Pediatric Allen

D.

Elster,

MD

Elias

G. Theros,

#{149}

MD

L. Lyndon

Autosomal Recessive Bone Marrow Imaging’ Technetium-99m

sulfur

colloid

scm-

tigraphy was performed prospectively mn12 mnfants and children autosomal recessive osteopetrosis, correlate

the

appearance

with to

of bone

mar-

row stores with advancing age. Baseline images were obtained in all patients, and one to five follow-up images were obtained in eight pafients after they began therapy with calcitriol, interferon-’y, or both. Conventional

radiography

was

per-

formed along with the nuclear studies in all cases. Magnetic resonance (MR) images of the head or lower extremities were also obtained in six patients and were correlated with the scintigraphic

findings.

Patterns

of

abnormal distribution of bone marrow appeared to be age-dependent. In patients younger than 1 year, marrow stores were primarily in the skull base and at the ends of the long bones. In patients aged 3-5 years, marrow stores shifted to the diaphyseal regions of long bones and to the calvarium. In the appendicular skeleton, areas of greatest bone marrow activity corresponded to regions of relative

decreased

opacity

on

radio..

graphs and areas of intermediate or high signal intensity on fl-weighted MR images. The skull base showed appreciable marrow activity in spite of densely sclerotic bone on radiographs.

Radiology

1992; 182:507-514

MD

Constance

O

STEOPETROSIS

tremely rare by defective

caused tion.

The

disease

of Radiology (A.D.E., and Pathology (CS.),

Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1022. Received July 18, 1991; revision requested September 13; revision received September 25; accepted October 3. Address reprint requests to A.D.E. C RSNA, 1992

computed orbits, tients

netic

transmission

autosomal

are

recessive

cranial

(CT) of the head, bones. Six of the pa-

and temporal also underwent

MR imaging

ject of a separate After

recognized:

and

high-resolution

tomography

of the

head and/or extremities for academic interest. The cranial CT and MR imaging findings in these patients will be the sub-

variety of synonyms: Albers-SchOnberg disease, osteosclerosis, osteopetrosis generatisata, and marble bones disease (1). At least two modes of ge-

their

workup,

autosomal

report.

initial

clinical

all patients

low-calcium

diet

and

radiologic

underwent

and

drug

a strict

therapy

with

(2). The autosomal domiis relatively benign, frequently being discovered incidentally in adulthood. Conversely, the autoso-

the vitamin D metabolite calcitriol at dosages of 1-32 g per day (4). Ten of the patients also underwent treatment with in-

mal

Six

dominant nant form

recessive

nant, bone

type

is usually

terferon-y

with death from infection or marrow failure often occurring

before adolescence (3). Because of the extreme osteopetrosis, relatively logic studies are available natural history have recently

under had the

to

an experimental the vitamin By obtaining

regimen

with catcitriol.

lite

radiographs and bone scans in these patients, able

to observe

with

marrow scintiwe have been

some

features concerning distribution of bone progression

medical D metabosequential

interesting

of the

AND

At the

patients

ranged

time

logic

workup.

this

protocol

treatment metabolic, The

included

imaging

filter, and the resulting for radiopharmaceutical

imaging

Scintigraphic

these

(A.D.E.)

to 9.8

status

male con-

involving and radio-

component

bone

marrow scintigraphy and routine wholebody skeletal radiography. Alt patients

at 6,000 counts

retrospectively

3 weeks

sequential

particles

product purity.

was

performed

by

10-minute and extremiwere ob-

per square

centime-

ter.

referral,

protocol clinical,

stethe

Patients were permitted to ingest nothing by mouth for 3-4 hours before the examination, to reduce sptanchnic blood flow. The radiopharmaceuticat was administered intravenously at a graduated dose scaled to body surface area (5). The doses administered for this study, therefore, were 40-285 MBq, depending on the size of each patient.

tamed

sistent with the known autosomat recessive inheritance pattern of the disease. All patients were prospectively enrolled

in a complex an extensive

coltoid

minutes after injection, with exposures used for the skull ties. Liver and spleen images

METhODS

from

tested

Whole-body

disease.

of initial

in age

sulfur

day.

using a gamma camera with a low-energy parallel-hole high-resolution collimator. Imaging was begun approximately 20-30

The study group comprised 12 infants and children with biopsy-proved osteopetrosis referred for imaging over a 6-year period.

