Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Osteoporosis – McCord
Document related concepts
Transcript
Scott McCord, PGY 2 What is it? “A common disease that is characterized by low bone mass, microarchitectural disruption, and skeletal fragility, resulting in an increased risk of fracture” Also defined as a value for bone mineral density 2.5 or more standard deviations below the young adult female reference mean (T-score less than or equal to 2.5 SD) on dual-energy x-ray absorptiometry (DXA) Epidemiology – How Common Is It? Stats from International Osteoporosis Foundation cited from medical literature: Worldwide: 8.9 million osteoporotic fractures annually, resulting in an osteoporotic fracture every 3 seconds Affects 200 million women worldwide 1 in 3 women over 50 will experience osteoporotic fractures, as will 1 in 5 men Pathogenesis 1. Peak bone mass acquisition Genetics – minimal contribution Ethnic variation – increased BMD in African Americans, decreased BMD in Asian Americans Environmental factors causing impaired bone accrual Poor growth Delayed maturation Malnutrition Muscle deficits Decreased physical activity Chronic inflammation Medications (glucocorticoids) 2. Old age Pathogenesis (cont.) Balance of bone formation and resorption becomes progressively negative with increasing age Age-related decline in number of osteocytes decreases bone strength 3. Sex steroid deficiency Estrogen or androgen deficiency Loss of bone due to increased remodeling rate, increased osteoblast and osteoclast numbers, and increased resorption and formation Reason for dramatic increase in risk for osteoporosis in post-menopausal women 4. Glucocorticoid excess (endogenous or pharmacologic) Predominant abnormality is decreased bone formation Directly suppresses osteoblastogenesis, strongly and rapidly stimulates osteoblast and osteocyte apoptosis, and prolongs the lifespan of osteoclasts. 5. Oxidized lipids Multiple studies show a link between atherosclerosis/CV disease and osteoporosis Assessing Risk Two primary factors to use in assessing risk for osteoporosis and osteoporotic fractures: Bone mineral density (BMD), generally measured using a DXA scan Clinical risk factors independent of BMD Most accurate way to assess fracture risk is utilizing both BMD and clinical risk factors Measuring Bone Mineral Density (BMD) Most commonly done with dual-energy x-ray absorptiometry (DXA) DXA measures bone mineral content (BMC, in grams) and bone area (BA, in sq cm), "areal" BMD in g/cm2 = BMC/BA T-score (value used for diagnosis of osteoporosis) is calculated by subtracting the mean BMD of a young-adult reference population from the patient's BMD and dividing by the standard deviation (SD) of young-adult population Z-score (used to compare the patient's BMD to a population of peers) is calculated by subtracting the mean BMD of an age-, ethnicity-, and sex-matched reference population from the patient's BMD and dividing by the SD of the reference population. Other methods rarely used: peripheral DXA, quantitative ultrasound, quantitative CT Measuring BMD (cont.) WHO criteria (T-scores) only applicable to postmenopausal women and men age 50 years and older Must use Z-score for premenopausal women and men less than 50 years old, as relationship between BMD and fracture risk is different Measuring BMD (cont.) Z-score Comparison of the patient's BMD to an age-matched population Z-score of -2.0 or lower is considered below the expected range for age, and should prompt further workup for coexisting problems that can contribute to osteoporosis Cannot make diagnosis of osteoporosis in pre- menopausal women and men younger than 50 years of age with BMD from Z-score alone Risk Factors (independent of BMD) Advanced age Previous low trauma fracture Long-term glucocorticoid therapy Low body weight - less than 58 kg (127 lb) Family history of hip fracture More fractures occur in Cigarette smoking patients with osteopenia Excess alcohol intake than osteoporosis Additional Risk Factors Medical diseases: all of these have been associated with decreased BMD RA Inflammatory bowel disease Celiac disease Cystic fibrosis Previous hyperthyroidism Type I and II DM CKD and ESRD Vitamin D deficiency Reduced functional mobility/recurrent falls Medications: androgen deprivation agents, aromatase inhibitors, PPI’s, SSRI’s, TZD’s, anti-convulsants Dementia, poor health/frailty Previous fractures between the ages of 18-20 Previous history of breast cancer (due to prior treatment with anti-hormonals) Fracture Risk Assessment Tool (FRAX) Introduced in 2008 by WHO task force Estimates the 10-year probability of hip fracture and major osteoporotic fracture (hip, clinical spine, proximal humerus, or forearm) for untreated patients between ages 40 and 90 years using easily obtainable clinical risk factors for fracture and femoral neck BMD using DXA http://www.shef.ac.uk/FRAX/ Smartphone app: search “FRAX” When to Screen with DXA USPSTF recommends BMD assessment in all women 65 years of age and older BMD screening in postmenopausal women less than 65 years if one or more risk factors are present Routine BMD measurements in premenopausal women is NOT recommended Routine BMD measurements