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Urinary calculi in Paget's disease (osteitis deformans)
URINARY CALCULI IN PAGET’S DISEASE (OSTEITIS DEFORMANS) * A. E. GOLDSTEIN, M.D., F.A.C.S. Associate in PathoIogy, University MaryIand School of Medicine
AND B. S. ABESHOLJSE,
M.D.
Instructor in Pathology, University Maryland SchooI of Medicine
of
BALTIMORE,
T
of
MD.
than commonly supposed. WhiIe the duration of the disease is indefinite, it has reIativeIy IittIe inffuence upon the genera1 heaIth of the patient, and is seIdom, if ever, the cause of death. The onset is insidious, manifesting a tendency to symmetrica invoIvement of the bones especiaIIy the tibia, femur, peIvic, fronta parieta1 and occipita1 bones. TypicaI cases involving singIe bones, especiaIIy the facia1 bones, phaIanges of the fingers or the Iong bones of the extremities have aIso been described. The disease is characterized cIinicaIIy by a hypertrophy and deformity of the bones invoIved which may or may not be associated with pain. The pathoIogy is essentiaIIy a rarefying osteitis combined with new bone formation. The etioIogy of Paget’s disease remains unsettIed. A direct relation between this disease and any constitutiona disease has not been estabIished. Some writers have suggested the reIation of an infectious process such as syphiIis, typhoid, maIaria, inffuenza, erysipelas to a IocaI or genera1 osteitis deformans, traumatic or neurotrophic bone Iesions, etc. It has been suggested by White that osteitis deformans may be but one stage of a deficiency disease. The disease can be reproduced in monkeys fed on a diet insufficient in its organic and vitamin content to which an excess of caIcium is added. Definite impairment of kidney function occurs in most cases of osteitis deformans as pointed out by ScuIIy. The pathoIogica1 changes of the kidney associated with this disease are primariIy a scIerosis of the
HE deveIopment of urinary caIcuIi in patients with osteitis deformans is infrequentIy observed as indicated by the scant references to this phenomenon in the literature. The contributions to this subject are Iimited to the report of a singIe case by Young and to genera1 statements by Squier, Keyser and others. In a comprehensive discussion of the etioIogic factors in nephroIithiasis, Squier stressed the roIe of caIcium metaboIism in the genesis of nephroIithiasis and the importance of considering the reIation of caIcium metaboIism to stone formation in the various bone diseases, i.e., osteitis deformans, osteomaIacia, osteoporosis, osteopsathyrosis, chronic coxitis, rickets, etc. The purpose of this paper is to present 6 cases of urinary caIcuIi in patients suffering with osteitis deformans and to brieffy discuss the possibIe etioIogica1 factors concerned in the production of urinary caIcuIi in this disease. The authors have aIso studied the occurrence of urinary caIcuIi in various other bone diseases, Le., arthritis, rickets, hyperparathyroidism, fractures of the long bones, fractures of the spine, etc., and the resuIt of this study wiI1 be pubhshed at a subsequent date.
OSTEITIS DEFORMANS Osteitis deformans was first described as a disease entity by Sir James Paget in 1876 and hence bears his name. It is a chronic disease of the bones found in both sexes and requires five to fifteen years to reach its maximum deveIopment. The disease is of more frequent occurrence * From the Department
PH.B.,
of Genito-Urinary 349
Surgery, Sinai Hospital
360
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interstitia1 tissue and a thickening of the waIIs of the bIood vessels. Young and Waters reported a case of
FIG. IA.
NOVEMBER,1~35
Paget’s disease. A roentgenogram of his spine was taken six months Iater and reveaIed a CaIcuIus in each kidney-
FIG. IB.
FIG. I. Case I. A. Roentgenogram of skuII shows typica changes of osteitis deformans. B. Roentgenogram of Iumbar spine aIso reveaIs same changes in Iumbar vertebrae. Arrow points to a smaI1 stone in Iower poIe of right kidney.
renaI and uretera caIcuIi in a man of fifty years. Roentgenograms showed very extensive bony changes characteristic of Paget’s disease, a marked trianguIar deformity of the peIvis, a stone measuring 0.8 X I .2 cm. in the right ureter near the peIvis and two smaI1 stones in the Iower caIyx of the right kidney. Examination of urine was negative except for a few pus ceIIs. PhthaIein excretion was 43 per cent for two hours. This case (Case I, A. C.) was seen and treated by us prior to the examination by Dr. Young and hence is reported in detai1 by us. CASE I. A. C., white, maIe, fifty years, married, merchant, referred by Dr. J. FriedenwaId. Admitted to Sinai HospitaI on March 14, 1925 with a compIaint of pain in the Ieft abdomen. The famiIy history was negative. Past history was unimportant with the exception that one year prior to admission he underwent a thorough examination and was toId he had
Present Illness: The patient had his first attack of Ieft renaI coIic six weeks ago. The attack recurred three days Iater but Iasted onIy two hours. A roentgenogram was taken at this time and a shadow was noted in the right and Ieft kidney regions, aIso one in the region of the Ieft ureter. The onIy urinary symptom present was diurna1 frequency. There was no history of hematuria, of passing of grave1 or stone. Physical Examination: The patient was short of stature, measuring 5 feet, 3 inches in height. His head appeared to be unusuaIIy large and buIging. There was an obvious increase in the antero-posterior diameter of the chest. A definite shortening of the spina coIumn was noted. SIight tenderness was present over the entire Ieft side of the abdomen. The Iower poIe of the Ieft kidney was paIpabIe. The externa1 genitalia were negative. The prostate was norma in size, shape and consistency. Laboratory Studies: A voided specimen of urine was negative for aIbumin and sugar and on microscopic examination an occasiona red bIood ceI1 and pus ceI1 were noted. The P. S. P. test gave an output of 18 per cent for
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the first hour and 17 per cent for the second hour. Course: A compIete cystoscopic and roentgenographic study was made ‘shortIy after admission. Cystoscopic and pyeIographic studies reveaIed a caIcuIus 3 cm. in diameter in a Iower major caIyx of the right kidney and a caIcuIus of simiIar size was noted in a simiIar position in the Ieft kidney. A Iarger ova1 shaped caIcuIus measuring I x 0.5 cm. was noted at the Ieft ureteropeIvic junction. The Ieft kidney presented a moderate hydronephrosis. Roentgenograms of the skuII and peIvic bones showed the typica changes of Paget’s disease (Figs. I and 2). A Ieft ureteroIithotomy was performed under gas anesthesia and the stone was removed. The patient made an uneventfu1 recovery. Diagnosis: (I) Paget’s disease; (2) nephroIithiasis, biIatera1; (3) Ieft ureteral caIcuIus. CASE II. F. R. S., white, maIe, aged sixty-one years, married, retired poIiceman, referred by Dr. Harvey Beck. He was seen for the first time of pain in on December 12, 1922 compIaining the Ieft abdomen and frequent urination. The famiIy history was negative. At the age of seventeen years, he contracted gonorrhea which was complrcated by gonorrhea1 arthritis involving both wrists, eIbows, knees, and ankIes. At the age of twenty-one years, he feI1 from a height of 4 feet and struck his back. At the age of thirtv-four he joined the police force when the minimum height was 5 feet, 7 inches. At the age of fifty-three, he was 5 feet, 255 inches taI1. He has been under a physician’s care with treatment for Paget’s disease for the past four years. Eighteen months ago, he passed a smaI1 stone following an attack of right renaI coIic. One year ago he had a simiIar attack of right renaI coIic accompanied by hematuria but did not pass a stone. Present Illness: This dates back six months during which time there had been a marked frequency, burning, dysuria, urgency, and poIIakiuria. He has compIained of severe coIicky pains in the left Iower quadrant radiating up to left Iumbar region for the past six months. Physical Examination: The patient was of a very short stature. When he stood with both heeIs together there was marked bowing outward and forward of the Iower extremities. There was a general bowing of both femurs, more marked on the right than on the Ieft. The peIvis was flattened anteroposteriorIy.
