Osteoporosis Flashcards
Factors associated with decreased BMD and/or osteoporotic fractures
1) Age
2) Hormonal deficiency
3) Body habitus
4) Social history
5) Medical history
6) Drug induced causes
7) Sex-specific factors
Age related factors in osteoporosis
Women older than 65 years
Men older than 70 years
Hormonal deficiency factors in osteoporosis
Estrogen deficiency in women
Androgen deficiency in men
Body habits factors in osteoporosis
Decreased BMI
Calorie-restricted weight loss
Social history factors in osteoporosis
Smoking Alcohol use (>2 drinks per day) High caffeine intake
Medical history factors in osteoporosis
Rheumatoid arthritis Cardiovascular disease Type 2 diabetes mellitus Celiac disease Asthma/COPD Autoimmune disorders Hepatic disease History of falls
Drug induced causes of osteoporosis
Antiepileptic agenst Immunosuppressants Lithium Proton Pump Inhibitors Systemic corticosteroids (>5mg /day of prednisone or equivalent for 3 months or more SSRI's Excessive thyroid hormone supplementation Tricyclic antidepressants Warfarin or heparin (long term use)
Sex-specific factors in osteoporosis
Women: - Anorexia nervosa - Medroxyprogesterone depot use - Excessive Vitamin A intake - Gastrointestinal malabsorption syndromes - Personal history of osteoporosis Men: - Loop diuretic use - Gonadotropin-releasing hormone agonists (prostate cancer) - Psoriasis
T-score
Reports how many standard deviations separate a patients’s BMD compared with the BMD of a young, healthy adult of the same sex
z score
Reports how many standard deviations separate a patient’s BMD compared with the BMD of another patient matched for age, sex, and ethnicity
Diagnosis based on T-Score
“Normal”: 0-1 SDs below the mean value
Osteopenic: 1-2.5 SDs below the mean value
Osteoporosis: >2.5 SDs below the mean value
Lumbar spine T-score
- reported as the average of L1-L4
- consider dx of osteoporosis if two individual lumbar spine measurements are greater than 2.5 SDs below the mean regardless of lumbar spine average
Osteoporosis diagnosis based on z score
If a patient’s z scores are greater than 2 SDs below the mean, the result is usually indicative of accelerated bone loss unrelated to menopause and/or aging
Quantitative Ultrasonography
- does not measure BMD
- assesses fracture risk using SOS (speed of sound and BUA (broadband ultrasound attenuation)
- Not associated with radiation exposure
Quantitative computed tomography
Able to predict fracture risk but with greater radiation than DXA (dual-energy x-ray absoptiometry)
Addition tests when evaluating for secondary causes of osteoporosis
25-hydroxy-vitamin D Creatinine Estradiol Serum protein electorphoresis Alkaline phosphatase Phosphate Free testosterone Calcium, serum TSH Parathyroid hormone
Calcium STEPS Analysis in Osteoporosis
Safety:
- questionable inc in MI with or without Vit D
- Nephrollithiasis risk slightly inc with carbonate
- Hypercalcemia in pts with late stage CKD
Tolerability
- constipation
- GI discomfort
Efficacy
- Calcium citrate preferred in instances of:
- Chronic acid suppression therapy
- Intolerance to Ca carbonate formulations
- NOF recommends daily intake of 1000-1500mg and should consider dietary calcium (max 600mg/dose)
- Calcium citrate usually requires 2 tabs/dose
- Should be used (at a minimum) in patients receiving chronic corticosteroid therapy
- Should be administered with an appropriate dose of vitamin D.
Simpliciaty:
- Various formulations available to meet patient needs:
- Tablets (varying sizes)
- Chewable tablets
- Soft chews and “gummy” formulations
- Liquid
Vitamin D available formulations
Vitamin D2 - ergocalciferol
Vitamin D3 - cholecalciferol
Vitamin D STEPS
Safety:
- Annual dosing alternatives (500,000 units) may result in higher rates of falls and fractures in older patients
Tolerability:
- Hypercalcemia
- Constipation
Preference (Pearls)
- Unclear whether vitamin D without calcium supplementation is effective for fracture prevention
- Toltal daily dose should be at least 800 Units
Simplicity:
- coformulated with calcium, but be sure patients are receiving at least 400 units/dose
- Administered daily as 400- to 1000- unit tabs/caps
- Option for quarterly dosing (100,000 units every 3 month) is available, but evidence show only in composite (any site NNT 44), not individual outcomes.
