1 Bone Tissue  Tissues and organs of the skeletal system  Histology of osseous tissue  Bone development  Physiology of osseous tissue  Bone disorders

2 Bone as a Tissue  Connective tissue with a matrix hardened by minerals (calcium phosphate)  Individual bones consist of bone tissue, marrow, blood, cartilage and periosteum  Continually remodels itself  Functions of the skeletal system support, protection, movement, electrolyte balances, acid-base balance and blood formation support, protection, movement, electrolyte balances, acid-base balance and blood formation

3 Shapes of Bones  Long bones – levers acted upon by muscles  Short bones – glide across one another in multiple directions  Flat bones – protect soft organs

4 General Features of Bones  Shaft (diaphysis) = cylinder of compact bone marrow cavity (medullary cavity) lined with endosteum (osteogenic cells and reticular connective tissue) marrow cavity (medullary cavity) lined with endosteum (osteogenic cells and reticular connective tissue)  Enlarged ends (epiphyses) spongy bone covered by compact bone spongy bone covered by compact bone enlarged to strengthen joint and attach ligaments enlarged to strengthen joint and attach ligaments  Joint surface covered with articular cartilage  Shaft covered with periosteum outer fibrous layer of collagen outer fibrous layer of collagen inner osteogenic layer of bone forming cells inner osteogenic layer of bone forming cells  Epiphyseal plate (growth plate)

5 Structure of a Long Bone  Compact and spongy bone  Marrow cavity  Articular cartilage  Periosteum

6 Structure of a Flat Bone  External and internal surfaces composed of compact bone  Middle layer is spongy bone and bone marrow  Skull fracture may leave inner layer of compact bone unharmed

7 Cells of Osseous Tissue (1)  Osteogenic cells in endosteum, periosteum or central canals give rise to new osteoblasts arise from embryonic fibroblasts multiply continuously  Osteoblasts mineralize organic matter of matrix  Osteocytes are osteoblasts trapped in the matrix they formed cells in lacunae connected by gap junctions inside canaliculi

8 Cells of Osseous Tissue (2)  Osteoclasts develop in bone marrow by fusion of stem cells  Reside in pits that they ate into the bone

9 Matrix of Osseous Tissue  Dry weight = 1/3 organic and 2/3 inorganic matter  Organic matter collagen, glycosaminoglycans, proteoglycans and glycoproteins collagen, glycosaminoglycans, proteoglycans and glycoproteins  Inorganic matter 85% hydroxyapatite 85% hydroxyapatite 10% calcium carbonate 10% calcium carbonate other minerals (fluoride, potassium, magnesium) other minerals (fluoride, potassium, magnesium)  Combination provides for strength and resilience minerals resist compression; collagen resists tension minerals resist compression; collagen resists tension bone adapts by varying proportions bone adapts by varying proportions

10 Histology of Compact Bone

11 Compact Bone  Osteon = basic structural unit cylinders formed from layers (lamellae) of matrix around central canal (osteonic canal) cylinders formed from layers (lamellae) of matrix around central canal (osteonic canal) collagen fibers alternate between right- and left- handed helices from lamella to lamella collagen fibers alternate between right- and left- handed helices from lamella to lamella osteocytes connected to each other and their blood supply by tiny cell processes in canaliculi osteocytes connected to each other and their blood supply by tiny cell processes in canaliculi  Perforating canals or Volkmann canals vascular canals perpendicularly joining central canals vascular canals perpendicularly joining central canals

12 Blood Vessels of Bone

13 Spongy Bone  Spongelike appearance formed by plates of bone called trabeculae spaces filled with red bone marrow spaces filled with red bone marrow  Trabeculae have few osteons or central canals no osteocyte is far from blood of bone marrow no osteocyte is far from blood of bone marrow  Provides strength with little weight trabeculae develop along bone’s lines of stress trabeculae develop along bone’s lines of stress

14 Spongy Bone Structure and Stress

15 Bone Marrow  In medullary cavity (long bone) and among trabeculae (spongy bone)  Red marrow like thick blood reticular fibers and immature cells Hemopoietic (produces blood cells) in vertebrae, ribs, sternum, pelvic girdle and proximal heads of femur and humerus in adults  Yellow marrow fatty marrow of long bones in adults  Gelatinous marrow of old age yellow marrow replaced with reddish jelly

16 Intramembranous Ossification  Condensation of mesenchyme into trabeculae  Osteoblasts on trabeculae lay down osteoid tissue (uncalcified bone)  Calcium phosphate is deposited in the matrix forming bony trabeculae of spongy bone  Osteoclasts create marrow cavity  Osteoblasts form compact bone at surface  Surface mesenchyme produces periosteum

