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Osteoporosis. Hilary Suzawa Med/Peds August 2005. Osteoporosis vs. Osteopenia. National Institutes of Health defined Osteoporosis A disease of increase skeletal fragility Low bone mineral density (a T-score below -2.5) Microarchitectural deterioration Osteopenia

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Hilary Suzawa


August 2005

osteoporosis vs osteopenia
Osteoporosis vs. Osteopenia
  • National Institutes of Health defined Osteoporosis
    • A disease of increase skeletal fragility
    • Low bone mineral density (a T-score below -2.5)
    • Microarchitectural deterioration
  • Osteopenia
    • T-score between -1.0 and -2.5
t score vs z score
T-score vs. Z-score
  • T-score: Number of SD the BMD is above or below the mean for young-normal bone density
  • Z-score: Number of SD the BMD is above or below the mean for an age and sex specific reference group
  • In the US, there are 1.5 million osteoporotic fragility fractures per year
    • Fractures occurring after trauma no greater than a fall from a standing height
  • Half of all post-menopausal women will have an osteoporosis-related fx during their lives
    • 25% will develop vertebral deformity
    • 15% will have hip fracture
risks for fracture
Risks for Fracture
  • Low bone mass—each decrease of 1 in T-score
  • Advancing age—each decade after age 50
  • Low body weight—less than 126 lb (57 kg)
  • Recent weight loss of >10 lbs
  • Delayed menarche—age>15 yrs
  • Maternal history of osteoporosis or history in a first-degree relative
  • Smokers
  • Direction of a fall (worse if fall backward and to one side)
  • History of a previous fracture—most important risk factor independent of BMD
risk factors medical conditions
Risk Factors: Medical Conditions
  • Inflammatory disorders involving musculoskeletal, GI, pulmonary systems
  • Chronic renal dz
  • Organ transplantation
  • Steroids, discontinuation of HRT, LHRH agonists (hypogonadism), sz drugs (Vit D)
  • Anorexia or “athlete triad”
  • Immobilization
  • There are no trials that have evaluated the effectiveness of screening for osteoporosis
  • A goal for screening is to provide an estimate of the absolute risk of any fragility fx during the next 5-10 years
  • The absolute 10 year risk of a fragility fx in a post-menopausal woman with T-score <-2.5 and no other risk factors is <5% at age 50 but >20% at age 65
bone density tests
Bone Density Tests
  • Dual energy x-ray absorptiometry (DEXA) is the gold standard
    • Most extensively validated test against fracture outcomes
  • Best location is the femoral neck
    • Best predictor of hip fracture
    • Comparable to forearm measurements for predicting fx at other site
  • USPSTF recommends
    • screening for all women age 65 or older
    • screening at age 60 for women at increased risk of osteoporotic fractures
  • Reasons for testing before age 65
    • Prior fragility fracture in a pre-menopausal woman or a man
    • FMH of fracture
    • Low body weight
    • Loss of either weight (5% of baseline weight) or height
  • Reasons for testing before age 65
    • Primary hyperPTH
    • Hyperthyroidism
    • Hypogonadism
    • Cushing’s syndrome
    • Long term steroids (prednisone at 5 mg or more/day for >6 mths)
  • No studies have evaluated the optimal interval for repeated screening
  • A minimum of 2 yrs may be needed to reliably measure change
  • Yield of repeated screening will be higher in older women, those with lower BMD at baseline, and those with other risk factors for fx
  • No data to determine appropriate age to stop screening
abnormal z score
Abnormal Z-score
  • For Z-score below -2.00
  • Workup for secondary causes of osteoporosis
    • Primary hyperparathyroidism
    • Vitamin D deficiency (low intake, lack of sunlight, malabsorption)
    • Multiple myeloma
treatment the basics
Treatment: The Basics
  • Calcium: 1200-1500 mg per day
    • Meta-analysis of 15 Ca trials involving healthy women and postmenopausal women with osteoporosis increase of ~2% in spine BMD after 2 years but no reduction in risk of vertebral or non-vertebral fracture
