BONE PHYSIOLOGY AND STRUCTURE
INTRODUCTION
Nicolas Andry coined the word from which the English word orthopaedics is derived when he wrote a book titled L'Orho'edie in
1741. Orthopaedics is derived from the two Greek words Andry chose: orthos, meaning straight or free from deformity, and pais, meaning child. Since that time orthopaedics has expanded to include the evaluation and treatment of all musculoskeletal injury and disorders. Until the later half of the twentieth century. orthopaedics was predominately the nonoperative treatment of fractures, treatment of musculoskeletal infections (often tuberculosis), and polio. As we enter the twenty-first century, orthopaedic surgery includes the replacement of
degenerated joints, operative fixation of fractures, arthroscopic repair of torn meniscus, rotator cuffs, and a whole host of other intra-articular abnormalities. Musculoskeletal research laboratories have found means of stimulating the body to make new bones and soon cartilage production will be accomplished. Gene therapies for a variety of musculoskeletal diseases are on the horizon. Orthopaedics is a dynamic field and orthopaedic surgeons treat both sexes and all ages of patients with a wide variety of skeletal, ligamentous, and muscular problems. Orthopaedics are involved in the management of a newborn's dislocated hip, a teenager's curved spine, an athlete's injury knee, a motor vehicle accident victim, an adult's worn-out joint, and an elderly woman's fracture hip The musculoskeletal system is a complex biomechanical organ. It is constantly responding to the demands of the patient. Bone is in constant turnover. It atrophies when not used. and hypertrophies when stressed. Overall bone mass is increased until some time between 30 and 35 years of age. after which there is an overall
decrease of bone as a consequence of more resorption than production. Bone can heal without leaving a scar. Articular cartilage is a special material because it has properties that people have not been able to reproduce. It is a wonderful shock absorber. yet when sliding with another surface of articular cartilage bathed in normal synovial fluid, the constant of friction is a fraction of that found with ice-on-ice. Unfortunately, upon reaching adulthood, the ability to generate new articular cartilage ceases and as it wears out or is injured, it is not replaced. Repair fibrocartilage. metal, and plastic are the materials currently substituted for articular cartilage.
Skeletal muscle accounts for almost 50% of the body's weight making it the single largest tissue mass in the human body. There is one basic structural unit in muscle fiber; however,
fibers varies depending on a particular muscle's function. Muscle fibers are either parallel or oblique with oblique fibers existing in various configurations
BONE PHYSIOLOGY
Bone is a specialized form of mesenchymal-derived connective tissue. It is a dynamic structure, with more functions than the obvious one of providing an artic ulating framework for muscles and soft tissues. Bones respond to the biomechanical stressesencountered, with subsequent adjustments in the architecture and mass of the skeleton (Wolff's law). In addition, bones provide the major store of the body's calcium and phosphate and so play an important role in mineral exchange.
Functions of bone
Supports body
INTRODUCTION
Nicolas Andry coined the word from which the English word orthopaedics is derived when he wrote a book titled L'Orho'edie in
1741. Orthopaedics is derived from the two Greek words Andry chose: orthos, meaning straight or free from deformity, and pais, meaning child. Since that time orthopaedics has expanded to include the evaluation and treatment of all musculoskeletal injury and disorders. Until the later half of the twentieth century. orthopaedics was predominately the nonoperative treatment of fractures, treatment of musculoskeletal infections (often tuberculosis), and polio. As we enter the twenty-first century, orthopaedic surgery includes the replacement of
degenerated joints, operative fixation of fractures, arthroscopic repair of torn meniscus, rotator cuffs, and a whole host of other intra-articular abnormalities. Musculoskeletal research laboratories have found means of stimulating the body to make new bones and soon cartilage production will be accomplished. Gene therapies for a variety of musculoskeletal diseases are on the horizon. Orthopaedics is a dynamic field and orthopaedic surgeons treat both sexes and all ages of patients with a wide variety of skeletal, ligamentous, and muscular problems. Orthopaedics are involved in the management of a newborn's dislocated hip, a teenager's curved spine, an athlete's injury knee, a motor vehicle accident victim, an adult's worn-out joint, and an elderly woman's fracture hip The musculoskeletal system is a complex biomechanical organ. It is constantly responding to the demands of the patient. Bone is in constant turnover. It atrophies when not used. and hypertrophies when stressed. Overall bone mass is increased until some time between 30 and 35 years of age. after which there is an overall
decrease of bone as a consequence of more resorption than production. Bone can heal without leaving a scar. Articular cartilage is a special material because it has properties that people have not been able to reproduce. It is a wonderful shock absorber. yet when sliding with another surface of articular cartilage bathed in normal synovial fluid, the constant of friction is a fraction of that found with ice-on-ice. Unfortunately, upon reaching adulthood, the ability to generate new articular cartilage ceases and as it wears out or is injured, it is not replaced. Repair fibrocartilage. metal, and plastic are the materials currently substituted for articular cartilage.
