Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 12, no.
4, 413e416, 2009
Copyright 2009 by The International Society for Clinical Densitometry
1094-6950/09/12:413e416/$36.00
DOI: 10.1016/j.jocd.2009.06.004
Editorial
Beyond FRAX: Its Time to Consider Sarco-Osteopenia
Neil Binkley* and Bjoern Buehring
University of Wisconsin-Madison Osteoporosis Clinical Center and Research Program, Madison, WI, USA
Alas, our frailty is the cause ..
William Shakespeare
A dictionary definition of frail includes easily
broken, fragile, and physically weak, the descriptors
often used to explain osteoporotic bone. However,
physicians recognize that it is not simply bone ab-
normalities, but rather the simultaneous presence
of muscle and bone weakness, often associated
with overall frailty, which contributes to high frac-
ture risk in their older patients. How can clinicians
optimally identify which patients are at highest
risk for fracture?
Bone mineral density (BMD) measurement by
dual-energy X-ray absorptiometry (DXA) has been
a key advance in care for patients at risk for fragility
fracture. Although DXA-measured BMD is excel-
lent at identifying those at higher risk, its use alone
is not optimal and including clinical factors im-
proves fracture risk estimation. To this end, the
World Health Organization (WHO) FRAX tool im-
proves targeting of pharmacologic therapy by com-
bining clinical risk factors and estimating 10-yr
fracture probability. Clearly, fracture risk increases
dramatically with advancing age (1); that this risk
markedly increases at the same BMD is easily
quantified using FRAX (depicted in Fig. 1). We
recognize the major contribution of FRAX to
patient care and further suggest, in addition to using
FRAX, that the time has come for clinicians
to consciously recognize muscle weakness as a
Received 5/19/2009; Revised 6/10/2009; Accepted 6/18/
2009.
*Address correspondence to: Neil Binkley, MD, University
of Wisconsin Osteoporosis Research Program, 2870 University
Avenue, Suite 100, Madison, WI 53705. Eemail: nbinkley@
wisc.edu
413
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contributor to age-related fracture risk. We ac-
knowledge that the increase in fracture risk with ad-
vancing age doubtlessly reflects multiple factors
including, among others, innate bone quality.
However, we believe that it is appropriate to em-
phasize that muscle mass loss (often referred to as
sarcopenia) plays a key role in fracture risk, as
this leads to a reduction in strength/power, func-
tional impairment, and falls (2,3).
The term sarcopenia (which literally means loss
of flesh) was coined a decade ago (4) to describe
the age-related decline in amount and function of
skeletal muscle. Although often appreciated by
clinicians, sarcopenia is rarely formally diagnosed.
This is not surprising, as there is currently no agree-
ment on an easily clinically applicable definition of
sarcopenia. One suggested approach is to assess
appendicular muscle mass by DXA, adjust this
value for height, and compare to a young normal
population. Sarcopenia would then be diagnosed
when an individuals value is 2 standard deviations
or more below young normal (5). Other work mod-
ifies this approach by adjusting for fat mass (6,7).
Comparing DXA data with those of a young normal
population is identical to the approach used in the
1994 WHO classification of low bone mass/osteope-
nia and osteoporosis. As such, this road has previ-
ously been traveled by the bone community and
found to be fraught with pitfalls, including differ-
ences in measured parameters between instruments,
differences in region of interest placement, and lack
of a standardized reference comparator population.
Moreover, this approach would cause healthy young
individuals with genetic low peak muscle mass to be
classified as low and therefore potentially receive
a disease diagnosis. Such a phenomenon is well
known to the osteoporosis community whereby
young individuals with low bone mass have been
414 Binkley and Buehring

simple muscle mass measurement by DXA

(16e19). Again, one is reminded of the osteoporosis
field where evaluation of bone structure and qual-
ity, and incorporation of these parameters into
clinical care, continues to evolve.
