Scurvy, Rickets and Osteomalacia

1. SCURVY
Scurvy is disease caused by severe Vitamin C deficiency which presents with
joint effusions, swelling over long bones, bleeding gums, loosening of teeth,
hematuria, and susceptibility to hemorrhage.
Diagnosis is made based on history, clinical and radiological picture, and
resolution of symptoms following vitamin C administration. Lab tests are
usually not helpful.
Treatment is prompt administration of Vitamin C.

2. RISK FACTORS
elderly, especially men who live alone
chronic malnutrition
overcooking destroys vitamin C
alcoholic
smokers
malabsorptive conditions (Whipple's disease, inflammatory bowel disease, cancer chemotherapy)
PATHOPHYSIOLOGY
humans are unable to synthesize L-ascorbic acid because the enzyme L-gluconolactone oxidase is
nonfunctional
Vitamin C deficiency leads to decrease in chondroitin sulfate and collagen synthesis and repair
impaired intracellular hydroxylation of collagen peptides
net effect is altered bone formatin with the greatest effect occuring in the metaphysis
defect in spongiosa of the metaphysis at the growth plate

3. PRESENTATION
History
 infant diet consisting of evaporated or condensed milk
 "tea and toast" diet in elderly
Symptoms
 malaise and fatigue
 pain
 bone pain
 myalgia, because of reduced carnitine production
 gum bleeding and loosening of teeth
 hematuria
 hematemesis
 hemorrhage
 iron deficiency

4. PHYSICAL EXAM
 petechiae and ecchymosis
 joint effusions
 swelling over long bones because of subperiosteal hemorrhage
 scorbutic rosary (costochondral separation)
o angular step-off deformity in children
o differentiated from rachitic rosary, which is rounded and nodular

5. IMAGING
 RADIOGRAPHS – wrist , knee, sternal ends of ribs
 FINDINGS
 the white line of Frankel
widened zone of provisional calcification
between epiphysis and metaphysis
 Trummerfeld zone
transvese radiolucent band in the metaphysis adjacent to
the Frankel line also known as the scurvy line
 Wimberger ring
ring of increased density surrounding epiphysis
 Pelkin spur and fracture
metaphyseal spurs and fractures
 corner sign of Park
metaphyseal clefts
 thin cortices ("pencil-point" cortex)
 decreased trabeculae with ground-glass osteopenia
 subperiosteal elevation
 epiphyseal separation
 fractures and dislocations

6. TREATMENT
Non-operative
 vitamin C replacement
 oral vitamin C at 250mg qid x 1 week in adults
Indications
 signs and symptoms of scurvy
 chronic malnutrition

7. RICKETS
Rickets is a metabolic bone disease caused by a defect in mineralization of
osteoid matrix caused by inadequate calcium and phosphate that occurs prior
to closure of the physis. Patients present with characteristic features such as
bowing of long bones, ligamentous laxity, brittle bones and enlargement of
costal cartilage.
Diagnosis is made based on a thorough evaluation of serum labs, clinical
features, and radiographic findings.
Treatment involves medical management to resolve the underlying etiology
of rickets.

8. Pathophysiology
 Vitamin D and PTH play an important role in calcium homeostasis
 disruption of calcium/phosphate homeostasis
 poor calcification of cartilage matrix of growing long bones
 occurs at zone of provisional calcification
 leads to increased physeal width and cortical thinning/bowing
orthopaedic manifestations include-
 brittle bones with physeal cupping/widening
 bowing of long bones
 ligamentous laxity
 flattening of skull
 enlargement of costal cartilage (rachitic rosary)
 kyphosis (cat back)

9. PRESENTATION
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

10. IMAGING
RADIOGRAPHS- AP and lateral of affected bone
FINDINGS
 physeal widening
 metaphyseal cupping
 decreased bone density
 Looser's zones
pseudofracture on the compression side of bone
 rachitic rosary
prominence of rib heads at the osteochondral junction
 lower extremity bowing
often genu varum
 codfish vertebrae
 cat back
dorsal kyphosis

11. CLASSIFICATION
 Vitamin D-resistant (familial hypophosphatemic)
 most common form of heritable rickets
 presents at 1-2 years of age
 caused by inability of renal tubules to absorb phosphate
 GFR is normal
 vitamin D3 response is impaired
Genetics
 X-linked dominant
 most common form
 results from mutation in PHEX gene
 leads to increased levels of FGF23, which decreases renal phosphate absorption and suppresses
renal 25-(OH)-1α-hydroxylase activity
 autosomal dominant
 results from mutation in FGF23
 leads to decreased FGF23 degradation
 autosomal recessive
 results from mutation in dentin matrix protein 1 (DMP1) gene
 leads to impaired osteocyte maturation and bone mineralization, and increased levels of FGF23

