Detection and Treatment of
Sublesional Osteoporosis Among
Patients with Chronic Spinal Cord
Injury: Proposed Paradigms
B.C. Craven, L.A. Robertson, C.F. McGillivray, and J.D. Adachi
Low hip and knee region bone mineral density (BMD) after spinal cord injury (SCI) results in an increased
risk of lower extremity fragility fractures or sublesional osteoporosis (SLOP). There are currently no guide-
lines for the identiﬁcation and treatment of SLOP among patients with chronic SCI. A paradigm for iden-
tiﬁcation (medical screening, fracture risk, and bone mineral density assessment) of persons with SLOP
who warrant treatment and selection of appropriate SLOP treatment(s) (lifestyle/nutrition modiﬁcations,
bisphosphonate/rehabilitation therapies) is proposed. Content is based on the authors’ opinions/expertise
and available published and unpublished literature and is intended for use by rehabilitation professionals.
Key words: bone mineral density, fracture, osteoporosis, treatment, spinal cord injury
B.C. Craven, MD, is a Clinician Scientist (Physiatry)
at the Toronto Rehabilitation Institute, Lyndhurst
Centre, Toronto, Ontario, and an Assistant Professor
in the Department of Medicine, University of Toronto,
Toronto, Ontario, Canada.
L.A. Robertson, MSc, is a Research Coordinator
at the Toronto Rehabilitation Institute, Lyndhurst
Centre, Toronto, Ontario, Canada.
C.F. McGillivray, MD, is a Clinician Teacher
(Physiatry) at the Toronto Rehabilitation
Institute, Lyndhurst Centre, Spinal Cord Rehab
Program, Toronto, Ontario, and an Assistant
Professor and Clinician Teacher in the Department
of Medicine, University of Toronto, Toronto, Ontario,
J.D. Adachi, MD, is a Professor and the Head of
the Division of Rheumatology in the Department
of Medicine, McMaster University, St. Joseph’s
Hospital and Hamilton Health Sciences, Hamilton,
ncreased survival and increased life
expectancy after SCI have shifted the
emphasis of medical intervention from
survival to minimizing secondary complica-
tions and maximizing quality of life.
lesional osteoporosis (SLOP) is a disease
process unique to persons with SCI charac-
terized by excessive bone resorption, dete-
rioration in lower extremity bone architec-
ture, and an increased propensity for lower
extremity fragility fracture. Bone mineral
density (BMD) of the hips, distal femur,
and proximal tibia are 28%, 37%–43%, and
36%–50% below that of age-matched peers
at 12–18 months post injury.
suggested that hip and knee BMD stabilize
1–2 years post SCI, at 25%–50% below that
of able-bodied peers.
Top Spinal Cord Inj Rehabil 2009;14(4):1–22
© 2009 Thomas Land Publishers, Inc.
2 Topics in spinal cord injury rehabiliTaTion/spring 2009
tions support a continual 3% per year BMD
decline, indicating that lower extremity
bone mineral homeostasis does not reach
steady state after SCI.
Twenty-ﬁve percent to 46% of persons
living with chronic SCI will develop fra-
Fractures of the distal
femur and proximal tibia predominate
and typically occur due to torsional stress on
lower extremity bones during a transfer, or
alternatively, compressive force at the knee
during a low velocity fall. Fragility fractures
often result in delayed union, nonunion,
malunion, or, in extreme cases, lower ex-
A fragility fracture
can initiate a cascade of events resulting
in increased morbidity (i.e., heel pressure
sore), decreased function (i.e., inability to do
independent transfers), and increased nurs-
ing and attendant care requirements during
Although fracture reduction is the ulti-
mate goal of SLOP detection and treatment,
no treatment trial to date has been designed
or adequately powered (sample size) to de-
tect fracture reduction.
Most studies have
used lower extremity BMD or bone resorp-
tion markers as proxy outcomes for fracture
reduction. Methods are established for
diagnosing SLOP via BMD testing. Health
screening, fracture risk assessment, and de-
termination of knee region BMD is needed
to select patients for treatment. For the pur-
poses of this discussion, chronic SCI refers
to persons with C1-T12 American Spinal
Injury Association Scale (AIS) A-D injury of
≥24 months duration. Treatments for SLOP
include amelioration of secondary causes of
osteoporosis, lifestyle modiﬁcations (smok-
ing cessation, restricted alcohol and caffeine
intake, mobility assessment, and counseling
regarding sports participation), calcium
and/or vitamin D supplements, rehabilitation
interventions, and bisphosphonate therapy.
Detection of SLOP
For ease of discussion and graphic repre-
sentation, we have identiﬁed three categories
of assessment a clinician should complete
to identify patients with SLOP who warrant
treatment: (1) health, (2) fracture risk, and
(3) BMD (Figure 1).
Figure 1. Paradigm for identiﬁcation of pa-
tients with sublesional osteoporosis (SLOP)
after SCI who require treatment.
Detection and Treatment of Sublesional Osteoporosis 3
Does my patient have secondary causes of
osteoporosis other than their SCI?
