Undergraduate teaching(MBBS) class regarding metabolic bone diseases

1. METABOLIC BONE DISEASES
DR. RAVI KUMAR
Assistant Professor
Dept. of Orthopaedics
AIMSR Chittoor

2. Composition of bone
Bone cells
Osteocytes
Osteoblasts
Osteoclast
Bone matrix
Organic components.
Inorganiccomponents.

3. Composition of Bone
• Theextracellular matrix
35% organic
 Type1 collagen(95%)
Proteoglycan
Osteocalcin/osteonectin
Phospholipids
 65% inorganic
Calcium hydroxyapatite Ca10(PO4)6(OH)2
Magnesium,SodiumandPotassium
• The cells
Osteo-clast/blast/cytes/progenitors

4. Physis
• It is the anatomical
differentiation between
growing and mature bone.
• It appears radiologically as a
lucency between the epiphysis
and the metaphysis.
• It represents the site where
longitudinal bone growth occurs.
• It is the primary site for the
effect of metabolic and
endocrine bone disorder.

6. Calcium metabolism
•99% of calcium stored in the bone
•Regulatory mechanisms maintaining the calcium
levels in the bone and the body
•Main regulators of calcium metabolism are
1.Parathyroid Harmone
2. Vitamin D
3. Calcitonin

8. Phosphate Metabolism

9. Parathyroid hormone(PTH)
• Synthesized and secreted by chief cells of
parathyroid gland
• Synthesized as pre-pro-PTH, cleaved
enzymatically to intact PTH
• Plasma calcium: primary physiological
regulator of PTH synthesis and secretion
• Normal ReferenceRange:10 -65 ng/L

10. Vitamin D
• Sources of vitamin D?
Diet
UV light exposure on precursor in skin
• Daily requirement?
400 International units

11. Calcitonin
• Secreted by parafollicular or C cells
distributed throughout thyroid gland
• Normal serum concentration
Men:<8.8 pg/mL
Women:<5.8 pg/mL
• Level Increases when serum Ca concentration
>2.25mmol/L

12. DISEASES

13. Metabolic bone diseases
Characterized by abnormalitiesin calcium metabolism and/or bone
cell physiology.
Four Groups
1. Inadequate Osteoid synthesis - Osteopenia
2.Inadequate Mineralisation of Osteoid
Osteomalacia & Rickets – a. Dietary b. Disuse
3.Decreased Osteoid synthesis and increased Osteolysis
Osteoporosis – a.Senile b.Post Menopausal
4.Increase in Bone Mass – Osteosclerosis
a.Paget”s disease, b.Osteopetrosis

14. • It is a disease of childhood characterized by failure
of mineralization of osteoid tissue in developing
skeleton, particularly at the growth plate.
• Age: 4-18 months.
May occur in older children with malabsorbtion
• Causes:
1.Abnormality in vitamin-D metabolism.
2.Abnormality in phosphate metabolism.
3.Calcium Deficiency.
RICKETS

16. Types of Rickets
Type 1
a)Vit Ddeficiency
low intake plus inadequate sunlightexposure
malabsorption
b)Abnormal vit Dmetabolism
Liver disease
Renal disease
Drugs(anticonvulsants)
Type2
a)Defective absorption of phosphate through kidney
Hypophosphatemic Vitamin Dresistantrickets(X-linked)
Fanconi syndrome, Renal tubular acidosis
b)Decreased intake or absorption of phosphates

17. •Craniotabes: This is the earliest manifestation of rickets 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.
• Bossing of the skull: Bossing of the frontal and parietal bones
becomes evident after the age of 6 months
. • Broadening of the ends of long bones, seen most prominently
around wrists and knees, are seen around 6-9 months of age.
• Delayed teeth eruption is noticed in infants
Clinical features

18. • Pigeon chest Thoracic kyphosis may
be present with deep narrow chest- ‘’.
• Harrison’s sulcus –indrawing of the
lower chest caused by the pull of the
diaphragmatic attachment to the soft
ribs.
• Rachitic rosary -Enlargement
of growth plates at
costochondral junction
Clinical features