Skeletal muscle accounts for almost 50% of the body's weight making it the single largest tissue mass in the human body. There is one basic structural unit in muscle fiber; however,
fibers varies depending on a particular muscle's function. Muscle fibers are either parallel or oblique with oblique fibers existing in various configurations
BONE PHYSIOLOGY
Bone is a specialized form of mesenchymal-derived connective tissue. It is a dynamic structure, with more functions than the obvious one of providing an artic ulating framework for muscles and soft tissues. Bones respond to the biomechanical stressesencountered, with subsequent adjustments in the architecture and mass of the skeleton (Wolff's law). In addition, bones provide the major store of the body's calcium and phosphate and so play an important role in mineral exchange.
Functions of bone
Supports body
Produces Facilitates movement produce blood cells haematopoiesis
Stores minerals such as reservoir of phosphate and calcium
Regulates calcium haemostasis
Protects organs eg thoracic cage, which also facilitates ventilation
What are Hormonal control of bone activity
Hormonal control of bone activity is necessary for bone remodelling and growth, and the regulation of mineral exchange
With respect to mineral exchange, bone provides an enormous reservoir of calcium from the body, and the main hormones acting on bone are involved with calcium homeostasis.Calcium is involved in many physiological functions (muscle contraction, intracellular messengers, control of neural excitability) and serum levels are under tight physiological regulation. Usually 50% of calcium is carried bound to albumin, and the remainder is in the free ionized form
Total serum calcium is 2.2-2.6 mmol/litre, depending upon the bound (albumin) fraction
What are Hormone acting on bone
Vitamin D
• Natural vitamin D (cholecalciferol) derives from the diet or indirect action of UV light on precursors in the skin
•Conversron to active metabolite requires liver (cholecalciferol to 25-hydroxy cholecaloterol and kidney to 1,25-dihydroxycholecalciferol, DHCC
• Production of 1,25 DHCC is controlled by PTH and phosphate increased PTH or decreased phosphate increases amount of 1.25 DHCC produced
• Increased 1, 25-DHCC. increases calcium and phosphate absorption from the intestine and stimulates osteoclasts lead to increases serum calcium
•Low vitamine D levels result in rickets and osteomalacia
Parathyroid hormone PTH
Fine regulator of calcium exchange (maintains extracellular calcium within narrow limits Produced by the chief cells of parathyroid glands in response to low calcium concerntration
• Target organs arebone and kidney
• Causes reabsopation of bone by osteoclasts in response to low serum calcium
• Decreases renal calcium excretion in response to low serum calcium (with subsequent increase In phosphate excretion, - this effect is rapid
• Primary hyperparathyroidism (eg parathyroid adenoma) causes hypercalcaemia
• Secondary hyperparathyroidism (eg renal disease) causes increased secretion of PTH with resultant de-calcification of bone and pathological fractures
• Hypoparathyroidism (eg surgical removal of parathyroid glands) causes hypocalcaemia with hyperphosphataemia
Calcitonin
•Opposite action of PTH
• Produced in parafollicular (C) cells of the thyroid
• Inhibits bone resorption by osteoclasts in response to high serum calcium
• Increases renal calcium excretion in response to high serum calcium
ThyroxineT4
• Catabolic (causing breakdown of bone tissue
• Hypercalcaemia and hypercalcuria are seen in thyrotoxicosis (low PTH level)
Growth hormone GH
• Normally released in response to hypoglycaemia from the pituitary gland in a negative feedback loop in the hypothalamic-pituitary axis
• Affects glucose metabolism and growth
• Stimulates production of IGF-1 in liver and other tissues (lGF-1 leads to increased bone growth)
• Too much growth hormone (eg pituitary adenoma) leads to gigantism prior to puberty or acromegaly after epiphyseal plates have fused. Acromegaly causes general thickening of bones and soft tissues
Glucocorticoids
High levels of glucocorticoids cause
• Reduced bone matrix
• Increased bone resorption
• Potentiation of PTH
• Reduced calcium absorption from gut
