rickets and osteomalacia

1. Rickets and osteomalacia
PRESENTATION: DR .SUSHIL POKHREL
MS ORTHOPEADICS RESIDENT

2. Review of Calcium & vitamin d metabolism
Introduction ,pathophysiology ,c/f,classification
&management of rickets
Introduction ,pathophysiology ,c/f and management
of osteomalcia
Hypophosphetemic rickets
Oncogenic osteomalacia
Review

3. Calcium metabolism

5. VitaminD
metabolism

6. Rickets : occurs in children before ephysial closure
- impaired mineralization of growth plate
- stunting
- bony deformity
Mineralization : incorporating calcium and phosphate
Hydroxyapatite crystal into osteoid to provide strength

7. Causes :
1. Vitamin D‐related rickets/osteomalacia
2. Calcium deficiency (with normal vitamin D status)
3. Hypophosphatemic rickets/osteomalacia
4. Mineralization inhibitors

8. 1.Vitamin D‐related rickets/osteomalacia
Severe vitamin D deficiency:
• Low sunshine exposure, low dietary intake
• Malabsorption (calcium absorption may also impaired): bariatric
surgery , bowel resection, celiac disease, cholestatic liver disease,
exocrine pancreatic insufficiency, gastrectomy, IBD
• Impaired hepatic 25‐hydroxylation: severe cirrhosis
• Impaired renal 1α‐hydroxylation: chronic kidney disease
• Increased renal losses: nephrotic syndrome
• Increased catabolism: enzyme‐inducing drugs (anticonvulsants,
rifampicin )

9. 1.Vitamin D‐related rickets/osteomalacia cont
Vitamin D‐dependent rickets:
• Type 1A: 1α‐hydroxylase deficiency
• Type 1B: 25‐hydroxylase deficiency
• Type 2: vitamin D‐dependent rickets with VDR mutation

10. 2.Calcium deficiency (with normal vitamin D
status)
Nutritional: very low dietary calcium intake
Calcium malabsorption (similar causes as vitamin D malabsorption)
Hypercalciuria in combination with renal phosphate wasting

11. 3.Hypophosphatemic rickets/osteomalacia
• Gastrointestinal causes: poor nutritional intake (eg, breastfed very
low birth weight infants), chronic diarrhea, excessive phosphate
binders,cystic fibrosis
• Tumor‐induced (oncogenic) osteomalacia: ↑ FGF23-inhibit 1αhydro-
oxylase ,↓ absorption of phosphate in PCT
• Fanconi syndrome: (medications like tenofovir, adefovir, ifosfamide,
expired tertracycline) ↓ absorption in PCT

12. 3.Hypophosphatemic rickets/osteomalacia
cont
• X‐linked hypophosphatemic rickets : (PHEX mutations) -↑FGF 23
• Autosomal dominant hypophosphatemic rickets:↓ FGF23 degredation
• Autosomal recessive hypophosphatemic rickets: ↑FGF 23 (matrix dentine
protein mutation)
• Hereditary hypophosphatemic rickets with hypercalciuria :
mutation in Na-P cotransportor in PCT
• Dent disease: -chloride channel mutation(clcn5)

13. 4. Mineralization inhibitors
• Metabolic acidosis: renal insufficiency, renal tubular acidosis (± renal
phosphate wasting), ileostomy and urinary diversion :↓ ph ↑osteoclastic
acrivity
• Aluminum toxicity (eg, from antacids, dialysis fluid): ↓hydoxyapipite
formation by ↓ca-p precipitation
• Fluorosis (including endemic fluorosis from borehole water): ↑osteoid
without mineralization
• Environmental intoxication with cadmium , strontium, : damage PCT
↓phosphate absorption

14. Pathophysiology
rickets

15. • Growth plate thickness determined by
two opposing processes:
chondrocyte: proliferation
:hyperthrophy
Vascular invasion :
: mineralization
delayed /prevented by
decrease ca /phosphorus

16. Decreased mineralization – growth plate cartilage accumulate
chondrocyte loose linear orientation
expansion of hypertrophic zone
growth plate thickens
metaphysis: Broadening of the ends of long bones
Defective mineralization ----defective osteoid
Altered geometry of bone - in an attempt to compensate for the
decrease in bone strength
Bone stability compromised-leading to bowing

