Definition A systemic skeletal disease characterized by low bone mass and micro architectural deterioration of bone tissue leading to bone fragility and susceptibility to fracture
Who Gets Osteoporosis? Immobilization Hypogonadal states Endocrine disorders Malnutrition, parenteral nutrition and malabsorption rheumatologic disorders Renal insufficiency Hematologic disorders Several inherited disorders
Osteoporosis Mechanisms causing osteoporosis Imbalance between rate of resorption and formation Failure to complete stages of remodeling Types of osteoporosis Type I Type II Secondary
Osteoporosis - Types Postmenopausal osteoporosis (type I) Caused by lack of estrogen Causes PTH to overstimulate osteoclast Age-associated osteoporosis (type II) Bone loss due to increased bone turnover Malabsorption Mineral and vitamin deficiency
Classification Primary Postmenopausal Bone loss – 2-3% per year of total bone mass Most common fx: vertebral, distal forearm Age related – 3rd decade of life starts slow decline in bone mass at rate of 0.5-1% per year Most common types of fx: hip and radius F>M Secondary
Secondary OsteoporosisDrugs Aluminum Anticonvulsants Excessive thyroxine Depo Provera (decreased bone mass reversible after stopping medication) Glucocorticoids GnRH agonists Heparin Lithium
Diagnosing Osteoporosis Outcome of interest: Fracture Risk! Outcome measured (surrogate): BMD Key: Older women at higher risk of fracture than younger women with SAME BMD! Other factors: risk of falling, bone fragility not all related to BMD
Prevalence of osteoporosis Osteopenia Osteoporosis Female 37-50% 13-18% Age > 50 year Male 28-47% 3-6% Age > 50 year
Physical examination No single maneuver is sufficient to rule in orrule out osteoporosis or vertebral fracturewithout further testing
Diagnosing Osteoporosis Laboratory Data Limited value in diagnosis Markers of bone turnover (telopeptide) more useful in monitoring effects of treatment than in diagnosis Helpful to exclude secondary causes Hyperthyroidism Hyperparathyroidism Estrogen or testosterone deficiency Malignancy Multiple myeloma Calcium/Vitamin D deficiency
Work-upScreen for secondary causes Serum calcium, phosphorus, alk phos PTH if calcium is high (hyperparathyroidism) 25-hydroxyvitamin D if low ca, low phos and high alk. phos (osteomalacia) Thyroid function tests (thyrotoxicosis) SPEP, UPEP (multiple myeloma) 24-hour urinary calcium (hyper or hypo calciuria) Serum testosterone (hypogonadism)
Methods to evaluate for osteoporosis Quantitative Ultrasonography Quantitative computed tomography Dual Energy X-ray Absorptiometry (DEXA) ?”gold standard” Measurements vary by site Heel and forearm: easy but less reliable (outcome of interest is fracture of vertebra or hip!) Hip site: best correlation with future risk hip fracture Vertebral spine: predict vertebral fractures; risk of falsely HIGH scores if underlying OA/osteophytes
Dual X-ray absorptiometry 2-dimensional study BMD = Amount of mineral Area Accuracy at hip > 90% Low radiation exposure Error in Osteomalacia Osteoarthritis Previous fracture
How to interpret the BMD T score: standard deviation of the BMD from the average sex matched 35-year-old Z score: less used; standard deviation score compared to age matched control For every 1 decrease in T score, double risk of fracture 1 SD decrease in BMD = 14 year increase in age for predicting hip fracture risk Regardless of BMD, patients with prior osteoporotic fracture have up to 5 times risk of future fracture!
Dual X-ray absorptiometry BMD compare with T score young adult femaleNormal < 1 SD below >/= -1Low bone mass ( Osteopenia ) 1-2.5 SD below < -1 > -2.5Osteoporosis >/= 2.5 SD below </= -2.5Severe osteoporosis >/= 2.5 SD below PLUS Fracture
Dual X-ray absorptiometry WHO criteria - Hip BMD Normal Low bone mass (Osteopenia) Osteoporosis Severe osteoporosis
Osteoporosis Can Be Assessed byDXA Relative Risk of Fracture DXA-assessed content is a per SD Decrease in BMD proven effective method for 3 assessing osteoporosis 2.5 related fracture risk. Relative Risk 2 Population surveys and Forearm 1.5 Hip research studies demonstrate 1 Spine a decrease in bone density 0.5 measured by DXA predicts 0 fracture at specific sites. m l p s ra ite Hi ar b lS re rte Fo Al Ve
Ultrasonic measurement Broad-band ultrasound attenuation No radiation exposure Cannot be used for diagnosis Preferred use in assessment of fracture risk
The calcaneus is the most common skeletal site for quantitative ultrasound assessment because -It has a high percentage of trabecular bone that is replaced more often than cortical bone, providing early evidence of metabolic change. -Also, the calcaneus is fairly flat and parallel, reducing repositioning errors.
