Mr. J. Oral MaxilloJac. Surg. 1993; 22.
368 370
PHnted #I Denmark. All Hghts reserved
Uremic mixed bone disease
A case report
H. Nadimi, J. Bergamini, B. Lilien: Uremic mixed bone disease. A case report.
Int. J. Oral Maxillofac. Surg. 1993," 22. 368-370. © Munksgaard, 1993
Abstract. Renal osteodystrophy (ROD) is a complex disease of bone caused by
renal failure. A case of uremic mixed bone disease with severe maxillofacial involve-
ment is reported. The pathogenesis and various pathologic features of ROD are
discussed.
Uremic bone disease, collectively
known as renal osteodystrophy (ROD),
is a broad term that encompasses a
number of distinctive skeletal abnor-
malities in patients with renal failure.
ROD includes five histologic subtypes:
1) osteitis fibrosa (high-turnover bone
disease), 2) osteomalacia (low-turnover
bone disease), 3) mixed bone disease, 4)
aplastic (adynamic) bone disease with
minimum osteoid formation, and 5)
aluminum-related (osteomalacia-aplas-
tic) lesions4. The link between renal fail-
ure and bone disease is due to progress-
ive loss of nephron mass, decreased
renal production of 1,25(OH)2D 3 (calci-
triol), decreased renal excretory func-
tion with resulting metabolic acidosis,
hyperphosphatemia, hypocalcemia, and
secondary hyperparathyroidism4. Trace
metals, particularly aluminum (A1) ac-
cumulation in dialysate water and inges-
tion of M-containing phosphat e
binders, further aggravate bone. dis-
ease 2.
Clinical symptoms of bone disease oc-
cur in less than 10% of patients with ad-
vanced renal failure4. Radiologically re-
vealed changes of hands, including
subperiosteal erosions of the middle
phalanges lI and III, and the complete
absence of lamina durae of the teeth are
the usual features seen in secondary
hyperparathyroidism. Radiologic ab-
normalities are observed in about 35% of
patients, after the changes at the cellular
Copyright (c) Munksgaard 1993
IntemarionaI]oumd of
Oral
MaxillofacialSurgery
ISSN 0901-5027
Hasan Nadimi, Jay Bergamini,
Brian Lilien
Department of Oral and Maxillofacial Surgery,
Loyola University Medical Center, Chicago,
IL, USA
Key words: renal osteodystrophy; jawbone;
mixed bone disease.
Accepted for publication 7 July 1993
level have been occurring for a long bility. The patient stated that she had first
time4. Computed tomography (CT) noticed the change approximately 6 months
scans are useful for early detection of previously. She sought surgical treatment for
osteopenia in sensitive bone sites such as the correction of the facial deformity.
Her past medical history was significant
femoral necks4. CT scans have similar
because of three unsuccessful renal trans-
value to detect early bone loss in jaw- plants: one living-related and two cadaveric
bones. donors. All kidneys were rejected and dialysis
Debilitating complications of the was resumed. The patient had been receiving
skeleton are incurred in end-stage kid- hemodialysis treatment 3 days a week for
ney disease with maintenance hemo- the last 20 years. Her medications included
dialysis. Uremic osteodystrophy at this aluminum hydroxide for the reduction of die-
stage is an iatrogenic disease; it can im-
pose severe orthopedic changes within
a short period when dialysis fails to pre-
vent morbid outcome.
Bone biopsy in ROD patients is im-
perative for identification of the disease
and its management. Bone biopsy indi-
cates the specific means of therapy such
as parathyroidectomy in osteitis fibrosa
or other therapeutic modalities such as
desferrioxamine (DFO) A1 chelation in
M-related osteomalacia6.
This paper presents a patient with
uremic mixed bone disease in whom se-
vere deformities of maxilla and man-
dible developed during a protracted
course of renal dialysis. The patho-
genesis and pathology of the disease are
discussed.
Case history
A 28-year-oldblack woman presented with a
chief complaint of slowly expanding maxilla, Fig,. 1. Maxillary expansion and the anterior
change in occlusion, and slight tooth mo- open bite.

