Ch. 6: Bone & Skeletal TissueSkeletal CartilagesClassification of BonesFunctions of BonesBone StructureDevelopmentBone Homeostasis: Remodeling & RepairHomeostatic Imbalances of BoneDevelopmental Aspects

Ch. 6: Bone & Skeletal TissueSkeletal system includes bone & cartilage

Skeletal CartilagesStructure, types, locations

All types of sk cart have chondros, extracell mtx, fibersHyaline c

most common, flexible, resilient, contain fine collagen fibersArticular, costal, respiratory (vb), nasal (ext nose)

Elastic clike hyaline; more elastic fibers; tolerate repeated bending; epigolttis, ext ear

FibrocartCross between hyal cart (chondros) & dense reg conn tiss (thick coll fibers); high tensile strengthResist high pressure & stretchMenisci in knees, intervert discs

GrowthAppositional; Interstitial

Figure 6.1

Ch. 6: Bone & Skeletal TissueClassification of Bones

Axial vs appendicularBy shape: long, short, flat, irregular

Functions of BonesSupportProtectionMovementStorage of minerals, growth factors, fatHematopoesis

Forces•Tension•Compression•Bending

Figure 6.2

Ch. 6: Bone & Skeletal TissueBone Structure

Gross AnatomyBone Markings – See Table 6.1Texture

Compact (lamellar): dense outer layer, naked eye smoothSpongy (cancellous): trabeculae, red or yellow marrow

Typical long bone structureDiaphysis: compact bone collar over marrow-filled medullary cavityEpiphyses: bone ends, compact over spongy, articular (hyaline) cartilage;

epiphyseal line (remnant of epiphyseal plate)Membranes: periosteum, endosteum, osteoblasts/clasts

Short, irregular, flat bone structureCompact over spongy; no marrow cavity

Hematopoetic tissue (red marrow): Trabecular parts of long bones (esp. heads of femur, humerus in adult) &

flat bones

Microscopic AnatomyChemical Composition

Table 6.1

Table 6.1

Figure 6.3

Figure 6.3a

Figure 6.3b

Figure 6.3c

Figure 6.5

Ch. 6: Bone & Skeletal TissueBone Structure

Gross AnatomyMicroscopic Anatomy

Cell types: osteogenic, osteoblasts, osteocytes, osteoclastsCompact bone

Microscopic passageways; osteons (Haversian systems)Multiple lamellae per osteon; alternating collagen fiber orient’nCentral canal; osteocytes btn lamellae

Spongy boneTrabeculae align with stress; no osteons

Chemical Composition (skeleton = 14-17% of total adult body weight i.e. ~ 10 kg)

OrganicCells & osteoid (ground substance & collagen fibers)

Inorganic (2/3 of skeleton weight – Trotter & Peterson, J Bone Jt Surg Am 1962)

Hydroxyapatite crystals (mainly calcium phosphate) (40% of hydroxyapatite is Ca; total body Ca ~ 2.5 – 3 kg for normal 70 kg person)

Figure 6.6

College or Department name here

Bone architecture(a) macroscopic bone,(b) osteons with circular arrangements of differently oriented collagen fibers. (c) collagen fiber = bundles of collagen fibrils. (d) collagen fibril = staggered arrangement of collagen molecules with embedded mineral crystals (blue). (e) collagen molecule triple helix.

Collagen: tensile and bending strength.Hydroxyapatite (calcium phosphate): compressive strength

Reinforced concrete

“Rebar” (steel reinforcing bars): tensile and bending strength.

Concrete:compressive strength.

Above: channel.nationalgeographic.com/series/la-hard-hats/all/Photos#tab-Photos/11

Left: www.bnl.gov/nsls2/sciOps/chemSci/softMatter.asp

Figure 6.6

Figure 6.6a

Figure 6.6b

Figure 6.6c

Ch. 6: Bone & Skeletal TissueDevelopment

Ossification (= osteogenesis)

Forming the bony skeletonIntramembranous ossifEndochondral ossif

Postnatal bone growthLength of long bones: epiphyseal plateHormonal regulation

GH. Sex hormones: growth spurt, epi plate closure

Figure 6.8.