Bisphosphonates: Available agents
1) Alendronate (Fosamax)
2) Idandronate (Boniva)
3) Risedronate (Actonel, Atelvia [delayed release])
4) Zeldronic acid (Reclast)
Bisphosphonate STEPS - safety
- concerns regarding osteonecrosis of the jaw with bisphosphonates still in question
- FDA issed warning regarding increased risk of atypical femur fractures in patients using bisphosphonates (More prevalent in patients on therapy for greater than 5 years
- Cautious us in patients with impaired renal function (<30ml/min for risedronate and ibandronate or less than 35ml/min for alendronate and zeledronic acid) or low serum calcium
- IN patients with hypocalcemia, resolve low calcium before starting.
Bisphosphonate STEPS - tolerability
- abdominal pain
- Acute-phase reaction (zoledronic acid and ibandronate infusions)
- arthralgias
- dyspepsia
- Cautious use in patients with sever esophageal reflux disease, Barrett esophagus, or esophageal strictures
Bisphosphonate STEPS - efficacy
- all bisphosphonates have evidence to support use for preventing vertebral fractures
- alendronate, risedronate, and zoledronic acid have evidence for preventing non-vertebral and hip fractures
- Ibandronate has not yet been proven efficacious for preventing non-vertebral fractures
- Limited data regarding preventing corticosteroid-induced osteoporotic fractures, but good efficacy to prevent decline in BMD
- Used in patient taking chronic systemic chorticosteroids to prevent BMD loss and subsequent fracture
Bisphosponate STEPS - Preference (Pearls)
- most oral doses should be taken with 6-8 oz of water at least 30-60 minutes before food, drink, or other medications risedronate delayed release should be taken with 4 oz of water right after breakfast)
- Patients should remain upright for at least 30 minutes after the administration of an oral dose (60 minutes with ibandronate)
- If a patient is unable to tolerate an agent, discontinue the agent until the adverse effect resolves, and off the patient the option to try another available agent
- Questionable efficacy beyond 5 years; may warrant reavaluation and possible discontinuation of therapy
Bisphosphonate STEPS - Simplicity
- once-daily, once-weekly and once-monthyly tablet
Alendronate: Prevention (5mg/day or 35mg/week and treatment (10mg/day or 70mg/week)
Risedronate: Prevention and treatment (5mg/daily, 35mg weekly, or 150mg monthly)
Ibandronate: Prevention (150mg monthly) and treatment (150mg monthly OR 3mg IV every 3 months
Zoledronic acid: Prevention (5mg IV every 2 years) and treatment (5mg IV every year) - All dosage fomrs and intervals are equally effective, so consider the patient’s prescription drug coverage (or lack of) when choosing a medication
- Alendronate and risedronate are available as generic medications
Estrogen Replacement STEPS - Saftey
- Based on information form the Women’s Health Initiative trial, the risk of using HRT exceeds the benefits associated with HRT use
- HRT is more likely to be associated with:
- CHD (estrogen/progesterone only)
- Stroke
- Invasive breast cancer (estrogen/progesterone only)
- Venous thromboembolic events
Estrogen Replacement STEPS - Tolerability
- breast discomfort
- GI symptoms
- headache disorders
- vaginal bleeding
- venous thromboembolism
Estrogen Replacement STEPS - Efficacy
- reduced risk of vertebral fractures
- reduced risk of nonvertebral fractures
Estrogen Replacement STEPS - Preference (Pearls)
- Results of the WHI found the benefit of fracture prevention to be similar-to-less than the patient’s risk of heart disease, stroke, venous embolism, and breast cancer
- Acts in conjunction with a bisphosphonate to increase BMD more than either agent alone
Estrogen Replacement STEPS - Simplicity
- once-daily oral dosing
- transdermal patch is approved for postmenopausal osteoporosis
SERMs
Selective Estrogen Receptor Modulators