It is crucial for clinicians to identify sec-
ondary causes of osteoporosis that can exac-
erbate or mask SLOP. The health evaluation
process includes (a) obtaining a detailed
medical history to identify secondary causes
of low BMD unrelated to SCI, (b) identify-
ing past and current medications known to
adversely affect BMD, and (c) screening
serum and urine for secondary causes of
osteoporosis amenable to medical interven-
tion. The health evaluation is presented as a
diagram (Figure 1), with three subsections:
medical history, medications, and serum and
Diseases or health conditions that ad-
versely inﬂuence BMD include thyroid and
parathyroid disease, hypogonadism, hy-
percalciuria, kidney stones, kidney failure,
chronic liver disease, multiple myeloma,
rheumatoid arthritis, mastocytosis, Crohn’s
and colitis (malabsorption), homocyste-
inuria, anorexia, osteogenesis imperfecta,
Marfan’s syndrome, prostate cancer, any
type of cancer managed with chemotherapy
or radiation therapy, as well as amenorrhea
and menopause in women. Medications
are also an important consideration, as
prolonged use of corticosteroids (>7.5 mg
for more than 3 months), anticonvulsants
(carbemazapine or dilantin), lithium, inad-
equate or excessive thyroid replacement,
loop diuretics, and blood thinners (heparin)
have adverse affects on BMD.
The 2002 Canadian Practice Guidelines for
the diagnosis and management of osteoporo-
sis, advise screening for secondary causes of
osteoporosis not apparent during the typical
history or physical examination.
tests include serum thyroid stimulating hor-
mone (TSH), parathyroid hormone (PTH),
ionized calcium, bone-specific alkaline
phosphatase, vitamin D (25–OH), protein
electrophoresis, CBC, follicle-stimulating
hormone (FSH), luteinizing hormone (LH),
testosterone (men) or estradiol (women),
urea, creatinine clearance, and urinary calci-
um (Table 1). Patients who report unique sec-
ondary causes of osteoporosis (i.e., Marfan’s
syndrome or a history of anorexia) would
need additional serum and urine screening.
Although this process is time consuming, it
has a high diagnostic yield, with about 30%
of our patients having identiﬁable coexisting
secondary etiologies of osteoporosis.
A recent retrospective cohort study com-
pleted at our centre, consisting of 133 men
and premenopausal women with chronic SCI
and low BMD (T scores < -2.0), identiﬁed 37
participants (28%) with a coexisting etiology
of osteoporosis. Twenty-two subjects had
serologic evidence of parathyroid disease,
thyroid disease, vitamin D deﬁciency, hypo-
gonadism, or chronic liver disease. Two sub-
jects had hypercalciuria. Thirteen subjects
had medical histories of alcoholism, Crohn’s
disease, or long-term anticonvulsant or loop
diuretic usage. The results emphasize that
not all decreases in BMD are due to SLOP;
as many as 33% of individuals with chronic
SCI have coexisting secondary etiologies of
osteoporosis that can be identiﬁed.
Fracture risk assessment
Does my patient have risk factors for fra-
The goal of SLOP treatment is to prevent
fractures, therefore an assessment of fracture
risk is essential to identify SCI patients with
a high fracture risk. Assigning fracture risk
4 Topics in spinal cord injury rehabiliTaTion/spring 2009
involves a detailed history and limited physi-
cal examination (height, weight, and exam
according to the International Standard for
Neurological Classiﬁcation of Spinal Cord
Prior fragility fracture
Has my patient had a prior fragility
It is important to distinguish between an
incident and fragility fracture. A fragility
fracture is “caused by injury that would be
insufﬁcient to fracture normal bone: the re-
sult of reduced compressive and/or torsional
strength of bone.”
Most lower extrem-
ity fragility fractures after SCI are spiral
fractures of the diaphysis or simple bending
fractures of the distal femur or proximal
Table 1. Serum and urine screening for secondary causes of osteoporosis
Category Test Indication Result normal
Serum TSH Thyroid disease ❏ Yes ❏ No
(men and women)
❏ Yes ❏ No
25-OH vitamin D Vitamin D deﬁciency ❏ Yes ❏ No
Ionized calcium If elevated, consider PTH, metastatic
cancer, or multiple myeloma.
If low, consider osteomalacia.
❏ Yes ❏ No
Alkaline phosphatase Screen for bone or liver disease ❏ Yes ❏ No
Multiple myeloma ❏ Yes ❏ No
Prostate cancer ❏ Yes ❏ No
CBC ❏ Yes ❏ No
Urine Creatinine clearance Renal impairment ❏ Yes ❏ No
Urinary calcium excretion Hypercalciuria ❏ Yes ❏ No
Note: TSH = thyroid-stimulating hormone; FSH = follicle-stimulating hormone; LH = luteinizing hormone; PTH = parathyroid
hormone; PSA= prostate speciﬁc antigen.
Only in patients ≥65 years or with a prior history of prior vertebral fracture.
Only in male patients ≥50 years or with a prior history of prior vertebral fracture.
Modiﬁed excerpt from Clinical practice guidelines for the diagnosis and management of osteoporosis. Scientiﬁc Advisory
Board, Osteoporosis Society of Canada. CMAJ. 1996;155(8):1120.
Detection and Treatment of Sublesional Osteoporosis 5
Common etiologies of
fragility fracture after SCI include leg tor-
sion during a car transfer or rolling in bed
or falling to the ﬂoor from a wheelchair or
commode on a ﬂexed knee.
fracture is caused by an injury sufﬁcient to
fracture normal bone (i.e., motor vehicle ac-
cident). Many patients with SCI have more
than one fracture, with some reporting ﬁve
or six, at different skeletal sites.
fractures concurrent with the onset of SCI do
not increase the future risk of fragility frac-
ture, whereas postinjury fragility fracture(s)
are a potent predictor of future fragility
Prior fracture management (conserva-
tive vs. operative) does not help distinguish
fragility fractures from incident fractures. In
general, fractures that occur above the knee
require an acute hospitalization and operative
intervention, for nondisplaced and displaced
femoral neck or intertrochanteric fractures,
or fractures of the femoral or tibial shaft,
while fractures which occur below the knee
joint line tend to be managed nonoperatively
with bivalve splints or casts.
increase patient morbidity from concomitant
cellulitis, osteomyelitis, deep venous throm-
bosis, femoral shortening, and, in rare cases,
The prevention of fractures is
therefore a potent incentive to initiate SLOP
screening and/or treatment.
