02_disease of bone_metabolic general.pdf

Metabolic diseases of bone structure

1. Metabolic Bone Diseases Metabolic Bone Diseases
AlfonsoLópez AlfonsoLópez Alfonso
 López Alfonso López
Atlantic Veterinary College Atlantic Veterinary College
University of Prince Edward Island University of Prince Edward Island
January January 18, 18, 2010 2010

2. Metabolic Bone Diseases Metabolic Bone Diseases
Metabolic bone diseasesare systemic disorders of the
skeletal system caused by various etiologies such as
dietary(nutritional), hormonaland toxic.
The best known metabolic bone diseases are:
•Rickets
•Osteomalacia
•Osteoporosis
•Fibrous osteodystrophy. The most common toxic osteodystrophies are:
•Hypervitaminosis A and D
•Osteofluorosis
•Lead poisoning
The fundamental problem in metabolic bone diseases is an
imbalance between bone formation and resorption in the
normal remodeling process of bones.

3. Osteoporosis Osteoporosis
Bone Atro
p
h
y
Bone Atro
p
h
y
Negative balance between formation
and resor
p
tion
pypy
p
Causes of Osteoporosis:
– Starvation, parasitism
Cli /Vit i Ddfii
NORMAL
–
C
a
lc
ium
/

Vit
am
in
D

d
e
fi
c
iency
– Cushing’s disease,
– Iatrogenic
–
Senile
– Disuses
Difficult to evaluate at PM Reduced thickness of cortical and
trabecular bone.
Pathologic fractures
OSTEOPOROSIS

4. Osteoporosis Osteoporosis
Normal
Osteoporosis
Notice the loss of trabecular bone
characterized by an enlarged medullary
dhi i A
space an
d
t
hi
nner cort
ices.
A
s you may
expect, the bones are fragile but not soft as
with rickets, osteomalacia or osteodystrophia
fibrosa.
The underlying problem in osteoporosis is a
negative balance between formation and
resorption of bone leading to reduction of bb
one mass.
A simple definition of os teoporosis is “there is
little bone, but what bone there is, is normal.”
Ot i i l f dt b O
s
t
eoporos
is
is a
lso re
f
erre
d

t
o as
b
one
atrophy.

5. Normal Bone Normal Bone
Osteoporosis Osteoporosis

6. Osteoporosis Osteoporosis
Note the reduced
Causes of osteoporosis include:
•Starvation
•
Parasitism
trabecular bone in the
metaphysis with some
visible cavitations in the
diaphyses.
•
Parasitism
• Chronic wasting diseases,
• Deficiencies of calcium and copper
• Hyperadrenocorticism •
Prolonged
administration of steroids
There are also thin
cortices and an enlarged
medullary spaces.
•
Prolonged

administration

of

steroids
.
It also results from physical inactivity (disuse
atrophy of bone) and senility. Osteoporosis is
an important disease in human beings an

important

disease

in

human

beings
,
particularly in older women (postmenopausal
osteoporosis).
))
.

7. Bilateral Fractures of Femur in a Calf Bilateral Fractures of Femur in a Calf
Note the bilateral femoral fractures.
These bones had thin cortices and
dd
bl
bPhlil
re
d
uce
d
tra
b
ecu
la
r
b
one.
P
at
h
o
log
ica
l
fractures are commonly seen in animals
with osteoporosis, rickets and
osteomalacia.
Osteoporotic bones are fragile but not soft as with rickets, osteomalacia or osteodystrophia fibrosa. Osteoporosis is difficult to evaluate grossly unless it is a severe case in which
a significant bone mass has been lost.

8. Ri
c
k
ets
. B
o
vin
e
.
Ca
l
f
Ri
c
k
ets
. B
o
vin
e
.
Ca
l
f
..
cets o eCa cets o eCa
Note the deformation of the forelegs and
enlarged carpal joints. The deformity is due
to softening of bone in addition to weight to

softening

of

bone

in

addition

to

weight

bearing when the animal stands.
Gross lesions in rickets are typically
characterized by an abnormal widening of characterized

by

an

abnormal

widening

of

the “growth cartilage” (growth plates), bone
softening, deformations, and swelling of the
cartilagineous joints.
The enlargement of the carpal joints is due to the accumulation of noncalcified cartilage at the site of
endochondral
ossification
the

site

of

endochondral
ossification
.

