Overview of rickets in children
Author: Thomas Carpenter, MD
Section Editor: Joseph I Wolfsdorf, MD, BCh
Deputy Editor: Alison G Hoppin, MD
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Sep 2023. | This topic last updated: Jul 11, 2023.
INTRODUCTION
Normal bone growth and mineralization require adequate calcium and
phosphate, the two major nutritional elements that constitute the crystalline
component of bone. Deficient mineralization can result in rickets and/or
osteomalacia. Rickets refers to deficient mineralization at the growth plate, as
well as architectural disruption of this structure. Osteomalacia refers to
impaired mineralization of the bone matrix. Rickets and osteomalacia usually
occur together as long as the growth plates are open; only osteomalacia
occurs after the growth plates have fused [1]. (See "Epidemiology and
etiology of osteomalacia".)
An overview of the pathogenesis, clinical presentation, and the differential
diagnosis of rickets is presented here. The etiology and treatment of
calcipenic and phosphopenic rickets are discussed separately. (See "Etiology
and treatment of calcipenic rickets in children" and "Hereditary
hypophosphatemic rickets and tumor-induced osteomalacia".)
TYPES OF RICKETS
Mineralization defects are classified according to the predominant mineral
deficiency:
●
Calcipenic rickets is caused by calcium deficiency, which usually is due
to insufficient intake of vitamin D or failure to metabolize dietary vitamin
D into its active form. In some cases, it is caused by insufficient intake or
absorption of calcium in the setting of normal vitamin D levels. Calcipenic
rickets may be associated with low serum calcium levels but also occurs
in the setting of normocalcemia.
●
Phosphopenic rickets is characterized by low serum levels of
phosphorus, usually caused by renal phosphate wasting and, less
commonly, by nutritional phosphorus deficiency.
PATHOGENESIS
Growth plate thickness is determined by two opposing processes [1]:
●
Chondrocyte proliferation and hypertrophy
●
Calcification of growth plate cartilage with subsequent vascular invasion
of the growth plate and conversion to primary bone spongiosa
Vascular invasion requires mineralization of the growth plate cartilage, which
is delayed or prevented by deficiency of calcium or phosphorus [1-3]. In these
circumstances, growth plate cartilage accumulates and the growth plate
expands. In addition, the chondrocytes of the growth plate become
disorganized, losing their columnar orientation [4-6] with characteristic
expansion of the hypertrophic zone and impaired mineralization [7]. In the
bone tissue below the growth plate (metaphysis), the mineralization defect
leads to the accumulation of osteoid [8].
These abnormalities alter the overall geometry of the involved skeletal sites,
leading to secondary increases in the diameters of the growth plate and
metaphysis. These changes may be regarded as an attempt to compensate
for decreased bone strength by increased bone diameter. Nonetheless, bone
stability is compromised. If the underlying condition does not improve, a
structural deformity, such as bowing, ensues.
CLINICAL MANIFESTATIONS
Calcipenic and phosphopenic rickets initially manifest at the distal forearm,
knee, and costochondral junctions. These are the sites of rapid bone growth,
where the demand for calcium and phosphorus accrual is greatest.
Skeletal findings — The skeletal findings are similar for calcipenic and
phosphopenic rickets. The typical findings of advanced rickets include [9]:
●
Delayed closure of the fontanelles
●
Parietal and frontal bossing
●
Craniotabes (soft skull bones)
●
Enlargement of the costochondral junction visible as beading along the
anterolateral aspects of the chest (the "rachitic rosary") (
●
image 1)
Formation of Harrison sulcus (or groove) at the lower margin of the
thorax caused by the inward pull by diaphragmatic attachments of the
softened lower ribs
●
Widening of the wrist and bowing of the distal radius and ulna
●
Progressive lateral bowing of the femur and tibia (
picture 1)
The site and type of deformity of the extremities depend upon the age of the
child and the weight-bearing patterns in the limbs. Thus, deformities of the
forearms and posterior bowing of the distal tibia are more common in
infants, whereas an exaggeration of the normal physiologic bowing of the
legs (genu varum) is a characteristic finding in the toddler who has started to
walk (
picture 1 and
image 2). In the older child, valgus deformities of the
legs ("knock-knees") or a windswept deformity (valgus deformity of one leg
and varus deformity of the other) may be apparent. The type of deformity
depends upon the biomechanical forces acting on the lower extremities at
the time when the structural weakness develops. (See "Approach to the child
with bow-legs", section on 'Rickets' and "Approach to the child with knockknees", section on 'Other causes'.)