18. Stages of calcium deprivation leading to nutritional rickets and osteomalacia

19. Clinical features- rickets
1.Depend usually on the age of presentation:
2.First 3 months of life (congenital rickets) –
c/f are rare :as active transport of calcium in palcenta
3.First 6 months of life-
presents with symptoms of hypocalcemia
-convulsions, apneic spells, twitching
- later there is failure to thrive,
- listlessness and muscular flaccidity rather then deformity

20. 4. between 6 and 18 months of age,:
- Classical features with bony
deformities is common
5. second peak occurring during the adolescent growth spurt

21. Craniotabes: seen in young infants, pressure over the soft
membranous bones of the skull gives the feeling of a ping pong ball
being compressed and released.
-d/d syphilis ,osteogenesis inperfecta ,
Normal infant

22. • Bossing of the skull: Bossing of the frontal and parietal bones
becomes evident after the age of 6 months

23. • Broadening of the ends of long bones
- most prominently around wrists and knees
- usually seen around 6-9 months of age

24. • Delayed teeth eruption
• Harrison's sulcus: A horizontal depression,
along the lower part of the chest,
corresponding to insertion of diaphragm.
Muscular hypotonia: The child's abdomen becomes protruberant
(pot belly) because of marked muscular hypotonia.
Visceroptosis and ↓lumbar lordosis occurs

25. • Rachitic rosary: The costo-chondral junctions on the anterior chest
wall become prominent, giving rise to appearance of a rosary.
• Pigeon chest: The sternum is prominent

26. Deformities: Deformities of the long bones resulting in knock knees or
bow legs is a common presentation of rickets, once the child starts
walking

27. Deformities seen
• Genu varum deformity occurs when the femoral intercondylar
distance exceeds 5 cm
common skeletal system deformity in infants with untreated rickets
• Genu valgum
• Kyphoscoliosis is observed after 2 years of age

29. Diagnosis
• A high index of suspicion - clinical
-biochemical
- radiographic features
• Clinical signs and symptoms alone are highly sensitive but
unfortunately not specific for diagnosis

30. Wrists and costochondral enlargement were the clinical signs with the best combination of sensitivity
(72% and 76%, respectively) and specificity (81% and 64%, respectively) for active rickets

31. Radiological Appearance
• X-rays of both wrists and knees – antero-posterior views are most
commonly used
severe diaseases : growth plate
- thickening
- widens
fraying d/t metaphyseal loss of sharp border
Cupping- d/t metaphyseal edge change
from convex/flat to concave
Early changes- radiolucent bones with thin cortices
- loss of the normal trabecular pattern
-

32. • Growth plate abnormalities :-delay bone age
:deformities of shafts of the long bones
1. Infant and young child varus deformities of the lower limbs are
common
2.Older children, valgus or windswept deformities of the lower limb
become more frequent

33. Laboratory findings
1.Serum calcium is usually normal or low:
maintained at the lower part of the normal range as a result of secondary
hyperparathyroidism
2.Serum phosphate is low.
3. Increased serum ALP
:other causes of increased ALP concentrations should be excluded, for example
cholestasis, Paget disease, or bone metastasis

35. Didorder Serum
calcium
Serum
phos
ALK
phos
PTH 25(oH)vit
D
1 25(oH)vit D Clinical
features
Urinary ca
1α hydroxylase
mutation of vit d receptor gene

36. Other Types of rickets
Congenital rickets –d/t severe vit d def in pegnency
- inadequate sun exposure,poor intake,closed space pregnency
c/f : hypocalcemia
:IUGR
:↓ ossification centres
:rachitic changes
Rickets of prematurity:80%transfer og ca/po4 occure in 3rd trimester
: most common <1000gm birth weight
c/f: 1-4 months after birth
: nontraumatic #
diagnosis: by radiological and lab parameters

