Bones and Skeletal Tissues 6 P A R T B Bones and Skeletal Tissues

Bone Growth & Development Figure 6.15

Developmental Aspects of Bones Mesoderm gives rise to embryonic mesenchymal cells, which produce membranes and cartilages that form the embryonic skeleton The embryonic skeleton ossifies in a predictable timetable that allows fetal age to be easily determined from sonograms At birth, most long bones are well ossified (except for their epiphyses)

Developmental Aspects of Bones By age 25, nearly all bones are completely ossified In old age, bone resorption predominates A single gene that codes for vitamin D docking determines both the tendency to accumulate bone mass early in life, and the risk for osteoporosis later in life

Bone Development Osteogenesis (aka ossification) – the process of bone tissue formation, which leads to: The formation of the bony skeleton in embryos Bone growth until early adulthood Bone thickness, remodeling, and repair

Formation of the Bony Skeleton Begins at week 8 of embryo development – two different types of bone formation: Intramembranous ossification – bone develops from inside a fibrous membrane – occurs in flat and irregular bones Endochondral ossification – bone forms by replacing hyaline cartilage – occurs in long and short bones

Intramembranous Ossification Formation of most of the flat bones of the skull and the clavicles Fibrous connective tissue membranes are formed by mesenchymal cells

Stages of Intramembranous Ossification An ossification center appears in the fibrous connective tissue membrane Bone matrix is secreted within the fibrous membrane Woven bone (precursor to spongy bone) and periosteum form Bone collar of compact bone forms, and red marrow appears

Stages of Intramembranous Ossification Figure 6.7.1

Stages of Intramembranous Ossification Figure 6.7.2

Stages of Intramembranous Ossification Figure 6.7.3

Stages of Intramembranous Ossification Figure 6.7.4

Endochondral Ossification Begins in the second month of development Uses patterns made of hyaline cartilage as models for bone construction Most bones are formed by this process Requires breakdown of hyaline cartilage prior to ossification, so more complex than intramembranous ossification

Stages of Endochondral Ossification Formation of bone collar around hyaline cartilage model. Hyaline cartilage Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. Formation of the medullary cavity as ossification continues; appearance of sec- ondary ossification centers in the epiphy- ses in preparation for stage 5. Ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages. Deteriorating matrix Epiphyseal blood vessel Spongy bone formation plate Secondary ossificaton center Blood vessel of periosteal bud Medullary cavity Articular Primary ossification Bone collar 1 2 3 4 5 Figure 6.8

Summary of Endochondral Ossification 1. Hyaline cartilage model 2. Compact bone from periosteum surrounds diaphysis in a bone collar 3. Primary Ossification Center in diaphysis converts cartilage into spongy bone 4. Core of P.O.C. eroded to make medullary cavity 5. Secondary Ossification Centers in epiphyses convert cartilage into spongy bone 6. Location where P.O.C meets S.O.C is the epiphyseal plate: cartilage remains here to allow the bones to continue growing with age

Stages of Endochondral Ossification I 1. Perichondrium converted to periosteum by increased nutrition from blood vessels 2. Formation of bone collar: osteoblasts in periosteum secrete osteoid, which surrrounds diaphysis in a collar of compact bone 3. Cavitation of the hyaline cartilage: Chondrocytes in the center of the diaphysis die, opening up cavities in the developing bone – this will become the Primary Ossification Center. Meanwhile, cartilage keeps growing at the epiphyses of the bone, increasing its length

Stages of Endochondral Ossification II 4. Periosteal bud invades the internal cavities, bringing arteries, veins, nerves, osteoblasts, and osteoclasts. This converts the cartilage and its cavities into spongy bone. 5. Formation of the medullary cavity by osteoclasts, which break down the spongy bone from the inside out. 6. Appearance of secondary ossification centers in the epiphyses: cartilage cavitated and replaced with spongy bone by periosteal bud (this occurs around birth) 7. Ossification of the epiphyses, with hyaline cartilage remaining only in the epiphyseal plates and on the articular surface of the epiphyses

