Interesting Bone Changes in Plain Urograms

THE: JOURNAL OF UROLOGY

Vol. 67, No. 4, April 1952 Printed in U.S.A.

INTERESTING BONE CHANGES IN PLAIN UROGRAlvrS W. L. F'ITZGERALD

AND

M. D. THOl\IAS,

JK

In urological practice patients frequently are seen ,vith the primary complaint of pain in the back, thighs, or limited to the right or left side of the abdomen. These patients may or may not have urinary symptoms associated with these pains. In an investigation of these cases the urologist is often the first physician to use recourse to an x-ray as a diagnostic aid in evaluating these complaints. Thus, the plain urogram may reveal the first evidences of the existence of pathological processes in the bone. It is the purpose of this presentation to give in a condensed manner a) some of the more important fundamental considerations prerequisite to proper identification of bone lesions, b) the classic appearance of some of these lesions as the urologist sees them, and c) the most important additional data ,vhich may be needed to substantiate the clinical diagnrn,is of such lesions. Due to the multiplicity of causes of bone lesions only those -will be discussed which, in our opinion, are of the most interest to the urologist or most commonly seen by him. No thought will be given to primary bone tumors, inflammatory diseases of the bones, or the various types of arthritis. Brevity likewise demands the exclusion of renal rickets and the now rarely seen osteomalacia. It is not within the scope of this discussion to enter into the minute diagnostic procedures ,vhich at times may be needed for a definitive diagnosis. The use of consultations ,vith radiologist, orthopedist, and internist ,,vill be desirable in many cases. BONE METABOLISM

Bone is a living tissue; bone metabolism iR a continuous, active process simultaneously involving osteoblastic and osteolytic activity, also deposition and absorption of calcium salts. The metabolic rate, however, as compared \\·ith other body tissues is very low. Some bone lesions are predominately osteoblastic ,vhile others are osteolytic. The fact that both processes occur side by side and simultaneously explains why mixed-type lesions are sometimes seen in the same disease. J\fetastatic carcinoma of the prostate and Paget's disease frequently present mixed-type lesions. CALCIUM

The calcium of the body 1s contained largely in the skeletal system, with smaller amounts in the tissues and the circulating blood. Calcium is absorbed in the small bmrnl; it is excreted in the small bmrnl and the urine. Variation in the calcium metabolism will cause variations in the amount of urinary calcium. The blood calcium is composed of both a nondiffusible and a diffusible or ionized calcium. The 11oncliffusible calcium is bound to the blood protein, and constitL1tcs apprnximatcly 60 per cent of the total calcium of the blood. The diffnsible eoJcium is the physiologically active calcium. If the total serum protein and serum calcinm values are known, use of the McLean-Hastings chart wiD Read at annual mcAting, Southeastern Section, American l:rological Association, :\lemphis, Tenn,, J\farch 8, 1D51. 5+7

548

W. L. FITZGERALD AND M. D. THOMAS, JR.

enable one to arrive at the correct diffusible calcium value. Abnormal total serum calcium values may be misleading unless this finding is correlated with that of total serum protein. This is of aid in arriving at the diagnosis of hyperparathyroidism. The Sulkowitch test of the urine may be used as a quick simple office procedure for screening patients and selecting those to be subjected to the expense of blood chemical determinations for further study. PHOSPHORUS

The serum phosphorus level has a definite clinical significance in these studies. Phosphorus metabolism is influenced by the parathyroid glands. It is believed that the essential action of the parathyroid hormone is to lower the renal threshold for phosphates, presumably by inhibiting the reabsorption of these substances in the kidney tubules. Thus, overactivity of these glands as in hyperparathyroidism is associated with increased phosphorus excretion by the kidney and decrease in serum phosphorus level. In hypoparathyroidism the reverse circumstance prevails. In states of renal insufficiency the serum phosphorus is elevated. PHOSPHATASE