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There was sIight tenderness in the Iower quadrants. The externa1 genitaIia were negative. Recta1 examination discIosed a first degree
FIG.
2. Case I. Roentgenogram reveals characteristic changes of osteitis deformans in bony pelvis.
enlargement of the prostate due to a benign hypertrophy. Laboratory Studies: Voided specimen of urine was alkaline in reaction and had a specific gravity of 1.020. Tests for aIbumin and sugar were negative. Microscopic examination showed an occasiona red bIood ceI1, pus ceI1, and hyaIine cast. BIood Wassermann reaction was negative. An intravenous phthaIein test showed 25 per cent for the first hour and 20 per cent for the second hour. Course: Cystoscopic and pyeIographic studies reveaIed two calculi, the size of pecans, in the bIadder and one, the size of a pea, in the Iower portion of the Ieft ureter. The caIcuIi in the bIadder were removed with a cystoscopic rongeur. After severa diIatations of the Ieft ureter the caIcuIus in the Ieft ureter was passed into the bladder and removed with a rongeur. FoIIowing this the patient had no further urinary disturbances. Roentgenographic studies were made of the entire skeIeta1 svstem while under our care (Fig. 3). The crania1 bones showed a moderate thickening with mottIed areas of bone condensation throughout but more marked in the fronta and upper parieta1 regions. PIates of the spine showed a definite decalcification of the bodies of a11 the vertebrae with a decrease in the vertica1 diameter of the bodies and a corresponding increase in the transverse diameter. The peIvic bones appeared to be thickened
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and presented diffuse mottIed areas of decaIcification. Both femur were bowed in a forward and outward direction.
FIG.
FIG. 3(Case
3~.
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Laboratory Studies: Voided specimen of urine was negative for albumin and sugar, but on microscopic examination severa Gus’ and
FIG.
38.
II. Roentgenograms showing typica changes of osteitis deformans in (A) skuII, (B) petvis and Iumbar vertebrae. Two smaII shadows, situated above symphysis pubis, are vesical calculi.
Diagnosis: (I) Paget’s disease; (2) vesical caIcuIi; (3) Ieft uretera caIcuIus. CASE III. B. B. F., white, maIe, aged sixtynine years, singIe, retired merchant, referred by Drs. J. FriedenwaId and Erwin Mayer. Admitted to the Sinai Hospital, March 4, 1926 with the complaint of pain in the left abdomen and left Iumbar region. The famiIy and past history were unimportant. Present Illness: About ten days ago, the patient deveIoped an acute attack of pain in the Ieft abdomen which radiated upward to the Ieft Iumbar region. The pain Iasted one-haIf hour and recurred in five hours. He has had two to three similar attacks daily. There was no nausea, vomiting, chiIIs or fever. The onIy urinary symptoms the patient compIained of were burning on urination and nocturia. Physical Examination: Definite tenderness was eIicited in the Ieft upper and Iower quadrants and in the Ieft Iimbar region. Neither kidney was paIpabIe. Recta1 examination discIosed a first degree enIargement of the prostate.
red blood cells were found. The bIood Wassermann reaction was negative. The bIood urea was within normal limits. Course: Cystoscopic examination was performed on March 4, 1926. There was a sIight intravesica1 buIging of the prostate posteriorly in the form of a median bar. The left ureterat orifice was diIated, edematous and injected and appeared as though something had passed through it. Twenty-four hours Iater a smaI1 rough caIcuIus, the size of a pea, was removed from the posterior urethra under cauda1 anesthesia. On cystoscopy a no. 6 catheter was passed up each ureter into the pelvis of the kidney without encountering any obstruction. A Ieft ureteropyelogram reveaIed a norma peIvis and caIyces. A roentgenogram of the genitourinary tract reveaIed no shadows in the kidney or uretera regions. The peIvic bones particuIarIy the ischia and pubes showed the typica changes of Paget’s disease (Fig. 4). The patient was discharged from the hospita1 eighteen days later in exceIIent condition.
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The patient was not seen again until Febto the ruary 1 I, 1928 when he was re-admitted hospitaI for further study. He had two attacks of renaI colic since Iast seen. A voided specimen of urine showed many red bIood ceIIs on microscopic .examination. On cystoscopy the Ieft uretera orifice was congested. A no. 6 catheter was passed up the Ieft ureter but encountered an obstruction 8 cm. up which was not overcome. The ureter was diIated up to the point of obstruction. A roentgenogram was taken but faiIed to revea1 any shadows in the kidney or uretera regions. Cystoscopy was repeated five days Iater and the same obstruction was encountered. A roentgenogram reveaIed a smaI1 but indistinct shadow at the tip of the catheter. Two uretera catheters were passed up to the point of obstruction and Ieft in pIace for twelve hours. Two days Iater the patient passed two smaI1 stones. A third stone, the size of a pea, was removed from the bladder by means of a cystoscopic rongeur five days Iater. One week after the caIcuIus was removed from the bladder the patient compIained of severe pain in the Ieft renaI region, accompanied fly nausea, vomiting and abdominal distention. The temperature rose to IOS’F. and continued to be high and septic in character. A bIood culture was taken two days Iater and was positive for Streptococcus hemoIyticus. Eleven days after the positive blood cuIture another cystoscopic examination was performed and again an obstruction was encountered in the Ieft ureter which was overcome. Despite al1 measures the blood stream infection persisted and the patient sank rapidIy and died twenty-four days after the first positive blood culture. A partia1 autopsy was obtained. Numerous smaI1 yeIIowish stones were found in the Ieft kidney which showed a severe pyeIonephritis. Subsequent roentgen examination of this kidney reveaIecI the caIcuIi to be of the nonradiable type. Diagnosis: (I) Paget’s disease; (2) nephroIithiasis, left. CASE I\.. This case is reported through the courtesy of the Iate Dr. Frontz. L. K., aged fifty-five years, married, jeweIer. Admitted to Sinai HospitaI on JuIy 24, 1932 with the compIaint of pain in the Iower right quadrant. Family and past history were negative. Present Illness: The onset dates back three
J,,,,rn;il01Surgrl-\ AI,w~c,,I~
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wee!
FIG. 4. Case III. Localized type of osteitis deformans involving pubic and ischial bones, particuIarIy on Ieft side. Finer details of changes in structure of these bones is Iost in process of photographic reproduction. Above tip of Ieft ureteral catheter is faint outline of smaI1 calcu’lus.
attack of renaI coIic on the right side. The plin radiated down to the right testicIe and \\a~ accompanied by nausea and vomiting but no chiIIs or fever. He has had a diurna1 frequency every two hours for the past two years but there is no history of dysuria, urgency, burning, tenesmus or passmg of gravel or stone. Physical Examination: His head appeared asymmetrica due to a buIging of the left parieta1 and tempora1 regions. There are no other bony changes noted. The heart and Iungs were negative. AbdominaI examination revealed tenderness in the right upper quadrant and in the right Iower quadrant along the course of the ureter. Recta1 examination discIosed a second degree enlargement of the prostate, which was soft and doughy. Laboratory. Studies: Urine, voided specimen, on June 24, 1932 was acid and had a specific gravity of 1.003. A faint trace of aIbumin was found but the test for sugar was negative. Microscopic examination showed an occasional red bIood ceI1 and few pus ceIIs per high power fieId. An intravenous phthaIein test showed 30 per cent for the first hour and IO per cent for the second hour. The blood urea was 43.1
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mg. per cent. The bIood Wassermann was negative. Course: Cystoscopic examination
FIG.