Stages of Endochondral Ossification Hyaline cartilage Primary ossification center Bone collar Formation of bone collar around hyaline cartilage model. 1 Figure 6.8

Stages of Endochondral Ossification Deteriorating cartilage matrix Cavitation of the hyaline carti- lage within the cartilage model. 2 Formation of bone collar around hyaline 1 Figure 6.8

Stages of Endochondral Ossification Spongy bone formation Blood vessel of periosteal bud Formation of bone collar around hyaline cartilage model. Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. 1 2 3 Figure 6.8

Stages of Endochondral Ossification Epiphyseal blood vessel Secondary ossificaton center Medullary cavity Formation of bone collar around hyaline cartilage model. Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. Formation of the medullary cavity as ossification continues; appearance of sec- ondary ossification centers in the epiphy- ses in preparation for stage 5. 1 2 3 4 Figure 6.8

Stages of Endochondral Ossification Epiphyseal plate cartilage Articular Spongy bone Formation of bone collar around hyaline cartilage model. Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. Formation of the medullary cavity as ossification continues; appearance of sec- ondary ossification centers in the epiphy- ses in preparation for stage 5. Ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages. 1 2 3 4 5 Figure 6.8

Stages of Endochondral Ossification Formation of bone collar around hyaline cartilage model. Hyaline cartilage Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. Formation of the medullary cavity as ossification continues; appearance of sec- ondary ossification centers in the epiphy- ses in preparation for stage 5. Ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages. Deteriorating matrix Epiphyseal blood vessel Spongy bone formation plate Secondary ossificaton center Blood vessel of periosteal bud Medullary cavity Articular Primary ossification Bone collar 1 2 3 4 5 Figure 6.8

Growth in length of long bones Postnatal Bone Growth Growth in length of long bones Cartilage on the side of the epiphyseal plate closest to the epiphysis is relatively inactive Cartilage on the diaphysis side of the epiphyseal plate organizes into a pattern that allows fast, efficient growth Cells of the epiphyseal plate form zones: resting, growth, transformation, and osteogenic

Functional Zones in Long Bone Growth Figure 6.9

Functional Zones in Long Bone Growth Growth zone or proliferation zone – cartilage cells undergo mitosis, pushing the epiphysis away from the diaphysis Transformation zone includes 2 sub regions – first, in the hypertrophic zone, older cartilage cells enlarge, second, in the calcification zone, the matrix becomes calcified, cartilage cells die, and the cartilage matrix begins to deteriorate Osteogenic zone or ossification zone – new bone formation occurs as osteoblasts deposit bone matrix

Long Bone Growth Growth in length – cartilage continually grows and is replaced by bone at the epiphyseal plates Growth in width – intramembranous ossification occurs under the periosteum Bone growth ends around age 18 in females and age 21 in males. The cartilage in the epiphyseal plates is completely replaced with bone, leaving an epiphyseal line. This event is known as epiphyseal plate closure.

Hormonal Regulation of Bone Growth During Youth During infancy and childhood, epiphyseal plate activity is stimulated by HGH (Human Growth Hormone) During puberty, testosterone and estrogens: Initially promote adolescent growth spurts Cause masculinization and feminization of specific parts of the skeleton Later induce epiphyseal plate closure, ending longitudinal bone growth

Bone Remodeling Remodeling (changing the bone shape) – old bone is resorbed by osteoclasts and new bone is added by osteoblasts – constant balance between resorption vs. deposition of bone matrix. Remodeling units – adjacent osteoblasts and osteoclasts deposit and resorb bone at periosteal and endosteal surfaces

Control of Remodeling Two control loops regulate bone remodeling 1. Mechanical and gravitational forces acting on the skeleton 2. Hormonal mechanism maintains calcium homeostasis in the blood