High levels of glucocorticoids therefore result in
• Osteoporosis
• Fractures
• Vertebral body collapse
• Avascular necrosis of femoral head
• Growth retardation in children
Oestrogens and androgens hormones
Stores minerals such as reservoir of phosphate and calcium
Regulates calcium haemostasis
Protects organs eg thoracic cage, which also facilitates ventilation
What are Hormonal control of bone activity
Hormonal control of bone activity is necessary for bone remodelling and growth, and the regulation of mineral exchange
With respect to mineral exchange, bone provides an enormous reservoir of calcium from the body, and the main hormones acting on bone are involved with calcium homeostasis.Calcium is involved in many physiological functions (muscle contraction, intracellular messengers, control of neural excitability) and serum levels are under tight physiological regulation. Usually 50% of calcium is carried bound to albumin, and the remainder is in the free ionized form
Total serum calcium is 2.2-2.6 mmol/litre, depending upon the bound (albumin) fraction
What are Hormone acting on bone
Vitamin D
• Natural vitamin D (cholecalciferol) derives from the diet or indirect action of UV light on precursors in the skin
•Conversron to active metabolite requires liver (cholecalciferol to 25-hydroxy cholecaloterol and kidney to 1,25-dihydroxycholecalciferol, DHCC
• Production of 1,25 DHCC is controlled by PTH and phosphate increased PTH or decreased phosphate increases amount of 1.25 DHCC produced
• Increased 1, 25-DHCC. increases calcium and phosphate absorption from the intestine and stimulates osteoclasts lead to increases serum calcium
•Low vitamine D levels result in rickets and osteomalacia
Parathyroid hormone PTH
Fine regulator of calcium exchange (maintains extracellular calcium within narrow limits Produced by the chief cells of parathyroid glands in response to low calcium concerntration
• Target organs arebone and kidney
• Causes reabsopation of bone by osteoclasts in response to low serum calcium
• Decreases renal calcium excretion in response to low serum calcium (with subsequent increase In phosphate excretion, - this effect is rapid
• Primary hyperparathyroidism (eg parathyroid adenoma) causes hypercalcaemia
• Secondary hyperparathyroidism (eg renal disease) causes increased secretion of PTH with resultant de-calcification of bone and pathological fractures
• Hypoparathyroidism (eg surgical removal of parathyroid glands) causes hypocalcaemia with hyperphosphataemia
Calcitonin
•Opposite action of PTH
• Produced in parafollicular (C) cells of the thyroid
• Inhibits bone resorption by osteoclasts in response to high serum calcium
• Increases renal calcium excretion in response to high serum calcium
ThyroxineT4
• Catabolic (causing breakdown of bone tissue
• Hypercalcaemia and hypercalcuria are seen in thyrotoxicosis (low PTH level)
Growth hormone GH
• Normally released in response to hypoglycaemia from the pituitary gland in a negative feedback loop in the hypothalamic-pituitary axis
• Affects glucose metabolism and growth
• Stimulates production of IGF-1 in liver and other tissues (lGF-1 leads to increased bone growth)
• Too much growth hormone (eg pituitary adenoma) leads to gigantism prior to puberty or acromegaly after epiphyseal plates have fused. Acromegaly causes general thickening of bones and soft tissues
Glucocorticoids
High levels of glucocorticoids cause
• Reduced bone matrix
• Increased bone resorption
• Potentiation of PTH
• Reduced calcium absorption from gut
High levels of glucocorticoids therefore result in
• Osteoporosis
• Fractures
• Vertebral body collapse
• Avascular necrosis of femoral head
• Growth retardation in children
Oestrogens and androgens hormones
Anabolic hormones which may promote epiphyseal closure
what are the effect of nutrition on bone
The prime requirements for a healthy skeleton are adequate calories, calcium, and vitamin along with phosphate, fluoride, magnesium and vitamin C . Even a very mild degree of malnutrition can lead to reduced bone density in the long term, increasing the risk of osteoporotic fractures.
Calories
Calorie deficiency and protein deficiency result in poor healing and poor recovery from fractures.
