Lecture 41+42: Osteoporosis Flashcards by Brooke Thornburg

Action of Drug therapies for Osteopororsis

-ensure adequate Ca and Vit D
-antiresorptive action
-anabolic action

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Romosozumab

-sclerostin inhibitor
-antiresorptive action AND anabolic action
-drug therapy for osteoporosis

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Antiresorptive action

-inhibits bone resorption
-maintain/inc bone mass
-reduce fracture risk

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Drug therapies with antiresorptive action

-romosozumab*
-bisphosphonates
-SERMs
-calcitonin
-Estrogen replacement therapy (ERT)
-RANK ligand inhibitor

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Anabolic action of osteoporosis drug therapy

-stimulate bone formation
-inc bone mass
-reduce frac risk

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Osteoporosis drug therapies with anabolic action

-Romosozumab*
-Parathyroid hormones (teriparatide, abaloparatide)

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Bisphonates products

-Alendronate (Fosamax)
-Risedronate (Actonel)
-Ibandronate (Boniva)
-Zoledronic acid (Reclast)

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Bisphonates use

-treatment/prevention of POSTmenopausal osteoporosis
-treatment of osteoporosis to inc bone mass in males
-treatment of glucocorticoid-induced osteoporosis in males and females

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Bisphosphonates contraindications

-hypocalcemia
-renal insufficiency
-esophageal abnormalities (except IV formulations)
-inability to sit/stand for at least 30 min (at least 60 min)
-avoid alendronate oral solution in patients at risk for aspiration
-avoid oral after bariatic surgery
-pregnancy or breast feeding (IV zoledronic acid)

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Absorption of Bisphosphates

-reduced w coffe/joice
-reduced before breakfast
-reduced taken during breakfast

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Metabolism of Bisphosphates

-does not affect hepatic CYP 450 system

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Elimination of Bisphosphates

-50% bone
-50% renal
->10 year half life in bone

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Adverse effects of oral bisphosphonates

-esophogeal irritation/ulceration
-ab pain
-musculoskeletal pain
-headache
-nausea
-thigh fracture
-occular inflammation
-aFib
-esophogeal cancer?
-osteonecrosis of the jaw

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Osteonecrosis of the jaw

-necrotic maxillary bone and sequestrum formation

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Bisphosphonates counseling

-must be taken on empty stomach 1st thing in the morning
-take delayed release after breakfast
-Full glass of water for tablet
-do not lie down at least 30 minutes after ingestion and until after first food of day (60 min for ibandronate)
-wait at least 30 min before eating, drinking, taking other meds (60 for ibandronate)
-avoid minaeral water w high calcium
-do NOT chew

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discontinue bisphosphonate use if

-dysphagia (trouble swallowing)
-odynophagia (painful swallowing)
-retrosternal pain
-heartburn

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Oral Bisphosphonate drug interations

-chelates w multivalent cations (Al, Ca, Fe, Mg)
-antacids
-mineral supplements
-vitamins
-osmotic laxatives (not magaldrate or sodium bicarbonate tho

-also inc GI side effects w NSAIDs

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Bisphosphonate dosing

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Menopausal Hormone Therapy for osteoporosis recommended for

-prevention of postmenopausal osteoporosis for women with SIGNIFICANT RISK

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SERMs for osteoporosis

-Raloxifene
-Bazedoxifene + conjugated estrogens

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Raloxifene use

-SERM
-prevent/treat postmenopausal osteoporosis
-breast cancer prophylaxis for postmenopausal women at high risk

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Bazedoxifene + conjugated estrogen (Duavee) use

-SERM
-prevention of osteoporosis in women w a UTERUS

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SERM contraindications

-active or past history of venous thromboembolic events
-pregnancy/lactating

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Raloxifene BLACK BOX warning

-inc risk of deep vein thrombosis and pulmonary embolism
-inc risk of stroke

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Raloxifene common side effects

-host flashes -leg cramps -weight gain -peripheral edema

SERM mech of action on hypothalamus

-act as antiestrogens -disrupts thermoregulation =hot flashes

SERM doses

slide 24

Salmon-calcitonin use

-TREAT postmenopausal osteoporosis in women >5years menopause

salmon-calcitonin analgesic effects

-acute and chronic pain associated with vertebral fracture -not shown to reduce pain in other instances

Calcitonin dosing

-200 units in ONE nostril qd -100 units SQ/IM qd

salmon-calcitonin intranasal side effects

-rhinitis -epistaxis -dryness -nasal irritation -inc cancer risk (prostate and liver)

