VOL.

No.

Is,

4

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RADIONUCLIDE BONE IMAGES IN HYPERTROPHIC PULMONARY OSTEOARTHROPATHY* By

DANIEL

W.

TERRY,

Ja.,

M.D.,

ALl

T.

ISITMAN,

MILWAUKEE,

I MPORTANT

advances

have

been

findings

gests

a specificity

image

in HPO.

* From Complex,

in

this

of

the

the Department of Radiology, Milwaukee, Wisconsin.

disease

and

radionuclide

A. HOLMES,

OF

A 61 year was admitted

old white to the

pleuritic

chest

loss

left

of

dullness

M.D.

upper and

deep

venous

with

disease. were

alkaline lobe

of the

roen

tgenograms

mass

obstructing

no

normal

normal.

in

skeletal

(Fig.

the

I,

bone

increased distal

the

type

the

positive

No

imaging

571

The

chest

strated

A

with

was

a

used

techne-

to

localize

metastatic foci were of radionuclide was the distal shafts and and left femurs, tibias

B).

and

images

The

(Fig.

uptake forearms,

pattern

of

associated bone

proximal

with

the

patient’s

therapy

Medical

bone

A

I,

formation

disease

(Fig.

changes

or in the

,

were

A

and

seen

in

phalanges.

cardiopulmonary

surgery,

treatment

with

A total of lung over

4,000

to

elected. the left

College

of Wisconsin,

was

both

roentgeno-

sites

poor

Less

at (Fig.

pulmonary

image

extremities

precluded

A-D).

2,

was noted and wrists

roentgenographic

Because

Medicine,

upper

on initial

and B; and 2, A-D). Corresponding grams revealed periosteal new

tion

upper

the

produced a “double stripe sign.” The stripe is due to circumferential increased by the cortical bone as viewed tangen-

discrete mid feet,

status

the

the

body

fibulas

tially

sug-

at

demon

tium 99 diphosphonate skeletal metastases. No seen but intense uptake noted superficially along metaphyses of both right

B). the

serum

biopsy.

Whole

of at

the

of

seen

cx-

for

was

; tomography

bronchoscopic

and

evident

left upper lobe bronchus. sputum examin ation demonstrated carcinoma which was confirmed by

Cytologic epidermoid

uptake double uptake

Cardiac

atelectasis

was

left

edema,

laboratory

which

lung

cord,

in the

clinically

except

Total

left

vocal ankle

Routine

phosphatase of

left sounds

of all extremities.

normal

arninations limit

of the

weight

examina-

non-pitting

clubbing

was

and

Physical

breath

painful

digital

status

hoarseness,

duration.

decreased

thorax,

CASE

male, a chronic smoker, hospital complaining of

paralysis

and

A

pain,

5 months’

revealed

tiOn

bone

of Nuclear

RICHARD

REPORT

administered Division

and

made

in radionuclide bone imaging since the introduction of technetium 99 polyphosphate in I97I’ and the subsequent development of diphosphonate and pyrophosphate radiopharmaceuticals.3’5 High quality bone images obtained with these agents have allowed earlier diagnosis and localization of a wider range of bone abnormalities than observed with conventional roentgenography. Primary and metastatic neoplasia, inflammatory disease, metabolic abnormalities, and periosteal disorders may frequently be detected on the radionuclide bone image long before they become apparent roentgenographically. Even if such abnormalities are noted on roentgenographic images, the extent of bone involvement can be more easily established and followed with bone imaging. Periosteal new bone formation which occurs in association with various pulmonary and non-pulmonary diseases has been extensively documented in the medical and radiologic literature.’#{176}’3”5 Recently, case reports have appeared demonstrating the scintigraphic appearance of hypertrophic osteoarthropathy associated with pulmonary malignancy (the Marie-Bamberger syndrome or hypertrophic pulmonary osteoarthropathy). These reports have emphasized the difficulty in differentiating metastatic bone disease from periosteal proliferation.2”4 A recent case of epidermoid lung carcinoma with hypertrophic pulmonary osteoarthropathy (HPO) illustrates the scmtigraphic

M.D.,

WISCONSIN

Milwaukee

radia-

r was

a 3 week County

Medical

D. W.

572 5’-

Terry,

Jr.,

A. T.

Isitman

and

R.