9. Porcine Rickets Porcine Rickets
This pig is reluctant to stand on its limbs to
avoid pain.
The etiopathogenesis of rickets is multifactorial but generally involves deficiencies of vitamin D or phosphorus or

phosphorus
.
Rickets is commonly found in animal housing
facilities where there is little sunlight or in areas facilities

where

there

is

little

sunlight
,
or

in

areas

where the soil is deficient in phosphorus.
In human rickets enlargement of the In

human

rickets
,
enlargement

of

the

costochondral joints is prominent forming the
so-called rachitic rosary.

10. Rickets Rickets
A
sagittal
section of a rachitic long bone.
A

sagittal
section

of

a

rachitic

long

bone.

Note the irregular thickening of the growth
plate (arrow).
In growing animals, endochondral ossification occurs when cartilage proliferates, matures, becomes h
ype
r
t
r
op
hi
c

a
n
d
fin
a
ll
y

dege
n
e
r
ates

a
n
d

ype t op c a d a y dege e ates a d
becomes mineralized forming woven bone.
In rickets
,
chondroc
y
tes
p
roliferate but do
Rickets
,
y
p
not mature and degenerate properly, thus
cartilage is retained and accumulates in
bones.

11. Normal Normal versus rachitic
g
rowth
p
lates versus rachitic
g
rowth
p
lates
Rickets Rickets
gp gp
Note the homogenous thickness in the normal
growth plate while the rachitic bone shows a
severe focal thickening of the
cartilage
plate.
severe

focal

thickening

of

the

cartilage

plate.

Thickening of the growth plate can be
detected by gross or radiological examination.
Normal
Rickets
Rickets

12. Rickets Rickets
Normal Normal
Histology Histology Normal Normal vs.vs.
affected growth affected growth
plates plates plates
.
plates
.
Notice the abnormal
retention and lack of
mineralization in the growth mineralization

in

the

growth

cartilage in the animal with
rickets (left picture).
Unmineralized osteoid
appears pink appears

pink
.
ff
f
Microscopically, a
ff
ected bones show a
f
ailure in mineralization
of osteoid and retention of cartilage matrixes which fails to
mineralize (arrows).

13. Canine Rickets
Soft bones Soft bones Soft

bones Soft

bones

14. Osteomalacia Osteomalacia / Bovine / Bovine
Note the deformity of the forelegs with lateral deviation of the radius and ulna lateral

deviation

of

the

radius

and

ulna
.
As in rickets, bone deformities and
abnormal limb curvatures in osteomalacia
result from bone softening and weight result

from

bone

softening

and

weight

bearing.
The accumulation of non-calcified
cartilage in the growth plate is not seen in cartilage

in

the

growth

plate

is

not

seen

in

osteomalacia since this later disease of
mature animals in which the growth plate
has already closed.
The etiology of osteomalacia is similar to that of rickets in that deficiencies of phosphorus and vitamin D are major contributors. contributors.

15. Osteomalacia Osteomalacia
Normal Normal

16. Fibrous Fibrous Osteodystrophy Osteodystrophy
Osteodystrophia Osteodystrophia Fibrosa Fibrosa. Equine. . Equine. Note the extreme swelling and deformity of
hlbI
dhi
t
h
e nasa
l
b
ones.
I
n osteo
d
ystrop
hi
a
fibrosa cranio-facial bones are more
severely affected.
Ot d t hi
itblib
O
s
t
eo
d
ys
t
rop
hi
a
is a me
t
a
b
o
li
c
b
one
disease characterized by increased
osteoclastic resorption of bone and
replacement by fibrous connective tissue
dt l dd i ti d
ue
t
o pro
longe
d
an
d
excess
ive secre
ti
on
of a parathyroid hormone (PTH).
Osteodystrophia fibrosa in horses is
litdithditihi
common
ly assoc
ia
t
e
d
w
ith

di
e
t
s r
ic
h

in
phosphorus and low in calcium as found in
bran. Hence, the disease in horses is
often referred to as "bran disease."

17. Fibrous Fibrous Osteodystrophy Osteodystrophy
Osteodystrophia Osteodystrophia Fibrosa Fibrosa. Goat. . Goat. Note the severe swelling and deformity of
the facial bones due to the accumulation
and proliferation of connective tissue. Because of osseous softening in the maxillary and mandibular bones, the teeth become rather loose. The fundamental mechanism is a reduced concentration of calcium in the plasma with a relative increase in phosphorus. Nutritional hyperparathyroidism results from a low-calcium/high phosphorus diet.

