Generalized Skeletal Abnormalities Chapter 9

75 Pages·2005·10.15 MB·English

Chapter 9 Generalized Skeletal Abnormalities
Alessandro Castriota-Scanderbeg,M.D.
Osteoporosis loss of the bone mass is an age-related event that is
more prominent in women than in men.Osteoporo-
(cid:1) [Net decrease in the bony mass] sis is established when bone loss is greater than ex-
pected for a person ofa given age,sex,and race (pre-
Osteoporotic bones are qualitatively normal but clinical state) or when it results in structural bone
quantitatively deficient. Since these bones appear deficiency manifested by fractures.Several classifica-
rarefied and radiolucent on radiograms,the term ‘os- tion systems for postnatal osteoporosis have been
teopenia’is often used to refer to ‘poverty’of bone developed.Osteoporosis has been classified as low-
(Hall and Lenchik 1999; Griscom and Jaramillo turnover and high-turnover types, depending on
2000).Radiolucent bones,however,are not seen ex- whether bone remodeling activity is decreased
clusively in osteoporosis, but also in osteomalacia, (steroid therapy, hepatic disease, hypothyroidism,
hyperparathyroidism,neoplasms,and several other systemic disease,malnutrition,parenteral nutrition,
conditions ofvarying pathogenesis (Resnick and Ni- certain forms of postmenopausal and senile osteo-
wayama 1995).Thus,the term ‘osteopenia’is not spe- porosis) or increased (anticonvulsant therapy,calci-
cific for,and cannot be used synonymously with,os- um deficiency states,gastrointestinal disease,hemo-
teoporosis. Additional radiographic features may chromatosis,hyperparathyroidism,hyperthyroidism,
help in identification ofthe specific cause ofosteope- juvenile osteoporosis,mastocytosis,and certain other
nia:for example,subperiosteal resorption character- forms of postmenopausal and senile osteoporosis).
istically occurs in hyperparathyroidism,while multi- Another classification system, which is taken as a
ple focal radiolucent bone areas may suggest plasma reference in the following discussion, distinguishes
cell myeloma. In osteomalacia the bone matrix is between a generalized (most of the skeleton involv-
normal but its mineralization is defective,resulting ed),a regional (one segment of the skeleton involv-
in the ‘osteopenic’appearance on radiograms.Again, ed),and a localized (focal areas ofosteoporosis with-
supplementary radiographic signs, including Loos- in a skeletal segment) form ofosteoporosis (Resnick
er’s lines, pseudofractures, and such deformities as and Niwayama 1995).
acetabular protrusion or a bell-shaped thorax, are In generalized osteoporosis,involvement is most
necessary to identify osteomalacia.In the absence of prominent in the axial skeleton (spine, pelvis, ribs
these signs,the differential diagnosis against osteo- and sternum) and proximal portions of the long
porosis can be difficult,which is why a ‘hedge’word bones of the appendicular skeleton.Involvement of
like osteopenia is used.Unfortunately,specific radi- the cranial vault is generally mild,with the exception
ographic features are often lacking in isolated osteo- ofhyperthyroidism and Cushing disease where it can
porosis,which cannot be reliably diagnosed except in be extensive.Senileand postmenopausal osteoporosis
the presence of typical clinical and histological fea- (OMIM 166710) are the most common causes ofgen-
tures (Resnick and Niwayama 1995). eralized osteoporosis.Radiographic signs ofaxial os-
Osteoporosis occurs when bone resorption ex- teoporosis, including osteopenia and vertebral col-
ceeds bone formation, a situation that can be pro- lapse, have been detected in about 30% of women
duced by a net decrease in bone formation,a net in- and 20% ofmen between the ages of45 and 95years
crease in bone resorption, or a combination of the (Targovnik 1977).Fractures at other sites,especially
two.Scurvy and osteogenesis imperfecta are remark- in the proximal femur and distal radius,are common.
