RICKETS

CHINYAMA SIMACHENYA
CBU 5YEAR MEDICAL STUDENT 2024
Table of content
• Definition
• Epidemiology
• Etiology
• Classification
• Pathophysiology
• History and physical examination
• Clinical findings
• Investigations
• Differentials
• Treatment
• References
Definition
• Rickets is a disease of growing bone that is unique to children and
adolescents
• It is caused by failure of the osteoid to calcify in a growing person, it
occurs prior to closure of the physes. When this occurs in adults it is
called osteomalacia.
EPIDEMIOLOGY
• In the United states, vitamin D deficiency does not occur in infants fed
with infant formulas because both formula and cow milk sold in the
United States contain about 400IU 0f vitamin D per liter, which meets
the needs of infants. According, except in pediatric patients with
chronic malabsorption syndromes or end-stage renal disease, nearly
all cases of rickets occur in breastfed infants who have dark skin and
receive no vitamin D supplementation.
• In Africa, low social economic status which leads to defienciencies in
mineral elements such as calcium,phosphorus and vitamin D is what
mostly leads to rickets
• Internationally , the frequency of rickets has been increasing possibly
due to recommendations for children to use sunscreen when playing
outdoors and a tendency for children to play indoors.
• Rickets are therefore seen mostly in developing countries than
developed countries.
ETIOLOGY
Vitamin D deficiency is by the far the most common cause of nutritional
rickets. Rarely , nutritional deficiency of calcium or phosphorus can
result in rickets. Other less frequent causes of rickets include genetic
causes, drug-induced rickets, and rickets secondary to liver
diseases. Medications that impair vitamin D metabolisms such as
diphenylhydantoin and rifampicin can result in rickets
 CLASSIFICATION
1. VITAMIN D RESISTANT (FAMILIAL HYPOPHOSPHATEMIA)
- This is the most common form of heritable rickets
- Presents at 1-2 years of age
- Due to inability of the renal tubules to absorb phosphate but the GFR is
normal.
- Increased loss of phosphorus through urine due to genetic mutations
involving;
a. Phosphate regulating-neural endopeptide(PHEX), which leads to increased
levels of FGF23 which reduces renal phosphate absorption and suppression
of renal 1,25 hydroxylase activity. This is an X-linked inherited mutation.
b. Dentin matrix acidic phosphoprotein1(DMP1)
Autosomal recessive condition which leads to impaired osteocyte
maturation and bone mineralization and increased levels of FGF23.
c. Mutation in FGF23 which leads to decreased FGF23 degradation.
FGF23 is a hormone produced by osteocytes which plays an important
roe in bone metabolism, it inhibits the synthesis of 1,25-dihydroxy
vitamin d and binds with FGF receptors and increases renal excretion of
phosphorus by reducing the number of the main renal phosphate
transporters, the sodium dependent phosphate transporters.
2. VITAMIN D DEFICIENT(NUTRITIONAL)
-Reduced dietary intake
- Presents at 6 months – 3years of age
Risk factors
- Prematurity
- Black children who are 6 months and still breastfed
- Children with malabsorption syndromes
- Vegans
- Low socioeconomic status
Low vit d levels leads to decrease in intestinal calcium absorption which leads to
compensatory high levels of PTH and bone resorption which leads to elevated alkaline
phosphatase levels.
3. VITAMIN D DEPENDENT(TYPE I AND II)
More severe but rare conditions.
Type I
Results from autosomal recessive mutation in renal 1,25 hydroxylase and therefore the active
form of vit d will not be formed , this leads to reduced levels of calcitriol.
The patient will present with hypotonia, muscle weakness, growth failure, hypocalcemic
seizures, joint pain/deformity and fractures in early infancy
Type II
It is inherited as an autosomal recessive condition. It is characterized by end-organ resistance
to the active form of vitamin D. It is caused by VDR gene mutations, and these mutations alter
the VitD receptor, often preventing the receptor from interacting with 1,25-dihydroxy vitamin
D. As a result, VDR cannot regulate gene activity, even with normal amounts of 1,25-
dihydroxy vitamin D in the body.
