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74 Cards in this Set
- Front
- Back
What is the definition of Osteoporosis?
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A skeletal disorder characterized by compromised bone strength, pre-disposing a person to an increased risk of fractures
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What factors contribute to Bone Strength?
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1) Bone Mineral Density (BMD)
2) Bone Quality (Rate of Turnover, Mineralization, Micro-architecture) |
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What are the components of bone?
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i) Organic (30%):
1) Cells (2%); Osetoblasts, Osteocytes, Osteoclasts 2) Matrix (98%); Collagen Type 1, Bone Proteoglycan ii) Minerals (70%): Hydroxyapatite and other minerals |
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What are the types of Bone?
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Cortical (compact) and Trabecular (Cancellous)
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What are the characteristics of Cortical (compact) bone?
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1) Dense and Solid with few spaces
2) Surrounds the marrow space 3) Mainly mechanical and protective function 4) Makes up 80% of adult skeleton |
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What are the characteristics of Trabecular (cancellous) bone?
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1) Mesh-like bone located in the center of the bone
2) Much larger % of surface area in contact with bone marrow, blood vessels 3) Both metabolic AND mechanical function 4) Makes up 20% of adult human skeleton 5) More active, subject to more remodelling and turnover |
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Which parts of the skeleton have more trabecular than cortical bone?
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Vertebrae
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Which parts of the skeleton have more cortical than trabecular bone?
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Forearm and Femoral Neck
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Which parts of the skeleton have equal portion of cortical and trabecular bone?
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Trochanteric Region (hip)
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What are the functions of Bone?
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1) Mechanical: (protects internal organs and acts as a site of insertion for muscles and joints)
2) Metabolic: (mineral reservoir for calcium and phosphate homeostasis) 3) Hematopesis: (Bone marrow is the site of blood cell production) |
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What is the definition of Bone Remodelling?
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The continous coupled process of bone breakdown and renewal
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What are the functions of Bone Remodelling?
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1) Repair areas of micro-damage to the skeleton
2) Maintain skeletal mass 3) Participate in regulation of Calcium Homeostasis |
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What are the functions of Osteoclasts?
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To resorb bone
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What are the functions of Osteoblasts?
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To form new bone matrix (osteoid)
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What are the functions of Osteocytes?
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Mechanoreceptors/ Effectors embedded in bone
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What are the functions of Lining Cells?
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Have receptors for hormones and factors that initiate remodelling and has a role in recruiting and activating osteoclasts.
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Which of the bone cells are formed from large multi-nucleated cells from Hematopetic precursors?
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Osteoclasts
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Which of the bone cells are formed from local mesenchymal stem cells?
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Osteoblasts
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Which of the bone cells are formed from osteoblasts trapped within the bone they're formed from?
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Osteocytes
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Which of the bone cells are formed from osteoblasts that remain on the surface of the bone?
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Lining Cells (Osteoblastic Stromal Cells)
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What are the steps of the bone remodelling cycle?
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1) Activation: Initiating the Cycle
2) Resorption by Osetoclasts 3) Reversal 4) Bone Formation |
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How does the process of activation of happen in the bone remodelling cycle?
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1) Osteoblastic stromal cells begin to produce factors (e.g. macrophage colony stimulating factor and RANK-Ligand) that binds to osetoclast precursors
2) This initiates their replication and differentiation into multi-nucleated functional Osteoclasts 3) Circulating T-Lymphcytes and Bone Lining Cells may also participate in the process of Osteoclast Activation |
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What are the proteins involved in regulating Osteoclast activation?
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RANK-Ligand and Osteoprogerin (OPG)
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What is the role of RANKL in regulating Osteoclast activation?
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Binds to receptor (RANK) on pre-osteoclasts. Stimulates their development into fully differentiated osteoclasts and increases their activity
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What is the role of OPG in regulating Osteoclast activation?
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Binds to RANK-Ligand and prevents its interaction with RANK.
This opposes the differentiation and activation of Osteoclasts. |
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What factors increase the ratio of RANKL/OPG? What effect does this have?
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Parathyroid Hormone, Vitamin D and Some Cytokines.
Increases Osteoclast activity and bone resorption. |
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What factors decrease the ratio of RANKL/OPG? What effect does this have?