FIG. 5. Case IV. GeneraLed
& Abeshouse-CalcuIi reaction
was
per-
NOVEMBER,
married, housewife. UnfortunateIy, a compIete history couId not be obtained in this case. The foIIowing information has been suppIied
5A.
type
FIG. of osteitis deformans points to small
involving (A) skull, calculus in Ieft ureter.
formed on June 25, 1932. The right uretera orifice was diIated and congested, indicating the passage of a smaI1 stone through this orifice. The kidney urine was negative except for an occasiona red bIood ceI1. Stereoscopic right uretero-pyelograms were taken and reveaIed a norma peIvis, caIices and ureter. Examination of the Iumbar spine and peIvis showed a marked increase in density of the lumbar vertebrae, sacrum and peIvis. There is no evidence of a destructive process in any of the Iumbar vertebrae. A moderate degree of scoliosis of the lumbar vertebrae to the Ieft is noted. A roentgenogram of the skuI1 showed the typical changes of Paget’s disease (Fig. 5). During his stay in the hospital the patient had no further urinary trouble. He was put on a diet rich in vitamins A and D. He was discharged from the hospita1 on July 5, 1932 in exceIIent condition. (2) right Diagnosis: (I) Paget’s disease; uretera caIcuIus, passed. CASE v. This patient is reported through the courtesy of Drs. J. Evans and C. GabrieI. C. F., white, femaIe, aged fifty-eight years,
,939
(B)
SB.
p e Ivis and lumbar
vertebrae.
Arrow
by Dr. Evans. The patient’s famiIy history was negative except that an older sister had had Paget’s disease which was confirmed by roentgen studies. The patient had enjoyed fairIy good heaIth but had suffered with symptoms of an upper urinary tract Iesion for many years. She had compIained of marked diurna1 and nocturna1 frequency, urgency, burning and dysuria. The patient feI1 and sustained a fracture of the Iower end of the left femur and died five days Iater. Death was sudden and was attributed to an acute myocardia1 faiIure. Examination of the patient revealed an advanced Paget’s disease invoIving practicaIIy a11 the long bones of the body. The head was markedIy enIarged and buIging due to invoIvement of a11 the crania1 bones. The chin was tapering in character. A kyphosis of the thoracic spine was present. The diagnosis of Paget’s disease of the bones was confirmed by roentgen examination. A roentgenogram taken to study the Iumbar vertebrae discIosed a large stone in the Ieft kidney region (Fig. 6). Diagnosis: (I) Paget’s disease; (2) nephroIithiasis, left.
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CASE VI. This patient was referred by Dr. M. B. Levin. H. B., maIe, aged seventy-two years, married, retired merchant. He was seen
FIG. 6. Case V. GeneraILed
type
of osteitis
Journ;~l of Surgery
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of his joints. His head is markedly emarged. There is a deformity of both elbows, wrists and joints of his fingers. The abdomen is very
deformans with advanced changes Iarge caIcuIi in Ieft kidney.
for the first time at home on October 3, 1932 complaining of frequency of urination. The famiIy history was essentiahy negative. The patient had been treated for “rheumatism” and arthritis for the past twenty years. For the past few years, he has received treatment for various foci of infection which incIuded diathermic treatment of the tonsiIs, remova of infected teeth, a nasa1 and sinus operation. He states that he had renaI coIic fifteen years ago but does not recaI1 on which side the pain occurred. He passed a stone from his hIadder thirty years ago. Present Illness: The onset of the present troubIe dates back severa months when he began to compIain of frequency, occurring every hour during the day and three to four times at night, diffrcuIty in starting his stream, straining, urgency, burning and intermittency. On two occasions in the past three months, he deveIopec1 an acute retention of urine and had to be relieved by catheterization. He has had in the chiIIs and fever at irreguIar intervaIs past few weeks. He has aIso complained of pain in both lumbar regions, more marked on the right than on the Ieft side. There is no radiation of pain. He occasionahy has a duI1 pain in the suprapubic region. The patient has been confined to bed for the past five years because of inabiIity to move his Iower extremities. The patient stated that his arthritis is becoming progressively worse. Physical Examination: Patient is a very stout obese maIe. He is unabIe to stand due to the pain and pressure attending movements
American
in skuI1 and peIvis.
There
are several
obese. Neither kidney is paIpabIe. There is slight tenderness in the right lumbar region but no tenderness over either kidney or ureter anteriorIy. Recta1 examination discIosed a benign hypertrophy of the prostate, first degree. Laboratory Studies: Voided specimen of urine was acid in reaction and had a specific gravity of 1.020. Tests for aIbumin and sugar were negative. Microscopic examination reveais many pus and red bIood ceIIs. Course: A pIain roentgenogram of the genitourinary tract reveaIed a shadow the size of a waInut in the region of the bIadder. Under cauda1 anesthesia, the vesica1 caIcuIus was crushed and removed. Two weeks later the patient returned complaining of pain in his right kidney region fohowing an automobiIe ride. A roentgenogram of the genitourinary tract revealed a shadow the size of a Iima bean in the Iower right ureter. Roentgen studies of the skull, pelvis and spine were taken and showed the typica osseous changes of Paget’s disease (Fig. 7). Diagnosis: (I) Paget’s disease; (2) vesica1 caIculus; (3) right uretera caIcuIus; and (4) arthritis deformans. DISCUSSION
The formation of urinary caIcuIi in osteitis deformans may be dependent upon one or more primary factors. These factors may pIay an etioIogica1 roIe in the production of the primary bone disease and secondariIy influence the formation of
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urinary factors to the
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calcuh. On the other hand, these may bear no etioIogica1 reIation bone disease but directIy or in-
NOVEMBER, ,933
in osteitis deformans and that this thickening is due to a deposition of Iime saIts in the wail of the blood vesseIs. Similar
FIG. 7~.
FIG. 7~.
FIG. 7. Case VI. Generalized type of osteitis deformans showing characteristic change in (A) skul1, pelvis. Large shadow opposite right ischial spine is vesical calculus.
directly as a resuIt of the bone disease, they may influence the subsequent formation of caIcuIi. Each of the foIIowing factors worthy of brief consideration as possibIe etioIogica1 agents in the production of urinary caIcuIi in osteitis deformans: (I) pathoIogica1 or physioIogica1 changes; (2) diet; (3) aItered caIcium metaboIism. I.
PATHOLOGICAL
AND
PHYSIOLOGICAL
CHANGES
PathoIogicaI studies have reveaIed the fact that the primary causative agent responsible for the deveIopment of the osseous changes is an endarteritis of the blood vesseIs in the bone. The vascuIar changes may be Iimited to the bIood vessels of the bones or may be part of a generaIized It vascuIar disease, i.e., arterioscIerosis. is we11 known that a characteristic thickening of the peripheral bIood vesseIs exists
(B)
spine and
scIerotic changes may be noted in the waIIs of the renaI vesseIs which may Iead to an interstitia1 fibrosis with a resuItant impairment in renaI function. The authors are of the opinion that the impairment in renaI function has no etioIogica1 significance in the deveIopment of the bone changes but are either secondary to the bone disease or mereIy an associated condition. However, as a result of the kidney changes, there may be some disturbance in the kidney parenchyma or to the formation of urinary caIcuIi. II.
