LITERATURE REVIEW

Is Charcot Arthropathy a Late Sequela of

Osteoporosis in Patients with Diabetes
Mellitus?
Michael Childs, DPM,1 David G. Armstrong, DPM,1 and Gary W. Edelson, MD2

It is well accepted that Charcot arthropathy is most frequently encountered in the diabetic population.
Also well known is the association between diabetes and osteoporosis, even in the absence of overt renal
dysfunction. Is it plausible that Charcot arthropathy is a late sequela of osteoporosis in diabetic patients,
and if so, can the osteoporosis be treated early, leading to a decrease in the ultimate prevalence of
Charcot arthropathy? The objective of this paper is to concisely review the literature detailing the course
of Charcot neuroarthropathy and to investigate the links between Charcot arthropathy and osteoporosis
among diabetic patients. (The Journal of Foot & Ankle Surgery 37(5):437 -439, 1998)

Key words: arthropathy, charcot, diabetes, osteoporosis

It is well accepted that neuropathic osteoarthropathy,
commonly referred to as "Charcot arthropathy" or "Charcot
joint" is most frequently encountered in the diabetic popu-
lation (1-4). Also well known is the association between
diabetes and osteoporosis, even in the absence of overt renal
dysfunction (5). Is it plausible that Charcot arthropathy is a
late sequela of osteoporosis in diabetic patients, and if so,
can the osteoporosis be treated early, leading to a decrease
in the ultimate prevalence of Charcot arthropathy? The
objective of this paper is to review concisely the litera-
ture detailing the course of Charcot neuroarthropathy and
to investigate the links between Charcot arthropathy and
osteoporosis among diabetic patients.
Charcot Arthropathy
Charcot neuroarthropathy is a debilitating disease
characterized by joint dislocation, pathologic fractures,
From Ithe Department of Orthopaedics, University of Texas Health
Science Center, San Antonio, TX and 2 the Department of Medicine,
Division of Endocrinology, Wayne State University School of Medicine,
Detroit, MI. Address correspondence to: David G. Armstrong, Assistant
Professor, Department of Orthopaedics, University of Texas Health
Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7776.
Received for publication April 1998; accepted in revised form for
publication June 1998.
The Journal of Foot & Ankle Surgery 1067-2516/98/3705-0437$4.00/0
Copyright © 1998 by the American College of Foot and Ankle Surgeons
and severe deformity of the foot of neuropathic patients
(1, 3). In the United States alone there are an estimated
375,000 patients with diabetes mellitus who suffer from
this condition. The malady was perhaps first described by
Musgrave in 1703 and later in 1868 by the renowned
French neurologist Jean Martin Charcot whose name
it now bears (6, 7). It was initially described in
patients with tertiary syphilis. However, as persons with
diabetes mellitus began to live longer, diabetes overtook
syphilis as the predominant disease associated with the
arthropathy (8). Today Charcot arthropathy affects up to
29% of diabetic patients with peripheral neuropathy with
apparently no gender predilection (9). Patients generally
are in their 5th or 6th decade of life, but the disease
may be seen in the younger diabetic patient (3). In a
study undertaken by Sinha and colleagues (10), out of
101 diabetic patients, two-thirds were in the 5th and 6th
decades, while 96 of 101 had diabetes for greater than
6 years. Boehm's study revealed the onset of Charcot
arthropathy in patients who had the disease between 2
and 12 years.
The etiology is controversial. However, it has, in the
past, included two potentially conflicting theories. The
first theory, known as the French theory, was initially
proposed by Charcot himself. He suggested that arthritic
changes were the result of damage to the central nervous
system within the centers that control bone and joint
nutrition (7). One may expand this theory to indicate