Risk factors for fracture
How many risk factors does my patient
The prevalence of fragility fractures in
persons with SCI is reported to be 25%–
although this is likely an underesti-
mate. Some individuals may be unaware of
having sustained a minor fragility fracture
and therefore did not seek medical attention
or alternatively received treatment at local
hospitals and were therefore not captured
by published studies.
The incidence of
fracture (fragility and incident) is 2%–6%
and it increases with the dura-
tion of SCI: 14% incidence at 5 years post
injury, 28% incidence at 10 years post injury,
and 39% incidence at 15 years post injury in
the United States.
The highest incidence
of fragility fracture occurs in the following
situations: SCI before age 16,
BMI ≤ 19,
intake of more than ﬁve servings per day,
complete versus incomplete SCI,
female versus male.
Table 2 provides a
list of common risk factors reported in the
literature; we propose that the presence of
three or more risk factors implies a moder-
ate risk for fracture, while ﬁve or more risk
factors implies a high risk.
Bone mineral density
Does my patient have SLOP? Is their BMD
an independent risk factor for fracture?
In other populations with osteoporosis,
combining BMD with clinical risk factors
provides a better estimate of fracture risk
than BMD or risk factors alone. For this
article, we make a similar assumption for
patients with SLOP. Following the diagram
in Figure 1 (Part III), BMD results are in-
terpreted using the WHO criteria (Table 3)
and fracture threshold criteria (Table 4) to
identify patients at greatest risk of fracture.
Areal and volumetric measures of BMD
are available using dual energy X-ray ab-
sorptiometry (DXA) and peripheral quanti-
tative computed tomography (p-QCT). DXA
is the standard tool for measuring areal BMD
(aBMD) and is used to diagnose osteoporo-
6 Topics in spinal cord injury rehabiliTaTion/spring 2009
sis and/or monitor treatment effectiveness.
During a DXA scan, the densitometer emits
pencil or fan beam X-rays of different energy
levels and records the differences in attenu-
ation to distinguish bone from surrounding
Areal BMD (aBMD) in g/cm
is calculated as the measured bone mineral
content (g)/area (cm
To validly detect a clinically important
change, changes in aBMD from serial scans
must be equivalent to or exceed the least
signiﬁcant change of the densitometer.
Follow-up BMD testing is typically done
when the expected change in BMD equals
or exceeds the least signiﬁcant change of the
densitometer (about 12–18 months depend
ing on the site measured).
recommendation of the International Society
of Clinical Densitometry (ISCD) is to moni-
tor response to treatment every 1–2 years at
the same facility, with the same densitom-
eter, using the same acquisition and analysis
DXA protocols are available for
measuring multiple skeletal sites including
the whole body, spine, hip, wrist, and heel.
The choice of measurement site is based on
the distribution of BMD decline and the abil-
ity of the DXA measure to predict regional
fracture risk. Measurements of spine and
Table 3. Diagnostic categories for osteoporosis
based on WHO criteria
Category Deﬁnition by BMD
Normal A value for BMD that is not
more than 1.0
SD below the
young adults mean value
Low bone mass
A value for BMD that lies be-
tween 1.0 and 2.5
SD below the
young adults mean value
Osteoporosis A value for BMD that is more
than 2.5 SD below the young
Note: BMD = bone mineral density; SD = standard deviation;
WHO = World Health Organization.
Table 2. Risk factors for lower extremity
fragility fracture after SCI
Yes No Risk factors
❏ ❏ Age at injury <16 years
❏ ❏ Alcohol intake >5 servings/day
❏ ❏ BMI <19
❏ ❏ Duration of SCI ≥10 years
❏ ❏ Female
❏ ❏ Motor complete (AIS A-B)
❏ ❏ Paraplegia
❏ ❏ Prior fragility fracture
❏ ❏ Family history of fracture
Note: BMI = body mass index; AIS = ASIA Impairment
Parsons K, Lammertse D. Epidemiology, prevention and sys-
tem of care of spinal cord disorders. Arch Phys Med Rehabil.
Morse LR., Battaglino RA. et al. Osteoporotic fracture and
hospitalization risk in chronic spinal cord injury. Osteoporos
Garland DE, Adkins RH, Kushwaha V, Stewart C. Risk fac-
tors for osteoporosis in the spinal cord injury population. J
Spinal Cord Med. 2004;27(3):212–213.
Garland DE, Atkins RH. Fracture threshold and risk
for osteoporosis and pathological fracture in individu-
als with spinal cord injury. Top Spinal Cord Inj Rehabil.
Slade JM, Bickel SC, et al. Trabecular is more deteriorated
in spinal cord injured women versus estrogen free women.
Osteoporos Int. 2005;16(3):263–272.
Ragnarson K, Sell G. Lower extremity fractures after spinal
cord injury: A retrospective study. Arch. Phys. Med. Rehabil.
Freehafer, AA, Limb fractures in patients with spinal cord
injury. Arch Phys Med Rehabil. 1995;76(9):823–827.
Vestergaard P, Krogh K, Rejnmark L, Mosekilde L. Fracture
rates and risk factors for fractures in patients with spinal cord
injury. Spinal Cord. 1998;36(11):790–796.
Detection and Treatment of Sublesional Osteoporosis 7
hip aBMD are commonly used due to ease
of measurement and their ability to predict
regional fracture risk for postmenopausal
The authors advocate measure-
ment of lumbar spine, hip, and knee (distal
femur and proximal tibia) BMD for persons
with chronic SCI.