12.  Vitamin D-deficient (nutritional)
 results from decreased dietary intake of Vitamin D
 rare now that Vitamin D is added to milk
 presents at 6 months - 3 years of age
risk factors
 premature infants
 black children > 6 months who are still breastfed
 patients with malabsorption syndromes (celiac sprue) or chronic parenteral nutrition
 Asian immigrants
 patients with unusual dietary choices (vegetarian diet)
pathophysiology
 low Vitamin D levels lead to decreased intestinal absorption of calcium
 low calcium levels leads to a compensatory increase in PTH and bone resorption
 bone resorption leads to increased alkaline phosphatase levels
 Vitamin D-dependent (type I & type II)
 rare disorder
 leads to clinical features similar to Vitamin D-deficient rickets but more severe

13. clinical characteristics
 type I
hypotonia, muscle weakness, growth failure, hypocalcemic seizures, joint pain/deformity,
fractures in early infancy
 type II
hypotonia, muscle weakness, growth failure, hypocalcemic seizures, growth retardation, bone
pain, severe dental caries or dental hypoplasia
pathophysiology
 type I
 results from autosomal recessive mutation in renal 25-(OH)-1α-hydroxylase
 responsible gene 12q14
 prevents conversion of inactive form of vitamin D to active form
 leads to decreased calcitriol
 type II
 results from autosomal recessive mutation in intracellular receptor for 1,25-(OH)2-vit. D
 leads to increased calcitriol

14. TREATMENT
NON-OPERATIVE
 calcitriol
Indications
 Vitamin D-resistant (familial hypophosphatemic) rickets
 type I Vitamin D-dependent rickets
 phosphate replacement
Indication - Vitamin D-resistant (familial hypophosphatemic) rickets
 Vitamin D
Indications
 Vitamin D-deficient (nutritional) rickets
 type II Vitamin D-dependent rickets (partial 1,25-(OH)2-vitamin D resistance)
 Calcium
Indication- type II Vitamin D-dependent rickets (total 1,25-(OH)2-vitamin D resistance)
 Burosumab
 human monoclonal antibody to FGF-23
 approved for the treatment of X-linked hypophosphatemia among children 1 year and older.

15. DOSES
•Calcitriol
•20-30 μg/kg/day split into 2-3 doses in children
•0.5-0.75 μg/day split into 2 doses in adults
•Phosphate replacement
•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
•Vitamin D
•5000 IU/day for 6-10 weeks
OPERATIVE
•corrective surgery (multilevel osteotomy)
indications
•severe tibial bowing
technique
•variety of fixation devices including K-wires, plates, intramedullary nails, and/or external fixation

16. OSTEOMALACIA
Osteomalacia is a metabolic bone disease where defective mineralization
results in a large amount or unmineralized osteoid.
Diagnosis is made based on a thorough evaluation of serum labs, clinical
features, and radiographic findings.
Treatment involves medical management with Vitamin D supplementation
and resolving the underlying etiology.

17. Risk factors
 vitamin-D deficient diets
 malabsorption e.g. celiac disease
 renal osteodystrophy
 hypophosphatemia
 chronic alcoholism
 tumors (tumor-induced osteomalacia)
drugs affecting bone mineralization
aluminium
etidronate
Fluoride
drugs associated with vitamin D deficiency
phenytoin
phenobarbital
rifampin
cholestyramine
cadmium
glucocorticoids
drugs affecting phosphate homeostasis
aluminium-containing phosphate-binding
antacid
ifosfamide

18. PRESENTATION
Symptoms
 generalized bone and muscle pain
 fractures of long bones, ribs and vertebrae
 proximal muscle weakness weakness
 Fatigue
Physical exam
 waddling gait
from hip pain and thigh weakness
 difficulty rising from chair and climbing stairs

19. IMAGING
RADIOGRAPHS FINDINGS
 Looser's zones (insufficiency fractures)
o medial femoral cortex
o pubic ramus
o scapula
 fractures (especially in the proximal femur/femoral neck)
 biconcave vertebral bodies
 trefoil pelvis
 protrusio acetabuli
BONE SCAN
 increased activity

20. TREATMENT
Nonoperative
 large doses of oral vitamin D (1000IU/day), treat underlying cause
specific subgroups of patients
 on long-term anticonvulsant therapy
supplement with 400-800IU/day of vitamin D
 with hepatobiliary disease
supplement with 25(OH)-vit D
 with renal disease
supplement with 1,25(OH)2 vit D

21. SERUM
CALCIUM
SERUM
PHOSPHAT
E
ALKALINE
PHOSPHATE
PTH 25 (OH) VIT
D
1, 25 (OH)
VIT D
URINARY
CALCIUM
OSTEOMALACIA LOW LOW HIGH HIGH LOW LOW LOW
OSTEOPOROSIS NORMAL NORMAL VARIABLE NORMAL NORMAL NORMAL NORMAL
TUMOR INDUCED
OSTEOMALACIA
LOW VERY LOW LOW LOW LOW LOW LOW
OSTEOPETROSIS NORMAL NORMAL HIGH NORMAL NORMAL NORMAL NORMAL