skeletal system structure & function development & growth bone homeostasis osteoporosis...

Skeletal Skeletal SystemSystem

Structure & Function Development & Growth Bone Homeostasis Osteoporosis & other bone disorders

The evil that men do lives after them, the good is oft interred with their bones.

—William Shakespeare (1564-1616) Julius Caesar, Act III, Scene 2

A Bone’s Shape Makes Possible A Bone’s Shape Makes Possible its Functionsits Functions

Sites of muscle attachments

• Shape & form

• Support

• Protection

• Movement

• Storage

• Hematopoiesis

Bone StructureBone Structure

Structures of a long bone:– periosteum: tough fibrous membrane covering

– diaphysis: shaft - b/t epiphyses, long axis of bone

– articular cartilage: portion of epiphysis covered w/ cartilage

– epiphysis: expanded ends of bone -- proximal & distal

– medullary cavity: hollow chamber w/in diaphysis, endosteum membrane lines cavity & marrow resides w/in

– compact bone (cortical): near surface, continuous ECM w/ no spaces -- dense & hard

– spongy bone (cancellous): w/in compact bone, consists of network of thin strands of trabeculae

Gross Anatomy of a Long Gross Anatomy of a Long BoneBone

Cellular Structure Cellular Structure of Boneof Bone

• Compact bone: cells, ECM & mineral salts form an osteon– contain blood vessels & nerves surrounded by CT

– perforating canals transverse central canals

– osteocytes lie in small concavities (lacunae) b/t lamellae

– canaliculi - provide communication b/t osteocytes

• Spongy bone: cells & ECM lie w/in trabeculae– no osteon or central canals – irregular lamellae & osteocytes

– trabeculae are formed where stress is exerted on the bone

– receive nutrients via diffusion from the canaliculi

Structural Unit of Compact Bone: OsteonStructural Unit of Compact Bone: Osteon

Lamella

Microscopic Structure of Spongy BoneMicroscopic Structure of Spongy Bone

Gross Anatomy of a Long Gross Anatomy of a Long BoneBone

Principal Cells of Bone Principal Cells of Bone TissueTissue

Chemical Chemical Composition of Composition of

BoneBone Organic components:

– Cells: osteogenic, osteoblasts, osteocytes & osteoclasts

– ECM: contribute to bone’s structure & tensile strength

Inorganic components: – mineral salts: calcium phosphate & carbonate which

account for bone’s hardness

OsteogenesisOsteogenesis Intramembranous ossification (flat & irregular):

- originate as sheet-like layers of CT

- partially differentiated CT form into osteoblasts

- deposit bony matrix -- forming spongy bone

Endochondral ossification (long & short):- develop from hyaline cartilage -- model for bone formation

- CT covering cartilage becomes infiltrated w/ blood vessels forming periosteum

- CT differentiates into osteoblasts forming spongy bone w/ ossification continuing deposition of compact bone occurs

Intramembranous Intramembranous OssificationOssification

Stages in Endochondral Stages in Endochondral Ossification Occurring in a Ossification Occurring in a

Long BoneLong Bone

EndochonEndochondral dral

OssificatioOssificationn

Forming skeleton of an embryonic chicken, stained with Alizarin Red and Alcian Blue to differentiate between hardened bone (in red) and the remaining cartilage model (in blue).

Bone Growth : elongation & Bone Growth : elongation & appositionalappositional

Epiphyseal Plate

http://highered.mcgraw-hill.com/classware/infoCenter.do?isbn=0072829532

X-ray Depicting Epiphyseal X-ray Depicting Epiphyseal PlatePlate

Osteoclasts & Medullary Osteoclasts & Medullary CavityCavity

Multinucleated cells originate from WBC -- break down calcified matrix (bone resorption):– lysosomal enzymes digest organic components– acids secreted dissolve inorganic portion of matrix– phagocytes digest bony matrix – osteoblasts invade depositing new bone

Formation of medullary cavity:– primary ossification center enlarges -- osteoclasts break down

spongy bone – cavity forms in center of diaphysis– cavity fills w/ marrow, blood & lymph vessels & nerve fibers

• red & yellow marrow

Bone–Resorbing Bone–Resorbing OsteoclastOsteoclast

Development of osteoblasts Development of osteoblasts &osteoclasts from bone &osteoclasts from bone

marrow progenitorsmarrow progenitors

Valsamis et al. Nutrition & Metabolism 2006 3:36  

Homeostasis: Homeostasis: Bone Bone

RemodelingRemodeling Continuous bone resorption

& bone deposition – regulated via 2 control loops: 1. negative feedback

(hormonal)

2. mechanical/gravitational

(Wolff’s law of bone)

Hormonal Control of Blood Hormonal Control of Blood CaCa++++

• When Ca++ intake is -- blood [Ca++] are also

• PTH stimulates osteoclasts -- releasing Ca++ salts from ECM into blood

• High intake blood [Ca++] inhibits osteoclasts activity

• Calcitonin -- stimulates osteoblasts activity, bone resorption & Ca++ excretion