DIET
The causa1 reIation of deficient diet to osteitis deformans may aIso serve as a possibIe expIanation of the simuItaneous occurrence of urinary caIcuIi in this disease. White was abIe to reproduce the bone disease in monkeys fed on a diet deficient
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in its organic and vitamin A content to which an excess of calcium was added. Other investigators have also stressed the association of a vitamin A deficient diet with osteitis deformans and osteoporosis. The experimenta production of urinary caIcuIi, composed of caIcium phosphate, in rats fed on vitamin A deficient diets was first observed by Osborne, MendeI and Perr\- and Iater verified by Fujumaki, McCarrison, Van Leersum, Higgins and others. The importance of these observations is further emphasized by the fact that urinary Iithiasis has been reported in the various bone diseases, i.e., rickets, osteitis deformans, osteomaIacia or osteoporosis which are presumabIy due to dietary deficiencies. Squier states that the association of vitamin A deficiency with the various bone diseases suggests the possibility that the formation of urinary caIculi in these bone diseases may be the result of a secondary disturbance of calcium metaboIism rather than the direct resuIt of the dietary. This theory appears to be quite IogicaI in view of the fact that the exact mechanism concerned in the formation of urinary caIcuIi resuIting from vitamin A deficiency is as yet undetermined. Se\:eraI theories have been offered to expIain urinary Iithiasis due to dietary deficiency. Some investigators (Osborne, MendeI, and Perry PerIman, and Weber and others) maintain that a diet deficient in vitamin A Iowers the resistance to infection and that this infection may occur in the urinary tract with subsequent stone formation. However, this process appears experimentaIIy at Ieast to be unassociated with infection. McCarrison stressed the toxic effect of the deficient diet on the renaI epitheIium and renaI function as a probable factor and considered stone formation to be the resuIt of the deposition of caIcium phosphate upon the effete ceIIs of the tubular epitheIium which serve as a nucleus. KiIIian has suggested that the increased aIkaIinity of urine which is due to formation of ammonia in cases of vitamin deficiency, may not be entirely
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the property of bacteria but aIso the result of a disturbance of renal function. He believed that vitamin A deficiency changes the character of the renaI epitheIium so that it is possibIe for crystaIIoids to become adherent to the epitheIia1 ceIIs. JoIy and Higgins are of the opinion that calculosis associated with vitamin deficiency is the resuIt of some action upon the urinary coIIoids which reduces their power of hoIding stone-forming saIts in soIution. III.
CALCIUM
METABOLISM
It is our belief that the causal relationship between osteitis deformans and urinary Iithiasis is to be sought in the disturbance of the caIcium and phosphorus metaboIism associated with osteitis deformans and the impaired secretory function of the kidneys so frequentIy encountered in this disease. Da Costa and his co-workers have found a retention of calcium, magnesium and phosphorus with an excessive excretion of suIphur. AnaIysis of the bone ash in osteitis deformans reveaIs the bone to be rich in caIcium despite their softness. In the case reported by Cuthbertson, the bIood caIcium was within norma Iimits and the figures for the CO2 reserve indicated the presence of a miid acidosis. As far as we have been abIe to determine, hypercaIcemia is not associated with osteitis deformans. However, it is we11 recognized that disturbances of caIcium metaboiism may occur without an increase in caIcium content in the bIood. Squier states that the reverse is more often the case in those conditions of disturbed caIcium metaboIism associated with renaI caIcuIus. IsraeI maintained that metastatic calcification may take pIace without decomposition of bone or hypercalcemia. The exact mechanism by which disturbances in caIcium metaboIism produce chemica1 or pathoIogica1 changes which uItimateIy resuIt in the precipitation of the urinary constituents with subsequent formation of urinary caIcuIi is by no means clearly established. The role of other
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metaboIic disturbances, i.e., phosphorus, magnesium, suIphur, etc., in the deveIopment of urinary Iithiasis is even more obscure. Urostasis and infection of the urinary tract apparentIy bear no great significance as etioIogica1 factors in the production of urinary caIcuIi in osteitis deformans. The presence of stasis or infection in cases of osteitis deformans, whiIe not a causa1 factor per se, certainIy favors the formation and recurrence of Iithiasis by keeping up the infection in the urinary tract. CONCLUSIONS
Our observations in 6 cases of urinary Iithiasis in patients suffering from osteitis deformans justifies the foIIowing concIusions : I. Urinary Iithiasis is an infrequent, though not uncommon, comphcation of osteitis deformans. 2. SeveraI probabIe etioIogica1 factors may be considered in estabIishing a causal
NOVEMBER, 1935
reIation between osteitis deformans and urinary Iithiasis: (a) a pathologica condition, i.e., arterioscIerosis or endarteritis, affecting primariIy the bones and secondariIy the kidneys; (b) dietary deficiency, (c) disturbance in caIcium metaboIism. 3. WhiIe the exact mechanism responsibIe for the formation of urinary caIcuIi in osteitis deformans is undetermined, the authors are of the opinion that most probabIe causa1 factor concerned in the formation of caIcuIi in these cases is a disturbance in the caIcium metaboIism with an associated impairment of renaI secretory function. 4. Since experimenta studies have cIearIy estabIished the roIe of vitamin A deficient diets in the production of urinary caIcuIi in the experimenta anima1 and in the production of osteitis deformans, it is obvious that carefuI attention shouId be paid to the diet in the treatment and prevention of caIcuIi in individuaIs afllicted with osteitis deformans.
REFERENCES
I. CONE, S. Pathology of osteitis deformans. J. Bone 0’ JO&t &Ug., 4: 751 (Oct.) 1932. 2. CUTHBERTSON, D. P. Note on the balance of calcium, magnesium and sulphur in a case of osteitis deformans. Glasgow M. J., 108: 218 (Oct.) 1927. 3. DACOSTA, J. C., FUNK, BERGEIM and HAWK. PubI. of Jefferson Med. College. PhiIa., 1915; 6: I. 4. FUJIMAKI, Y. Experimenta production of caIcuIi in the kidney and bladder. Japan Med. World, 6:2 (Feb. 15) 1926. 5. HIGGINS, C. C. Experimental production of urinary caIcuIi. J. Ural., 29: 157 (Feb.) 1933. 6. ISRAEL, W. BiIateraI nephroIithiasis with spondyIarthritis ankyIopoeitica. Ztscbr. f. Ural., 16: 321, 1922. 7. JOLY, S. J. Stone and caIcuIous disease of the urinary organs. St. Louis, Mosby, 1931. 8. KEYSER. L. D. Urinarv lithiasis: its cause and orevention. An evaluation of contributions to our knowledge during the past decade. Southern M. J., 25: 1031 (Oct.) 1932. Q. KILLIAN. In discussion of RandalI’s articIe. AM. J. SURG., 18: 432 (Dec.) 1932.
IO. MCCARRISON, L. Experimenta production of stone in the bladder. B&. M. J., I : 717 (ApriI 16) 1927. I I. OSBORNE. T. B.. MENDEL. L. B.. and PERRY. E. L. The incidence of phosphatic’urinary calculi in rats fed on experimental rations. J. A. M. A., 69: 32 (July 7) 1917. 12. PERLMAN, S., and WEBER, W. Experimenta production of urinary calculi. titinchen. med. Wcbnscbr.. 77: 680 (AoriI 18) 10~0. 13. SCULLY, F. J. Kidney function in osteitis deformans. Med. J. CY Rec., 120: 62 (JuIy 16) 1924. 14. SQUIER, J. B. CaIcuIous disease of the kidney and ureters. Chap. x, Lewis’s Practice of Surgery, Hagerstown, Tice, 1931. 15. VAN LEERSUM, E. C. Vitamin A deficiency and urolithiasis. &it. M. J., 2: 873 (Nov. 12) 1927. 16. WELLS, H. G. Metastatic calcification. Arch. Int. Med., 15: 574, 1915. 17. WHITE, E. P. C. Osteitis deformans in monkeys. Arch. Int. Med., 30: 790, 1922. 18. YOUNG, H. H. Practice of UroIogy. PhiIa., Saunders, 1926, I: 377; 2: 661. IQ. YOUNG, H. H., and WATERS, C. A. UroIogicaI Roentgenology. Annals of RoentgenoIogy. N. Y., Hoeber, 1928, 7: 412.459, 482. I
II
,a
,,*
AND B. S. ABESHOLJSE,
M.D.