Fig. 2. Close-up panoramic radiograph showing patchy areas of osteosclerosis and lack of
lamina durae.
Fig. 3. Undecalcified bone biopsy showing darkly stained sclerotic woven bone in the midpor-
tion of trabeculae (large arrow) surrounded by lightly stained osteomalacic osteoid seam
(small arrows). Active osteoblasts are generally absent (trichrome stain, x 250).
tary phosphate, iron supplement for the
treatment of normocytic/normochromic ane-
mia, and medication for hypertension.
Physical examination revealed a 150-cm,
39.6-kg anemic woman with an obvious
asymmetric facial deformity of the anterior
aspect of her right maxilla. The expanded
mass caused displacement of the ala on the
affected site (Fig. 1). Oral examination re-
vealed an expanded maxilla and mandible
on the right side. The maxillary expansion
almost obliterated the right vestibule and the
palatal vault. There was an anterior open bite
with slight mobility of the teeth, particularly
in the anterior region but without any patho-
logic tooth migration. The patient's teeth
were sound with no sensitivity to percussion.
Periapical and panoramic radiographs and
computed orthopantomograms showed a
generalized absence of lamina dnra, trabecu-
lar obliteration, loss of cortical bone thick-
ness, bone condensations (osteosclerosis),
and osteopenic changes (Fig. 2). Hand radio-
graphs showed severe subperiosteal erosions
of the phalanges and complete resorption of
the terminal distal phalangeal tuft of the
Uremic mixed bone disease 369
fourth digit. A cervical radiograph revealed
enhanced subchondral bone condensations in
the upper and lower margins of cervical ver-
tebrae, producing the so-called rugger-jersey
spine. Serum biochemical analysis showed in-
creases in serum phosphorus, alkaline phos-
phatase, immunoreactive PTH (iPTH), and
osteocalcin, and a decrease in ionized/
nonionized calcium in multiple determi-
nations. Serum 1,25 D 3 was undetectable, and
serum A1 level in one determination was
within the normal limit. A bone biopsy from
the anterior aspect of the right maxillary
mass showed changes suggestive of both oste-
iris fibrosa caused by secondary hyperpara-
thyroidism and areas of mineralization de-
fect, suggestive of osteomalacia. Histologic
features consistent with osteitis fibrosa in-
cluded bone trabeculae lined by osteoblasts,
osteoclastic bone resorption, and peritrabec-
ular fibrosis. Histologic features consistent
with osteomalacia included spongy bone with
relatively thick osteoid, unremarkable osteo-
blastic rimming, and a smooth interface at
the mineralization front between osteoid rim
and osteosclerotic woven bone (Fig. 3). These
microscopic findings were consistent with a
mixed lesion of ROD.
Discussion
The occurrence o f b o n e lesions in R O D
is complex a n d is related mainly to re-
duced v i t a m i n D m e t a b o l i s m a n d sec-
o n d a r y h y p e r p a r a t h y r o i d i s m . While a
high level o f P T H in chronic renal fail-
ure leads to a high rate of b o n e f o r m a -
tion a n d resorption, m a i n t e n a n c e dialy-
sis a n d the ingestion of p h o s p h a t e
binders act as inhibitors o f osteoblastic
f u n c t i o n a n d b o n e f o r m a t i o n 3. Thus,
b o n e b i o p s y in R O D patients m a y show
combinations of hyperparathyroid bone
disease a n d o s t e o m a l a c i a in a setting o f
n o r m a l , reduced (osteopenic) or in-
creased (osteosclerotic) b o n e f o r m a -
tion 3.
Osteitis fibrosa ( h i g h - t u r n o v e r b o n e
disease) is a remodeling disorder o f
b o n e - f o r m i n g a n d b o n e - r e s o r b i n g cells 7.
