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Endocrine and Women's Health > Osteoporosis > Flashcards

Osteoporosis Flashcards

1
Q

what is osteoporosis?

what is osteopenia?

A

What is it?

bone disorder characterized by low bone density, impaired bone architecture, and compromised bone strength that predisposes a person to increased fracture risk. Four fold risk of fracture

Osteopenia: AKA low bone mass but not to the point of osteoporosis

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2
Q

epidemiology

A

Epidemiology

mostly occurs in non-hispanic white women.
disease prevalence greatly increases with age.
occurs more frequently in women than men

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3
Q

Pathophysiology of Osteoporosis

what contributes to peak bone mass?

what are the 2 main causes and their patho for osteoporosis?

A

Pathophysiology of Osteoporosis

a persons peak bone mass is attributed to multiple factors such as physical activity, genetic factors, nutrition

Postmenopausal osteoporosis: a.estrogen deficiency increases proliferation, differentiation, and activation of new osteoclasts (responsible for absorption of bone)
b. increase of IL-1, IL-6, TNF level result in more RANKL .
increased expression of RANK, RANKL (increase osteoclasts activity)

Aging

a. decreased replicative activity of osteoprogenitor cells
b. decreased synthetic activity of osteoblasts
c. decreased biologic activity of matrix-bound growth fctors
d. reduced physical activated

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4
Q

Types of Osteoporosis

Primary

Secondary

A

Types of Osteoporosis

Primary

a. post menopausal female
b. age related (female >male

Secondary

a. medications: glucocorticoids, anti epileptic drugs, depo,edrxyprogesterone, Heparin,aromatase inhibitors, PPI, TZD, SGLT-2i (canagliflozin)
b. medical conditions: hypogonadism, hyperthyroidism, hyperparathyroidism, malnutrition, rheumatoid arthritis, COPD, vitamin D deficiency, diabetes, renal insufficiency

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5
Q

AACE/ACE Diagnostic criteria for osteoporosis

A

AACE/ACE Diagnostic criteria

  1. T-score -2.5 or below in the lumbar spine, femoral, neck, or radius
  2. Low trauma spine or hip fracture (regardless of BMD and T-score)
  3. Osteopenia/ low bone mass (T-score between -1 and -2.5) AND a fragilty fracture of the proximal humerus, pelvis, or distal forearm
  4. Osteopenia/ low bone mass AND high FRAX fracture probability
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6
Q

WHO Fracture Risk Algorithm (FRAX)

A

WHO Fracture Risk Algorithm (FRAX)
a. measures 10 year probability of hip fracture
10 year probability of a major OP fracture (vertebral, HIP, Forearm or proximal humerus.
FRAX score includes
age, gender, prior op fracture, femoral neck BMD, low BMI, oral glucocorticoids (5 mg or more of prednisone or equivalent for 3 months or more, RA, secondary OP, parental hx of hip fracture, current smoking, alcohol intake of 3 or more drinks/day

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7
Q

what factors are included in the WHO FRAX score

11 of them

A

age, gender, prior op fracture, femoral neck BMD, low BMI, oral glucocorticoids (5 mg or more of prednisone or equivalent for 3 months or more, RA, secondary OP, parental hx of hip fracture, current smoking, alcohol intake of 3 or more drinks/day

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8
Q

Clinical representtion

A

Clinical representtion

Symptoms:
pain
immobility
depression, fear, low self-esteem

signs:
shortened stature (loss of >/= 1.5 inches from tallest recorded height)
kyphosis
lordosis
vertebral, hip, wrist, or forearm fractures
low bone mineral density (BMD) on radiology

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9
Q

Interpeting T-scores

A

Interpeting T-scores
normal: -1.0 and above
low bone mass(osteopenia): between -1.0 and -2.5
osteoporosis: at or below -2.5
severe or established osteoporosis: at or below -2.5 with one or more fractures

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10
Q

Nonpharmacologic Treatment

A

Nonpharmacologic Treatment

  1. balanced diet
  2. limit caffeine to 1-2 servings per day
  3. cessation of tobacco use
  4. avoidance of excessive alcohol intake
  5. regular weight bearing and muscle strengthening exercise
    a. improve agility, strength, posture, balance
    b. reduce risk of falls
    c. modestly increases bone density
    d. benefits are lost when a person stops exercising
  6. fall prevention
  7. calcium intake:
  8. Vitamin D intake
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11
Q
  1. calcium intake through diet
A
  1. calcium intake:
    a. adults aged 50+-> 1200 mg/day. dietary intake preffered.
    b. best absorbed in amounts of 500-600 mg or less
    I. 300 mg of calcium is one serving. so need 4 servings of calcium a day
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12
Q
  1. Vitamin D intake

sources:

risk factors for deficiency:

formulations:

recommendations:

optimal Vitamin D levels:

deficient vitamin D levels:

