49

THE COMPLICATIONS OF OSTEITIS DEFORMANSBy BmINARD LENNOX, M.D.

Department of Pathology, Post Graduate Medical School of London

Paget's disease of bone was formerly regarded asa rarity. In the 24 years following its first descrip-tion in I877 only 66 cases were published (Packardet al., I90I) and these probably were very nearlyall the cases diagnosed in the world. Now singleclinics can produce series of over a hundred cases.This hospital has admitted 88 cases in the lastten years and the disease is becoming almnost acommonplace of the wards. Improved diagnosis,especially radiological, is chiefly responsible forthis, but the steady ageing of our population isalso an important factor. Paget's disease is verylargely a disease of the elderly and must take itsshare of the increasing interest in geriatric prob-lems.The general picture of the disease, especially of

the skeletal changes, is familiar. The multiplicityof secondary effects of these bony lesions is notperhaps so widely realized. They are important,however, for the presenting symptom of Paget'sdisease is more often a complication than thedisease itself, and although for the disease itselfonly symptomatic treatment is available, some ofthe complications demand active measures.

Paget's original clinical description (I877) isstill unsurpassed. On the more general aspects ofthe disease Snapper (I943) gives the best recentreview. On the aetiology much has been writtenbut little of value has emerged; it is best to confessignorance. On the pathology Higbee and Ellis(i9iI), Knaggs (I926), Schmorl (I926, 1930, I932)and Jaffe (I933) have contributed most.The best recorded modern series are those of

O'Reilly and Race (1932) and Kay et al. (I934Kay (I930), Gutman and Kasabach (I936) andReifenstein and Albright (i944) cover the bio-chemistry and Koller (I946) the genetics.The present account is chiefly based on a search

of the literature of the disease, both old and new,which was originally undertaken for anotherpurpose. This has been reinforced by a studyof the material at Hammersmith Hospital. Autop-sies have been made on I5 cases of extensivePaget's disease (0.34 per cent. of 4,450 postmortems in I3j years). Clinical records are avail-able of 88 cases for the ten years I938/47 (0.I2 percent. of 76,ooo admissions).

It may be worth while considering parentheti-

cally the extraordinary variation in figures for theincidence of the disease. They vary from 3 percent. (Schmorl, 1932) to O.OI3 per cent. (Koller,1946). The reasons for this need not be detailedbut are obvious enough when one studies theseries concerned; they emphasize, however, thedifficulty of any statistical study and are theprincipal reason why no attempt has been madehere to assess in any but the broadest terms theincidence of the various complications.

Classification of ComplicationsOne may classify complications by systems, but

for the present purpose it is of greater service touse a pathogenetic classification based on the wayin which the complication derives from the originaldisease

i. Local effects.I. I Fractures.1.2 Osteosarcoma.I.3 Effects on other systems produced by

the enlarged and distorted bones.1.3I Arthritis (?).I.32 Pressure effects on the nervous

system.I.321 VIlIth nerve.1.322 Other cranial nerves.1.323 Posterior fossa (basilar in-

vagination).I.324 Spinal cord.

I.33 Effects on nose, sinuses and jaws.1.34 Thoracic deformity (?).

2. General effects.2.I Disorders of calcium metabolism.

2.1I Hypercalcaemic episodes and acutemetastatic calcification.

2.12 Arterial calcification.2.I3 Heart valve calcification and heart

block.2.14 Calcification of avascular struc-

tures.2.15 Renal calculi (?).

2.2 Endocrine disorders (?).2.3 Effects of the arteriovenous shunt

through vascular bones.2.3I High output heart failure.2.32 Varicose veins (?).

BI

copyright. on July 12, 2021 by guest. P

rotected byhttp://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.25.280.49 on 1 February 1949. D

ownloaded from

POST GRADUATE MEDICAL JOURNAL

A distinction of immediate practical importancemay be made between the two main groups. Thelocal effects may be seen in cases with localized oreven monostotic disease; the general effects onlyappear in cases with many bones involved.

1.1. FracturesSurprise has often been expressed at the ease

with which the thick and heavy bones of Paget'sdisease are fractured. The radiologist, who cansee loss of trabecular structure, is less likely tobe surprised than the clinician, and the path-ologist, who can handle the bones, even less so.At post mortem it is obvious that the bones haveentirely lost their characteristic temper, the steelyhardness and elasticity of normal bone givingplace to a brittle frangibility like that of softsandstone. At its best (or most sclerotic) the bonebreaks like cast iron ; at its worst (or most osteo-porotic) like Edinburgh rock. The skull cap shownin Fig. i, twice the normal thickness, broke cleanaway from the base while being sawn; in anothercase the iliac crest was broken between finger andthumb. Wolff's law (' the structure of bone isgoverned by its function ') no longer operates,and the bone is a mass of osseous tissue, abundantenough but not organized to resist strain.

