bone disesa

2. ⦁ Skeletal metastases are the mostcommonvariety of bone
tumors and should always beconsidered in the differential
diagnosis, particularly in olderpatients
.
⦁ Cancersof thebreast, prostate, lung, andkidneyaccount for
80%of all metastaticcancerstobone.

3. ⦁ Inchildrenaged5yearsandyounger,neuroblastomais
usuallytheprimary tumor responsible for metastaticdisease
.
⦁ Tumor cellsseemtoacquireaspecial “geneticsignature”
that enablesthemto metastasize. In addition, the
microenvironment inbone, especiallymarrowstemcells,
supports cancercells in homing,differentiation, andsurvival.

4. ⦁ cancer cellsinfluenceosteoblastsandosteoclastsby
secretedfactors suchasparathyroidhormone–related
peptide(PTHrP) or endthilin1.Thisleadstoosteolyticor
osteoblasticmetastasesin bone;however,even osteoblastic
metastasesareaccompaniedbyincreasedboneresorption,
asisclinicallyevident bythetreatment responseto
bisphosphonatesinosteoblasticmetastasesof prostate
cancer.

5. ⦁ Stimulatedtumorcells releasefactorsthat induceosteoblasts
tosecrete RANK(receptor activator of nuclear factor kappa
b)–ligand orRANKL,whichis apotentfactor for osteoclast
formationandactivity.Osteoclasts,in turn, resorb boneand
thusreleaseadditional growthfactors that enhancethe
accumulationof cancer cells

6. ⦁ Relativelyrareinpatients<ageof 40.Therefore, patient age
is animportantdiscriminating factor in thediagnosis.
⦁ Metastasesusuallyinvolvetheaxial skeleton (skull, spine,
andpelvis) andthemostproximal segmentsof limbbones.

7. ⦁ Mostmetastatic lesionsarefoundin thevertebrae, ribs,
pelvis, skull, femur, andhumerus.
⦁ Themajorityof skeletal metastasesare silent.
⦁ When symptomatic,painis themainclinical feature,rarely
pathologicfracture.

8. ⦁ Clinical andlaboratoryexaminations.
⦁ weight loss,
⦁ anemia,
⦁ fever,
⦁ elevated erythrocyte sedimentationrate.
⦁ serumcalciumandalkalinephosphataselevelsareusually
elevated

9. ⦁ 30%to50%of normal bonemineral must belost beforea
bonemetastasis becomesvisible onaradiograph .
⦁ Radionuclidebonescan- bestscreeningmethodforearly
detectionof metastatictumors.
⦁ (PET)scanning, - most sensitive.
⦁ Onradiography
, ametastaticlesionmayresembleanyof the
benignor malignant lesions.

10. ⦁ There are no radiographic characteristics of metastasis. The
type of bone destruction maybe geographic, moth-eaten, or
permeative, andthemarginsmaybewell orpoorly defined
.
⦁ Aperiostealreactionandasofttissuemassmayormaynot
bepresent, althoughthelatter situationismore common.

11. ⦁ Metastasescanbesolitaryor multiple, andtheycanbe
furthersubdivided into purelylytic, purelysclerotic, andmixed
lesions.
⦁ Lyticlesions. Osteolytic metastasesarethemost
common, representingabout 75%ofall metastatic
lesions.Theprimarysourceisusuallyacarcinomaofthe
kidney
, lung, breast, gastrointestinal (GI) tract, or thyroid

12. Osteolytic metastases. A: Osteolytic metastasis to the proximal femur from
carcinoma of the colon in a 52-year-old woman. B: Osteolytic metastasis to
the left ilium from carcinoma of the thyroid in an 83-year-old man.