A
  1. Vitamin D intake
    a. ingested from food (egg yolks, fish liver supplements, fortified milk and cereals). synthesize din skin but not reliable as sole source of vitamin. D
    b. risk factors for deficiency: malabsorption disorders, chronic renal insufficiency, meds that increase vitamin. d metabolism (i.e antiepileptics), housebound pts, obesity.
    c. recommendations: adults >/= 50 y.o: 1000 IU/day
    d. D2 OR D3. D2 plant derived.
    optimal level: 25(OH) Vit D >/30 ng/mL
    e. if deficient (<20 ng/mL)
    I. treat with 5000 IU of d3 DAILY FOR 8-12 WEEKS, FOLLOWED BY 1000-2000 iu OF d3 Daily
    II. OR 50,000 IU of D3 weekly for 8-12 weeks, followed by 1000-2000 IU of D3 daily
    f. safe upper limit for general adult intake=4000 IU/da
    g. can also be used as adjunct to osteoporosis therapy, or in pts who cannot tolerate osteoporosis therapy
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13
Q

Goals of Therapy

A

Goals of Therapy

  1. stop or reverse bone loss
  2. increase bone mamss
  3. decrease osteoporotic fractres
  4. decrease falls
  5. pain control, increase QOL in pts. with fractures
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14
Q

Osteoporosis Pharmacotherapy agents

what are the 2 categories

A

Osteoporosis Pharmacotherapy agents

  1. Antiresorptive Agents
  2. Anabolic Agents
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15
Q

antiresorptive agents

A
  1. Antiresorptive Agents
    a. Biphosphonates
    b. RANK-ligand inhibitors
    c. Estrogens
    d. EAA
    e. Mixed estrogen agonist and tissue selective estrogen complexes
    f. calcitonin
    g. Romosozumab
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16
Q

Anabolic Agents

A

Anabolic Agents

  1. parathyroid hormone analogs
  2. Romosozumab
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17
Q

Biophosphonates

Examples:

Class:

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs):

Monitoring Parameters: –

Pearls:

include first line agents in this group, how to take, CI, rare side effects

A

Biophosphonates

Examples: END IN-DRONATE (except zeledronic acid)
Oral agents-Alendronate (Fosomax, Binosto),Risedronate (actonel, altevia), Ibandronate (Boniva)
once a year- Zoledronic acid (recast)

Class: Biophosphonate

Indication: Treatment of osteoporosis in postmenopausal females and to increase bone mass in males with osteoporosis

Mechanism of Action: Binds to bone hydroxyapatite and specifically inhibits the activity of osteoclasts

Effects of mechanism of Action: decrease rate of bone resorption and indirect increase in bone mineral density.

Adverse Effects: Nausea/ dyspepsia (oral), transient influenza-like illness (arthralgia, myalgia, headaches, fever. may pretreat with APAP) (injectable). Rare -> GI perforation/ulceration/ oral bleeding, musculoskeletal ain, osteonecrosis of the jaw (make sure to put in flash cards), atypical fracture (PUT IN FLASH CARDS)

Absolute Contraindications:Crcl < 30-35 mL/min, hx of esophageal cancer

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): calcium and other multivalent cations decrease absorption, other foods/ drugs can decrease absorption when given simultaneously

Monitoring Parameters: –

Pearls:
FIRST LINE for osteoporosis. specific first line agents are Alendronate and risendronate
require drug holidays after 3 years (IV) or 5 years (oral) in those with stable BMD and no fractures to prevent osteonecrosis of jaw (ONJ) and other side effects. duration of holiday unknown, but sondierresatrting if fracture or significant BMD loss
1.administration issues:
a. have pt sit up for 30-60 minutes after administration
b.alendronate/ resendronte IR: take on empty stomach first thing in AM, wait atleast 30 min before eating/ drinking, remain upright for 30 min
c. Risendronae DR: take with plain water immediately after breakfast, remain uprgight for 30minute
d. Ibandronate: empty stomach, take first hinge in the a, wait at least 60 minutes before eating/ drinking, remain upright for 60 minutes
2. not recommended in CrcL < 30-35 mL/min
3. avoid PO therapy if esophageal stricture, achalasia, inability to remain upright for 30-60 minus, increased risk for aspiration
4. rare incidence of osteonecrosis of the jaw in pts. taking higher doses or IV. recommend completion of major dental work prior to beginning therapy
5.rare instance of atypical fractures. therapy of >3-5 years increases risk. discontinue BP therapy uf atypical fractures occur