Transverse zones of radiolucency in the convexmargin of the femur, well seen in Fig. 2, aresometimes a source of fracture (Reifenstein andAlbright, I944). Schmorl (1932) showed (butthis has yet to be confirmed) that they are partialfractures (or ' infractions ') which are slow toheal completely. He believed that they are res-ponsible for the bowing of a bone without de-crease in length which can sometimes be demon-strated. They must not be confused with therather similar Looser's nodes of osteomalacia.The actual frequency of fracture in Paget's

disease may be exaggerated and its significancehas even been denied. As will be pointed outlater in connection with renal calculi, in any con-dition in which X-rays are a routine, the examina-tion will bring to light many unsuspected andpossibly incidental cases of Paget's disease. Butapart from the a priori probabilities, a study ofcases in which fractures occur repeatedly throughaffected bones, sparing normal bones, is verystrong evidence that the association is real (Rogersand Ullin, 1936). 'Our 88 cases at Hammersmithincluded seven with fractures (Fig. 3).

Fractures usually involve the lower limb or pelvis,sometimes the vertebrae or humerus, apparentlynever the skull. Transverse fractures just belowthe greater trochanter and of the upper third ofthe tibia are especially common. They are rarelyquite spontaneuous but result from relativelyminor trauma. Pain is often remarkably slight.

Treatment presents no unusual difficulties,though Kuntscher nailing for the subtrochantericfracture and the Smith-Petersen pin for fracturesof the femoral neck cannot be used. Callus isformed abundantly; union is rarely delayed andmay be exceptionally rapid; the vascularity andcellularity of the bone are presumably responsiblefor this. Vitamin D and a high calcium diet maybe dangerous, as will be shown later (see 2.Il)A fracture may be the first sign of sarcoma

(Fig. 4).1.2. Osteosarcoma

Paget's original case (I877) died of a sarcoma ofthe radius with lung metastases (it has been un-kindly suggested that this was a lung carcinomawith bony secondaries, but on no very goodgrounds). In a later paper (I889) Paget statedthat he had followed eight cases to death and fiveof these had died with tumours of some sort.Sarcoma and carcinoma were not clearly dis-tinguished in his day, and he seems to have be-lieved that tumours in general were unusuallyfrequent. There is no evidence in any recentwork of increased frequency of any tumour butbone sarcoma.The old controversy on this subject is now only

of historical interest. Since Coley and Sharpe'sdemonstration (I93I) that 28 per cent. of bonesarcomata in those over the age of 50 occur inbones affected by Paget's disease no one doubts thereality of the relation. Sarcoma is so rare innormal bones in the elderly that one is surprisedthat their figure is no higher than 28 per cent.The exact incidence of sarcoma remains un-

certain. The available larger series of cases show alow incidence of sarcoma, but on closer examina-tion- this loses significance. The only largepathological series (Schmorl, 1932) consists mainlyof cases with minimal lesions, which do not de-velop sarcomata. The large clinical series ofO'Reilly and Race (1932), Kay et al. (I934),Gutman and Kasabach (1936), Sugarbaker (I940),Nichols and Raines (I94I) and Newman (I946)contain a high proportion of cases of extensivedisease and very few sarcomata, but what is re-corded in each case in these series is usually onlya single study at the time of first diagnosis. Sar-coma commonly forms only a brief episode at theend of a prolonged disease during which manypatients pass out of the sight of those who havemade the original diagnosis. Only an analysis ofthe actual causes of death in a large series of caseswill give a reliable figure, and none is available.Our own autopsy records show two sarcomataamong I5 cases, and of the 30 other cases with fullautopsy reports collected by Harrison and Lennox

February 1949so

copyright. on July 12, 2021 by guest. P

rotected byhttp://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.25.280.49 on 1 February 1949. D

ownloaded from

LENNOX: The Complications of Osteitis Deformans

(I948), seven had sarcomata. The incidencesuggested by these figures is probably exaggeratedby the 'news value' of the sarcomata, but it seemsprobable that as many as io per cent. of cases ofextensive Paget's disease die of osteosarcoma.Men are four or five times as often affected as

women though Paget's disease itself has no sexbias and osteosarcoma in the mass only a slightmale bias. The average age of onset in the 76cases collected by Sumney and Pressly (1946) iS58 years, with a range from 32-78. The femur isthe commonest site, closely followed by thehumerus, skull and tibia. The tumours occuroccasionally in other bones, but have not beenreported in the fibula or sternum or in the hand,foot or face bones. They are frequently multiplein 26 of Sumney and Pressly's 76 cases more thanone bone was involved. The possibility thatmultiple tumours arise by metastasis from a singleprimary can be discounted in most of these cases.Von Albertini (I929) showed that even in a casewith only a single sarcoma there may be multiplefoci of premalignant osteoblastic proliferation.The first symptom is often a fracture (Fig. 4) andthough this is usually obviously an effect of thetumour, in some cases the time relations have beensuch as to suggest that it may have been a cause.One cannot, however, escape a suspicion that insome of these cases the tumour has been missed inthe earliest radiographs.The histology of these tumours is unremarkable.