13. ⦁ . Osteoblasticmetastasesrepresentapproximately15%ofall
metastaticlesions. Inmentheyarecausedmainlybyaprostatic
glandcanceroraseminoma . Inwomen theprimarysourceis
usuallycarcinoma of thebreast, uterus(particularlycervix), or ovary
. In bothgenders,metastasesmayoriginate fromcarcinoid tumors,
bladder tumors, certain neurogenictumors, including
medulloblastoma, andosteosarcoma

14. Sclerotic metastases. A: Multiple sclerotic foci of carcinoma of
the prostate. B: Sclerotic metastases of breast carcinoma

15. ⦁ Mixedlesions.Mixedosteoblasticandosteolyticlesions
represent approximately10%of all metastaticlesions.Any
primary tumorcangiverise to mixedmetastases,themost
commonprimaries beingbreast andlungtumors.
⦁ Occasionally,someprimary neoplasmsmaygiverise toboth
lyticandscleroticmetastases

16. Osteolytic and sclerotic metastases. Osteolytic metastasis in the
medial endof the clavicle (arrows) andsclerotic metastasis in the
humeral head (open arrow) in a 27-year-old woman with a bronchial
carcinoid tumor.

17. ⦁ Thespreadof malignant cellstoinvolvetheskeletonusually
takesplacevia thehematogenous route. In suchinstances,
thebulkof thetumor lodgesinthemarrowandspongybone.
Therefore,theinitial radiography of metastatic lesionsin the
skeletonrevealsthedestructionof cancellousbone; only
after further tumorgrowthis thecortexaffected.

18. ⦁ Primary carcinomas of thekidneyandbladder and
melanomamayalsogiverise to cortical metastases. It is of
interestthatthemajorityof cortical metastasesaffect the
femur.
⦁ somtimesthemorphologicappearanceofametastasismay
suggestaspecific siteof origin. Forexample,bubbly,highly
expansive, so-called blow-out metastatic lesionsoriginate
fromaprimarycarcinomaof thekidneyorthyroid. Multiple
round,densefoci ordiffuseincreases in bonedensity are
oftenseeninmetastaticcarcinomaof theprostate.

19. ⦁ Ingeneral, metastaticbonediseaseischaracterized bya
combinationof boneresorptionandboneformation.
Radiographicimagingof thelesionswill reveal the
predominantprocess. Whenosteolysispredominates,the
lesionsappearlytic, andwhenboneformationis dominant,
theyappearsclerotic . Multiple sclerotic metastasesmay
present either in afocal pattern(multiple snowball
appearance)ormayhaveadiffusepattern(generalized
radiopacityof bones.

20. ⦁ Bonedestructionis alwaysmediatedbytumor-induced
osteoclasticresorption.

21. ⦁ It must bepointedout, however, that after treatment
(radiation therapy,chemotherapy,or hormonaltherapy),
purely lyticlesionsmaybecomesclerotic.Scintigraphy is
almost invariablypositiveinbonemetastases, and
increaseduptakeisobservedinbothscleroticandlytic
lesions.Thisphenomenonissecondarytotheincreased
boneturnoverandreactive repair at theperiphery of the
lesion . Radionuclide bonescanis helpfulfor distinguishing
metastaticdiseasefrommultiple myelomabecausethe
latter usually presentswith anormaluptakeof atracer

22. ⦁ Occasionally,widespread metastatic diseaseproducesa
diffuselyincreaseduptake throughout theskeleton rather
thandiscretehotspots.Thisso-called superscanappearance
is identified bytheabnormallyintenseboneuptake
⦁ Sometimesmetastasescausecoldspots(photopenic
defects)whenthereisbonedestructionbutinsignificant
reactiveboneformation; thismaybeobserved inmetastases
fromlungandbreast carcinoma.

23. Metastases distal to the elbowsandthe knees.A: Diffuse osteolytic
metastases to the ulna in a66-year-old woman with breast carcinoma. B:
Osteolytic metastasis to the midshaft of the right fibula of a 41-year-old woman
with hypernephroma.

24. Acrometastases. A: Osteolytic metastasis to the proximal phalanx of the left
thumbin a63-year-old manwith bronchogenic carcinoma. B:Osteolytic
metastasis to the distal phalanx of the right thumb( arrow) in a50-year-old
woman with breast carcinoma.

