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In Depth Tutorials and Information
mass. Joint laxity with a stress fracture leads to consider-
ation of a “connective tissue disorder.” DEXA bone den-
sity scans may show diminished bone mass. Biochemical
and genetic testing is negative. There may be associated
family stress because the child insists on continuing the
exercise program which led to the fractures.
Disuse Osteoporosis
Improved treatment of a wide variety of congenital
and acquired conditions has led to a longer lifespan for
many individuals with significant physical disabilities.
This has resulted in a new generation of individuals
who may not be weight bearing or otherwise active, liv-
ing much longer. Since weight bearing stimulates bone
mineral accretion, lack of such activity is a significant
risk factor for osteoporosis. Additionally, the underly-
ing chronic illness may lead to vitamin and mineral defi-
ciencies.
20
Finally, many such individuals may develop
or be at risk for contractures and therefore receive
physical therapy using passive range of motion or other
therapist-initiated movements and manipulations.
The osteoporosis from disuse and nutritional deficien-
cies, along with involuntary stretching, may result in
pathologic fractures and, in those with limited commu-
nication skills, the diagnosis of a fracture can be delayed
or missed. Disuse osteoporosis can be differentiated
from OI based upon history and radiographic evidence
of gracile bones, as opposed to the disorganized bone
structure seen in OI.
Hypophosphatasia (HPP)
During childhood and adolescence the main mani-
festations of hypophosphatasia are rickets or osteo-
malacia, low bone mass, growth delay and dental
problems. Although occurring more frequently in
adults, bone fragility and fractures may occur in hypo-
phosphatasia in childhood. Premature exfoliation of
primary teeth may be the only clinical manifestation of
HPP in children. The childhood types of HPP may be
associated with premature fusion of cranial sutures and
cause intracranial hypertension and displacement of
the cerebellar tonsils.
19
In older children with mild dis-
ease, the clinical manifestations including dental abnor-
malities may be overlooked but the serum alkaline
phosphatase level will be found to be depressed.
Iatrogenic Osteoporosis
Many medications can cause osteoporosis, even with
adequate nutritional intake of vitamins and minerals.
Common medications that may lead to bone loss and
osteoporosis include:
Ehlers-Danlos Syndrome (EDS)
In children who have significant joint hyperex-
tensibility, with fractures and blue sclera, both EDS
and OI may be diagnostic considerations. Combined
EDS and OI phenotypes are due to unique mutations
in the N-anchor domain of the N-terminal region of
COL1A1
. These children do not exhibit other findings
of Ehlers-Danlos syndrome such as “cigarette paper”
scars, scoliosis, hyperextensible skin, mulloscoid skin
lesions or cardiac lesions. This is differentiated from
EDS type III (hypermobility type) by the absence of
recurrent fractures in EDS type III. EDS type VII (arthro-
chalasia type) is caused by mutations in type I collagen
genes and has overlap with OI including blue sclerae,
micrognathia, large fontanelles, Wormian bones and
growth retardation. Inguinal herniae are also a feature
but not dislocation of the hips or loose joints.
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Corticosteroids
●
Antiseizure medications, such as dilantin and
tegretol
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Selective serotonin reuptake inhibitors
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Heparin
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Aluminum-containing antacids
●
Proton pump inhibitors, such as Nexium and
Prilosec
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Oral diabetes medications, such as Avandia and
Actos
●
Injected birth control medications, such as Depo-
provera and Lupron
●
Drug treatment of hematologic and other
malignancies in children
Malabsorption Syndromes
Short gut disease (due to resection) and celiac disease
may result in malabsorption, including vitamin D defi-
ciency, which may be associated with osteoporosis and
fractures. Measurement of 25-hydroxyvitamin D lev-
els as well as testing for anti-gliadin antibodies, endo-
mysial and tissue transglumaninase antibodies should
be considered.
Abuse and nutritional deficiencies may cause frac-
tures in older children and adolescents but the causes
and factors distinguishing them from OI are not sig-
nificantly different in this age group and so will not be
repeated here.
SUMMARY
A wide variety of disorders may present with recur-
rent fractures due to bone fragility, and the mechanisms
of bone fragility include both increased and decreased
bone density, as well as focal lesions of bone. History,
physical examination and routine laboratory and radio-
graphic studies are essential in differentiating among
these many conditions. Although both OI and child
abuse are diagnostic considerations in the child with