0.22-p.m

new

the location and marrow stores

p.g per

administered basis during

were prepared in a standard fashion with a Technecoll kit (Mallinckrodt, St Louis). The solution was passed through a sterile was

We

study 12 children with the autosomal recessive form of this disorder who underwent

of 10-40

clinical trials. Technetium-99m

rarity of few radioto detail its treatment. opportunity

at dosages

of the patients were roids on an intermittent

malig-

(median, 1.9 years). Five were and seven were female, a distribution From the Departments E.G.T.), Pediatrics (L.L.K.),

MD

also underwent

is a family of exbone disorders osteoclast funcis known under a

years

I

Stanton,

#{149}

Osteopetrosis:

PATIENTS Index terms: Bones, osteochondrodysplasias, 40.1552 #{149}Bone marrow, radionucide studies, 10.1299, 40.1299

Key,

#{149}

Radiology

of

images

of marrow

evaluated

who of each

by

was blinded patient

were

a radiologist

to the clinical

as well

as to the

findings at MR imaging and conventional skeletal radiography. First, a general assessment of the marrow stores as a function of age was performed on the basis of published literature concerning the known normal distribution patterns of bone marrow in children of different ages (6-24).

Qualitative

visual

assessments

of

liver and spleen sizes were also performed, these being supplemented with the quantitative criteria of Holder et at (25) 507

Figure 1. Scintigraphic scoring the skull. (a) Scintiscan obtained at age 3 months illustrates grade

system for in patient 3 1. Marrow

activity is substantially greater at the skull base than in the calvanum. (b) Lateral skull radiograph corresponding to a. (c) Scintiscan obtained in patient 9 at age 2.5 years illustrates grade 2. Marrow activity is evenly dis-

tributed ium.

between

the skull

base

and

corresponding obtained in patient grade 3. Marrow

calvar-

(d) Radiograph

(e) Scintiscan years

illustrates

now

greater

in the calvanum.

corresponding

to e. Note

to c.

9 aged

5

activity

is

(f) Radiograph

“hair-on-end”

ap-

pearance.

and Spencer et al (26) when visual assessment was equivocal. A three-tier scoring system

was

allow ity

next

applied

qualitative

in the

to the

grading

lower

images

to

of marrow

extremities

and

the

activskull

(Table 1). These grading schemes are illustrated in Figures 1 and 2. After the review and scoring of the scm-

tigraphic images, nonblinded correlations were made with the simultaneously acquired conventional radiographs (and MR images where available). A review of medical charts was also undertaken to evaluate changes in clinical status related to treat-

ment and disease progression. Follow-up imaging was performed in eight of the 12 patients at intervals of 1 month years after their baseline studies. four

patients

low-up

who

imaging

did

not

at our

undergo

institution

to

4’/2

Those fol-

had

died, gone elsewhere for care, or only just enrolled in the study at the time data for this paper were being compiled. Clinical response and individual problems dictated the precise timing of the follow-up examinations for each patient. RESULTS The observed distribution of bone marrow stores in the skull and lower extremities is recorded in Table 2 and illustrated in Figures 1-4. At inspection of this Table and the associated images, several trends become immediately apparent. In most of the infants younger than 1 year of age, marrow stores were seen to be widely distributed throughout the entire skeleton, including the hands and feet. Focal areas of greater concentration were noted in the lower extremities near the ends of the long bones (metaphyseal-epiphyseal regions). In the skull, activity was confined primarily to the skull base. Hepatosplenomegaly was not prominent in the younger

With

infants.

age and course of the disease, a different pattern of marrow distribution was noted. The marrow spaces in the lower extremities were seen to shift toward the diaphyseal regions. In the skull, the calvar508

advancing

#{149} Radiology

ium

became

row activity. Hepatomegaly

the

principal

site

or splenomegaly

of mar-

present in 11 of 12 patients. Intense activity in these large organs precluded accurate scintigraphic aswas

Febu.jy

1992......

ventional

radiography.

of all patients

base

densely sclerotic ture of this disease less,

a.