Volumetric BMD (vBMD) in g/cm
calculated as the measured bone mineral
content (g)/volume (cm
). p-QCT scans al-
low assessment of bone architecture, speciﬁ-
cally cortical thickness, trabecular volume,
and bone cross-sectional area in addition to
vBMD. Currently, p-QCT is predominantly a
research tool and is not routinely available in
clinical settings. However, p-QCT has been
used to study changes in vBMD after SCI in
Europe, Australia, and Canada.
less of the methodology, it is crucial that knee
region BMD be assessed as it is the best pre-
dictor of knee fracture risk after SCI.
individuals with chronic SCI, below average
aBMD or vBMD is typically due to low peak
bone mass or excessive resorption.
Does my patient meet the WHO criteria
Using World Health Organization (WHO)
criteria, the diagnosis of osteoporosis among
able-bodied postmenopausal women is
based on an aBMD T score, which is ≥ 2.5
SD below the young adult mean (Table
The T score is the number of standard
deviations BMD is above or below gender-
speciﬁc young adult mean peak bone mass.
WHO diagnostic thresholds for osteopenia
and osteoporosis have been widely adopted
for identifying postmenopausal women with
osteoporosis and identifying men/women
with substantial fracture risk.
WHO diagnostic criteria are often confused
with treatment thresholds or inappropriately
applied to other patient groups including
patients with chronic SCI.
The WHO diagnostic criteria for osteo-
porosis were intended for postmenopausal
women. There remains uncertainty in os-
Table 4. Fracture thresholds and fracture breakpoints for knee region BMD among patients with
Name Value Deﬁnition
≤ 0.78 g/cm
Knee region BMD values below which fragility
Knee region BMD values at which the majority of
fragility fracture occur
Note: BMD = bone mineral density; aBMD = areal BMD (DXA); vBMD = volumetric BMD (p-QCT).
Mazess R. Bone densitometry of the axial skeleton. Orthop Clin North Am. 1990;21(1):53–63.
Garland DE. Fracture threshold and fragility fracture risk after SCI. Topics Spinal Cord Inj Rehabil. 2005;11:61–69.
Eser P, Frotzler A, et al. Assessment of anthropometric, systemic and lifestyle factors inﬂuencing bone status in the legs of
spinal cord injured individuals. Osteoporosis Int. 2005;16(1):26–34.
8 Topics in spinal cord injury rehabiliTaTion/spring 2009
teoporosis literature as to how to diagnose
osteoporosis or identify patients in other
groups (e.g., men under age 50 and premeno-
pausal women) in need of treatment based on
The majority of patients with
chronic SCI fall into the group for whom
there is uncertainty over both diagnostic cri-
teria and rational intervention thresholds.
The ISCD has recommended a Z score
of ≤ -2.0 SD as a rational threshold for ini-
tiation of therapy in men under age 50 and
Z scores indicate
how an individual’s BMD compares to
age-matched peers. The National Osteopo-
rosis Foundation (USA) recommends the
initiation of “therapy to reduce fracture risk
in postmenopausal women with BMD T-
scores by DXA below -2.0 in the absence of
risk factors and in postmenopausal women
with T-scores below -1.5 if one or more risk
factors are present.”
An association be-
tween SLOP (i.e., low BMD of the hips and
knee region) and fracture risk post SCI has
been consistently described.
For men with
SCI, Lazo et al demonstrated a 2.8 increase in
relative risk of fracture for each 1
ment in femoral neck BMD T score. After
consideration of other confounding vari-
ables, including the subjects’ age and time
post injury, low BMD was found to be the
strongest predictor of fracture risk.
intervention threshold of a hip or knee region
Z score of ≤ -2.0 is proposed after SCI for
premenopausal women and young men with
three or more risk factors for fracture. This
intervention threshold is intended to have
face validity among osteoporosis and SCI
Does my patient have a knee region BMD
below the fracture threshold?
Fracture thresholds are BMD values be-
low which fractures begin to occur, whereas
fracture breakpoints are values at which the
majority of fractures occur.
of a fracture threshold has been rejected for
postmenopausal osteoporosis based on recent
which demonstrated a lin-
ear relationship between BMD and fracture
risk. In contrast, use of a fracture threshold
appears to be gathering support among SCI
clinicians and researchers, based on data from
recent studies that identify aBMD and vBMD
threshold values below which there are sig-
niﬁcant increases in the incidence of lower
extremity fragility fractures. aBMD values of
the distal femur and proximal tibia are able to
distinguish SCI patients at increased risk for
lower extremity fragility fracture.
Among male SCI patients, Garland and
colleagues reported fracture thresholds
at the knee of 0.78 g/cm
and a fracture
breakpoint of 0.49 g/cm
In another study,
fracture thresholds for the femur and tibia
were identiﬁed as a distal femoral epiphy-
sis trabecular vBMD <114 mg/cm
proximal tibia epiphysis trabecular vBMD
among patients with motor
These vBMD values cor-
respond to 46% of mean femur aBMD and
29% of mean tibia aBMD, respectively, for
their reference group without SCI. Distal
femur BMD below the fracture threshold and
fracture breakpoint results in moderate and
high fracture risk, respectively. Increases in
BMD may be a suitable surrogate outcome
measure for fracture reduction when assess-
ing the effectiveness of SLOP therapy, with
“optimal therapy” resulting in an increase
in knee region BMD above the fracture
threshold. We advocate treatment of SLOP
among persons with chronic SCI based on
the criteria proposed in Table 5.
Detection and Treatment of Sublesional Osteoporosis 9
Should I offer treatment to my patient?
Having identiﬁed a patient with low BMD
of the hip or knee region (Z score ≤ -2.0) and
an increased risk of lower extremity fragility
fracture (≥3 risk factors), the clinician must
then consider treatment. Figure 2 presents
a diagram outlining a four-step process for
treatment: health status, lifestyle, nutrition,
and bone factors.
