,18.
Additional screening should be
performed as guided by the Fracture
Risk Assessment Tool (FRAX) and dual
x-ray absorptiometry (DXA) scanning.
Using the calculator, the FRAX score
estimates the 10-year probability of hip
fracture or combined risk of major os-
teoporotic fractures (hip, spine, shoul-
der, or wrist) based on exposure to risk
factors. Medical treatment is recom-
mended if the estimated risk is .3% for
hip fracture or .20% for any fragility
fracture19. The DXA score analyzes the
bone mineral density at the distal part
of the radius, hip, and lumbar spine.
The U.S. Preventive Services Task
Force and World Health Organization
recommendations advise that DXA
scans be performed for women who
are .65 years of age, men who
are .70 years of age, and younger at-
risk women20. The T-score represents
the difference in bone mineral density
between the patient and a young adult
of the same race and sex, expressed
in standard deviations. A normal score
is within 1 standard deviation of the
mean. Osteopenia is defined as a bone
mineral density between 1 and 2.5
standard deviations below the mean,
whereas osteoporosis is defined as a
bone mineral density at least 2.5 stan-
dard deviations below the mean. Severe
osteoporosis includes the addition of a
fragility fracture. For patients at risk
because of age, history, or evaluation
and with a T-score within normal
limits, a repeat DXA scan is recom-
mended every 3 to 5 years21.
Medical Treatments
The mainstay of treatment for all
patients is calcium and vitamin D
supplementation. An estimated 70%
of all patients presenting with fragility
fracture have low 25-OH vitamin D
levels22. The recommended minimal
daily intake is 1,000 mg for calcium,
AUGUST 2017 · VOLUME 5, ISSUE 8 · e4
The Management of Osteoporosis After Fragility Fracture
in the form of calcium citrate, and
2,000 units for vitamin D3. Studies
have shown that vitamin D3 absorp-
tion may be enhanced when taken
with meals containing fats23.
Osteoporosis medications are
divided into two categories: anti-
resorptive agents and bone stimulants.
Antiresorptive agents include bisphos-
phonates, denosumab, calcitonin, es-
trogen, and selective estrogen receptor
modulators. Bone stimulants include
recombinant parathyroid hormone
and strontium ranelate.
Bisphosphonates are non-organic
pyrophosphate analogs that bind to
calcium in bone. There are 2 main
categories, non-nitrogen-containing
and nitrogen-containing. The non-
nitrogen-containing bisphosphonates
are the older generation and less potent.
They generate toxic analogs of adeno-
sine triphosphate (ATP) that accumu-
late inside osteoclasts and inhibit
their function and causes apoptosis.
Nitrogen-containing bisphosphonates
are more potent and require less
frequent dosing. They function by
inhibiting farnesyl transferase in oste-
oclasts, resulting in dysregulation
and apoptosis. Examples include
zoledronic acid (Reclast and Zometa;
Novartis), ibandronate (Boniva;
Genentech), alendronate (Fosamax;
Merck), and risedronate (Actonel; Nor-
wich). They are prescribed for the treat-
ment of osteoporosis, Paget disease, and
hypercalcemia in the context of meta-
static bone disease. Multiple randomized
controlled trials have found them to re-
duce the risk of hip fractures and vertebral
compression fractures and to be cost-
effective24-26. Previously, there has been
concern for delayed bone-healing if bis-
phosphonates are started too soon after a
fragility fracture; however, these findings
were refuted in hip fractures and fractures
of the lower extremities27,28.
The most common side effects
of bisphosphonates are upper gastro-
intestinal disorders. Approximately
20% to 30% of people who take oral
bisphosphonates report symptoms of
upper gastrointestinal disorders29.
|
Age and use of nonsteroidal anti-
inflammatory drugs were associated
with increased prevalence. Dosing in-
structions to avoid these effects include
taking the pill with a sufficient amount
of water, not chewing the pill, and
staying upright for at least 30 minutes
after ingestion29.
The most catastrophic side effects
are atypical femoral fractures and osteo-
necrosis of the jaw. Atypical femoral
fractures are relatively rare, but their
exact prevalence is difficult to deter-
mine because they are commonly
grouped with subtrochanteric and di-
aphyseal femoral fractures. However,
17% to 29% of all low-energy subtro-
chanteric and diaphyseal femoral
fractures in patients who are .65 years
of age have been determined to be
atypical30,31. The mechanism of atyp-
ical femoral fractures is unknown at
this time, but it appears to be a chronic
disorder of bone remodeling. The
clinical presentation often includes a
history of prolonged bisphosphonates,
thigh pain, fracture resulting from
low-energy mechanism of injury, radio-
graphs demonstrating lateral cortical
thickening, and transverse subtrochan-
teric fracture with medial beaking32.