The term phosphatase is used to designate an enzyme which may be measured in the circulating blood serum. The phosphatase activity measures, in arbitrary units, the ability of this enzyme to decompose a pure, known amount of phosphate ester under controlled conditions of time, temperature, and pH. If the reaction is carried out under acid conditions the result is a measure of the acid phosphatase activity of the serum; if the reaction is carried out in an alkaline medium the result is a measure of the alkaline phosphatase activity of the serum. The alkaline phosphatase is believed to be produced by the osteoblasts or bone forming cells. It is absorbed by the lymphatics and the blood stream. Its excretion is by way of the biliary system. Therefore in the absence of obstructive jaundice, an elevation of the serum alkaline phosphatase is an indication of increased bone formation. In the presence of Paget's disease of the bone it may be elevated as much as forty times its normal reading, though in an early localized Paget's there may be no significant elevation of this enzyme. It may also be elevated in the presence of osteoblastic type of metastatic carcinoma, and in 100 per cent of cases of hyperparathyroidism with bone involvement. The serum acid phosphatase is produced by the tissues of the prostate gland. The ability to produce acid phosphatase in large amounts is retained by prostatic carcinoma. This enzyme apparently does not enter the blood stream in any significant clinical amounts except in extension of carcinoma of the prostate through the prostatic capsule. It has been found to be elevated in 85 per cent of the cases of carcinoma of the prostate with demonstrable metastases. It is not elevated in any significant clinical amounts in any other disease. The fate of this enzyme in the body has not been clearly established. The following diseases have been chosen for discussion. The most important data on each are presented in the accompanying charts.

549

BONE CHANGES IN PLAIN UROGRAMS

Senile osteoporosis

L

TABLE

BLOOD CHEMISTRY

KTJB

OTHER BO~ES

/1.GE

I

Phos)tase

I

F

Acid Alk. - - - - - - - - - 1 - - - - - - - · · - - - - - - · - - - - ··--· · - -

General decalcification

TABLE

2.

N

Same as KUB

Advanced 3°ears

N

N

N

Hyperparathyroidisrn

------------------- --------------------

--------·----

BLOOD CHEMISTRY KUB

OTHER BONES

URliNE

Phos'tase

p

Ca Acid Alk. ----------- ------·---- -- --

Renal calcinosis calculus

* Increased

or

Localized cystic changes Large bony swellings

"'*

N

---

i

1.\

High

Low

Increased Ca excretiont

100% of cases with bone changes. test,

t Sulkowitch

TABLE

Paget's (osteitis deformans)

3.

I

I

KUB

SKULL, OTHER

AGE

BONES

BLOOD CHEMISTRY

Phos'tase Acid

Localized or general fibr o-c3·stic changes Pelvis and vertebra Trabeculations

I

Mid-life to advanced years

TABLE

Thickening of skull Motheaten Sabre shin

N

Alk. ---

Ca

p

--

--

Very N high

I

-- I

J. Multiple rnyeloma

:BLOOD CHEMISTRY

KUB

OTHER

BONES

Phosphatasf:

Ca Acid

Multiple, small

RS

N

p

Alk. l\T to sL high

Blood Protein

BLOOD

BONE

COUNT

MARROW

----'----/N to very I high

punchedout osteo-

N

l\1yelom9, Elevated in Atypical 50% w bile cells cells

of Nephritis

A-G Ratio reversed

High in

relYJ.S, verte-·

I

bra, ribs ----~----·-

5oc;1a

,Globulin I ele"''ated

-------------

Progress Hypochromic anemia

Bence-Jones Protien (60%)

----------'-----

SENILE OSTEOPOROSIS

This condition is not uncommon. The plain urogram -will shmr uniform de-· creased density of the bones of the vertebrae and the pelvis. It is said to less affect the skull or the extremities. The basic pathological 1s

550

,V. L. FITZGERALD AND M. D. THOMAS, JR. TABLE

5.

Metastatic: Thyroid, breast, kidney, lung BLOOD CHEMISTRY

I I

I Phos 'tase

OTHER BONES

KUB

~1

iAcid

Osteolytic lesions

i

Spine o r long bones

GENERAL

I

--·

N*II

IN

p

Ca

N

N

History phys. Exam. Pyelogram chest film Search for primary source

Ca

P

;

Localized or general Kidney shadow

High in rapid bone destr.

I 1.

I

* Increased in rare osteoblastic lesions. TABLE

lVletastatic: Carcinoma of prostate

6.

I _____ K_U_B________

Localized or diffuse lesions Osteoblastic or osteolytic Pelvis, vertebra, ribs (late)

BLOOD CHEMISTRY

1_:··

M'"'

Acid

Alkaline

--------1--------1----- -------

Skull to rule out Paget

Highin85% cases with bone metas.

I I

-------

I

N

BLOOD CHEMISTRY

General decalcific Renal calcinosis or calculus

Paget's

Fi bro-cystic changes Local-general Small punchedout lesions

Multiple myeloma

Metastatic: Thyroid, Breast, ney, Lung

Lesions osteolytic or osteoblastic

Metastatic: Ca Prostate

Lesions osteoblastic and/or osteolytic

K

Very rare except in assoc. with other metas.

I'

_P_h_o_s_p_h-at_a_s_e_ _ _ _ _ _ • PR~~~~~s Acid

Senile osteoporosis Hyperparathyroidism

N

May be elevated in predom. osteoblastic lesions

7. Important findings

TABLE

KUB

LUNG

Phosphatase

Ca

P

High

Low

URI.:-{E

BOKE MARROW

GEKERAL

Alk.