It is characterized by a n accelerated
w o v e n (calcified) osteoid p r o d u c t i o n
(osteosclerosis) a n d increased n u m b e r
of osteoblasts a n d osteoclasts, b o t h o f
which are secondary to high level o f
PTH. W o v e n osteoid in osteitis fibrosa
differs f r o m the n o r m a l lamellar osteoid
in that the f o r m e r exhibits a "crisscross"
a r r a n g e m e n t o f collagen fibers a n d
w h e n it b e c o m e s mineralized, it lacks
the trajectorial p a t t e r n o f n o r m a l can-
cellous b o n e trabeculae. T h e u n m i n e r a l -
ized, excess osteoid f o r m a t i o n , the so-
called hyperosteoidosis, can result also
from a slow rate of m a t r i x mineraliza-
tion (osteomalacia). In this case, the his-
370 Nadimi et al.
tologic appearance of reduced numbers
of both osteoblasts and osteoclasts de-
termines the diagnosis of low-turnover
bone disease.
The histologic distinction between
osteitis fibrosa and osteomalacia is
more than academic, since the diagnosis
determines treatment approach in these
patients. Although hyperosteoidosis is
a fundamental feature of osteomalacia,
not all instances of excess osteoid repre-
sent osteomalacia. In end-stage renal
disease, the quantity of osteoid seam
reflects the two kinetic events of: 1) en-
hanced seam thickness (osteitis fibrosa)
and 2) retarded mineralization (osteo-
malacia). Through standard (static) his-
tologic features, the accelerated ostoid
synthesis in osteitis fibrosa corresponds
to an abundance of cuboidal, lining-se-
creting osteoblasts. Osteitis fibrosa gen-
erally shows also peritrabecular fibrosis
which is caused by a proliferation of
osteoprogenitor cells in juxtaposition to
trabecular bony surfaces. Unlike osteitis
fibrosa, osteomalacic osteoid seams are
generally covered by fusiform cells, and
not by cuboidal and active osteoblasts.
Bone biopsy in this patient showed
mixed features of both osteitis fibrosa
and osteomalacia, known as a mixed
bone lesion. Biochemically, it correlated
with high levels of serum PTH, phos-
phate, osteocalcin, and alkaline phos-
phatase, indicative of osteoblastic activ-
ity. The osteomalacic lesion in this pa-
tient in the absence of a heavy load of
A1 was thought to be induced by low
vitamin D and by hypocalcemia5. The
probable pathogenic mechanism of the
mixed bone disease in this case might
relate to a long-standing osteitis fibrosa
and a recently developing hypocalcemic
osteomalacia. Mixed bone lesions may
also be induced by a heavy load of A1.
In these patients, bone biopsy will show
significant stainable cation at the site of
the mineralization front 3.
Uremic osteosclerosis occurs because
of an enhanced osteoblastic activity.
Since ROD patients are usually in nega-
tive calcium balance, sclerosis is due
mainly to bone remodeling and redistri-
bution. Osteosclerosis in ROD is exclus-
ively a trabecular phenomenon, result-
ing from osteoclastic degradation of
cortical bone and increased thickness
and number of trabeculae in spongy
bone, along with an excess deposit of
amorphous calcium phosphate. Uremic
osteosclerosis manifests most com-
monly in the maxilla, which is predom-
inantly trabecular, with resulting bone
enlargement, whereas when the man-
dible is affected, it becomes more po-
rotic and the cortical thickness becomes
markedly reduced. Panoramic radio-
graphic findings of mandibular cortical
bone loss have been used in diagnosing
ROD ~. By examining CT scans, we
found evidence of mandibular cortical
osteopenia in the patient described.
Management of patients with ROD
comprises high dietary calcium and vit-
amin D supplementation or supple-
mentation via the dialysate, and reduc-
tion in dietary phosphate in the early
stages of the disease is highly effective.
The reversal of osteitis fibrosa with vit-
amin D metabolites, by the direct effect
of the vitamin on PTH secretion, occurs
dramatically in 3 6 months after ther-
apy. Unlike osteitis fibrosa, renal osteo-
malacia fails to respond to vitamin D
treatment in some cases. In patients
with AI intoxication, DFO for 6-12
months and polysulfone dialyzers are
useful in treating Al-related osteoma-
lacia.
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Address:
Hasan Nadimi, DMD, M S
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Hoffman Estates, IL 60195-2618
USA