18. Fibrous
osteodystrophy
in
dogs
is most frequently
associated with chronic renal disease
Fibrous Fibrous Osteodystrophy Osteodystrophy / Dog / Rubber Jaw / Dog / Rubber Jaw
Fibrous

osteodystrophy
in

dogs

is

most

frequently

associated

with

chronic

renal

disease

(secondary hyperparathyroidism due to renal failure).
End stage renal End stage renal
amyloidosis amyloidosis
Renal osteodystrophy results from the inability of the kidneys to excrete P. Excess P in blood
and a relative reduction of blood Ca
++
(hypocalcemia) activate parathyroid glands to secrete
PTH
Thi h i
hli
iit C
fb i
tlt
PTH
.
Thi
s
h
ormone
is
h
yperca
lcem
ics
ince
it
removes
C
a
++
f
rom
b
ones v
ia os
t
eoc
las
t
s
(osteoclastic osteolysis) and osteocytes (osteocytic osteolysis). PTH also increases absorption
of Ca
++
in the intestine. In addition, animals with renal disease are unable to activate Vitamin D
3
in kidneys.

19. Fibrous Fibrous Osteodystrophy Osteodystrophy / Pig/ Pig
Note the swollen gums and missing teeth.
Deformation of the facial bones is due to resor
p
tion of bone and an excessive
p
deposition of connective tissue. Dental alveoli are weakened and teeth become loose. .

20. Fibrous Fibrous Osteodystrophy Osteodystrophy / Iguana / Iguana
Osteod
y
stro
p
hia fibrosa is extremel
y
common in ca
p
tive re
p
tilians. Even with a
g
ood feedin
g

yp
ypp gg
practice, animals in captivity often develop secondary hyperparathyroidism.
The pathogenesis of Osteodystrophia fibrosa in captive reptiles is the same as in domestic animals.

21. Osteodystrophia Osteodystrophia
Fibrosa Fibrosa
Osteodystrophia Osteodystrophia
Fibrosa Fibrosa
. .
Primate Primate
Note the swollen gums and missing Note

the

swollen

gums

and

missing

teeth. This disease is common in
primates kept in captivity due to dietary
imbalances particularly when there is a
calcium deficiency and an excess of calcium

deficiency

and

an

excess

of

phosphorus.
A lack of exposure to ultraviolet A

lack

of

exposure

to

ultraviolet

(sunlight) is another contributing factor.
Note the angular deformity of the Note

the

angular

deformity

of

the

forelimb. This bone would be rather soft
to the point that it can be cut with a
knife. A cross section of this bone is
shown in next slide shown

in

next

slide
.

22. Osteodystrophia Osteodystrophia Fibrosa Fibrosa. .
Primate Primate
A
cross section of lon
g
bones.
g
Note the marked swelling and deformation
of the bones with extensive proliferation of
fibrous tissue. Fibrous tissues fills most of
the medullary space.
Osteodytrophia fibrosa is also known as
"osteitis c
y
stica fibrosa" in human medicine
y
due to formation of numerous cysts in affected bones as seen in this primate. Cysts are only occasionally seen in domestic animals. Osteodytrophia fibrosa may be reversed if the cause is removed.

23. Fibrous Fibrous Osteodystrophy Osteodystrophy
Normal Normal

24. Osteodystrophia Osteodystrophia Fibrosa Fibrosa. . An histologic section stained
(Hematoxylin-eosin stain). Note the
bone resorption characterized by Howship
lacunae
(white arrows)
Howship
lacunae

(white

arrows)
containing osteoclasts(arrowheds)
and extensive replacement of bone
with fibrous connective tissue (ct). Histologic sections stained for connective tissue (Masson connective

tissue

(Masson
-
Trichrome stain). Note the reduced
number of trabecular bone (red) and
extensive deposition of fibrous
connective tissue (blue) connective

tissue

(blue)
.
In severe cases there is no need to
decalcify the bone samples to cut
histological sections histological

sections
.

