ENDOCRINOLOGY

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Ovid: Pediatrics

Editors: Tornetta, Paul; Einhorn, Thomas A.; Cramer, Kathryn E.; Scherl, Susan A.

Title: Pediatrics, 1st Edition

> Table of Contents > Section III: – Specialty Clinics > 25 – ENDOCRINOLOGY

ENDOCRINOLOGY

25.1 RICKETS

James F. Mooney III

The diagnosis of rickets includes a series of disease
processes with a common pathologic mechanism. In each situation, a
relative decrease in serum calcium, phosphorus, or a combination of
each, causes abnormalities of normal physeal development and
mineralization in the immature patient. While these abnormalities
affect both the axial and appendicular skeleton, it is the effect on
the extremities that becomes most clinically apparent, and is of most
interest and concern to the pediatric orthopaedic surgeon. Similar
perturbations of serum chemistries may be found in adults, as seen in
association with renal disease, and with some malignancies, but the
classic clinical appearance of rickets is found only in the skeletally
immature.

PATHOGENESIS

Multiple underlying diagnoses present with similar
clinical symptoms and signs. As such, there is no singular disease that
can be termed rickets. Classic (dietary) rickets
is secondary to dietary abnormalities and deficiency of vitamin D,
which in turn lead to abnormalities in calcium uptake and metabolism.
This is relatively infrequent in the Western world, but troubling
reports have appeared recently of an increased incidence of dietary
(vitamin D deficiency) rickets in children who are exclusively
breast-fed.

Breast milk contains a minimal amount of either inactive
or activated vitamin D. As such, infants who are exclusively breast-fed
require vitamin D supplementation prior to the introduction of more
advanced foods. This is particularly problematic in those infants with
darker skin color, in whom melatonin competes with vitamin D for the
ultraviolet (UV) radiation in the skin cells, thus increasing the
amount of sun exposure required to activate an appropriate level of
vitamin D. Premature infants, and those of families with particular
religious considerations that require significant coverage of the head
and face, particularly in females, may be at greater risk for rickets
secondary to a lack of activated vitamin D.

This is also more of a problem in northern latitudes,
especially in fall and winter months in which the opportunity for
natural UV exposure is limited both by the cold and by clothing cover.
Other groups that may develop similar findings include children with
severe milk allergies who do not receive appropriate supplementation,
and children made to follow a strict vegetarian diet, which may be low
in vitamin D content. Overall, rickets secondary to deficiency of
vitamin D is uncommon in modern Western society, but does occur,
particularly in some cultures, and the pediatric orthopaedic surgeon
must remain vigilant.

Other causes of rickets involve abnormalities of
calcium, phosphate, or vitamin D metabolism. Many of these have an
underlying genetic basis. The most common genetic abnormality is hypophosphatemic rickets
which is usually transmitted in an X-linked dominant pattern, but may
occur secondary to a spontaneous mutation. Females appear to be more
commonly affected than males. Patients with this disorder possess a
defect within the proximal and distal convoluted renal tubules, which
inhibits appropriate resorption of phosphate, thereby leading to
profound hypophosphatemia due to severe phosphate wasting in the urine.
Such abnormal levels of serum phosphate inhibit normal mineralization
and cause development of changes similar to those seen in classic
rickets, despite normal calcium intake and uptake, and normal intake
and ability to activate vitamin D. This type of rickets is often termed
vitamin D resistant, as the levels and
activity of vitamin D are generally normal, and further vitamin D
supplementation without addressing the phosphate issue does not improve
the clinical situation. Medical management of such patients requires
significant oral supplementation with neutral phosphate to maintain
appropriate serum levels in the face of persistent renal loss.

Various other genetic and metabolic conditions may cause clinical signs and symptoms consistent with rickets.

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The most problematic of those remaining would be renal osteodystrophy
in patients with chronic renal insufficiency. These patients will have
the well established underlying problem of chronic renal disease, and
the skeletal manifestations should be expected to varying degrees. The
causes described previously make up most cases seen by pediatric
orthopaedic surgeons, and certainly the most common causes of clinical
findings for which the pediatric orthopaedic surgeon would be the
primary diagnostician. More detailed descriptions of these less common
entities are beyond the scope of this review, and one should consult
standard pediatric and endocrinology texts for further information.