able examples of osteoporosis caused by impaired The male-to-female distribution of osteoporosis is
bone formation and mineralization, while hyper- about 1:4 before the age of80years and tends to ap-
parathyroidism is an example ofosteoporosis caused proach 1:1 after this age (Dunn 1967).In women after
by increased bone resorption.In normal individuals, the menopause, the magnitude of cancellous bone
502 Chapter 9 · Generalized Skeletal Abnormalities
loss with relative sparing of cortical bone is greater occur in association with a number of inherited or
than in the premenopausal age,probably accounting acquired disorders, including hyperparathyroidism
for the increased incidence of vertebral collapse in (Perez and Pazianos 2001),hyperthyroidism (Ober-
postmenopausal women (Mazess 1982; Riggs et al. mayer-Pietsch et al. 2000; Liote and Orcel 2000),
1982;Firooznia et al.1986a,b).Whether or not a frac- acromegaly (Bell and Bartter 1967;Longobardi et al.
ture occurs in an osteoporotic patient depends upon 1998), steroid therapy (van den Bergh et al. 2001;
a variety offactors.However,the single most impor- Kirchgatterer et al.2000),heparin therapy (Javier et
tant determinant is a decrease in bone mineral densi- al. 1999), alcoholism (Dalen and Feldreich 1974),
ty to under a critical threshold (Genant et al.1989). plasma cell myeloma (Bolzonella et al.1984),nutri-
Moreover,the bone mineral density achieved during tional deficiencies (Chase et al.1980;Coin et al.2000),
early adulthood is a major determinant ofthe overall diabetes mellitus (Campos Pastor et al.2000),chron-
risk ofthe development ofosteoporosis in later years. ic liver disease (Heathcote 1999; McCaughan and
Although the pathogenesis of senile and postmeno- Feller 1994), prolonged immobilization (Dalen and
pausal osteoporosis is unclear,different mechanisms Olsson 1974),immunodeficiency states (Kirchner et al.
are probably implicated. Bone formation, which 1985;Paton et al.1997),Gaucher’s disease (Katz et al.
seems to be preserved in postmenopausal osteoporo- 1987),and glycogen storage disease (Lee et al.1995).
sis (Carbonare et al.2001;Lafferty and Fiske 1994),is Scurvy,a metabolic disorder caused by long-term
likely to be deficient in senile osteoporosis,possibly deficiency ofdietary vitamin C (ascorbic acid),man-
as a result ofimpaired osteoblast function or recruit- ifests in infants and children (infantile scurvy) with
ment (Jackson and Kleerekoper 1990; Rosenberg characteristic skeletal changes related to impaired
1991).Increased bone resorption resulting from es- osteoblastic and osteoclastic cellular function,with
trogen deficiency has been implicated in osteoporo- preserved noncellular activities, including calcium
sis after the menopause, whether physiological or deposition.The skeletal alterations are most promi-
surgical (Jowsey 1966;Aloia et al.1983).Despite the nent at the end of tubular bones and at costochon-
unequivocal contribution ofhormonal factors to the dral junctions;they include a transverse band of di-
process of osteoporosis, as supported by its occur- minished density on the metaphyseal side of provi-
rence in young oophorectomized women (Genant et sional zone of calcification (the ‘scurvy’ line) and
al.1982,2000;Dalen et al.1974) and in hereditary go- thickening and sclerosis of its epiphyseal side. De-
nadal dysgenesis syndromes (Elliott et al.1959),it is spite heavy calcification,the provisional zone ofcal-
possible that both postmenopausal and senile osteo- cification is brittle and often presents subepiphyseal
porosis are involutional processes in which the di- clefts and fractures. Small beaklike marginal out-
minished production oforganic matrix has an essen- growths of the metaphyses and periosteal elevation
tial role (Resnick and Niwayama 1995).There is com- with new bone formation due to subperiosteal hem-
pelling evidence implicating genetic factors (Seeman orrhage are also typical (Fig.9.1a,b).Similar changes
et al.1989;Armamento-Villareal et al.1992;Prockop in the epiphyses produce a radiodense shell around
1998).Bone mass is lower in women than in men,and the ossification center (thickening of provisional
in Caucasians than in African Americans.Bone min- zone), with central rarefaction owing to atrophy of
eral density is a complex trait probably influenced by spongiosa.In the diaphyses,generalized atrophy of
multiple genes,each with partial effects (Devoto et al. the cortex and spongiosa produces a radiolucent or
1998). Up to 80% of the variance in bone mineral “ground glass” appearance. Subperiosteal hemor-
density is thought to be related to heritable factors. rhage and periosteal elevation can be striking and
Defects in type I collagen similar to those encoun- are usually most frequent in the large tubular bones,
tered in osteogenesis imperfecta may give rise to a such as the femur,tibia,and humerus.The adult form
phenotype suggesting involutional osteoporosis. of scurvy can be observed in severely malnourished
Polymorphisms in the type I collagen (COL1A1) persons,especially the elderly,and is marked by the
gene,the type II collagen (COL1A2) gene,the estro- hemorrhagic manifestations, with hemarthrosis,
gen receptor (ESR1) gene, the vitamin D receptor bleeding at synchondroses, and skin petechiae and
(VDR) gene,the calcitonin receptor (CALCR) gene, ecchymoses (Bevelaque et al. 1976; Haslock 2002).