18
Q

Pearls for biophosphonates

A

Pearls:
FIRST LINE for osteoporosis. specific first line agents are Alendronate and risendronate
require drug holidays after 3 years (IV) or 5 years (oral) in those with stable BMD and no fractures to prevent osteonecrosis of jaw (ONJ) and other side effects. duration of holiday unknown, but sondierresatrting if fracture or significant BMD loss
1.administration issues:
a. have pt sit up for 30-60 minutes after administration
b.alendronate/ resendronte IR: take on empty stomach first thing in AM, wait atleast 30 min before eating/ drinking, remain upright for 30 min
c. Risendronae DR: take with plain water immediately after breakfast, remain uprgight for 30minute
d. Ibandronate: empty stomach, take first hinge in the a, wait at least 60 minutes before eating/ drinking, remain upright for 60 minutes
2. not recommended in CrcL < 30-35 mL/min
3. avoid PO therapy if esophageal stricture, achalasia, inability to remain upright for 30-60 minus, increased risk for aspiration
4. rare incidence of osteonecrosis of the jaw in pts. taking higher doses or IV. recommend completion of major dental work prior to beginning therapy
5.rare instance of atypical fractures. therapy of >3-5 years increases risk. discontinue BP therapy uf atypical fractures occur

19
Q 
Alendronate
class
brand name
route
doses
A

biophosphonate
Fosomax, Binosto
PO
5-10 mg daily or 35-70 mg weekly

20
Q 
Risendronate
class
brand name
route
doses
A

Biophosphonate
Actonel, Atelvia
PO
5 mg daily, 35 mg weekly, 75 mg 2 consecutive days/month, 150 mg monthly

21
Q 
Ibandronate
class
brand name
route
doses
A

biophosphonate
Boniva
PO, IV
vary

22
Q 
Zoledronic acid
class
brand name
route
doses
A

biophosphonate
Reclast
IV
VARY

23
Q

Osteonecrosis of Jaw

what is it

risk factors

management

A

exposed necrotic bone in the maxillofacial region (jaw bone is exposed. bone cells of jajw start to break down)

invasive bone procedures, cancer, concomitant chemotherapy, corticosteroids, poor oral hygiene, ill-fitting dentures, comorbid disorders (anemia, coagulopathy, infection, preexisting dental or periodontal disease

recommend completion of major dental work prior to beginning osteoporosis therapy

24
Q

atypical femur fractures

what is it ?

when do they occur?

incidence?

A

fractures that are characterized by unique radiographic features and locations such as
subtrochantric femur
Diaphyseal femur

occur after little or no trauma

low incidence. rare

25
Q

RANK Ligand inhibitors
Examples:

Class:

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:–
Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:

A

RANK Ligand inhibitors
Examples: Denosumab

Class: RANKL inhibitor

Indication: Treatment of osteoporosis in postmenopausal females with high risk of fracture and to increase bone mass in males with osteoporosis

Mechanism of Action: Human monoclonal antibody that binds to RANKL, which is essential for the formation, function, and survival of osteoclasts

Effects of mechanism of Action: Prevention of RANK/RANKL interaction inhibits osteoclast formation, function, and survival, decreasing bone resorption and increasing bone mass.

Adverse Effects:musculoskeletal pain (bone, joint, or muscle), dermatologic reactions (dermatitis, eczema, rashes), hypocalcemia, serious infections (skin, abdomen, urinary tract, ear), Osteonecrosis of the Jaw, Atypical femur fractures

Absolute Contraindications:–
Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:
FIRST LINE AGENTS
1.may cause preexisting hypocalcemia. correct preexisting hypocalcemia prior to therapy.
2. bone loss is rapid after D/C. consider alternate agents to maintain BMD

26
Q

Pearls of RANKL inhibitors

A

Pearls:
FIRST LINE AGENTS
1.may cause preexisting hypocalcemia. correct preexisting hypocalcemia prior to therapy.
2. bone loss is rapid after D/C. consider alternate agents to maintain BMD

27
Q

Estrogen/ Hormone therapy
Examples: –

Class: –

Indication:

Mechanism of Action:

Effects of mechanism of Action:
Adverse Effects:–

Absolute Contraindications:–
Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:
is this the preffered treatment:
risk of treatment:

A

Estrogen/ Hormone therapy
Examples: –

Class: –

Indication: Treatment of osteoporosis in postmenopausal females with high risk of fracture

Mechanism of Action: reduce bone resorption due to reduced levels of estrogen in post-menopausal women.