25. Fibrous Fibrous Osteodystrophy Osteodystrophy / Parathyroid Adenoma / Parathyroid Adenoma
PA PA
It is imperative to check the parathyroid glands and kidneys in any animal with
Osteodystrophia fibrosa.
In this do
g
the
p
arath
y
roid
(
PA
)
was re
p
orted to be adenomatous and
p
resumabl
y
activel
y

PAPA
gp y() p
pyy
secreting large amounts of PTH. A normal parathyroid gland would be approximately one
fifth of this size.
parathyroid gland parathyroid gland
parathyroid gland parathyroid gland
PthidH li PthidH li
Normal Normal
Thyroid gland Thyroid glandThyroid gland Thyroid gland
P
ara
th
yro
id

H
yperp
las
ia
P
ara
th
yro
id

H
yperp
las
ia
Primary hyperparathyroidism is relatively rare in domestic animals Most
cases in animals
Primary

hyperparathyroidism

is

relatively

rare

in

domestic

animals
.
Most

cases

in

animals

are due to secondary hyperparathyroidism as a result of nut ritional imbalances or due to
renal diseases with impairment in the excretion of phosphorus.

27. Odontofluorosis Odontofluorosis / Bovine / Bovine
Note the dark discoloration, excessive
and abnormal wear pattern in the
incisive teeth. Affecting only fetuses and growing herbivorous, fluorosis interferes with the normal metabolism of bones and teeth teeth
.

28. Osteofluorosis Osteofluorosis / Bovine / Bovine
A cross sectional view of normal (n) and
affected metatarsal bones
(
f
)
. Note the
()
increased thickening of cortical bone due to new periosteal bone formation (red
line).
Osteofluorosis results from a chronic
ingestion of fluorides present in water,
plants and rocks in some geographical
re
g
ions.
g
In cattle fluorosis only occurs when the concentrations of fluoride reach more than 2,500
pp
m in bones.
pp
Growing bones (metatarsal, mandibles, the pelvis) become thickened due to excessive
p
eriosteal ossification.
p

29. Vitamin A Toxicity / Cat Vitamin A Toxicity / Cat
Note the extensive hyperostosis and
deformation of the periosteal surfaces of
the bones. The vertebrae are commonly affected in cats with vitamin A toxicity and in severe cases the periosteal proliferation results in
tb lf i Thi f i f ti
ver
t
e
b
ra
l
f
us
ion.
Thi
s
f
us
ion o
f
con
ti
guous
bones is referred to as ankylosis.
Cats are highly susceptible to vitamin A
tiit Itd l f tl h t t
ox
ic
it
y.
It

d
eve
lops
f
requen
tl
y w
h
en ca
t
s
are fed livers from grazing cattle which are
rich in Vitamin A. Also when animals are
given excess vitamin A supplement.
Although the pathogenesis is poorly understood, it has been suggested that high levels of retinoid and other vitamin A
t b lit ti l t
tblti
ti it
me
t
a
b
o
lit
es s
ti
mu
la
t
e os
t
eo
bl
as
ti
cac
ti
v
it
y.

30. Metabolic Bone Diseases Metabolic Bone Diseases Metabolic Bone Diseases Metabolic Bone Diseases
If you have any comments, criticisms or suggestions about this or any If you have any comments, criticisms or suggestions about this or any
other

tutorial

module

please

let

me

know

other

tutorial

module

please

let

me

know


other tutorial module please let me know
.
other tutorial module please let me know
.
Also
,
if
y
ou find an
y
errors or t
yp
os
p
lease let me know too. Thanks!

Also
,
if
y
ou find an
y
errors or t
yp
os
p
lease let me know too. Thanks!

,y y ypp ,y y ypp
[email protected] [email protected]

31. 
Some images were acquired from veterinary colleges of Some images were acquired from veterinary colleges of

Some

images

were

acquired

from

veterinary

colleges

of

Some

images

were

acquired

from

veterinary

colleges

of

Canada, United States and Mexico and the names of Canada, United States and Mexico and the names of
pathologists who contributed with some slides are pathologists who contributed with some slides are unknown unknown. .
Their valuable contribution is sincerely acknowledged Their valuable contribution is sincerely acknowledged Their

valuable

contribution

is

sincerely

acknowledged
.
Their

valuable

contribution

is

sincerely

acknowledged
.
I would like to thank Adriana I would like to thank Adriana Ló
p
ez
,
S Ló
p
ez
,
S--LP LP and Eileen Kinch for and Eileen Kinch for
p, p,
editorial assistance; Dr. María Forzán, Atlantic Veterinary editorial assistance; Dr. María Forzán, Atlantic Veterinary
College, for critically reviewing these modules. College, for critically reviewing these modules.