PATHOPHYSIOLOGY
• The osseous tissue in the growing long bones is created from the
cartilage by a process called endochondral ossification. The
chondrocytes in the cartilage grow to form the hypertrophic
chondrocytes, which then start producing the cartilage matrix. This
cartilage matrix is then calcified, which is reabsorbed and replaced
with woven bone, which is later replaced by mature lamellar bone. In
these processes, there is a formation of unmineralized bone tissue
(osteoid), and the osteoid is mineralized in the presence of adequate
calcium and phosphate levels. Any defect in osteoid mineralization
may cause rickets. In all types of rickets, the characteristic features
occur at the growth plate.
• Cholecalciferol (ie, vitamin D-3) is formed in the skin from 5-
dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps.
The first hydroxylation occurs at position 25 in the liver, producing
calcidiol (25-hydroxycholecalciferol), which circulates in the plasma as
the most abundant of the vitamin D metabolites and is thought to be
a good indicator of overall vitamin D status.
• The second hydroxylation step occurs in the kidney at the 1 position,
where it undergoes hydroxylation to the active metabolite calcitriol
(1,25-dihydroxycholecalciferol). This cholecalciferol, which circulates
in the bloodstream in minute amounts, is not technically a vitamin
but a hormone.
• Calcium and phosphorus are required for the normal matrix
mineralization. Reduction in these minerals causes abnormal
mineralization. Normal serum calcium levels require sufficient dietary
calcium intake, normal calcium absorption through the
gastrointestinal tract, and adequate active form of vitamin D.
• This increase of calcium and phosphorus in extracellular fluid, in turn,
leads to the calcification of osteoid, primarily at the metaphyseal
growing ends of bones but also throughout all osteoid in the skeleton.
HISTORY AND PHYSICAL
EXAMINATION
• A detailed history and a thorough physical examination are essential to
diagnose patients with rickets. History should include the age of the child,
details of sunlight exposure, dietary history including intake of supplements,
developmental/growth history, and pertinent family history. Positive family
history of skeletal abnormalities, stunted growth, alopecia, dental
abnormalities, parental consanguinity may suggest a genetic cause of rickets.
• Physical examinations should include detailed skeletal examination (with
attention to any tenderness, deformities, softening, asymmetry, and
neurological abnormalities) as well as a detailed dental evaluation. History
and physical examination usually give clues to diagnose rickets. However, the
absence of clinical signs of rickets doesn’t exclude this diagnosis, especially
in the early stages.
CLINICAL FINDINGS
Symptoms
• Listlessness,irritability,generalized weakness
Physical exam
• tibial bowing ,due to widened proximal tibial physes
• rachitic rosary-enlargement of costochondral junction
• bowing of knees
• retarded bone growth
• muscle hypotonia
• waddling gait
• dental abnormalities -delayed dental eruption,defective enamel
• pathologic fractures
bowing of legs
INVESTIGATIONS
• IMAGING
AP and lateral Xrays of the affected bone
Findings
1.Physeal widening
2.Metaphyseal cupping
3.Decreased bone density
4.looser’s zones- pseudofracture on the compression side of bone
5.Rachitic rosary
• Prominence of rib heads at osteochondral junction
junction
6.Codfish vertebrae
7. Cat back – dorsal kyphosis
Laboratory
Serum measurements
1. Calcium
2. Phosphorus
3. Alkaline phosphatase
4. Parathyroid hormone
5. 25 dihydroxycholecalcifefol
6. 1,25 dihydroxycholecalciferol
Differentials
• Renal osteodystrophy
• Hypophosphatasia
• Genu varus
Treatment
1.Non operative
a. Calcitriol
Vit d resistant rickets and type I vit d dependent rickets
20-30 μg/kg/day split into 2-3 doses in children
0.5-0.75 μg/day split into 2 doses in adults
b. Calcium
Type ii vit d dependent rickets
c. Burosumab
Human monoclonal antibody to FGF23, for tx of X-linked hypophosphatemia
among one year and older children.
d.Vitamin D
technique
5000 IU/day for 6-10 weeks
e.Phosphate replacement
• technique
• 20-40 mg/kg/day split into 3-5 doses in children
• 750-1000 mg/day split into 3-4 doses in adults
• Must be given in combination with active vitamin D (i.e. calcitriol) in
XLH patients, as this prevents the development of secondary
hyperparathyroidism as seen in patients treated with phosphate salts
alone
2.Corrective surgery (multilevel osteotomy)
• technique
• variety of fixation devices including K-wires, plates, intramedullary
nails, and/or external fixation
References
• Medscape
• Orthobullets
• NCBI bookshelf