The current recommendations for
management of atypical femoral frac-
tures include placement of a reamed
intramedullary nail, cessation of bis-
phosphonates, initiation of calcium
and vitamin D supplementation, eval-
uation of the contralateral femur,
and possible initiation of recombinant
parathyroid hormone. If the contralat-
eral femur does not demonstrate a
progressing fracture but the magnetic
resonance image (MRI) demonstrates
edema, then recombinant parathyroid
hormone should be prescribed for 3
months33,34. If there is a progressing
fracture with or without pain, then
prophylactic, reamed intramedul-
lary nailing is recommended.
Bisphosphonate-related osteonecrosis
of the jaw is rare. The estimated inci-
dence is 0.7 per 100,000 persons per
year35. To prevent bisphosphonate-
related osteonecrosis of the jaw, all
3
 | The Management of Osteoporosis After Fragility Fracture
planned dental work should be completed
prior to starting bisphosphonate treat-
ment. The current protocol for bisphos-
phonate therapy to minimize the risk of
these side effects is to withdraw oral bis-
phosphonates after 5 years and intrave-
nous bisphosphonates after 3 years and to
then resume modified dosing when bone
mass decreases on DXA scanning or NTX
increases36. Intermittent use capitalizes
on the medication’s protective effect and
reduces the risk of fracture.
Denosumab is a monoclonal an-
tibody to RANKL (receptor activator
of nuclear factor kappa-B ligand). It
functions to inhibit bone resorption by
binding to RANKL after it is released
by osteoblasts. This prevents the acti-
vation of osteoclasts. When treatment
was compared with placebo in women
with osteoporosis, there was significant
reduction in vertebral fractures (2.3%
compared with 7.2%; p , 0.001), non-
vertebral fractures (6.5% compared
with 8.0%; p 5 0.01), and hip fractures
(0.7% compared with 1.2%; p 5 0.04)
in a randomized controlled trial37.
Other antiresorptive medications
include calcitonin, estrogen, and se-
lective estrogen receptor modulators.
Calcitonin has been shown to decrease
the risk of future vertebral compression
fractures in patients with previous ver-
tebral compression fractures38. In some
small randomized trials, it has been
shown to decrease the pain associated
with acute vertebral compression frac-
tures39. Estrogen therapy has been
shown to decrease hip and vertebral
fractures, but to have increased risk of
cardiovascular disease, thromboem-
bolic disease, and breast cancers40,41.
Selective estrogen receptor modulators
have selective binding to estrogen re-
ceptors in bone and have fewer associated
vascular events and malignancies. These
modalities are reserved for patients who
cannot tolerate bisphosphonates or are
not candidates for bisphosphonate ther-
apy, because bisphosphonates remain
more effective at preventing fractures.
Recombinant parathyroid hor-
mone is described as a bone-stimulant
medication because of its anabolic effect
4 AUGUST 2017
on bone when dosed intermittently. It is
composed of a chain of 34 amino acids
from parathyroid hormone. Chronic
exposure to supraphysiologic levels of
recombinant parathyroid hormone re-
sults in bone resorption, and intermit-
tent dosing has demonstrated greater
bone formation than bone resorption.
A randomized controlled trial demon-
strated improvement in bone mineral
density with 20 mg/day and 40 mg/day
dosing of recombinant parathyroid
hormone42. The medication has also
been associated with faster healing
for distal radial fractures and pubic
rami fractures42,43. The most common
short-term side effects are nausea, head-
ache, and hypercalcemia42. In rat
models, long-term, high-dose use has
been associated with osteosarcoma,
whereas a long-term, low-dose treatment
regimen resulted in increased bone mass
without neoplasm formation44,45. As a
result, this medication should not be
used for longer than 2 years. To main-
tain gains achieved after taking recom-
binant parathyroid hormone, it is
recommended that patients be transi-
tioned to a bisphosphonate46.
Discussion
Bone strength is a function of architec-
ture, bone remodeling, and mineraliza-
tion of the matrix. The end result of
decreased bone strength is a fragility
fracture, commonly located in the distal
part of the radius, vertebral body, pelvis,
or hip. The orthopaedic surgeon is com-
monly the first physician and sometimes
the only physician that a patient with a
fragility fracture sees once he or she has
been diagnosed. As orthopaedic sur-
geons, we have a unique opportunity to
impact the progression of the underlying
cause of the fragility fractures. The
most common cause is osteoporosis.
Figure 1 demonstrates an algorithm
for the managing orthopaedic surgeon
to follow. There are 4 basic steps to
management: risk factor assessment,
clinical evaluation, medication, and
counseling. Immediately after sustain-
ing a fracture, the patient’s risk factors
need to be reviewed. The laboratory
tests that should be obtained during
each visit are complete blood-cell
count, serum calcium, serum phos-
phorus, 25-OH vitamin D, and intact
parathyroid hormone. A fasting com-
prehensive metabolic panel should be
obtained at the first visit, followed by
a basic metabolic panel at each visit.