Most are poorly differentiated osteosarcomata, butpure fibrosarcoma has been reported and one ofour cases had massive lung metastases of welldifferentiated osteochondrosarcoma. Everythingpoints to an origin from osteoblasts and to con-tinuous osteoblastic stimulation as the cause.The prognosis is at present hopeless, and no

cures have been reported. This is the more sur-prising in that osteosarcoma arising in normalbones shows a rather better prognosis than usualin the higher age groups (Badgely and Batts,I941). Late diagnosis (the symptoms beingascribed to the pre-existing disease) is one factorand multiple tumours another, but the tumoursseem to be exceptionally malignant. Platt's case(I946/7) with a two-year survival is quite unusual.

1.31. ArthritisOsteoarthritis is common in sufferers from

Paget's disease, but it has not been shown to becommoner than in control series of the same age.It is, in fact, remarkable how little gross bonechanges may effect the related joints.

1.32. Pressure Effects on the NervousSystemThe soft tissues are remarkably resistant to

damage by the enlargement and distortion of thebones. Arteries and veins have, to the writer'sknowledge, never been proved to be obstructed inthis way. The meningeal vessels may becomealmost buried in the bone of the thickened skullcap (Fig. ib) but remain perfectly permeable.Considering the close investment of much of thenervous system by bone, nervous complicationsmight be expected to be frequent, but except fordeafness thev are in fact uncommon. They dohowever, occur in considerable variety, can presentsome interesting diagnostic problems and aresometimes amenable to surgical treatment.

1.321. VIIITH NERVEThe position of the ear is exceptional, for it is

more intimately related to bone than any othernerve structure. Indeed it is, strictly speaking,wrong to classify this as a pressure effect on thenervous system, for here we are dealing with adirect disorganization of the receptor.

Deafness of some degree is common enough tobe a reliable sign of the disease. Newman (1946)found it in 20 of 82 cases. Tamari (1941) claimsit to be demonstrable in all cases with skull in-volvement, and this is probably no great exaggera-tion. It may be of conductive or nerve type but isusually mixed; vestibular function is less in-volved than hearing. Loudness recruitment testshave not been recorded. The pathology has beenthe subject of several painstaking studies (Tamari)but, except that the lesion lies chiefly in the cochleaand not in the VIIIth nerve itself, the results seeminconclusive. Probably deformity of the bonyframework of the inner ear is the real trouble,though Brunner and Grabscheid (I936/7) believedthey had demonstrated a serous inflammation. Inthe type of deafness and in some pathologicalfeatures there are similarities to otosclerosis, andit has even been suggested (Jenkins, I923) that oto-sclerosis is a localization in the petrous temporal ofPaget's disease.

I.322. OTHER CRANIAL NERVESOther cranial nerves may be affected. Anosmia

is second only to deafness in frequency, if Guillainand Messimy's work (I9) iS accepted. Am-blyopia is often mentioned as a complication buthas not been studied in detail. It was an importantfeature in two of Newman's 82 cases and one of our88. It is usually of ' retro-bulbar neuritis ' type,with peripheral and often central scotomata.Postic (1940) records a case with radiologicalevidence of narrowing of the optic foramen. Someother eye lesions such as transverse opacity of thecornea (Cass, I939) and tigroid fundi have beenrecorded but may be coincidences.

Pierre Marie and Leri (Leri, 1913) demonstrated

February I1949 5I1copyright.

on July 12, 2021 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.25.280.49 on 1 F

ebruary 1949. Dow

nloaded from

POST GRADUATE MEDICAL JOURNAL

narrowing of the foramina at the base of the skulland believed that this was the cause of the nervelesions, but it seems likely that stretching of thenerves due to distortion of the base of the skull isat least as important. It is noteworthy in thisconnection that in spite of its long intra-osseouscanal, the VIIth nerve is one of the least oftenaffected.

Cranial nerve involvement is sometimes mul-tiple. If this occurs in the presence of grosscranial deformity (Gregg, I926) diagnosis is easy,but much more difficulty will be found when, assometimes happens (Lehoczky, I939), the bonelesions are limited to the cranial base.

1.323. BASILAR INVAGINATIONDistortion of the base of the skull in Paget's

disease is common and can be important. Theheavy and plastic skull, supported over too smallan area by the cervical vertebrae, droops down andproduces a tam-o'-shanter effect. Seen frominside, the effect is one of a central boss protrudinginto the cranial cavity from below, its apex at theclivus forming a convex hump which may riseabove the sella turcica. Secondary effects are aflattening of both posterior fossae and pituitaryfossae and a narrowing and tilting of the foramenmagnum. Such a deformity, may in theory besecondary to any bone-softening disease, but iscommonest in Paget's disease. There is, however,a ' primary' deformity of very similar appearance,produced by congenital malformation of the basi-occiput and neighbouring bones (Walsh et al.,I941). Names for the deformity, whether primaryor secondary, are numerous-convexobasie (Leri,19I3), kyphosis of the clivus (Dubois-Ferriere,1940), platybasia, basilar invagination, basilar im-pression and many others. Platybasia is a mistakenimportation from-anthropometry, and basilar im-pression is a mistranslation of ' basale Impressiondes Schadels,' used by older German authors forthe primary lesion, so basilar invagination remainsthe least unsatisfactory English term.The lesion in its milder forms is fairly common,