17 Intramembranous Ossification 1  Produces flat bones of skull and clavicle.

18 Intramembranous Ossification 2  Note the periosteum and osteoblasts.

19 Stages of Endochondral Ossification

20 Endochondral Ossification 1  Bone develops from pre-existing model perichondrium and hyaline cartilage perichondrium and hyaline cartilage  Most bones develop this process  Formation of primary ossification center and marrow cavity in shaft of model bony collar developed by osteoblasts bony collar developed by osteoblasts chondrocytes swell and die chondrocytes swell and die stem cells give rise to osteoblasts and clasts stem cells give rise to osteoblasts and clasts bone laid down and marrow cavity created bone laid down and marrow cavity created

21 Primary Ossification Center and Primary Marrow Cavity

22  Secondary ossification centers and marrow cavities form in ends of bone same process same process  Cartilage remains as articular cartilage and epiphyseal (growth) plates growth plates provide for increase in length of bone during childhood and adolescence growth plates provide for increase in length of bone during childhood and adolescence by early twenties, growth plates are gone and primary and secondary marrow cavities united by early twenties, growth plates are gone and primary and secondary marrow cavities united Endochondral Ossification 2

23 Secondary Ossification Centers and Secondary Marrow Cavities

24 The Metaphysis Zone of reserve cartilage = hyaline cartilage Zone of reserve cartilage = hyaline cartilage Zone of proliferation Zone of proliferation chondrocytes multiply forming columns of flat lacunaechondrocytes multiply forming columns of flat lacunae Zone of hypertrophy = cell enlargement Zone of hypertrophy = cell enlargement Zone of calcification Zone of calcification mineralization of matrixmineralization of matrix Zone of bone deposition Zone of bone deposition chondrocytes die and columns fill with osteoblastschondrocytes die and columns fill with osteoblasts osteons formed and spongy bone is createdosteons formed and spongy bone is created

25 Fetal Skeleton at 12 Weeks

26 Bone Growth and Remodeling  Bones increase in length interstitial growth of epiphyseal plate interstitial growth of epiphyseal plate epiphyseal line is left behind when cartilage gone epiphyseal line is left behind when cartilage gone  Bones increase in width = appositional growth osteoblasts lay down matrix in layers on outer surface and osteoclasts dissolve bone on inner surface osteoblasts lay down matrix in layers on outer surface and osteoclasts dissolve bone on inner surface  Bones remodeled throughout life Wolff’s law of bone = architecture of bone determined by mechanical stresses Wolff’s law of bone = architecture of bone determined by mechanical stresses action of osteoblasts and osteoclastsaction of osteoblasts and osteoclasts greater density and mass of bone in athletes or manual worker is an adaptation to stress greater density and mass of bone in athletes or manual worker is an adaptation to stress

27 Dwarfism  Achondroplastic long bones stop growing in childhood normal torso, short limbs spontaneous mutation during DNA replication failure of cartilage growth  Pituitary lack of growth hormone normal proportions with short stature

28 Mineral Deposition  Mineralization is crystallization process osteoblasts produce collagen fibers spiraled the length of the osteon osteoblasts produce collagen fibers spiraled the length of the osteon minerals cover the fibers and harden the matrix minerals cover the fibers and harden the matrix ions (calcium and phosphate and from blood plasma) are deposited along the fibersions (calcium and phosphate and from blood plasma) are deposited along the fibers ion concentration must reach the solubility product for crystal formation to occurion concentration must reach the solubility product for crystal formation to occur  Abnormal calcification (ectopic) may occur in lungs, brain, eyes, muscles, tendons or arteries (arteriosclerosis) may occur in lungs, brain, eyes, muscles, tendons or arteries (arteriosclerosis)

29 Ion Imbalances  Changes in phosphate levels = little effect  Changes in calcium can be serious hypocalcemia is deficiency of blood calcium hypocalcemia is deficiency of blood calcium causes excitability of nervous system if too lowcauses excitability of nervous system if too low muscle spasms, tremors or tetany ~6 mg/dL muscle spasms, tremors or tetany ~6 mg/dL laryngospasm and suffocation ~4 mg/dL laryngospasm and suffocation ~4 mg/dL with less calcium, sodium channels open more easily, sodium enters cell and excites neuronwith less calcium, sodium channels open more easily, sodium enters cell and excites neuron hypercalcemia is excess of blood calcium hypercalcemia is excess of blood calcium binding to cell surface makes sodium channels less likely to open, depressing nervous systembinding to cell surface makes sodium channels less likely to open, depressing nervous system muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL  Calcium phosphate homeostasis depends on calcitriol, calcitonin and PTH hormone regulation

