Musculoskeletal Disease

1. Musculoskeletal Disease By S.S Eghbali APCP Bushehr 2008

2. Normal Skeletal System • The skeletal system is as vital to life as any organ system because it plays an essential role in: • 1) mineral homeostasis • 2) houses the hematopoietic elements • 3) provides mechanical support for movement • 4) protects & provides body size and shape

3. Normal Skeletal System • Bone is a type of connective tissue • Biochemically, it is defined by its special blend of organic matrix (35%) and inorganic elements (65%) • The inorganic component, calcium hydroxyapatite is the mineral that give bone strength and hardness and is the storehouse for 99% of the body’s calcium

5. Normal Skeletal System • Bone also contains 85% of the body’s phosphorus and 65% of the sodium and magnesium • The rate of mineralization can vary but normally there is a 12-15 day lag time between the formation of the matrix and its mineralization; bone that is unmineralized is known as OSTEOID

6. Normal Skeletal System • The organic component includes the cells of bone and proteins of the matrix; the bone-forming cells include: • 1) OSTEOPROGENITOR cells are pluripotential mesenchymal stem cells that are located in the vicinity of all bony surfaces; they can undergo cell division and produce offspring that differentiate into osteoblasts

7. Normal Skeletal System • 2) OSTEOBLASTS are located on the surface of bone & synthesize, transport, & arrange the many proteins of the matrix; they also initiate mineralization; once surrounded by matrix they are called • 3) OSTEOCYTES: these are the most numerous bone-forming cells & although encased in bone communicate via CANALICULI

8. Normal Skeletal System • OSTEOCLASTS are the cells responsible for bone resorption and are derived from hematopoietic progenitor cells that also give rise to monocytes and macrophages; the scalloped resorption pits they produce and often reside in are known as HOWSHIP LACUNAE; as bone is broken down to its elemental units, substances are released that initiate its renewal

9. Normal Skeletal System • The proteins of bone include type 1 collagen (90% of organic component) and a family of noncollagenous proteins that are derived mainly form osteoblasts • Osteoblasts deposit collagen either in a random weave known as WOVEN BONE or in an orderly layered manner called LAMELLAR BONE

10. Normal Skeletal SystemWoven vs Lamellar bone • The presence of woven bone in the adult is always indicative of a pathologic state • Lamellar bone, which gradually replaces the woven bone of the fetal skeleton, is deposited much more slowly and is stronger than woven bone; there are 4 different types of lamellar bone: circumferential, concentric, interstitial (in cortex) & trabecular lamellae

11. Diseases of Bone

12. Malformations of Bone • Congenital ones are uncommon & include: • 1) failure of development; e.g. rib absence • 2) formation of extra bones; e.g. extra digit • 3) fusion of bones; e.g. syndactylism(digits) • 4) development of long, spider-like digits; e.g. arachnodactylism • 5) craniorachischisis (failure of closure of skull and spinal column

13. Achondroplasia • Is the most common disease of the growth plate and is a major cause of dwarfism • Is an autosomal dominant disorder with approx. 80% representing new mutations • Pt. has shortened proximal extremities, a trunk of relative normal length and an enlarged head • Not associated with changes in longevity, intelligence or reproduction

15. Diseases Associated With Abnormal Matrix Osteogenesis imperfecta & Osteoporsis

16. Osteogenesis imperfecta • Osteogenesis imperfecta or “brittle bone disease” is a group of hereditary conditions characterized by abnormal development of type I collagen • This spectrum of disorders of varying severity are united by the common feature of abnormal collagen synthesis and the resulting bone fragility

17. Osteogenesis imperfecta • Most variants are inherited as autosomal dominants • Is characterized by multiple bone fractures which may occur in utero in the severe forms • Other findings include: blue sclerae (caused by decreased collagen); hearing loss (ear bone abnormalities; dental imperfections

19. Osteoporosis • Is a term that denotes increased porosity of the skeleton resulting from a reduction in bone mass • It may be localized, e.g. disuse osteoporosis of a limb, or generalized as a manifestation of a metabolic bone disease

20. Osteoporosis • When used in an unqualified manner, osteoporosis usually refers to the most common forms, senile and postmenopausal osteoporosis, in which the critical loss of bone mass makes the skeleton vulnerable to fractures

21. Osteoporosis • Peak bone mass is achieved during young adulthood and is largely determined by hereditary factors, especially the allele for the vitamin D receptor molecule • Physical activity, muscle strength, diet and hormonal state also contribute • Age-related bone loss (approx. 0.7%/yr) is a normal biological phenomenon

22. Osteoporosis • Both sexes are affected equally and Whites more so than Blacks • Differences in the peak skeletal mass in men vs women and Blacks vs Whites may partially explain why certain populations are prone to develop the disorder • Much remains unknown; the following are related to the development of osteoporosis:

23. OsteoporosisMain risk factors • 1) Age:Age-related changes; in older people bone-forming cells have diminished capacity to make bone • 2) Physical activity:Reduced physical activity; mechanical forces are important stimuli for normal bone remodeling • 3) Genetic factors:Genetic factors; importance of vitamin D receptors

24. Osteoporosis • 4) Body’s calcium nutritional state; adolescent girls with insufficient calcium intake are later at greater risk of developing osteoporosis • 5) Hormonal influences; postmenopausal osteoporosis is characterized by a hormone-dependent acceleration of bone loss; estrogen replacement protects against bone loss • Race : whites are in more risk than blacks