but the brain, at least above the tentorium, cansurvive a good deal of distortion without clinicaleffect (Griinthal, 193I). Below the tentorium thegrosser degrees of the deformity can do con-siderable damage, the medulla, pons and cere-bellum suffering in varying degrees, producingneurological effects which vary considerably indetail. It has recently been shown (Wycis, I944)that an occipital decompression with high cervicallaminectomy is a valuable measure for the reliefof this condition.Of cerebral effects the only one of any im-

portance is the occasional appearance of epilepsywhich, as- Mufson and Chodoff (I946) have shown,

is only likely to appear in those inherently pre-disposed to epilepsy. Paget himself remarked onthe preservation of the intellect in the presence ofgross cranial deformity.

1.324. SPINAL CORDParaplegia is not very rare; Schwarz and

Reback (I939) published nine cases and Turner(I940) seven. A progressive compression of thecord by thickening of the surrounding bone is theusual mechanism. The majority occur in thethoracic region, where the spinal canal is narrow-est, but two cervical cases are recorded withactual displacement and a more sudden onset(Garcin et al., I937; Whalley, I946). In mostof the reported cases the Paget's. disease hasbeen relatively localized, but in our only examplethe lesion was terminal in a long-standing andvery extensive case (the case A.H. of Edholm etal., 1945).The gradual onset, thoracic level, and ' girdle

sensations' due to root pressure (Turner dis-tinguishes these from root pains, which are rarein Paget's disease) are of importance in diagnosis.Laminectomy, first recorded by Wyllie in I92I, iSa remarkably successful procedure, at least 75 percent. of recorded cases being cured or substantiallyimproved, and it should be carried out whenpossible. As Turner records, the disease mayrecur after years of freedom. Occasionally para-plegia may be due to osteosarcoma supervening onPaget's disease (Campbell and Whitfield, 1943).

1.33. Nose, Sinuses and JawsThough relatively infrequent, involvement of

the facial bones in Paget's disease does un-doubtedly occur (Glickman and Glidden, I942).The important secondary effects of these are:

I.33I. Nasalobstruction. Therelativeimportanceof this and of olfactory nerve involvement in pro-ducing anosmia has not been determined.

1.332. Sinus obstruction. The paranasal sinusesmay be compressed and even obliterated, orobstruction of their ducts may cause sinusitis(Gregg, 1926; Moore, 1927; Brunner andGrabscheid, 1938; Harris, I944). Frontal sinu-sitis from this cause is probably not uncommon;one of our cases presented in this way.

I.333. Displacement and loss of teeth.I.334. Pseudo-tumour of the maxilla. Enlarge-

ment of the maxilla due to Paget's disease is notvery rarely misdiagnosed as tumour, and ex-tensive operations have been undertaken underthis diagnosis. Neither radiography nor biopsyhas always avoided the error. One might almostexalt into a syndrome the succession of diagnosesof tumour of the maxilla, osteoporosis cranii

-FIbruary 194952copyright.

on July 12, 2021 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.25.280.49 on 1 F

ebruary 1949. Dow

nloaded from

February 1949 LENNOX: The Complications of Osteitis Deformans

2 1f @ w=0 /S,

<l41-3 D -

mw1Ef

(a) (b)FIG. i.-Skull cap in a case of Paget's disease. The lateral view (a) shows a half--made saw cut ; the

skull cap broke away from the base before it could be completed. The deep grooves of themeningeal vessels are well seen in the view (b) from below. They show that vessels can be sur-rounded by Paget's bone without being compressed.

FIG. 2.-Transverse ' infractions ' of the shaft of thefemur; note that they avoid the concave marginand (in this case) the outermost zone.

I.

FIG. 3.-Fracture of the great trochanter; an unusualfracture in Paget's disease, but in the usual neigh-bourhood. The disease in the femur is early, inthe pelvis more advanced.

82

copyright. on July 12, 2021 by guest. P

rotected byhttp://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.25.280.49 on 1 February 1949. D

ownloaded from

54 POST GRADUATE MEDICAL JOURNAL February 1949

lili:ii·'

II.-----'i:.B '3·rss.r Ilr · .b.l.8.f.i;.'ii. ··· ··i

ii ii

··!i

a···;i

·iii.8i.·

sa% L'

iii..i'

:

:f'·'i'

ri.:

"'

:ii . ij.lB.TirBB .s. 1BBIB8gi

ii:i.

::i:

'j.:'i''i:·':l IssBae·8llsl.·llhueePlll;i irp Ir Ir IOg.:

·tii'· ii'"9 CI. Bs.i;;

FIG. 4.-Pathological fracture due to an osteolyticendosteal osteosarcoma arising in a humerusaffected by Paget's disease.