Currently, sarcopenia remains a condition without
consensus definition or optimal tools to identify and
monitor it and lacks consensus outcomes on which
to base efficacy of proposed therapeutic interven-
tions. Given the multiple existing uncertainties in
this area, is it premature to consider sarcopenia
when one is evaluating a patients fracture risk? We
Fig. 1. Effect of advancing age on fracture risk. The think that such consideration is not premature. More-
fracture risk for a 64-inch tall white US female weighing over, as falls and fractures are well defined and are ac-
135 pounds with a femur neck T-score of 3.0 was cepted outcomes, with quantifiable clinical costs and
calculated for various ages. A progressive increase in 10- consequences, we suggest that falls and fracture be
year fracture risk for both major osteoporosis-related considered as important (potentially the most impor-
fracture and hip fracture with advancing age is evident. tant) clinical consequences of sarcopenia. Although
Specifically, from age 50 to 80 year, the risk of major frac- astute physicians may consciously, or subcon-
ture increases approximately 3-fold from 11% to 32%. sciously, include the combined concept of bone weak-
ness and sarcopenia into their treatment decisions, we
believe that the time has come to emphasize the im-
diagnosed with osteopenia and inappropriately
portance of this duality, and suggest that the condition
prescribed therapy. Thus, we suggest that caution
of sarco-osteopenia or sarco-osteoporosis be
is required before embracing DXA-measured mus-
cle mass, and comparing the result with a young
normal referent, as the sole diagnostic criterion for
sarcopenia.
It seems probable that a consensus definition of
sarcopenia will emerge including not only muscle
mass but also muscle performance and quality (8)
(again, similar to the constructs of bone mass, struc-
ture and quality in the osteoporosis field) (9). DXA
does have advantages for the clinical diagnosis of
sarcopenia in that it is quantitative, widely available,
uses only a minimal amount of radiation, and carries
only modest expense. However, disadvantages to
a simple muscle massebased approach are worthy
of consideration, as (again, similar to bone) mass
is only part of the equation in muscle function. In
fact, while muscle mass declines with advancing
age, loss of strength is much more rapid than loss
of mass, documenting a decline in muscle quality
(10,11). As such, functional tests of muscle power/
function, for example, the timed up and go test, Fig. 2. We propose that patients with both low bone
chair-rising test, or tandem stance, more closely cor- mass and low muscle mass and/or performance be diag-
nosed with sarco-osteopenia or, if there is a clinical or
relate with subsequent risk of adverse health events,
densitometric diagnosis of osteoporosis, with sarco-
including functional limitation, hospitalization, and osteoporosis. This combination could be expected to
even death, than does muscle mass (12e15). Addi- identify individuals as being at higher fracture risk than
tionally, other age-related changes in muscle quality currently appreciated. Identification of this high-risk
occurring at the neuromuscular, tissue/cellular (e.g., group could lead to nonpharmacologic and ultimately
fiber composition/ muscle fat infiltration), or subcel- to use of pharmacologic treatments that enhance bone
lular (e.g., mitochondrial) level will be missed with and muscle function.

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Beyond FRAX
proposed to facilitate identification of patients at high
fracture risk. Using this approach, sarco-osteope-
nia would be appropriate for individuals with low
bone mass and low muscle mass, whereas sarco-os-
teoporosis would be applied to those with low mus-
cle mass and clinical or densitometric osteoporosis.
Combining loss of bone and muscle strength into
a single diagnosis of sarco-osteopenia (schemat-
ically represented in Fig. 2) seems rational, given
the abundant literature documenting the positive re-
lationship of muscle and bone mass, due in part to
muscle-induced skeletal strain (20e22). Addition-
ally, age-related declines in bone mass and muscle
mass/strength often coexist and may well result
from common pathophysiologic mechanisms, such
as inflammation (23) or low vitamin D status (24).
Moreover, that sarco-osteopenia is a reasonable
diagnostic and therapeutic consideration is sup-
ported by observations that falls cause fractures,
that fracture risk increases with aging (even at the
same BMD as noted above), and that virtually all
osteoporosis therapies reduce fragility fracture risk
by only approximately 50%, perhaps implying that
medications affecting only bone to the exclusion
of other patient factors, for example, muscle, may
have reached a near maximal benefit. Consistent
with a need to consider muscle parameters in frac-
ture risk assessment, we find the recent report of
Lang et al (25) to be a landmark work documenting
that combining muscle size and a measure of intra-
muscular fat, as determined by quantitative com-
puted tomography (QCT) with age, height, body
mass index, and BMD, maximized the true-positive
rate of identifying those with hip fracture.
Is it feasible to bring the sarco-osteopenia concept
to clinical care? If so, how can this be accomplished?