Does my patient have causes of low BMD
amenable to treatment?
Health status treatments focus on treating
the identiﬁed condition, decreasing dosages
or changing to an alternate medication, and
longitudinal monitoring of the condition if
warranted. Identifying and targeting a single
secondary cause of osteoporosis is relatively
simple, however, multiple etiologies are often
identiﬁed. For example, a 52-year-old male
with T10 paraplegia is identiﬁed as having
hypogonadism and neuropathic pain for
which he takes carbamazepine. Treatment of
his hypogonadism will result in substantial
BMD accrual; switching from carbamazepine
to pregabalin for treatment of his neuropathic
pain may prevent further declines in BMD.
An alternate example is a 42-year-old pre-
menopausal woman with C6 tetraplegia,
hypothyroidism, and vitamin D deﬁciency.
Her vitamin D deﬁciency has resulted in
secondary hyperparathyroidism, and she has
been taking excessive doses of her thyroid
replacement because of the associated fatigue.
Correcting her vitamin D deﬁciency will re-
duce her serum calcium level and perceived
fatigue and, provided she is eucalcemic, al-
low her thyroid replacement to be titrated to
within the normal reference range with serial
monitoring. There are many published guide-
lines for the treatment of non-SCI causes of
osteoporosis. The reader is advised to visit the
appropriate osteoporosis society websites for
links to these guidelines.
Are there lifestyle factors that, if targeted,
would improve my patient’s BMD or reduce
his or her fracture risk?
The second area to consider when initiat-
ing treatment for SLOP is the inﬂuence of
lifestyle factors, in particular, the effects of
Table 5. Deﬁnition of sublesional osteoporosis (SLOP)
Age range Deﬁnition
Men ≥ 60 years or
Hip or knee region T score ≤-2.5
Men <59 years or
Hip or knee region Z score <-2.0 with ≥3 risk factors for
Men or women age 16–90 Prior fragility fracture and no identiﬁable etiology of
osteoporosis other than SCI
10 Topics in spinal cord injury rehabiliTaTion/spring 2009
Figure 2. Paradigm for treatment of sublesional osteoporosis (SLOP) and/or fragility fracture
risk after SCI.
Detection and Treatment of Sublesional Osteoporosis 11
alcohol, smoking, and caffeine consump-
tion on BMD and the effects of aging and
mobility on fracture risk. The intake of each
of these substances can be determined with
formal standardized assessment tools or by
asking the patient about current and past
alcohol consumption, smoking, and caffeine
intake. Although no longitudinal studies
have prospectively evaluated the relation-
ship between smoking, caffeine, alcohol, and
BMD among persons with SCI, their effects
on global health and the weight of evidence
from meta-analyses of their inﬂuence on
BMD in able-bodied persons suggest they
are prudent behavioral targets.
Does my patient consume excessive
amounts of alcohol?
Alcohol consumption is one of the most
common risk factors for low BMD among
This warrants signiﬁcant
attention given that 21% of patients post re
habilitation discharge fall in the “alcoholic
range” or the “at risk range” on the Short
Michigan Alcoholism Screening Test.
Canada’s low-risk drinking guidelines rec-
ommend no more than 2 standard drinks per
day, no more than 9 servings of alcohol per
week for women, and no more than 14 per
week for men.
Our recent cohort study
(previously discussed) assessed alcohol con-
sumption among study subjects (bottles per
week, glasses of wine per week, and ounces
of liquor per week). Thirty-one percent of
the cohort reported alcohol intake in excess
of 17 servings per week, a clear target for
Which smoking cessation strategy would
be best to recommend?
Several studies from the United States
have reported that a simple history of smok-
ing duration is as good (in terms of valid-
ity) as trying to obtain detailed smoking
There are sufﬁcient data from
able-bodied osteoporosis studies to identify
a causal relationship between smoking and
low BMD. BMD is lower in smokers versus
nonsmokers, and the difference increases
linearly with age.
have demonstrated higher rates of decline in
BMD among male smokers versus nonsmok-
ers. Smoking cessation may slow or partially
reverse the inﬂuence of longitudinal smok-
ing on BMD. The prevalence of smoking in
patients with chronic SCI is 31%–35%.
The National Health Interview Study in the
United States revealed that smoking among
young women with disabilities is nearly
double the rate of smoking among young
women in the general population.
reader is directed to several guidelines for
assisting patients with smoking cessation.
Interventions include, but are not limited to,
counseling strategies and seven medications
that have been shown to be efﬁcacious in
facilitating smoking cessation.
no published contraindications to current
smoking cessation programs for persons
Is my patient’s caffeine intake excessive?
In our cohort study, many subjects (51.5%,
n = 33) were current caffeine drinkers, with
a mean intake of two cups per day (range
0–6). A caffeine intake greater than three
servings per day increases urinary calcium
excretion, potentially exacerbating bone
resorption. Because the amount of caffeine
in a single serving of cola, coffee, and tea
varies signiﬁcantly, the reader should famil-
12 Topics in spinal cord injury rehabiliTaTion/spring 2009
iarize himself or herself with a caffeine
It is also important
to consider the compounding effects alcohol,
caffeine, and smoking history may have in a
single individual with SLOP.
Does my patient participate in high risk
activities or contact sports?
Many individuals with SCI participate in
contact or high-risk sports that have numer-
ous physical and psychological beneﬁts.
As a result, patients should be counseled
regarding (a) their choice of sport or high-
risk activity (i.e., parachuting); (b) the role of
protective equipment (helmet, shin guards,
wrist guards, and wheelchair modifica-
tions); and (c) the need for a high index of
suspicion when they note regional swelling
or visible deformity or after a collision/fall.
