Menopause and Osteoporosis

Question 1

Absolute contrainidcations to hormone therapy

Answer 1

Breast or endometrial cancer
CV disease
Active liver disease
Undiagnosed vaginal bleeding

Question 2

Genitourinary syndrome of menopause (GSM)

Answer 2

Common symptom of menopause -
Genital symptoms: dryness, burning, irritation
Urinary symptoms: dysuria, urgency, recurrent UTI
Sexual symptoms: pain, dryness

Loss of estrogen leads to pruritis and pain

Question 3

Vasomotor symptoms

Answer 3

Hot flashes - most common reason for HT due to impact to quality of life

Increased skin temperature, nausea, dizziness, headache, palpitations, sweats

Usually occurs within 12-24 months after last period

Question 4

Recommend HT for these postmenopausal women

Answer 4

<60 y/o
Menopause onset within 10 years
Low risk of breast cancer and CV disease

Question 5

Avoid HT for these postmenopausal women

Answer 5

High risk of breast cancer or CV disease
Age >60
Menopause onset >10 years ago

Question 6

HT for postmenopausal women with high risk of VTE

Answer 6

Non-oral route
Lowest possible dose

Question 7

HT for postmenopausal women with high risk of CVD

Answer 7

Known MI
CVD
PAD
Abdominal aortic aneurysm
DM
CKD
ASCVD >10%

Nonhormonal therapy

Question 8

HT for postmenopausal with moderate risk of CVD

Answer 8

Transdermal estradiol with progestogen

Question 9

Benefits of estrogen

Answer 9

Relieves genitourinary atrophy
Relieves vasomotor instability (improves sleep)
Reduces hip fractures & vertebral fractures
Reduces rate of bone resorption (does not reverse bone loss)

Question 10

Risks of estrogen

Answer 10

AE: bloating, HA, breast tenderness
Endometrial cancer
Breast cancer
CHD
Gallbladder effects (gallstones, cholecystitis, cholecystectomy)

Question 11

Endometrial cancer & estrogen

Answer 11

Increased risk if UNOPPOSED estrogen in women with intact uterus

Avoid if history of endometrial cancer

a progestogen is recommended in all people with an intact uterus using estrogen

Question 12

Breast cancer & estrogen

Answer 12

Uncertain risk but avoid in women with history of breast cancer

Risk increases with use of progestogen .
Risk is related to length of use (>5 yr)

Question 13

Benefits of progestogen

Answer 13

Decrease risk of estrogen-induced irregular bleeding
Decrease risk of endometrial hyperplasia and carcinoma

Question 14

Risks of progestogen

Answer 14

AE: bloating, weight gain, irritability, depression

Unpredictable endometrial bleeding w/ continuous estrogen-progestin during first 8-12 months

Question 15

Is Conjugated estrogen + medroxyprogesterone acetate appropriate for secondary CHD prevention?

Answer 15

No - not indicated for secondary prevention

Long-term use may be associated with decreased MI/ CHD death but increased risk of VTE and gallbladder disease

Question 16

HT and stroke

Answer 16

EPT & ET have increased risk of stoke

50-59 y/o, EPT group had no significant increase in stroke
50-59 y/o ET group had double risk of stroke

Question 17

HT therapy duration for postmenopausal women

Answer 17

-Lowest dose for least amount of time
-Reassess in 3 months to 1 year.
-D/C if asymptomatic.
-Treat for additional 3 months if symptoms recur.
-Limit to < 5 years

Question 18

Menostar patch

Answer 18

Lowest-dose patch available
Indicated ONLY for prevention of postmenopausal osteoporosis

Question 19

Benefit of SERM

Answer 19

Endometrial protection, so no need for progestogen

Question 20

SERMs for postmenopausal patients

Answer 20

Ospemifene (Osphena) - indicated for vaginal dryness or severe dyspareunia

Duavee: mod-severe vasomotor symptoms & prevention of osteoporosis

Similar ADE, contraindications as estrogen

Question 21

Alternatives to HT

Answer 21

Vasomotor symptoms:
Fezolinetant (veozah) - neurokinin 3 receptor antagonist
SSRI/SNRI paroxetine 7.5mg (briselle) is only SSRi with indication for vasomotor symptoms

No FDA approval:
soy isoflavones, evening primrose oil, black cohosh (liver tox)
Clonidine, gabapentin/pregabalin, acupuncture, hypnosis, lifestyle changes

Question 22

Low bone mass definition (osteopenia)