The

skull

was found to be as an invariable fea-

(Fig i). Neverthe-

stores of marrow (grades 1 or 2) were

appreciable skull base

in

the detected with nuclear imaging in ii of the 12 patients at some time during their evaluations. In the calvarium, a better correlation was noted. In three older patients, marrow activity definitely shifted to the calvarium (grade 3). In each of these patients, as well as in one grade 2 patient, a prominent “hair-on-end” pattern of the calvarium was noted on conventional radiographs (Fig le, if). MR imaging revealed a similar pattern of involvement, with marrow-containing spaces of intermediate signal intensity inter-

b.

posed spicules

between

low-signal-intensity or osteopetrotic

of reactive

bone. DISCUSSION Osteopetrosis represents a spectrum of skeletal abnormalities characterized by a generalized increase in

the density of bone. There is now a consensus that the origin of this disorder lies in defective osteoclast function (27,28). As a direct result of this defect, bone remodeling is impaired, and the primary calcified substantia spongiosa

d.

C.

scoring system for the tower extremities. A = ankle, K = knee. (a) Scintiscan obtained in patient 4 aged 3 months illustrates grade 1. Marrow activity is greatest near the ends of the long bones. (b) Radiograph corresponding to a. (c) Scintiscan obtained in patient 8 aged 2.3 years illustrates grade 2. Marrow activity is evenly distributed along the entire bone. (d) Radiograph corresponding to c. Note bands of decreased opacity near the metaphyseal-diaphysealjunctions (arrows) (Fig 2 continues). Figure

2.

Scintigraphic

ossium

versely,

the

autosomal

of osteopetrosis typically

sessment of marrow activity in the pelvis, spine, and chest in most cases. Extramedullary hematopoiesis was at pathologic examination in one patient whose spleen was removed for hypersplenism, and a similar process was found in both the

verified

liver and spleen of a second patient examined at autopsy. In general, correlation of the scintigraphic images with conventional radiographs and MR images was good. In the appendicular skeleton, Volume

182

#{149} Number

2

areas of greatest bone marrow activity corresponded to regions of relative decreased opacity on conventional

radiographs

(Fig 3). These same rean intermediate to high signal intensity on T2-weighted MR images (Fig 4). Conversely, only poor differentiation of sclerotic from marrow-containing bone was seen on the Ti-weighted MR images. At the skull base, there was a less clear-cut correlation between findings at marrow imaging and those at congions

possessed

cannot

be

reab-

sorbed. With time, the normal marrow spaces may become obliterated, resulting in pancytopenia and death in severe cases. Several forms of the disorder, with different prognoses and modes of genetic transmission, are now recognized (2). The autosomal dominant type was originally described in 1904 by the German radiologist AlbersSchonberg (29). Persons affected with this form are frequently asymptomatic but may present in adulthood with pathologic fractures, mild anemia, or cranial nerve palsies. Con-

appear

recessive

types

are more severe and in infancy or early

childhood. As a general rule, the earher the clinical presentation, the more malignant the disease. Clinical abnormalities in the autosomal recessive forms include failure to thrive, hepatosplenomegaly, severe anemia, and cranial nerve dysfunction. Progressive obliteration of the marrow space by abnormal bone leads

to pancytopenia

and predis-

poses to recurrent infection, with early patient demise. The autosomal recessive forms may be associated Radiology

#{149} 509

with

renal tubular acidosis (30) and neuronal storage disorders (31). In addition to the classic benign and malignant

forms

tosomal

of osteopetrosis,

an au-

of intermediate severity is now recognized (32). This form appears later in childhood and has a milder clinical course than the

recessive

infantile

The

form

malignant form. of osteopetrosis not a challenge, since

diagnosis

generally

radiologists easily recognize acteristic dense and poorly bones seen on conventional graphs.