DIAGNOSIS

Physical Examination and History

Findings on physical examination of patients with possible rickets vary, but some consistencies do exist.

Generally, patients are of short stature, but often heavier than children of similar chronologic age.
Classically, their demeanor has been described as lethargic or irritable.
Examination of the appendicular and axial
portions of the skeleton, as well as the bones of the skull, provides
reliable findings.
- □ Frontal bossing, flattening of the
  skull due to changes of the growth regions about the cranial suture
  lines, and varying levels of dental disease.
- □ Enlargement of the growth centers of
  the ribs (costal cartilages) has been described as “rachitic rosary”
  because it feels like a string of beads, and pectus carinatum can be
  seen occasionally.
The patient may develop an increased
thoracic kyphosis, termed “rachitic catback,” but significant scoliosis
associated with, or attributable to, rickets is uncommon.

Abnormalities of the appendicular skeleton are extremely
common in patients with rickets, and are often the primary reason for
pediatric orthopaedic evaluation.

There is generalized shortening of all
long bones, and the joints will appear bulbous and widened, especially
in the face of severe, untreated disease.
The humeri usually develop varus deformities, while the lower extremities may demonstrate either varus or valgus angulation.
Commonly, the younger the patient, the
more likely the lower extremities will present in varus, rather than
valgus, and overall varus deformities of the lower extremities are much
more common than valgus.
In contrast, skeletal manifestations of
chronic renal disease generally become apparent later in development,
and the lower extremity deformities in these patients tend toward
valgus.
In addition to the structural
abnormalities, children with rickets may present with significant
ligamentous laxity, which will exacerbate the angular deformities,
particularly in the lower extremities during weightbearing.

Radiographic Features

The radiographic evaluation of patients with suspected
or known rickets relies exclusively on the use of standard radiographs.
No special studies using computed tomography, magnetic resonance
imaging, or bone scan are necessary.

The histologic abnormalities resulting
from the alterations in physeal development and maturation lead to
standard radiographic changes directly adjacent to the growth plates.
Plain radiographs demonstrate widening,
irregularity, and cupping of the growth plates of all bones that
undergo endochondral ossification (Fig. 25.1-1).

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The zone of provisional calcification is much less distinct than that of an unaffected individual.
As a result of these abnormalities, the
metaphyses of the appendicular skeleton appear widened or flared, and
angular deformities will occur over time and may be influenced by
weightbearing.
Similar changes may be seen in the long
bones of those patients with a number of the metaphyseal dysplasias,
most commonly those of the Schmid or McKusick type.
- □ Assessment of serum chemistries may be
  necessary to differentiate patients with certain skeletal dysplasias
  from those with changes secondary to rickets.
Radiographic abnormalities are also evident within the diaphyseal regions of the more tubular bones.
Deposits of nonossified osteoid present as transverse radiolucent lines that may resemble fractures.
- □ These areas are often referred to as
  Looser lines, or Milkman pseudofractures, and may be seen in up to 25%
  of patients with rickets (Fig. 25.1-2).
- □ These lesions classically occur along
  the compressive sides of long bones, including the proximal femur, as
  well as the ribs, clavicle, and pelvis.
- □ The etiology of Looser lines is
  unclear, but they may be the result of incomplete fractures through
  areas weakened by the generalized abnormality of bone maturation and
  development.

Figure 25.1-1
The changes in the epiphyseal plates of the wrist and hand are clearly
seen in this radiography of an 8-year-old child with florid rickets.
The distal radial and ulnar epiphyseal lines are markedly increased in
axial height and show cupping; the zone of provisional calcification is
absent. The changes in the slower-growing physes of the more distally
placed bones are less marked, emphasizing the fact that rickets is a
disease of the growing skeleton (in contrast to osteomalacia), and, if
the physeal regions grow slowly, the findings are less prominent. (From
Zaleske DJ. Metabolic and endocrine abnormalities. In: Morrissey RT,
Weinstein SL, eds. Lovell and Winter’s pediatric orthopaedics, 4th ed.
Vol 1. Philadelphia: Lippincott Williams & Wilkins, 2001:189.)