25. Cortical metastases. A: Osteolytic
cortical metastasis to the femur (arrow) in
a 62-year-old man with bronchogenic
carcinoma. Band C: Osteolytic cortical
metastases to the femur of an 82-year-old
man with bronchogenic carcinoma. Note
characteristic cookie-bite appearance of
the lesion on the lateral radiograph
(arrows). In three different patients, a 70-
year-old man(D), a 46-year-old woman
(E), and a 72-year-old woman (F), all with
bronchogenic carcinoma, computed
tomography sections demonstrate cortical
metastases in the femora

26. Skeletal metastases. A52-year-old man with
renal cell carcinoma (hypernephroma)
developed asolitary metastatic lesion in the
acromial endof the left clavicle. A: Radiograph
of the left shoulder shows an expansive blown-
out lesion associated with asoft tissue mass
destroying the distal endof the clavicle.C: In
another patient, a59-year-old womanwith
hypernephroma, ablown-out lesion is
associated with a soft tissue mass destroying
the acromial end of the right clavicle, acromion,
and glenoid.

27. Skeletal metastasis: (CT). A: An anteroposterior radiograph of the left hip
of a 50-year-old man with hypernephroma shows an osteolytic lesion almost
completely destroying the ischium (arrows). B: CT section demonstrates the
extent of bone destruction and a soft tissue extension of metastasis.

28. Skeletal metastasis: magnetic resonance imaging (MRI). A: Anteroposterior radiograph
of the left hip shows a diffuse osteolytic metastatic lesion in the proximal
femur of a 60-year-old woman with breast carcinoma. B: Coronal T2*-
weighted (MPGR, TR 550, TE 15, flip angle 15 degrees) MRI demonstrates
increased signal of the lesion. The uninvolved bone marrow remains of low
signal intensity

29. ⦁ MRIis moresensitivethantechnetiumscansfor detectionof
metastatic disease. Focallytic metastasesarecharacterized
byalowsignalonT1-weightedsequences,becomingbright
onT2-weighting.
⦁ Focalsclerotic metastases,suchasthosefromaprimary
carcinomain breastorprostate, induceanosteoblastic
reactionwithnewboneformation.Therefore,bothT1-and
T2-weightedimagesrevealalowsignalintensity.

30. ⦁ Metastatictumor isoftenhistologicallyidentical or very
similar totheprimary
, thusenablingaccurate identification.
⦁ Onmicroscopic examination, twoaspectsmustbe
considered.Thefirst is that of thetumortissueitself.
⦁ Thesecondhistologic aspectis the effect of themetastasis
onthebone,whichconstitutesacombinationof reactive
bonedestruction andreactiveproliferation.

31. Skeletal metastasis:(CT). Anteroposterior (A) andlateral (B)
radiographs of the distal arm of a 78-year-old man with bronchogenic
carcinoma show an osteolytic lesion in the posterolateral cortex of the
distal humerusassociated with periosteal reaction. C: CT section
shows cortical destruction, periosteal reaction, and a soft tissue mass

32. ⦁ Therearenocharacteristic radiologicfeaturesof metastasis.
Ametastaticlesionmaylooklikeaprimary benignor
malignant tumor,like afocus ofinfection, like ametabolic
disease, or evenlikeapost-traumatic abnormality
⦁ Thelengthof thelesionis oftenahelpful cluebecauselong
lesions(10cmorgreater)frequentlyrepresentaprimary
malignant tumor, whereas most metastaticlesionsare
smaller, between2and4cminlength

33. ⦁ Arecent studyevaluatedtheusefulnessof MRI in
discriminatingosseousmetastasesfrombenignlesions.The
so-called bull'seyesign(afocusof highsignal intensityin the
centerof anosseouslesion) provedto beasignof abenign
disease,whereasahalo sign(arimof highsignalintensity
aroundanosseouslesion) provedtobeasignof metastasis
.

34. ⦁ Asinglemetastaticbonelesionmustbedistinguishedfrom
primarybenign lesionsandmalignant tumors .
⦁ Inadditiontothelengthof thelesion, whichcanhelpin
distinguishingaprimaryfrom a metastatictumor, other
helpful features arethepresence(or absence)of aperiosteal
reactionandasoft tissuemass.Ametastaticlesionusually
presentswithout or withonlyasmall soft tissuemass

35. ⦁ . Aperiosteal reactionis usuallyabsentunlessthemass
breaksthroughthecortex.
⦁ Inthespine, metastaticlesionsusuallydestroythepedicle
, auseful featurefor distinguishingthislesionfrommyeloma
or neurofibromaerodingthevertebral body.