Instructor in Pathology, University Maryland SchooI of Medicine
of
BALTIMORE,
T
of
MD.
than commonly supposed. WhiIe the duration of the disease is indefinite, it has reIativeIy IittIe inffuence upon the genera1 heaIth of the patient, and is seIdom, if ever, the cause of death. The onset is insidious, manifesting a tendency to symmetrica invoIvement of the bones especiaIIy the tibia, femur, peIvic, fronta parieta1 and occipita1 bones. TypicaI cases involving singIe bones, especiaIIy the facia1 bones, phaIanges of the fingers or the Iong bones of the extremities have aIso been described. The disease is characterized cIinicaIIy by a hypertrophy and deformity of the bones invoIved which may or may not be associated with pain. The pathoIogy is essentiaIIy a rarefying osteitis combined with new bone formation. The etioIogy of Paget’s disease remains unsettIed. A direct relation between this disease and any constitutiona disease has not been estabIished. Some writers have suggested the reIation of an infectious process such as syphiIis, typhoid, maIaria, inffuenza, erysipelas to a IocaI or genera1 osteitis deformans, traumatic or neurotrophic bone Iesions, etc. It has been suggested by White that osteitis deformans may be but one stage of a deficiency disease. The disease can be reproduced in monkeys fed on a diet insufficient in its organic and vitamin content to which an excess of caIcium is added. Definite impairment of kidney function occurs in most cases of osteitis deformans as pointed out by ScuIIy. The pathoIogica1 changes of the kidney associated with this disease are primariIy a scIerosis of the
HE deveIopment of urinary caIcuIi in patients with osteitis deformans is infrequentIy observed as indicated by the scant references to this phenomenon in the literature. The contributions to this subject are Iimited to the report of a singIe case by Young and to genera1 statements by Squier, Keyser and others. In a comprehensive discussion of the etioIogic factors in nephroIithiasis, Squier stressed the roIe of caIcium metaboIism in the genesis of nephroIithiasis and the importance of considering the reIation of caIcium metaboIism to stone formation in the various bone diseases, i.e., osteitis deformans, osteomaIacia, osteoporosis, osteopsathyrosis, chronic coxitis, rickets, etc. The purpose of this paper is to present 6 cases of urinary caIcuIi in patients suffering with osteitis deformans and to brieffy discuss the possibIe etioIogica1 factors concerned in the production of urinary caIcuIi in this disease. The authors have aIso studied the occurrence of urinary caIcuIi in various other bone diseases, Le., arthritis, rickets, hyperparathyroidism, fractures of the long bones, fractures of the spine, etc., and the resuIt of this study wiI1 be pubhshed at a subsequent date.
OSTEITIS DEFORMANS Osteitis deformans was first described as a disease entity by Sir James Paget in 1876 and hence bears his name. It is a chronic disease of the bones found in both sexes and requires five to fifteen years to reach its maximum deveIopment. The disease is of more frequent occurrence * From the Department
PH.B.,
of Genito-Urinary 349
Surgery, Sinai Hospital
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interstitia1 tissue and a thickening of the waIIs of the bIood vessels. Young and Waters reported a case of
FIG. IA.
NOVEMBER,1~35
Paget’s disease. A roentgenogram of his spine was taken six months Iater and reveaIed a CaIcuIus in each kidney-
FIG. IB.
FIG. I. Case I. A. Roentgenogram of skuII shows typica changes of osteitis deformans. B. Roentgenogram of Iumbar spine aIso reveaIs same changes in Iumbar vertebrae. Arrow points to a smaI1 stone in Iower poIe of right kidney.
renaI and uretera caIcuIi in a man of fifty years. Roentgenograms showed very extensive bony changes characteristic of Paget’s disease, a marked trianguIar deformity of the peIvis, a stone measuring 0.8 X I .2 cm. in the right ureter near the peIvis and two smaI1 stones in the Iower caIyx of the right kidney. Examination of urine was negative except for a few pus ceIIs. PhthaIein excretion was 43 per cent for two hours. This case (Case I, A. C.) was seen and treated by us prior to the examination by Dr. Young and hence is reported in detai1 by us. CASE I. A. C., white, maIe, fifty years, married, merchant, referred by Dr. J. FriedenwaId. Admitted to Sinai HospitaI on March 14, 1925 with a compIaint of pain in the Ieft abdomen. The famiIy history was negative. Past history was unimportant with the exception that one year prior to admission he underwent a thorough examination and was toId he had
Present Illness: The patient had his first attack of Ieft renaI coIic six weeks ago. The attack recurred three days Iater but Iasted onIy two hours. A roentgenogram was taken at this time and a shadow was noted in the right and Ieft kidney regions, aIso one in the region of the Ieft ureter. The onIy urinary symptom present was diurna1 frequency. There was no history of hematuria, of passing of grave1 or stone. Physical Examination: The patient was short of stature, measuring 5 feet, 3 inches in height. His head appeared to be unusuaIIy large and buIging. There was an obvious increase in the antero-posterior diameter of the chest. A definite shortening of the spina coIumn was noted. SIight tenderness was present over the entire Ieft side of the abdomen. The Iower poIe of the Ieft kidney was paIpabIe. The externa1 genitalia were negative. The prostate was norma in size, shape and consistency. Laboratory Studies: A voided specimen of urine was negative for aIbumin and sugar and on microscopic examination an occasiona red bIood ceI1 and pus ceI1 were noted. The P. S. P. test gave an output of 18 per cent for
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the first hour and 17 per cent for the second hour. Course: A compIete cystoscopic and roentgenographic study was made ‘shortIy after admission. Cystoscopic and pyeIographic studies reveaIed a caIcuIus 3 cm. in diameter in a Iower major caIyx of the right kidney and a caIcuIus of simiIar size was noted in a simiIar position in the Ieft kidney. A Iarger ova1 shaped caIcuIus measuring I x 0.5 cm. was noted at the Ieft ureteropeIvic junction. The Ieft kidney presented a moderate hydronephrosis. Roentgenograms of the skuII and peIvic bones showed the typica changes of Paget’s disease (Figs. I and 2). A Ieft ureteroIithotomy was performed under gas anesthesia and the stone was removed. The patient made an uneventfu1 recovery. Diagnosis: (I) Paget’s disease; (2) nephroIithiasis, biIatera1; (3) Ieft ureteral caIcuIus. CASE II. F. R. S., white, maIe, aged sixty-one years, married, retired poIiceman, referred by Dr. Harvey Beck. He was seen for the first time of pain in on December 12, 1922 compIaining the Ieft abdomen and frequent urination. The famiIy history was negative. At the age of seventeen years, he contracted gonorrhea which was complrcated by gonorrhea1 arthritis involving both wrists, eIbows, knees, and ankIes. At the age of twenty-one years, he feI1 from a height of 4 feet and struck his back. At the age of thirtv-four he joined the police force when the minimum height was 5 feet, 7 inches. At the age of fifty-three, he was 5 feet, 255 inches taI1. He has been under a physician’s care with treatment for Paget’s disease for the past four years. Eighteen months ago, he passed a smaI1 stone following an attack of right renaI coIic. One year ago he had a simiIar attack of right renaI coIic accompanied by hematuria but did not pass a stone. Present Illness: This dates back six months during which time there had been a marked frequency, burning, dysuria, urgency, and poIIakiuria. He has compIained of severe coIicky pains in the left Iower quadrant radiating up to left Iumbar region for the past six months. Physical Examination: The patient was of a very short stature. When he stood with both heeIs together there was marked bowing outward and forward of the Iower extremities. There was a general bowing of both femurs, more marked on the right than on the Ieft. The peIvis was flattened anteroposteriorIy.