and the interleukin-6 gene have been correlated with Osteoporosis is prominent in the axial skeleton,
decreased bone mineral density and the risk of os- especially the spine,and in the tubular bones of the
teoporotic fractures (Grant et al.1996;Uitterlinden et appendicular skeleton.
al. 1998; Becherini et al. 2000; Masi et al. 1998; Several bone dysplasias and syndromes exhibit
Taboulet et al. 1998). Generalized osteoporosis can osteoporosis on a generalized basis.A reduced bony
Osteoporosis 503
mass may result from an inherent bone defect,with
deficient production of woven bone and deficient
mineralization, or to decreased in-utero mobility.
In patients with all types of osteogenesis imperfecta
(OMIM 166210, 166200, 259420, 166220, 166240,
166260),osteoporosis results from defective synthe-
sis ofcollagen matrix,coupled with deficient miner-
alization ofthe matrix.The degree ofosteoporosis is
highly variable,ranging from bones with a normal
appearance on standard radiograms to severe osteo-
penia with multiple fractures. Decrease in osseous
density involves equally the axial and the appendicu-
lar skeleton (McKusick 1972).Cole-Carpenter dyspla-
sia(OMIM 112240) is a disorder similar to osteogen-
esis imperfecta in which multiple fractures and bone
deformities occur in association with orbital hypo-
plasia and ocular proptosis,hydrocephalus,and dis-
tinctive facial features (Cole and Carpenter 1987).
Osteopenia, pathologic fractures, discolored teeth,
a b
blue sclerae,and easy skin bruising suggest a connec-
Fig.9.1a,b. Scurvy in a female newborn.a Anteroposterior tive tissue disorder, but type I collagen is normal
and blateral projection ofthe left femur,showing the classic (MacDermot et al.1995;Amor et al.2000).The fea-
features of scurvy:osteoporosis,a sclerotic metaphyseal line
tures of Bruck syndrome (osteogenesis imperfecta
with a radiolucent line (‘scurvy line’) below it,metaphyseal ir-
with congenital joint contractures, OMIM 259450)
regularities, and subperiosteal hemorrhage with periostitis.
(From Dammeier et al.1999) include those of osteogenesis imperfecta plus sym-
metrical contractures of the knees, ankles, and feet
that are reminiscent ofarthrogryposis multiplex con-
genita (Fig.9.2) (Viljoen et al.1989).The bones are
osteoporotic and fragile, and multiple fractures re-
sulting in long bone deformities occur following triv-
ial trauma. Vertebral collapses can produce spinal
malalignment. Wormian skull bones are additional
findings,while blue sclerae,dentinogenesis imperfec-
ta,clubfeet,and pterygia are sometimes but not uni-
formly present (Sharma and Anand 1964;Brenner et
al. 1993). The collagen abnormality in Bruck syn-
drome is different from that occurring in osteogene-
sis imperfecta, being related to deficiency of bone-
specific telopeptide lysyl hydroxylase resulting in
aberrant crosslinking of bone collagen (Bank et al.