FIG. 5.-Calcified femoral artery in a case of generalizedPaget's disease. Note the ring shadows of aMonckeberg's sclerosis; the lumen is clear. (Toobtain a satisfactory print from this X-ray differentexposures of the two halves were necessary ; it wasthought wiser to make this obvious in the finishedprint.)

;:::i

r·;il

t:

:;·

;3·1'fu.

:!:fh.'If:

:r

··' ·-:` .'.nC.LB.EI.';T"·'':·151..h, :::

FIG. 6.-The femur of the case illustrated in Figs. 7, 8 and 9, showing typical Paget's disease.

copyright. on July 12, 2021 by guest. P

rotected byhttp://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.25.280.49 on 1 February 1949. D

ownloaded from

LENNOX: The Complications of Osteitis Deformans

FIG. 7.-Medial calcification in an artery of the renal boundary zone.

FIG. 8.-X-ray of a transverse slice of the heart including the valves, showing irregular calcificationinvolving especially the posterior part of the mitral ring and extending on to the membranousseptum. There is also some calcification of the coronary arteries.

Febtruary I949 Sscopyright.

on July 12, 2021 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.25.280.49 on 1 F

ebruary 1949. Dow

nloaded from

56 POST GRADUATE MEDICAL JOURNAL February I949

....-.- ..... -- -t-- * -- ................t...+....-...-- --i------- ---+. ----.-.............t......-....-- --- -J ---- ~ ~ ~ ~r.. . -- - ' .- - -- 7- --t ---- -- - - -, =- -

...- 4.....- - -.-.+-~-.-* . . - ..- -. . ........ ...... - - . H-u.--s.- .--w-- ^---:----t :-!:.-!-:-- ,, - -

-S I #I h;}EiF F+t* +

I_ ; :r:r5.....- - ---.. #Wi

.. .* =i2 -C ............................ -- ;---. -- ; ..........ij,. .4 f--- ........l1 ...;II|:...,Ig1T...;

FIG. 9.-Electrocardiogram (standard leads) showing complete heart block, the result of the lesionshown in Fig. 8.

.. ....

Mi

FIG. io.-A case of Paget's disease with skull involve-ment, showing the prominent temporal arteries.

copyright. on July 12, 2021 by guest. P

rotected byhttp://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.25.280.49 on 1 February 1949. D

ownloaded from

LENNOX: The Complications of Osteitis Deformans

circumscripta and Paget's disease of the skull(Kasabach and Gutman, I937; Elkeles, 1947).We have recently seen such a case, now in thesecond stage.Some of the difficulties of diagnosis of Paget's

disease in this region are due to its early appear-ance. Whether skull and facial deformities bringpatients to their doctor earlier than lesions else-where, or whether there is some real variation inthe natural history of the disease is uncertain.It is clear, however, that in nearly all cases inwhich Paget's disease is diagnosed in the 20'sand 30's it is the skull which is chiefly involved.The old controversy over hyperostosis cranialisand the more recent one over osteoporosis craniicircumscripta both refer to conditions now recog-nized (Prince, 1902 ;' Kasabach and Dyke, 1932)as forms of Paget's disease, and both derive fromthe apparent age difference.

1.34. Thoracic DeformityRespiratory embarrassment and cor pulmonale

due to thoracic deformity might be expected to becommon and the earliest accessible case (Wilks,I 869) was believed to have died in this way.Subsequent experience shows it to be rare.Loeschke (1926) showed that it is the sharplyangulated spinal deformity which is especiallylikely to cause cardiorespiratory effects, and thekyphosis of Paget's disease is usually a smoothcurve.

2.11 Hypercalcaemic Episodes andMetastatic CalcificationNo metabolic disorders except those of the

calcium phosphate complex have been establishedin Paget's disease. Of those established only theraised alkaline phosphatase (Kay, 1930) is constantand characteristic. The blood calcium andphosphate are usually normal, and there is nothingto suggest that any general disorder of calciummetabolism lies at the root of the disease. It hasrecently been shown, however, that it can be veryreadily disturbed in at least two ways:-

(a) By immobilization. Reifenstein and Al-bright (I944) studied two cases of generalizedPaget's disease who suffered fractures. Both werekept on a normal hospital diet with plenty of milk.In both, the blood calcium and phosphorus rose,phosphatase dropped, urinary calcium rose, andthere was marked gastric distress and evidence ofincreasing renal insufficiency. Both appeared tohave been saved from renal failure only by forcedfluids and a low calcium diet.

(b) By Vitamin D. Wells and Holley (I942)and Seligman and Nathanson (945) describedcases in which doses of Vitamin D were; givenwhich, though large, were within therapeutic

limits. Both developed extensive metastaticcalcification and died.The practical lessons of these two observations

are obvious. Vitamin D, though necessary for thebed-ridden patient, must be given in minimaldoses. Immobilization is dangerous. If it is in-evitable, extra fluids and a low calcium diet mustbe given. Episodes of hypercalcaemia, howevercaused, may well be the origin of the variousmetastatic calcifications now to be described,which are common in Paget's disease. It is to benoted that the regions involved are those in whicheither abundant arterial blood or minimal meta-bolic activity produce a low CO2 tension and alow calcium solubility.