Although

the

is

most the charremodeled radio-

diagnosis

is

straightforward, its therapy is complex. Proper medical management requires the combined sophisticated skills of the endocrinologist, hematologist, and radiologist. In 1980, Coccia et al (3) first demonstrated that osteopetrosis could be cured with bone marrow transplantation. It is unfortunate that an appropriate marrow donor cannot always be found, and transplantation is successful only in a minority of patients. Fortunately, a variety of medical therapies have been developed and proved useful in ameliorating the course of this disorder. Key et al (4) first demonstrated that administration of the vitamin D metabolite calcitriol in conjunction with a diet low in calcium could result in increased bone turnover and clinical improvement in severely affected patients. The addition of interferon--)’ to this regimen at our institution has more recently been shown to further heighten the metabolic response (Key LL, personal communication, 1991). Since the primary cause of death in these patients is marrow failure, accurate assessment of the status of bone marrow stores plays a pivotal role in management decisions. A variety of radiologic techniques are now available for assessing bone marrow, in-

cluding scintigraphy, CT, and conventional

of these,

only

bone

radiography. marrow

scintigra-

teopetrosis.

510

#{149} Radiology

f.

MR imaging,

phy provides a direct, whole-body method for visualizing the marrow space. Until the present series, however, the value of this technique in assessing and following up patients with osteopetrosis has, to our knowledge, been unpublished and largely unrecognized. In other marrow disorders (such as sickle cell anemia and thalassemia), however, bone marrow scintigraphy has a proved record of great clinical utility (15,18,19,33-36). It is thus not surprising that it could also prove helpful in evaluating os-

MR imaging

e.

Figure 2 (continued). (e) Scintiscan obtained in patient 9 aged 5 years illustrates grade 3. Marrow activity in the diaphyses (arrows) generally exceeds that near the bone ends. A = ankle, K = knee. (f) Radiograph corresponding to e. Note decreased opacity throughout the diaphyses (arrows) corresponding to regions of greatest marrow activity. Vertical striations of decreased opacity (arrowheads) are noted more distally in the metaphyses, which also correspond to marrow-containing spaces.

has also proved

useful

in defining

the marrow organ in both normal patients and those with a vanety of diseases (19-22). The MR imaging

appearance

of marrow-containing

by the relative proportions of three primary components: mineral content, hematopoietic (“red”) marrow, and fatty (“yellow”) marrow. The contribution to the total MR signal from each of these components will vary by site, age, and sometimes even sex. Vogler and Murphy have provided an excellent recent review of the patterns of marrow conversion during skeletal maturation seen at MR imaging and scintigraphy

bone

(19).

is determined

The high mineral content of trabecand cortical bone tends to reduce its MR signal with all pulse sequences, ular

especially

gradient-echo

techniques.

reduction results from the relative paucity of hydrogen protons within the mineral matrix as well as from susceptibility effects at mineralsoft tissue interfaces. Fatty marrow tends to have relatively high signal intensity on Ti-weighted images because of the naturally short Ti of fat. Hematopoietic marrow (with longer Ti and T2 values) has a lower signal intensity on Ti-weighted images and higher signal intensity on T2weighted images than does yellow

This

February

1992

row

spaces

are typically

opaque

less

than the surrounding sclerotic on conventional radiographs

be of higher signal intensity rotic bone on T2-weighted ages.

bone

and may than scleMR im-

We fully recognize several confounding features in the preceding analysis. First, we may not be record-

ing the natural history of bone marrow stores in osteopetrosis per se, but rather osteopetrosis under treatment with calcitriol and interferon. Since it would provide

a.

b.