30 Hormonal Control of Calcium Balance  Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.

31 Calcitriol (Activated Vitamin D)  Produced by the following process UV radiation and epidermal keratinocytes convert steroid derivative to cholecalciferol - D3 UV radiation and epidermal keratinocytes convert steroid derivative to cholecalciferol - D3 liver converts it to calcidiol liver converts it to calcidiol kidney converts that to calcitriol (vitamin D) kidney converts that to calcitriol (vitamin D)  Calcitriol behaves as a hormone that raises blood calcium concentration increases intestinal absorption and absorption from the skeleton increases intestinal absorption and absorption from the skeleton increases stem cell differentiation into osteoclasts increases stem cell differentiation into osteoclasts promotes urinary reabsorption of calcium ions promotes urinary reabsorption of calcium ions  Abnormal softness (rickets) in children and (osteomalacia) in adults without vitamin D

32 Calcitriol Synthesis and Action

33 Calcitonin  Secreted (C cells of thyroid gland) when calcium concentration rises too high  Functions reduces osteoclast activity as much as 70% reduces osteoclast activity as much as 70% increases the number and activity of osteoblasts increases the number and activity of osteoblasts  Important in children, little effect in adults osteoclasts more active in children osteoclasts more active in children deficiency does not cause disease in adults deficiency does not cause disease in adults  Reduces bone loss in osteoporosis

34 Correction for Hypercalcemia

35 Parathyroid Hormone  Glands on posterior surface of thyroid  Released with low calcium blood levels  Function = raise calcium blood level causes osteoblasts to release osteoclast-stimulating factor (RANKL) increasing osteoclast population causes osteoblasts to release osteoclast-stimulating factor (RANKL) increasing osteoclast population promotes calcium resorption by the kidneys promotes calcium resorption by the kidneys promotes calcitriol synthesis in the kidneys promotes calcitriol synthesis in the kidneys inhibits collagen synthesis and bone deposition by osteoblasts inhibits collagen synthesis and bone deposition by osteoblasts  Sporatic injection of low levels of PTH causes bone deposition

36 Correction for Hypocalcemia

37 Other Factors Affecting Bone  Hormones, vitamins and growth factors  Growth rapid at puberty hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth plate hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth plate girls grow faster than boys and reach full height earlier (estrogen stronger effect) girls grow faster than boys and reach full height earlier (estrogen stronger effect) males grow for a longer time and taller males grow for a longer time and taller  Growth stops (epiphyseal plate “closes”) teenage use of anabolic steroids = premature closure of growth plate and short adult stature teenage use of anabolic steroids = premature closure of growth plate and short adult stature

38 Fractures and Their Repair  Stress fracture caused by trauma car accident, fall, athletics, etc car accident, fall, athletics, etc  Pathological fracture in bone weakened by disease bone cancer or osteoporosis bone cancer or osteoporosis  Fractures classified by structural characteristics break in the skin break in the skin multiple pieces multiple pieces

39 Types of Bone Fractures

40 Healing of Fractures 1  Normally weeks (longer in elderly)  Stages of healing fracture hematoma (1) - clot forms, then osteogenic cells form granulation tissue fracture hematoma (1) - clot forms, then osteogenic cells form granulation tissue soft callus (2) soft callus (2) fibroblasts produce fibers and fibrocartilagefibroblasts produce fibers and fibrocartilage hard callus (3) hard callus (3) osteoblasts produce a bony collar in 6 weeksosteoblasts produce a bony collar in 6 weeks remodeling (4) in 3 to 4 months remodeling (4) in 3 to 4 months spongy bone replaced by compact bonespongy bone replaced by compact bone

41 Healing of Fractures 2

42 Treatment of Fractures  Closed reduction fragments are aligned with manipulation and casted fragments are aligned with manipulation and casted  Open reduction surgical exposure and repair with plates and screws surgical exposure and repair with plates and screws  Traction risks long-term confinement to bed  Electrical stimulation used on fractures if 2 months necessary for healing if 2 months necessary for healing  Orthopedics = prevention and correction of injuries and disorders of the bones, joints and muscles

43 Fractures and Their Repairs

44 Osteoporosis 1  Bones lose mass and become brittle (loss of organic matrix and minerals) risk of fracture of hip, wrist and vertebral column risk of fracture of hip, wrist and vertebral column complications (pneumonia and blood clotting) complications (pneumonia and blood clotting)  Postmenopausal white women at greatest risk by age 70, average loss is 30% of bone mass by age 70, average loss is 30% of bone mass black women rarely suffer symptoms black women rarely suffer symptoms

45 Osteoporosis 2  Estrogen maintains density in both sexes (inhibits resorption) testes and adrenals produce estrogen in men testes and adrenals produce estrogen in men rapid loss after menopause, if body fat too low or with disuse during immobilizaton rapid loss after menopause, if body fat too low or with disuse during immobilizaton  Treatment ERT slows bone resorption, but increases risk breast cancer, stroke and heart disease ERT slows bone resorption, but increases risk breast cancer, stroke and heart disease PTH slows bone loss if given daily injection PTH slows bone loss if given daily injection Forteo increases density by 10% in 1 yearForteo increases density by 10% in 1 year may promote bone cancermay promote bone cancer best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40 best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40

46 Spinal Osteoporosis