VOLUME 37, NUMBER 5, SEPTEMBER/OCTOBER 1998 437

that changes consistent with Charcot arthropathy are due
to an autonomic neuropathy causing vasodilation and
increased blood flow due to the loss of sympathetic
tone and constrictive control of the blood vessel. This
would then lead to osseous hyperemia and resultant osteo-
porosis. This concept was given support by the work of
Edmonds and co-workers, who reported a link between
neuropathy and increased bony uptake of radiopharma-
ceutical (11).
The second theory, known as the German theory,
was popularized by Volkman and Virchow. This concept
suggests that the changes in the bone were a result of
"a multiplicity of subclinical traumata which went unper-
ceived because of the insensitivity of the affected joints"
(12, 13). Armstrong and Lavery indirectly lent support
to this theory by identifying significantly increased fore-
foot pressures in new-onset midfoot Charcot arthropathy
compared with neuropathic patients without arthropathy,
suggesting that this phenomenon, coupled with the pull
of the Achilles tendon in the rearfoot, may precipitate the
most common patterns of pedal Charcot arthropathy (14).
The current theory suggests that following the develop-
ment of autonomic neuropathy, there is an increased blood
flow to the extremity, resulting in osteopenia (1). Subse-
quently, motor neuropathies result in muscle imbalance,
which places abnormal stress on the affected extremity,
while sensory neuropathy renders the patient unaware
of the often profound osseous destruction taking place
(1). Treatment is directed at immobilizing the extremity
until the inflammatory process has resolved (3). It is
expected that the bones are much more demineralized in
the state of hyperemia and the foot should remain immo-
bilized until temperatures equilibrate with the contralat-
eral limb and show evidence of coalescence on x-
ray (15, 16).
Osteoporosis
Osteoporosis is a systemic skeletal disease character-
ized by low bone mass and microarchitectural deteri-
oration of bone tissue with a consequent increase in
bone fragility and susceptibility to fracture (17). It is
an important problem affecting 15- 20 million persons
in the United States (17). Prevalence of the disease
favors women by a factor of 2:1. However, among
diabetic patients there is no sexual predilection (5, 18).
Osteoporosis is characterized by an imbalance between
bone resorption and bone formation whereby bone mass
is lost over time. In general, once peak adult bone
mass is achieved, men without secondary causes and
women prior to the age of menopause lose approximately
0.25%-1 % of bone mass yearly. In the perimenopausal
period, women may lose 2%-5% of bone mass per
438 THE JOURNAL OF FOOT & ANKLE SURGERY
year. Without a doubt, the greatest single contributor
to bone is loss of gonadal function. Additional primary
factors associated with osteoporosis include advancing
age, Caucasian or Asian race, petite body habitus, rela-
tive physical inactivity, calcium poor diet, and long-term
use of antiepileptics or corticosteroids. In addition, there
are an extensive number of secondary causes of osteo-
porosis including diabetes mellitus, primary and secondary
hyperparathyroidism, hypovitaminosis D, and rheumatoid
arthritis (17).
Osteoporosis will affect those who have one or more
of a multitude of systemic problems including diabetes
mellitus (as described above) and the use of pharma-
cologic agents such as oral hypoglycemics (5). Because
bone mass is directly related to bone strength, the risk
of osteoporotic fracture increases with decreasing bone
mass. Furthermore, there is microarchitectural damage to
the trabecula of bone, which further contributes to bone
fragility. It is this element of the pathophysiology of osteo-
porosis which is essentially not reversible and is the reason
why prevention of the disease process is of such signifi-