These strategies may reduce the incidence
of sports-related fractures and increase the
detection of fragility fractures.
Mobility and aging
Has there been an interim decline in my
patient’s mobility or transfers?
Not infrequently, individuals aging with
SCI develop functional declines in their mo-
bility that manifest as changes in gait, use of
mobility aids, and deteriorating transfers.
A careful review of functional abilities and
transfer technique may prevent future fragil-
ity fractures. For individuals who walk, a
discussion of strategies to reduce the risk of
falls in the home is suggested.
Does my patient’s nutrition status contrib-
ute to their SLOP?
Ensuring SCI patients with SLOP receive
sufﬁcient calcium and vitamin D, either
from diet or supplements, is essential; how-
ever, there are currently no evidence-based
recommendations or consensus statements
addressing optimal calcium intake after
SCI. What follows is a discussion of cal-
cium metabolism, assessment of dietary
adequacy, and treatment recommendations
based on our experience and the able-bodied
Does my patient have an adequate, but not
excessive, calcium intake?
Given that calcium is required for miner-
alization of bone and vitamin D promotes
mentation has been an important adjunct to
The current Cana-
dian treatment guidelines for osteoporosis
recommend “routine supplementation with
calcium (1000 mg/d) and vitamin D3 (800
IU/d) as a mandatory adjunct therapy to the
main pharmacologic interventions (antire-
Canada recommends a dietary calcium in-
take of 1000 mg daily for men and women
age 10–50 years and 1500 mg per day for men
and women over 50 years of age.
Individuals with SCI have dietary calcium
intakes that are less than or equivalent to age-
After SCI, Levine et al
reported mean calcium intake to be 550.0 ±
268.3 mg and 525.0 ± 262.9 mg per day for
men and women, respectively. Tomey re-
ported a mean calcium intake of 755 ± 268.3
mg per day for men with chronic SCI; 43%
did not meet the recommended minimum
calcium requirements of 670 mg/day.
We found that the mean calcium intake of
patients with SCI (n = 87) was 870–1087
mg for men and 848–1087 mg per day for
Detection and Treatment of Sublesional Osteoporosis 13
women, based on 24-hour dietary recall data.
The majority of men ingested less than two
thirds of the Osteoporosis Canada guideline,
with the most deﬁcient group being men and
women 51 to 68 years old.
Factors that decrease calcium absorption
include dietary ﬁber, phytates, oxalate found
in vegetables (spinach, okra, celery), fruit
(berries, currants), nuts (peanuts, pecans),
caffeinated beverages (tea, cocoa), free
fatty acids, magnesium, and phosphorous.
Calcium absorption is increased by 1,25
hydroxyvitamin D levels and lactose. Some
medications including but not limited to
glucocorticoids, anticonvulsants, and alumi-
num-containing antacids decrease calcium
absorption. Excessive dietary calcium intake
can precipitate renal or bladder stones post
SCI in persons with hypercalciuria
can exacerbate constipation. Asymptom-
atic renal and bladder stones are frequently
identiﬁed during routine renal and bladder
ultrasounds or cystoscopy in patients with
SCI. Symptomatic stones present as shale or
blood in the urine or as urosepsis and renal
failure in the event of ureter obstruction.
Current calcium intake can be quantiﬁed
during a patient encounter via a food fre-
quency questionnaire or food record. Dietary
adequacy is determined by adding the total
dietary intake (mg) to any supplements.
We generally recommend a dietary calcium
intake of 1000 mg per day for patients with
SCI and SLOP and no premorbid or post-
SCI history of renal or bladder calculi. This
calcium recommendation is equivalent to
the Osteoporosis Canada guideline
the treatment of osteoporosis in men and
women 19 to 49 years old. This level of
intake is intended to promote increases in
BMD while minimizing the risk of renal and
bladder stone formation. SCI patients with
a history of recurrent calcium oxalate or cal-
cium citrate stones or with signiﬁcant renal
impairment should be advised to lower their
calcium intake to 500––666 mg and start a
low oxalate diet; however, the instructions
to the patient depend on the severity of renal
impairment and stone type. There is a small
subset of SCI patients for whom 1500 mg
per day of calcium is recommended. These
include young men or women who have
not achieved peak bone mass, pregnant or
breast-feeding women, and elderly patients
with insufﬁcient dietary intakes.
For patients with insufﬁcient calcium
intake, calcium absorption can be enhanced
by taking supplements in divided doses, no
more than 400–500 mg at a time. Absorp-
tion is maximized when calcium is ingested
concurrently with a meal, while avoiding
co-ingestion of oxalate and phytates. Op-
timal calcium intake refers to the level of
consumption necessary for an individual
with SLOP to (a) maximize peak adult BMD,
(b) maintain BMD, and (c) minimize decline
in BMD with aging. No prior study has dem-
onstrated that adequate calcium intake alone
will maintain BMD; however an adequate
intake is an essential adjunct to oral alendro-
nate in patients with SCI and SLOP.
Does my patient have an adequate but not
excessive vitamin D intake?
Adequate, but not excessive, dietary
calcium intake is important for maintaining
BMD after SCI, but adequate vitamin D
intake is also necessary to facilitate calcium
absorption. Adequate doses of vitamin
D have been shown to augment BMD as
well as reduce coronary artery disease and
cancer risk among able-bodied persons.
Osteoporosis Canada recommendations and
14 Topics in spinal cord injury rehabiliTaTion/spring 2009
regional practices suggest a daily supple-
ment of 800–1000 IU of vitamin D
Others advocate a sliding scale for vitamin
supplementation: <30 years of age, 4,000
IU/day; 30–40 years of age, 3,000 IU/day;
41–50 years of age, 2,000 IU/day; and 51–75
years of age, 1,000 IU/day.
