Conditions Affecting the Musculoskeletal System and PharmacotherapyPart Three: Metabolic DX – Osteoporosis and Fractures Flashcards
Exam 4 (Final)
Normal A&P: Calcium
What are the roles of calcium?
Blood coagulation
Integrity
Normal A&P: Calcium
Roles of Calcium: Integrity of what?
Bones, nerves, muscle, heart
Bones remodel continuously
Normal A&P: Calcium
Roles of Calcium: Integrity
Bones remodel continuously what is involved?
osteoclasts resorb (breakdown) old bone
osteoblasts lay down new bone
Osteoclasts
Resorb (breakdown) old bone
Osteoblasts
lay down new bone
Normal A&P: Calcium
Where is the majority of calcium stored?
Majority stored in bone ~ 98%
Normal A&P: Calcium
Factors affecting regulation of calcium include:
PTH
Vitamin D
Calcitonin
Normal A&P: Calcium
When not stored in the bones, where is calcium located?
Remainder present in blood
Normal A&P: Calcium
What are normal levels?
Normal (Total): 8.9 to 10mg/dL
Normal A&P: Calcium
When in the blood, what is calcium binded to?
50% bound to albumin, citrate, & phosphate
Normal A&P: Calcium
When in the blood, calcium is binded to proteins, when not attached to protein how is it?
50% free, active, ionized, clinically important & participates in bodily processes
Normal A&P: Calcium
Calcium absorption: Where is calcium absorbed?
Small intestines ~ ingested calcium
Normal A&P: Calcium
Calcium absorption: What is calcium absorption increased by?
Increased by PTH & vitamin D
Normal A&P: Calcium
Calcium absorption: What is it reduced with?
Meds:
Oxalic acid
Phytic acid & insoluble fiber
Normal A&P: Calcium
Calcium absorption: What meds reduce calcium absorption?
GCs, Cinacalcet, some chemo, TCNs, Levothyroxine, Phenytoin, Phenobarb, Loops
Normal A&P: Calcium
Calcium absorption: What are examples of oxalic acid that reduce calcium absorption?
Oxalic acid ~ spinach, rhubarb, swiss chard, beets
Normal A&P: Calcium
Calcium absorption: What examples of Phytic acid & insoluble fiber
that reduce calcium absorption?
bran, grain cereals
Normal A&P: Calcium
Calcium excretion: Where is it primarily excreted?
Primarily through kidney
Normal A&P: Calcium
Calcium excretion: Calcium primarily excreted through the kidney is determined by what?
Loss determined by GFR & tubular reabsorption
Normal A&P: Calcium
Calcium excretion: Calcium primarily excreted through the kidney-what is excretion reduced by?
Excretion reduced by PTH & vitamin D, & thiazides
Normal A&P: Calcium
Calcium excretion: Calcium primarily excreted through the kidney-what is excretion increased by?
Increased excretion ~ loops, calcitonin
Normal A&P: Calcium
What happens when there is Low Serum Calcium?
PTH (pulls) secretion
Normal A&P: Calcium
When there is Low Serum Calcium, PTH pulls secretion, what does this promote?
Ca resorption from bone
Tubular reabsorption of Ca from kidney
Activation of vitamin D promotes increased absorption of calcium from the intestine
Pulls from bones –> demineralized
Normal A&P: Calcium
What does Vitamin D do?
Increases calcium resorption from bone
Decreases calcium excretion by the kidney
Increases calcium absorption from the intestine
Normal A&P: Calcium
What does Vitamin D work similar to?
Works similar to PTH
Normal A&P: Calcium
What does a high serum calcium do?
Ca leaves blood, causing a Suppression of PTH release
and no vitamin D activation
Normal A&P: Calcium
What happens when calcitonin (keeps) is released by thyroid?
decrease plasma Ca levels
Inhibits calcium resorption in bone
increase in renal excretion
No effect on calcium absorption
Slide 5
Normal A&P: Vitamin D3
Pharmokinetics: Where is Vitamin D3 absorbed from?
Absorbed from small intestine
Normal A&P: Vitamin D3
Pharmokinetics: What is needed for Vitamin D3 to be absorbed?
Need bile for absorption
Normal A&P: Vitamin D3
Pharmokinetics: Where is Vitamin D3 stored?