Long Bone Growth vs. Remodeling Figure 6.10

Bone Deposition Occurs where bone is injured or added strength is needed Requires a diet rich in protein, vitamins C, D, and A, calcium, phosphorus, magnesium, and manganese An enzyme called alkaline phosphatase is essential for mineralization of bone

Sites of new matrix deposition are revealed by the: Bone Deposition Sites of new matrix deposition are revealed by the: Osteoid seam – unmineralized band of bone matrix Calcification front – abrupt transition zone between the osteoid seam and the older mineralized bone

Bone Resorption Accomplished by osteoclasts Resorption bays – grooves formed by osteoclasts as they break down bone matrix Resorption involves osteoclast secretion of: 1. Lysosomal enzymes that digest organic matrix 2. Acids that convert calcium salts into soluble forms Dissolved matrix is transcytosed across the osteoclast’s cell where it is secreted into the interstitial fluid and then into the blood

Calcium Balance

Roles of Calcium in the Body Along with bone formation, Calcium is necessary for: Transmission of nerve impulses Muscle contraction Blood coagulation/ clotting Secretion by glands and nerve cells Cell division

Hormonal Mechanism of Calcium Balance PTH (parathyroid hormone) is the main hormone responsible for Ca2+ homeostasis – Calcitonin also contributes, but most in children Falling blood Ca2+ levels signal the parathyroid glands to release PTH (parathyroid hormone) PTH signals osteoclasts to degrade bone matrix and release Ca2+ into the blood Rising blood Ca2+ levels slow PTH release and trigger the thyroid to release calcitonin Calcitonin stimulates calcium salt deposition in bone (osteoblasts are activated)

Hormonal Mechanism Thyroid Parathyroid

Hormonal Control of Blood Ca PTH drops; calcitonin secreted Calcitonin stimulates calcium salt deposit in bone Thyroid gland Rising blood Ca2+ levels Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) PTH Figure 6.11

Hormonal Control of Blood Ca Rising blood Ca2+ levels Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Imbalance Figure 6.11

Hormonal Control of Blood Ca Thyroid gland Rising blood Ca2+ levels Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Imbalance Figure 6.11

Hormonal Control of Blood Ca PTH; calcitonin secreted PTH drops; Thyroid gland Rising blood Ca2+ levels Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Imbalance Figure 6.11

Hormonal Control of Blood Ca PTH; calcitonin secreted PTH drops; PTH; calcitonin secreted Calcitonin stimulates calcium salt deposit in bone Thyroid gland Rising blood Ca2+ levels Calcium homeostasis of blood: 9–11 mg/100 ml Figure 6.11

Hormonal Control of Blood Ca Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Figure 6.11

Hormonal Control of Blood Ca Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Thyroid gland Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) Figure 6.11

Hormonal Control of Blood Ca Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Thyroid gland Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) PTH Figure 6.11

Hormonal Control of Blood Ca Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) PTH Figure 6.11

Hormonal Control of Blood Ca Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) PTH Figure 6.11

Hormonal Control of Blood Ca PTH drops; calcitonin secreted PTH; calcitonin secreted Calcitonin stimulates calcium salt deposit in bone Thyroid gland Rising blood Ca2+ levels Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) PTH Figure 6.11

Bone Injuries and Diseases

Response to Mechanical Stress Wolff’s law – a bone grows or remodels in response to the forces or demands placed upon it Observations supporting Wolff’s law include Long bones are thickest midway along the shaft (where bending stress is greatest) Curved bones are thickest where they are most likely to buckle Trabeculae form along lines of stress Large, bony projections occur where heavy, active muscles attach

Response to Mechanical Stress Figure 6.12

Bone Fractures (Breaks) Bone fractures are classified by: The position of the bone ends after fracture The completeness of the break The orientation of the fracture to the long axis Whether or not the bone’s ends penetrate the skin Some breaks are considered specialty fractures

Position of bone ends: Nondisplaced – bone ends retain their normal position Displaced – bone ends are out of normal alignment