1999).The defect,caused by mutation at chromosome
location 17p12,is unique to bones,cartilage and liga-
ments showing unaltered telopeptide hydroxylation
and normal crosslinking.Singleton-Merten syndrome
(OMIM 182250) is an early lethal,autosomal recessive
condition characterized by dental dysplasia,progres-
Fig.9.2. Bruck syndrome in a 5.5-month-old baby girl.Note sive aorta calcification, aortic stenosis, generalized
healing diaphyseal fracture at the mid-diaphysis ofradius and osteoporosis,and expansion ofthe marrow cavities in
ulna,prominent osteoporosis,and flexion contraction of the
metacarpals and phalanges. Generalized muscle
elbow due to mild pterygia.Fixed contractures were also found
weakness and atrophy may also be observed (Single-
at several other joint locations,including the fingers,hip,knee,
and feet (not shown).(From Leroy et al.1998) ton and Merten 1973;Gay and Kuhn 1976).In geroder-
ma osteodysplastica hereditaria (OMIM 231070),an
autosomal recessive condition of premature aging,
504 Chapter 9 · Generalized Skeletal Abnormalities
osteoporosis,and susceptibility to fractures are cardi- any cause, including fractures, amputation, motor
nal features (Bamatter et al.1950).The bones show paralysis, and bone or joint inflammation. Osteo-
multiple lines like the growth rings oftrees.The skin porosis ofimmobilized individuals is associated with
is lax, although it is not hyperelastic as it is in the increased bone resorption (Akeson et al. 1987), as
Ehlers-Danlos syndromes. The face has been de- evidenced by increased urinary and fecal calcium
scribed as peculiar, with a “droopy, jowled, prema- excretion. Hypercalciuria can lead to renal calculi
turely aged appearance” (Hunter et al. 1978). This (Clouston and Lloyd 1987).A more diffuse pattern of
condition is phenotypically similar to the progeroid bone involvement,which is somewhat reminiscent of
syndrome ofDe Barsy (OMIM 219150) and cutis laxa senile osteoporosis, is observed in individuals who
with bone dystrophy (OMIM 219200).A peculiar type are totally paralyzed.However,the predominant in-
ofgeneralized osteoporosis due to excessive bone re- volvement ofthe appendicular skeleton with relative
sorption is that seen in prepubertal children and re- sparing of the axial skeleton clearly differentiates
ferred to as idiopathic juvenile osteoporosis (OMIM these cases from those ofgeneralized osteoporosis of
259750) (Teotia et al.1979).This is a self-limiting con- the elderly.In regional osteoporosis the radiographic
dition characterized by axial osteoporosis,sometimes appearance is usually one of uniformly diminished
combined with vertebral collapse resulting in spinal cortical and trabecular bone. Round or bandlike
kyphosis.The appendicular skeleton can also be af- areas of radiolucency in the periarticular or sub-
fected,with thin cortices and fracture lines along the chondral regions ofthe involved skeletal segment are
shafts of the tubular bones or,most typically,at the less common findings (Jones 1969). Insufficiency
metaphyses ofthe knees and ankles (Resnick and Ni- fractures are frequent complications.Regional osteo-
wayama 1995).The differential diagnosis against os- porosis is a typical feature ofreflex sympathetic dys-
teogenesis imperfecta tarda can be difficult,although trophy(OMIM 604335),a condition occurring in as-
the metaphyseal changes described can help in the sociation with a number of pathologic conditions,
identification of idiopathic juvenile osteoporosis notably trauma,myocardial infarction,stroke,degen-
(Krassas 2000; Smith 1995). Osteoporosis pseudo- erative cervical spine disease and disc herniation,
glioma syndrome(OMIM 259770) is an autosomal re- surgery,vasculitis,and neoplasms.Middle-aged indi-
cessive disorder (gene map locus at 11q12-q13) (Gong viduals are most commonly affected, with no male
et al.1996) due to mutation of LDL receptor-related or female predominance. The pathogenesis is not
protein 5 (LRP5) (Gong et al.2001) and characterized known,but hyperactivity ofthe sympathetic nervous
by diffuse osteoporosis starting in childhood. It is system and local hyperemia seem to play a major
possible that this recessive gene is clinically expressed part in it, which is the reason for the designation.