19. .
•Muscular hypotonia: The child's
abdomen becomes protruberant (pot-belly)
because of marked muscular hypotonia;
visceroptosis and lumbar lordosis occurs
•Deformities: Deformities of the long bones
resulting in knock-knees or bow-legs is a
common presentation of rickets once the child
starts walking
Clinical features

21. Clinical features
Mnemonic
R-Rachitic rosary
I-Pigeons Chest
C- Craniotabes
K-Knock Knees
E-Ends of long bones becomes
widened
T-Teeth: Delayed eruption of teeth
S-Skull: Bossing of skull in children
<6 months

22. Serum calcium - low
Serum phosphorus - low
Serum alkaline phosphatase- elevated
Serum 25(OH)D - low
Biochemical examination

23. What to look for on X-rays??

24. Early radiological changes are observed in
the lower ends of the radius and ulna
• Delayed appearance of epiphyses
.
• Widening of the epiphyseal plates: Normal
is 2-4 mm,
. • Cupping of the metaphysis: Normally, the
metaphysis meets the epiphyseal plate as a
smooth line of sclerosis (zone of provisional
calcification). In rachitic bones, this line is
absent and the metaphyseal end appears
irregular. The cartilage cells accumulating at
the growth plate create a depression in the
soft metaphyseal end, giving rise to a cup-
shaped appearance
Radiological features

25. • Splaying of the metaphysis: The end of the
metaphysis is splayed because of the pressure by
the cartilage cells accumulating at the growth plate
. • Rarefaction of the diaphysial cortex occurs late
. • Bone deformities — Knock-knees, bow-legs
and coxa vara are common deformities in older
children
Radiological features

26. 1)Medical
2)Orthopaedic treatment.
MEDICAL TREATMENT:
-Single oral dose of vitamin D, 6,00,000 units
-Maintenance dose of 4001.U. of vitamin D per day
- 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 maybe repeated. If there is no response even after the
second dose, a diagnosis of refractory rickets is made.
Treatment

27. ORTHOPAEDIC TREATMENT: It is required for the correction of
deformities by conservative or operative methods.
a) Conservative methods: Mild deformities correct spontaneously as
rickets heals.
-Specially designed splints (Mermaid splints) or orthopaedic shoes
for correction of knee deformities.
b) Operative methods: Moderate or severe deformities often require
surgery. This can be performed any time after 6 months of starting the
medical treatment.
-Corrective osteotomies, depending upon the nature of deformities,
are performed
Treatment

28. Rickets pre-treatment: irregular
widened epiphyseal plates, with
cupping and fraying of the
metaphyses, and bowing of long
bones.
Rickets post-treatment: the
epiphyses and metaphyses assume
a more normal appearance

29. Vitamin D resistant rickets
X-linked hypophosphatasia
Rare X-linked dominant disorder of renal tubular
reabsorption characterized by impaired reabsorption of
P04 in prox. renal tubule (due to defect in renal brush
border membrane).
 Hypophosphataemia, hyperphosphaturia, elevated
serum alkaline phosphatase, normal plasma &urine
calcium, normal serum vit-D.
 Rickets clinically become evident at about 6-12
months of age.

30. • A variety of renal dysfunction syndromes produce
rickets and osteomalacia. These include:
-Hypercalcaemia
- Renal po4 loss
-Secondary hypophosphataemia
- Aminoaciduria & renal tubular acidosis.
• In renal tubular acidosis, affected patients demonstrate
growth retardation ,short stature, changes of rickets/
osteomalacia, nephrolithiasis, nephrocalcinosis.
Vitamin D resistant rickets associated
with renal tubular disorders

31. Osteomalacia
Osteomalacia refers to lack of mineralization of
osteoid in the mature skeleton resulting from
Vitamin D deficiency .
C/F:
• Bone pain
• Spontaneous fractures
• Malaise
• Muscular weakness
Biochemical findings:
Serum calcium
Serum phosphorus
Serum ALK phosphatase