(hypercalcemia)

(hypocalcemia)

Hormonal Control of CaHormonal Control of Ca++++ BalanceBalance

• Parathyroid hormone (PTH) – responsible for plasma [Ca++]– mobilize Ca++ from bone ( bone resorption)– enhances renal reabsorption of Ca++ – intestinal absorption of Ca++ (indirectly)

• Vitamin D3 – 1,25-dihydroxycholecalciferol (calcitriol):– obtained from diet & sunlight– supports effect of PTH – enhancing Ca++ uptake in small

intestine– PTH & prolactin regulate production

• Calcitonin:– released in association w/ plasma [Ca++]– bone resorption & renal excretion (action opposite to PTH)

Factors Affecting Bone Factors Affecting Bone Development, Growth & Development, Growth &

RepairRepair Nutrition: calcium, phosphorus, vitamins D, A, C & K

UV radiation: dehydrocholesterol

Hormones: hGH, T3 & T4, PTH and male & female sex hormones

Physical activity: weight bearing exercise & skeletal muscle contraction (Wolff’s Law)

Fractures & RepairFractures & Repair

• Fracture: classified by cause & nature of break (e.g., traumatic, compound)

– Blood vessels & periosteum rupture -- hematoma, swelling & inflammation to surrounding tissue

– Angiogenesis: osteoblasts invade hematoma generating spongy bone nearby & fibroblast produce fibrocartilage (cartilaginous callus) and ECM

– Phagocytic cells remove blood clot & osteoclasts resorb bone fragments

Key Steps in Repair of a Key Steps in Repair of a FractureFracture

Types of FracturesTypes of Fractures

Rickets & OsteomalaciaRickets & Osteomalacia

• Pathology: failure of osteoid to calcify in a growing person, most commonly assoc. w/ vitamin D deficiency in hypocalcemia

• Signs & Symptoms: muscular hypotonia, thickening of skull, softening of long bones (bowlegs), knobby deformity in long bones & ribs, kyphoscoliosis

• Risk factors: dark skin, inner-city dwellers, breastfeed infants w/o vitamin D supplementation

• Treatment: UV light, vitamin D, calcium & phosphorus supplements,

OsteoporosisOsteoporosis

• Pathology: bone mass & mineral content - w/in affected bones trabeculae are lost -- spaces/canals enlarge filling w/ fibrous & fatty tissues

• Signs & symptoms: bones fracture easily (long bones), spontaneous breaks - unable to support body weight

• Risk factors: Ca++ & vitamin D intake, phys. act., estrogen levels, cigarette smoking, alcohol abuse, medications: gender, age, body

size, ethnicity & genetics

• Screening & Treatment: DEXA; bisphosphonates; estrogen therapy (ERT); PTH & exercise

Bone Mineral Bone Mineral Acquisition During Acquisition During PubertyPuberty

Gap in CaGap in Ca++++ Intake Intake

• Females reach 95% of adult BMD by age 18 yrs & w/ only modest gains up to 3rd decade of life

• Bone mineral density (BMD) most rapidly b/t ages of 11-14 yrs in girls & 14-17 yrs in boys

• 86% of girls & 65% of boys aged 12-18 yrs fail to meet RDA of 1200 mg/d for Ca++

• Intake for Ca++ -- 1300 mg/d; gap b/t the recommended & actual intakes has widened

• Ca++ content of common foods: http://www.nof.org/

• Meeting RDA of Ca++ is challenging when dairy products are not consumed. Ca++ -fortified products offer a means of boosting Ca++ consumption through nondairy foods

• Nondairy sources of Ca++ such as breads, cereals, vegetables, and fish, have a lower content or less bioavailable form. Ca++ -rich foods such as DGLV, tofu, nuts, legumes & sardines are not part of the standard diet

• Inadequate vitamin D intake, lack of exposure to sunlight & reduced vitamin D receptors in older adults all contribute

• Lack of phys. act., smoking, excessive alcohol consumption, diets Na & phosphorus

Barriers to Calcium Intake & Other Barriers to Calcium Intake & Other Factors Affecting Bone Mineral Factors Affecting Bone Mineral DensityDensity

Spinal Deviations of the Vertebral ColumnSpinal Deviations of the Vertebral Column

Intervertebral Disc & Intervertebral Disc & HerniationHerniation

Carpal Tunnel SyndromeCarpal Tunnel Syndrome

• Pathology: swelling of tendons reduces tunnel space -- squeezing & injuring median nerve

• Symptoms: numbness, tingling, pain, inflammation & clumsiness of the hand

• Diagnosis & treatment: Tinel’s test, Phalen’s test, nerve conductionvelocity studies, patient history & occupational evaluation; anti-inflammatory drugs, splints, avoidance of activities causing condition,surgery and alternative therapies