Chapter 7 Osseous Tissue and Bone Structure 1

Skeletal System: Bone Tissue • Skeletal system is not just composed of bone. Also includes: • Cartilage- forerunner of bone; allows for resistance • Dense connective tissue • Adipose tissue • Blood tissue • Epithelial tissue • Nervous tissue. • Each bone is considered an organ • Bone (osseous) tissue consists of cells and extracellular matrix. • Two types of bone structure: COMPACT AND SPONGY • Bone matrix is hardened by minerals • Continually remodels itself © 2012 Pearson Education, Inc. 2

Bone functions: Skeletal System 1. Support: composes framework of body 2. Protection: protects vital organs (heart, lungs) 3. Blood formation: contains red bone marrow where blood is formed. • Red bone marrow found in developing bones of fetus and in the pelvis, ribs, sternum and ends of long bones in arm and thigh of the adult 4. Movement: attachment site for skeletal muscle 5. Mineral homeostasis: minerals are mobilized or stored in bones 6. Lipid storage: contains yellow bone marrow where triglycerides can be stored 3 © 2012 Pearson Education, Inc.

Classification of Bones Six Bone Shapes 1. Sutural bones- between the flat bones of the skull 2. Irregular bones-complex shapes with short, flat, notched, or ridged surfaces- vertebrae, pelvic 3. Short bones: boxlike in appearance- wider than long– carpals, tarsals 4. Flat bones- skull, ribs, sternum, scapula 5. Long bones – longer than wide - femur, humerus, tibia, phalanges 6. Sesamoid bones often develop inside tendons -patella 4 © 2012 Pearson Education, Inc.

Long Bones Arm Forearm Fingers Thigh Leg Toes 5 Copyright © 2016 Mc. Graw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of Mc. Graw-Hill Education

Short Bones Patella Carpals Sesamoid bone of Hallux Sesamoid bone of Pollex Tarsals 6 Copyright © 2016 Mc. Graw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of Mc. Graw-Hill Education

Flat Bones Frontal bone Parietal bone Sternum Scapula Sternum and Ribs Copyright © 2016 Mc. Graw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of Mc. Graw-Hill Education 7

Irregular Bones Cervical vertebra Ethmoid bone Os coxae Sphenoid bone Copyright © 2016 Mc. Graw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of Mc. Graw-Hill Education 8

Bone Markings • Depressions or grooves • Along bone surface • Tunnels • Where blood and nerves enter bone • Elevations or projections • Where tendons and ligaments attach • At articulations with other bones 10 © 2012 Pearson Education, Inc.

Bone Cells OSTEOPROGENITOR CELLS: • Mesenchymal stem cells that divide to produce osteoblasts • Located in endosteum, the inner cellular layer of periosteum; lines medullary cavity • Assist in fracture repair; produce new bone matrix in a process called ossification. OSTEOBLASTS - Immature actively dividing bone cells • secrete matrix compounds and collagen fibers; have extensive ER with ribosomes to produce fibers and hydroxyapatite • OSTEOID — soft form of matrix produced by osteoblasts, but not yet calcified or mineralized to form bone • Osteoblasts surrounded by hardened matrix become osteocytes • Osteoid and cells are organic components of the matrix 12 © 2012 Pearson Education, Inc.

Bone Cells http: //www. mhhe. com/ biosci/ap/histology_mh /canalicl. jpg OSTEOCYTES Mature bone cells that maintain the protein and mineral content of the bone matrix; help in repair of damaged bone • Live within lacunae organized around blood vessels • Lie between layers (“lamellae”) of matrix • Connect by cytoplasmic extensions through canaliculi in lamellae • Form pathways for blood vessels for nutrients and wastes • Do not divide or undergo mitosis • Regulates calcium, phosphorus concentrations OSTEOCLASTS - modified white blood cells (WBC) that secrete enzymes and acids used to dissolve bone (bone resorption) releasing calcium into blood (osteolysis). • Giant, multinucleate cells develop in bone marrow by fusion of 3 -50 stem cells which produce macrophages § Create the medullary cavity of long bones § Ruffled border increase surface area for bone resorption © 2012 Pearson Education, Inc.

