The cartilage skeleton of a foetus is sometimes known as a ‘temporary skeleton’.
Define Bone ?Bones are rigid organs that form part of the endoskeleton of vertebrates.They function to move, support, and protect the various organs of the body,produce red and white blood cells and store mineralsDefine Bone ?
3OssificationOssification is the process by which bone is formedfrom cartilage. The cartilage cells die off and arecalcified to produce bone.As a baby grows the cartilagebecomes bone and hardens. This ispart of the process of bone growth.In the womb the skeleton of thefoetus is initially formed from anelastic tissue called cartilage(except for the clavicle and partsof the cranium).
4Types of OssificationIntramembranous Ossification&Endochondral Ossification
Intramembranous Ossification• Some bones of the skull (frontal, parietal, temporal, and occipitalbones), the facial bones, the clavicles, the pelvis, the scapulae, andpart of the mandible are formed by intramembranous ossification• Prior to ossification, these structures exist as fibrous membranesmade of embryonic connective tissue known as mesenchyme.• Some bones of the skull (frontal, parietal, temporal, and occipitalbones), the facial bones, the clavicles, the pelvis, the scapulae, andpart of the mandible are formed by intramembranous ossification• Prior to ossification, these structures exist as fibrous membranesmade of embryonic connective tissue known as mesenchyme.
6Formation of the Bony Skeleton• Mesenchymal cells firstcluster together and startto secrete the organiccomponents of bonematrix which thenbecomes mineralizedthrough the crystallizationof calcium salts. Ascalcification occurs, themesenchymal cellsdifferentiate intoosteoblasts.• The location in the tissuewhere ossification beginsis known as an ossificationcenter.• Some osteoblasts aretrapped w/i bony pockets.These cells differentiateinto osteocytes.
7• The developing bone grows outward from the ossificationcenter in small struts called spicules.• Mesenchymal cell divisions provide additional osteoblasts.• The osteoblasts require a reliable source of oxygen andnutrients. Blood vessels trapped among the spicules meetthese demands and additional vessels branch into the area.These vessels will eventually become entrapped within thegrowing bone.
8• Initially, the intramembranous bone consists only of spongybone. Subsequent remodeling around trapped blood vesselscan produce osteons typical of compact bone.• As the rate of growth slows, the connective tissue around thebone becomes organized into the fibrous layer of theperiosteum. Osteoblasts close to the bone surface become theinner cellular layer of the periosteum.• Initially, the intramembranous bone consists only of spongybone. Subsequent remodeling around trapped blood vesselscan produce osteons typical of compact bone.• As the rate of growth slows, the connective tissue around thebone becomes organized into the fibrous layer of theperiosteum. Osteoblasts close to the bone surface become theinner cellular layer of the periosteum.
Endochondral Ossification• Begins with the formation of a hyaline cartilage model whichwill later be replaced by bone.• Most bones in the body develop via this model.• More complicated than intramembranous because the hyalinecartilage must be broken down as ossification proceeds.• We’ll follow limb bone development as an example.
Endochondral Ossification – Step 1• Chondrocytes near the centerof the shaft of the hyalinecartilage model increasegreatly in size. As these cellsenlarge, their lacunae expand,and the matrix is reduced to aseries of thin struts. Thesestruts soon begin to calcify.• The enlarged chondrocytes arenow deprived of nutrients(diffusion cannot occur throughcalcified cartilage) and theysoon die and disintegrate.
Endochondral Ossification – Step 2• Blood vessels grow into the perichondrium surrounding the shaft ofthe cartilage. The cells of the inner layer of the perichondrium in thisregion then differentiate into osteoblasts.• The perichondrium is now a periosteum and the inner osteogeniclayer soon produces a thin layer of bone around the shaft of thecartilage. This bony collar provides support.