Figure 6.8

Figure 6.9

Figure 6.10

Figure 6.11

Figure 6.15

Ch. 6: Bone & Skeletal TissueBone Homeostasis: Remodeling & Repair

RemodelingAt periosteum & endosteumRemodeling unit w/ osteoblasts, osteoclastsOsteocytes (stimulated by osteoblasts) secrete matrixControl of remodeling

By hormones to regulate plasma [Ca]

PTH ↑when [Ca] ↓, stimulates osteoclastsIn response to mechanical stressBone strongest where stress acts

Long bone hollow ctr; shaft thickest at middleCurved bones thickest where most likely to breakSpongy bone trabeculae line up along stress linesProjections (tuberosity, crest,…) where muscles attach

Ch. 6: Bone & Skeletal TissueBone Homeostasis: Remodeling & Repair

Remodeling animation with description of osteoporosis (54 s):http://www.youtube.com/watch?v=5uAXX5GvGrI

Figure 6.12

Figure 6.13

Ch. 6: Bone & Skeletal TissueBone Homeostasis: Remodeling & Repair

RepairClassification of fractures

Bone end positions: displaced or nondisplacedComplete or incompleteOrientation: linear (long axis) or transverseSkin penetration: open (compund) or closed (simple)By nature, location of break – see Table 6.2

Repair process – see Fig 6.15

Table 6.2

Table 6.2

Radiograph Showing a Subtrochanteric Stress Fracture. Kwek et al., NEJM 359:316, 2008.

Not the most common site for stress fracture. Common stress fracture sites: tibia (runners), metatarsals (dancers, skaters), fibula…) From article about possible increase in fracture risk in patients on bisphosphonates (osteoporosis drugs). See also JAMA 305: 783-789, 2011.Some data suggests that the risk of rare fractures is a lot higher after 6-8 years on bisphosphonates than after 2 yrs; some suggest a bisphosphonate holiday after 5 yrs (NYT 2011-03-06).

A current debate: Do some osteoporosis drugs increase the rate of “rare” fractures?

Figure 6.15

Ch. 6: Bone & Skeletal TissueHomeostatic Imbalances of Bone

OsteomalachiaFailure to mineralize; weak bonesRickets in childrenDue to Ca deficiency, maybe secondary to vit D deficiency

OsteoporosisResorption > formation; ↓ bone density, massElderly susceptible; vertebral, femoral neck fxEstrogen, testosterone slow osteoclasts, stimulate blastsPost-menopausal fall in estrogenRemodeling animation with description of osteoporosis (41 s):http://www.youtube.com/watch?v=NKVKNqIOnh0&feature=related

Paget’s diseaseDisorganized (Pagetic) bone; spongy/compact too highElderly susceptible; affected bone weak

Figure 6.16

Hip Fractures

• 300,000 hip fractures annually in US• Majority related to osteoporosis and falls in older people• Enormous public health implications and economic burden• A top cause of immobilization in elderly• Patients who have sustained a hip fracture

• 2-year mortality rate of 36%

• Immobility → increased bone resorption, predisposition to 2nd hip fracture

• Many don’t regain prefracture level of mobility; lose independence, QOL

• Risk of subsequent skeletal fracture up 2.5x

• Risk of new hip fracture up 5x – 10x

Editorial: Calis KA, Pucino F, NEJM 2007: Sep 17, epub ahead of print

College or Department name here

Drug therapy for osteoporosisCa, Vitamin D supplementationBisphosphonates

Many have names ending in –dronateFosamax/alendronate, Actonel/risedronate, etc.

Reduce activity of osteoclastsReduce bone remodelingSide effects: osteonecrosis of jaw, uncommon fractures, etc.

PTH analogsForteo/teriparatide34 aa fragment of PTH (84 aa)Mechanism of action mysterious

Further reading:

NYTimes Sep 23 2009

Can vitamin D improve athletic performance?http://well.blogs.nytimes.com/2009/09/23/phys-ed-can-vitamin-d-improve-your-athletic-performance/

Vitamin D essential for absorption of Ca from gut; it also helps other cells including muscle cells use Ca. Many of us with a “normal” diet and occasional outdoor time are vitamin D deficient and we may benefit from more D.

Vitamin D Status and Its Relation to Muscle Mass and Muscle Fat in Young Women. 59% of sample (16-22 yo ♀ in Calif) had insufficient 25OH-D (<30 ng/ml), including 24% who were deficient in 25OH-D (<20 ng/ml) (surprisingly large %). Vitamin D insufficiency was associated with increased fat infiltration in muscle. Gilsanz, …, Kremer. J Clin Endocrinol Metab 2010; DOI: 10.1210/jc.2009-2309

Further reading:

NY Times Sep 1 2009

Does ibuprofen help or hurt during exercise?http://well.blogs.nytimes.com/2009/09/01/phys-ed-does-ibuprofen-help-or-hurt-during-exercise/

Many athletes regularly take ibuprofen. Article describes increasing evidence that "vitamin I" has negative side effects including blunted growth response of bone to applied stress, decreased post-workout collagen production, etc. One scientist wrote recently in Brit J Sports Med that regular ibuprofen use around the time of exercise diminishes the expected increase in skeletal strength that otherwise comes from exercise. http://bjsm.bmj.com/cgi/content/full/43/8/548