Osteoporosis

Question 1

osteoporosis literal meaning

Answer 1

porous bone

Question 2

osteoporosis defination

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A combination of decreased bone mass and micro-damage to the bone structure that results in an increased susceptibility to fracture

Question 3

Primary Osteoporosis etiology

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Most common, occurs in both genders, yet follows menopause in females and occurs later in life in males

Post-menopausal/estrogen deficient
Age related/senile
Mild/prolonged negative calcium balance

Question 4

Secondary Osteoporosis etiology

Answer 4

associated with medication, other conditions, or diseases

Cortico-steroids/heparin/anti-convulsants/alcohol/mal-nutrition/endocrine disorder

Question 5

Most common metabolic bone disease

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osteoporosis

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When affected, men have a higher

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morbidity and mortality rate compared to women (30% compared to 9%)
Men are affected at a later age, therefore, prognosis is worse

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Bone: 2 purposes

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1) rigid framework for the body

2) readily available and interchangeable calcium pool

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Appropriate balance must exist between

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formation and resorption

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Mineral resorption occurs at

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the expense of bone formation

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Bone: Composed of a

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complex meshwork of collagen fibers inlaid with calcium and phosphate, mixed with water resulting in a hard, cement-like substance called hydroxyapatite/osteoid.

Question 11

Minerals in bone

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Sodium, magnesium, and potassium are also present in smaller concentrations

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Bone composition:

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Trabecular bone: (spongy or cancellous bone) is the central meshwork of bone

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@ 20% of the adult skeleton/

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large surface area

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Bone Very sensitive to

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metabolic and/or hormonal influences

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Cortical bone: (compact bone)

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found primarily in the shafts of long bones and comprising 80% of skeletal mass

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80%-90% of cortical bone is calcified, whereas

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only 15% to 25% of trabecular bone mass is calcified

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The remaining volume of bo e

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is composed of bone marrow, fat, and blood vessels

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Bone resorption is a

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surface area event

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Bone renews itself through a constant process called

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remodeling

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Remolding

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Repeated cycle of osteoclastic, which is breaking down the existing bone (resorption) and osteoblastic activity which is laying down new bone cells for mineralization(formation)

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BMD: Increases during

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growth and development

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Peak bone mass achieved in

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the third decade of life

This is the reserve for the rest of the person’s life

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Osteoporosis: begins when bone formation

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falls behind resorption

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Menopause: reduction in circulating concentrations of

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estradiol and progesterone

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Bone strength is a function of

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skeletal load

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May be the only natural process in order to induce formation modeling in

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mature bone

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Young bone responds tremendously well

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to loading

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New theories regarding remodeling: | Voltage potential generated from

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muscle contraction

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Remodeling: Maintains the

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strength and integrity of the skeleton by replacing fatigued/older/weakened bone with new bone

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Remolding makes a

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Storage site for vital minerals

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Calcium:

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Heart rate regulation, muscle contraction, blood pressure

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When low plasma Ca++, then calcium is

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resorbed from the bone via PTH mechanism

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Bone Remodeling:

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Modified by immune triggers | T and B cells and neural pathways

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Modified by immune triggers derived from

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T-cell and neural pathways

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Estrogen deficiency triggers reproductive aging through:

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Amplification of TNF producing T-cells Lack of trabecular estrogen receptor stimulation results in reduced anabolic stimulus Increased bone resorption by inducing inflammation responses to heightened levels of: Interleukin-1 and TNF Occurs most prevalently in trabecular bone Femoral neck/vertebral body/calcaneous/carpals

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Interleukin-1 and TNF are the most

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potent osteoclastic stimulators

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Estrogen deprivation results in:

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Increased T-cell concentrations in the bone marrow TNF is produced from those T-cells, in conjunction with IL-1, enhance bone resorption through lysosome stimulation SERMs block this cascade