Radiographic findings — The changes of rickets are best visualized at the
growth plates of rapidly growing bones, where mineral demand is greatest.
Thus, in the upper limbs, the distal ulna is the site that best demonstrates the
early signs of impaired mineralization (
image 3). In the lower extremities,
the metaphyses above and below the knees are the most useful sites.
Radiographic signs include:
●
Epiphyseal/metaphyseal interface – Early signs of rickets are widening
of the epiphyseal plate and loss of definition of the zone of provisional
calcification at the epiphyseal/metaphyseal interface (
image 3). As the
disease progresses, this region becomes more disorganized, with
cupping, splaying, formation of cortical spurs, and stippling. The
appearance of the epiphyseal bone centers may be delayed or they may
be small, osteopenic, and ill defined [10].
●
Long bones – The shafts of the long bones are osteopenic, and the
cortices may become thin. The trabecular pattern is reduced and
becomes coarse. Deformities of the shafts of the long bones are often
present.
●
Looser zones and fractures – In severe rickets, pathologic fractures and
Looser zones (also known as Milkman pseudofractures or insufficiency
fractures) may be noted [11]. Looser zones represent partial-thickness
cortical fractures and are radiographically apparent as narrow
radiolucent lines 2 to 5 mm in width, often with sclerotic borders, usually
perpendicular to the cortical margin. They are characteristic of severe
osteomalacia (
image 4) and are often observed in the femur (at the
femoral neck or under the lesser trochanter) or at pubic and ischial rami.
The ulna, scapula, clavicle, rib, and metatarsal bones also may develop
these lesions and show increased radionuclide uptake ("hot spots") on
bone scans [12].
Extraskeletal findings — The extraskeletal manifestations of rickets vary
depending upon the primary mineral deficiency. Hypoplasia of the dental
enamel is a typical finding of calcipenic rickets, whereas dental abscesses
occur more often in heritable forms of phosphopenic rickets. (See
"Developmental defects of the teeth", section on 'Enamel defects'.)
Calcipenic rickets can affect the musculoskeletal system with decreased
muscle tone, leading to delayed achievement of motor milestones [13-15].
Presentation with hypocalcemic seizures occurs most frequently in the first
year of life [14]. Transient cardiomyopathy may be evident [16,17]. Children
with calcipenic rickets also are particularly prone to acquiring infectious
diseases [18,19]. (See "Clinical manifestations of hypocalcemia".)
Laboratory findings — Biochemical findings vary depending upon the type
of rickets (
●
table 1) [20]:
Calcium – The serum calcium concentration may be either decreased or
normal in calcipenic rickets, depending on the stage of rickets; serum
calcium usually is normal in phosphopenic rickets.
●
Phosphorus – Serum phosphorus concentrations usually are low in both
calcipenic and phosphopenic rickets.
●
Parathyroid hormone (PTH) – The serum concentration of PTH typically
is elevated in calcipenic rickets. In contrast, PTH concentrations are
usually normal or only modestly elevated in phosphopenic rickets. If
phosphorus deficiency is nutritional or not mediated by fibroblast growth
factor 23 (FGF23), PTH levels may be in the low-normal range.
●
Alkaline phosphatase – Serum alkaline phosphatase activity usually is
increased markedly over the age-specific reference range in nutritional
rickets (often up to 2000 international units/L), whereas the level is
elevated to a lesser extent (400 to 800 international units/L) in the
common form of heritable phosphopenic rickets (X-linked
hypophosphatemia [XLH]). Alkaline phosphatase participates in the
mineralization of bone and growth plate cartilage and is an excellent
marker of disease activity [21].
●
Vitamin D – Serum concentrations of 25-hydroxyvitamin D (25OHD)
reflect the amount of vitamin D stored in the body and, consequently, are
low in vitamin D deficiency. (See 'Calcipenic rickets' below.)
