Lecture 41+42: Osteoporosis Flashcards
Action of Drug therapies for Osteopororsis
-ensure adequate Ca and Vit D
-antiresorptive action
-anabolic action
Romosozumab
-sclerostin inhibitor
-antiresorptive action AND anabolic action
-drug therapy for osteoporosis
Antiresorptive action
-inhibits bone resorption
-maintain/inc bone mass
-reduce fracture risk
Drug therapies with antiresorptive action
-romosozumab*
-bisphosphonates
-SERMs
-calcitonin
-Estrogen replacement therapy (ERT)
-RANK ligand inhibitor
Anabolic action of osteoporosis drug therapy
-stimulate bone formation
-inc bone mass
-reduce frac risk
Osteoporosis drug therapies with anabolic action
-Romosozumab*
-Parathyroid hormones (teriparatide, abaloparatide)
Bisphonates products
-Alendronate (Fosamax)
-Risedronate (Actonel)
-Ibandronate (Boniva)
-Zoledronic acid (Reclast)
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
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)
Absorption of Bisphosphates
-reduced w coffe/joice
-reduced before breakfast
-reduced taken during breakfast
Metabolism of Bisphosphates
-does not affect hepatic CYP 450 system
Elimination of Bisphosphates
-50% bone
-50% renal
->10 year half life in bone
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
Osteonecrosis of the jaw
-necrotic maxillary bone and sequestrum formation
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
discontinue bisphosphonate use if
-dysphagia (trouble swallowing)
-odynophagia (painful swallowing)
-retrosternal pain
-heartburn
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
Bisphosphonate dosing
Menopausal Hormone Therapy for osteoporosis recommended for
-prevention of postmenopausal osteoporosis for women with SIGNIFICANT RISK
SERMs for osteoporosis
-Raloxifene
-Bazedoxifene + conjugated estrogens
Raloxifene use
-SERM
-prevent/treat postmenopausal osteoporosis
-breast cancer prophylaxis for postmenopausal women at high risk
Bazedoxifene + conjugated estrogen (Duavee) use
-SERM
-prevention of osteoporosis in women w a UTERUS
SERM contraindications
-active or past history of venous thromboembolic events
-pregnancy/lactating
Raloxifene BLACK BOX warning
-inc risk of deep vein thrombosis and pulmonary embolism
-inc risk of stroke
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