32. Radiological features
Common sites
-Pubic rami
-Proximal femur
-Scapula
-Lower ribs & ulna
Generalised
bone density
Looser’s
Zones
Coarsened indistinct
trabecular pattern
Bone
softening
Biconcave vertebra
Bowing of long bones
Protrusio acetabuli
Tri-radiate pelvis
Basilar invagination
Common sites

33. Osteomalacia. ‘Looser”s zone’ of the proximal
femoral metaphysis

34. Osteomalacia. Marked biconcavity of the
vertebral bodies(codfish vertebrae Pattern).

35. Bilateral Looser’s zones

36. Defective intake - vitamin D 6,00,000 units followed by
daily maintenance doses of 4001.U. is sufficient.
Mal-absorption - higher dose or intramuscular dose may
be needed.
Renal disease - alfa-calcidol (an activated form of vitamin
D) may be used. Calcium supplementation should also be
given. In addition, the underlying cause is treated
Treatment

37. Scurvy
•Scurvy is a nutritional disorder occurs due to long term
deficiency of vitamin C.
•Vitamin C is necessary for hydroxylation of proline to
hydroxyproline which is vital for collagen synthesis.
About 90% of the matrix of mature bone is collagen &
hence a lack of collagen will have a severe effect on
bone formation . In children, this gives rise to scurvy.
•Age : Scurvy is rare before 6months of age.
•Predisposed by feeding with pasteurized /boiled milk

38. Radiological features
1. Wimberger’s sign-Epiphyses is
small,sharply marginated by sclerotic rim
2. White line of Frankel-Zone of provisional
calcification is dense
3. Trumerfeld zone-a lucent zone
4. Pelkan’s spur

39. Scurvy. The margins of the epiphyses are sclerotic . There isa
narrow epiphyseal plate, with increased density of the zone of
provisional calcification. Lucent zone beneath this is
trumerfeld zone.

40. Scurvy:
Subperiosteal
new bone has
elevated the
periosteum.
Wimberger’s sign
Frankel’s line
Marked periosteal
new bone formation

41. OSTEOPOROSIS
Age:
• Usually begins around 5th decade in women
and around 6th decade in men.
•Loss of bone mass approx 3-10%/decade.
•Commonest metabolic bone disease.
• Diffuse reduction in the bone density due to a decrease in
the bone mass.
• It occurs when the rate of bone resorption exceeds the rate
of bone formation.

42. • Senility
• Post-immobilisation e.g. a bed-ridden patient
• Postmenopausal
• Protein deficiency - Inadequate intake—old age, illness
- Mal-nutrition
- Mal-absorption
- Excess protein loss (3rd degree burns, CRF etc.)
• Endocrinal - Cushing's disease
- Cushing's syndrome
- Hyperthyroid state
• Drug induced - Long term steroid therapy
- Phenobarbitone therapy
Causes of Osteoporosis

43. •Asymptomatic disorder unless complications (predominantly
fractures) occur.
• The loss of bone mass leads to loss of strength
•Increased succeptable to fracture the dorso-lumbar spine being
the most frequent site.
•Colles' fracture and fracture of the neck of the femur
•A slight loss of height and increased kyphosis due to compression
of the anterior part of the vertebral bodies is seen in most cases
•Generalised bone pains
Clinical Features

44. Normal bone
Osteoporosis-destuction of trabeculae
reuslting in loss of continuity &
interconnectivity.

45. Post menopausal osteoporosis
• Occur in women of 50-65 years.
• There is a disproportionate loss of trabecular bone.
• Fractures involving vertebral bodies (crush
fractures)and distal radius (colles’fracture).
Senile osteoporosis
• Both men and women over 75 yrs of age.
• Proportionate loss of both cortical and trabecular bone.
• Fracture occur in the femoral neck, vertebral
body(wedge fracture), proximal humerus, tibia and
pelvis.
• M:F=1:2

46. Radiology of osteoporosis
Radiological evidence of decreased bone mass is more
reliable, but about 30 per cent of the bone mass must be
lost before it becomes apparent on X-rays
•Loss of vertical height of a vertebra due to collapse
• Cod-fish appearance
• Ground-glass appearance of the bones,
• Singh's index-based on femoral neck trabeculae
• Metacarpal index and vertebral index are other
methods of quantification of osteoporosis.