in heterozygotes (Superti-Furga et al.1986).Affected Sympathetic fibers located in the periosteum and ca-
children show musculoskeletal (osteoporosis,wormi- pable ofinducing both local vasodilatation and bone
an bones, platyspondyly, bowing deformity of long resorption are likely to mediate a reflex response ini-
bones,vertebral collapse,multiple fractures,muscu- tiated by painful stimuli (Hohmann et al.1986;Davis
lar hypotonia,joint hypermobility) and ocular (mi- et al. 1987). Characteristic sites of involvement are
crophthalmos,vitreoretinal abnormalities,cataracts, the shoulder and the hand,but others,including the
iris and lens abnormalities,ocular calcifications) ab- lower extremities and the spine,can also be involved
normalities (Bianchine et al.1972;Briard and Frezal (Franck et al.1982).Distribution is commonly bilat-
1976).Differentiation from osteogenesis imperfecta is eral and asymmetrical in terms of the degree of in-
possible by means ofbiopsy examination ofthe iliac volvement.Pain,swelling,tenderness,and restricted
crest (McDowell and Moore 1992).Interestingly,two movement are common presenting symptoms. In
additional mendelian disorders involving changes in the late stages (months after onset), trophic skin
the bone mineral density have been linked to 11q12- changes, such as pigmentary abnormalities, skin
q13:osteopetrosis,infantile type (OMIM 259700) and atrophy,and hypertrichosis,are observed (Birklein et
a disorder with isolated increase in bone mass al.2000;van der Laan et al.1998).Clinical symptoms
(OMIM 601884) in the absence of other clinical fea- can either subside or persist for years.Radiographic
tures or sequelae (Johnson et al.1997).It may be that manifestations include soft tissue swelling and
the same chromosomal region,11q12-q13,has a key regional osteoporosis, the latter presenting with a
role in the development ofosteoporosis in the gener- metaphyseal, subperiosteal, intracortical, endosteal,
al population (Koller et al.1998). or juxta-articular pattern of bone resorption
Regional osteoporosis is seen most commonly in (Genant et al. 1975). The designation transient re-
association with limb immobilizationor disusefrom gional osteoporosis refers to a self-limiting form of
Osteoporosis 505
regional osteoporosis characterized by acute onset,
peculiar involvement of the periarticular regions,
and absence of any identifiable cause (Resnick and
Niwayama 1995). There are two well-recognized
forms oftransient regional osteoporosis,one involv-
ing the hip and the other with a characteristic migra-
tory pattern.Whether these two forms ofosteoporo-
sis represent related but distinct disorders,or differ-
ent manifestations ofthe same disease,is not known
(Rosen 1970; Corbett et al. 1977). Certainly, both
forms share the same clinical picture of pain,
swelling, and restriction of joint motion at the in-
volved site, and also an identical radiographic ap-
pearance showing periarticular osteoporosis with
unchanged articular joint spaces. In addition, such
mechanisms as incomplete ischemic necrosis and
neurogenic reflexes similar to those ofreflex sympa-
thetic dystrophy have been implicated in the patho-
genesis ofboth forms (Resnick and Niwayama 1995;
Dihlmann and Delling 1985). Uncertainty also sur-
a
rounds the relationship between transient regional
osteoporosis and reflex sympathetic dystrophy,as a
positive history of trauma and similarities in the
pattern ofskeletal involvement are features common
to both disorders (Resnick and Niwayama 1995).
Transient osteoporosis of the hip affects young and
middle-aged adults,especially pregnant women,in a
strictly unilateral distribution. Interestingly, the left
hip is almost always the location in women, while
either hip can be involved in men.Clinical symptoms
(hip pain, limp, limitation of joint motion) usually
subside within a few months without sequelae.Occa-
sionally,femoral neck fracture may be a complication.