2.12. Arterial CalcificationThe radiographic observation of calcified ar-

teries was first made by Beclere in I9OI. O'Reillyand Race (1932) found it in 40 per cent. of theircases. The calcification is a M6nckeberg'ssclerosis, a medial calcification (Figs. 5 and 7), andthe arteries are not obstructed. Clinically thelesion is of no importance.

2.13. Heart Valve Calcification and HeartBlockPaget's original case developed a calcific mitral

stenosis during the course of his illness. Harrisonand Lennox (I948) found such lesions in 40 percent. of cases coming to autopsy, five times thefrequency in controls of the same age and sex.The mitral and aortic valves only are involved;calcium is not deposited from venous blood.Probably the lesion begins by deposition of calciumsalts in an area of hyaline collagen degenerationand once established tends to spread. The valvelesions themselves are rarely important, but theprocess sometimes spreads into the interventricularseptum and interrupts the bundle of His (Figs. 8and 9). The relation of heart block to Paget'sdisease in this way has been only recently recog-nized (Windholtz and Grayson, 1947; Harrisonand Lennox, I948).

Heart block of this type may be commoner thanthe lack of reported cases would suggest. Thereare many unexplained deaths from ' heart failure 'in the literature of Paget's disease, and some ofthese (Higbee and Ellis, I9 iI; Clegg, 1937) hadcalcified septa.

2.14. Calcification of Avascular StructuresThese are common and too various for detail.

Scars of all sorts, old fibroids, old goitres, and thepineal body are the commonest.

2.15. Urinary CalculiThe significance of the association of Paget's

February I1949 57copyright.

on July 12, 2021 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.25.280.49 on 1 F

ebruary 1949. Dow

nloaded from

POST GRADUATE MEDICAL JOURNAL

disease and stone is doubtful. Goldstein andAbeshouse (1935) reported seven cases with bothconditions, and io per cent. of Snapper's (1943)and 4.9 per cent. of Newman's (1946) cases hadcalculi. These figures are weighted by the fre-quency with which unsuspected Paget's disease isdiscovered during routine X-ray for stone, thelumbar spine and pelvis being the commonestsites of such unsuspected disease.The high incidence of stone in hyperpara-

thyroidism is, of course, due to the high urinaryexcretion of calcium (Barney and Sulkowitch,1937). No such hyperexcretion occurs in Paget'sdisease, and it may be doubted whether theoccasional episodes of hypercalcaemia alreadydescribed can be sufficient to produce stones.Even in hyperparathyroidism the incidence ofstone varies geographically (Wilder and Howell,1936) and statistics on the subject would bedifficult to assess. Our own figures show onecase of certain stone in 88 of Paget's disease(I.I per cent.) against a general incidence of 0.4per cent. of stones, hardly very conclusive figures.The incidence of stone in Paget's disease must beof minor importance.

2.2 Endocrine DisordersOne must mention here only to dismiss the

observations of Moehlig and Adler (I937) whofound a high incidence of diabetes and gigantismin relatives of their patients, and who ascribedthe disease to a pituitary disorder. Their argu-ments are, to say the least, unconventional andtheir facts have not been confirmed.

Davie and Cooke (I937) recorded a deficiency ofoxyphil cells in the parathyroids in their twocases. The observation has been confirmed butits significance is quite uncertain.

2.31.. High Output Heart Failure; theArteriovenous ,ShuntRedman (I889) seems to have been the first to

point out the existence of any circulatory abnor-mality. In a brief note in a special number of theIllustrated Medical News devoted to the disease(with many interesting, if repetitive, articles byfamous men), he produced a single sphygmographshowing a pulse which he describes as ' of hightension, regular, and visibly pulsatile.' Frenchauthors around the turn of the century, beginningwith Pierre Marie (I892) continued to note thefrequency of vascular abnormalities, especiallyheart murmurs; such murmurs often derive fromthe calcific valve lesions already noted, but this isnot the whole story. Klippel and Weil (I908)noted warm skin and dilated veins in the affectedleg of a man with unilateral disease, but quite mis-interpreted the findings. Kay et al. (I934) noted

the frequency of high pulse pressures, and theircarefully recorded series bears the fullest witnessto the frequency of circulatory abnormalities.

In 1943 a man was admitted to HammersmithHospital under Prof. McMichael with general-ized Paget's disease and the signs of congestiveheart failure. The two were then regardedas coincidental. About this time a great dealof work was in progress in the hospital on cardiaccatheterization, cardiac output and the varieties ofheart failure (Sharpey-Schafer, I944; McMichaeland Sharpey-Schafer, I944). On readmission ofthe patient in I944 it was at once recognized thathis warm extremities, full pulse and capillarypulsation were evidence of high cardiac output.The jugular venous blood was bright red incolour. Cardiac catheterization confirmed thehigh output (I3 litres per minute instead of thenormal 4-5 litres). The conditions were those metwith in a gross arteriovenous shunt. Surgical ex-perience of the vascularity of the bone in othercases suggested that the shunt might be throughthe bone. By an ingenious plethysmographictechnique it was shown that the blood flow throughaffected bones was 20 times that through thenormal. This was found to be adequate to explainthe raised output and the heart failure (Edholm,Howarth and McMichael, 1945).

