Comprehensive Review of Skeletal System Function, Structure, and Pathophysiology

1. Review of Skeletal System

2. Skeletal System • Function: • Protection • Hematopoiesis • Mineral homeostasis • Calcium • Phosphorus • Carbonate • Magnesium

3. Structure • Bone is a connective tissue: • Matrix • Collagen fibers for flexibility and tensile strength • Calcium for rigidity • Hydroxyapatite Ca5(PO4)3OH

4. Cells: • Osteoblast • Form organic components of matrix • Osteocyte • Osteoclasts • From monocytes • Secrete citric and lactic acids • Collagenases and other enzymes • Stimulated by PTH • Inhibited by Calcitonin

7. Types of Bone • Dense or Compact (85%) • Osteon (Haversian System) • Central (Haversian) canal • Lamellae • Lacunae with osteocytes • Canaliculi • Spongy (cancellous) bone (15%) • trabeculae

11. Periosteum • Outer layer is dense, irregular CT with nerves and blood vessels • Inner layer • Osteoblasts • Anchored to bone by collagen fibers that penetrate into bone

12. Joints • Degree of movement • Synarthrosis – immovable joint • Amphiarthrosis – slightly movable joint • Diarthrosis – freely movable joint

13. Synovial joints • Joint capsule • Fibrous CT • Tendons and ligaments • Nerves, blood and lymph vessels • Synovial membrane • Loose fibrous CT • Many blood vessels – good repair • Joint (synovial) Cavity

15. Synovial fluid • Plasma filtrate • Synovial cells and leukocytes phagocytize debris and microbes • Articular cartilage • Reduce friction • Distribute force

16. Bone Pathophysiology • Inherited conditions: • Osteogenesisimperfecta • Inherited defect in collagen synthesis • Osteopenia and brittle bones • Often- defective tooth formation, blue sclera, faulty hearing, other defects • Inheritance can be dominant, recessive or by new mutation • Several degrees of severity ( I,II,III,IV) • Biphosphate treatment can improve bone mass in all types of the disorder

19. Achondroplasia • Involves a defect in normal cartilage development • Epiphyseal plates close early in long bones; individual has short arms and legs, but normal spine and skull • Dominant inheritance, but frequent new mutations • Other organs develop normally • Individuals live a normal lifespan

20. Jyoti Amge, 15, just about 59.69 cm in height and 5.25 kg in weight, is the world's smallest girl recognized by the Indian Book of Records.

23. Acquired disorders • Osteoporosis – “porous bone” • Most common metabolic bone disease in North America • Can be attributed to genetics, diet or hormones • Most osteoporosis is idiopathic osteoporosis • Bone loss due to an identifiable cause is secondary osteoporosis • Bone tissue is mineralized normally, but over time the structural integrity of bone is lost and it becomes thinner and weaker, and more prone to fractures.

24. Key features: bone fracture and the associated pain. • WHO defines osteoporosis by bone density: • Normal bone > 833 mg/cm2 • Osteopenia 833 to 648 mg/cm2 • Osteoporosis < 648 mg/cm2 • Can be generalized, involving major portions of the axial skeleton • Can be regional, involving one segment of the appendicular skeleton

27. Remodeling is constant • Teen years more bone is laid down than reabsorbed • Peak bone mass or maximum density reached at around 30 years of age • After age 30, bone is reabsorbed faster than it is laid down (loss of about 0.7% /year) • In women, bone loss is most rapid in the first years after menopause, but continues throughout postmenopausal years • Est. 55% of people over 50 have osteoporosis or low bone mass.