A. Holmes

AUGUST,

1975

-

-..

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245I’86

-.

I

R

4

.-

FIG.

I.

(A) Anterior

and

view,

intense

symmetric

distal

femurs

and

wrists, site.

hands,

period.

tibias

ankles

(“double

and

feet.

Symptomatically,

the

later,

roentgenography

before

bone

could

bone images uptake

stripe

with Tc”

sign”).

Less

discrete

uptake

at the

right

patient

improved

imaging

He was disdied there 3 and

diphosphonate. is seen localized

of radionuclide

Increased

and his left upper lobe re-expanded. charged to a nursing home but months

_______

--.-:--

(B) posterior circumferential

skeletal

be repeated.

DISCUSSION

More than 8 decades have passed since Marie and Bamberger described hypertrophic pulmonary osteoarthropathy. A bewildering array of pulmonary and non-

increased elbow

pulmonary

uptake

is caused

diseases

Especially to the

is noted

by infiltration

has

been

on the periosteum

anterior of the

in the forearms, at the

injection

described

as

associated with periosteal proliferation in the long bones. Fischer et al.7 in 1964 reviewed and listed many of these diseases. Since then several additional etiologies have been described.9”6 They encompass a wide variety of benign and malignant lesions in a number of organ systems. Disorders that have been associated with hypertrophic

osteoarthropathy

include:

VOL.

124,

No.

Hypertrophic

4

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I

-

-

C

--

Pulmonary

:

-‘-

Osteoarthropathy

573

245186

C.

.;C-

-

-

-

.

-.

‘_5 -.

C:

‘S.-.

c,.’lr

f

t#{149}’.

-

-

FIG.

2. Selected

carpals, localized

FIG.

-

C-

.-:--

gamma

and metacarpals to the distal

j.

(A

and

B)

-

C

‘.5

.

. -

camera

images

Reactive

areas

periosteal

depicted

Figure I. (A and B) Increased uptake in the distal The phalanges are normal. (C and D) Circumferential periosteum (‘double stripe sign”) is shown.

from

is demonstrated. femoral and tibial

new

in the

bone

deposition

diphosphonate

is present

bone

image

roentgenograpl....y

(arrows).

at

radius, uptake

the

D.

574

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I.

W.

Terry,

Jr.,

A. T.

c.

Mediastinal Hodgkin’s Tumors

d.

e.

medullary

reticulosis

disease of thyroid

and

Gastrointestinal diseases Tumors of esophagus,

disease prosthesis

stomach,

and

colitis

clubbing

is

be

and

osteoarthropathy.

made

rounded

between

usually

confined

the

almost

osteo-

at the

might of

distal

stripe

sign”

be the

earli-

active

or

acropachy

thickening

of

of

the

underlying

deepest part of the reconstruction and cortex. The process is symmetrical in distribution and to the diaphysis of tubular bones,

for

periosteal

localization

diphosphonate

suggests

the

a process

tech-

areas

remains accepted

of conhy-

of chemisorption

radiopharmaceutical

crystal

of

in

new bone formation The currently

distinctly

With time undergoes with the

are

“double

indicator

99

have

cortex. deposit merges

swelling

mechanism

droxyapatite

from

hypertrophic

imaging

objective

the distal phalangeal soft tissues resulting in loss of the normal nail-phalanx angle, without periostosis.7 Hypertrophic pulmonary osteoarthropathy, on the other hand, is characterized histologically by an osteoperiosteal deposit composed of trabecular primitive bone which in its early phase is demarcated

of

and

The

bone

periosteal troversial. pothesis

hypertrophic

true

Clubbing by

characterized

findings.

with

The netium

should

deposits

deposition.

atresia

cirrhosis

Distinction digital

est

biliary

1975

ends of the involved bones are the commonest symptoms, although the degree of debility parallels the severity of the underlying disease. The onset of symptoms may be gradual with negative early roentgenoseen

enteritis

Congenital Portal

Pain

graphic

Ulcerative

AUGUST,

The

form

arthropathy.

