what-when-how
In Depth Tutorials and Information
●
Parathyroid hormone (elevated in primary
hyperparathyroidism and in secondary
hyperparathyroidism due to severe vitamin D
deficiency or malabsorption)
●
Phosphate (low in hypophosphatasia and renal loss;
high in pseudohypoparathyroidism)
●
Anti-gliadin antibodies, tissue transglutaminase and
endomysial antibodies (elevated in celiac disease)
●
25-Hydroxyvitamin D (low in nutritional deficiency/
/
rickets and renal disease)
●
Urine phosphate and creatinine (ratio elevated in
hypophosphatemic rickets)
●
Urine calcium excretion (elevated in certain children
with OI, idiopathic hypercalcuria as related to
diminished bone mass
1
)
achievement of full enteral feeds, sepsis and surgical
procedures.
4
Hypophosphatasia
Hypophosphatasia (perinatal and infantile forms) is
an autosomal recessive disorder that may present pre-
natally, at birth or in the first months of life. Deficiency
of the enzyme tissue non-specific alkaline phosphatase
(TNSP) results in defective skeletal mineralization and
manifests as severe osteoporosis or rickets.
5
This is dif-
ferentiated from OI by laboratory findings of low serum
alkaline phosphatase and elevated phosphoethanol-
amine concentration in blood or urine and elevated pyr-
idoxal-phosphate in blood. While there are radiographic
similarities, the perinatal form of hypophosphatasia has
more significant undermineralization of the skull and
bones of the hand as compared with severe forms of
OI; in the infantile form, the radiographs demonstrate
rachitic changes, including flaring of the metaphyses,
poorly ossified epiphyses and enlargement of the costo-
chondral junctions (known as the “rachitic rosary”).
6
DNA or more specialized testing may be needed or
recommended, depending upon the differential diagno-
sis. Information about and resources for genetic testing
may be found on GeneTests (
www.genetests.org
)
or the
GTR: Genetic Testing Registry (
http:
//
www.ncbi.nlm.
Radiographic studies may be helpful in the diagnos-
tic evaluation of recurrent fractures and may include:
Abuse
OI may be mistaken for child abuse in infancy (also
called non-accidental trauma); similarly, claims of an
OI diagnosis are often made for children who are vic-
tims of abuse. Abuse may be distinguished from OI
based upon the type of fracture and associated radio-
graphic findings and history. In severe types of OI (i.e.,
types III and IV) most fractures are of the shafts of long
bones or rarely lateral rib fractures, and radiographs
reveal disorganized and bent bones with thin bone cor-
tices or other evidence of osteoporosis. As mentioned in
previous chapters, fractures in severe forms of OI may
occur with minimal trauma. In non-ambulatory chil-
dren with type I OI, multiple fractures without a clear
etiology are
atypical
and child abuse should be investi-
gated. Fractures that are
not
typical of OI and that are
relatively specific for abuse include: metaphyseal cor-
ner fractures; epiphyseal separation fractures; multiple,
posterior rib fractures; scapular fractures; sternal frac-
tures; clavicular fractures and fractures of the vertebral
spinous processes.
7
In nearly all cases, history, physical
examination, laboratory and radiographic studies can
distinguish OI from abuse and thus DNA or collagen
biosynthesis testing is typically not warranted.
●
Cranial radiographs to evaluate for Wormian bones
●
Skeletal survey, including hands and feet
●
Assessment of bone mineral density (this may be
done by DEXA scan or measuring the metacarpal
cortical thickness
2
)
●
Bone age based on wrist and hand X-rays
DIFF
ERENTIAL DIAGNOSIS, BY
AGE
The differential diagnosis for recurrent fractures due to
low bone density varies somewhat by age. In the discus-
sion below, it is presumed that other causes of fractures
mentioned above (increased bone density, focal lesions of
bone, etc.) have been excluded as a cause for fractures.
Newborn
/
Infant
Prematurity
Premature infants may be osteopenic. The published
incidence of fractures in premature neonates is between
1.2 and 10.5%.
3
In a survey of 435 admissions to the
NICU in Cardiff, UK, from 1998 to 2007, Wei et al. found
71 fractures in 27 patients with a gestational age of 28
(23.6-40.4) weeks and birthweight of 920 (485-4875)g.
This included 17 anterior or lateral rib, 28 posterior rib, 5
humeral, 3 ulnar, 4 radial, 8 femoral, 1 tibial, 4 clavicular
and 1 skull fractures. The estimated fracture risk was
1.6%. Rib fractures were associated with osteopenia, lon-
ger oxygen therapy, length on parenteral nutrition, later
Arthrogryposis Multiplex Congenita
Arthrogryposis is a descriptive term meaning
“hooked joint” and refers to the presence of multiple
joint contractures at birth. It is a sign seen with many
genetic syndromes and clinical conditions and does not
imply any particular etiology. It is distinguished from
OI by multiple joint contractures that may be fixed in
either flexion or extension. Causes of arthrogryposis