Subcutaneous salmon-calcitonin side effects

-Flushing (vasomotor sx) -Nausea -Rash -Allergic reaction

RANK ligand inhbitor drug

Denosumab

Denosumab use

-TREAT osteoporosis in MEN and postmenopausal women at HIGH risk -treat bone loss in women w breast cancer on aromatase inhibitor therapies -failed or intolerant to other therapy -Glucocorticoid-induced osteoporosis in men and women

Denosumab contraindication

-HYPOcalcemia

Denosumab rebound effect

-inc risk of vertebral fracture after discontinuation of denosumab

CONSIDER INDEFINATE TREATMENT OF BLANK

SLIDE 32

NEED CAREFUL STRATEGY CONSIDER BLANK

SLIDE 32

Denosumab common side effects

-back pain -high cholesterol -musculoskeletal pain -bladder infection, uti

denosumab serious side effects

-dermatitis, cellulitis, rash eczema -hypocalcemia -serious infections -osteonecrosis of the jaw -Atypical femur fractures -Hearing Loss? -Deafness?

Denosumab dosing

-60 mg SQ every 6 months -admin in office -$4K/year

Parathyroid hormone drugs

-Teriparatide -Abaloparatide

Parathyroid hormone use

-TREAT postmenopausal women w HIGH risk of fractures -inc bone mass in MEN w osteoporosis -glucocorticoid-induced osteoporosis in men and women (teriparatide only)

High risk candidates for parathyroid hormone therapy

-hist of osteoporotic fracture -multiple risk factors for fracture -extremely low BMD (T-score below -3.5) w/o fragility fracture) -failer/intolerant to other osteoporosis therapy

Black Box warning of parathyroid hormones

-inc incidence of osteosarcoma (bone tumor)

Contradindication od parathyoid hromones

-pts w higher risk of osteosarcoma -Paget's disease of bone -unexplained elevations of alkaline phosphatase -Pts w open epiphyses (head of bone) -prioir radition therapy involving skeleton -bone metastases -hist of skeletal malignancies -metabolic bone diseases other than osteoporosis -pre-existing hyper calcemia

Parathyroid hormone adverse effects

-dizzinees -orthostatic hypotension (lay down during admin) -nausea -leg cramps -arthralgias (joint pain) -hypercalciuria -hypercalcemia (dec Ca intake or change to QOD dose)

TeriPARAtide (parathyroid hormone) dosing

-20 mcg SQ daily -2 years max duration (allow repeat if appropriate) -28 days discard

AbaloPARAtide (parathyroid hormone) doing

-80 mcg SQ daily -18 month max duration -30 days discard

Other parathyroid hormone condiserations

-subsequent resorptive agent - extensive pt education -must refrigerate 36-46F -must discard after 1st use -expensive

AACE TREATMENT CONDISERATIONS

SLIDE 43!!

Monoclonal anti-sclerostin antibody drug

Romososzumab

Romosozumab (Evenity) use

-TREAT osteporosis in POSTmenopausal women at HIGH risk of fracture -hist of fracture -low BMD -failed/intolerant osteoporosis therapy

Romosozumab (evenity) contraindications

-Uncorrected Hypocalcemia

Discontinuation of romosozumab results in

-bone loss -return of pre-treatment BMD levels

When discontinuing, Romosozumab,

-consider subsequent treatment w bisphosphonate or denosumab

Romosozumab Black box warning

-inc risk of myocardial infarction, stroke, cardiovascular death

Romosozumab adverse effects

-headache -hypocalcemia -arthralgias (joint pain) -injection site reactions

Romosozumab dosing

-210mg as 2 injections SQ monthly

Romosozumab considerations

-12 month max duration -extensive pt education -must refrigerate 36-46F -must discard after 30 days

Which drugs should be carefully administered to patients w chronic kidney disease

-Alendronate -Risendronate -Ibandronate -Denosumab -Raloxifene/Bazedozifene -Teriparatide

Which drugs ware contraindicated in pts w chronic kidney disease w GFR < 35

-Alendronate -Risendronate -Ibandronate

Glucocorticoid-induced osteoporosis should be treated

aggressively esp in high risk pts

Monitoring Treatment

-assess BMD changes w DXA -look for stable/inc BMD and no new fractures -renal, calcium, vit D tests every 1-2 years -duration of therapy needs to be individualized

Consider stopping oral bisphophonate after

5 years

consider stopping IV bisphosphonate after

3 years

High-risk patients benefit from

longer treatments