In calcipenic rickets, serum concentrations of 1,25-dihydroxyvitamin D
(1,25[OH]2D) can be low, normal, or increased and thus are not the ideal
primary laboratory indicators of the type of rickets present. However, in
some forms of phosphopenic rickets (those mediated by excess FGF23,
such as XLH and tumor-induced osteomalacia [TIO]), serum
concentrations of 1,25(OH)2D may be low or inappropriately normal (in
view of the ambient hypophosphatemia, which would normally increase
production of 1,25(OH)2D). In other forms of phosphopenic rickets (those
not mediated by excess FGF23, such as hereditary hypophosphatemic
rickets with hypercalciuria [HHRH]), the serum concentration of
1,25(OH)2D may be elevated. (See "Hereditary hypophosphatemic rickets
and tumor-induced osteomalacia".)
EVALUATION
The evaluation of a child with clinical signs of rickets should include a dietary
history, with particular attention to calcium and vitamin D intake, along with a
medication history and a history of sun exposure. Radiographic evaluation of
a child with rickets should include, at a minimum, plain films of the wrist and
hand or knees to evaluate the growth plates at rapidly growing sites. (See
'Radiographic findings' above.)
Initial classification — Serum parathyroid hormone (PTH), alkaline
phosphatase, inorganic phosphorus, and calcium concentrations are used to
determine the initial classification of rickets (
algorithm 1). Rickets is an
unlikely diagnosis if all of these values are normal. Serum creatinine and liver
enzymes should be measured to screen for renal and liver disease,
respectively. (See 'Rickets associated with chronic kidney disease' below and
'Disorders that mimic rickets' below.)
●
Calcipenic rickets – If the serum PTH is considerably elevated and
phosphorus concentration is normal or low, then a provisional diagnosis
of calcipenic rickets can be made. Serum calcium may be normal in
calcipenic rickets or may be low in advanced disease. The diagnosis is
confirmed if appropriate healing is observed on a radiograph during the
course of therapy. (See 'Calcipenic rickets' below.)
●
Phosphopenic rickets – If the serum PTH is normal or only mildly
elevated and the phosphorus concentration is low, then phosphopenic
rickets should be suspected. Demonstration of renal phosphate wasting
will identify most forms of phosphopenic rickets, but in cases of
inadequate supply of dietary phosphorus (albeit an uncommon event),
enhanced renal conservation of phosphate should be evident. (See
'Phosphopenic rickets' below.)
Further evaluation — The causes of rickets include conditions that lead to
hypocalcemia and/or hypophosphatemia as a result of decreased intake,
malabsorption, and/or increased excretion of calcium, phosphate, or vitamin
D(
table 2). To determine the optimal treatment, the common nutritional
causes of rickets must be distinguished from the forms caused by a
gastrointestinal or renal disease or an inherited disorder.
Calcipenic rickets — If the serum PTH is considerably elevated and
phosphorus concentration is low, then a provisional diagnosis of calcipenic
rickets can be made. Most cases of acquired rickets are calcipenic.
Calcipenic rickets can be further divided into the following disorders, which
can be distinguished by measuring serum levels of 25-hydroxyvitamin D
(25OHD) and, in rare cases, 1,25-dihydroxyvitamin D (1,25[OH]2D)
(
algorithm 2 and
●
table 1):
Low serum 25OHD
• Nutritional rickets – Calcipenic rickets is usually caused by dietary
deficiency of vitamin D. Occasionally, nutritional rickets is caused by
deficiency of dietary calcium or a mixed deficiency of both vitamin D
and calcium. 25OHD levels are typically low, but they may be normal if
calcium deficiency is the primary nutritional deficiency. (See "Etiology
and treatment of calcipenic rickets in children", section on 'Nutritional
rickets'.)