36. Skeletal metastasis with soft tissue mass.A70-year-old woman with
breast carcinoma developed a skeletal metastasis to the thoracic vertebra.
Note a large associated soft tissue mass

37. Skeletal metastases. Metastases from bronchogenic carcinoma in a
45-year-old woman destroyed the right pedicles of vertebrae T8 and
T10 (arrows).

38. ⦁ Asolitary osteoblasticmetastasisshouldbedifferentiated
fromtheboneisland(enostosis).
⦁ Onradiography
, boneislandsexhibit characteristicthorny
radiations that blendimperceptibly withthenormaltrabeculae
of thehostbone,afeaturenotpresent inmetastasis.

39. ⦁ Further confirmationisprovidedbytheradionuclidebone
scan,whichis invariably positive in metastaticdiseasebutis
usuallynormal inboneislands
.
⦁ Attimes,ascleroticmetastasis withexuberantsunburst
periosteal reaction, suchasmetastasisfromaprostatic
carcinoma, cansimulatetheappearanceof osteosarcoma

40. ⦁ Asinglesclerotic lesionat themedial (sternal) endof the
clavicle, whichoftenis mistakenfor ametastasis,mayin fact
representcondensingosteitisof theclavicle.
⦁ Clinically,this conditionmanifests withpain, aswell aslocal
swellingandtenderness. Radiographyrevealsa
homogeneouslydensesclerotic patch,usuallylimited to the
inferior marginof themedial endof theclavicle

41. Condensing osteitis of the clavicle. A:
Radiograph shows a sclerotic lesion in
the inferior aspect of the right clavicle
(arrow), originally thought to represent
sclerotic metastasis. B:Trispiral
tomography shows that the superior
aspect of the clavicle is not affected.
There is noevidence of periosteal
reaction. C:Computedtomography
section through the sternal endsof the
clavicles shows homogeneous sclerosis
of the right clavicular head and soft
tissue swelling adjacent to it anteriorly.

42. ⦁ Asclerotic vertebra (“ivoryvertebra”)resulting from
metastasis shouldbedifferentiated fromlymphoma,
sclerosing hemangioma, andPagetdisease.
⦁ Involvement by alymphomais usually indistinguishablefrom
metastatic disease, although the clinical and laboratory data
maybehelpful.

43. ⦁ In Hodgkinlymphomathereis anoccasional anterior
scallopingof thevertebral body
, whichaccentuatesthe
anterior vertebral concavityandthusprovidesauseful
differentiatingfeature.
⦁ Hemangiomaoftenpresentswithtypical vertical striations or
ahoneycombpattern. Paget diseasecharacteristically
enlargesaffectedvertebrae andcausesdisappearanceor
coarseningof thevertebral endplates

44. ⦁ If apictureframeappearancetypicalforPagetdiseaseis
present, metastasis canbesafelyruledout. Conversely,in
metastaticlesionstothevertebrae theendplatesremain
preserved.

45. Skeletal metastasis. Sclerotic metastasis to the lumbar vertebra of a 72-year-
old man with prostatic carcinoma mimics Paget disease. Note, however, that
the vertebral endplates are preserved and vertebral body is not enlarged

46. ⦁ Osteolyticmetastasesmustbedifferentiated from multiple
myelomaandbrowntumorsof hyperparathyroidism.
⦁ In youngerpatients, Langerhans cell histiocytosis mustbe
considered.
⦁ Probablythebestmodalityfor distinguishing metastasesfrom
multiplemyelomais the radionuclide bonescanbecause

47. ⦁ Helpful indistinguishingbrowntumors of
hyperparathyroidism areother hallmarks of thiscondition,
suchasdiffuseosteopenia, lossof thelaminadura of the
toothsockets,subperiostealboneresorption,andsofttissue
calcifications.
⦁ Becauseof their expansivenature,multiple metastasesfrom
kidneyandthyroidshouldbedifferentiatedfrom
pseudotumors of hemophilia