Increased calcium excretion

High

Skull and tibia Total high BenceMyeloma A-G Ratio Jones cells reversed protein

High

I

Search for primary Rectal palpation

apparently a failure of osteoblastic activity. Thus, one would not expect any significant changes in the blood chemistry. There may be some increase in the urinary calcium excretion in the early stages of the disease. See table 1.

BOKE CHANGES IK PLAIN UROGRAJ\!IS

Fro . l

5-5)

Senile osteoporosis. Appearance of generalized bony decalcification

FIG. 2 . A, hyperparat.hyroidism. Renal calcinosis. No bone changes. Consistently high blood calcium and low blood phosphorus. B, hyperparathyroidism. Unilateral renal ca] .. culi. Generalized osteitis fibrosis cystica. HYPERPARATHYROIDISM

This disease is caused overactivity of the parathyroid gland due to adenomas or accessary parathyroid tissue. The clinical findings are due to the bone

552

W. L. FITZGERALD AND M. D. THOMAS, JR.

changes, urinary tract disease, and hypercalcernia. In many cases no bone lesions are present. When bone changes are present they consist of generalized decalcification, with superimposed cysts or tumors, i.e. osteitis fibrosa cystica. There is an increase in both the osteoblasts and osteoclasts in these lesions. There is

r

Fm. 3. A, advanced Paget's disease of bone. Increased thickness and heavy appearance of bones, due to osteoblastic activity and subperiosteal ossification. Fibrocystic areas. B, moderately advanced Paget's disease. Typical bony changes throughout left side of pelvis. Bony trabeculations in ilium adjacent to hip joint. C, early Paget's disease. Thickening of cortex and fibrocystic changes in left ilium. Bony trabeculations.

an absence of the lamina dura around the teeth. The skull may have a ground glass appearance in addition to cysts. The urinary tract lesions may be nephrocalcinosis or one or more kidney stones. Bilateral diffuse calcification in the renal parenchyma may be due to other causes, however, the persistence of a high serum calcium and a low serum phosphorus is diagnostic of hyperparathyroidism. The urinary calculi seen in the stage prior to secondary bacterial invasion are of the calcium oxalate or the calcium phosphate variety. The most constant chemical findings are hypercalcemia, hypophosphatemia, and hypercalcuria.

r

BONE CHANGES IN PLAIN TJROGRAMS

553

The serum alkaline phosphatase is elevated only in cases with bone involvemect. See table 2.

Fm. 4. A, skull in Paget's disease. lVfoth-eaten appearance. Thickening of skull place. B, Paget's disease. Sabre -shin.

Frn. 5. A, multiple myeloma. Typical punched-out osteolytic lesions of left ilium, transverse process L3 and twelfth rib, left. B, carcinoma of breast. Widespread osteolytic process. Film made 5 years following radical am.putation of breast. PAGET 1S DISEASE OF BO."\:BJ

This disease is characterized by simultaneous osteolytic and osteoblastic activities, both of which are increased in tempo. The cortex of the bone exhibits an overgrowth and thickening. Portions of the bone structure are replaced by

554

W. L. FITZGERALD AND M. D. THOMAS, JR.

fibrous tissue some of which degenerates leading to cysts, thus, the term "fibrocystic" is applied to the appearance of the bone. Irregular trabeculations of bone are present. There are cases in which deficient calcification and abnormal structure are apparent and this results in deformities due to relative lack of rigidity in the bony skeleton. This disease is of particular interest to the urologist because it produces bone lesions which are most likely to be confused with metastatic carcinoma of the prostate. Distinguishing features of Paget's, however, in addition to the appearance of the bone lesions in the plain urogram are typical skull involvement, sabre shin, normal acid phosphatase, and very high serum alkaline phosphate. See table 3.

Fm. 6. Carcinoma of kidney. Destructive osteolytic process localized to one lumbar vertebra. MULTIPLE MYELOMA

Bone lesions in this disease can vary but the typical case presents small punched-out osteolytic areas. Ribs, spine, pelvis, and skull are commonly involved. Much confirmatory evidence is available where the bone lesions suggest multiple myeloma, namely, urine findings including the Bence-Jones protein, bone marrow studies, hyperproteinemia with reversal of the A-G ratio, due to increased blood globulin. Therefore, since approximately one half of blood calcium is combined with the proteins, total blood calcium determinations will in many cases be above normal. Blood phosphorus will ordinarily be found normal, except in terminal cases where renal insufficiency and consequent retention of phosphorus occurs. See table 4. METASTATIC: CARCINOMA OF THYROID, BREAST, KIDNEY, AND LUNG

These lesions arise principally from the sites enumerated. Hans E. Walther in 1948 analysed a series of 470 cases of carcinoma which had metastasized to bone.