• Genetic disorders – 25-hydroxylase deficiency ( MIM #600081) is
caused by variants in
CYP2R1, the gene encoding the enzyme that
converts vitamin D to the major circulating vitamin D metabolite,
25OHD, thus limiting the biosynthesis of 25OHD [22]. Activating
variants in the enzyme that enhances clearance of 25OHD ( CYP3A4,
MIM #619073) can also cause early-onset rickets [23]. These
disorders are exceedingly rare and may be suspected when
pharmacologic doses of vitamin D used in the treatment of nutritional
rickets do not result in appropriate correction of the serum level of
25OHD. The differential diagnosis includes poor compliance with
medication or fat malabsorption. (See "Etiology and treatment of
calcipenic rickets in children", section on 'Genetic disorders'.)
• Secondary defects in vitamin D metabolism or absorption of
calcium or vitamin D – This can occur in extremely severe liver
disease or in intestinal disorders such as celiac disease. The circulating
25OHD level may be low or normal, depending on whether the calcium
malabsorption is mediated by vitamin D deficiency or another process.
●
Normal serum 25OHD
• 1-alpha-hydroxylase deficiency – 1-alpha-hydroxylase deficiency
( MIM #264700) is a rare disorder caused by variants in
CYP27B1,
which encodes the vitamin D 1-alpha-hydroxylase enzyme that
converts 25OHD into the active metabolite 1,25(OH)2D. Serum levels of
25OHD are normal, and 1,25(OH)2D levels are low. This was previously
known as vitamin D-dependent rickets type I or pseudovitamin D
deficiency.
• Hereditary resistance to vitamin D – Previously referred to as
vitamin D-dependent rickets type II, hereditary resistance to vitamin D
( MIM #277440) is a rare form of calcipenic rickets usually caused by
variants in the gene that encodes the vitamin D receptor ( VDR),
leading to vitamin D resistance. 25OHD levels are normal, and
1,25(OH)2D levels are usually high or very high.
The diagnosis and management of each of these disorders are discussed in a
separate topic review. (See "Etiology and treatment of calcipenic rickets in
children".)
For children with a provisional diagnosis of calcipenic rickets who do not heal
appropriately during the course of therapy, an alternate diagnosis should be
considered.
Phosphopenic rickets — Phosphopenic rickets is characterized by low
serum phosphorus concentration; PTH concentrations are usually normal,
although levels may be slightly elevated (and, rarely, even higher) at the time
of presentation of X-linked hypophosphatemia (XLH) (
table 1).
Phosphopenic rickets in children and adolescents is almost always caused by
renal phosphate wasting, which may be isolated or part of a generalized renal
tubular disorder. Occasionally, it is caused by nutritional phosphate
deficiency. The causes are outlined below.
The steps in the evaluation are:
●
Tubular reabsorption of phosphorus (TRP) and TmP/GFR – Perform a
fasting urine collection (usually for two hours) and obtain a blood sample
during the course of the urine collection with measurement of
phosphorus and creatinine concentrations in both the blood and the
urine samples. These values are then used to calculate the TRP,
expressed as a percentage of filtrate, and maximal renal tubular
threshold for phosphate, expressed per glomerular filtration rate
(TmP/GFR). The finding of very low TmP/GFR confirms renal phosphate
wasting. In contrast, very high TRP and TmP/GFR indicate renal
conservation of phosphate, implicating compromised dietary supply or
intestinal absorption.
●
Other urine studies – If renal phosphate wasting is present, perform a
routine urinalysis to determine pH and glucose, and an assessment of
urinary calcium excretion.
For screening purposes, we usually obtain a random spot urine specimen
for calcium and creatinine and determine the ratio. It should be kept in
mind that normative values differ when using SI units as compared with
conventional (mass) units, even though a ratio is employed. A more
precise evaluation in the older child can be performed by obtaining these
measurements in a 24-hour urine collection. If renal loss of multiple
solutes is suspected, obtain urinary amino acids to assess for renal
Fanconi syndrome.
●
Serum 1,25(OH)2D – If renal phosphate wasting is present, measurement
of serum 1,25(OH)2D may help to distinguish the causes that are
mediated by fibroblast growth factor 23 (FGF23) from those that are not.