Figure

3.

creased

(a) Scintiscan

tient 9 at 6.3 years. long

Table

(b) radiograph

on conventional

opacity

these

and

bones

of left

radiographs

that

Marrow space has migrated away from the more (ie, proximal humerus and distal radius and ulna).

areas

of relative

stores,

rapidly

de-

seen in pa-

growing

ends

of

Scintigraphy Marrow

Patient

Age at Imaging

1/F 2/F

3wk 2mo 3mo 3mo 4mo 3mo 6mo lOmo 9mo l.2y 2.3y l.8y 2.Sy 3.5y 5.0y 6.3y 4.Oy

3

2

H,S

4.5y 6.7y 6.9y 9.8y

3 2 2 2

2 2 2 3

H,S H,S H,S H,S

1O.5y

2

3

H,S

11.5y l2.Oy

2 3

3 3

H,S H,S

7mo

10/M

hIM 12/M

system

#{149} Number

or

in Table 1. neither, S = splenomegaly. splenectomy before imaging.

described N

=

marrow. Numerous other factors (such as iron content and microscopic fat droplets within red marrow stores), however, must also be considered for a more complete explanation of the MR signal changes within developing marrow (21). This study has demonstrated that a definite shift in bone marrow stores occurs with time in patients undergo182

Hepatomegaly Splenomegalyt

N S H,S H H H,S H,S H,S H,S H,S H,S H,S H,S H,S H,S H,S H

5/F

Scoring

SCOre*

Extremities

1 1 2 1 1 1 1 1 1 2 2 2 2 2 2 3 3

4/M

t H = hepatomegaly, t Patient underwent

ACtiVity

1 1 1 I 1 1 1 1 1 2 2 2 2 2 3 3 3

3/M

6/F 7/F 8/F 9/F

Skull

2

ing treatment for osteopetrosis. In infants aged less than 1 year, marrow stores are concentrated primarily at the ends of the long bones and at the skull base. By 3-5 years, in most cases, these initial marrow spaces are crowded out by sclerotic bone. Marrow stores shift to the diaphyseal regions of the lower extremities, the spleen, and the calvarium. These mar-

unethical of treatment

not

to to

these patients when the disease is first recognized, this study is probably as close as we can ever come to witnessing the true natural history of the disease. We take some comfort in six of our 12 patients having not undergone calcitriol therapy until they were aged more than 1 year and each of these patients presenting with grade 2 or 3 distributions of marrow activity before the initiation of therapy. Thus, we

of Bone Marrow

No./Sex

Volume

illustrate

with active marrow

2

Results

*

arm

correlate

be medically some form

believe

the

progression

of bone

marrow 3 does course

distribution from grades 1 to indeed represent the natural of the disease, although the rate of transformation may be affected by therapy. A second potential error in our analysis may have resulted from using a reticuloendothelial agent (Tc99m sulfur colloid) rather than a true hematopoietic agent (such as iron-52) to image bone marrow stores. We should thus be aware that what we are really describing are shifts in reticuloendothelial activity, which may or may not correspond to changes in the true marrow space. In some circumstances, such as aplastic anemia secondary to chemotherapy, a frank dissociation between reticuloendothelial and erythroblastic function has been demonstrated most marrow disorders,

(37-39).

For

however, the two types of nuclear studies are generally recognized to give congruent results (18). The characteristic histopathologic features of osteopetrosis correlate well with the imaging findings we have described. In Figure 5a, a photomicrograph of the proximal humerus of a child dying from osteopetrosis, we see that bone development initially proceeds normally in the region of the growth plate. The expected normal primary trabeculae of the cartilage core can be observed forming just below and among the hypertrophied calcifying cartilage cell columns. In Figure Sa and Sb, we see persistence of these primary trabeculae well into the metaphysis at a point Radiology

511

#{149}

where these cartilage cores should have begun to disappear. Abnormal “globular” bone deposition on the calcified

cartilage

Although veloping sistence

which added, spaces yseal

cores

is also

seen.

some marrow cells are dein marrow spaces, the perof cartilage core trabeculae, enlarge as bone continues to be leaves scant room for marrow to be maintained. In the diaphregion