Calcium
Potential causes of decreased calcium absorption
Phytates from cereals. peas, beans and nuts reduce calciurn absorption. These phytates are inactivated by the enzyme phytase. Yeast contains phytase (the human gut does not) levened breads is not a problem; large quantities of unlevened breads on the diet may result in inadequate calcium absorption
Steatorrhoea insoluble calcium soaps in the gut reduce absorption
Potential causes of increased urinary calcium loss
High sodium intake
Caffeine
High ratio of protein to calcium intake (only a problem when calcium intake and absorption are low)
Vitamin D
Vitamin D deficiency leads to rickets
Other important nutrients
• Magnesium: Important in hydroxyapatite crystallisation
, Vitamin C: scurvy is the result of inadequate dietary vitamin C; it results in failure of collagen synthesis and clotting abnormalities, and results in subperiosteal haemorrhage
, Vitamin K
• Zinc
• Manganese
• Copper
• Boron
What are the effects of ageing on the structure of bone?as noticed that Continued bone resorption and formation occur throughout life. 'This process is known as remodelling . during growth the bone increases in size, and new bone is added by endochondral ossification (at the physis), subperiosteal appositional ossification at the surface and endosteal resorption (to expand the medullary cavityBetween the ages of 20 and 40 cortical thickness increases, and Haversian canals and intertrabecular spaces-fill in, making bone heavier and stronger.
• After40 there is a slow, steady loss of bone, with enlargement of the Haversian spaces, thinning of the bony trabeculae and expansion of the medullary space. Bone mass therefore decreases. This age-related osteoporosis is accelerated in women at the menopause due to oestrogen withdrawal
With further advances in age, bone loss Increases, with additional factors such as malnutrition lack of weight-bearing exercise, and chronic disease also contributing .
. BONE STRUCTURE
Bone is a connective tissue. It is unique in that it normally mineralises. It consists of an organic matrix and an inorganic matrix.
Organic matrix (35%) is composed of bone proteins (predominantly type 1collagen) and bone-forming cells - osteoprogenitor cells, osteoblasts and osteocytes (derived from osteoblasts). The generation and stimulation of these cells is regulated by cytokineSand growth factors.
Inorganic matrix (65%) is composed of mainly calcium hydroxyapatite, which contains 99% of the body's calcium store and 85% of body phosphorus. The inorganic matrix also houses 65% of sodium and magnesium stores.
Bone proteins
The proteins of bone include type I collagen and non collageneous proteins that are derived from osteoblasts remember that bone in different situations is composed of differing amounts of bone components
Type I collagen
This makes up 90% of the organic component. Osteoblasts deposit collagen either in a random weave (woven bone) or an orderly layered manner (lamellar bone). These differences can be seen histologically.
Non-collagenous proteins
these are bound to the matrix. They are adhesion proteins, calcium-binding proteins, unerahsauon proteins, enzymes, cytokines, and growth factors,
Bone cells
osteoblasts and osteoclasts act in coordination and are considered the functional unit one They are instrumental in the processes of bone formation and bone resorption,
osteoprogenitor cells Derived from pluripotential mesenchymal stem cells
located in the vicinity of all bony surfaces
• The only bone cells which divide
Daughter cells are called osteoblasts
:Osteoblasts
• Derived from osteoprogeritor cells
, Their function is to build bone
• Located on the surface of bone
• Synthesise. transport and arrange the many proteins of the matrix
Initiate mineralisation
Exhibit cell surface receptors that bind to PTH, vitamin D, oestrogen, cytokines,growth factors and extracellular matrix proteins
• Pole in hormonal regulation of bone resorption
Osteocytes
, Derived from osteoblasts (osteoblasls surrounded by matrix are known as osteocytes,these are mature bone cells
• Their function is to maintain bone
Most numerous type of bone cell in mature bone
Communicate With each other and with surface cells via a network of tunnels through the matrix (canaliculi); this network may control the fluctuations in serum calcium and phosphate by altering their concentration in the local extracellular fluid Translate mechanical forces into biological activity eg bone remodelling
OSTEOCLASTS
Derived from haematopoietic progenitor cells of monocyte/macrophage lineage
• Their tunction is to reabsorb bone
Cytokines are crucial tor osteoclast differentiation and maturation (II-1. IL-3, IL-6 and IL-l1. TNF and GM-CSF
Mature osteoclasts are multinucleated (15-20 nuclei
, Found at sites of active bone resorption, close to the bone surface in pits known as howship,s lacunae
How does an osteoclast break down bone?
Osteoclast activity is initiated by binding to matrix adhesion proteins. The osteoclast cell membrane becomes modified by villous extensions on the matrix interface, which increases the surface area. The plasmalemma bordering this region forms a seal with the underlying bone, preventing leakage of digestion products and creating a self contained extracellular space. The osteoclast acidifies this space with a hydrogen pump system that solubilises the mineral. It then releases a multitude of enzymes that break down the matrix proteins into amino acids and liberate and activate growth factors and enzymes. Thus. as bone is broken down to its elemental units. substances are released that initiate its renewal.