in all men is NOT recommended by USPSTF, but is recommended in men who have: Clinical manifestations of low bone mass, such as radiographic osteopenia, history of low trauma fractures, and loss of more than 1.5 inches in height Risk factors for fracture, such as long-term glucocorticoid therapy, androgen deprivation therapy for prostate cancer, hypogonadism, primary hyperparathyroidism, hyperthyroidism, and intestinal disorders Clinical Manifestations and Diagnosis Osteoporosis has no clinical manifestations until there is a fracture Many patients without symptoms assume they do not have osteoporosis Many patients with achy joints/hips/feet assume their symptoms are due to osteoporosis, which is not likely in the absence of a fracture, and pain without a fracture is more typical of osteomalacia Vertebral fractures are by far most common, and 2/3 are asymptomatic and diagnosed incidentally on chest or abdominal xrays Hip fractures followed by distal radius (Colles) fracture and next most common Clinical diagnosis can be made by presence of fragility fracture alone (fractures occurring from a fall from standing height or less without major trauma). BMD measurement not necessary for clinical diagnosis Evaluation Initial workup: CMP, CBC, 25-OH Vit D, Phos If diagnosed by fragility fracture, can get DXA scan later on a non-urgent basis to obtain BMD and monitor response to therapy If low Z-score, need more extensive workup to r/o coexisting problems: 24 hour urine for Ca and Cr, PTH, urinary cortisol excretion, celiac screen, Mag, TSH, FSH, LH, 1,25-OH Vit D, SPEP, CRP/ESR, Rf, iron panel Treatment: When to Treat? As per the NOF and WHO, for postmenopausal women and men aged 50 years and older: A hip or vertebral (clinical or morphometric) fracture T-score ≤ -2.5 at the femoral neck or spine after appropriate evaluation to exclude secondary causes Low bone mass (T-score between -1.0 and -2.5 at the femoral neck or spine) and a 10-year probability of a hip fracture ≥ 3% or a 10-year probability of a major osteoporosis-related fracture ≥ 20% based on the USadapted WHO algorithm Clinicians judgment and/or patient preferences may indicate treatment for people with 10-year fracture probabilities above or below these levels Treatment Lifestyle modifications should be initiated in all patients Diet, exercise, Ca/Vit D supplement, smoking cessation Bisphosphonates – inhibit bone resorption, increase bone mass, reduce the incidence of fractures First line pharmacotherapy, correct hypocalcemia and/or vitamin D deficiency prior to initiation Oral preparations: alendronate (Fosamax), once weekly, cheapest risedronate (Actonel), once weekly ibandronate (Boniva), once monthly Calcium/vitamin D taken concurrently, but should be taken at least 1 hour after bisphosphonate to avoid interfering with absorption IV preparations: zoledronic acid (Reclast or Zometa), once yearly ibandronate (Boniva), every 3 months Use IV in patients not able to tolerate po medicines or dosing requirements, or in patients with Barrett’s esophagus or strictures/achalasia (po bisphosphonates contraindicated) Other treatment options Concurrent therapies with bisphosphonates not recommended, have not shown benefit over bisphosphonates alone, are primarily indicated if patient not able to tolerate bisphosphonates SERM – raloxifene or tamoxifen, often used if concurrent breast cancer prophylaxis or treatment is needed Intermittent PTH administration – stimulates bone formation more than resorption Denosumab – monoclonal antibody against RANKL, reduces osteoclastogenesis Estrogen/progestin therapy – only used for persistent menopausal symptoms, as they carry increase risk of breast cancer, stroke, and VTE Treatment in Men Main difference from treatment in women is that if a man’s primary cause of osteoporosis is hypogonadism, testosterone therapy should in initiated Bisphosphonates still first line for osteoporosis in men who do not have hypogonadism If risk of fracture is very high in male with hypogonadism, or if BMD is not improved after 2 years on testosterone therapy, adding a bisphosphonate to testosterone therapy is currently recommended Monitoring No consensus on optimal strategy for monitoring patients on therapy Multiple guidelines published, generally recommend follow up DXA 2 years after starting therapy If improvement seen, can do less frequent monitoring thereafter More frequent monitoring may be needed in conditions of rapid bone loss (glucocorticoid excess) References UpToDate Johnell O and Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726. Kanis JA (2007) WHO Technical Report, University of Sheffield, UK: 66. Melton LJ, 3rd, Atkinson EJ, O'Connor MK, et al. (1998) Bone density and fracture risk in men. J Bone Miner Res 13:1915. Melton LJ, 3rd, Chrischilles EA, Cooper C, et al. (1992) Perspective. How many women have osteoporosis? J Bone Miner Res 7:1005. Kanis JA, Johnell O, Oden A, et al. (2000) Long-term risk of osteoporotic fracture in Malmo. Osteoporos Int 11:669. 2013 ISCD Official Postions - Adult http://www.iscd.org/officialpositions/2013-iscd-official-positions-adult/ “FRAX calculation tool” http://www.shef.ac.uk/FRAX/index.aspx Thanks guys!!