47. Biochemistry: Serum calcium, phosphates and alkaline
phosphatase are within normal limits.
- The total plasma proteins and plasma albumin may be low
. Densitometry: ultrasound based
x-ray based.
DEXA scan is an x-ray based bone densitometry, and is the gold
standard in the quantification of bone mass.
• Neutron activation analysis: In this method, calcium in the
bone is activated by neutron bombing, and its activity measured.
• Bone biopsy
Other investigations

48. Osteoporosis—vertebral osteoporosis and fracture. (A) Lateral radiographof
normal vertebrae. (B) Thereis loss of the transverse trabeculae, resulting in
prominence of the vertical trabeculae, giving a striated appearance. (C)
Lateral thoracicradiograph with multiple wedge and end-plate osteoporotic
vertebral fractures of varyinggrades.

49. Principle objectives of treatment are
1.Alleviation of pain and
2. Prevention of fractures.
Treatment can be divided into
a) Medical
b) Orthopedic
Treatment

50. MEDICAL TREATMENT:
• High protein diet
• Calcium supplementation
• Androgens - anabolic effect
• Estrogens
• Vitamin D
• Fluoride- still under study.
• Alandronate: These are used in once a day doze, empty stomach.
• Calcitonin: Parentral administration of calcitonin helps in building up
the bone mass and also acts as an analgesic.

51. ORTHOPAEDIC TREATMENT:
• Exercises: Weight-bearing is a major stimulus to
bone formation and increased gaurded activity would
therefore be of benefit to the patient.
• Bracing: Prophylactic bracing of the spine by using
an ASH brace or Taylor brace may be useful in
prevention of pathological fractures in a severely
osteoporotic spine

52. This condition is divided into primary,
secondary and tertiary forms.
HYPERPARATHYROIDISM

53. Clinical Features in HYPERPARATHYROIDISM
- More common in women.
- 3rd to 5th decades of life.
• Bone pains - most common initial feature.
Tenderness on palpation on bones,
A/W general weakness, pallor and hypotonia.
• Pathological fracture - Common sites of fractures are dorso-lumbar
spine, neck of the femur and pubic rami.
• Brown's tumour - This is an expansile bone lesion - a collection of
osteoclasts.
- Commonly the maxilla or mandible.

54. • Anorexia, nausea,
vomiting and abdominal
cramps are common
presenting complaints.
• Occasionally, renal
colics with haematuria,
because of renal calculus,
may occur
Clinical Features contd…

55. Radiological Features:
 Subperiosteal bone resorption of phalanges
 Salt pepper appearance of skull bones
Subchondral bone resorption
Central collapse of vertebrae
Browntumoursin mandibleandmaxilla
Generalized osteopenia
Loss of lamina dura of teeth
Renal calculi

56. Hyperparathyroidism: marked subperiosteal resorption
of the radial aspect of phalanges and erosion of the tufts.

57. Brown Tumour:
Brown tumours are locally destructive areas
of intense osteoclastic activity. They present
as well defined multi loculated lytic lesion
which may be expansive & destroy over
lying cortex. Pathological fracture may
occur.
Chondrocalcinosis-
Deposition of calcium pyrophosphate dihydrate in
articular & fibrocartilage -identified on hand
(triangular ligament), knees(articular cartilage &
menisci) ,symphysis pubis.
Brown tumour in
tibia
Chondrocalcinosis
as illustrated in the
knee & symphysis
pubis.