Radiographic manifestations, with osteoporosis in-
volving the femoral head (Fig.9.3a,b) and,to a lesser
extent,the acetabulum,usually become apparent sev-
eral weeks after symptom onset.Familial cases have
been described (Albert and Ott 1983).In regional mi-
gratory osteoporosisthe knee,ankle,and foot are most
commonly involved,while the hip and the spine are
usually spared (Duncan et al. 1969; Mavichak et al.
b
1986; Banas et al.1990).Men are affected more fre-
Fig.9.3a,b. Transient osteoporosis ofthe hip in a 33-year-old
quently than women.A migratory unpredictable pat-
pregnant woman with a 2-month history of left hip pain.
tern ofjoint involvement is typical,with clinical exac-
aNote circumscribed area ofdecreased radiodensity in the su-
erbations alternating with periods ofquiescence. perolateral portion of the femoral head (arrowheads), with
Localizedosteoporosis accompanies various focal normally preserved joint space.bAt the 8-month radiograph-
lesions ofthe skeleton,including arthritis,infections, ic follow-up,the osteoporotic area is no longer visible.(From
Yamamoto et al.1999)
and several neoplasms.A discussion ofthese entities
is beyond the scope ofthis book.
506 Chapter 9 · Generalized Skeletal Abnormalities
Radiographic Synopsis Associations
Conventional radiology is not sensitive to the early • Acromegaly
manifestations of osteoporosis (approximately 20– • Addison disease
40% of the skeletal calcium must be lost before • Alkaptonuria
changes can be detected on radiograms).A quantita- • Aluminum intoxication
tive measure of cortical resorption can be obtained • Anemias
by radiographic morphometry,with the midpoint of (sickle cell anemia,spherocytosis,thalassemia)
the shaft of the second metacarpal bone used as the • Arthrogryposis multiplex congenita
reference point.The outer diameter,the width ofthe • Aspartylglucosaminuria
medullary canal, and the width of the cortex are • Asphyxiating thoracic dysplasia
measured. The combined cortical thickness is then • Calcium hydroxyapatite crystal deposition disease
derived as the difference between the first two meas- • Calvarial doughnut lesions-osteoporosis-dentino-
urements,and final values are compared against ref- genesis imperfecta
erence values (Garn et al.1971).Such techniques as • Celiac disease
photon absorptiometry,transaxial CT scanning,dual- • Cerebro-oculo-facio-skeletal syndrome
energy radiographic absorptiometry,and ultrasonog- • Chromosomal trisomy syndromes (13,18,21)
raphyare currently used for detection and quantita- • Cockayne syndrome
tive assessment ofosteoporosis. • Contractural arachnodactyly,congenital
1. Generalized osteoporosis,with major involvement (Beals syndrome)
ofaxial skeleton and proximal portions ofappen- • Copper deficiency
dicular skeleton;decrease in number of vertebral • Cranioectodermal dysplasia
trabeculae,especially horizontal trabeculae;verte- • CREST syndrome
bral body deformation (wedge-shaped,biconcave, • Cushing syndrome
‘fish-like,’flattened vertebrae);increased Schmorl’s • Cystic fibrosis
nodes; coarsened trabecular pattern and cortical • Deprivation dwarfism
thinning of pelvis and thorax;trabecular resorp- • Diabetes mellitus
tion at femoral neck;femoral neck fractures com- • Duchenne muscular dystrophy
mon (senile and postmenopausal osteoporosis) • Ehlers-Danlos syndrome
2. Sclerosis ofprovisional zone ofcalcification;bone • Epidermolysis bullosa dystrophica
rarefaction beneath the calcified band; metaphy- • Estrogen deficiency (postmenopausal)
seal clefts and fractures; marginal metaphyseal • Fanconi syndrome
spurs;periosteal elevation and periostitis;‘ground • Farber disease
glass’appearance ofdiaphyses (infantile scurvy) • Fibrodysplasia ossificans progressiva
3. Generalized osteoporosis, with involvement of • Fibrogenesis imperfecta ossium
both the axial and appendicular skeleton;exuber- • Flynn-Aird syndrome
ant bone callous formation; multiple fractures; • Focal dermal hypoplasia (Goltz-Gorlin syndrome)
pseudarthrosis; bone deformities (osteogenesis • Focal scleroderma