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Estrogen, TGF-β and Mechanical Force.
Decreases Osteoclast activity and bone resorption. |
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How do Oseoclasts perform resorption?
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1) Osteoclasts attach to the bone and integrins and forms a ruffled border
2) H+ is generated by the action of intracellular Carbonic Anhydrase II (CAII) is actively transported across the membrane of the ruffled border by the "H-ATPase proton pump". 3) A chloride channel coupled to the proton pump balances the charge of ions across the membrane 4) The organic matrix of the bone is removed by proteases such as Cathepsins and Collagenases |
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What happens after Bone Resorption and before Bone Formation?
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1) After resorption is complete; Osteoclasts detach and undergo Apoptosis
2) Other mononuclear cells cover the surface and form a cement line 3) This marks the limit of bone resorption and cements together the old and new bone |
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What are the steps of Bone formation?
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1) Mesenchymal stem cells are recruited and differentiate into pre-osteoblasts (by factors such as IGF-1 and TGF-β) there they proliferate and differentiate into mature osteoblasts
2) Osteoblasts secrete proteins of the bone matrix (osteoid) largely collagen. Unmineralized osteoid slowly re-fills the cavity 3) During this process some Osteoblasts become trapped in the newly formed Osteoid (to become Osteocytes) 4) Some osteoblasts undergo apoptosis and others become lining cells 5) Mineralization of bone with Hydroxyapatite then takes place |
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What are examples of Bone Remodelling Cycle Activators?
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Parathyroid Hormone (PTH), Vitamin D, Thyroid Hormones, Interleukins and TNF-α
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What are examples of Bone Remodelling Inhibitors?
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Calcitonin and Estrogen
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How does bone mass change with age in men and in women?
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Generally increases with age and levels off at around 35-40 yrs, and begins to decrease with age.
Women decrease more rapidly with the loss of Estrogen |
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What factors affect peak bone mass?
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1) Heredity 2) Mechanical Forces
3) Gender 4) Hormones 5) Nutrition 6) Risk Factors |
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What are the mechanisms of AGE related bone loss?
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1) Rate of initiation of bone remodelling cycles increases
2) Slight imbalance between Osteoclast and Osteoblast activity in each remodelling cycle (more bone is resorbed than formed again) |
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What are the effects of Estrogen on bone remodelling?
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i) Inhibits Osteoclast Precursors (reduced differentiation and activation)
ii) Inhibits Osteoclasts (decreased activity, increased apoptosis) iii) Increased Osteoblast lifespan and anabolic activity |
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What are the mechanisms of ESTROGEN deficient bone loss?
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1) Increased Osteoclast Activation and recruitment of increased BMU activation frequency
2) Reduced Osteoclast Apoptosis 3) Decreased activity and increased apoptosis of Osetoblasts |
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What are the effects of Glucocorticoids on bone remodelling?
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Rate of bone density loss is estimated to be 10-30%/year.
Bone density loss begins within first 3 months of use, peaks at 6 months and then drops to a slower steady rate. |
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What are the mechanisms of GC-induced bone loss?
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1) Inhibition of intestinal Ca absorption and increased urinary Ca loss
2) Direct Stimulation of bone resorption via increased RANKL expression 3) Decreased Osteoblast mediated bone formation 4) High dose of GCs also suppress Gonadotropin production |
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What are the effects of accelerated bone loss on bones?
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i) Cortical Bone becomes thinner and more porous
ii) Trabecular bone becomes weaker (due to decreased bone density, increased number of resorption pits, loss of trabecular connectivity) |
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"Thinning and eventual loss of trabecular connectivity in greatly weakened bones" True or False?
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TRUE
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What type of osteoporosis is associated with disproportionate loss of trabecular bone?
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Post-Menopausal
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What type of osteoporosis is associated with slower, steady loss of bone, proportionally from cortical and trabecular sites?
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Age Assoicated
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What are the common fracture sites of Post Menopausal Osteoporosis?
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Vertebral body and Distal Radius (wrist)
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What are the common fracture sites of Age Associated Osteoporosis?
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Vertebral body and Proximal Femur (Hip)
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What are the characteristics of Vertebral Body fractures?
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Most common type of fracture.
