Osteoporosis Flashcards
Osteoporosis screening for all
Women >65
Men >70
Patients taking oral steroids: What do we do to screen?
Assess fracture risk with a DEXA scan in men or women aged >50 taking prednisone >5mg/day for 3 months
T score ranges (DEXA scan results)
Normal: -1.0 and above
Osteopenia: Between -1 and -2.5
Osteoporosis: Below -2.5
FRAX model parameters
- based on BMD at femoral neck & patient risk factors
- Age, gender, hx of fractures, hx of hip fractures, BMI, oral steroid use, smoker, ETOH use > 3/day
Who gets pharmacologic treatment for osteoporosis
- T score > -2.5
- Patients with a 10-year risk for hip fracture of >3%, and a 10-year risk of major osteoporotic fracture of >20%
- History of fracture of hip or spine
Prevention of Osteoporosis
- Dietary intake of calcium (1000-1200 mg)
- Adequate intake of vitamin D
- Regular weight bearing exercise
- Smoking cessation
- Prevention of falls
“Bone Protecting” Meds
- Calcium/Vitamin D
- Estrogen
- SERMs
- Bisphosphonates
- Anti-RANK Ligand antibodies
“Bone Building” Meds
-Parathormone (PTH) or parathyroid hormone-related protein (PTHrP) analogs
Anti-resorptive AND anabolic agents
Sclerostin inhibitors
Calcium pearls
- Incomplete absorption –> Usually need Vit D for complete absorption
- Constipation is common
Calcium citrate
- Can be taken with or without food
- causes less Gi intolerance
- Higher absorption rate, especially in patients with higher gastric pH
Estrogen +/- progestin pearls
- Women with an intact uterus should take a progestin in addition to estrogen to decrease risk of endometrial cancer
- No longer first line*** due to increased risk of breast CA, VTE, CVA
SERMs (Selective Estrogen Receptor Modulator)
- Raloxifene
- Tamoxifene (not FDA approved for osteoporosis)
MOA: SERM with estrogen-like effects on bone and anti-estrogen effects on uterus/breast
Raloxifene
-Used for the prevention AND treatment of osteoporosis
SERM ADRs
- Hot flashes and leg cramps may occur
- Increase the risk of VTE
- Short term studies have not shown an increased incidence of endometrial hyperplasia of uterine CA
Bazedoxifene
SERM with estrogen like effects on bone and antiestrogen effects on uterus
-MOA: Inhibits stimulating effect of conjugated estrogens
Bazedoxifene indications/interactions
- Tx of moderate-severe vasomotor symptoms
- PREVENTION of osteoporosis in postmenopausal women with intact uterus
-Estrogens are CYP3A4 substrates
Bisphosphonates
- Alendronate*
- Risedronate
- Zoledronic acid* (IV qyear or q2years)
Bisphosphonates MOA
- Inhibits enzyme in mevalonate pathway which disrupts protein prenylation
- Promotes apoptosis, leads to reduced bone resorption
Bisphosphonates Pk (best absorbed when? Half life?)
- Absorbed best on empty stomach
- Plasma half life = 1 hour, can persist in bone for lifetime
Clinical Indications for Bisphosphonates
- Prevention and tx of osteoporosis
- Hypercalcemia associated with malignancy and Paget’s
Pearls of Bisphosphonates
- Increased BMD leads to decreased vertebral and nonvertebral/hip fx with osteoporosis
- Prevents bone loss in early PMP women
- Prevents bone loss associated with steroid therapy
How exactly should a patient take bisphosphonates?
- With 8 ounces of plain water after an overnight fast, remain upright and NPO except water for 30-60min
- Decreases risk of esophagitis
- Take on empty stomach
When would IV dosing be beneficial?
- Esophageal abnormalities
- Esophageal intolerance
- Pts who cannot remain upright for 30-60 min
- Pts who forget to take them
Bisphosphonates monitoring
- Reeval at 1 month to assess tolerance
- CTX at 3 and 6 months
- DEXA at 1 year, q2year after to check BMD
CI with Bisphosphonates
- GFR <35mL/min
- Vit D depletion (25-hydroxy vit D <30 before starting)
- Osteomalacia
- Hypocalcemia
- Impaired swallowing/esophageal disorders
- Pregnancy or lactation
Interactions with Bisphosphonates
- No CYP
- Food and multivalent cations (Fe2+/Ca2+ supplements, antacids) can interfere with absorption
Bisphosphonates ADRs
- PO: GI symptoms (chemical esophagitis rare with nondaily regimens)
- IV: transient flu-like febrile illness
- IV>PO: ocular effects**, call if decreased vision, eye pain, light sensitivity, or redness
- Osteonecrosis of the jaw** (IV»>PO): refer to dental BEFORE starting bisphosphonates
- Atypical femur fractures** often report it “doesn’t feel right”, consider imaging bilaterally
Minimizing ADRs of Bisphosphonates
- Use FRAX to decide if they need it
- Stop after 3 (IV) or 5 years (PO) in pts at low risk
- Wait additional 3-5 years before taking holiday if high risk
- Check BMD with DEXA/FRAX +/- turnover markers
- Continue if high risk
Anti-RANK Ligand Abs, drug and MOA
Denosumab
MOA: shuts down development of osteoclasts
Clinical indications of Anti-RANK Ligand Abs
- Tx of osteoporosis in postmenopausal women at high risk who have not responded to bisphosphonates
- Prevention of skeletal-related events in pts with bone metastases
Anti-Rank Ligand Abs - CI and ADRs
- CI: hypocalcemia pts
- ADRs: fatigue MC, hypocalcemia, ONJ/atypical fx reported
PTH/PTHrP Analogs - drugs and MOA
- Teriparatide
- Abaloparatide
- MOA: stim osteoblast function, increase GI Ca2+ absorption, increase renal tubular reabsorption of Ca2+
Clinical Indications of PTH/PTHrP Analogs
-Tx of osteoporosis in pts at high risk of fracture (for up to 2 years)
What should you start after stopping PTH/PTHrP analogs?
Antiresorptive drug
CI with PTH/PTHrP analogs
- Associated with osteosarcoma***
- Don’t use in pts with hx of skeletal metastases, hyperPTH, pre-existing hypercalcemia
ADRs of PTH/PTHrP analogs
- Nausea
- HA, dizziness
- Arthralgias/myalgias
- Hypercalcemia/hypercalciuria (limit Ca2+ intake <1000mg)
Sclerostin Inhibitors - drug and MOA
- Romosozumab
- MOA: increase osteoblast activity and bone formation and decreased bone resorption
Clinical Indications of Sclerostin Inhibitors
-Tx of osteoporosis in postmenopausal women who are at high risk, failed or cannot tolerate other drugs
CI with Sclerostin Inhibitors
CV risk
ADRs with Sclerostin Inhibitors
- Arthralgias and HA most common
- Atypical fx/ONJ