imperfecta, Cole-Carpenter dysplasia, Bruck syn- • Gaucher disease
drome,osteoporosis-pseudoglioma syndrome) • Geroderma osteodysplastica hereditaria
4. Generalized osteoporosis; expansion of the mar- • Glycogenesis,type I
row cavities in metacarpals and phalanges (Single- • GM1 gangliosidosis
ton-Merten syndrome) • Gout
5. Generalized osteoporosis;multiple fractures;mul- • Grant syndrome
tiple bony lines resembling the growth rings of • Hajdu-Cheney syndrome
trees (geroderma osteodysplastica hereditaria) • Hallermann-Streiffsyndrome
6. Generalized osteoporosis, predominantly axial; • Hemochromatosis
vertebral collapse in some but not all cases;meta- • Hemophilia
physeal fractures in lower limbs (idiopathic juve- • Homocystinuria
nile osteoporosis) • Hypercalcemia,idiopathic
7. Regional osteoporosis with uniform diminution of • Hyperparathyroidism
cortical and trabecular bone;periarticular areas of • Hyperphosphatasemia
radiolucency; insufficiency fractures (reflex sym- • Hyperthyroidism
pathetic dystrophy,transient regional osteoporosis) • Hypogonadism
Osteoporosis 507
• Hypoparathyroidism • Trichorrhexis nodosa syndrome
• Hypophosphatasia (peripheral osteopenia)
• Hypopituitarism • Turner syndrome
• Hypothyroidism • Vitamin D intoxication
• Infantile multisystem inflammatory disease • Waldenström syndrome
• Kawasaki syndrome • Wegener granulomatosis
• Keratosis palmaris et plantaris familiaris • Werner syndrome
• Laron syndrome • Wilson syndrome
• Liver disease • Winchester syndrome
• Lowe syndrome • Wolman disease
• Malabsorption syndrome
• Malnutrition
• Mannosidosis References
• Mauriac syndrome
• Mediterranean fever Akeson WH,Amiel D,Abel MF,Garfin SR,Woo SL.Effects of
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• Mixed connective tissue disease tern Med 1983;143:1700–4
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• Osteoporosis-megaepiphyseal dysplasia tive collagen crosslinking in bone,but not in ligament or
cartilage,in Bruck syndrome:indications for a bone-spe-
• Osteoporosis-pseudoglioma syndrome
cific telopeptide lysyl hydroxylase on chromosome 17.Proc
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• Phenylketonuria Evidence of a linkage disequilibrium between polymor-
phisms in the human estrogen receptor-alpha gene and
• Prader-Willi syndrome
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• Progeria pausal Italian women.Hum Molec Genet 2000;9:2043–50
• Pseudohypoparathyroidism Bell NH, Bartter FC. Studies of 47Ca metabolism in acro-
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• Regional migratory osteoporosis Harrison HE. Generalized osteoporosis with bilateral
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• Rickets tive tissue:report ofthree families and review ofthe litera-
• Rothmund-Thomson syndrome ture.Am J Hum Genet 1972;24:34
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• Scleroderma
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• Thoracic outlet syndrome
508 Chapter 9 · Generalized Skeletal Abnormalities
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510 Chapter 9 · Generalized Skeletal Abnormalities
Van der Laan L,Veldman PH,Goris RJ.Severe complications of diographic patterns ofspongy bone hyperdensity are
reflex sympathetic dystrophy: infection, ulcers, chronic recognized,and pertinent disorders are discussed.
edema,dystonia,and myoclonus.Arch Phys Med Rehabil
1998;79:424–9
Disorders Manifesting with Single or Multiple Spotty
Viljoen D,Versfeld G,Beighton P.Osteogenesis imperfecta with
congenital joint contractures (Bruck syndrome). Clin Lesions of Increased Density. Focal, homogenously
Genet 1989;36:122–6 dense lesions localized within the cancellous bone or
Yamamoto T, Kubo T, Hirasawa Y, Noguchi Y, Iwamoto Y, occasionally on the internal surface ofthe cortex are
Sueishi K. A clinicopathologic study of transient osteo-
termed enostoses,or bone islands.These are discrete,
porosis ofthe hip.Skeletal Radiol 1999;28:621–7
usually solitary, foci of compact bone, ovoid or
round,measuring 1mm to 2cm in greatest diameter.