liver

Regional

canal.

significant

thymus

Cardiovascular diseases Cyanotic congenital heart Bacterial endocarditis Infected abdominal aortic

R. A. Holmes

always symmetric, circumferential and confined to the periosteum in HPO (Fig. A and B). The Marie-Bamberger syndrome is perhaps the best known and clinically most

diseases

Mediastinal

and

tapering toward the metaphysis.’#{176} The proximal and middle phalanges are rarely involved and the terminal phalanges are never involved in spite of the soft tissue “clubbing” which is usually present. The connection between the periosteal new bone formation and the many pulmonary and non-pulmonary diseases associated with it remains obscure. It seems certain, however, that the periosteal reaction does not represent metastasis in the cases of neoplastic disease. Most frequently, osseous metastasis is seen on bone images as asymmetrical deposits of radionuclide in the

Primary Hypertrophic Osteoarthropathy a. Pachydermoperiostosis b. Thyroid acropachy Secondary Hypertrophic Osteoarthropathy a. Benign pulmonary diseases Asthma Cystic fibrosis Bronchiectasis Pulmonary abscess Pulmonary cyst Sarcoidosis b. Malignant pulmonary disease Adenoma Epidermoid carcinoma Pleural mesothelioma

II.

Isitman

onto

the

hy-

More recent experimental evidence suggests that the process may actually involve complexing of the labeled diphosphonate to receptors such as the enzyme alkaline phosphatase.’t

Areas

showing

increased

creased

ceptor phonate

locally

of active

increased

alkaline

teoarthropathy.

bone

deposition

bone.

metabolism

osteoblastic

blood

phosphatase

complexing of could therefore

periosteal

cortical

of

activity

flow activity.

and

inRe-

the labeled diphosexplain its selective in

hypertrophic

os-

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VOL.

124,

Hypertrophic

No.

Pulmonary

‘4

.T).

Osteoarthropathy

575

-

A FIG.

4.

(ii)

to the right with normal

In

B

A woman with breast carcinoma demonstrates the tibia. (B) Our patient demonstrates the distinct medullary concentration of radionuclide.

a patient

such

as

ours,

the

accurate

HPO and its differentiation from bone metastasis are essential, since the choice of therapy rests on this distinction. Resolution of the osteoarthropathy was anticipated in our patient, as tumor control was achieved with radiation therapy6’8; unfortunately we were unable to repeat the diagnosis

of

asymmetric

medullary

Symmetric,

bone

image

the

greatest

uptake

circumferential

when

his

of metastasis uptake

lung

cancer

roentgenographic

of HPO

showed improve-

ment.

of

Many questions hypertrophic

pathy

are

lates

periosteal

Is

the

as yet

stimulus

about the pulmonary

pathogenesis osteoarthro-

unanswered. proliferation removed

What

stimu-

in lung

cancer?

with

therapeutic

D.

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576

W.

Terry,

Jr.,

A. T.

Isitman

W.

ECKELMAN,

and bone 6.

7.

10.

II.

2.

A.

BROWER,

C.,

and

3.

14.

H. J. Scintiosteoarthro10,

TEATES,

C.

4.

bone-scanning ethylene-i-disodium

F. P., and CALLAHAN, agent SSmTclabeled phosphonate.

Med.,

13,

1972,

CHAUDHURI,

D.

Positive

R. J. New -hydroxy7. Nuclear

i

823-827.

T. K., CHAUDHURI,

i6.

196-200.

scan in case of metastatic and hyperpulmonary osteo7. Nuclear Med., 1974, 15, 53-54.

