Prevention/Treatment of Osteoporosis Flashcards
Goals of Care
- Optimize bone mineral density - prevention and treatment
- Optimize calcium and vitamin D levels
- Reduce osteoporosis risk factors when possible
- Prevent fractures - huge consequences on quality of life and costs, especially the older patients
Osteoporosis
BMD at least 2.5 SDs below mean for young adults
Osteopenia
BMD between 1-2.5 SDs below mean for young adults
Normal BMD
Between +/- 1 SD
BMD
-Dual x-ray absorptiometry
-Hip/lumbar are recommended sites
Two scores:
-Z-score: age matched
-T-score: expected for young, normal adults
Endogenous Risk Factors
- Age
- Female
- White/Asian
- Hereditary
- Small stature
- Low weight (<128 lbs)
- Early menopause or oophorectomy
Exogenous Risk Factors
- Sedentary lifestyle
- Low mobility
- Low calcium intake
- Excessive alcohol
- Cigarette smoking
- High caffeine intake
- Minimal sun exposure
Medical Problems + Osteoporosis
- Hyperthyroiddism
- Hypogonadism
- Cushing’s Syndrome
- Rheumatoid arthritis
- High fall risk increases risk of fractures
Drugs + Osteoporosis
- Glucocorticoids
- Long-term heparin
- Lithium
- Anticonvulsants
- Thiazolidinedione
- Proton pump inhibitors
- Drugs altering calcium absorption/elimination
Patient-Related Falling Risk Assesment
- Medications
- Cognitive impairment
- Balance/gait disorders
- H/O stroke
- LE arthritis
- Advanced age
- Orthostatic HTN
- Visual deficiencies
- Weakness
- Impaired ADLs
- Depression
Environmental Factors for Fall Risk Assessment
- Obstacles/clutter
- Walking surface
- Bumps from others
- Poor lighting
- Stairs
Indications for BMD Testing
- Women >= 65 y.o.
- Men >= 70 y.o.
- Postmenopausal women and men 50-69 y.o. based on risk profile
- Postmenopausal women and men >50 y.o. who fracture
Indications for Vertebral Imaging
- All women >= 70 y.o. and men >= 80 y.o. if T-score < -1.0 SD at spine, hip , or femoral neck
- Women 65-69 y.o., men 70-79 y.o. if BMD T-score =< -1.5 SD at spine, hip , or femoral neck
Postmenopausal women and men >= 50 y.o. if they have one of the following:
- Low trauma fracture
- Historical height loss of +1.5 inches
- Prospective height loss of +0.8 inches
- Recent/ongoing long term glucocorticoid treatment
Osteoporosis Prevention
- Avoid vitamin deficiency states
- Weight bearing exercise
- Modify exogenous risk factors if possible to reduce the likelihood of falling
Calcium/Vitamin D in Diet
- Calcium: milk, yogurt, broccoli, cheddar, spinach
- Vitamin D: salmon, tuna, egg yolk, milk, cereal, cod
Vitamin D Deficiency
-25-OH vitamin D levels: Goal > 30 ng/dL
Supplementation:
- 50,000 IU every week for 8 weeks OR
- 6,000 IU daily then 1,500-2,000 IU daily
Preventing Falls
- Strategies for 65+ y.o. who have increased risk of falls in community dwelling:
1. Exercise or physical therapy
2. Screening for osteoporosis
3. Vitamin D Supplementation - benefit by 12 months, 600 IU for 50-70 y.o., 800 IU for +70 y.o.
Who to Treat?