Completeness of Fracture Complete – bone is broken all the way through Incomplete – bone is not broken all the way through

Orientation of Fracture Linear – the fracture is parallel to the long axis of the bone Transverse – the fracture is perpendicular to the long axis of the bone

Skin Penetration Compound (open) – bone ends penetrate the skin Simple (closed) – bone ends do not penetrate the skin

Specialty Fractures I Comminuted – bone fragments into three or more pieces; common in the elderly Spiral – ragged break when bone is excessively twisted; common sports injury Depressed – broken bone portion pressed inward; typical skull fracture

Specialty Fractures II Compression – bone is crushed; common in porous bones Epiphyseal – epiphysis separates from diaphysis along epiphyseal line; occurs where cartilage cells are dying Greenstick – incomplete fracture where one side of the bone breaks and the other side bends; common in children

Common Types of Fractures Table 6.2.1

Common Types of Fractures Table 6.2.2

Common Types of Fractures Table 6.2.3

Stages in the Healing of a Bone Fracture 1. Hematoma formation Torn blood vessels hemorrhage A mass of clotted blood (hematoma) forms at the fracture site Site becomes swollen, painful, and inflamed Figure 6.13.1

Stages in the Healing of a Bone Fracture 2. Fibrocartilaginous callus forms Granulation tissue (soft callus) forms a few days after the fracture Capillaries grow into the tissue and phagocytic cells begin cleaning debris Figure 6.13.2

Stages in the Healing of a Bone Fracture 2. (Continued) The fibrocartilaginous callus forms when: Osteoblasts and fibroblasts migrate to the fracture and begin reconstructing the bone Fibroblasts secrete collagen fibers that connect broken bone ends Osteoblasts begin forming spongy bone Osteoblasts furthest from capillaries secrete an externally bulging cartilaginous matrix that later calcifies

Stages in the Healing of a Bone Fracture 3. Bony callus formation New bone trabeculae appear in the fibrocartilaginous callus Fibrocartilaginous callus converts into a bony (hard) callus Bone callus begins 3-4 weeks after injury, and continues until firm union is formed 2-3 months later Figure 6.13.3

Stages in the Healing of a Bone Fracture 4. Bone remodeling Excess material on the bone shaft exterior and in the medullary canal is removed Compact bone is laid down to reconstruct shaft walls Figure 6.13.4

Homeostatic Imbalances Osteomalacia Bones are inadequately mineralized causing softened, weakened bones Main symptom is pain when weight is put on the affected bone Caused by insufficient calcium in the diet, or by vitamin D deficiency

Homeostatic Imbalances Rickets Bones of children are inadequately mineralized causing softened, weakened bones Bowed legs and deformities of the pelvis, skull, and rib cage are common Caused by insufficient calcium in the diet, or by vitamin D deficiency

Isolated Cases of Rickets Rickets has been essentially eliminated in the US Only isolated cases appear Example: Infants of breastfeeding mothers deficient in Vitamin D will also be Vitamin D deficient and develop rickets

Homeostatic Imbalances Osteoporosis Group of diseases in which bone reabsorption outpaces bone deposit Spongy bone of the spine is most vulnerable Occurs most often in postmenopausal women Bones become so fragile that sneezing or stepping off a curb can cause fractures

Osteoporosis: Treatment Calcium and vitamin D supplements Increased weight-bearing exercise Hormone (estrogen) replacement therapy (HRT) slows bone loss Natural progesterone cream prompts new bone growth Statins increase bone mineral density

Paget’s Disease Characterized by excessive bone formation and breakdown Pagetic bone with an excessively high ratio of woven to compact bone is formed Pagetic bone, along with reduced mineralization, causes spotty weakening of bone Osteoclast activity wanes, but osteoblast activity continues to work

Paget’s Disease Usually localized in the spine, pelvis, femur, and skull Unknown cause (possibly viral) Treatment includes the drugs Didronate and Fosamax