Figure 25.1-2
Looser lines seen in the rib cage of a child with florid rickets. These
linear transverse radiolucent lines, which resemble incomplete
fractures, are localized accumulations of osteoid of unknown cause.
They are pathognomic for rickets and osteomalacia. (From Zaleske DJ.
Metabolic and endocrine abnormalities. In: Morrissey RT, Weinstein SL,
eds. Lovell and Winter’s pediatric orthopaedics, 4th ed. Vol 1.
Philadelphia: Lippincott Williams & Wilkins, 2001:190.)

TABLE 25.1-1 SERUM LEVELS IN RICKETS

Type	Calcium	Phosphate	25(OH) Vitamin D	1,25(OH)₂ Vitamin D	Alkaline Phosphotase
Vitamin D deficiency	↓ or ↔	↓	↓	↓	↑
Calcium deficiency (rare)	↓	↔	↔	↔	↑
Phosphate deficiency	↔	↓	↓	↓ or ↔	↑
Malabsorption rickets	↓	↓	↓	↓ or ↔	↑
Vitamin D resistant (hypophosphatemic)	↔	↓	↔	↔	↑
Renal osteodystrophy	↓	↑	↓	↓	↑
Diminished vitamin D activation	↓	↓	↔	↓	↑

Laboratory Data

Serum blood chemistry evaluation is an essential part of
the diagnosis of rickets, and is the basis of the differential
diagnosis process, particularly since the radiographic findings are
fairly consistent within multiple etiologies. Information regarding the
differences in laboratory values between the various causes of rickets
of interest to the pediatric orthopaedic surgeon is presented in Table 25.1-1.

TREATMENT

Management of rickets begins with determination of the
exact cause of the bone changes, thereby allowing initiation of
appropriate medical care. It cannot be stressed too highly that medical therapy directed toward correction of the underlying biochemical abnormality must be the initial step.
Any surgical intervention in the face of untreated or active rickets is
doomed to fail and presents significant risk to the patient. Because of
this, coordination between health care professionals providing
medical/endocrinologic care and those providing orthopaedic management
is essential.

Once adequate medical intervention is established, and
improvement is documented through biochemical data and radiographic
evidence of stabilization or improvement of the growth plates, it is
then appropriate to contemplate surgical management. Bracing of the
lower extremities may be instituted during the period of attempted
medical treatment; however, there is controversy in the literature

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regarding
benefit. Some very young patients with dietary (or vitamin D sensitive)
rickets demonstrate spontaneous improvement of their limb deformities
after the metabolic issues are stabilized and do not require any
surgical or orthotic intervention.

Surgical management of angular
deformities associated with rickets involves realignment osteotomies,
and such procedures are required most frequently for distal femoral and
proximal tibial deformities.
- □ Traditionally, corrections have been
  performed acutely within the metaphyseal regions of the involved bones,
  and have been stabilized with transfixing pins, compression plating, or
  casts.
- □ Modern methods of angular correction
  using external fixation (monolateral or circular frames) have greatly
  enhanced the process through more precise correction and improved
  stability of fixation, thereby eliminating the need for additional cast
  immobilization.
- □ Compartment syndromes, delayed unions
  and malunions, and superficial and deep infections are reported risks
  of realignment procedures, particularly of the tibia.
Either acute or gradual correction may be
obtained using external fixation techniques, and both allow greater
patient mobility and activity in the postoperative period than those
methods requiring supplemental cast treatment.
Immobility is a particular problem in
this patient population as it may cause significant shifts in serum
calcium levels, exposing the patient to the inherent risks posed by
such changes.
Regardless of the type of procedure or
fixation system, there is a significant risk of recurrence for any
skeletally immature patient in whom medical or dietary management of
the underlying process is not maintained.
This is more of a problem for those
patients with rickets secondary to genetic abnormalities of mineral
absorption or excretion, or vitamin D metabolism.
Because of heightened awareness and
greater vigilance regarding appropriate intake and the need for
adequate UV light exposure, dietary rickets rarely recurs.