Effects of mechanism of Action: estrogen inhibits RANKL. inhibits osteoclast formation, function and survival, decreasing bone resorption and increasing bone mass.

Adverse Effects:–

Absolute Contraindications:–
Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:

  1. many products/ forms
  2. non estrogen treatments preferred
  3. concern of longterm treatment. increased risk of MI, stroke, breast cancer, pulmonary embolism, DVT
28
Q

Pearls for estrogen/ Hormone therapy

A

Pearls:

  1. many products/ forms
  2. non estrogen treatments preferred
  3. concern of longterm treatment. increased risk of MI, stroke, breast cancer, pulmonary embolism, DVT
29
Q 
Denosumab
class
brand name--
route
doses
A

RANKL inhibitor
SQ
60 mg SQ q 6 months

30
Q

Estrogen Agonist/ Antagonist (EAA)

Examples:

Class: –

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:

A

Estrogen Agonist/ Antagonist (EAA)

Examples: Raloxifine

Class: –

Indication: Osteoporosis: may be used to reduce risk of vertebral fracture in patients in whom first-line therapies are not appropriate, or in osteoporosis patients who are at an increased risk of invasive breast cancer.

Mechanism of Action: Appears to act as an estrogen agonist in bone. it decreases resorption of bone and bone turnover, increases BMD, and decreases fracture incidence

Effects of mechanism of Action: decreasing bone resorption and increasing bone mass.

Adverse Effects:hot flushes, leg cramps, peripheral edema, gallbladder disease, cataracts (rare)

Absolute Contraindications:use with systemic estrogens. BLACK BOX WARNING: VTE, STROKE. avoid in women with increased risk of stroke,

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:

  1. not first line
  2. use with systemic estrogens not recommended.
  3. BBW: vte, stroke, avoid in women with increased risk of stroke
31
Q

Pearls for EAA

A

Pearls:

  1. not first line
  2. use with systemic estrogens not recommended.
  3. BWW: VTE, stroke, avoid in pts with increased risk of stroke
32
Q

Tissue-specific estrogen complex:

Examples:

Class: –

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:
BBW:

A

Tissue-specific estrogen complex:

Examples: Bazedoxifene/ Conjugated Equine Estrogen (Duavee)

Class: –

Indication: WOMEN who suffer from moderate-to-severe vasomotor symptoms (hot flashes, night sweats) associated with menopause and to prevent osteoporosis after menopause

Mechanism of Action: conjugated estrogen: act as an estrogen agonist
bazedoxifene: estrogen agonist/antagonist depending on tissue

Effects of mechanism of Action: combo provides relief of vasomotor symptoms and maintenance of bone mineral density in post menopausal females with a uterus, while bazedoxifene reduces the risk of endometrial hyperplasia (concaminant progestin not needed)

Adverse Effects:Muscle spasms, nausea, diarrhea, dyspepsia, upper abdominal pain, Oropharyngeal pain, dizziness, neck pain

Absolute Contraindications: BBWs: endometrial cancer, CVD, dementia, risk vs benefit
Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:
BBWs: endometrial cancer, CVD, dementia, risk vs benefit

33
Q

Pearls for tissue specific estrogen complex

A

Pearls:
dont use with other systemic estrogens
BBWs: endometrial cancer, CVD, dementia, risk vs benefit

34
Q

Salmon Calcitonin

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:
formulation:

A

Salmon Calcitonin

Indication: Treatment of osteoporosis in women who are at least 5 years out-menopausal when alternative treatments are not suitable

Mechanism of Action: not fully understood, calcitonin receptors have been discovered on osteoclasts and osteoblasts.

Effects of mechanism of Action: marked transient inhibition of the ongoing bone resorption process. with prolonged use, there is a persistent, smaller risk in the rate of bone resorption

Adverse Effects: rhinitis, epistaxis, symptoms of the nose, headache, arthralgia, back pain

Absolute Contraindications: salmon allergy

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –
Monitoring Parameters: –

Pearls:
1. nasal spray formulation and SQ injection formulation

35
Q

Bazedoxifine/ Conjugated Equine estrogen
brand name:
class:
dosage form:

A

Duavee
Bazedoxifine/ Conjugated Equine estrogen
PO

36
Q

Parathyroid Hormone Analogs

Examples:

Class:

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:

Pregnancy:

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –

Monitoring Parameters: –

Pearls:

A

Parathyroid Hormone Analogs

Examples: Teriparatide (Forteo), Abaloparatide (Tymlos)

Class: PTH analog

Indication: Treatment of osteoporosis if biphosponate therapy is not appropriate.