58. Primary hyperparathyroidism: granular
appearance of the vault—the so-called salt-and-
pepper skull.

59. Serum calcium - high,
Phosphates - low
Alkaline phosphatase - high.
• Urinary excretion of calcium is low and that of
phosphates high, as found on 24-hour urine analysis
. • Investigations for finding the underlying cause of
hyperparathyroidism i.e., C.T. scan of the neck for
parathyroids, and for the evaluation of other organs for
ectopic secretion of parathormone
Investigations

60. Treatment consists of
(i) Removal of the basic cause- surgical excision of the hormone-
secreting tissue
(ii) Orthopaedic treatment- adequate protection of the softened bones
- Established deformities may be corrected surgically
(iii) Urologic treatment-removal of calculi and maintenance of
renal functions
Treatment

61. Paget’s Disease (Osteitis Deformans)
•Common in elderly
•Progressive deformities of spine and limbs
•Uncommon in india
Etiology
•Unknown
•Increased bone resorption and disorganised bone formation
•Both stages of increased osteoblastic and osteoclastic activities are seen
•Demineralisation followed by excessive reparative bone formation

62. Clinical Features
3 Presentations
1.Monoostotic form - involves single bone (clavicle or tibia)
2.Polyostotic form - involves multiple bones
3.Fascial type – affecting the jaws
•Severe pain in the bones or back
•Enlarged skull and kyphosis of spine
•Tibia,femur spine,skull affected
•Thickening and bending of the tibia and femur
•The bones are thicker and warmth over subcutaneous bones such
as tibia due to intraosseous arteriovenous shunts

63. Complications
•Pathological fracture or localised bone swelling due to
sarcomatous changes
•Cranial nerve palsies with deafness
•Cord symptoms due to spinal canal stenosis
•Osteoarthritis ,Hypercalcaemia,and high output cardiac failure
are seen
Radiology – Honeycoomb or spongy appearance
-Pelvis and calacaneum may show striated paterrn
-Vertebrae shows uniform increased density
-Circumscribed patch of osteoporosis in skull
(Osteoporosis circumscripta)

64. Investigations
•Serum calcium and phosphororus are normal
•Serum alkaline phosphatase is increased
•Increased excretion of hydroxyproline
Treatment
•Symptomatic
•Analgesics
•Calcitonin and diphosphonates –reduce bone
turnover
•Pathological fractures and bone sarcoma
need active management

65. •Excessive deposition of calcium occurs in bone and soft-
tissues.
• It results from excessive ingestion of fluorides in drinking
water.
•The fluoride content of normal water is less than 1 PPM.
• Most common in some states of India i.e., Punjab, Andhra
Pradesh, Tamil Nadu etc
FLUOROSIS

66. a)Skeletal fluorosis - Pain in the back and joints.
- Stiffness of the spine and paraesthesias in the limbs.
In advanced stages - spastic paraparesis and anaemia.
Paraparesis - cord compression - calcification of the posterior
longitudinal ligament and subsequent pressure on the cord.
b) Dental fluorosis - Earliest sign of fluorosis.
- The earliest to occur is mottling of the enamel,
- Common in the incissors of the upper jaw.
- Later the teeth get eroded and fall off
Clinical features:

67. Radiological features:
• Spine: Increased density, calcification of the posterior longitudinal
ligament.
• Pelvis: Increased density, calcification of the ischio-pubic and sacro-
iliac ligaments.
• Forearm and leg: Interosseous membrane calcification
Other Investigations
•Elevated serum fluoride levels
• Elevated fluoride levels in urine and drinking water
•A biopsy shows high fluoride levels in bones

68. FLUOROSIS
Interosseous membrane calcification

69. Treatment:
Prevention is the most important aspect
of treatment of this difficult disease.
Defluorination of the water is carried
out as a public health programme.
Patients improve symptomatically once
the defluorinated water is used for
some time. Fluorosis. There is markedincreased
density of all bones.

70. Thank you