28. Men also lose bone density, but start out with more bone mass so takes longer. • By age 90 about 17% of males have had a hip fracture, vs. 32 % of females • Vertebral fractures also occur → kyphosis • Most common in whites, but affects all races. • African Americans have about half the fracture rates of whites (higher peak bone mass)

31. Risk factors • Family history • White race • Increased age • Female sex • Small stature • Fair or pale skin • Thin build • Early menopause (natural or surgical) • Late menarche

32. Risk factors cont. • Nulliparity • Obesity • Weight below a healthy range • Acidosis • Low dietary calcium and vitamin D • High caffeine intake • Sedentary life style • Smoker • Excessive alcohol consumption • Liver, kidney disease, rheumatoid arthritis, etc.

33. Often progresses silently for decades until fracture occurs • Bones can fracture spontaneously • Most severe in spine, wrist and hips • Estrogens and androgens may be factors in both sexes • Testosterone is converted into estrogen in peripheral tissues and decreases bone loss • Rapid bone loss is osteoclast mediated • Slow bone loss is osteoblast mediated

34. Clinical manifestations • Pain and bone deformity • Kyphosis caused by vertebral collapse • Fractures of long bones • Fatal complications include fat or pulmonary embolism, pneumonia, hemorrhage and shock • 20 % die as a result of surgical complications

35. Treatment • No known cure • Slow bone loss and promote bone deposition • Calcium and vitamin D supplements • Nasal or subcutaneous calcitonin • Hormone replacement therapy • Biophosphates – inhibit osteoclasts • Dual x-ray absorptiometry for diagnosis • PREVENTION

36. Prevention • Intake of calcium, vitamin D, magnesium and possibly boron • Regular, weight-bearing exercise • Avoid tobacco and glucocorticoids • No alcoholism • Hormone replacement? • Testosterone for men and possibly women

37. Rickets and Osteomalacia • Inadequate mineral deposition in essentially normal organic matrix • Softened bone: • Subject to malformation and distortion –pain

38. Rickets • Dietary vitamin D deficiency causes inadequate mineralization of the developing skeleton in infants and children • Rarely seen in Western nations • Poverty • Ignorance • Bones are soft and easily deformed • Tendency to fractures • Therapy: supply vitamin D and calcium

42. Osteomalacia • Rarely due to vitamin D deficiency • Usually GI malabsorption, renal defect or chronic kidney or liver diseases. • Elderly often affected due to inadequate diet or lack of outdoor activity • May accompany and complicate osteoporosis.

44. Joint Disorders • Osteoarthritis • Most common joint disease in North America • Minimal inflammatory component • Differentiated from inflammatory disease by: • Absence of synovial membrane inflammation • Lack of systemic signs and symptoms • Normal synovial fluid • Much of the pain and loss of mobility associated with aging.

45. Osteoarthritis • Incidence increases with age: 85% of people age 65 have some joint degeneration • Incidence similar, but women more severely affected • Exceptional stress on joints: gymnasts, etc. • Biochemical defect in cartilage • Malformed joint, obesity and postural defects • Genetic component • Torn ACL or meniscectomy

46. Osteoarthritis • When associated with known risk factors it is secondary Osteoarthritis • No risk factors – idiopathic Osteoarthritis • Pathological characteristics: • Erosion of the articular cartilage • Sclerosis of subchondral bone • Formation of bone spurs or osteophytes

48. Osteoarthritis • Begins in articular cartilage • Yellow-grey or brownish gray • Thin, irregular, frayed • Cracks or fissures develop (fibrillation) • Fluid filled cysts may form • Microfractures of subchondral bone • Formation of fibrocartilage repair plugs • Bone surface exposed • Bone responds by becoming dense and hard

49. Osteoarthritis • Synovial membrane is indirectly affected • Fragments of fibrocartilage cause inflammation –pain • Fibrous repair of joint capsule restricts motion • Osteophytes form – pain and loss of motion

50. Osteoarthritis • Affects one or more weight-bearing joints • Hand, wrist, lower cervical spine, lumbar spine and sacroiliac, hip, knees, ankles, feet • Aches and stiffness • Symptoms increase with activity; diminish with rest • Usually no swelling or redness of adjacent tissues • Sometimes nocturnal pain – may be referred