Mechanism of Action:recombinant formation of PTH. actions similar to physiologic activity of PTH.causes preferential stimulation of osteoblastic activity over osteoclastic activity

Effects of mechanism of Action: stimulates new bone formation on trabecular and cortical bone surfaces

Adverse Effects: TEriparatide: leg cramps, dizziness/ orthostatic hypotension, pain/ arththralgia, nausea, cough, injection site reaction, hypercalcemia
Abaloparatide: dizziness/orthostatic hypotension, palpitations, nausea, hyperuricemia, hypercalciuria, injection site reaction, hypercalcemia

Absolute Contraindications:BBW: do not give to patients with increased risk of developing osteosarcoma. radiation, bone metastesis, hypercalcemia, hx of skeletal malignancy

Pregnancy:DO NOT USE

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –

Monitoring Parameters: –

Pearls:

  1. BBW: osteosarcoma
  2. once therapy is stopped, bone loss can be rapid.alternative agents should be considered upon discontinuation.
  3. only indicated for 2 years
37
Q

Pearls for PTH analogs

A

Pearls:

  1. BBW: osteosarcoma
  2. once therapy is stopped, bone loss can be rapid.alternative agents should be considered upon discontinuation.
  3. only indicated for 2 years
38
Q

Sclerostin Inhibitor

Examples:

Class:

Indication:

Mechanism of Action:

Effects of mechanism of Action:

Adverse Effects:

Absolute Contraindications:

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –

Monitoring Parameters: –

Pearls:
how long is therapy?:
formulation

A

Sclerostin Inhibitor

Examples: Romosozumab (Evenity)

Class: Sclerostin Inhibitor

Indication: treatment of post menopausal osteoporosis in patients who are at high risk for fracture, or in patients who are at high risk of fracture

Mechanism of Action: humanizedmonoclonal antibody that binds to sclerotin. increases osteoblast synthesis, differentiation, and bone matrix building. decreases RANKL and increases OPG

Effects of mechanism of Action: increases bone formation AND decreases bone resorption

Adverse Effects: nasopharyngitis, arthralgia, injection site reactions, hypocalcemia, Osteonecrosis of the Jaw (ONJ), atypical femur fracture

Absolute Contraindications:BBW: risk of MI, stroke, CV death

Pregnancy:–

Warning/ Precautions: –

Drug-Drug Interactions (DDIs): –

Monitoring Parameters: –

Pearls:

  1. therapy limited to 12 months. anabolic effect wanes after 12 months. follow up therapy with an antiresorptive.
  2. weigh risk and benefit in patients with other CV factors
  3. available SQ formulation administered by a health care professional
  4. bbw: risk OF mi, STROKE, CV death
39
Q

when to initiate osteoporosis therapy

A

Initiate therapy:
I. t-score lower than -2.5
II. t-score btw -1.0 and -2.5 AND a hx of fragility fracture in the hip or spine
III. t score btw -1.0 and -2.5 AND FRAX hip fracture probability >/= 3% OR FRAX major osteoporosis-related fracture >/= 20%

40
Q

how to use osteoporosis guidelines

A

When using treatment algorithm, use left side if patient is initiating osteoporosis therapy for the first time and has no hx of fracture.

41
Q

Monitoring for Efficacy and Toxicity

A

Monitoring for Efficacy and Toxicity

  1. DXA. baseline and q1-2 years
  2. bone turnover markers. must see reduction after 3-6 mo. of antiresrptive therapy. increase 1-3 mo of anabolic therapy, means its working.
  3. continue to monitor based on other meds
  4. adherence
  5. AE
  6. review risk factors and modifiable lifestyle changes
  7. encourage Ca (as appropriate) and Fit D
  8. accurate height measurement annually
42
Q

calcium supplementation

formulations:

ADverse effects:

increased risk for:

DDI:

counseling for each formulation

A

c. supplements may increase risk of MI and stroke, cause kidney stones, AE like bloating, constipation, gas, acute distress.
d. H2RA and PPI decrease absorption of calcium carbonate. calcium supplements decrease absorption of levothyroxine, quinolone, tetracycline ABX. counsel pt on adequate timing of medication administration.
d. serum calcium not reflective of calcium intake
e. calcium supplementation formulations
1. Calcium carbonate
a. acid dependent: take with food
b. H2-RA and PPIs will decrease absorption of calcium carbonate because needs acid
2. Calcium citrate
a. take with or without food
f. can also be used as adjunct to osteoporosis therapy, or in pts who cannot tolerate osteoporosis therapy

Endocrine and Women's Health (14 decks)

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