Stored in liver
Normal A&P: Vitamin D3
Pharmokinetics: Where is Vitamin D3 excreted?
Excreted in bile
Normal A&P: Vitamin D3
Pharmokinetics: What converts Vitamin D3 to its active form?
Kidney converts it to active form
Normal A&P: Vitamin D3
Pharmokinetics: How is Vitamin D3 excreted in urine?
Urinary excretion minimal
Vitamin D:
What are the forms of Vitamin D?
Ergocalciferol (vitamin D2)
Cholecalciferol (vitamin D3)
Vitamin D:
What form of Vitamin D occurs in plants?
Ergocalciferol (vitamin D2)
Vitamin D:
What is Ergocalciferol (vitamin D2) used for? In what form are they?
Used for hypoparathyroidism,
Vit D-resistant rickets,
hypophosphatemia
Capsules & solution
Vitamin D:
How is Cholecalciferol (vitamin D3)
produced?
Produced naturally from sunlight
Vitamin D:
What food has Cholecalciferol (vitamin D3)? How else is D3 available?
Animal-sourced foods (oily fish, egg yolk, butter)
Available pharmaceutically (multiple doses)
Vitamin D:
What are therapeutic uses of Cholecalciferol (vitamin D3)? How is it available?
Therapeutic uses
Deficiency – px & tx
Bone health
Calcium absorption
Capsules, liquid, tablets
Vitamin D: What are Physiologic actions similar to?
Similar to PTH
Vitamin D: What are Physiologic actions of Vitamin D?
Increases Ca & Phos
Vitamin D:
Physiologic actions of Vitamin D: How does Vitamin D increase Ca and Phos?
↑ intestinal Ca absorption
↑ resorption Ca in bone
↓ renal Ca excretion
Vitamin D toxicity:
What are early symptoms?
Early symptoms: Weakness, fatigue, nausea, vomiting, anorexia, abdominal cramping, constipation
Vitamin D toxicity:
What are later symptoms?
Later symptoms:
Kidney function is affected:
resulting in polyuria, nocturia, and proteinuria
Vitamin D toxicity:
What are neurological symptoms?
Neurologic: Seizures, confusion, ataxia
Vitamin D toxicity:
What other issues can it lead to?
Cardiac dysrhythmia
Coma
Calcium deposition in soft tissues – can damage heart, BVs, lungs, kidneys
Decalcification of bone
Vitamin D toxicity:
What is treatment?
Stopping vit D intake
IV fluids
GCs suppress calcium absorption
If severe, renal excretion of Ca accelerated by furosemide
Normal A&P of bones;
How does continuous remodelling occur?
Continuous remodeling ~ marrow
Normal A&P of bones;
What happens to bone mass over time?
Bone Mass △ across lifespan
Normal A&P of bones;
When does bone mass peak?
Peaks in third decade
Normal A&P of bones;
When does bone mass stay stable until? What then happens?
Remains stable to 50yo –> slow decline (less than 1% a year)
Normal A&P of bones;
Why does bone mass Remain stable to 50yo –> slow decline (less than 1% a year)?
Resorbed bone not replaced with new bone –>fragile
Normal A&P of bones:
Postmenopausal females: What happens to bone mass?
Accelerated loss (2-3% yearly)
Resorption outpaces > deposition new bone
Normal A&P of bones:
Where do both osteoclasts and osteoblasts originate from?
Both osteoblasts & clasts originate in bone marrow
Normal A&P of bones:
Where do Osteoclasts (“the chewers”) develop?
Cells that develop from (spongy) bone marrow
Normal A&P of bones:
Where do Osteoblasts (“the builders”) originate?
Originate from stem cells
Normal A&P of bones:
How do Osteoblasts (“the builders”) create new bone?
Create new bone matrix by depositing minerals and collagen
Normal A&P of bones:
When do Osteoblasts (“the builders”) create new bone?
Lay down/rebuild new bone during remodeling process
What are the steps to how old bone is removed and new bone is placed?
- Bone with lining cells covering the surface.
- Resorption of old bone by osteoclasts
- Osteoblasts migrate to the absorption site
- Osteoblasts deposit osteoid, matrix of collagen and other proteins.
- Osteoid undergoes calcification
What is the most common disorder of calcium metabolism?
Osteoporosis
Osteoporosis: What occurs with this disease? What does this do to patients?