Most individuals with SCI have inad-
equate dietary vitamin D intake and require
supplements to ensure optimal intake.
though many persons with SCI take supple-
ments, optimal vitamin D intake should be
established via repeated measurement of
serum levels to ensure they are within the
A 32% prevalence of
vitamin D deﬁciency (25-hydroxyvitamin
D serum levels) and 24% prevalence of as-
sociated mild secondary hyperparathyroid-
ism was reported in a cohort of 100 subjects
with chronic SCI.
A more recent study
reported a 100% prevalence of vitamin D
deﬁciency among subjects with chronic SCI
living in Chicago and 67% of subjects with
chronic SCI living in Alabama.
exposure to sunlight is often inadequate
and compounded by lifestyle or environ-
ment-imposed mobility restrictions. Other
etiologies of vitamin D deﬁciency include
sunscreen, lactose intolerance, and altered
vitamin D metabolism due to prescription
(cholecalciferol) is synthe-
sized in the skin from dehydrocholesterol in
response to ultraviolet light exposure (UV
B). Vitamin D
(ergocalciferol) is found in
plants. Dietary sources of vitamin D are rare
but include fortiﬁed milk, margarine, eggs,
and ﬁsh oils. Carbamazepine and valproic
acid are medications commonly used for the
treatment of neuropathic pain post SCI that
may accelerate vitamin D metabolism.
Baumann and colleagues studied the relative
potency of vitamin D
versus vitamin D
SCI subjects and reported that vitamin D
was 9.5 times as potent as vitamin D
etiology of the difference in potency between
post SCI, as opposed to
the general population, is unclear. Baumann
et al recommended a minimum daily intake
of 800 IU vitamin D
in the ﬁrst 0–24 months
This recommended vitamin D
intake is consistent with the Osteoporosis
Canada recommendations. In summary, cal-
cium 1000 mg/day and vitamin D
IU/day are recommended routinely for
chronic SCI, provided there is no history of
renal or bladder stones, renal impairment,
or heterotopic ossiﬁcation. For SCI patients
with these impairments, vitamin D
should be adjusted to maintain serum levels
in the lower limits of the normal range. Op-
timal vitamin D intake should be conﬁrmed
with serial measurements of vitamin D (1,25
and 25-OH) levels. Once optimal intake is
achieved, interim monitoring of adherence
Is my patient’s BMD low enough or fracture
risk high enough to warrant treatment?
After implementing diet and lifestyle
modifications, clinicians must consider
rehabilitation and/or drug treatments for
SLOP. In addition, we advocate addressing
any modiﬁable risk factors for fracture and
counseling the patient regarding common
mechanisms of fracture and how to reduce
fracture risk during transfers. Despite the
high prevalence of lower extremity fragility
fractures and associated morbidity, no guide-
lines currently exist regarding the treatment
of SLOP after SCI. The following is a brief
review of the current SLOP treatment litera-
ture and the clinical implications.
Detection and Treatment of Sublesional Osteoporosis 15
Will my patient beneﬁt from rehabilitation
There are 18 published studies that have
examined the treatment of SLOP after
Two evaluate the efﬁcacy of oral
bisphosphonate therapy and are discussed
in detail in the section on bisphosphonate
trials. Sixteen are rehabilitation interven-
tion studies: seven evaluate the efﬁcacy
of weight-bearing exercise, one evaluates
vibration, and eight evaluate different forms
of functional electrical stimulation (FES).
Evaluated weight-bearing activities include
passive standing, tilt table, reciprocating
gait orthoses, and body weight–supported
treadmill training. To date, none of the
weight-bearing studies have demonstrated
a signiﬁcant or sustained increase in BMD
of the hip or knee region.
evaluated vibration with modest results.
FES refers to a group of therapies in which an
electrical current is applied to muscle(s) via
an implanted or surface electrode to stimu-
late weak or paralyzed muscles to contract.
Microprocessors can generate contractions
in controlled sequences thereby facilitating
the performance of functional activities such
as walking, standing, and bicycling— activi-
ties that would not be possible otherwise.
Of the eight FES studies, ﬁve evaluated
and three evalu-
ated FES of the quadriceps.
and colleagues reported increased lower
extremity BMD in paraplegic men following
6 months of FES-cycle ergometry, but the
increase in BMD was not sustained follow-
ing discontinuation of FES.
In summary, none of the 16 rehabilitation
interventions led to sustained increases in
hip or knee region BMD in subjects with
SCI and SLOP. A recent systematic review
by Biering-Sorensen et al provides a detailed
evaluation of the nonpharmacological inter-
ventions for prevention of bone loss after
spinal cord injury and further highlights the
lack of efﬁcacy of rehabilitation interven-
In persons with chronic SCI and
SLOP, rehabilitation interventions may be
ineffective due to prolonged suppression of
osteocyte and osteoblast activity.
It is also
plausible that short durations of treatment,
small sample sizes, or insufﬁcient mechani-
cal stress may have resulted in the lack of
treatment effect to date. Relative contrain-
dications for these therapies include a sub-
luxed or dislocated hip, hip and knee ﬂexion
contractures >30 degrees (combined hip and
knee angle), nonunion of lower extremity
fractures, and a strong hip ﬂexor synergy.
Rehabilitation interventions may be offered
as an SLOP treatment option, provided the
limitations of the current literature and lim-
ited efﬁcacy are discussed with the patient
prior to initiation.