BONE CHANGES IN PLAIN UIWGRAMS

555

Carcinoma of the breast led the list with 47 per cent exhibiting bone 1netastases. Then followed, in order, carcinoma of prostate 42 per cent, thyroid 30 per

Fm. . A, advanced carcinoma of prostate. Widespread lesions, predominantly osteobbstic. B, moderately advanced careinoma of prostate. Osteoblastic lesions of right ilium. C:, carcinoma of prostate. Rather rare pure osteolytic lesions involving pubic n1mus, right. Serum acid phosphatase 80 units.

lung 29 per cent, and kidney 19 per cent. These are the commonest muses of the metastatic bone lesions seen the urologist.. These metastatic lesions, in contrast to metastatic carcinoma of the prostate, are usually ostcolytic in appear·

556

W. L. FI'l'ZGERALD AND M. D. THOMAS, JR.

ance. The sites of metastasis may be seen in the spine and pelvis and also in other bones. There are no characteristic changes in the blood chemistry, except in cases of rapid and widespread bone destruction which may result in a high blood calcium. To be emphasized in the diagnosis of these conditions is a thorough clinical history and a general physical examination. Pyelograms and x-rays of the chest will be of value in the search for the primary source. See table 5. METASTATIC: CARCINOMA OF PROSTATE

This is the bone lesion most often seen by the urologist in the plain urogram. It is the bone lesion in which he is most interested and which he must differentiate as positively as possible from all others. In contrast to most other metastatic bone lesions, metastatic carcinoma of the prostate is predominately osteoblastic though mixed-type lesions are seen, and rarely pure osteolytic changes occur. Pelvis, spine, and ribs are usually involved in that order. The most valuable confirmatory finding in suspected metastatic carcinoma of the prostate is elevation of the serum acid phosphatase. It is increased in 85 per cent of cases with bone metastasis. Alkaline phosphatase is increased in proportion to the amount of osteoblastic activity. Lung metastases are very rare except in association with other metastases. A solitary metastatic lesion in the lung, without evidence of other metastases, is practically never due to carcinoma of the prostate. See tables 6 and 7, and figures 1 to 7. CONCLUSIONS

An attempt has been made to condense and tabulate the pertinent data on bone changes in cases in which the urologist most frequently sees in his daily study of the plain urogram. The presentation consists of 1) elementary but fundamental considerations needed in the interpretation of bone lesions, 2) discussion and tabulation in condensed form of the classic features of some bone lesions in which the urologist is most interested, and 3) suggestions as to additional clinical, laboratory and x-ray data which are of value in proving or disproving a diagnosis of a presenting bone lesion, and 4) illustrative x-ray films. 422 Ingraham Bldg., Miami 32, Fla. REFERENCES ALBRIGHT, F. AND REIFENSTEIN, E. C. JR.: Parathyroid Glands and J\ietabolic Bone Disease. Baltimore: Williams and Wilkins Co., 1949. ANDERSON, W. A. D.: Synopsis of Pathology. St. Louis: C. V. Mosby Co., 1942. BEST, C.H. AND TAYLOR, N. B.: Physiological Basis of Medical Practice. Baltimore: Williams and Wilkins Co., 1945, 4th ed. BoDANSKY, M. AND BoDANSKY, 0.: Biochemistry of Disease. New York: The Macmillan Co., 1945. ELLSWORTH, R.: J. Olin. Investig., 11: 1011, 1932. ENGEL, W. J.: Nephrocalcinosis. J.A.M.A., 145: 288, 1951. GUTMAN, A. B.: Tumor of the skeletal system. Medical aspects. Bull. N. Y. Acad. Med. 23: 512, 1947. GUTMAN, A. B., TYSON, T. L. AND GuT!vIAN, E. B.: Serum calcium, inorganic phosphorus and phosphatase activity in hyperparathyroidism, Paget's disease, multiple myeloma and neoplastic disease of the bone. Arch. Int. Med., 57: 379, 1936. KrNSELL, L. W.: Consideration of calcium and phosphorus metabolism. Am. Pract., 3: 499, 1942. WALTHER, H. E.: Krebsmetastasen. Basel: Bruno Schwalbe, 1948. WOODARD, H. Q. AND DEAN, A. L.: Significance of phosphatase finding in carcinoma of prostate. J. Urol., 57: 158, 1947. REZEK, Philipp, Miami, Fla., personal communication.