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There was sIight tenderness in the Iower quadrants. The externa1 genitaIia were negative. Recta1 examination discIosed a first degree
FIG.
2. Case I. Roentgenogram reveals characteristic changes of osteitis deformans in bony pelvis.
enlargement of the prostate due to a benign hypertrophy. Laboratory Studies: Voided specimen of urine was alkaline in reaction and had a specific gravity of 1.020. Tests for aIbumin and sugar were negative. Microscopic examination showed an occasiona red bIood ceI1, pus ceI1, and hyaIine cast. BIood Wassermann reaction was negative. An intravenous phthaIein test showed 25 per cent for the first hour and 20 per cent for the second hour. Course: Cystoscopic and pyeIographic studies reveaIed two calculi, the size of pecans, in the bIadder and one, the size of a pea, in the Iower portion of the Ieft ureter. The caIcuIi in the bIadder were removed with a cystoscopic rongeur. After severa diIatations of the Ieft ureter the caIcuIus in the Ieft ureter was passed into the bladder and removed with a rongeur. FoIIowing this the patient had no further urinary disturbances. Roentgenographic studies were made of the entire skeIeta1 svstem while under our care (Fig. 3). The crania1 bones showed a moderate thickening with mottIed areas of bone condensation throughout but more marked in the fronta and upper parieta1 regions. PIates of the spine showed a definite decalcification of the bodies of a11 the vertebrae with a decrease in the vertica1 diameter of the bodies and a corresponding increase in the transverse diameter. The peIvic bones appeared to be thickened
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and presented diffuse mottIed areas of decaIcification. Both femur were bowed in a forward and outward direction.
FIG.
FIG. 3(Case
3~.
NOVEMRER, rgsf
Laboratory Studies: Voided specimen of urine was negative for albumin and sugar, but on microscopic examination severa Gus’ and
FIG.
38.
II. Roentgenograms showing typica changes of osteitis deformans in (A) skuII, (B) petvis and Iumbar vertebrae. Two smaII shadows, situated above symphysis pubis, are vesical calculi.
Diagnosis: (I) Paget’s disease; (2) vesical caIcuIi; (3) Ieft uretera caIcuIus. CASE III. B. B. F., white, maIe, aged sixtynine years, singIe, retired merchant, referred by Drs. J. FriedenwaId and Erwin Mayer. Admitted to the Sinai Hospital, March 4, 1926 with the complaint of pain in the left abdomen and left Iumbar region. The famiIy and past history were unimportant. Present Illness: About ten days ago, the patient deveIoped an acute attack of pain in the Ieft abdomen which radiated upward to the Ieft Iumbar region. The pain Iasted one-haIf hour and recurred in five hours. He has had two to three similar attacks daily. There was no nausea, vomiting, chiIIs or fever. The onIy urinary symptoms the patient compIained of were burning on urination and nocturia. Physical Examination: Definite tenderness was eIicited in the Ieft upper and Iower quadrants and in the Ieft Iimbar region. Neither kidney was paIpabIe. Recta1 examination discIosed a first degree enIargement of the prostate.
red blood cells were found. The bIood Wassermann reaction was negative. The bIood urea was within normal limits. Course: Cystoscopic examination was performed on March 4, 1926. There was a sIight intravesica1 buIging of the prostate posteriorly in the form of a median bar. The left ureterat orifice was diIated, edematous and injected and appeared as though something had passed through it. Twenty-four hours Iater a smaI1 rough caIcuIus, the size of a pea, was removed from the posterior urethra under cauda1 anesthesia. On cystoscopy a no. 6 catheter was passed up each ureter into the pelvis of the kidney without encountering any obstruction. A Ieft ureteropyelogram reveaIed a norma peIvis and caIyces. A roentgenogram of the genitourinary tract reveaIed no shadows in the kidney or uretera regions. The peIvic bones particuIarIy the ischia and pubes showed the typica changes of Paget’s disease (Fig. 4). The patient was discharged from the hospita1 eighteen days later in exceIIent condition.
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The patient was not seen again until Febto the ruary 1 I, 1928 when he was re-admitted hospitaI for further study. He had two attacks of renaI colic since Iast seen. A voided specimen of urine showed many red bIood ceIIs on microscopic .examination. On cystoscopy the Ieft uretera orifice was congested. A no. 6 catheter was passed up the Ieft ureter but encountered an obstruction 8 cm. up which was not overcome. The ureter was diIated up to the point of obstruction. A roentgenogram was taken but faiIed to revea1 any shadows in the kidney or uretera regions. Cystoscopy was repeated five days Iater and the same obstruction was encountered. A roentgenogram reveaIed a smaI1 but indistinct shadow at the tip of the catheter. Two uretera catheters were passed up to the point of obstruction and Ieft in pIace for twelve hours. Two days Iater the patient passed two smaI1 stones. A third stone, the size of a pea, was removed from the bladder by means of a cystoscopic rongeur five days Iater. One week after the caIcuIus was removed from the bladder the patient compIained of severe pain in the Ieft renaI region, accompanied fly nausea, vomiting and abdominal distention. The temperature rose to IOS’F. and continued to be high and septic in character. A bIood culture was taken two days Iater and was positive for Streptococcus hemoIyticus. Eleven days after the positive blood cuIture another cystoscopic examination was performed and again an obstruction was encountered in the Ieft ureter which was overcome. Despite al1 measures the blood stream infection persisted and the patient sank rapidIy and died twenty-four days after the first positive blood culture. A partia1 autopsy was obtained. Numerous smaI1 yeIIowish stones were found in the Ieft kidney which showed a severe pyeIonephritis. Subsequent roentgen examination of this kidney reveaIecI the caIcuIi to be of the nonradiable type. Diagnosis: (I) Paget’s disease; (2) nephroIithiasis, left. CASE I\.. This case is reported through the courtesy of the Iate Dr. Frontz. L. K., aged fifty-five years, married, jeweIer. Admitted to Sinai HospitaI on JuIy 24, 1932 with the compIaint of pain in the Iower right quadrant. Family and past history were negative. Present Illness: The onset dates back three
J,,,,rn;il01Surgrl-\ AI,w~c,,I~
363
wee!
FIG. 4. Case III. Localized type of osteitis deformans involving pubic and ischial bones, particuIarIy on Ieft side. Finer details of changes in structure of these bones is Iost in process of photographic reproduction. Above tip of Ieft ureteral catheter is faint outline of smaI1 calcu’lus.
attack of renaI coIic on the right side. The plin radiated down to the right testicIe and \\a~ accompanied by nausea and vomiting but no chiIIs or fever. He has had a diurna1 frequency every two hours for the past two years but there is no history of dysuria, urgency, burning, tenesmus or passmg of gravel or stone. Physical Examination: His head appeared asymmetrica due to a buIging of the left parieta1 and tempora1 regions. There are no other bony changes noted. The heart and Iungs were negative. AbdominaI examination revealed tenderness in the right upper quadrant and in the right Iower quadrant along the course of the ureter. Recta1 examination discIosed a second degree enlargement of the prostate, which was soft and doughy. Laboratory. Studies: Urine, voided specimen, on June 24, 1932 was acid and had a specific gravity of 1.003. A faint trace of aIbumin was found but the test for sugar was negative. Microscopic examination showed an occasional red bIood ceI1 and few pus ceIIs per high power fieId. An intravenous phthaIein test showed 30 per cent for the first hour and IO per cent for the second hour. The blood urea was 43.1
364
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mg. per cent. The bIood Wassermann was negative. Course: Cystoscopic examination
FIG.