What are Bone types
Woven bone which is characterized by
• Immature bone seen in fetal skeleton. growth plates and callus
• Product of rapid bone formation
• Irregular and disorganised arrangement of collagen
• Mechanically weak
• Indicative pathological state in adult eg in circumstances requiring rapid repair such as fractures
• Forms around site of infection
• Comprises the matrix of bone-forming tumours
Lamellar bone which is characterized by
• Regular orderly arrangement of collagen fibres into sheets lamellae
• Mechanically strong
• Graduallv replaces woven bone, but is deposited much more slowly
Can be cortical (compact) or cancellous (trabecular) bone
, Cortical bone is rigid and has no marrow. with well defined Haversian canals lying parallel to the long axis of the bone providing good vascular supply Cancellous bone lies inside the cortical layer, contains marrow in spaces between trabeulae. and has no blood vessels (therefore osteocytes rely on diffusion from medullary blood vessels)
Periosteum
Bones are covered by periosteum, a moderately thick layer of fibrocellular tissue which is attached in the underlying bone strongly by Sharpey's fibres. There are two layers: the carmbrial inner and the fibrous outer.
functions of the periosteum include
Anchor: provides a firm attachment for tendons and ligaments
Source of osteoprogenitor cells: required for bone remodelling and fracture healing loss of the periosteum significantly impairs fracture healing
• Nutrition: blood vessels running within the deep layer supply the underlying bone
Development, ossification, and growth of bone
Bone develops from the condensation of mesenchymal tissue during the 5th week of embryonic development. Bones may ossify directly (intramembranous, as in the clavicle) or chondrocytes may produce a hyaline cartilage template which then ossifies (endochondral ossification. as in the tibial.
long bone development
A typical long bone develops by endochondral ossification and consists of: Diaphysis (shaft): a tube of cortical bone
Metaphysis: a conical area of cancellous bone facilitating load transfer from the
articular surface to the diaphysis
Physis: .a growth plate, the zone of growth and ossification
Epiphysis: .articular surface and thin zone of cancellous bone above dividing chondrocytes
The primary ossification centre of a long bone appears in the diaphysis. Secondary centres appear in the epiphysis in some bones there may be multiple secondary centres, as in the distal humerus. At the ossification centre the chondrocytes hypertrophy and die. The cartilage becomes calcified The majority of each bone is ossified at birth.
Longitudinl growth of the bone occurs at the growth plate. Circumferential growth occurs below the periosteum. Osteogenic cells in the cambrial layer produces new bone; this layer is very thick and vascular in children.
Growth plates develop between primary and secondary centres
The physis (or growth plate) has four zones
• Resting zone: resting chondrocytes on epiphyseal side of physis
• Proliferative zone: dividing chondrocytes
Hypertrophic zone: maturing chondrocytes
• Zone of provisional calcification: new bone is formed on the metaphyseal side of the physis
physeal fractures occur between the hypertrophic and calcification zones
Bone is a dynamic structure that constantly undergoes remodelling. The trabeculae are formed in response to the loads placed upon the bone, and the trabecular pattern will changed if the Loads are changed. This is Wolff,s law. As the bone grows, remodetltng occurs
Blood supply of bone
The vascular supply to bone is important for bone growth and healing, for calcium metabolism and haematopoiesis. It has a role in tumour dissemination and in the response to bone infection 5-10% of the total cardiac output is distributed to the bone
Generally the vascular supply to bone includes
Nutrient artery: perforates cortex of the bone and supplies bone marrow and tabecular bone
Vessels accompanying tendons and ligaments: supply periosteum and adjacent bone cortex
• Circulus vasculosus an arterial plexus surrounding the epiphysis derived from regional arterial branches, which supplies the epiphysis prior to union with the main bone; after union, vessels communicate with the vascular supply of the main bone
The blood supply of the long bone is from four sources nutrient artery:supplies the diaphysis marrow and trabeculae
• Metaphyseal vessels :from the surrounding joint anastomosis supply the epiphyseal end of the diaphysis the metaphyseal region is the most vascularised part of bone
• Epiphyseal vessels : from surrounding joint vessels
• Periosteal vessels
Venous flow is from the cortical capallaries draining to sinusoids and then into emissary venous system
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