cant importance.
Diabetes has been well documented as a secondary
cause of osteoporosis with a prevalence of 41-44% among
type 1 diabetic persons (5, 18). Levin also reported an
80% prevalence among those with type 2 diabetes (5).
Levin suggested that the inhibitory effects of insulin on
cyclic AMP caused persons with type 1 diabetes to be
somewhat spared as compared to those on oral hypo-
glycemic because the insulin causes a decrease in cyclic
AMP which in turn may relatively retard bone resorption.
Oral hypoglycemics, on the other hand, have the reverse
effect, causing an increase on cyclic AMP which increases
bone resorption (6). McNair and co-workers reported that
osteoporosis begins in the first 2 years after the onset of
diabetes and progresses steadily up to 5 years before stabi-
lizing (18).
Clinical aims of treatment for osteoporosis are to reduce
the risk of fracture and additionally to decrease the
morbidity due to existing fractures in patients with estab-
lished osteoporosis. Treatment for osteoporosis generally
is focused on medications which are inhibitors of bone
turnover. These include calcium, estrogens, and bisphos-
phonates (17). Additionally, treatment may include agents
that may assist in bone formation such as fluorides and
anabolic steroids. However, there is no current widespread
medical protocol for treatment used to treat diabetic
patients with osteoporosis.
Discussion
Certainly, the most compelling questions in this
milieu remain: What is the etiology of Charcot
neuroarthropathy and is it preventable? Can we treat
diabetic osteoporosis and decrease the incidence of the
debilitating pathologic fractures encountered in Charcot
arthropathy? We are unaware of any reports in the medical
literature conclusively linking Charcot arthropathy and
osteoporosis. To date, there have been a few relatively
small studies which have both directly and indirectly
indicated that there is an increased rate of bone remodeling
occurring in Charcot foot disease. Employing a urinary
marker of bone resorption, such as cross-linked N-
telopeptides of type I collagen (NTX), has indicated
increased levels of collagen breakdown in subjects with
Charcot neuroarthropathy (19). More recently, Gough and
co-workers (20) assayed both markers of osteoblastic and
osteoblastic activity in the foot as well as systemically.
They found that alkaline phosphatase was significantly
higher in patients with Charcot arthropathy compared to a
control group. Furthermore, the pyridinoline cross-linked
carboxy-terminal telopeptide domain of type I collagen
(ICTP) was significantly more prevalent in diabetic
patients with acute Charcot neuroarthropathy. These
results suggest that the acute Charcot foot demonstrates
excessive osteoblastic activity without the concomitant
increase in osteoblastic activity. Edmonds et al. found
reduced bone density in Charcot patients, suggesting
that autonomic neuropathy leads to increased osteoblastic
activity. This association was further corroborated by
Young and co-workers (21), who found significant loss of
bone mineral density in the lower limbs of patients with
Charcot arthropathy compared with matched neuropathic
non-Charcot patients. The synthesis of these concepts
would support the hypothesis that patients with Charcot
arthropathy have increased bone resorption accounting
for low bone mass. In the only interventional study
published to date, Selby and co-workers (22) performed
a nonrandomized, unblinded study using intravenous
pamidronate to determine its effects on limiting bone
destruction in acute Charcot arthropathy. In their study
of six consecutive patients, there was a significant and
rapid reduction in skin temperatures and plasma alkaline
phosphatase levels following pamidronate therapy. This
one study suggests that bisphosphonate may be a
potentially useful treatment for Charcot arthropathy