(Figure

Sc),

we

see

mar-

row spaces that are larger but again encroached upon by primary cartilage core trabeculae. The numerous marrow cells are markedly proliferative, with deeply staining nuclei, and al-

though

this

is a hyperplastic

attempt

at hematopoietic compensation, this absolute decrease in total marrow space may lead to marrow insufficiency with severe clinical consequences.

help of osteopetrosis we have described, in particular, the passage from grade 1 to grade 3 at bone marrow scintigraphy (Tables 1, 2). As the bone develops in osteopetrosis, the marrow spaces in the metaphysis are crowded out first, since the earliest and most prolific bone production occurs in this region. As a result of this crowding, nuclear activity in the bone marrow diminishes in the metaphyses and increases elsewhere in the bone where space is still available for marrow production. This crowding continues from the metaphyses to the center of the diThese

pathologic

explain

the

specimens

imaging

features

tigraphic

middle of the shaft (passage from grade 1 through grade 3). Findings corresponding to these scintigraphic shifts of marrow activity may also be appreciated on conventional radiographs. Areas of abnormal opacity on conventional radiographs have long been known to correspond to the pathologic regions of calcified primary trabeculae and globular secondary bone deposition (1,2). The marrow-containing spaces thus correspond to regions of relative decreased opacity on these same radiographs. The exact distribution of sclerotic regions and regions of decreased opacity

within by

site.

osteopetrotic In the

femur,

bones for

exam-

ple, relatively equal activity of the growth plate occurs at either end. As a result, both ends of the femur become progressively sclerotic and marrow activity shifts toward the center of the diaphysis (Fig 4). In the humerus, however, the proximal growth plate is much more active than the distal one. The sclerotic region of the 512

b.

C.

d.

and eventually, marrow scmactivity is greatest at the

aphysis,

varies

a.

Radiology

#{149}

Figure 4. Simultaneously obtained (a) radiograph, (b) marrow scintiscan, and (c, d) MR images of the lower extremities in patient 12 at 10.5 years. (a) Conventional radiograph shows ends of the femurs to be sclerotic, with bands of central decreased opacity, especially in the diaphyses. (b) Scintiscan shows activity throughout bone but especially in the middle of the shaft (arrows) (grade 3). (c) Ti-weighted (600/20 [repetition time msec/echo time msec]) coronat MR image shows bones to be of generally low signal intensity and marrow-containing regions to be only a little higher in intensity (arrows). (d) On a T2-weighted image (2,300/60), these marrow-containing regions acquire a higher, intermediate signal intensity (arrows).

humerus seen on conventional radiographs is consequently much larger proximally than distally (Fig 3). Areas of greatest marrow activity and corresponding relative decreased opacity are likewise found in the distal diaphysis and metaphyseal-diaphyseal region rather than more centrally within this bone. Osteopetrosis is an extremely rare disease, and its medical management is varied, complex, and constantly changing. Accordingly, no clear consensus has yet emerged that defines the exact role or timing for imaging studies in this disorder. On the basis of our experience at a major referral

we believe that marrow scmis important in the management of autosomal recessive osteopetrosis, even considering the vast array of other clinical and laboratory tests available. For example, during medicat therapy, patients with osteopetrosis frequently develop progressive anemia, which may be due to hypersplenism, the effects of chemothercenter,

tigraphy

apy,

or marrow

space

encroachment

by osteopetrotic bone. The independent assessment of total marrow stores with marrow scintigraphy is especially useful in this situation and in many others. The role of MR imaging is less well investigated but may February

1992

a.

b.

c.

