ANA Testing Carrie Marshall 1/18/08

Osteoporosis Epidemiology The Most Commom Metbolic Disease In The World In US Female>50: Osteoporosis=17% Osteopenia= 42% Male>50: Osteoporosis=4% Osteopenia =33%

Osteoporosis Bone Structure Cortical & Trabecular Bone Bone Cells: Osteoblasts Osteoclasts Osteocytes Bone Proteins & Minerals

BONE PHYSIOLOGY Bone Resorption –Osteoclast Bone Formation –Osteoblast Bone Remodeling Unit –Positive < age 30 –Negative > age 30 Bone Resorption –Osteoclast Bone Formation –Osteoblast Bone Remodeling Unit –Positive < age 30 –Negative > age 30

Osteoporosis Pathogenesis: *Peak Bone Mass *Bone Loss *Bone Quality

Osteoporosis: Is a systemic skeletal disease characterized by: 1-Low bone mass 2-Microarchitectural deterioration of bone tissue 3-Increase in bone fragility and susceptibility to FX fracture*Consensus Development Conference Statement 1993

Background  By the end of the first menopausal decade, 50% of white females have osteopenia or osteoporosis  Prevalence of osteoporosis increases from 15% in yo to 70% in women aged 80 years  1/3 of all cases with osteoporosis have been dx  1/7 Americans with osteoporosis received tx

Types of Osteoporosis Primary osteoporosis -progressive bone loss assoc with aging (80%) –Type 1-due to estrogen deficiency-usu in postmenopausal women –Type 2-senile involutional osteoporosis-after 35 yo, affects both trabecular and cortical bone Secondary osteoporosis -resulting from underlying medical conditions (20%)

Determinants of Peak Bone Mass Peak bone mass related to Genetics Physical activity Diet Concomitant diseases Lifestyle-tobacco and etoh (decreases bone formation) Other drugs 11

Pathogenesis High turnover osteoporosis- increased bone resorption greater than increased bone formation Estrogen deficiency-amenorrhea/ oophorectomy Hyperparathyroidism Hyperthyroidism Hypogonadism Drugs: Steroids, ….. 12

Pathogenesis Low turnover osteoporosis- decreased bone formation more pronounced than decreased bone resorption Liver disease-primary biliary cirrhosis Anorexia nervosa Age above 50 years 13

Glucocorticoid Excess Reduces bone formation and accelerates bone resorption Reduction in bone formation Increased in bone resorption (non-mature osteoclasts) 14

Symptoms?

Fractures Hip, vertebral, and other sites fxHip, vertebral, and other sites fx Fragility fracture?Fragility fracture? 16

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Secondary Complications of Fractures Pain Deformity Disability Physical deconditioning due to inactivity Change in self image 18

History and Physical  Ask about risk factors Tobacco and etoh hx, exercise hx Calcium intake  Record height and weight  Pay attention to sign and sx of remediable secondary causes or contributing factors to osteoporosis Cushing’s syndrome, steroid tx, diabetes, hyperparathyroidism, gastrointestinal or hepatic diseases, immobilization. Signs of cancer, especially multiple myeloma  Reproductive hx-time of menopause, sx of hypogonadism (decreased libido, impotence, testicular atrophy) 19

Adverse Effects Specific to Vertebral Body Compression Fractures Loss of height Kyphosis-dowager hump Crowding of internal organs Back pain Prolonged disability Increased mortality 20

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تشخيص

Laboratory studies Cbc, chem, mineral panel, TSH, LFT –Normal bicarbonate, calcium, creatinine, TSH excludes metabolic acidosis, renal insufficiency, hyperthyroidism, hyperparathyroidism –Normal calcium, phosphate, alkaline phosphatase and albumin mitigate against osteomalacia –Normal cbc, total protein, calcium and creatinine makes multiple myeloma unlikely –An isolated AP elevation is of limited diagnostic benefit in pt with an acute fx –Serum testosterone should be checked in men with osteoporosis, esp if they had diminished libido, impotence or testicular atrophy 23

Additional Laboratory Studies 25-OH vitamin D and PTH should be obtained in elderly with poor Vitamin D intake or has hx of GI diseases (malabsorption or gastrectomy), liver disease, or anticonvulsant tx. Vitamin D deficiency is associated with low 25-OH Vitamin D and high PTH (secondary hyperPTH) Urinary cortisol excretion or overnight dexamethasone suppression test should be ordered if Cushings syndrome is suspected PTH should be measured in pts with hypercalcemia, hypercalciuria, hx of renal stones or osteopenia that his most prominent in cortical sites SPEP and UPEP should be obtained if there is unexplained anemia, weakness, wtloss, hypercalcemia, renal insufficiency with bland urine sediment or other constitutional sx 24

Laboratory studies Markers for bone turnover are not recommended routinely for the diagnosis of osteoporosis  Useful for monitoring efficacy of antiresportive therapy 25

Laboratory studies Bone resorption markers  Urinary DPD (deoxypyridinoline crosslinks)  Is % higher in subjects c osteoporosis  Urinary excretion of NTX (cross-linked N-telopeptides of type 1 collagen)  Urinary hydroxyproline Bone formation markers  Serum osteocalcin concentration  Tends to correlate with BMD of spine 26

راديوگرافی كم شدن تراكم: ۳۰ تا ۵۰ ٪ پر رنگ شدن خط دور مهره فرو رفتگی كفه مهره مهره ماهي شكل كم شدن ارتفاع مهره در هم فرو رفتن

Methods of Screening 1.Dual x-ray absorptiometry 2.Quantitative computed tomography 3.Ultrasonography 29

Who should be screened for Postmenopausal Osteoporosis? 1.All nonfrail females >65 years 2.All females with history of fragility fractures 3.Younger postmenopausal females with other risk factors: 1.Low body weight (<127#) 2.Family hx of spine or hip fracture 3.Current smokers *National Osteoporosis Foundation 1998 *Framingham Osteoporosis Study evaluating RF for bone loss in elderly M/F 30

Indications for Bone Densitometry Same as for osteoporosis screening criteria Help guide a decision about estrogen replacement therapy at time of menopause Women with osteopenia Pts on long-term steroids, anticonvulsant tx, HRT Pts with asx primary hyperparathyroidism in whom surgery might not otherwise be recommended. 31

Dual x-ray absorptiometry  Gold standard-costs btw 500, ,000Rls.  1/10 the radiation of the CXR 32

Spine Dexa 33

Hip Dexa 34

Site of Measurement Hip vs spine vs other peripheral sites 35

Hip vs Spine vs other Peripheral Sites BMD at one site usually correlates well with BMD at other sites (only 15% discordance) Some studies suggest the risk for fx at a particular site is best estimated by measuring BMD at that site. Best if can measure BMD at 2+ sites esp if you suspect pt has regional osteopenia—ie pt with childhood poliomyelitis 36

Hip vs Spine vs other Peripheral Sites Hip is usually preferred at any age but spine BMD is more reliable in those <65 yo bc less vascular calcification and osteophytes 37