Will my patient beneﬁt from oral alen-
Alendronate inhibits osteoclast-mediated
bone resorption and binds to hydroxyapatite
To date, two trials (n = 84 subjects
have evaluated the efﬁcacy of
alendronate for treatment of SLOP in men
and premenopausal women. Using a ran-
domized open-label design, Zehnder et al
evaluated the effectiveness of alendronate
10 mg daily and elemental calcium 500 mg
daily versus elemental calcium 500 mg daily
(alone) for 24 months on BMD after SCI.
The study cohort consisted of 55 men with
motor complete SCI (para/tetraplegia, AIS A
or B) living in Switzerland. Injury duration
ranged from 1 month to 29 years post SCI,
16 Topics in spinal cord injury rehabiliTaTion/spring 2009
with group means of 10 years post injury.
The primary outcome was change in tibia
epiphysis BMD from baseline measured
using DXA. Secondary outcomes included
changes in BMD at the wrist, spine, and
total hip region and changes in biochemical
markers of bone turnover (i.e., osteocalcin).
The key ﬁndings included an 8.0% decline in
tibia epiphysis BMD in the control group and
relative maintenance of tibia epiphysis BMD
(-2.0%) in the treatment group (p < .001).
Changes in total hip BMD were similar to
the tibia, lumbar spine BMD increased in
both groups, and there were no signiﬁcant
changes in wrist BMD. Limitations of this
trial included the lack of blinding, failure
to stratify/randomize by duration of injury
or present subgroup analysis (e.g., separate
acute from chronic SCI), lack of an objective
evaluation of subject adherence to treatment
(self-report as opposed to pill counts), and
lack of concurrent treatment with vitamin D
Moran de Brito et al
conducted a 6-
month randomized control clinical trial (n =
19) of men age < 50 and women age < 35,
with paraplegia/tetraplegia, AIS A, B or C,
13–255 months post SCI in Sao Paulo, Bra
zil. The treatment group (n = 10) received
alendronate 10 mg daily and calcium 1000
mg daily, while the placebo group received
calcium 1000 mg daily. The outcomes of
interest were change in aBMD at 6 months,
as assessed by T and Z scores of the whole
body and upper and lower extremities mea-
sured via DXA. The mean increase in wrist
BMD was greater in the alendronate-treated
group. There were no signiﬁcant between-
group differences in the mean change of
lower extremity T scores or lower extremity
BMD. Strengths of this study include the
randomization and blinding procedures and
inclusion of a representative sample. Limita-
tions include the short duration of follow-up,
lack of a single primary outcome measure,
and failure to include biochemical markers
to assist in discerning whether a Type II
error had occurred. Although it is easy to
ﬁnd fault with trial data, these two opposing
studies are seminal in nature and should not
Based on the Zehnder data, we recom-
mend that patients with SLOP
and motor complete injuries (AIS A, B) be
treated with alendronate (10 mg daily or 70
mg weekly) and calcium (1000 mg daily in
divided doses). We also advocate titration
of vitamin D supplements to ensure a thera-
peutic serum level. As with all medications,
there are side effects and contraindications to
consider. Side effects of alendronate include
side effects (1%–10%), including abdomi
nal pain and dyspepsia,
and diarrhea; and rare but serious events
including osteonecrosis of the jaw, atrial
Alendronate should be used with caution in
premenopausal women due to the unknown
teratogenic effects of these medications;
patients with a prior history of cancer or
radiotherapy due to the risk of osteonecrosis
of the jaw; and patients taking acetylsalicylic
acid, corticosteroids, or nonsteroidal anti-
inﬂammatory drugs (NSAIDS) as concur-
rent use increases the relative risk of devel-
oping a gastric ulcer or bleeding. Periodic
assessment of adherence to alendronate is
indicated as >20% of the general population
stops treatment during the initial 6 months
of therapy due to gastrointestinal side effects
and cost. Alendronate may be taken safely
for 10–13 years after which a drug holiday
and/or discontinuation of therapy should be
Data from postmenopausal
non-SCI women suggest BMD should be
Detection and Treatment of Sublesional Osteoporosis 17
monitored at least alternate years in patients
who stop taking oral bisphosphonates. Those
with a rapid decline in BMD of >10% in 2
years or >5% from initial baseline should
be switched to alternate treatment or resume
There are no clinical trials evaluating drug
treatments of SLOP among patients with
motor incomplete injuries (AIS C and D).
Recent p-QCT data from Frotzler describ-
ing longitudinal changes in lower extremity
cortical and trabecular vBMD over time
suggest there is a therapeutic window (2–8
years post injury) during which antiresorp-
tive therapies are most likely to be effective
for SCI patients; after which they propose
that therapies which target bone formation
or osteoblast activity would be more ap-
propriate (i.e., recombinant PTH, whole
body vibration, FES-cycle ergometry).
further complicate the decision making, no
study has identiﬁed or evaluated the impact
of any intervention on fracture reduction,
the primary impetus for the detection and
treatment of SLOP.
The paradigms presented for the detection
and treatment of SLOP are based on our opin-
ions/expertise and interpretation of avail-
able published and unpublished literature
and are intended to guide clinician decision
making while highlighting the controversies
and gaps in the current SLOP literature. We
welcome discussion and dialogue regarding
the proposed paradigms.
We acknowledge Dr. Joanne Bugar-
esti for her thoughtful review and editorial
comments. Funding for the enclosed work
was provided by the Ontario Neurotrauma
Foundation, University of Toronto Division
of Physiatry, and the New Women’s Col-
lege Hospital, Toronto, Ontario. The authors
(B.C.C., L.A.R., and C.F.M.) also acknowl-
edge the support of Toronto Rehabilitation
Institute, which receives funding from the
Ministry of Health and Long Term Care in
Ontario through the Provincial Rehabilita-
tion Research Program.
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