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Intramembranous Ossification • Produces flat bones of skull and clavicle. • Note the periosteum and osteoblasts. 7-1 Endochondral Ossification 7-2 Endochondral Ossification • Bone develops from pre-existing model – 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 – chondrocytes swell and die – stem cells give rise to osteoblasts and clasts – bone laid down and marrow cavity created 7-3 Primary Ossification Center and Primary Marrow Cavity 7-4 Endochondral Ossification • Secondary ossification centers and marrow cavities form in ends of bone – same process • Cartilage remains as articular cartilage and epiphyseal (growth) plates – 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 7-5 Secondary Ossification Centers and Secondary Marrow Cavities 7-6 Fetal Skeleton at 12 Weeks 7-7 Bone Growth and Remodeling • Bones increase in length – interstitial growth of epiphyseal plate – 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 • Bones remodeled throughout life – Wolff’s law of bone = architecture of bone determined by mechanical stresses • action of osteoblasts and osteoclasts – greater density and mass of bone in athletes or manual worker is an adaptation to stress 7-8 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 7-9 Mineral Resorption from Bone • Bone dissolved and minerals released into blood – performed by osteoclasts – hydrochloric acid (pH 4) dissolves bone minerals – enzyme (acid phosphatase) digests the collagen 7-10 Calcium and Phosphate • Phosphate is component of DNA, RNA, ATP, phospholipids, and pH buffers • Calcium needed in neurons, muscle contraction, blood clotting and exocytosis 7-11 Ion Imbalances • Changes in calcium can be serious – hypocalcemia is deficiency of blood calcium • causes excitability of nervous system if too low – muscle spasms, tremors or tetany ~6 mg/dL – laryngospasm and suffocation ~4 mg/dL • with less calcium, sodium channels open more easily, sodium enters cell and excites neuron – hypercalcemia is excess of blood calcium • binding to cell surface makes sodium channels less likely to open, depressing nervous system – muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL • Calcium homeostasis depends on calcitriol, calcitonin and PTH regulation 7-12 Carpopedal Spasm • Hypocalcemia demonstrated by muscle spasm of hands and feet. 7-13 Hormonal Control of Calcium Balance • Calcitriol, PTH and calcitonin maintain normal blood calcium concentration. 7-14 Calcitriol (Activated Vitamin D) • Produced by the following process – UV radiation and epidermal keratinocytes convert precursor to vitamin D3 – liver converts it to calcidiol – 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 stem cell differentiation into osteoclasts – promotes urinary reabsorption of calcium ions • Abnormal softness (rickets) in children and (osteomalacia) in adults without vitamin D 7-15 Calcitonin • Secreted (C cells of thyroid gland) when calcium concentration rises too high • Functions – reduces osteoclast activity as much as 70% – increases the number and activity of osteoblasts • Reduces bone loss in osteoporosis 7-16 Correction for Hypercalcemia 7-17 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 increasing osteoclast population – promotes calcium resorption by the kidneys – promotes calcitriol synthesis in the kidneys – inhibits collagen synthesis and bone deposition by osteoblasts 7-18 Correction for Hypocalcemia 7-19 Other Factors Affecting Bone • Hormones, vitamins and growth factors • Growth rapid at puberty – hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth plate – girls grow faster than boys and reach full height earlier (estrogen stronger effect) – 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 7-20 Fractures and Their Repairs 7-21 Fractures and Their Repair • Stress fracture caused by trauma – car accident, fall, athletics, etc • Pathological fracture in bone weakened by disease – bone cancer or osteoporosis 7-22 Healing of Fractures 7-23 Healing of Fractures • Normally 8 - 12 weeks (longer in elderly) • Stages of healing – fracture hematoma (1) - clot forms, then osteogenic cells form granulation tissue – soft callus (2) • fibroblasts produce fibers and fibrocartilage – hard callus (3) • osteoblasts produce a bony collar in 6 weeks – remodeling (4) in 3 to 4 months • spongy bone replaced by compact bone 7-24 Osteoporosis • Bones lose mass and become brittle (loss of organic matrix and minerals) – risk of fracture of hip, wrist and vertebral column • Postmenopausal white women at greatest risk – by age 70, average loss is 30% of bone mass – black women rarely suffer symptoms 7-25 Osteoporosis • Estrogen maintains density in both sexes (inhibits resorption) – testes and adrenals produce estrogen in men – 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 – PTH slows bone loss if given daily injection – best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40 – calcitonin 7-26 Spinal Osteoporosis 7-27