Severe congestive heart failure from this causemay be uncommon, but a high proportion of casesshow some evidence of raised cardiac output. Ifone excluded the prominence of some arteriesdue to the high blood flow through them, and themedial calcification of others, little is left of the' arteriosclerosis' often described in Paget'sdisease. The prominent temporal arteries so oftenseen in cases with skull involvement (Fig. io)probably derive from both causes. Arteriosclerosisin the sense of occlusive vascular disease is nocommoner than in the general population.

2.32. Varicose VeinsVaricose veins and varicose ulcer occur fre-

quently, especially in earlier accounts of the disease(e.g. Hall, I897; Oettinger and Agasse-Lafont,I905). This may be mere coincidence, but itseems possible that the veins of the leg may bedistended by the constant excessive venous return,and an enlarged or bowed tibia may increase thefrequency of varicose ulcer.

SummaryThe more important of the complications of

Paget's disease of bone listed here are(a) Fracture.(b) Osteosarcoma.(c) A variety of pressure effects on the nervous

system, of which deafness is important because of

58 Feb-ruary I1949copyright.

on July 12, 2021 by guest. Protected by

http://pmj.bm

j.com/

Postgrad M

ed J: first published as 10.1136/pgmj.25.280.49 on 1 F

ebruary 1949. Dow

nloaded from

February 1949 LENNOX: The Complications of Osteitis Deformans

its frequency, and paraplegia and basilar in-vagination because they can be treated surgically.

(d) A tendency to hypercalcaemia and variousmetastatic calcifications.

(e) Heart block due to septal calcification.(f) High output heart failure due to the shunt

through the vascular bones.

ACKNOWLEDGEMENTSProfessor J. McMichael and Dr. C. V. Harrison

were responsible for my original interest in thissubject and have given a great deal of help.Professor E. P. Sharpey Schafer, Dr. DuncanWhite and Dr. J. C. Corall lent radiographs, andMr. E. V. Willmott overcame considerable tech-nical difficulties in their reproduction. Mr. B. B.Bonner of the records department is partlyresponsible for the estimates of frequency ofcomplications in our own material. To all thesemy thanks are due. Figs. 6-9 are reproduced bykind permission of the Editor of the British HeartJournal.

BIBLIOGRAPHYBADGELEY, C. E., and BATTS, M. (I94I), Arch. Stirg., Chicago,

43, 541.BARNEY, J. D., and SULKOWITCH, H. W. (I937), J. Urol.,

37, 746.BECLERE, M. A. (I9OI), Btull. Soc. med. Hop., Paris, 3me Ser., I8,

929.BRUNNER, H., and GRABSCHEID, E. (I936/7), Virchows Arch.,

298, I95.

BRUNNER, H., and GRABSCHEID, E. (I938), Iirchows Arch.,301, 237.

CAMPBELL, E., and WHITFIELD, R. D. (1943), N.Y. St. j.Med., 43, 93I.

CASS, E. E. (I939), Proc. R. Soc. Med., 32, 760.CLEGG, J. F. (1937), Lancet, ii, I28.COLEY, B. L., and SHARP, G. S. (I931), Arch. Surg., Chicago,

23, 9I8.DAVIE, T. B., and COOKE, W. E. (I937), Brit. J7. Surg., 25, 299.DUBOIS-FERRIERE, H. (I940), Schweiz. Z. alg. Path. Bakt.,

3, 22.EDHOLM, 0. G., HOWARTH, S., and McMICHAEL, J. (1945),

Clin. Science, 5, 249.ELKELES, A. (I947), Proc. Roy. Soc. Med., 40, 466.GARCIN, R., VARAY, A., and DIMO, H. (I937), Rev. Neurol.,

67, 76I.GLICKMAN, I., and GLIDDEN, H. S. (1942), Y. Amer. dent.

Assn., 29, 2I44.GOLDSTEIN, A. E., and ABESHOUSE, B. S. (1935), Amer. J.

Surg., 30, 359.GREGG, D. (I926), Arch. Neurol. Psychiat., IS, 6I3.GRUNTHAL, E. (193I), Z. ges. Neurol. Psychiat., 136, 656.GUILLAIN, G., and MESSIMY, R. (1939), C. R. Soc. Biol.,

Paris, 131, 499.GUTMAN, A. B., and KASABACH, H. (1936), Amer. J'. med.

Sci., 191, 36I.HARRIS, H. E. (1944), Cleveland Clin. Quart., II, 74.HARRISON, C. V., and LENNOX, B. (I948), Brit. Heart. J1.

IO, I67.