Up to 2/3 are asymptomatic but acute fractures are often very painful. Results in loss of height and curvature of spine. |
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What are the characteristics of Hip Body fractures?
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Most serious type of fracture.
Occurs more commonly in women than men over 80. Associated with 20-30% mortality within 1 year. |
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What are the characteristics of Wrist fractures?
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Also known as the Colles fracture
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What are "Crash Fractures"?
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Whole vertebrae gives out and collapses
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What are "Wedge Fractures"?
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One side of the vertebrae collapes but not the other side
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What are "Codfishing Fractures"?
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The center of the vertebrae collapes but the sides remain upright
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"Most hip fractures occur in the area just above the ball of the femur" True or False?
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False; Usually it is just below the ball of the femur (femoral neck region) and the area just below this (interochanteric region)
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What are the techniques used for measuring BMD?
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1) Dual Energy X-ray Absorptiometry (DEXA)
2) Single Energy X-ray Absorptiometry (SEXA) 3) Quantitative Computed Tomography (QCT) 4) Ultrasonography |
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What are the common sites of measuring BMD with a DEXA scan?
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Lumbar spine and Proximal Femur
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What are the common sites of measuring BMD with a SEXA scan?
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Forearm and Heel
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What are the common sites of measuring BMD with a QCT scan?
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Spine
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What are the common sites of measuring BMD with an Ultrasonography?
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Heel, Fingers, Tibia, Patella
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What are the characteristics of a DEXA scan?
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1) Precise
2) Low Radiation Exposure 3) Needs Skilled Operator 4) Currentlty the gold standard |
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What are the characteristics of a SEXA scan?
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1) Inexpensive
2) Measures sites unresponsive to therapy 3) Does not need skilled operator |
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What are the characteristics of a QCT scan?
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1) Poor reproducibility outside experienced labs
2) Accuracy comparable to DEXA 3) More expensive than DEXA |
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What are the characteristics of Ultrasonography?
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1) Inexpensive
2) Less Precise 3) Fairly Portable |
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What is the mechanism of a DEXA scan?
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X-rays from two different sources directed towards bone in alternating pattern.
As the emitted photons pass through the subject's tissues they are attenuated to an extent that depends on the tissues mineralization |
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How does the WHO define Osteoporosis?
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Based on comparison of patients BMD with the mean BMD obtained in a healthy, young adult populations
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What is the definition of the "T-score"?
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The number of standard deviations below or above the mean BMD of the young healthy adult population
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What is definition of Normal Bone?
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T-score greater than or equal to -1.0
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What is the definition of Osteopenia?
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T-score between -1.0 and -2.5
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What is the definition of Osteoporosis?
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T-score less than -2.5
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What is the definition of established (severe) Osteoporosis?
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Includes the presence of a non-traumatic fracture
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"For every 1 standard deviation decrease in BMD; the risk of fracture increases by ___"
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2
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"For the same level of BMD, 80 year olds have the same fracture risk as 60 year olds" True or False?
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False; For the same level of BMD, 80 year olds have 5 times increased fracture risk when compared with 60 year olds
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What are the major risk factors fro Osteoporotic Fractures?
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1) Age >65
2) Personal history of Fragility fractures 3) Systemic glucocorticoid therapy for more than 3 months 4) First degree relative with Osteoporotic fracture 5) Hypogonadism 6) Early Menopause (before age 45) 7) Pre-disposing medical conditions such as malabsorption and hyperparathyroidism |
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What are the minor risk factors for Osteoporotic Fractures?
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1) Past history of clinical hyperparathyroidism
2) Chronic Anti-convulsant therapy 3) Low dietary calcium intake 4) Smoking 5) Excessive Alcohol intake 6) Excessive Caffeine intake (>4 cups coffee/day) 7) Weight <57kg 8) Short term weight loss >10% from weight at age 25 9) Chronic Heparin Therapy 10) Rheumatoid Arthritis |
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What are the current BC health guidelines for when to recommend measuring BMD?
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Patients who have at least ONE MAJOR (or TWO MINOR) risk factors for Osteoporosis AND if the results are likely to Alter Patient Care
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What are the only groups of patients you would re-measure BMD within one year?
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1) Patients receiving >7.5mg Prednisone equivalents for more than 3 months
2) Patients with very low BMD 3) Patients with existing fractures |