2nd lecture Laila Diseases of Bone and Joints_eec154af834df8a61df0ee925d4bbeda.pdf

Pathology

1. Musculoskeletal
Pathology
Prof. LailaElbarghati

2. Acquired disease of bone
development
Nutritional deficiency:
•VitC in scurvy
•VitD in rickets, osteomalacia
Endocrine:
•Primary & secondary hyperparathyroidism
•Osteoporosis
Idiopathic
•Paget disease

3. Rickets & osteomalacia
•Defective bone mineralization result in
over abundant non mineralized osteoid.
•Rickets in children (1year).
•Osteomalaciain adult almost in female.

5. Causes
1)Deficiency of vitD in diet
2)Deficiency of vitD metabolites due to lack
of sun light
3)Intestinal malabsorption
4)Renal or liver disease
5)Drugs as phenytoin

6. Function of vitD
1.Stimulate intestinal ca & phosphorus
absorption.
2. Increase renal ca reabsorption in distal
tubules.
3. Stimulate bone ca mobilization.

7. Clinical features of Rickets
•Growth retardation due to defective
calcification of epiphysealcartilage.
Bones are soft, bent & deformed:
•Bowing of long bones (bow legs).
•Swelling of costochondraljunctions
causing (rachitic rosary).

8. •Thorax deformity (pigeon chest).
•Harrison sulcusor grooveat the
lower end of the rib cage.
•Skull flattening, frontal bossing, soft skull
(Crainotabes).
•Defective calcification of teeth.
•Pelvic deformities can lead to childbirth
difficulty.

9. Rickets in Humerus& Femur

11. Rickets chest

12. Clinical features of osteomalacia
•Long bones or pelvis show spontaneous,
incomplete microfracturesof cortical plate
& trabecular bone that appear on x-ray as
losserzone.
•The limb’s proximal muscle are painful &
weakproducing Waddling gait.

13. •Pelvic deformities in female interfere with
child birth.
•Long standing soft bones causing bowing
of long bones of lower limbs.

14. Losserzone

15. Waddling gait

16. Osteomalacia(femur)

17. Osteomalacia(M/E)

18. Diagnosis
•Low ca, phosphorus due to vitD
deficiency.
•High PTH due to low Ca
•High alkaline phosphatase

19. Hyperparathyroidism
•Parathyroid hormone play a central role in
Ca hemostasis:
1. Osteoclastsactivation.
2. Increase ca reabsorptionby renal tubules.
3. Increase urinary excretion of phosphate.
4. Increase synthesis of active vitD by
kidney that enhance Ca absorption from
gut & mobilize bone Ca by inducing
RANKL.

21. Osteoporosis
•It is a reduction of bone mass to a level
below that required for normal support,
however mineralization is normal.

22. Causes
•Localized: Prolonged immobilization.
•Generalized:
I.*Primary:Postmenopausal, senile, idiopathic
II.Secondary: Hyperparathyroidism, hypo or
hyperthyroidism, Addison disease, D.M
-Multiple myeloma
-Malabsorption
-Corticosteroid, chemotherapy

23. •Physical activity. Because mechanical
forces stimulate bone remodelling.
•Calcium nutritional state. A majority of
adolescent girls (but not boys) have
insufficient dietary calcium during a
period of rapid bone growth.

24. MENOPAUSE (Type 1) AGING (Type 2)
Decreased serum estrogen Decreased replicative activity of
osteoprogenitorcells
Increased IL-1, IL-6,
TNF levels
Decreased synthetic activity of
osteoblasts
Increased expression of RANK,
RANKL
Decreased biologic activity of
matrix-bound growth factors
Increased osteoclastsactivityReduced physical activity

25. Pathogenesis
•RANK ligand& M-CSF synthesized by
stromalcells & osteoblasts.
•RANK (receptor activator for NFкB)
activated by interaction with RANK ligand.

26. •The above convert macrophages to
bone crunching osteoclastsfor bone
resorption.
•Such interaction is inhibited by
osteoprotegerin(OPG) also released by
osteoblasts.

28. Morphology
•More in spine & femoral neck as they
contain more cancellous (trabecular) bone.
•The osteoporotic vertebral body collapse
& shortened by compression fractures.
C/S:The osteoporotic vertebral body shows
marked loss of cancellous bone, (Bone
trabeculae are reduced in number & thin).

29. Osteoporosis
Normal

32. Osteoporosis
Normal

33. Clinical course
•Asymptomatic.
•Bone pain with fractures e.g. fractures of
wrist, hip, and spinal bones.
•Pulmonary embolism & pneumonia are
common complications of fractures & result
in 50,000 deaths annually.
•Skeletal deformities i.e. kyphosis or scoliosis
& loss of height.

34. Stages of osteoporosis
Skeletal deformities i.e.kyphosis or scoliosis & loss of height

35. •Serum Ca, phosphate, PTH & alkaline
phoshataseare normal.
•Bisphosphonates cause apoptosis of
osteoclasts.

36. Dietary calcium intake, vitamin D &
exercise at age of 30to maximize
the peak bone mass.

37. OSTEOMALACIA OSTEOPOROSIS
Size of bone trabeculaeNormal Small
Number of bone trabeculaeNormal Reduced
Bone mineralization Defective, with excessive
and thick uncalcified
osteoid tissue
Normal calcification or
mineralization
Osteoblasts Often increased Normal number
Seum alkaline phosphataseIncreased Normal
Serum phosphate Low Normal
Serum calcium Low Normal
Muscles Weak Normal
Looser zones Present No

38. Paget disease of bone
•Also called OsteitisDeformans.
•Disorder of normal bone remodelling
process to maintain normal Ca level. The
new bone is enlarged, brittle & prone to
fracture.
•Mid-to late adulthood.
•Common in much of Europe & US.

39. Pathogenesis
It passes through 3 stages:
1. Osteolyticstage
2. Mixed osteolytic& osteoblasticstage
3. Osteoscleroticstage

40. •Idiopathic
•Paramyxovirusesinduce IL-1 & IL-6
secretion from infected cells with M-CSF
can activate osteoclasts.
•10% have germline mutations in
sequestrosome1 gene SQSTM1, which
encodes a protein that increase
osteoclastogenesis.

41. Morphology
•Solitary lesion (monostotic) 15%
•Multiple lesions (polyostotic) 85%
•There is a gain in bone mass however, the
bone is disordered & weaklike dried
bread.
•Bones are enlarged & misshapen.

42. M/E
•Lyticphase: osteoclasts& lacunae are
numerous.
•Mixed phase: osteoclastswith
osteoblastslining the bone surface.
•The newly formed bone is abnormal
lamellar bone with a mosaic pattern
(likened to a jigsaw puzzle).

43. 43

44. Mosaic pattern of lamellar bone

46. Clinical course
•High-output congestive heart failure.
•Cranial nerve compression.
•Bone deformation & chalkstickfracture under
stress.
•Secondary Osteosarcoma 1%.
•Increased urinary excretion of hydroxyproline.

47. •Increase osteoblastsactivity increase
alkaline phosphatsecause alkaline
environment for bone mineralization.
•Ca, phosphorus, vit D, PTH all are normal.
•Treatment: Calcitonin, Bisphosphonate
inhibit osteoclastsactivity.

48. Thanks