Bone (Osseous) Tissue • Healthy Bone 50% the strength of steel in resisting COMPRESSION (directed PUSHING FORCES; when limit of compressive strength is reached, bone will be CRUSHED) • 100% as strong as steel in resisting TENSION (stress applied while being STRETCHED OR PULLED) • Specialized cells make up only 2% of bone mass • Osteogenic (stem cells), Osteoblast, Osteocytes, Osteoclast • Extracellular matrix- provides compression and tension ability • Ground substance 2/3 of matrix varied consistency • Produces solid matrix of calcium salt deposits around collagen fibers Contains calcium phosphate; “concrete”- can withstand considerable compression but shatters with sudden impacts, twisting. Reacts with calcium hydroxide, to form hydroxyapatite, which combines with other calcium salts and ions; most calcium deposits are in this form • Fibers- (1/3) of bone matrix is collagen protein fibers, osteoid • provides tensile strength-resist stretching and twisting “rebar” allows for flexibility; cannot withstand compression 15 © 2012 Pearson Education, Inc.

Ground Substance Fibers 16 © 2012 Pearson Education, Inc.

Spongy Bone Compact Bone 17 © 2012 Pearson Education, Inc.

• 80% of bone mass • Provides support, movement, and resistance to weight stress in LIMITED range of motion or directions • Accounts for most of diaphysis of long bone---below the periosteum Osteon is the basic unit • Osteocytes are arranged in concentric (circular) lamellae ** • Around a central canal containing blood vessels/nerves • Perforating canals (Volkmann’s canals) • Perpendicular to central canal • Carry blood vessels into bone and marrow; connect osteons Circumferential Lamellae • wrapped around the long bone; bind osteons together; produce bone growth © 2012 Pearson Education, Inc. COMPACT Bone ** Layers of matrix produce a target pattern 19

Compact Bone Rings of matrix Collagen fibers “corkscrew” down the matrix of the lamella giving it a helical arrangement Helices coil in one direction in one matrix lamella and in the opposite direction in the next matrix lamella for added strength 20 © 2012 Pearson Education, Inc.

SPONGY Bone • Sponge-like appearance • Matrix forms an open network of trabeculae (thin plates of bone) arranged in lamellae. • Trabeculae have no central canals nutrients reach osteocytes by diffusion along canaliculi that open onto the surface of the tracebulae. Blood vessels woven through open spaces in the trabeculae • Between trabeculae are spaces that contain red bone marrow involved in hemopoiesis (blood cell formation). Spaces DECREASE WEIGHT OF BONE making it easier for muscle to move bones Spongy bone found in 1) Flat bones 2) Short bones 3) Irregular bones 4) Sesamoid bones 5) Epiphyses 21 6)© 2012 Medullary cavity of long bones (except clavicle which has no Pearson Education, Inc.

Classification of Bones Structure of a Flat Bone • Ex: the parietal bone of the skull • Resembles a sandwich of spongy bone between two layers of compact bone • Within the cranium, the layer of spongy bone between the compact bone is called the diploë 23 © 2012 Pearson Education, Inc.

The Distribution of Forces Long Bones and stress • Compact bone located where stresses are limited in direction • The femur transfers weight from hip joint to knee joint • Causing tension on the lateral side of the shaft • And compression on the medial side • Spongy bone located where stresses are MULTI-DIRECTIONAL © 2012 Pearson Education, Inc. “pulling forces” “pushing forces” 24

The Distribution of Forces – spongy bone • Trabeculae provide maximum strength similar to braces used to support a building; oriented to follow the lines of stress and can realign if the direction of stress changes from several directions. • Forces as much as 6 x body weight are transmitted across the hip. The orientation of the trabeculae is affected by the mechanical stress to which the bone is exposed. • Improper weight distribution can adversely affect nerve and spinal alignment. For example, sitting on a wallet. The wallet is pushing on the sciatic nerve and causing you to sit off center, so to sit up straight, you must curve your spine. This puts an uneven load on the sacroiliac joints and on the lower back. 25 © 2012 Pearson Education, Inc.

Skeletal System: Bone structure Long bones contain the following structures: • Diaphysis: the “shaft” of the bone • Epiphyses: both ends of the bone • Articulating cartilage: hyaline cartilage covering the epiphyses. Allows smooth articulation at joints. • Metaphyses: between the epiphyses and diaphysis of bone • Contain a epiphyseal plate at each end---hyaline cartilage growth allows for linear growth. Eventually replaced by osseous tissue, transforming plate into epiphyseal line. 26 © 2012 Pearson Education, Inc.