In this regard, DXA may well be an excellent technol-
ogy to identify sarco-osteopenia. Obviously, appen-
dicular lean mass, perhaps limited to the legs, or
altered by fat mass or other yet to be defined
approach, could be formally obtained by total body
measurement at the time of routine clinical DXA. Ad-
ditionally, routine hip DXA can provide not only
BMD data but also an estimate of lean muscle mass.
With such DXA measurements of muscle mass, it
seems likely that no one cutpoint approach to de-
fine sarco-osteopenia will apply to all individuals
and that clinical judgment/individualization of care
will be required, an approach very analogous to
BMD. Although it is premature to recommend thera-
peutic interventions based on sarco-osteopenia cut-
points, we note that the National Osteoporosis
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415
Foundation Clinicians Guide clearly states Deci-
sions on whom to treat and how to treat should be
based on clinical judgment using this guide and all
available clinical information. We suggest that low
muscle mass/function in the setting of low bone
mass (i.e., sarco-osteopenia) falls into the use of
all available clinical information category.
How to optimally define sarco-osteopenia remains
to be determined. Despite this, the sarco-osteopenia
concept can be clinically applied at this time to en-
courage use of readily available options to reduce
falls and fracture risk. Although review of such ap-
proaches is beyond the scope of this article, activities
to reduce falls risk and enhance muscle strength can
be encouraged once sarco-osteopenia is recognized.
Such interventions include, but are not limited to, nu-
tritional evaluation and correction of deficiencies, in-
cluding optimization of vitamin D status, physical
therapy, strength and balance training, gait-assistive
devices, home environment alterations, and discon-
tinuation of medications associated with increased
falls risk. These approaches are currently part of com-
prehensive fracture reduction care but are easy to
overlook; formal appreciation of the sarco-osteopenia
concept may enhance use of these interventions. Al-
though we believe that appreciation of sarco-osteope-
nia will enhance fracture reduction, we recognize that
it is not an all-encompassing diagnosis to identify
those at increased fracture risk. Importantly, it does
not include other morbidities amenable to existing
therapies (e.g., visual and cognitive impairment)
that must be addressed. It is apparent that evaluation
of the patient, rather than just the bone or bone and
muscle status, is essential for optimal fracture
reduction.
In conclusion, we suggest that the sarco-osteope-
nia concept be consciously incorporated into routine
clinical care. It is not the purpose of this perspective
to recommend precisely how, or in which patients,
to do so at this time. Rather, it is our goal to promote
this concept, to call for additional research to further
refine the relationship of muscle mass/performance
with fracture risk, and to define how to optimally in-
corporate the sarco-osteopenia model clinically,
thereby reducing morbidity, mortality, and expense
of fragility fractures. Additionally, based on the his-
tory of osteoporosis diagnosis, we suggest that if
DXA becomes a key tool in diagnosing sarcopenia
or sarco-osteopenia, it is essential to determine
whether results obtained by densitometers of various
manufacturers provide comparable results. More-
over, if comparison with a young reference
Volume 12, 2009
416
population is used, prompt agreement on, and adop-
tion of, a standard reference database is necessary. Fi-
nally, continued improvement in understanding the
basic mechanisms of sarcopenia/sarco-osteopenia is
required, as is further evaluation, and perhaps devel-
opment, of clinical tools to optimize identification
of impaired muscle function in older adults. Ulti-
mately, one could envision nonpharmacologic and
pharmacologic interventions treating both the muscle
and bone components of sarco-osteopenia, with resul-
tant prolongation of healthy life span and reduction of
health care costs related to fragility fractures.
References
1. Cooper C, Melton LJ. 1992 Epidemiology of osteoporosis.
Trends Endocrinol Metab 3:224e229.
2. Morley JE. 2008 Sarcopenia: diagnosis and treatment.
J Nutr Health Aging 12:452e456.
3. Janssen I, Heymsfield SB, Ross R. 2002 Low relative skel-
etal muscle mass (sarcopenia) in older persons is associated
with functional impairment and physical disability. J Am
Geriatr Soc 50(5):889e896.
4. Rosenberg IH. 1997 Sarcopenia: origins and clinical rele-
vance. J Nutr 127(5 Suppl):990Se991S.
5. Baumgartner RN, Koehler KM, Gallagher D, et al. 1998
Epidemiology of sarcopenia among the elderly in New
Mexico. Am J Epidemiol 147(8):755e763.
6. Newman AB, Kupelian V, Visser M, et al. 2003 Sarcopenia:
alternative definitions and associations with lower extremity
function. J Am Geriatr Soc 51:1602e1609.