Raloxifene (Evista)
lasofoxifene (Fablyn) - Not FDA approved
SERM STEPS - Safety
- increased risk of fatal stroke in women with a history of coronary heart disease
- increased risk of venous thromboembolism
SERM STEPS - Tolerability
- arthralgias
- hot flashes / flushes
- peripheral edema
- sweating
SERM STEPS - efficacy
- increased BMD
- reduced incidence of clinical vertebral fractures
SERM STEPS - Preference (Pearls)
- The rates of venous thromboembolism are about the same as the rates of clinical vertebral fracture prevention
- Evidence to support its use in patients to prevent invasive breast cancer
SERM STEPS - Simplicity
Fixed-dose, once-daily dosing
Parathyroid hormone - available agents
Teriparatide (biosynthetic parathyroid hormone 1-34) (Forteo)
Parathyroid Hormone STEPS - Safety
Avoid use in patients with:
-Alkaline phosphatase elevation (unexplained)
-Open epiphysis
-Paget’s disease
-Prior skeletal radiation
Associated with osetosarcoma (in rats) after 24 months of therapy (3-60 times the human dose)
Parathyroid Hormone STEPS - Tolerability
Influenza-like symptoms
Hypercalcemia
Injection site pain and/or rash
Urolithiasis
Parathyroid Hormone STEPS - Efficacy
- decreased incidence of new or worsening vertebral fractures in postmenopausal women
- Increases vertebral and total hip BMD
- Prevents BMD loss and vertebral fractures in patients receiving chronic systemic corticosteroid therapy
Parathyroid Hormone STEPS - Preference (Pearls)
- diminished efficacy if used concurrently with bisphosphonate
- after discontinuing teriperatide, adding a bisphosphonate preserves BMD benefits
Parathyroid Hormone STEPS - Simplicity
Once-daily injection
Available as a prefilled (3ml) pen
RANKL antagonist
Denosumab (Prolia)
RANKL antagonist STEPS - Safety
- Cellulitis was the most common serious adverse event in clinical trials
- Osteonecrosis of the jaw
RANKL antagonist STEPS - Tolerability
- eczema
- flatulence
RANKL antagonist STEPS - Efficacy
- decreased incidence of cerebral, nonvertebral, and hip fractures in patients with osteoporosis
- increases bone mineral density in the hip and lumbar spine
RANKL antagonist STEPS - Preference (Pearls)
- National Institute for Health and Clinical Excellence (NICE) in the United Kingdom recommends denosumab for patients at risk of an osteoporotic fracture and unable to adhere to the dosing recommendations or tolerate and oral bisphosphonate
RANKL antagonist STEPS - Simplicity
Subcutaneous injection every 6 months
Calcitonin (brands)
Miacalcin, Fortical
Calcitonin STEPS - Safety
Anaphylactoid and anaphylaxis reactions associated with injection
Calcitonin STEPS - Tolerability
Injection: - GI sympoms - Injection site reaction - Flushing Nasal spary - Rhinitits - Nasal congestion - Mucosal irritation
Calcitonin STEPS - Efficacy
- Reduced incidence of vertebral fractures
- Beneficial effects on BMD
Calcitonin STEPS - Preference (Pearls)
- Inferior with respect to BMD effects compared with alendronate
- May help relieve bone pain associated with fractures, but is not an indication to choose as the primary treatment
Calcitonin STEPS - Simplicity
Nasal administration is only ONE nostril per day, alternating nostrils each day
Osteoporosis follow-up
1) Dual-energy x-ray absorptiometry (DXA)
- recheck @ ~24mo to evaluate changes
- not tx failure if initial, solitary evaluation shows net bone loss
- patients NOT receiving drug therapy may recheck DXA every 5 years unless patient has developed risk factors
2) Medication adherence
- review at least every 6 months
- as may as 50% will d/c therapy within first 6 months
3) Resources
- handouts from American Family Physician website
- National Library of Medicine Medline Plus has patient oriented materials at no cost
- National Osteoporosis and Prevention Campaign examination room booklets and posters
