Osteoporosis Flashcards
Concept:
2 Types of Bone
Cortical: outer shell, makes up 75% of all bone mass
Trabecular:
spongy, interlacing network forming internal support
-Concentrated in vertebral bodies/bony pelvis; 25% all bone mass, however makes up most volume of bone
larger surface area
higher turnover rate than cortical bone
Most likely to show bone loss
Also most likely to show response to therapy
Concept:
Bone Life
- Formation in balance with resorption
- Bone mass peaks at age 30 both sexes
- 0.4% bone lost per year in both genders, PLUS 2% cortical and 5% of trabecular per year in women for first 5-8 years post menopause
- Immediately after menopause, most loss due to excess resorption. Later, most loss is due to decreased formation
Concept:
Secondary Osteoporosis:
Oral Glucocorticoid Induced
- 25% of cases of osteoporosis
- Up to 30% decrease in bone mineral density after 6 months
- 400% increase in fractures at prednisone 7.5 mg/day
- No “safe dose”
Concept:
Calcium and Vitamin D
Diet and Exercise
-Calcium (milk) helps build dense bones
-Vitamin D: Cheese, butter, fortified milk, healthy cereals, fatty fish
Calcium: food sources of calcium dairy products, green leafy veggies, and salmon and sardines
Childhood Dietary Recommendations
Age (Calcium/Vit D)
4-8 (1000/600)
9-18 (1200/600)
Adult Dietary Recommendations
Calcium
- Women under 50 or men under 70
- 1,000 mg/day - Women 50+ or men over 70
- 1,200 mg/day
Vitamin D
- age 70…need 600 IU/day
- Age 70+ …need 800 IU/day
FRAX
Online fracture risk calculator
Developed by WHO
Gives 10-year probability of hip fracture and of major osteoporotic fracture
Treatment recommended for osteopenic patients with 10-year hip fracture risk > 3% or major osteoporotic fracture risk >20%
Only for treatment-naïve patients
Medication Management Options
- Calcium and Vit. D
- Bisphosphonates
- HRT
- Raloxifene
- Calcitonin
- N 1-34 PTH (teriparatide
- denosumab
Calcium/Vitamin D
adjuvant therapy for all individuals (esp > 65 y/o)
WHI study – modest benefit in bone health
Statistically significant only with FULL doses and in older population
Otherwise – small increase in BMD with small decrease in hip fractures.
Carbonate vs Citrate
difference is in absorption; ALWAYS TAKE WITH FOOD!
Citrates (Citracel) absorb better! But need to take more pills.
Calcium carbonate (Tums) is fewer pills but must be taken with food!
elemental Calcium (read the serving size to see how many you need to get to the correct amount) (500-600 mg can be absorbed at a time)
Bisphonsphonates
Alendronate, risedronate, ibandronate, zoledronic acid
MOA: Increase bone mass, reduce incidence of fractures by inhibiting osteoclast activity
Use: Effective for treatment and prevention of osteoporosis
Complications – osteonecrosis of the jaw (seen mostly in cancer pts getting IV bisphosphonates)
Warnings: pill induced esophagitis (reflux, GERD, other esophageal abnormalities); MUST take on empty stomach and remain upright for 30 - 60 min; Cat X in child-bearing age women (stays in bone 7-10 yrs); Uveitis/Scleritis (low-risk)
Monitoring: DXA -Bone turnover markers; Formation-Alk phos
Resorption: Urine NTX, Urine CTX
Medicare will cover-DXA w/o Tx-every two years; DXA w/ Tx-once a year
Biphosphonates: Alendronate (Fosamax)
Ind: Osteoporosis prevention (35mg) and Tx (70 mg/week); Paget’s Disease
ADRs: dyspepsia!! abd pain, acid reflux, contipation, diarrhea, msk pain, nausea; hypocalcemia; uveitis/scleritis
BLACK BOX: thigh or groin pain requires eval for trochanteric fracture
Make sure they get their dental workup before starting and let their dentist know
Bisphosphonates: Osteonecrosis of the Jaw
- Usually after dental extraction
- More common with IV bisphosphonates
- Cases in oral alendronate-1:1000 per year – 1:100000
- Most cases in pts after 5 years of use
- Recommend good oral hygiene, dental exam or extractions prior to starting bisphosphonates if possible
Biphosphonate:
Risedronate (actonel, Atelvia)
Dosing- weekly to twice a month or a month
same instructions as general
Zoledronate (Reclast
- Yearly 5mg IV infusion over >15minutes
- Reduced spine fractures by 70%, hip fractures by 41% over 3 years
- Flu-like infusion reactions in 32% of patients with the first dose, 7% with the second dose, 3% with the third dose