FIG. 5. Case IV. GeneraLed
& Abeshouse-CalcuIi reaction
was
per-
NOVEMBER,
married, housewife. UnfortunateIy, a compIete history couId not be obtained in this case. The foIIowing information has been suppIied
5A.
type
FIG. of osteitis deformans points to small
involving (A) skull, calculus in Ieft ureter.
formed on June 25, 1932. The right uretera orifice was diIated and congested, indicating the passage of a smaI1 stone through this orifice. The kidney urine was negative except for an occasiona red bIood ceI1. Stereoscopic right uretero-pyelograms were taken and reveaIed a norma peIvis, caIices and ureter. Examination of the Iumbar spine and peIvis showed a marked increase in density of the lumbar vertebrae, sacrum and peIvis. There is no evidence of a destructive process in any of the Iumbar vertebrae. A moderate degree of scoliosis of the lumbar vertebrae to the Ieft is noted. A roentgenogram of the skuI1 showed the typical changes of Paget’s disease (Fig. 5). During his stay in the hospital the patient had no further urinary trouble. He was put on a diet rich in vitamins A and D. He was discharged from the hospita1 on July 5, 1932 in exceIIent condition. (2) right Diagnosis: (I) Paget’s disease; uretera caIcuIus, passed. CASE v. This patient is reported through the courtesy of Drs. J. Evans and C. GabrieI. C. F., white, femaIe, aged fifty-eight years,
,939
(B)
SB.
p e Ivis and lumbar
vertebrae.
Arrow
by Dr. Evans. The patient’s famiIy history was negative except that an older sister had had Paget’s disease which was confirmed by roentgen studies. The patient had enjoyed fairIy good heaIth but had suffered with symptoms of an upper urinary tract Iesion for many years. She had compIained of marked diurna1 and nocturna1 frequency, urgency, burning and dysuria. The patient feI1 and sustained a fracture of the Iower end of the left femur and died five days Iater. Death was sudden and was attributed to an acute myocardia1 faiIure. Examination of the patient revealed an advanced Paget’s disease invoIving practicaIIy a11 the long bones of the body. The head was markedIy enIarged and buIging due to invoIvement of a11 the crania1 bones. The chin was tapering in character. A kyphosis of the thoracic spine was present. The diagnosis of Paget’s disease of the bones was confirmed by roentgen examination. A roentgenogram taken to study the Iumbar vertebrae discIosed a large stone in the Ieft kidney region (Fig. 6). Diagnosis: (I) Paget’s disease; (2) nephroIithiasis, left.
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CASE VI. This patient was referred by Dr. M. B. Levin. H. B., maIe, aged seventy-two years, married, retired merchant. He was seen
FIG. 6. Case V. GeneraILed
type
of osteitis
Journ;~l of Surgery
365
of his joints. His head is markedly emarged. There is a deformity of both elbows, wrists and joints of his fingers. The abdomen is very
deformans with advanced changes Iarge caIcuIi in Ieft kidney.
for the first time at home on October 3, 1932 complaining of frequency of urination. The famiIy history was essentiahy negative. The patient had been treated for “rheumatism” and arthritis for the past twenty years. For the past few years, he has received treatment for various foci of infection which incIuded diathermic treatment of the tonsiIs, remova of infected teeth, a nasa1 and sinus operation. He states that he had renaI coIic fifteen years ago but does not recaI1 on which side the pain occurred. He passed a stone from his hIadder thirty years ago. Present Illness: The onset of the present troubIe dates back severa months when he began to compIain of frequency, occurring every hour during the day and three to four times at night, diffrcuIty in starting his stream, straining, urgency, burning and intermittency. On two occasions in the past three months, he deveIopec1 an acute retention of urine and had to be relieved by catheterization. He has had in the chiIIs and fever at irreguIar intervaIs past few weeks. He has aIso complained of pain in both lumbar regions, more marked on the right than on the Ieft side. There is no radiation of pain. He occasionahy has a duI1 pain in the suprapubic region. The patient has been confined to bed for the past five years because of inabiIity to move his Iower extremities. The patient stated that his arthritis is becoming progressively worse. Physical Examination: Patient is a very stout obese maIe. He is unabIe to stand due to the pain and pressure attending movements
American
in skuI1 and peIvis.
There
are several
obese. Neither kidney is paIpabIe. There is slight tenderness in the right lumbar region but no tenderness over either kidney or ureter anteriorIy. Recta1 examination discIosed a benign hypertrophy of the prostate, first degree. Laboratory Studies: Voided specimen of urine was acid in reaction and had a specific gravity of 1.020. Tests for aIbumin and sugar were negative. Microscopic examination reveais many pus and red bIood ceIIs. Course: A pIain roentgenogram of the genitourinary tract reveaIed a shadow the size of a waInut in the region of the bIadder. Under cauda1 anesthesia, the vesica1 caIcuIus was crushed and removed. Two weeks later the patient returned complaining of pain in his right kidney region fohowing an automobiIe ride. A roentgenogram of the genitourinary tract revealed a shadow the size of a Iima bean in the Iower right ureter. Roentgen studies of the skull, pelvis and spine were taken and showed the typica osseous changes of Paget’s disease (Fig. 7). Diagnosis: (I) Paget’s disease; (2) vesica1 caIculus; (3) right uretera caIcuIus; and (4) arthritis deformans. DISCUSSION
The formation of urinary caIcuIi in osteitis deformans may be dependent upon one or more primary factors. These factors may pIay an etioIogica1 roIe in the production of the primary bone disease and secondariIy influence the formation of
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urinary factors to the
Journal
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calcuh. On the other hand, these may bear no etioIogica1 reIation bone disease but directIy or in-
NOVEMBER, ,933
in osteitis deformans and that this thickening is due to a deposition of Iime saIts in the wail of the blood vesseIs. Similar
FIG. 7~.
FIG. 7~.
FIG. 7. Case VI. Generalized type of osteitis deformans showing characteristic change in (A) skul1, pelvis. Large shadow opposite right ischial spine is vesical calculus.
directly as a resuIt of the bone disease, they may influence the subsequent formation of caIcuIi. Each of the foIIowing factors worthy of brief consideration as possibIe etioIogica1 agents in the production of urinary caIcuIi in osteitis deformans: (I) pathoIogica1 or physioIogica1 changes; (2) diet; (3) aItered caIcium metaboIism. I.
PATHOLOGICAL
AND
PHYSIOLOGICAL
CHANGES
PathoIogicaI studies have reveaIed the fact that the primary causative agent responsible for the deveIopment of the osseous changes is an endarteritis of the blood vesseIs in the bone. The vascuIar changes may be Iimited to the bIood vessels of the bones or may be part of a generaIized It vascuIar disease, i.e., arterioscIerosis. is we11 known that a characteristic thickening of the peripheral bIood vesseIs exists
(B)
spine and
scIerotic changes may be noted in the waIIs of the renaI vesseIs which may Iead to an interstitia1 fibrosis with a resuItant impairment in renaI function. The authors are of the opinion that the impairment in renaI function has no etioIogica1 significance in the deveIopment of the bone changes but are either secondary to the bone disease or mereIy an associated condition. However, as a result of the kidney changes, there may be some disturbance in the kidney parenchyma or to the formation of urinary caIcuIi. II.