CASTRONOVO,

C.,

KUBOTA,

Med.,

1974,

15,

H., for 279-

J., and HODES, P. J. Roentgen Diagnosis of Diseases of Bone. Williams & Wilkins Company, Baltimore, 1973, 822-8 25. FISCHER, D. S., SINGER, D. H., and FELDMAN, S. M. Clubbing: review with emphasis on hereditary acropachy. Medicine, 1964,43,459-

EDEIKEN,

H. A. Hypertrophic pulmonary osteoarthropathy simulating rheumatoid arthritis: subsidence after pneumonectomy for carcinoma. New England 7. Med., 1952, 247, 283285. GIBSON, T., JOYCE, J., SCHUMACHER, H. R., and AGARWAL, B. Localized hypertrophic osteoarthropathy with abdominal aortic prosthesis and infection. Ann. mt. Med., 1974, 8i, 6557. GREENFIELD, G. B., SCHORSCH, H. A., and SHKOLNIK, A. Various roentgen appearances of pulmonary hypertrophic osteoarthropathy. AM. J. ROENTGENOL., RAD. THERAPY & NuCLEAR MED., 1967, 101, 927-93!. HAMMERSTEN, J. F., and O’LEARY, J. Features and significance of hypertrophic osteoarthropathy. A.M.A. Arch. mt. Med., 1957, 99, 431FRANK,

HARMER,

C.

L.,

BURNS,

M. Value

J. E.,

of fluorine-8

SAMS,

A.,

and

for scanning

tumours. Clin. Radiol., 1969,20, 204-212. H. E., and BRODY, R. S. Pulmonary hypertrophic osteoarthropathy. A.M.A. Arch. mt. Med., 1957, 99, 43 I-44I. KAY, C. J., and ROSENBERG, M. A. Positive esmTc..polyphosphate bone scan in case of secondary hypertrophic osteoarthropathy. 7. Nubone

“Tc-polyphosphate osteogenic sarcoma arthropathy.

R.

44!. 12.

15.

E. U., and ALBRECHT, picture of hypertrophic Nuclearmedizin, 1971,

7. Nuclear

imaging.

HOLLING,

clear Med.,

graphic pathy.

REBA,

J. S. 9’Tc-pyrophosphate

479. 8.

13.

REFERENCES BIEHLER,

C.,

STEVENSON,

SPITTLE,

i.

5975

283.

9.

Holmes, M.D. of Radiology Nuclear Medicine College of Wisconsin County Medical Complex Wisconsin Avenue Wisconsin 53226

AUGUST,

121.

5.

SUMMARY

Richard A. Department Division of The Medical Milwaukee 8700 West Milwaukee,

R. A. Holmes

R. L., and CHRISTIE, J. H. Positive 8’”Sr bone scan in case of hypertrophic pulmonary osteoarthropathy. 7. Nuclear Med., 1972, 13, 120-

control of the neoplasm? If it is, how long after control is established will the cessation of appositional bone deposition be expected to convert the labeled diphosphonate bone image to normal? Conversely, if hypertrophic osteoarthropathy is present in lung cancer, can its “disappearance” be considered indicative of cure of the primary disease, or at least a prognostic improvement? If answers to some or all of these questions are to be obtained, evaluation must include images, roentgenograms, and histologic correlations following the institution of therapy.

Hypertrophic Pulmonary Osteoarthropathy (HPO) can be differentiated from osseous metastasis on conventional bone images using technetium 99 radiopharmaceuticals. Periosteal new bone formation appears as symmetric circumferential deposition of radionuclide in the diaphyseal cortex of tubular bones. In contrast, asymmetrical deposits in the medullary canal are indicative of metastatic disease. The etiologies of hypertrophic osteoarthropathy are discussed.

and

T. K., SHAPIRO,

17.

i8.

1974,

15,

312-313.

E. S., and FISHER, H. P. Hypertrophic osteoarthropathy in pulmonary malignancies. Ann. mt. Med., 1953,38, 239-246. SHAPIRO, R. F., and ZVAIFLER, N. S. Concurrent intrathoracic Hodgkin’s disease and hypertrophic osteoarthropathy. Chest, 1973, 63, 912916. SUBRAMANIAN, G., and MCAFEE, J. G. New complex of 99mTc for skeletal imaging. Radiology, 1971, 99, 192-196. ZIMMER, A. M., ISITMAN, A. T., Sci-iMrrr, G. H., and HOLMES, R. A. Enzymatic inhibition by diphosphonate: proposed mechanism of tissue uptake. 7. Nuclear Med., 1974, 15, 546. RAY,