Hold periosteum to bone matrix 27 © 2012 Pearson Education, Inc.

Periosteum • A dense irregular connective tissue covering of the diaphysis. Isolates the bone from surrounding tissues • Attachment of ligaments and tendons • Contains cells involved in bone growth (width) • Provides a route for blood (nutrients and gas exchange) and nerve supply. • fibrous layer = dense irregular CT • Cellular/osteogenic layer = nourish & help with repairs • Sharpey’s perforating fibers penetrate the bone to attach periosteum to the matrix of the bone. • Fibers are art of the outer fibrous layer of periosteum, entering into the outer circumferential and interstitial lamellae of bone Near joints periosteum becomes continuous with ligaments and tendons 28 © 2012 Pearson Education, Inc.

Bone Marrow • Medullary cavity: cavity found in the diaphysis; consisting mostly of compact bone, walls composed of spongy bone and lined with a thin, vascular membrane the endosteum. • bone marrow –composed of tissue stem cells which produce blood cells inside cavity of long bone and small spaces between trabeculae of spongy bone • red marrow (myeloid tissue) • hemopoietic tissue - produces white and red blood cells • in nearly every bone in a child • in adults, found in skull, vertebrae, ribs, sternum, part of pelvic girdle, and proximal heads of humerus and femur • yellow marrow found in adults • most red marrow turns into fatty yellow marrow no longer produces blood cells but fat, cartilage and bone 29 Copyright © The Mc. Graw-Hill Companies, Inc. Permission required for reproduction or display. © 2012 Pearson Education, Inc.

Red and Yellow Bone Marrow http: //projectskeletal. tripod. com/bonestuff. jpg © 2012 Pearson Education, Inc. http: //en. wikipedia. org/wiki/Bone_marrow#mediaviewer/File: 619_Red_and_Yellow_Bone_Marrow. jpg 30

Bone marrow transplant http: //www. riversideonline. com/source/images/imag e_popup/r 7_bonemarrowaspiration. jpg http: //women. texaschildrens. org/uploadedimages /Pages/Health_Topics/1129. jpg 31 © 2012 Pearson Education, Inc.

External / Internal Bone structure Endosteum: membrane lining of the medullary cavity • An incomplete cellular layer: • Lines the medullary (marrow) cavity • Covers trabeculae of spongy bone • Lines central canals • Contains osteoblasts, osteoprogenitor cells, and osteoclasts • Active in bone growth and repair 32 © 2012 Pearson Education, Inc.

Bone Formation and Growth BONE IS NEVER FORMED AS A PRIMARY TISSUE. IT ALWAYS REPLACES AN EXISTING TISSUE SUCH AS CARTILAGE OR DENSE CT!!! • Human bones can grow until about age 25 • Ossification: Bone formation • Two main forms of ossification 1. Intramembranous ossification • Occurs in the dermis • Produces dermal (flat) bones such as mandible (lower jaw) and clavicle (collarbone) and skull • No cartilage present • Injured bones use this process when healing 2. Endochondral ossification • involves the replacement of a hyaline cartilage “skeleton” with osseous tissue. Most bones originate as hyaline cartilage • Calcification the depositing of calcium salts Good animation https: //www. youtube. com/watch? v=p-3 Pu. LXp 9 Wg © 2012 Pearson Education, Inc. 33

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Bone Formation and Growth Intramembranous Ossification • Also called dermal ossification because it occurs in the dermis • Produces dermal flat bones such as mandible, clavicle, skull and is responsible for remodeling or repairing injuries to bone • Bone is formed in fibrous connective tissue membranes Process: • Mesenchymal stem cells cluster and differentiate into osteoblast • Osteoblast secrete soft matrix called osteoid • As calcium phosphate and other mineral deposits move into osteoid it hardens the matrix. With the help of osteoclasts bony interconnected trabeculae form and thicken effectively creating spaces in the bone. • The hardened matrix traps the osteoblasts in cavities called lacunae. The osteoblasts are no longer able to reproduce and become osteocytes. Surface mesenchyme produces periosteum • Blood vessels move in between trabeculae and release progenitor cells that will form the red bone marrow and future blood cells. • Surface bone is filled in by bone deposits of osteoblasts effectively converting spongy bone to compact bone. 35 © 2012 Pearson Education, Inc.