This evaluation will help to distinguish among the causes of phosphopenic
rickets, as outlined below (
●
algorithm 3):
Renal phosphate wasting (low TRP and TmP/GFR)
• Renal tubular disorders – Renal tubular disorders such as Fanconi
syndrome can cause rickets due to renal loss of phosphate. Fanconi
syndrome is characterized by hypophosphatemia due to phosphaturia,
variably accompanied by renal glucosuria (glucosuria with a normal
plasma glucose concentration), aminoaciduria, tubular proteinuria,
and/or proximal renal tubular acidosis. (See "Etiology and clinical
manifestations of renal tubular acidosis in infants and children",
section on 'Fanconi syndrome'.)
• FGF23-mediated disorders (normal or low serum 1,25[OH]2D and
urinary calcium excretion) – Many forms of renal phosphate wasting
are mediated by an excess of FGF23, which acts on the kidney to
induce renal phosphate wasting:
- XLH – XLH ( MIM #307800) is the most common cause of isolated
renal phosphate loss, caused by variants in the
PHEX gene. Renal
phosphate wasting is apparent beginning shortly after birth, but
the disorder is generally recognized clinically when the child begins
to walk, causing bowing of the legs. (See "Hereditary
hypophosphatemic rickets and tumor-induced osteomalacia",
section on 'X-linked hypophosphatemia'.)
Less common autosomal dominant and autosomal recessive forms
of hypophosphatemic rickets also exist. (See "Hereditary
hypophosphatemic rickets and tumor-induced osteomalacia",
section on 'Autosomal dominant hypophosphatemia' and
"Hereditary hypophosphatemic rickets and tumor-induced
osteomalacia", section on 'Autosomal recessive hypophosphatemic
rickets'.)
- Tumor-induced osteomalacia (TIO) – TIO also causes isolated
phosphate loss. It is an acquired disorder caused by a tumor, which
usually, but not always, is benign. These tumors express FGF23
and, in some cases, other phosphaturic factors. The treatment of
choice is complete removal of the tumor, which will remove the
source of FGF23, thereby curing the disorder. However, other
measures may be required if the tumor is not localized or is unable
to be resected completely. TIO may present in late childhood and
adolescence but is more commonly seen in adults. (See "Hereditary
hypophosphatemic rickets and tumor-induced osteomalacia",
section on 'Tumor-induced osteomalacia'.)
- Other causes of excess FGF23 production – Phenotypes of FGF23mediated renal phosphate loss and rachitic bone disease may be
observed in other conditions, which generally occur in sporadic
fashion. These disorders include cutaneous skeletal
hypophosphatemia syndrome, also known as epidermal nevus
syndrome [24], and fibrous dysplasia of bone, as occurs in McCuneAlbright syndrome [25].
• Not FGF23-mediated (increased serum 1,25[OH]2D and urinary
calcium excretion):
- Hereditary hypophosphatemic rickets with hypercalciuria
(HHRH) – HHRH ( MIM #241530) is an autosomal recessive
disease and is another rare cause of phosphopenic rickets. This
disorder is distinguished from the FGF23-mediated forms of
hypophosphatemic rickets by an elevated serum 1,25(OH)2D
concentration and increased urinary calcium excretion. Because the
treatment for this disorder is distinct, it is important to evaluate for
HHRH in every patient with phosphopenic rickets before initiating
therapy by measuring serum 1,25(OH)2D and urinary calcium
excretion. The disorder is due to loss of function variants in NPT2C
(encoded by
SLC34A3), a sodium-phosphate transporter
expressed in renal tubules. Variable renal phenotypes can be
observed in heterozygotes. (See "Hereditary hypophosphatemic
rickets and tumor-induced osteomalacia", section on
'Hypophosphatemic rickets with hypercalciuria'.)
●
No renal phosphate wasting (high TRP and TmP/GFR)
• Nutritional phosphate deficiency – Occasionally, hypophosphatemic
rickets is caused by nutritional phosphate deficiency, which is
characterized by very high TRP and TmP/GFR, indicating renal
conservation of phosphate. This may occur in premature infants who
receive breast milk as their sole source of nutrition and reflects the
relatively low phosphate content of breast milk. It was also reported in
several case series of young children with complex disease who were
fed Neocate brand formula (an elemental formula designed for
children with multiple food allergies), suggesting a problem with
phosphate bioavailability compared with standard formulas [26-28].