Osteosclerosis,Hyperostosis ‘Giant’bone islands measuring more than 2cm occa-
sionally occur (Smith 1973). A characteristic radi-
(cid:1) [Increased density oftrabecular bone ographic pattern is one ofthickened bony trabeculae
(osteosclerosis),thickening ofcortical bone radiating in streaks from the lesion and blending in-
(hyperostosis) (Whyte 1997)] timately with the surrounding trabeculae of the
spongiosa (Greenspan 1991).Histologically,a mature
Increased bone mass, the result of focal or wide- lamellar structure and haversian system of nutrient
spread osteosclerosis and/or hyperostosis,can occur canals is observed.Bone turnover activity is absent
in association with any ofa variety ofconditions,in- or minimal,with only rare foci of osteoblastic and
cluding metabolic and endocrinological disorders, osteoclastic activity (Hall et al.1980;Greenspan et al.
neoplasms, infections, trauma, skin disorders, vari- 1991).Enostoses are totally asymptomatic,their clin-
ous arthritides, sickle cell anemia, and several pri- ical importance residing only in their differentiation
mary or secondary disorders of bone. In addition, from sclerosing bone metastases. Osteopoikilosis
there is a sizable group ofsclerosing bone dysplasias (OMIM 166700),an autosomal dominant disorder,is
characterized by variable clinical, radiologic, and marked by the presence of multiple small, well-
histopathological manifestations and caused by dif- defined,circular or ovoid bone islands clustered in
ferent gene defects (Greenspan 1991).Of the several the spongiosa at the ends ofbones and in the periar-
classification systems developed during the last ticular regions (Melnick 1959).
decades for these disorders,many have emphasized
their roentgenographic appearance (Rubin 1964; Disorders Associated with Metaphyseal Striations. The
Norman and Greenspan 1986;Spranger 1992).This is radiographic hallmark of osteopathia striata is the
because the diagnosis ofmany sclerosing bone disor- presence of fine linear striations of hyperdensity
ders is based on radiograms.A valuable initial step in situated in the metaphyses and diaphyses of bones,
the roentgenographic evaluation ofa sclerosing bone occasionally crossing into the epiphyses and running
disorder is to identify whether sclerosis involves parallel to the long axis ofthe bony shafts.In the iliac
primarily the spongiosa or the cortex of bone.This wings, a fan-shaped pattern of striations may be
‘target-site’ approach usually narrows significantly seen, whereas the hands and feet, skull and facial
the spectrum of diagnostic possibilities.In addition, bones,and vertebrae are usually not involved.Osteo-
it may provide insights into understanding of pathia striata can occur in association with other
whether the endochondral or membranous bone for- sclerosing disorders, such as osteopoikilosis, melo-
mation is disturbed in a given disorder – indeed, rheostosis (Fig.9.4a,b),and osteopetrosis (Brennan
the spongiosa develops by means of endochondral et al.2002).Osteopathia striata with cranial sclerosis
ossification, while the cortex is formed by way of (OMIM 166500) is marked by progressive cranial
intramembranous ossification (Greenspan 1991).De- sclerosis with cranial nerve palsies as a distinguish-
spite the several cases in which both the spongiosa ing feature in addition to the vertical striations in the
and cortex are involved by the sclerosing process, long bones (Horan and Beighton 1978).A pattern of
and the rare situations in which two or more scle- metaphyseal dense striations similar to that ofosteo-
rosing disorders coexist in the same individual pathia striata occurs in SPONASTRIME dysplasia
(so-called overlap syndromes), differentiation be- (OMIM 271510) in association with vertebral and
tween the two bone compartments retains most ofits nasal defects;and in focal dermal hypoplasia(Goltz-
diagnostic value.The disorders manifesting with cor- Gorlin syndrome,OMIM 305600) in association with
tical hyperostosis are discussed in Chapter5,section osteopenia and multiple bone lesions resembling
“Cortical Thickening.”In the current section,five ra- giant cell tumors.