through its moderation of underlying bone destruction.
This association, however, clearly calls for further
research. However, based on these data, it is our opinion
that Charcot arthropathy is a metabolic bone disease that
presents locally but may have systemic manifestations as
well, with a pathophysiology analogous to osteoporosis.
As such, in the future, the optimal management of acute
Charcot arthropathy may include antiresorptive agents
such as those currently used in the prevention and
treatment of osteoporosis.
VOLUME 37, NUMBER 5, SEPTEMBER/OCTOBER 1998
References
I. Armstrong, D. G., Lavery, L. A. Acute Charcot's arthropathy of the
foot and ankle. Phys Ther. 78:74-80, 1998.
2. Frykberg, R. G. Osteoarthropathy. Clin. Podiatr. Med. Surg.
4:351-356, 1987.
3. Armstrong, D. G., Todd, W. F., Lavery, L. A., Harkless, L. B. The
natural history of acute Charcot's arthropathy in a diabetic foot
specialty clinic. Diabetic Med. 14:357-363, 1997.
4. Sanders, L. 1., Frykberg, R. G. Charcot's joint. In: The Diabetic
Foot, edited by M. E. Levin, L. W. O'Neal, 1. H. Bowker, 2nd ed.,
Mosby-Year Book, St. Louis, 1993.
5. Levin, M. E., Boisseau, V. c., Avioli, L. V. Effects of diabetes
mellitus on bone mass in juvenile and adult-onset diabetes. N. Engl.
1. Med. 294:241-245, 1976.
6. Kelly, M. William Musgrave's de arthritide symptomatica (1703):
His description of neuropathic arthritis. Bull. Hist. Med. 37:372- 376,
1963.
7. Charcot, J. M. Sur quelaques arthropathies qui paraissent depender
d'une lesion du cerveau ou de la moele epiniere. Arch. Physiol.
Norm. Pathol. 1:161-171, 1868.
8. Jordan, W. R. Neuritic manifestations in diabetes mellitus. Arch.
Intern. Med. 57:307-312, 1936.
9. Cofield R. H., Morrison, M. J., Beabout J. W. Diabetic neuro-
arthropathy in the foot: Patient characteristics and patterns of radio-
graphic change. Foot Ankle 4:15-22, 1983.
10. Sinha, S., Munichoodapa, C. S., Kozak, G. P. Neuroarthropathy
(Charcot joints) in diabetes mellitus. Medicine 51:191-210, 1972.
II. Edmonds, M. E., Clarke, M. B., Newton, J. B., Barrett, 1., Watkins,
P. 1. Increased uptake ofradiopharmaceutical in diabetic neuropathy.
Q.1. Med. 57:843-855, 1985.
12. Eloesser L. On the nature of neuropathic affections of the joint.
Ann. Surg. 66:201-206,1917.
13. Brower, A. C., Allman, R. M. Pathogenesis of the neurotrophic joint:
Neurotraumatic vs. neurovascular. Radiology 139:349-354, 1981.
14. Armstrong, D. G., Lavery, L. A. Elevated peak plantar pres-
sure in patients with Charcot arthropathy. 1. Bone Joint Surg.
80A:365-369, 1998.
15. Armstrong, D. G., Lavery, L. A., Liswood, P. L., Todd, W. F.,
Tredwell, J. Infrared dermal thermometry of the high risk diabetic
foot. Phys. Ther. 77:169-177,1997.
16. Armstrong, D. G., Lavery, L. A. Monitoring healing of acute
Charcot's arthropathy with infrared dermal thermometry. J. Rehabil
Res. Dev. 34:317-321, 1997.
17. Kanis, J. A. Textbook of Osteoporosis, Blackwell Science,
Cambridge, MA, 1996.
18. McNair, P., Madsbad, S., Christiansen, C. Faber, O. K., Transbol, I.
Binder, C. Osteopenia in insulin-treated diabetes mellitus. Diabeto-
logia 15:87 -90, 1978.
19. Edelson, G. W., Jensen, 1. L. Kaczynski, R. Identifying acute
Charcot arthropathy through urinary cross-linked N-telopeptides.
Diabetes 45(suppl. 2): 108A, 1996.
20. Gough, A., Abraha, H., Li, F., Purewal, T. S., Foster, A. V.,
Watkins, P. J., Moniz, c., Edmonds, M. E. Measurement of
markers of osteoclast activity in patients with acute and chronic
diabetic Charcot arthropathy. Diabetic Med. 14:527-531, 1997.
21. Young, M. J., Marshall, A. Adams, J. E., Selby, P. L., Boulton,
A. J. M., Osteopenia, neurological dysfunction, and the develop-
ment of Charcot neuroarthropathy. Diabetes Care 18:34-38, 1995.
22. Selby, P. L., Young, M. 1., Boulton, A. 1. Bisphosphonates: a new
treatment for diabetic Charcot neuroarthropathy? Diabetic Med.
11:28-31,1994.
439