38. MEDICAL Treatment
• Residual deformity is rare after medical treatment of nutritional rickets
there is no specific orthopedics treatment of nutritional rickets
• Hypocalcemia: emergency treatment
• CALCIUM DEFIENT RICKETS :Vitamin D deficiency
calcium carbonate : neonates: 50-150 mg/kg/day orally given in 4-6
divided doses, maximum 1 g/day
infants and children: 45-65 mg/kg/day orally given in 4 divided
AND
ergocalciferol (vitamin D2)/cholecalciferol (vitamin D3) : 3000 to 10,000 units
orally once daily for 3-6 months; or 150,000 to 300,000 units orally, given as
a single dose, repeat every 3 months if needed

39. • CALCIUM DEFIENT RICKETS :CALCIUM deficiency
calcium carbonate : neonates: 50-150 mg/kg/day orally given in 4-6
divided doses, maximum 1 g/day; infants and children: 45-65 mg/kg/
AND
ergocalciferol (vitamin D2) : 800 units orally once daily

40. • CALCIUM DEFIENT RICKETS:pseudovitamin D deficiency
calcitriol
CALCIUM DEFIENT RICKETS: vitamin DR resistance
calcium carbonate : neonates: 50-150 mg/kg/day orally given in 4-6
divided doses, maximum 1 g/day
infants and children: 45-65 mg/kg/day orally given in 4 divided doses
AND
ergocalciferol (vitamin D2) : 12,000 to 500,000 units orally once daily
OR SOME PATIENT NEED HIGH DOSES

41. • HYPOPHOSTEMIC RICKETS : X LINKEd
calcitriol :
• and
sodium phosphate/potassium phosphate
• stoss therapy :Megadoses of vitamin D (eg, a 500,000 IU intramuscu-lar or oral dose) should be
avoided if possible because of the risk of hypervitaminosis D in the first months, which may be
associated with an increased risk of falls and fractures
• calcifediol (25OHD) may be useful in patients with fat malabsorp-tion, because it is a more polar
metabolite absorbed mainly via the portal venous system.

42. MONITERING treatment:
• If the line of healing (a line of sclerosis on the metaphyseal side of the
growth plate) is not seen on X-rays within 3-4 weeks of therapy, same dose
may be repeated.
• In cases where the child responds to vitamin D therapy, a maintenance dose
of vitamin D is given per day.
• If there is no response even after the second dose, a diagnosis of refractory
rickets is made.
• Multi speciality team of nephrologist, endocrinologist and physician is
needed.

43. Orthopaedic treatment
It is required for the correction of deformities:
• Conservative methods:
Mild deformities correct spontaneously, as rickets heals.
Specially designed splints (mermaid splints) or orthopaedic
shoes for correction of knee deformities.

44. • Operative methods:
Genu varum : usually correct by 3-4 years
• Moderate or severe deformities often require surgery.
• Corrective osteotomies are performed as require
Genu valgum :hemiepiphysodesis, corrective osteotomies

45. OSTEOMALACIA
Osteomalcia : occure in adult
-impaired mineralization of ostoid
histolological hallmark : hyperosteoidosis
:prolong mineralization lag time
• Osteon – organic matrix of collagen & glycosaminoglycans that is
secreted by osteoblast to form unmineralized framework of bone

47. EPIDEMOLOGHY
• Osteomalcia: common in Asian & adult middle east due to low
calcium intake
ETIOLOGY : AS DICUSSED IN RICKETS
Patho

50. Clinical Features
• Osteomalacia: usually - insidious course
:patients may complain of relatively non-specific symptoms
such as widespread bone pain and muscle weakness.
• Carpopedal spasm as a result of teatany. ( hypocalcemia )
• Unexplained pain in the hip or one of the long bones due to a stress
fracture.

51. • Spontaneous fractures occur usually in spine, and may result in
kyphosis
• Osteomalacia increases the risk of fractures throughout the skeleton.
• When present, muscle weakness is of a proximal distribution, causing
a ‘waddling’ gait.