  • Vitamin D: 400-800 IU per day
    • Several studies show decreases in hip fracture and other non-vertebral fractures
    • Decreased risk of falling
treatment the basics15
Treatment: The Basics
  • Regular physical activity
    • Weight-bearing and resistance exercise is effective in increasing BMD of the spine and strengthening muscle mass
    • No trials establish if weight-bearing exercise reduces fracture risk
treatment fall prevention
Treatment: Fall Prevention
  • Muscle strengthening, balance training
  • Assess home for fall hazards
  • Withdrawal of medications that increase fall risk
  • Hip protector
treatment pharmacology
Treatment: Pharmacology
  • Two main classes of drugs
  • Antiresorptive agents
    • Block bone resorption by inhibiting osteoclasts
    • HRT, SERM, bisphosphonates, calcitonin, strontium ranelate
  • Anabolic agents
    • Stimulate bone formation by acting on osteoblasts
    • Sodium fluoride, parathyroid hormone
hormone replacement therapy
Hormone Replacement Therapy
  • Estrogen slows bone resorption by blocking cytokine signaling to osteoclast
  • Reduces incidence of new vertebral fractures by ~50%
  • In WHI trial, patients who received estrogen had reduction of hip fracture of 33%
  • Discontinuation of estrogen results in bone loss
  • Same mechanism as estrogen
  • Raloxifene decreases risk of vertebral fracture by 40% in women with osteoporosis
  • Raloxifene has no effect on risk of non-vertebral fracture
  • First line therapy for post-menopausal osteoporosis
  • Alendronate and risendronate
  • In women with osteoporosis, reduce the incidence of hip, vertebral, and nonvertebral fx by nearly 50%, esp during 1st year of tx
  • Alendronate can be safely administered for at least 7 years
  • Discontinuing long-term (>5 yrs) alendronate results in minimal bone loss over the next 3-5 years
  • Nasal calcitonin at 200 IU/day has been shown to decrease incidence of vertebral (but not non-vertebral) fx
  • Only one randomized trial and method has been questioned
strontium ranelate
Strontium ranelate
  • In post-menopausal women with osteoporosis, reduces the risk of vertebral fracture by 40%
  • Used in Europe
  • No currently approved by FDA
anabolic agents
Anabolic Agents
  • Synthetic parathyroid hormone
  • 20 ug of PTH SQ per day increased BMD and reduced vertebral and non-vertebral fx by more than 50%
  • Black box warning b/c osteosarcoma in rats
  • No cases of osteosarcoma in humans
  • PTH limited to patients w/ moderate to severe osteoporosis and duration not to exceed 2 years
  • Side effect of mild but asymptomatic hyperCa (10.5-11)
clinical case
Clinical Case
  • 63 yo Asian female presents to clinic for a routine visit. No significant PMH or PSH. She has NKDA and does not take any medications. She is a smoker. Her height is 5 ft and weight 95 lbs. Menarche was at age 13 yrs and menopause at age 51 yrs. Pt’s mother had osteoporosis and had a hip fracture.
clinical case25
Clinical Case
  • What are the patient’s risk factors?
    • Race—Asian
    • Post-menopausal
    • Low body weight—less than 126 lbs
    • Smoker
    • FMH of osteoporosis and fracture
  • Would you screen her for osteoporosis?
    • Yes, with DEXA of femoral neck
clinical case26
Clinical Case
  • Pt’s T-score is -2.6 and Z-score is -1.7. How would you treat her?
    • Calcium
    • Vitamin D
    • Weight-bearing exercise
    • Start bisphosphonates
    • Fall precautions
  • Screen patients 65 years or older
  • Screen younger patients with risk factors for osteoporosis, esp. if have h/o fx
  • DEXA of femoral neck is the best test
  • Bisphosphonates decrease fx by 40-50%
  • If the Z-score is abnormal, look for secondary causes of osteoporosis
  • Nelson et al. Screening for Postmenopausal Osteoporosis. Ann of Intern Med. 2002; 137 (6): 529-541.
  • Raisz, L. Screening for Osteoporosis. NEJM. 2005; 353: 164-71.
  • Rosen, C. Postemenopausal Osteoporosis. NEJM. 2005; 353: 595-603.
  • USPSTF. Screening for Osteoporosis in Postmenopausal Women. Ann of Intern Med. 2002; 137 (6): 526-528.