Low bone mass and increased bone fragility
Renders patients vulnerable to fractures from minor trauma.
Osteoporosis: How are fracture risks?
Spontaneous
Secondary to minor events
coughing, rolling over in bed, falling from standing position
↑ mortality
Osteoporosis:
What are the most common sites of osteoporotic fractures are:
Most common sites of osteoporotic fractures are the vertebrae, wrist, hip, ribs, and long bones of the arms and legs.
Osteoporosis:
Who does osteoporosis occur in mainly? Why?
Mainly in the elderly, because after age 50 men and women experience aging-related bone loss that is slow but relentless.
women experience several years of accelerated bone loss after menopause
Osteoporosis:
What is the primary prevention?
Calcium, vitamin D, lifestyle
Patho of Osteoporosis: What is the main idea?
Osteoblast activity < osteoclast activity
Patho of Osteoporosis:
Osteoblast activity < osteoclast activity
What does this mean?
Old bone resorbed faster than new bone formed
Patho of Osteoporosis:
What is a protein used to control bone breakdown?
RANKL
Patho of Osteoporosis:
How does RANKL work?
binds to a receptor on osteoclasts, activating them
Patho of Osteoporosis:
What stops RANKL work?
OPG (Osteoprotegerin) that acts like a “brake” on RANKL
Patho of Osteoporosis:
Why would
Osteoblast activity < osteoclast activity
occur (having to do with proteins)
Too much RANKL and not enough OPG
Patho of Osteoporosis
What happens to bone?
Spongy bone become porous
Patho of Osteoporosis:
When spongy bone becomes porous, what happens?
Leads to a significant reduction in BMD, bones –> brittle, fragile.
Compact bone becomes thin
Patho of Osteoporosis:
How can it occur?
Can occur as primary or secondary
Patho of Osteoporosis:
Secondary osteoporosis: caused by?
Hormonal imbalances, hyperPTH, malabsorption
Tobacco
Meds
Patho of Osteoporosis:
Secondary osteoporosis: What kind of meds lead to osteoporosis?
Heparin, GCs, seizure meds, PPIs
Epidemiology of Osteoporosis
Prevalence in men and women?
Can occur in women and men (equal rate of bone mass decline)
Epidemiology of Osteoporosis
In men how is acceleration of disease?
In men no accelerated phase because no menopause
Epidemiology of Osteoporosis
How is osteoporosis in women occur?
Women tend to have lower calcium intake than men.
Women have less bone mass because of their generally smaller frames.
Bone resorption begins earlier in women and increases at menopause.
Pregnancy and breastfeeding deplete a woman’s skeletal reserve.
Women live longer, greater likelihood of osteoporosis.
Epidemiology of Osteoporosis
Prevalence: Who else can it occur in?
People with absorption issues (eg Celiacs)
1:2 women vs. 1:4 men over age 50 will sustain an osteoporosis-related fracture
Osteoporosis
Risk Factors: Nonmodifiable?
Advancing age (>65 yr)
Female sex (smaller body habitus)
White, Norwegian, or Asian ethnicity
Estrogen deficiency in women (surgical or age-related menopause)
Hereditary predisposition
Osteoporosis
Risk Factors: Modifiable?
Cigarette smoking
Low body weight
Diet low in calcium, vitamin D deficiency, or decreased intestinal absorption of calcium
Sedentary lifestyle
Excessive use of alcohol (>2 drinks/day)
Low testosterone in men
Glucocorticoid/cortisol use
Hormonal factors such as hyperPTHydism (either 1° or 2° due to renal disease), menopause, Cushing’s syndrome, hyperthyroid, or continuous GCs
Excessive caffeine intake
Geographic location: those living in higher latitudes getting less sun exposure resulting in lower vitamin D production in the skin
Clinical Manifestations of Osteoporosis
Spontaneous fractures
Loss of height and/or kyphosis
Bone pain
Clinical Manifestations of Osteoporosis:
Why does spontaneous fractures occur?
The loss of bone mass causes the bone to become mechanically weaker and prone to spontaneous fractures or fractures from minimal trauma.
Clinical Manifestations of Osteoporosis
What happens if even 1 vertebral fracture occurs?
One vertebral fracture due to osteoporosis increases risk of having a second vertebral fracture within 1 year.