**ONJ- higher incidence!
Different dosing and formulation for cancer
Ind: hypercalcemia of malignancy, MM, bone mets
Monitor renal fxn
Ibandronate (Boniva)
Once a month oral dose; once IV every three months
60 minute wait time before eating or drinking
Pamidronate (Aredia)
IV bisphosphonate
- less potent than zoledronic acid
- similar uses
Biphosphonates: Concerns and Issues
- GI side effects
- Infusion reactions
- Osteonecrosis of the jaw
- Arrhythmias
- Bone quality
- Uveitis/scleritis
Concept:
Osteoporosis Incidence
osteoporosis-related fractures in women is greater than the incidence of MI, CVA, and breast cancer combined
Concept:
Hip Fracture Pt Outcomes
24% die within one year.
20% require long-term nursing home care.
15% regain limited function.
Only 20-40% return to pre-fracture level of independence.
Men tend to have poorer outcomes.
Hormones
MOA: Regulates bone re-modeling by suppressing osteoclast-mediated bone resorption
-estrogen-progesterone therapy no longer first-line approach for osteoporosis treatment in postmenopausal women due to increased risk of breast cancer, stroke, VTEs, and possibly CAD.
Indications: persistent menopausal symptoms, inability to tolerate other options, failure to respond to other options.
Initial recommendations – start hormone therapy within 5-10 years after menopause
SERMs
MOA: Mixed estrogenic and antiestrogen properties depending on tissue
Raloxifene (Evista)
- increases BMD
- Decreases incidence of vertebral fractures (ARR: 2.4%; RRR: 55%)
- lowers risk of breast Ca without stimulating endometrial hyperplasia
ADRs: increased risk of DVTs and increased vasomotor symptoms
(hot flashes, etc)
Black box: DVT, stroke risk
Calcitonin (Miacalcin, Fortical)
MOA: Inhibits bone resorption
Ind: women > 5 years post menopause who cannot take estrogen; Not terribly effective for osteoporosis; Increases vertebral BMD modestly
ADR: Fracture risk…meh
Teriparatide (Forteo)
MOA: synthetic parathyroid hormone; helps build bone by stimulating osteoblast activity
-Effects blunted by bisphonphonates being started first
Ind: Female –postmenopausal OP with high fracture risk
Male - primary or hypogonadal OP with high fracture risk
(not first line, but can use in major osteoporosis)
ADRs: Transient + persistent hyperCa+;
HA; Transient myalgia/arthralgia
CI: Paget’s disease, pregnant/nursing, pediatrics/young adults, prior radiation therapy, bone mets, skeletal malignancies, hypercalcemia
Black Box: Osteosarcoma risk
Denosumab (Prolia, Xgeva)
MOA: Monoclonal antibody that blocks RANK ligand which stimulates osteoclasts; Principal final mediator of osteoclastic bone resorption
Indications:
Prolia: treatment of postmenopausal women with osteoporosis at high risk for fracture
(reduces non-verterbral and non-vertebral fractures)
Xgeva: giant cell bone tumors; increase bone mass and precent SREs with bone mets from solid tumors
Every 6 months SubQ
Take w/ Ca+ and Vit D
ADRs: cellulitis, eczema, flatulence, fatigue, asthenia, hypophosphatemia, nausea, dyspnea, arthralgia, headache
Warnings: hypocalcemia, ONJ, rash, infection, atypical fracture
Preg Cat D
Guidelines Drugs
- Use alendronate, risedronate, zoledronic acid or denosumab first line
- Use ibandronate as a second-line agent
- Use raloxifene as a second- or third-line agent
- Use calcitonin last line
Use first-line teriparatide for patients with VERY HIGH fracture risk or patients in whom bisphos therapy failed
Advise against the use of combination therapy
Guidelines: Monitoring
Monitoring- Obtain a baseline DXA, and repeat DXA every 1 to 2 years until findings are stable; follow-up DXA every 2 years or at a less frequent interval
Monitor changes in spine or total hip bone mineral density (BMD)
Follow-up of patients should be in the same facility, with the same machine, and, if possible, with the same tech
Bone turnover markers may be used at baseline to identify patients with high bone turnover and can be used to follow the response to therapy