Answer 22

T score between -1 and -2.5

Question 23

Osteoporosis

Answer 23

T score < -2.5

Question 24

Severe/established osteoporosis

Answer 24

T score < -2.5 + fragility fracture

Question 25

Osteoporosis in postmenopausal women diagnosis

Answer 25

T score <-2.5 OR Low-trauma spine or hip fracture, regardless of BMD OR Osteopenia + fragility fracture (proximal humerus, pelvis, distal forearm) OR Osteopenia + high FRAX fracture probability

Question 26

Calcium & vitamin D recs

Answer 26

At least 1000mg calcium/day Avoid doses >2500mg/day (increased risk of constipation, kidney stones, inhibited absorption zinc, iron) Vitamin D 800-1000 units (<70 y/o = 600 units; >=70 y/o = 800 units) Goal level = 30 ng/mL

Question 27

Gold standard for BMD

Answer 27

Dual-energy x-ray absorptiometry (DXA) Measures hip, lumbar spine BMD

Question 28

Drugs that can cause osteoporosis/fractures

Answer 28

Antineoplastics Anticonvulsants Glucocorticoids GnRH agonists Heparin Levothyroxine (excessive) Lithium PPIs SGLT2i SSRI

Question 29

FRAX

Answer 29

Fracture Risk Assessment Tool Estimates fracture risk Useful if pt has osteopenia, to determine need for pharmacologic treatment **Not validated for pts on drug therapy for osteoporosis**

Question 30

When to initiate drug therapy for osteoporosis

Answer 30

1. Hip or spine fracture 2. T score <-2.5 at spine, hip, or femoral neck 3. T score -1 to -2.5 at femoral neck or spine AND FRAX 10 year probability is >=3% OR FRAX probabiltiy >=20%

Question 31

Length of osteoporosis drug therapy

Answer 31

Reassess at 5 years (PO), 3 years (IV) High risk of fracture: continue max of 10 years (PO) or 6 years (IV) If fracture risk decreased, then drug holiday for 2-3 years

Question 32

Bisphosphonate General ADRs

Answer 32

GI irritation (do not lay for 30 min) Decrease in serum Ca, Phos in first month Osteonecrosis of jaw (if high dose IV prolonged therapy - usually in patients with cancer) A fib possible but not sure.

Question 33

Bisphosphonate shown to decrease mortality

Answer 33

Zoledronic acid Decreases mortality in high risk patients w/ hip fracture

Question 34

Bisphosphonates

Answer 34

First line therapy for osteoporosis Alendronate Risedronate Ibrandronate (second line therapy) (women only) Zoledronic acid

Question 35

Renal adjustment for bisphosphonates

Answer 35

Not recommended: CrCl <35: alendronate, zoledronic acid CrCl <30: risedronate, ibandronate

Question 36

IV bisphosphonate options

Answer 36

Ibandronate (PO & IV) Zoledronic acid (IV only)

Question 37

Denosumab (Prolia)

Answer 37

Inhibits activation of RANKL - cytokine essential for formation, function, survival of osteoclasts Preferred alternative to first line therapy -Intolerant to bisphosphonates -Poor renal function First line if patient has very high risk or previous fractures Must take calcium, vitamin D as it can cause hypocalcemia

Question 38

Raloxifene (Evista)

Answer 38

SERM Prevention & treatment of osteoporosis in postmenopausal women PLUS risk reduction for invasive breast cancer Decreases resorption in bone Decreases overall bone turnover Risk of VTE- avoid if pt history. Highest risk first 4 months. Interacts with warfarin, levothyroxine (separate by 12 hours)

Question 39

Conjugated estrogens & bazedoxifene (Duavee)

Answer 39

SERM + estrogen HT. Indicated for prevention of osteoporosis - mainly in patients with persistent menopausal symptoms who cannot tolerate other drugs CI: VTE, hepatic impairment, similar to estrogen

Question 40

Parathyroid hormone related peptide analogs

Answer 40

Teriparatide (Forteo) & Abaloparatide (Tymlos) Both SC daily Indicated for treatment of osteoporosis in postmenopausal women Forteo can also be used in men Recommended first line therapy if very high risk or prior fractures (use x2 yrs) Do not use longer than 2 years (possible osteosarcoma) Increases risk of digoxin toxicity

Question 41

Romosozumab (evenity)

Answer 41

Sclerostin inhibitor, builds bone, decreases bone resorption SC monthly x12 months Recommended first line therapy if very high risk or prior fractures Do not use if MI or stroke in past year No renal adjustments, but may be at higher risk for hypocalcemia

Question 42

Calcitonin-salmon (miacalcin)

Answer 42

Nasal spray. Inhibits bone resorption Typically not recommended b/c weak effect on BMD but can be used short-term for bone pain Higher chance for malignancies