HIGBEE, W. S., and ELLIS, A. G. (i9II), J. med. Research, 24,43.

HALL, F. DE H. (I897), Trans. med. Soc., London, I9, 4I8.JAFFE, H. L. (1933), Arch. Path., xS, 83.JENKINS, G. J. (I923), J. Laryng. Otol., 38, 344.KASABACH, H. H., and DYKE, C. G. (I932), Amer.Y. Roentgenol.,

28, I 92.KASABACH, H. H., and GUTMIAN, A. B. (I937), Amer. J.

Roentgenol., 37, 577.KAY, H. D. (I930), J. biol. Chem., 89, 249.KAY, H. D., SIMPSON, S. L., and RIDDOCH, G. (I934),

Arch. intern. Med., 53, 208.KLIPPEL, J., and WEIL, L. (I908), Rev. neurol., I6. I228.KNAGGS, R. L. (I926), Brit. J. Surg., I3, 206.KOLLER, F. (1946), Helv. med. Acta., 13, 389.LOESCHKE, H. (1928), in Henke-Lubarsch 'Handbuch,' Berlin

Bd., 3, I, p. 6I i.LEHOCZKY, T. (I939), Rev. neurol., 71, 727.LERI, A. (1913), Nouv. Iconogr. Salpet., 26, 452.McMICHAEL, J., and SHARPEY-SCHAFER, E. P. (944),

Quart. J. Med., 37, 123.MARIE, P. (I892), Bull. Soc. med. Hop., Paris, 3me Ser., 9, 4I6.MOEHLIG, R. C., and ADLER, S. (1937), Surg. Gynec. Obstet.,

64, 737.MOORE, S. (I927), Ann. Otol., St. Louis, 36, 662.MUFSON, J. A., and CHODOFF, P. (1946), Ann. intern. Med.,

I6, 762.NEWMAN, F. W. (I946), J. Bone yt. Surg., 28, 798.NICHOLS, B. H., and RAINES, J. R. (1941), Cleveland Clin.

Quart., 8, 139.OETTINGER, L., and AGASSE-LAFONT, E. (1905), Nouiv.

Iconogr. Salpet., 18, 292.O'REILLY, J. J., and RACE, J. (1932), Quart. j. Med., 25, 471.PACKARD, F. A., STEELE, J. D., and KIRKBRIDGE, T. S.

(I90I), Trans. Assoc. Amer. Phys., I6, 666.PAGET, J. (I877), Med. Chir. Trans., 60, 37.PAGET, J. (I889), Illust. med. News, 2, I8I.PLATT, H. (I946/7), Brit. Y. Surg., 34, 232.POSTIC, S. (1940), Arch. Ophthal., I41, 564.PRINCE, M. (I902). Amer. Y. med. Sci., n.s., X24, 796.REDMAN, W. E. (I889), Illust. med. News, 2, I89.REIFENSTEIN, E. C. Jk., and ALBRIGHT, F. (I944), New

Engl. J. Med., 70, 295.ROGERS, M. H., and ULLIN, R. V. (1936), J. Bone Jt. Surg.,

I8, 914.SCHMORL, G. (1926), Verh. dtsch. path. Ges., 2I, 71.SCHMORL, G. (I930), Verh, dtsch. path. Ges., 25, 205.SCHMORL, G. (1932), Virchows Arch., 283, 694.SCHWARZ, G. A., and REBACK, S. (I939), Amer. Y. Roentgenol.,

42. 345.SELIGMAN, B., and NATHANSON, L. (1945), Ann. intern.

Med., 23, 82.SHARPEY-SHAFER, E. P. (I944), Clin. Sci., S, 125.SNAPPER, I. (1943), 'Medical Clinics on B% Diseases,' New York.SUGARBAKER, E. D. (I940), Amer. 3'. Surg., 48, 414.SUMNEY, T. J., and PRESSLEY, C. L. (I946), Ann. Surg., 123,

I35.TAMARI, M. (s94I), Ann. Otol., St. Louis, Si, I70.TURNER, J. W. A. (I940), Brain, 63, 321.VON ALBERTINI, A. (1929), Virchows Arch., 268, 259.WELLS, H. G., and HOLLEY, S. W. (1942), Arch. Path., 34, 435.WALSH, M. N., CAMP, J. D., and CRAIG, W. McK. (I941),

Proc. Mayo Clin., I6, 449.WHALLEY, N. (1946), Y. Neurol. Neurosurg. Psychiat., 9, 84.WILDER, R. M., and HOWELL, L. P. (I936), 3. Amer. med. Ass.,

Io6, 427.WILKS, S. (I869), Trans. path. Soc., London, 20, 273.WINDHOLTZ, F., and GRAYSON, C. (1947), Amer. 3.

Roentgenol., 58, 5 Is.WYCIS, H. T. (I944), 3'. Neurosurg., I, 299.WYLLIE, W. G. (I92I), Brain, 46, 336.

copyright. on July 12, 2021 by guest. P

rotected byhttp://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.25.280.49 on 1 February 1949. D

ownloaded from