DIET
The causa1 reIation of deficient diet to osteitis deformans may aIso serve as a possibIe expIanation of the simuItaneous occurrence of urinary caIcuIi in this disease. White was abIe to reproduce the bone disease in monkeys fed on a diet deficient
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in its organic and vitamin A content to which an excess of calcium was added. Other investigators have also stressed the association of a vitamin A deficient diet with osteitis deformans and osteoporosis. The experimenta production of urinary caIcuIi, composed of caIcium phosphate, in rats fed on vitamin A deficient diets was first observed by Osborne, MendeI and Perr\- and Iater verified by Fujumaki, McCarrison, Van Leersum, Higgins and others. The importance of these observations is further emphasized by the fact that urinary Iithiasis has been reported in the various bone diseases, i.e., rickets, osteitis deformans, osteomaIacia or osteoporosis which are presumabIy due to dietary deficiencies. Squier states that the association of vitamin A deficiency with the various bone diseases suggests the possibility that the formation of urinary caIculi in these bone diseases may be the result of a secondary disturbance of calcium metaboIism rather than the direct resuIt of the dietary. This theory appears to be quite IogicaI in view of the fact that the exact mechanism concerned in the formation of urinary caIcuIi resuIting from vitamin A deficiency is as yet undetermined. Se\:eraI theories have been offered to expIain urinary Iithiasis due to dietary deficiency. Some investigators (Osborne, MendeI, and Perry PerIman, and Weber and others) maintain that a diet deficient in vitamin A Iowers the resistance to infection and that this infection may occur in the urinary tract with subsequent stone formation. However, this process appears experimentaIIy at Ieast to be unassociated with infection. McCarrison stressed the toxic effect of the deficient diet on the renaI epitheIium and renaI function as a probable factor and considered stone formation to be the resuIt of the deposition of caIcium phosphate upon the effete ceIIs of the tubular epitheIium which serve as a nucleus. KiIIian has suggested that the increased aIkaIinity of urine which is due to formation of ammonia in cases of vitamin deficiency, may not be entirely
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the property of bacteria but aIso the result of a disturbance of renal function. He believed that vitamin A deficiency changes the character of the renaI epitheIium so that it is possibIe for crystaIIoids to become adherent to the epitheIia1 ceIIs. JoIy and Higgins are of the opinion that calculosis associated with vitamin deficiency is the resuIt of some action upon the urinary coIIoids which reduces their power of hoIding stone-forming saIts in soIution. III.
CALCIUM
METABOLISM
It is our belief that the causal relationship between osteitis deformans and urinary Iithiasis is to be sought in the disturbance of the caIcium and phosphorus metaboIism associated with osteitis deformans and the impaired secretory function of the kidneys so frequentIy encountered in this disease. Da Costa and his co-workers have found a retention of calcium, magnesium and phosphorus with an excessive excretion of suIphur. AnaIysis of the bone ash in osteitis deformans reveaIs the bone to be rich in caIcium despite their softness. In the case reported by Cuthbertson, the bIood caIcium was within norma Iimits and the figures for the CO2 reserve indicated the presence of a miid acidosis. As far as we have been abIe to determine, hypercaIcemia is not associated with osteitis deformans. However, it is we11 recognized that disturbances of caIcium metaboiism may occur without an increase in caIcium content in the bIood. Squier states that the reverse is more often the case in those conditions of disturbed caIcium metaboIism associated with renaI caIcuIus. IsraeI maintained that metastatic calcification may take pIace without decomposition of bone or hypercalcemia. The exact mechanism by which disturbances in caIcium metaboIism produce chemica1 or pathoIogica1 changes which uItimateIy resuIt in the precipitation of the urinary constituents with subsequent formation of urinary caIcuIi is by no means clearly established. The role of other
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& Abeshouse-CaIculi
metaboIic disturbances, i.e., phosphorus, magnesium, suIphur, etc., in the deveIopment of urinary Iithiasis is even more obscure. Urostasis and infection of the urinary tract apparentIy bear no great significance as etioIogica1 factors in the production of urinary caIcuIi in osteitis deformans. The presence of stasis or infection in cases of osteitis deformans, whiIe not a causa1 factor per se, certainIy favors the formation and recurrence of Iithiasis by keeping up the infection in the urinary tract. CONCLUSIONS
Our observations in 6 cases of urinary Iithiasis in patients suffering from osteitis deformans justifies the foIIowing concIusions : I. Urinary Iithiasis is an infrequent, though not uncommon, comphcation of osteitis deformans. 2. SeveraI probabIe etioIogica1 factors may be considered in estabIishing a causal
NOVEMBER, 1935
reIation between osteitis deformans and urinary Iithiasis: (a) a pathologica condition, i.e., arterioscIerosis or endarteritis, affecting primariIy the bones and secondariIy the kidneys; (b) dietary deficiency, (c) disturbance in caIcium metaboIism. 3. WhiIe the exact mechanism responsibIe for the formation of urinary caIcuIi in osteitis deformans is undetermined, the authors are of the opinion that most probabIe causa1 factor concerned in the formation of caIcuIi in these cases is a disturbance in the caIcium metaboIism with an associated impairment of renaI secretory function. 4. Since experimenta studies have cIearIy estabIished the roIe of vitamin A deficient diets in the production of urinary caIcuIi in the experimenta anima1 and in the production of osteitis deformans, it is obvious that carefuI attention shouId be paid to the diet in the treatment and prevention of caIcuIi in individuaIs afllicted with osteitis deformans.
REFERENCES
I. CONE, S. Pathology of osteitis deformans. J. Bone 0’ JO&t &Ug., 4: 751 (Oct.) 1932. 2. CUTHBERTSON, D. P. Note on the balance of calcium, magnesium and sulphur in a case of osteitis deformans. Glasgow M. J., 108: 218 (Oct.) 1927. 3. DACOSTA, J. C., FUNK, BERGEIM and HAWK. PubI. of Jefferson Med. College. PhiIa., 1915; 6: I. 4. FUJIMAKI, Y. Experimenta production of caIcuIi in the kidney and bladder. Japan Med. World, 6:2 (Feb. 15) 1926. 5. HIGGINS, C. C. Experimental production of urinary caIcuIi. J. Ural., 29: 157 (Feb.) 1933. 6. ISRAEL, W. BiIateraI nephroIithiasis with spondyIarthritis ankyIopoeitica. Ztscbr. f. Ural., 16: 321, 1922. 7. JOLY, S. J. Stone and caIcuIous disease of the urinary organs. St. Louis, Mosby, 1931. 8. KEYSER. L. D. Urinarv lithiasis: its cause and orevention. An evaluation of contributions to our knowledge during the past decade. Southern M. J., 25: 1031 (Oct.) 1932. Q. KILLIAN. In discussion of RandalI’s articIe. AM. J. SURG., 18: 432 (Dec.) 1932.
IO. MCCARRISON, L. Experimenta production of stone in the bladder. B&. M. J., I : 717 (ApriI 16) 1927. I I. OSBORNE. T. B.. MENDEL. L. B.. and PERRY. E. L. The incidence of phosphatic’urinary calculi in rats fed on experimental rations. J. A. M. A., 69: 32 (July 7) 1917. 12. PERLMAN, S., and WEBER, W. Experimenta production of urinary calculi. titinchen. med. Wcbnscbr.. 77: 680 (AoriI 18) 10~0. 13. SCULLY, F. J. Kidney function in osteitis deformans. Med. J. CY Rec., 120: 62 (JuIy 16) 1924. 14. SQUIER, J. B. CaIcuIous disease of the kidney and ureters. Chap. x, Lewis’s Practice of Surgery, Hagerstown, Tice, 1931. 15. VAN LEERSUM, E. C. Vitamin A deficiency and urolithiasis. &it. M. J., 2: 873 (Nov. 12) 1927. 16. WELLS, H. G. Metastatic calcification. Arch. Int. Med., 15: 574, 1915. 17. WHITE, E. P. C. Osteitis deformans in monkeys. Arch. Int. Med., 30: 790, 1922. 18. YOUNG, H. H. Practice of UroIogy. PhiIa., Saunders, 1926, I: 377; 2: 661. IQ. YOUNG, H. H., and WATERS, C. A. UroIogicaI Roentgenology. Annals of RoentgenoIogy. N. Y., Hoeber, 1928, 7: 412.459, 482. I
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