Figure 5. Characteristic histologic findings in osteopetrosis (Armed Forces Institute of Pathology case no. 56-10164). (a) Low-power photomicrograph of the junction between the lower end of the growth plate (upper third of the field) and subjacent metaphysis of the humerus in a child with osteopetrosis (original magnification, x 100). Arrows denote hypertrophied calcifying cartilage cell columns, while asterisks (*) overlie several calcified primary trabeculae. Arrowheads indicate new bone deposition on the scaffolding of calcified cartilage cores. The fundamental problem in osteopetrosis is the failure to remove these normally formed primary cartilage core trabeculae so that they can be replaced by

adult

(secondary)

trabeculae

composed

entirely

3 cm below the field in a (original While this is a normal finding

even

marrow

cells are developing

in marrow

spaces

x260).

core

magnification,

have deeply

staining

Cartilage

nuclei

of bone.

magnification,

junction preciated.

near

trabeculae

is limited by the exuberof the liver and spleen.

In summary, we have tried to demonstrate pathologically and radiologically the shift in bone marrow stores that accompanies the clinical progression of osteopetrosis. In the long bones, marrow activity (and relative decreased opacity at radiography) shifts from the metaphysis toward the diaphysis, with the final position dictated by the relative growth rates of each bone end. In the skull, marrow activity is initially concentrated at the skull base, with extension and subsequent dominance of the calvarium as the disease progresses. It is hoped that knowledge of this natural history of bone marrow stores will prove useful in assessing medical therapy in the treatment of this difficult disorder. #{149} References 1.

2.

182

#{149} Number

plate,

it should

(S). (c) Intermediate-power (*) are

3,

4,

5.

6.

7.

8. 9.

10.

11.

Edeiken J, Dalinka M, Karasick D. Edeiken’s roentgen diagnosis of diseases of bone. 4th ed. Baltimore: Williams & Wilkins, 1990; 1625-1628. McAlister WH. Osteochondrodysplasias, dysostoses, chromosomal aberrations, mucopolysaccharidoses, and mucolipidoses. In: Resnick D, Niwayama C, eds. Diagnosis

Volume

growth encroaching

photomicrograph deposition (arrows) never

be seen

at the

photomicrograph on

the

marrow

spaces

obtained near the metaphyseal-diaphyseat on calcified cartilage cores (*) is better metaphyseal-diaphyseal

of the diaphysis (S). The

marrow

from cells

are

junction.

the same markedly

bone

ap-

Some

(original

proliferative

and

(arrows).

be helpful in evaluating marrow stores in the pelvis and spine, where scintigraphy ant activities

the

(b) Intermediate-power x 260). Globular bone

2

12.

of bone and joint disorders. 2nd ed. Philadelphia: Saunders, 1988; 3478-3483. Coccia PF, Krivit W, Cervenka J, et al. Successful bone-marrow transplantation for infantile malignant osteopetrosis. N Englj Med 1980; 302:701-708. Key L, Carnes D, Cole 5, et at. Treatment of congenital osteopetrosis with high-dose calcitriol. N EnglJ Med 1984; 310:409-415. Chilton HM, Witcofski LR. Nuclear pharmacy. Philadelphia: Lea & Febiger, 1986; 47. Trabowitz 5, Davis S. The bone marrow matrix. In: The human bone marrow: anatomy, physiology, and pathophysiology. Boca Raton, Fla: CRC, 1982; 43-76. Kricun ME. Red-yellow marrow conversion: its effect on the location of some solitary bone lesions. Skeletal Radiol 1985; 14: 10-19. Hashimoto M. Pathology of bone marrow. Acta Haematol 1%2; 27:193-216. Dunnill MS. Anderson JA, Whitehead R. Quantitative histological studies on age changes in bone. J Pathol Bacteriol 1967; 94:275-291. Williams AG, Mettler FA, Christie JH. Sulfur colloid distribution in normal hips. Clin Nuci Med 1983; 8:490-492. EmeryJL, Follett GF. Regression of bonemarrow hemopoiesis from the terminal digits in the foetus and infant. Br J Haematol 1964; 10:485-489. Custer RP. Studies on the structure and function of bone marrow. I. Variability of the hemopoietic pattern and consideration of method for examination. J Lab Clin Med 1932; 17:951-959.

13.

14.

15.

16.

17.

18.

19. 20.

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