Endochondral Ossification – Step 3• Blood supply to the periosteum, andcapillaries and fibroblasts migrateinto the heart of the cartilage,invading the spaces left by thedisintegrating chondrocytes.• The calcified cartilaginous matrixbreaks down; the fibroblastsdifferentiate into osteoblasts thatreplace it with spongy bone.• Bone development begins at thisprimary center of ossification andspreads toward both ends of thecartilaginous model.• While the diameter is small, theentire diaphysis is filled with spongybone.Notice the primaryossification centers in thethigh and forearm bonesof the above fetus.
Endochondral Ossification – Step 4• The primary ossification center enlargesproximally and distally, while osteoclastsbreak down the newly formed spongy boneand open up a medullary cavity in the centerof the shaft.• As the osteoblasts move towards theepiphyses, the epiphyseal cartilage is growingas well. Thus, even though the shaft isgetting longer, the epiphyses have yet to betransformed into bone.
Endochondral Ossification – Step 5Around birth, most long bones have abony diaphysis surrounding remnantsof spongy bone, a widening medullarycavity, and 2 cartilaginous epiphyses.At this time, capillaries and osteoblastswill migrate into the epiphyses andcreate secondary ossification centers.The epiphysis will be transformedinto spongy bone. However, a smallcartilaginous plate, known as theepiphyseal plate, will remain at thejuncture between the epiphysis andthe diaphysis.Articularcartilage Epiphyseal plate
Growth in BoneLength• Epiphyseal cartilage(close to theepiphysis) of theepiphyseal platedivides to create morecartilage, while thediaphyseal cartilage(close to thediaphysis) of theepiphyseal plate istransformed into bone.This increases thelength of the shaft.
•As a result osteoblasts beginproducing bone faster than therate of epiphyseal cartilageexpansion. Thus the bone growswhile the epiphyseal plate getsnarrower and narrower andultimately disappears. A remnant(epiphyseal line) is visible on X-rays (do you see them in theadjacent femur, tibia, and fibula?)At puberty, growth in bone lengthis increased dramatically by thecombined activities of growthhormone, thyroid hormone, andthe sex hormones.
Growth in Bone Thickness• Osteoblasts beneath the periosteum secretebone matrix on the external surface of thebone. This obviously makes the bone thicker.• At the same time, osteoclasts on theendosteum break down bone and thus widenthe medullary cavity.• This results in an increase in shaft diametereven though the actual amount of bone in theshaft is relatively unchanged.
19Functions of the skeletonThe skeleton performs many functions in the body.Shape – The skeleton gives us ourshape and determines our size.Blood cell production – bloodcells are made in the bone marrow.Movement – The skeleton allows us to move. Musclesare attached to the bones and move them as levers.Protection – The skeleton protects delicateparts of the body like the brain and lungs.Support – The skeletonsupports muscles and organs.12345
Bone• 206 bones in the human skeleton• Provide support, anchorage for muscles and protection for organs egribs• Bone is a storage area for calcium and phosphorous salts and has animportant role in blood formation• Before birth the skeleton is made of cartilage most of which isgradually replaced by bone via a process called ossification.• Bones of the human skeleton can be divided into long bone and flatbones• Long bones are tubular and weight bearing and are made of a denseouter layer of compact (cortical) bone and central region (medulla)made up of trabecular (spongy) bone• Trabecular bone makes up most of the short, flat and irregular shapedbones and the epiphyses (ends) of the long bones• It is much lighter than cortical bone and has a good strength to weightratio
211. Less calcium intake2. Age3. Smoking4. Diet5. Long use of corticosteroids6. High body massWhat are the reason for boneloss ?Bone loss in women occurs fastest in the first few years after menopause, butbone loss continues into old age
23Arthritis and osteoporosis are two distinct conditionsthat are very common, especially in olderindividuals. While osteoporosis generally affectsolder women who are of postmenopausal age,arthritis can affect any individual at any time. Insome cases, the conditions can be combined into adisease which is known as arthritis osteoporosis orosteoarthritis. Arthritis osteoporosis is a diseasethat attacks the bone joints as well as bone mass.