7. Delmonico MJ, Harris TB, Lee JS, et al. 2007 Alternative
definitions of sarcopenia, lower extremity performance,
and functional impairment with aging in older men and
women. J Am Geriatr Soc 55:769e774.
8. Rolland Y, Czerwinski S, Abellan Van Kan G, et al. 2008
Sarcopenia: its assessment, etiology, pathogenesis, conse-
quences and future perspectives. J Nutr Health Aging 12:
433e450.
9. Seeman E, Delmas P. 2006 Bone qualitydthe material and
structural basis of bone strength and fragility. N Engl J Med
354:2250e2261.
10. Metter EJ, Conwit R, Tobin J, Fozard JL. 1997 Age-associ-
ated loss of power and strength in the upper extremities in
women and men. J Gerontol A Biol Sci Med Sci 52A:
B267eB276.
11. Goodpaster BH, Park SW, Harris TB, et al. 2006 The loss of
skeletal muscle strength, mass and quality in older adults: the
health aging and body composition study. J Gerontol A Biol
Sci Med Sci 61A:1059e1064.
Journal of Clinical Densitometry: Assessment of Skeletal Health
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For personal use only. No other uses without permission. Copyright 2017. Elsevier Inc. All rights reserved.
Binkley and Buehring
12. Bean JF, Leveille SG, Kiely DK, et al. 2003 A comparison
of leg power and leg strength within the InCHIANTI study:
which influences mobility more? J Gerontol A Biol Sci
Med Sci 58A:728e733.
13. Cesari M, Kritchevsky SB, Newman AB, et al. 2009 Added
value of physical performance measures in predicting ad-
verse health-related events: results from the health, aging
and body composition study. J Am Geriatr Soc 57:
251e259.
14. Guralnik JM, Ferrucci L, Pieper CF, et al. 2000 Lower ex-
tremity function and subsequent disability: consistency
across studies, predictive models, and value of gait speed
alone compared with the short physical performance battery.
J Gerontol A Biol Sci Med Sci 55(4):M221eM231.
15. Newman AB, Kupelian V, Visser M, et al. 2006 Strength, but
not muscle mass, is associated with mortality in the health,
aging and body composition study cohort. J Gerontol A
Biol Sci Med Sci 61:72e77.
16. Waters DL, Mullins PG, Qualls CR, et al. 2009 Mitochon-
drial function in physically active elders with sarcopenia.
Mech Ageing Dev 130:315e319.
17. Hakkinen K, Kraemer WJ, Newton RU, Alen M. 2001
Changes in electromyographic activity, muscle fibre and
force production characteristics during heavy resistance/
power strength training in middle-aged and older men
and women. Acta Physiol Scand 171:51e62.
18. Hakkinen K, Kraemer WJ, Kallinen M, et al. 1996 Bilat
eral and unilateral neuromuscular function and muscle
cross-sectional area in middle-aged and elderly men and
women. J Gerontol A Biol Sci Med Sci 51A:B21eB29.
19. Goodpaster B, Chomentowski P, Ward BK, et al. 2008 Ef-
fects of physical activity on strength and skeletal muscle fat
infiltration in older adults: a randomized controlled trial.
J Appl Physiol 105:1498e1503.
20. Burr DB. 1997 Muscle strength, bone mass, and age-related
bone loss. J Bone Miner Res 12:1547e1551.
21. Proctor DN, Melton LJI, Khosla S, et al. 2000 Relative in-
fluence of physical activity, muscle mass and strength on
bone density. Osteoporos Int 11:944e952.
22. Khosla S, Atkinson EJ, Riggs BL, Melton LJI. 1996 Rela-
tionship between body composition and bone mass in
women. J Bone Miner Res 11:857e863.
23. Cauley JA, Danielson ME, Boudreau RM, et al. 2007 In-
flammatory markers and incident fracture risk in older
men and women: the Health Aging and Body Composition
study. J Bone Miner Res 22:1088e1095.
24. Wicherts IS, van Schoor NM, Boeke AJP, et al. 2007 Vita-
min D status predicts physical performance and its decline
in older persons. J Clin Endocrinol Metab 92:2058e2065.
25. Lang T, Koyama A, Li C, et al. 2008 Pelvic body compo-
sition measurements by quantitative computed tomography:
association with recent hip fracture. Bone 42:798e805.
Volume 12, 2009