Intramembranous Ossification 1) In mesoderm embryonic germ layer mesenchymal cells (connective tissue stem cells) form clusters and differentiate into osteoblast which secrete a soft organic matrix – the osteoid. 2) Mineral salts are then deposited and begins to form bony spicules called trabeculae 3) The osteoblasts get trapped in the matrix and become osteocytes embedded in lacunae. Calcification occurs with the increased accumulation of calcium and mineral salts 37 © 2012 Pearson Education, Inc.

As calcium phosphate (non-livinginorganic) is deposited it hardens the matrix forming bony interconnected trabeculae which thicken forming spaces in the bone. • Osteoclasts create marrow cavity. • Blood vessels grow into the matrix between the trabeculae and differentiate into the red bone marrow (produces 500 billion blood cells per day) Osteoblasts form compact bone at surface; surface mesenchyme produces periosteum 38 © 2012 Pearson Education, Inc.

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Endochondral Ossification This process uses hyaline cartilage as the model for long bone formation. Most bones are formed by this process. 1) MSC stem cells differentiate into chondroblast • chondroblast form a hyaline cartilage model • Hyaline model is surrounded by the perichondrium -layer of dense irregular connective tissue • perichondrium will become periosteum- containing undifferentiated cells (osteoprogenitor cells) which later become osteoblasts. • Expanding cartilage matrix encases chondrocytes in lacunae. © 2012 Pearson Education, Inc. http: //www. sybilfp 7. eu/sites/default/files/styles/large/public/na ture 01659 -f 1. 2. jpg? itok=d 89 rrhk. V 40

Endochondral Ossification 2) Collar formation: • About the 3 rd month of development periosteum (dense irregular connective tissue) forms around hyaline cartilage replacing the perichondrium. • Concurrently the nutrient artery penetrates the perichondrium and invade the inner cavity of the cartilage model. • The hole that the vessels poke through are called the nutrient foramen. Fibroblasts migrate from the artery and differentiate into osteogenic cells (stem cells) which then become osteoblasts. • The osteoblasts secrete osteoid (un-mineralized bone) against the shaft of the cartilage model (Appositional Growth). This serves as support for the new bone. • The end result is a bony collar on the outside of the cartilage. 41 © 2012 Pearson Education, Inc.

Endochondral Ossification 3) Cavity formation: • As the bony collar is forming the cartilage continues to enlarge, causing the chondrocytes to increase in size. • The cells crowd out the matrix reducing it to strut-like projections in the center of the model that will ossify/harden to form bone. • The calcification/hardening of the center makes the inner cartilage impermeable to the diffusion of nutrients which results in the massive death of the chondrocytes. • As the cartilage starts deteriorates a cavity is formed. • The remaining cartilage is broken down by osteoclasts forming the marrow cavity. The osteoblasts along with fibroblasts from the invading blood vessels begin formation of trabeculae (spongy bone) This centered cartilage is called the primary ossification center. 43 © 2012 Pearson Education, Inc. https: //i 0. wp. com/lifenews. wpengine. netdna-cdn. com/wp-content/uploads/2014/11/ultrasound 4 d 55. png

Endochondral Ossification 4) Elongation: as blood vessels, osteoclasts, and osteocytes continue to invade the bone the shaft (diaphysis) starts to elongate (interstitial growth). The medullary cavity forms and the diaphysis will slowly continue to lengthen during embryonic development. • Vessels bud into the hyaline cartilage at the ends (epiphysis) of the long bones forming what are called secondary ossification centers. These centers and marrow cavities form at ends of bone • Osteogenic cells differentiate into osteoblast laying down bony matrix. Spongy bone formation proceeds outward towards the periphery. No formation of medullary cavity • Hyaline cartilage is left on the ends of the bones (called articular cartilage) and the epiphyseal plates (growth plates) are also formed. The articular cartilage and epiphyseal plates are the only remains of the original hyaline cartilage model • CARTILAGE CONTINUES TO BE REPLACED BY BONE at the EPIPHYSEAL PLATE. 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 44 © 2012 Pearson Education, Inc.

http: //upload. wikimedia. org/wikipedia/commons/c/cf/Bone_growth. png 46 © 2012 Pearson Education, Inc.