Pending the results of the risk factor
assessment, additional laboratory test
results should be obtained as per
Table I. Immediately after surgical
treatment of the fracture, the patient
should be given calcium at 1,000 mg
per day and vitamin D3 at 2,000 IU
per day. However, providers should
weigh patients’ other medical comor-
bidities and should consult medical
colleagues where appropriate before
universally initiating calcium supple-
mentation at the aforementioned dos-
age. For instance, historically, to our
knowledge, no prospective studies
have supported the theory that calcium
restriction leads to reduced nephrolithi-
asis or urolithiasis, but recent retrospec-
tive data suggest that supplementation
may predispose to higher stone growth
rate in known stone formers47,48. The
patient should also be counseled on
preventable risk factors and strategies to
minimize his or her risks, such as
smoking cessation, improving nutri-
tion to achieve ideal body weight, or
limiting alcohol intake. The patient
should also undergo clinical evaluation
for fall risk assessment.
Three months after the injury,
the patient should undergo an updated
history, clinical evaluation, and coun-
seling similar to the previous ones.
Additionally, it is recommended that
all patients undergo a DXA scan and
FRAX assessment to create a baseline
for future comparison, to determine
their current risk of fracture, and to help
to guide medical management. Patients
should be given oral bisphosphonates
as a first-line agent. Recombinant para-
thyroid hormone is a first-line agent
in cases of severe osteoporosis or a
second-line agent if the patient cannot
tolerate oral bisphosphonates. The rec-
ommended first-line bisphosphonates
· VOLUME 5, ISSUE 8 · e4

are alendronate, given at 10 mg
each day by mouth or 70 mg per
week by mouth, or risedronate, given
at 35 mg per week by mouth. Recom-
binant parathyroid hormone is given
at 20 mg each day subcutaneously.
If the patient is not a candidate
for oral bisphosphonates, consider
zoledronic acid, given at 5 mg intrave-
nously every 2 years, or denosumab,
given at 60 mg subcutaneously every
6 months.
Fracture liaison services and
orthogeriatric services have been
shown to be medically and financially
beneficial. Decreased inpatient and
long-term mortality has been ob-
served when these services either co-
manage or closely follow, with the
orthopaedic surgeon, patients with
hip fracture. The co-managed service
is cost-effective when case volume is
AUGUST 2017 · VOLUME 5, ISSUE 8 · e4
The Management of Osteoporosis After Fragility Fracture
.54 cases per year. Cost savings were
realized when .318 patients were
seen annually. After the orthopaedic
surgeon has initiated antiresorptive
and bone-stimulating medications, it
may be financially beneficial to tran-
sition patients to long-term follow-up
with geriatricians, as they are reim-
bursed for the long-term medical care
of patients2.
Once an antiresorptive or bone-
stimulating medication has been ad-
ministered, patients must be followed
for the duration of treatment by the
orthopaedic surgeon, fracture liaison
services, or orthogeriatric services. Oral
bisphosphonates should only be taken
for 5 years, and intravenous bisphos-
phonates should only be taken for 3
years. Further treatment is determined
by the NTX level and the T-score on
DXA scanning. Recombinant
|
Fig. 1
Algorithm for management of osteopo-
rosis after fragility fracture. PTH 5 para-
thyroid hormone, CBC 5 complete
blood-cell count, BMP 5 basic metabolic
panel, post-op 5 postoperatively,
FRAX 5 Fracture Risk Assessment Tool,
and DXA 5 dual x-ray absorptiometry.
parathyroid hormone can only be taken
for 2 years. At that point, medical
management should be switched to
bisphosphonates. Repeat DXA scan-
ning and FRAX assessment should be
performed every 3 to 5 years for all
patients with fractures.
Conclusions
Osteoporosis is one of the most com-
mon causes of fragility fractures.
The orthopaedic surgery community
has a unique opportunity to prevent
further fractures by determining the
appropriate medication and initiating
treatment. During the scheduled
follow-up for fracture management,
additional testing and counseling
will help to guide the appropriate
medical management. The underly-
ing goal is to reduce the prevalence
of fragility fractures.
5
 | The Management of Osteoporosis After Fragility Fracture
Jonathan Morris, MD1,
Alexa J. Karkenny, MD1,
Jose B. Toro, MD2
1Jacobi
Medical Center, Bronx, New York
2Peaconic Bay Medical Center,
Riverhead, New York
E-mail address for J. Morris: morris.jonathan.
m@gmail.com
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