27. Osteoporosis • Clinical manifestations may include: vertebral fractures, lumbar lordosis and kyphoscoliosis; pulmonary embolism and pneumonia may result from overt fractures of the femoral neck, pelvis or spine

28. Osteoporosis • Diagnosis is on the base of : • Plaine X-ray isnot fully effective specially when bone loss <30-40% • Bone densitometery • Bone biopsy is the most effective

29. Diseases Caused by Osteoclast Dysfunction Osteopetrosis & Osteitis deformans (Paget dis.)

30. Osteopetrosis (Marble Bone or Albers-Schonberg Disease) • Osteopetrosis refers to a group of rare hereditary diseases characterized by osteoclast dysfunction resulting in diffuse symmetric skeletal sclerosis • Clinical features: fractures, anemia, optic atrophy, hydrocephaly, deafness, facial paralysis and serious infections may occur; manifestations depend on form of disease

31. Paget Disease (Osteitis Deformans) • Is a unique disorder characterized by episodes of localized, frenzied osteoclastic activity with bone resorption followed by exuberant bone formation with a net effect of a gain in bone mass • Paget disease usually begins during middle adulthood and becomes progressively more common thereafter

32. Paget Disease • As the result of the repetitive bone destruction and formation 3 phases of Paget can be identified: • 1) An initial phase of osteoclastic activity, hpervascularity and bone loss • 2) A phase of mixed osteoclastic and osteoblastic activity • 3) A late, osteosclerotic phase

34. Paget Disease • The disease is usually asymptomatic but can frequently be diagnosed from radiographic findings; many patients manifest elevated serum alkaline phosphatase levels • Pain is most common problem; headache, hearing & visual disturbances, enlargement of the head (leontiasis ossea), bowing and chalkstick-type fractures of legs, variety of tumors/ tumor-like conditions occur

35. Diseases Associated With Abnormal Mineral Homeostasis Hyperparathyroidism

36. Hyperparathyroidism • Hyperparathyroidism is classified into primary and secondary types • Primary type results from autonomous hyperplasia or a tumor (usually an adenoma) of the parathyroid gland • Secondary is commonly caused by prolonged states of hypocalcemia resulting in compensatory hypersecretion of PTH

37. Hyperparathyroidism • The skeletal manifestations of hyperparathyroidism are caused by unabated osteoclastic bone resorption • The entire skeleton is affected to more or lesser degree • Anatomic changes of severe hyperparathyroidism are known as osteitis fibrosa cystica

38. Hyperparathyroidism • Secondary hyperparathyroidism is usually not as severe or as prolonged as primary and hence skeletal changes are milder • The hallmark of PTH excess is increased osteoclastic activity with bone resorption • Resorption may be generalized or localized, e.g. diffuse radiolucency, surface erosion or “brown tumor”

39. Hyperparathyroidism • The decrease in bone mass predisposes to fractures, deformities caused by the stress of weight bearing and joint pain and dysfunction

40. Renal Osteodystrophy • The term is used to describe collectively all of the skeletal changes of chronic renal disease • There are two major types: • 1) high-turnover osteodystrophy characterized by increased bone resorption and formation with the resorption predominating

41. Renal Osteodystrophy • 2) low-turnover (aplastic) characterized by a marked reduction in the rate of bone mineralization, formation and resorption

42. Renal Osteodystrophy • The skeletal changes include: • 1) increased osteoclastic bone resorption • 2) delayed matrix mineralization (osteomalacia) • 3) osteosclerosis • 4) growth retardation • 5) osteoporosis

43. Infections of Bone Osteomyelitis

44. Osteomyelitis • Osteomyelitis denotes inflammation of bone and marrow and the common use of the term virtually always implies infection • All type of organisms including viruses, parasites, bacteria, and fungi can produce osteomyelitis but infections caused by certain pyogenic bacteria and mycobacteria are the most common

45. Pyogenic Osteomyelitis • Pyogenic osteomyelitis is almost always caused by bacteria • Organism may reach bone by: 1) hematogenous spread (most common route); 2) extension from a contiguous site; or 3) direct implantation • Long bones and vertebral bodies most commonly involved

46. Pyogenic Osteomyelitis • S. aureus is responsible for 80-90% of cases • E. coli, Pseudomonas and Klebsiella are more commonly isolated from pts. with GUT infections or are drug users • Mixed infections seen in cases of surgery or open fractures • Neonatal period: H. influenzae and group B strept.; Salmonella ( sickle cell Anemia)

47. Pyogenic Osteomyelitis • Location of lesions within specific bones is influenced by vascular circulation and varies with age • Clinically hematogenous osteomyelitis may manifest as an acute systemic illness with malaise, fever, chills, leukocytosis and throbbing pain over affect site • Diagnosis is on the base of: X-rays, biopsy & cultures

48. Pyogenic Osteomyelitis • The combination of antibiotics and surgical drainage is usually curative • In 5-25% of cases, acute osteomyelitis fails to resolve and persists as chronic infection • Complications may include: pathologic fracture, endocarditis , sepsis, multiple small abcess (brian,lung,liver) and etc.

49. Tuberculous Osteomyelitis • 1-3% of pts. with pulmonary or extrapulmonary T.B. have osseous infection • Typically, pts. present with pain on motion, localized tenderness, low-grade fevers, chills and weight loss • Severe destruction of vertebrae (Pott’s disease) may cause skeletal deformities and neurologic deficits

50. Tumors of Bone Benign Bone-Forming Tumors