52. Radiological examination

53. Looser's zone (pseudo-fractures): radiolucent
zones occurring at sites of stress.
:caused by rapid resorption
:slow mineralisation
surrounded by a collar of callus.
• Common sites :
pubic rami, axillary border of scapula,
ribs and the medial cortex of the neck of
the femur.
±

54. Triradiate pelvis in females: protusion of hip and spine in soft pelvis with
Protrusio-acetabuli i.e., the acetabulum protruding into the pelvis
Indentation of the acetabula producing the trefoil or
champagne glass pelvis

55. Biconcave vertebrae. Feature of secondary
hyperparathyroisdism:
sub periosteal erosion at site of maxium
remodeling eg radial aspect of middle and
index finger ,medial aspect of proximal
humerusfemoral neck

56. Bone biopsy:
• A transiliac bone biopsy after tetracycline double labeling provides a
definitive diagnosis –assessed by fluorescence microscopy
three criteria: osteoid volume greater than 10%,
:uncorrected osteoid thickness greater than 15 µm
: mineralization lag time of more than 100 days
• The characteristic histological finding is excessive uncalcified osteoid.

57. Lab
• serum calcium level is low,
• phosphates are low and
• alkaline phosphatase high
• A combination of raised ALP and raised PTH with low calcium or
phosphate has the best diagnostic properties

58. We recommend a diagnosis of osteomalacia in the presence of high ALP, high PTH, low dietary
calcium intake (<300 mg/day) and/or low serum 25OHD (<30 nmol/L).

59. Treatment
• Nutritional osteomalacia : low doses of calcium (eg, 1000 mg of
elementary calcium) and vitamin D (eg, 800 to 1200 IU/day)
• When gastrointestinal absorption is severely impaired,
some patients may require high to very high
doses of oral calcium (eg, 1000 to 4000 mg/day) and
vitamin D (eg, 4000 to 10,000 IU/day of vitamin D3)

60. Familial hypophosphataemic rickets
• X-linked dominant inheritance,
• caused by a mutation in the PHEX gene, which leads to inappropriately elevated FGF23
levels.
• Starts in infancy or soon after and causes bony deformity of the lower limbs if it is not
recognized and treated.
• During infancy they appear normal but develop genu valgum or varum as they bear
weight.
• No myopathy
• In adulthood there is a tendency to develop heterotopic bone formation around some of
the larger joints and in the longitudinal ligaments of the spinal canal producing
enthesopathies and neurological symptoms.

61. • Increased risk of fractures including stress fractures but the bones appear sclerotic.
• Biochemically these patients have low levels of phosphate, but serum calcium and PTH levels are usually
normal.
• Treatment :
• phosphate (up to 3 g per day, to replace that which is lost in the urine)
• large doses of vitamin D (to prevent secondary hyperparathyroidism due to phosphate administration).
• Calcitriol (plasma calcium concentration should be monitored in order to forestall the development of
hypercalciuria and nephrocalcinosis).
• FGF23-blocking antibodies holds out the option of more effective and better tolerated treatment.
• Bony deformities may require bracing or osteotomy.

62. Oncogenic osteomalacia
• This is caused by FGF- 23-secreting tumours, particularly vascular tumours such as
haemangiopericytomas, and also fibrohistiocytic lesions such as giant cell tumours and
pigmentedvillonodular synovitis.
• The tumour is clinically silent more often and patients present with symptoms such as
bone pain related to osteomalacia.
• Diagnosis is confirmed by finding of an elevated serum FGF23.
• Resection of the primary leads to prompt resolution,
• Identifying the site of the primary can be challenging and requires extensive imaging.

63. Review
• Rickets and ostemalacia occur in children and adult occurs either due
to ca/vitamin D/phosphorus deficiency
• Deficiency of ca/po4/vit D leads to defective mineralization
• Clinical picture ranges from hypocalcemia , deformity ,even to
fractures
• Usually medical management is sufficient surgical management is
done for deformity correction
• Diagnosis is mainly by clinical and radilological with lab as supporting

65. References
• MILLER’S REVIEW OF ORTHOPAEDICS SEVENTH EDITION
• Apley and Solomon’s System of Orthopaedics and Trauma
• Primer on the Metabolic Bone Diseases and Disorders of Mineral
Metabolism, Ninth Edition.
• Nelson pediatrics 20 edition
• Internet

66. Thank you