Reformulated products designed to avoid this complication were
subsequently introduced to alleviate this problem. H2-receptor
blocking agents have also been associated with a similar problem.
Rickets associated with chronic kidney disease — Renal dysfunction is an
important cause of bone disease (renal osteodystrophy), which can include
rickets. In children with suspected rickets, renal function should be evaluated
by measuring serum creatinine.
Bone disease occurs in children with renal insufficiency for many reasons,
including reduced formation of 1,25(OH)2D, metabolic acidosis,
administration of aluminum, and secondary hyperparathyroidism. (See
"Pediatric chronic kidney disease-mineral and bone disorder (CKD-MBD)".)
DISORDERS THAT MIMIC RICKETS
A variety of conditions cause signs or symptoms that resemble rickets:
Skeletal abnormalities or bowing
●
Skeletal dysplasias – Skeletal dysplasia (eg, achondroplasia,
pseudoachondroplasia, metaphyseal chondrodysplasia) is another cause
of bilateral, symmetric bowed legs. The radiographic features can be
similar to those of rickets. However, serum inorganic phosphorus and
parathyroid hormone (PTH) concentrations usually are normal in children
with skeletal dysplasia. (See "Approach to the child with bow-legs",
section on 'Skeletal dysplasia' and "Skeletal dysplasias: Approach to
evaluation".)
●
Blount disease – Blount disease is a pathologic varus deformity of the
knee that results from disruption of normal cartilage growth at the
medial aspect of the proximal tibial physis. It can be distinguished from
rickets by distinct radiographic findings and normal serum biochemistry
values. (See "Approach to the child with bow-legs", section on 'Blount
disease'.)
Laboratory abnormalities
●
Liver disease – Elevations of serum alkaline phosphatase activity is seen
in rickets but also can be caused by liver disease. The possibility of liver
disease can be further evaluated by measuring liver enzymes (serum
alanine aminotransferase [ALT], aspartate aminotransferase [AST], and
gamma-glutamyl transpeptidase [GGT]). (See "Approach to the patient
with abnormal liver biochemical and function tests", section on 'Elevated
alkaline phosphatase'.)
●
Transient hyperphosphatasemia – Children with isolated elevations of
serum alkaline phosphatase but normal liver enzymes and no
radiographic evidence of rickets may have transient
hyperphosphatasemia of infancy and early childhood. This is usually a
benign condition that arises after a minor infectious illness and
spontaneously remits over a several-month period. (See "Transient
hyperphosphatasemia of infancy and early childhood".)
●
Primary hypoparathyroidism – Primary hypoparathyroidism causes
marked hypocalcemia but is usually not associated with rickets. This
observation suggests that low serum phosphorus and/or PTH itself may
play roles in mediating the growth plate lesion. (See "Etiology of
hypocalcemia in infants and children", section on 'Hypocalcemia with low
PTH (hypoparathyroidism)'.)
●
Hypophosphatasia – Hypophosphatasia is a rare genetic disorder of
alkaline phosphatase activity [29]. Like rickets, it is characterized by bone
demineralization. In contrast to rickets, serum alkaline phosphatase
activity is very low. Childhood forms are characterized by premature loss
of primary teeth. (See "Epidemiology and etiology of osteomalacia",
section on 'Hypophosphatasia' and "Periodontal disease in children:
Associated systemic conditions", section on 'Hypophosphatasia'.)
●
Other – Occasionally, patients, usually infants, may present with
hypocalcemia, elevated phosphorus and PTH levels, and normal 25hydroxyvitamin D (25OHD) concentrations. This combination of findings
is consistent with:
• Pseudohypoparathyroidism. (See "Etiology of hypocalcemia in infants
and children", section on 'End-organ resistance to PTH
(pseudohypoparathyroidism)'.)
• Dietary calcium deficiency (severe). (See "Etiology and treatment of
calcipenic rickets in children", section on 'Calcium deficiency'.)
• Longstanding vitamin D deficiency with a recent dosing of vitamin D.
In this case, the hyperphosphatemia has been attributed to transient
resistance to PTH. (See "Etiology and treatment of calcipenic rickets in
children", section on 'Vitamin D deficiency'.)