47 http: //classconnection. s 3. amazonaws. com/436/flashcards/844436/jpg/long_bone 1319071915389. jpg © 2012 Pearson Education, Inc.

Bone Formation and Growth Interstitial growth for increasing LENGTH • Results from the deposition of bony matrix on the diaphysis side of the epiphyseal plate. • Cartilage cells closest to the epiphysis divide, increasing the thickness of the cartilage. • At the diaphyseal side the cartilage is replaced with bony tissue resulting in longer bone. Epiphyseal plate • Continues to allow interstitial growth until the age of 18 for females and 21 for males. • Cartilage stops dividing under the influences of hormones and ossifies into an epiphyseal line • Presence of epiphyseal line indicates that linear bone growth is no longer possible. • Premature ossification of epiphyseal plate of one bone in the extremities may result in unequal bone lengths 48 © 2012 Pearson Education, Inc.

Bone Growth at an Epiphyseal Cartilage 49 © 2012 Pearson Education, Inc.

Bone Formation and Growth Appositional Growth • Results in increased thickness (WIDTH) of bone • Differentiation of cells at the periosteum into osteoblasts that begin to deposit collagen fibers and extracellular matrix; forming bony ridges • Osteoblast become osteocytes as they become surrounded by bony matrix. • Extracellular matrix ridges surround periosteal blood vessels and periosteum becomes endosteum forms circumferential lamellae and central canals Animation: https: //www. youtube. com/watch? v=X 6 E 5 Rz 9 t. OKE 50 © 2012 Pearson Education, Inc.

Appositional Bone Growth 51 © 2012 Pearson Education, Inc. Figure 6. 10 a

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Bone Tissue = Homeostasis/Remodeling • Homeostasis is controlled by a balance of hormonal actions influenced by diet, exercise, and physical health stasis • Bone building (osteoblasts) and bone recycling (osteoclasts) must balance. Bone continually remodels, recycles, and replaces • If deposition is greater than removal, bones get stronger • If removal is faster than replacement, bones get weaker • More breakdown than building, bones become weak • Exercise, particularly weight-bearing exercise, causes osteoblasts to build bone- when a bone is placed under stress bone cells migrate to the stressed area and begin to form new bone. Cells secrete collagen which is deposited between cells. Mineralization follows. • Heavily stressed bones become thicker and stronger • Bone degenerates quickly. Up to 1/3 of bone mass can be lost in a few weeks of inactivity • Vitamin C required for collagen synthesis, osteoblast differentiation • Vitamin A stimulates osteoblast activity • Vitamins K and B 12 help synthesize bone proteins 53 © 2012 Pearson Education, Inc.

Exercise, Hormones, and Nutrition 1. Growth hormone and thyroxine (T 4) stimulate bone growth • Before Puberty most bone growth is stimulated by: § Human growth hormone (h. GH) produced by anterior pituitary 2. Estrogens androgens stimulate osteoblasts • After Puberty bone growth is stimulated/regulated by: § Sex hormones estrogen androgen stimulate bone growth; Estrogen promotes the programmed death of osteoclast; therefore is protective in the adult female 3. The Skeleton is a Calcium Reserve • Bones store calcium and other minerals • Calcium is the most abundant mineral in the body. The hormone calcitriol (Vitamin D); formed in the kidneys necessary for absorption of Ca and P from digestive tract. • Calcium ions are vital to: • Blood coagulation • Nervous system function • Muscular contraction • Enzymatic function © 2012 Pearson Education, Inc. 54

Result of hypersecretion of human growth hormone (h. GH) characterized by excessive growth and

Calcium Homeostasic Control • Parathyroid Hormone (PTH) releases Ca 2+ into blood • Produced by parathyroid glands in neck • Increases calcium ion levels by: 1. Stimulating osteoclasts – causing bone breakdown 2. Increases intestinal absorption of calcium 3. Decreasing calcium excretion at kidneys 4. Increases production of vitamin D (calcitriol) • Calcitonin causes bone cells to absorb Ca 2+ • Secreted by C cells (parafollicular cells) in thyroid • Decreases calcium ion levels: 1. Inhibits osteoclast activity 2. Increases calcium excretion at kidneys 3. Lowers the amount of calcium absorption from intestines 4. Increases the amount of bone formation by increasing numbers of osteoblasts which then utilize the excess calcium for mineralization of new bone matrix 56 © 2012 Pearson Education, Inc.