Clinical Manifestations of Osteoporosis
Loss of height and/or kyphosis: Why does this occur? What develops?
Over time, vertebral fractures and wedging cause gradual loss of height.
Patients develop humped thoracic spine (kyphosis, or “dowager’s hump”).
Clinical Manifestations of Osteoporosis
Bone pain: Why does this occur?
Patients often complain of achiness in their long bones of the legs and arms due to weakening of the bone and inflammation of the periosteum from mechanical stress.
Diagnosis & Assessing Fracture Risk:
How is it diagnosed?
Dx’d by measuring bone mineral density (BMD), Dual-energy x-ray absorptiometry (DEXA) scan.
Diagnosis & Assessing Fracture Risk:
How does WHO diagnose osteoporosis?
The World Health Organization (WHO) diagnostic criterion for osteoporosis is a BMD more than 2.5 standard deviations below the mean BMD for young adults.
Diagnosis & Assessing Fracture Risk:
Who is routine testing done for?
Routine testing for all women at age 65 & younger for post-menopausal at increased risk
Diagnosis & Assessing Fracture Risk:
When are men tested?
Testing for men 70 yrs and older
Diagnosis & Assessing Fracture Risk:
What does BMD measure?
Measures BMD wrist, hip, spine
Primary Prevention of Osteoporosis
Calcium: What does it do in early life?
Early life ~ maximizes bone growth
Primary Prevention of Osteoporosis
Calcium: What does it do in later life?
Later ~ maintains bone integrity
Primary Prevention of Osteoporosis
Calcium: What diet is it in?
Diet: dairy, green veggies, processed foods that are fortified (eg cereals)
Primary Prevention of Osteoporosis
Recommendations (RDA)
Teens/young adults/older female adults?
Adolescents & teens ~ 1300mg/d
Young adults ~ 1000mg/d
Older female adults ~ 1200mg/d
Primary Prevention of Osteoporosis
Vitamin D: What does it do?
Ensures Ca absorption
Primary Prevention of Osteoporosis
Lifestyle
Regular weight-bearing exercise
⍉ excessive EtOH
⍉ smoking
Primary Prevention of Osteoporosis
Lifestyle:
Regular weight-bearing exercise includes?
Walking, yoga, dancing, racquet sports, weightlifting, stair climbing
Agents for Primary Prevention for osteoporosis?
Calcium supplementation (oral): When is it used?
Used if diet insufficient to meet the requirement, mild hypocalcemia
Agents for Primary Prevention for osteoporosis?
Vitamin D supplementation
Calcium supplementation (oral)
Calcium salts
Agents for Primary Prevention for osteoporosis?
Calcium supplementation (oral): What are adverse effects?
Adverse effects: hypercalcemia, GI disturbances, nephrolithiasis, renal destruction, lethargy
Agents for Primary Prevention for osteoporosis:
Calcium salts: How does it differ from calcium supplementation? Are they interachangable?
Differ in % of elemental calcium
⍉ interchangeable
Agents for Primary Prevention for osteoporosis:
Calcium salts: What is max absorption dose at one time?
Max 600mg per dose at one time = adequate absorption
Nursing Implications
Calcium salts
What should you advise against? How should they be taken? What should be avoided? What should you inform patient about?
Advise pts against switching to a different preparation
Take calcium carbonate with meals for best absorption
Take with large glass of H2O
Avoid taking Ca with foods that can suppress Ca absorption
Inform pt about s/s hypercalcemia
Nursing Implications
Calcium salts
Avoid taking Ca with foods that can suppress Ca absorption- like what?
Oxalate foods: spinach, Swiss chard, beets
Phytic acid & insoluble fiber: bran, whole-grain cereals
Nursing Implications
Minimize drug interactions?
GCs – reduce Ca absorption
TCNs – Ca binds to TCNs, reducing TCN absorption. Separate by 1 hr
FQs (eg levofloxacin)
Levothyroxine – reduced TH absorption – separate by several hours
Thiazides decrease renal excretion of Ca in exchange for sodium (hypercal)
Loops – increase Ca excretion (hypocal)
Pharmacotherapy for Osteoporosis
Agents that ↓ bone resorption- How?
Reduce osteoclast activity
Pharmacotherapy for Osteoporosis
What is the purpose of them?
Agents that ↓ bone resorption