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected
countries and regions around the world are provided separately. (See "Society
guideline links: Vitamin D deficiency" and "Society guideline links: Pediatric
bone health".)
SUMMARY AND RECOMMENDATIONS
●
Definition – Rickets refers to the disorganized expansion and deficient
mineralization of growth plate cartilage. Osteomalacia refers to impaired
mineralization of bone and, in children, typically accompanies rickets.
(See 'Introduction' above.)
●
Classification – Rickets is classified according to the predominant
mineral deficiency. Phosphopenic rickets usually is caused by renal
phosphate wasting. Serum calcium levels are often, but not always,
decreased in calcipenic rickets. (See 'Types of rickets' above.)
• Calcipenic rickets usually is caused by dietary deficiency of vitamin D
and/or calcium; this is the most common cause of rickets worldwide.
Rarely, it is caused by genetic defects in vitamin D metabolism or
action leading to vitamin D resistance. (See 'Calcipenic rickets' above.)
• Phosphopenic rickets in children and adolescents is almost always
caused by renal phosphate wasting, which is usually an isolated
phenomenon but may be part of a generalized tubular disorder such
as Fanconi syndrome. Rarely, it may result from inadequate dietary
phosphorus or intestinal malabsorption. Renal phosphate wasting
syndromes can be fibroblast growth factor 23 (FGF23)-mediated or
occur independent of FGF23 excess. (See 'Phosphopenic rickets'
above.)
●
Skeletal findings – The skeletal findings are similar for calcipenic and
phosphopenic rickets and may include delayed closure of the fontanelles,
parietal and frontal bossing, enlargement of the costochondral junction
("rachitic rosary"), widening of the wrist, and lateral bowing of the femur
and tibia (bow legs) (
picture 1). (See 'Skeletal findings' above.)
●
Radiographic findings – Radiographic findings of rickets include
expansion of the growth plate and loss of definition of the zone of
provisional calcification at the epiphyseal/metaphyseal interface,
progressing to disorganization of the growth plate with cupping,
splaying, and formation of cortical spurs (
image 3). The changes are
best seen in the distal ulna and the metaphyses above and below the
knee. (See 'Radiographic findings' above.)
●
Laboratory findings – Serum alkaline phosphatase activity is elevated in
both types of rickets and is a good marker of disease severity in children.
Other biochemical findings may include hypocalcemia and
hypophosphatemia, but the pattern varies depending on the type and
severity of the rickets (
table 1). Serum concentration of parathyroid
hormone (PTH) typically is quite elevated in calcipenic rickets but not in
phosphopenic rickets. (See 'Laboratory findings' above.)
●
Identifying the cause – Measurements of serum PTH and inorganic
phosphorus serve to distinguish calcipenic from phosphopenic rickets
(
algorithm 1). (See 'Initial classification' above.)
• Calcipenic rickets – For children with calcipenic rickets,
measurements of serum 25-hydroxyvitamin D (25OHD) help to
distinguish rickets caused by vitamin D deficiency (the most common
form) from other causes of calcipenic rickets (
algorithm 2). (See
'Calcipenic rickets' above and "Etiology and treatment of calcipenic
rickets in children".)
• Phosphopenic rickets – For children with phosphopenic rickets, an
assessment of renal excretion of phosphate should be performed (as
tubular reabsorption of phosphorus [TRP] or maximal renal tubular
threshold for phosphate, expressed per glomerular filtration rate
[TmP/GFR]) (
algorithm 3).
- Low TRP or TmP/GFR suggests renal phosphate wasting. Causes of
renal phosphate wasting should be investigated with assessment
of serum 1,25-dihydroxyvitamin D (1,25[OH]2D), a routine urinalysis
to determine pH and glucose, and an assessment of urinary
calcium excretion.
- High TRP or TmP/GFR indicates renal conservation of phosphate
and is consistent with nutritional phosphate deprivation. This may
be due to insufficient phosphate content or decreased
bioavailability in formula products and other nutritional
supplements.
(See 'Phosphopenic rickets' above and "Hereditary
hypophosphatemic rickets and tumor-induced osteomalacia".)
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