24Osteoporosis)• Osteoporosis is a chronic disease that has late clinicalconsequences and has been referred to as a silent epidemicbecause there are no associated signs or symptoms beforefracture.
Risk factors for Osteoporosis• Age- bone mineral density (BMD) decreases with age• Hormones- lower levels of oestrogen after menopauseaccelerate bone loss due to increased activity ofosteoclasts.• Premature menopause or hysterectomy causes earlieracceleration of bone loss. Likewise surgical or chemicalcastration in men• Gender- women are at increased risk of osteoporosis asthey start out with smaller bones and bone masscompared to men• Genetic factors- family history of osteoporotic fracture,especially hip fracture, increases risk
27The Role of CalciumCalcium is needed for our heart, muscles, and nerves tofunction properly and for blood to clot. Inadequate calciumsignificantly contributes to the development of osteoporosis.Many published studies show that low calcium intakethroughout life is associated with low bone mass and highfracture rates. National nutrition surveys have shown thatmost people are not getting the calcium they need to growand maintain healthy bones. To find out how much calciumyou need, see the Recommended Calcium Intakes (inmilligrams) chartCalcium is needed for our heart, muscles, and nerves tofunction properly and for blood to clot. Inadequate calciumsignificantly contributes to the development of osteoporosis.Many published studies show that low calcium intakethroughout life is associated with low bone mass and highfracture rates. National nutrition surveys have shown thatmost people are not getting the calcium they need to growand maintain healthy bones. To find out how much calciumyou need, see the Recommended Calcium Intakes (inmilligrams) chart
First, Let’s Take a Look at ThisDiagram…… Homeostasis of Calcium
Where Do I Get My Calcium?% 70 inorganic matrix composedof Calcium Salts inHydroxyapatiteCa10(PO4)6(OH)2.The skeleton is resevoir for theminerals Calcium (andphosphorous).Resorption: the process ofdissolving bone and releasingits minerals into the blood forother uses. TheOSTEOCLAST secretesACID PHOSPHATASE orsometimes HCL to digestbone matrix. Secreted bylysosomes.
Resorption and RemodelingResorptionOsteoclasts dothis using HCLand ACIDPHOSPHATASEto dissove bonematrixRemodelingOstoblasts do thisCollagen fibers andhydroxyapatitematrix
Calcium alone is not enough• Important co-factor nutrients that work with calciumfor healthy bonesVitamin D3MagnesiumVitamin CFolic Acid, B12, B6SiliconBoronVitamin KSeleniumZinc, Copper, ManganeseLycopene
Its Role in CalciumHomeostasisVITAMIN DTThe vitamin That WorksLike a hormone
To Make Me D, Warm Me Up andHydroxylate Me..3X!
Vitamin D3 Recommendation• Vitamin D3 continues to be overlooked – despite standardmedical care, research shows that over 50% of NorthAmericans with osteoporosis have inadequate Vitamin Dstatus!• Supplementation studies at 800 IU (the exact dosage in thebone builder blend) show reduced fracture incidence anddecreases cancer risk• National Osteoporosis Foundation recommends 400-800IU Vitamin D3 daily.• Health Canada is now recommending increasing upwardsto 2000 IU daily
Vitamin D3 at work• Drives bone health, measured best by 25OH)D test• Helps calcium be absorbed into bone-building cells• Inhibits formation of bone breakdown cells• Helps to prevent Calcium loss through the kidneys• Assists in the absorption of Calcium from the intestines.(Holick M. Mayo Clin Proc 2006)
Vitamin D Deficiency Diseases• 16 different types of cancer• 62% increased risk of heart disease & stroke• Multiple sclerosis• Juvenile Diabetes• Influenza• Osteoporosis• Fracture Incidence• Large population studies show that dietary Vitamin D3(or sunlight exposure) is associated with protectionagainst osteoporosis and fractures.(Nieves. Am J Clin Nutr 2005)(Circulation: Jan 7, 2008)
How Does “D” Compare ToHormones?Vitamin D3 is not secreted by a classical endocrinegland, the active form of the hormone is releasedfrom the kidney and acts at distant sites or locally.Each of the forms of vitamin D is hydrophobic, and istransported in blood bound to carrier proteins.Only a very remains in a free form in the circulationand has a serum t1/2 of about 5 hours small proportionof vitamin D
So..Exposure to Sun and Then, FortifiedFoods….Give Us the D We Need
How Does Vitamin D FacilitateCalcium Absorption in the Intestines??