Question 38

``` Loss of height (real or pseudo?) Postural Changes: Unstable abdominal/lumber stabilization muscles Forward head, kyphosis (dowager’s hump) Loss of lumbar lordosis Posterior pelvic tilt Scapular protraction All resulting in significant loss of height Contributing to loss of height are vertebral compression fractures Muscular pain: Lumbar paraspinal extensor spasm/burning Thoracic musculature burning Fractures: Vertebral bodies Hip Radius Ribs Femur ```

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Clinical manifestions for osteop

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Diagnosis:

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History/Observation: posture/loss of height Bone mineral density testing: osteoporosis is labeled at > -2.5 standard deviations from the norm, with osteopenia labeled at -1.0 to -2.5 standard deviation from normal bone mass Dual Energy X-ray absorptiometry (previously DEXA, now called DXA) most sensitive CT scan X-ray: can detect osteopenia and fractures Laboratory testing: biochemical markers of bone turnover

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Two modes: of treatment

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``` Antiresorptive Drugs Bisphosphonates Selective Estrogen Receptor Modulators (SERMs) Anabolic Drugs Parathyroid Hormone ```

Question 41

Bisphosphonates: Indications:

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Treatment and prevention of osteoporosis in men, post menopausal women, post glucocorticoid use, and treatment of Paget’s disease Generic/trade names: Alendronate/Fosamax etidronate/didronel ibandronate/Boniva Excreted in the kidneys, rapidly absorbed from the blood stream into the bones Adverse reactions: Abdominal pain, nausea, dyspepsia, constipation, diarrhea, Gerd, bone and muscle pain, osteonecrosis of the jaw and femur

Question 42

Bisphosphonates: Mechanism of action

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Demonstrates preferable localization to sites of bone resorption on hydroxyapatite Sites of bone resorption are in conjunction with osteoclasts Inhibit the activity of osteoclasts 10x more attracted to osteoclasts than osteoblasts Studies show that normal bone forms on top of the bisphosphonate Must be continuously added as it is not pharmacologically active, or else the new bone formation will be resorpted

Question 43

Ultimately, bisphosphonates slow the rate of

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bone turnover, so bone formation exceeds bone resorption Not to be taken for more than 10 years as it weakens bones, which resulted in: Musculoskeletal pain Osteonecrosis of the jaw Femoral fractures Renal impairment

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Selective Estrogen Receptor Modulators:

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Activate estrogen receptors on some tissues and blocks the receptors on other tissues Activate receptors on bone and vascular tissue Act as estrogen antagonists (blockers) on uterine and breast tissue Produce favorable effects on bone mineralization and cardiovascular tissue Reduce the carcinogenic effects of estrogen on breast and uterine tissue

Question 45

Parathyroid Hormone:

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Synthesized in the cells of the parathyroid gland Regulated by the concentration of plasma calcium Calcium receptor located on the surface of the parathyroid gland Decrease in plasma calcium activates the receptor Increase in plasma calcium results in receptor inhibition Alters calcium metabolism in bone, kidney, and gastrointestinal tract PTH directly affects skeletal tissue by increasing bone turnover, resulting in calcium liberation from skeletal storage.

Question 46

High levels of PTH result in increased osteoclastic activity, releasing calcium into the blood . PTH increases reabsorption of calcium from the kidneys Results in decreased phosphate levels through increased phosphate excretion Increases calcium digestion from the gastrointestinal tract PTH increases the conversion of Vit D to calcitriol which directly stimulates calcium absorption from the intestine Normal, or intermittent PTH release has been shown to enhance bone formation (stimulates osteoblastic activity and promotes bone formation: Very anabolic) Can utilize calcitonin to decrease plasma calcium concentrations and add mineralization to the bones, but less effective than bisphosphonates Vitamin D toxicity can cause death Calcium supplements: help to prevent bone loss, mildly effective Supplements alone cannot prevent osteoporosis: Encourage bone formation in conjunction with Wolfe’s Law

Answer 46

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Question 47

Performing weight bearing and resistive exercise, most beneficially early in life while skeletal tissue is more anabolic opposed to catabolic, appeared to be the most significant mode to prevent osteoporosis. Bone: Physical activity increased blood supply to muscle which also resulted in circulatory enhancement to bone tissue with increased nutritional supply, hormones, oxygen, etc. Bone growth: Reacted to rhythmic physical activities Tended to be insensitive to static loading Required intermittent GH and PTH Exercise during premenopausal/young adulthood rarely increased bone mass as that individual’s bone mass had already been maximized

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Question 48

Exercise into adulthood serves to preserve BMD (Turner, et al.,2006). Study: Post-menopausal former athletes compared with non-athletes All participants demonstrated similar levels of activity for the 15 years prior to the study The sedentary control group demonstrated significantly lower BMD when compared to the groups of former athletes

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Question 49

Wallace, Boxall, & Riddick (2004) reported that women were more willing to alter their diet than increase physical activity Sinaki (2008) reported that most osteoporotic related non-vertebral fractures were a direct result of fall Study: Femoral neck T-score based on DXA Exercise group (resistance/aerobic/balance/joint mobility)/control group 11 month protocol Femoral neck T-score significantly improved in the exercise group BMD decreased in the control group Exercise group also demonstrated improved QOL scores and improved scores on physical function tests

Answer 49

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Question 50

A major contributor to osteoporosis that is rarely mentioned in the literature is the calcium carbonate buffer system that is essential to the maintenance of a neutral physiologic environment. Under conditions of physiological high acid loads, which tend to be derived from: Standard American diet (SAD) Lifestyle Medications Bone becomes demineralized in an attempt to neutralize the physiologic state of reduced pH Over a prolonged time period, this environment results in osteopenia, and osteoporosis �

Answer 50

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