48. ⦁ Sclerotic metastasesshouldbedifferentiated from
osteopoikilosis . Osteopoikilosisisclassifiedamongthe
sclerosing dysplasias ofendochondral failure of bone
formationandremodeling.
⦁ Sclerotic foci in osteopoikilosis aretypically distributed near
thelarge joints,suchaships, knees,andshoulders
⦁ osteopoikilosis, unlike scleroticmetastases,exhibits anormal
radionuclidebonescan

49. ⦁ Erdheim-Chesterdisease,arare formof histiocytosis, can
radiographically mimicscleroticmetastases.Thiscondition
usuallyexhibits bilateral, symmetric,patchy,or diffuse
sclerosis of themedullarycavityof thelongbones,sparing
theepiphyses.

50. Osteopoikilosis. Anteroposterior radiograph of the right shoulder of a34-
year-old manshows typical periarticular distribution of sclerotic foci of
osteopoikilosis.

51. Skeletal metastases. Diffuse sclerotic metastases to
the pelvis and left femur causing a pathologic fracture in
a 68-year-old man with prostate carcinoma mimic
sclerotic changes of Paget disease

52. Erdheim-Chester disease resembling sclerotic metastases.
Diffuse sclerosis of the radius maybemistaken for blastic
metastases

53. ⦁ Asolitary cortical metastasis shouldbedifferentiated,among
otherpossibilities, fromosteoidosteoma,cortical bone
abscess,plasmacytoma,hemangioma,andcortical
osteosarcoma.Corticalinvolvementassociatedwithasoft
tissuemassmustbedifferentiated fromananeurysmalbone
cyst andaprimary soft tissuetumor invadingthebone,
includingsynovial sarcoma.
⦁ Multiplecortical metastasesshouldbedifferentiated from
hemangiomatosis andanyvascular lesioninvolvingthe
cortex

54. ⦁ Histologically,metastatic tumorsareeasier to diagnosethan
manyprimarytumorsbecauseof their essentially epithelial
pattern
⦁ Ametastatic lesion mayexhibitacharacteristic morphologic
patternthat stronglysuggestsaprimarytumor,suchasthe
clearcells of renalcarcinoma,follicularorgiantcell
carcinomaof thethyroid,orthepigmentproductionof
melanoma

55. ⦁ Zoledronicacid(ZA)isapotent thirdgeneration
nitrogen-containingbiphosphonate,whichhasbeen
widelyusedin thetreatmentofPaget’sdiseaseof
bone, hypercalcemia, multiplemyeloma, breast
cancerBMs, prostatecancerBMs, lungcancer
BMs andosteolyticBMs.

56. ⦁ Sclerosisof bonemetastaseshasbeen
documentedbyCTimagingafter ZAtreatmentin
studies[24–26] conductedonpatientsat an
advancedstageof cancer. However, theCT
changesofthenormalboneafter ZAtreatmentin
oncologicalpatientshasnotyetbeenestablished

57. ⦁ intravenousZA4mg, by15-mininfusionevery28
daythroughaperipheraloracentralvenousaccess
andmonitorforatleast3 months and a maximum
of 24 months.Accordingtostandardprocedures,
supplementationwithvitaminD(400Units/die)and
calcium(500mg/die) wasadded.All patientswere
monitoredfor skeletalrelatedevents

58. ⦁ Long-termtreatmentwithZAincreasestrabecular
bonedensityin oncologic patients,whereasnormal
cortical bonechangesarenot detectable.
⦁ Thesefindingsmayhaveimportantimplicationsin
tumor treatment andinthemanagement of
osteoporoticpatientswhoaretreatedwithmuch
lowerdosesof ZA.

59. ⦁ ZAis athird generationbisphosphonatethathas
beenshowntobemoreeffectivethanother
biphosphonatesandsignificantlyreducesskeletal
relatedcomplications comparedwithplaceboin
patientswithBMs