IN THE INTESTINEIt facilitates intestinal absorption of calcium, aswell as stimulates absorption of phosphate andmagnesium ions.In the absence of vitamin D, dietary calcium is notabsorbed at all efficiently.Vitamin D stimulates the expression of a numberof proteins involved in transporting calciumfrom the lumen of the intestine, across theepithelial cells and into blood.
The vitamin D form, 1,25-dihydroxcholecalciferol [1,25(OH)2D3],1. stimulates the synthesis of the epithelialcalcium channels in the plasma membranecalcium pumps , and2. induces the formation of the calbindins.
Structure and Synthesis-Vitamin DThe term vitamin D actually refers to a groupof steroid molecules. Vitamin D3, alsoknown as cholecalciferol is generated in theskin of animals when light energy isabsorbed by aprecursor molecule 7-dehydrocholesterol.
Structure and Synthesis-Vitamin DVitamin D is thus not a true vitamin, because individualswith adequate exposure to sunlight do not requiredietary supplementation.There are dietary sources of vitamin D, including egg yolk,fish oil and a number of plants.The plant form of vitamin D is called vitamin D2 orergosterol. However, natural diets typically do notcontain adequate quantities of vitamin D, and exposureto sunlight or consumption of foodstuffs purposefullysupplemented with vitamin D are necessary to preventdeficiencies.
Vitamin D, as either D3 or D2, does not have significant biologicalactivity.Rather, it must be metabolized within the body to the hormonally-active form.This transformation occurs in 2 steps, as depicted in the diagram onthe next slideWithin the liver, cholecalciferal is hydroxylatedto 25-hydroxycholecalciferol by the enzyme 25-hydroxylase.Within the kidney, 25-vitamin D serves as a substrate for1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form ofvitamin D.
Physiological Effects of Vitamin DVitamin D is well known as ahormone involved in mineralmetabolism and bone growth.Its most dramatic effect is tofacilitate intestinal absorption ofcalcium, although it also stimulatesabsorption of phosphate andmagnesium ions.
Physiological Effects of Vitamin DIn the absence of vitamin D, dietary calciumis not absorbed at all efficiently.Vitamin D stimulates the expression of anumber of proteins involved intransporting calcium from the lumen of theintestine, across the epithelial cells and intoblood. The best-studied of these calciumtransporters is calbindin, an intracellularprotein that ferries calcium across theintestinal epithelial cell.
Physiological Effects of Vitamin DVitamin D receptors are present in most ifnot all cells in the body. Additionally,experiments using cultured cells havedemonstrated that vitamin D has potenteffects on the growth and differentiation ofmany types of cells.Hence, vitamin D has physiologic effectsmuch broader that a role in mineralhomeostasis & bone function.
Diseases and Conditionsthat Vitamin D Helps Prevent• Rickets and other bone diseases• Internal cancers• Multiple sclerosis• Helps in pregnacy to make bonestronger
Vitamin D3 Must be Vitamin D3, also known ascholecalciferol. Dose is 75 IU per pound body weight or 165IU per kilogram body weight. Children with blood levels of 25-hydroxyexceeding 80 ng/mL have shown the mostimprovement in immune response. Very important in immune function.
Outline• Historical science perspective• Diseases and conditions affected byvitamin D• Sources of vitamin D• How much we need in our blood• Concerns regarding ultravioletradiation• Sources of additional information