$Bone Fracture Cracks or breaks in bone caused by physical stress. Common bone fractures:$

Bone Fracture Cracks or breaks in bone caused by physical stress. Common bone fractures: • Closed (simple)- simple bone break • Open (compound)- fracture where bone punctures skin • Comminuted- ends of broken bones splinter leaving fragments between broken ends • Greenstick- Partial fracture on one side of the bone as the bone BENDS rather than breaking cleanly; seen in children • Impacted- broken end of one bone driven into the other © 2012 Pearson Education, Inc. 57

$Fractures • Transverse fractures- breaking of a bone shaft across its axis • Displaced$

Fractures • Transverse fractures- breaking of a bone shaft across its axis • Displaced fractures –produce new and abnormal bone arrangements • Compression fractures –occur in vertebrae (hard landing on buttock) • Spiral fractures- twisting stresses Common bone fractures: • Pott’s fracture- fracture of distal fibula, usually resulting in damage to medial aspect of ankle joint • Colle’s fracture- fracture of distal radius often seen upon falling on outstretched arm. • Stress fractures- microscopic fractures seen with repeated stress to bones. © 2012 Pearson Education, Inc. 58

Fracture Repair 1. Bleeding/Inflammation • Extensive bleeding causes swelling and redness, increase in WBC activity • Produces a clot (fracture hematoma) • Bone cells in the area die; removed by osteoclasts/macrophages 2. Soft callus formation • Fibroblasts migrate from endosteum and periosteum forming soft CALLUS=mass of tissue that forms at fracture site; connects the broken ends of the bone together • External callus - CARTILAGE AND BONE surrounds and stabilizes the break • Internal callus develops in medullary cavity at the ends of the broken bones as a network of SPONGY BONE unites the inner surface depositing collagen forming granulation tissue. © 2012 Pearson Education, Inc. 59

Fracture Repair 3. Osteoblasts • Cartilage of external callus is replaced by bone and spicules of spongy bone help to unite the broken ends of the bone forming a bony matrix- HARD CALLUS. 4. Osteoblasts and osteocytes remodel the fracture for up to a year • Reducing bone calluses • Swelling may mark the area for some time but will eventually fade. Often the new bone is stronger than previous older bone. 60 © 2012 Pearson Education, Inc.

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Steps in the Repair of a Fracture 62 © 2012 Pearson Education, Inc.

Bone Repair Obstacles § Weight bearing too soon – moves bone fragments before restored § Smoking – constricts blood vessels decreasing circulation § Health conditions: Diabetes, hormone problems, vascular disease § Medications that inhibit immune process: § Ex: corticosteroids § Infection § Advanced age § Poor nutrition and metabolism 63 © 2012 Pearson Education, Inc.

Bone and Aging Bone deposition (deposit) outpaced by Resorption (breakdown) at middleage. With increased age demineralization of bone and brittleness occurs • Demineralization: the loss of bone mass resulting from the loss of calcium and other minerals. • Results in fragile limbs; reduction in height; tooth loss • Menopausal women are at greater risk for demineralization due to the rapidly decreased levels of estrogen. • Males at lower risk due to continued production of testosterone late into life • Decreased protein synthesis results in brittleness of bone • Fewer osteoblasts and osteocytes 64 © 2012 Pearson Education, Inc.

$Bone Disorders Osteoporosis • Results from decrease bone mass; bones more prone to fracture$

Bone Disorders Osteoporosis • Results from decrease bone mass; bones more prone to fracture • Predominantly seen in menopausal women due to decreased estrogen levels • Estrogen INCREASES OSTEOBLAST activity and STIMULATES bony matrix deposition • Estrogen INHIBITS OSTEOCLAST activity preventing bone loss. Decreases in estrogen levels lead to an increase in osteoclast activity that can produce bone loss. • Can also be seen in female elite athletes that have stopped menstruating due to low body fat (unable to produce adequate levels of estrogen) • Risk increases with family history, thin/small build, diet poor in calcium or vitamin D, sedentary life style, smoking, drinking 65 alcohol and Caucasian or Asian ethnicity. © 2012 Pearson Education, Inc.