Postmenopausal women and men >= 50 y.o. who
- Hip/vertebral fractures
- T score =< -2.5 SD at femoral neck, total hip, or lumbar spine by DXA
- Low bone mass (T-score between -1 and -2.5 SD at femoral neck, total hip, or lumbar) + 10 year risk of hip fracture >= 3% OR 10 year major osteoporosis fracture >= 20%
Osteoporosis Guidelines
- Women with known osteoporosis should be offered pharmacologic treatment to reduce hip/vertebral fracture (Alendronate, risedronate, zoledonic acid, prolia) for 5 years
- Men with osteoporosis should use BPs to reduce risk of vertebral fractures
- Recommend AGAINST BDM monitoring during 5-year treatment in women with osteoporosis, women using menopausal estrogen, or women using raloxifene
- Clinician should decide whether to treat osteopenic women 65 y.o.+ on patient preferences, fracture risk profile, benefit v.s. harms, and cost of medications
Type of Therapeutic Regimens
- Bisphosphonates (BP)
- Denosumab
- Teriparatide and Abaloparatide
- Calcitonin
- Estrogens and SERMs (Raloxifene)
Estrogen + Osteoporosis
- Indication: treat/prevent osteoporosis
- Slows bone loss and increase BMD in some studies
- Increases risk of MI, breast cancer, stroke, and emboli
- Don’t use for osteoporosis alone
SERMs + Osteoporosis
- Raloxifene
- MoA: selective estrogen receptor modulator
- Approved to treat/prevent osteoporosis
- Increases BMD in spine and femoral neck and reduces vertebral fracture
- Indication: 1st line in postmenopausal women who are contraindicated for BP/denosumab
- *Consider SEs**
SERM AEs
- Chest pain
- Peripheral edema
- Venous and pulmonary thromboebolism
- Hot flashes
- Weight gain
Duavee
- Basedoxifene/conjugated estrogen
- Tissue-selective estrogen complex
- Indication: women with intact uterus with menopause and to prevent postmenopausal osteoporosis
BP
- Structural analog of pyrophosphonate
- Binds to resportive surfaces, integrates into bone matrix
- Taken up by osteoclasts and inhibits binding proteins for their function
- Increases BMD
- Decreases vertebral and nonvertebral fractures
- Oral ones approved for osteoporosis (others for cancer) like Alendronate, Ibandronate, and Risedronate
BP SE
- GI
- Osteonecrosis of jaw (rare)
- Atypical fracture (rare)
- CI: CrCl < 30-35 mL/min due to renal excretion
Osteonecrosis of Jaw
- Requires dental appointment before treatment is started
- Higher risk with injectable BP in cancer patients
Atypical Fractures
- Uncommon
- Usually connected to long term BP use
- Ongoing safety review
Atypical Fracture Provider Advice
- Be aware of the possible risk of atypical subtrochanteric & diaphyseal femur fractures
- Follow drug label recommendations
- Discuss known benefits & potential risks of using BPs w/ pts
- Evaluate any patient who presents with new thigh or groin pain to rule out a femoral fracture
- D/C potent antiresorptive meds in pts who have evidence of a femoral shaft fracture
- Consider periodic reevaluation of the need for continued BP therapy, particularly in patients who have been treated for over 5 years
- Report any adverse events with the use of BPs to the FDA’s MedWatch program
Denosumab
- Prolia
- Fill-length human monoclonal IgG2
- RANKL inhibitor
- Treats postmenopausal women with osteoporosis with high risk of fractures
- SQ every 6 months
Teriparatide
- Forteo
- Recombinant PTH
- Stimulates osteoblasts and transiently increases plasma Ca+
- EXPENSIVE
- Only for specific patients
Teriparatide Patients
- Post-menopausal women
- Primary or hypogonadal osteoporosis in men
- Glucocorticoid-induced osteoporosis
- Failed/intolerant to other therapies
Teriparatide SE/CI/Warnings
- SE: Dizziness, leg cramps
- CI: Paget’s disease, increased alkaline phosphatase, h/o radiation treatment
- Black Box Warning: osteosarcoma, don’t use for more than 2 years
Abaloparatide
- Thymlos
- PTHrR analog
- Indication: Postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy
- Self-administered with pre-filled pen
Abaloparatide AE
- Most common: hypercalcemia, dizziness, nausea, headache, palpitations, fatigue, stomach pain, vertigo
- Orthostatic hypertension within 4 hours of dose
- Warning: Osteosarcoma, don’t use for more than 2 years
Calcitonin
- MoA: hypocalcemic hormones secreted by follicular cells of thyroid gland
- Increase mineral stores in bones and decrease the number/activity of osteoclasts
- Increases spine BMD by 1-3%
- Cancer risks have been shown to outweight the benefits in many cases, taken off certain markets
- *May treat pain from acute vertebral compression fractures**
Osteoporosis Conclusions
- Prevention is of the utmost importance
- BMD screening is recommended in all women >= 65
years and men >= 70 years - Treatment-Refer to NOF/ACP guidelines
- Consider side effects and length of therapy (reassess after 3-5 years of treatment)
- Bisphosphonates and denosumab are typically 1st-line
therapies for osteoporosis/high risk osteopenia (based on FRAX) - Hormone therapy reduces fracture risk, however the risks generally outweigh the benefits.
- Teriparatide, abaloparatide, romosozumab are approved for specific patients with severe osteoporosis at high risk for fractures
Romosozumab-aqqg
- Evenity
- Monoclonal antibody binds to sclerostin, an osteocyte-derived inhibitor of osteoblast activity
- Use: postmenopausal women at high risk of fracture
- SE: ONJ, atypical fractures
- Injection, 12 mo max duration
- Possible risk of MI, stroke, and CV death
- Brand new possible therapy, had a hard time making it to market do to side effects/risks