The McCue CUBA: UltrasonometryTechnology That Can Assess Osteoporosis
Heel BUA is Significantly Lower inSubjects With Future Hip Fracture. 60 BUA (dB/sq MHz) 50 40 30 20 10 0 Fracture No FractureSubjects who developed hip fracture showed significantly (p<0.001) lowerheel BUA results.
CT scan True volumetric study Quantitative Computed Tomography (QCT) utilizes CT technology to detect low bone mass and monitors the effects of therapy in patients undergoing treatment. It is a fast, non-invasive exam that detects low bone mass earlier and more accurately than other bone density exams
The trabecular BMD is indicated as the most important parameter, and interpreted using the Felsenberg classification, based on the following cut-off values: Normal BMD > 120 mg/cc Osteopenia < 120 mg/cc Osteoporosis < 80 mg/cc Very high fracture risk < 50 mg/cc
Advantages over DXA: Ability to separate cortical and trabecular bone Provides true volumetric density in units of mg/cc No errors due to spinal degenerative changes or aortic calcification
Clinicians and researchers favor DXA because-scanners are readily available and relativelyinexpensive.-The radiation dose is negligible-The T-score scale, defined by the WHO specifically forDXA, provides a standardized classification.
Plain radiography Low sensitivity High availability Subclinical vertebral fracture is a strong risk factor for subsequent fractures at new vertebral site and other sites
The main radiographic features of generalizedosteoporosis are cortical thinning and increasedradiolucency
Singh Index The Singh index describes the trabecular patterns in the bone at the top of the thighbone (femur). X-rays are graded 1 through 6 according to the disappearance of the normal trabecular pattern. Studies have shown a link between a Singh index of less than 3 and fractures of the hip, wrist, and spine.
Assessment of fracture risk DXA and quantitative ultrasound Clinical risk factors Markers of bone turnover Bone formation Bone resorption
Assessment of fracture risk DXA Risk of fracture = 1.5-3.0 for each SD decrease in BMD Low sensitivity ( comparable to BP in predicting stroke ) Screening is not recommended Quantitative ultrasound Risk of fracture = 1.5-2.0 for each SD decrease in BMD
Assessment of fracture risk Markers of bone turnoverBone formation markers Bone resorption markers Alkaline phosphatase Hydroxyproline Bone isoenzyme AP Pyridinium crosslinks & Osteocalcin associated peptides Procollagen propeptides of type I collagen
Assessment of fracture riskMarkers of bone turnover Associated with osteoporotic fracture independent of bone density 2-Fold increase in fracture risk ? Combined approach with BMD to increased sensitivity
Assessment of fracture riskClinical risk factors for fracture Low bone mass History or falls Impaired cognition ( plus medication adverse effect ) Low physical function Presence of environmental hazards Long hip axis length Chronic glucocorticoid use Existing fracture Chronic use of seizure medications Renal, hepatic, thyroid, parathyroid, malabsorptive disorder, vitamin D deficiency, MM and local neoplasia to be ruled out National Osteoporosis Foundation 1998
Assessment of fracture riskPredictors of low bone mass Female Advanced age Gonadal hormone deficiency ( estrogen or testosterone ) White race Low body weight & BMI Family history of osteoporosis Low calcium intake Smoking / excessive alcohol intake Low level of physical acitivity Chronic glucocorticoid use History of fracture National Osteoporosis Foundation 1998
When to Measure BMD inPostmenopausal Women All women 65 years and older Postmenopausal women <65 years of age: Ifresult might influence decisions about intervention One or more risk factors History of fracture
When Measurement of BMD Is NotAppropriate Healthy premenopausal women Healthy children and adolescents Women initiating ET/HT for menopausal symptom relief (other osteoporosis therapies should not be initiated without BMD measurement)