Chapter 17 - Osteoporosis and Current
Therapeutic Management
• Kellie F. Flood-Shaffer, MD, FACOG
Learning Objectives
Identify prevalence & causes of osteoporosis
Understand pathophysiology of osteoporosis
Recognize current therapeutic options for the
prevention and treatment of osteoporosis
Prevalence of Osteoporosis in the
United States
National Osteoporosis Foundation. 2003.
National Institutes of Health. JAMA 2001;285:785–795.
Osteoporosis is Common
Among US Women
Riggs et al. Bone 1995;17:505S–511S.
American Heart Association. Heart and Stroke Facts: Statistical Update, 1996.
American Cancer Society. Cancer Facts & Figures, 1996.
WHO Classification of BMD
Factors Influencing Risk of
Osteoporotic Fractures
Heaney. Endocrinol Metab Clin North Am 1998;27:255–265.
Bone Architecture
• BMD is not the only determinant of bone
strength, although it is the best predictor;
it does not reflect all aspects of bone
quality
• The microarchitecture of trabecular bone
contributes to bone strength
– Honeycomb structure comprises vertical and
horizontal struts
– Loss of struts increases fracture risk
– Improvement in trabecular bone decreases
fracture risk
Microarchitectural Changes
Dempster et al. J Bone Miner Res 1986;1:15–21.
Prior Fracture as a Risk Factor: 1-Year Fracture
Incidence Following Incident Fracture
*P < 0.05 vs. patients without prevalent vertebral fracture.
Lindsay et al. Osteoporos Int 2000;11(suppl2):S112.
Primary Osteoporosis:
Risk Factors
• Advanced age
• Genetics
– Family history of osteoporosis
– Caucasian race
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Inadequate calcium, vitamin D intake
Low achieved peak bone mass
Sedentary lifestyle
Cigarette smoking
Heavy alcohol consumption
Early menopause
Postmenopausal Osteoporosis
• Diminishing estrogen levels lead to a
disturbance in the balance between
osteoclasts and osteoblasts
• In first 5 to 8 years after menopause,
women lose 2% of cortical bone and 5% of
trabecular bone per year
Secondary Osteoporosis: Causes
• Medications
• Genetic disorders
• Disorders of calcium
balance
• Endocrine disorders
• Hypovitaminosis D
• Gastrointestinal
diseases
• Nutritional disorders
• Rheumatoid arthritis
• Chronic renal disease
• Cancer
Secondary Osteoporosis:
Medication Causes
Fitzpatrick. Mayo Clin Proc 2002;77:453–468.
Mechanisms of Corticoidinduced Bone Loss
Segal et al. J Musculoskeletal Med 1997;14:43–56.
Secondary Osteoporosis:
First-level Diagnostic Tests
• Complete blood cell count
• Serum chemistries
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Calcium
Phosphorus
Creatinine
Alkaline phosphatase
Albumin
Thyroid-stimulating hormone
Liver enzymes
Secondary Osteoporosis:
Second-level Diagnostic Tests
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Urinary calcium excretion
Parathyroid hormone
Urinary free cortisol
Markers of bone remodeling
Erythrocyte sedimentation rate
25-hydroxyvitamin D
Protein electrophoresis
Bone biopsy
Secondary Osteoporosis: Diagnosis
Harper et al. Endocrinol Metab Clin North Am 1998;27:325–348.
Clinical Evaluation
• Height measurement
• Physical examination
• Medical history
– Risk factor assessment
– Signs and symptoms
• Laboratory tests (as appropriate)
• Spinal radiograph (if symptomatic)
• BMD testing
BMD Assessment
• Dual energy x-ray absorptiometry (DXA)
– Gold standard
– Sites usually measured: lumbar spine,
proximal femur, total hip
• Quantitative computed tomography
• Ultrasound
Indications for BMD Testing
• Postmenopausal women age <65 with
additional risk factors (other than being
white)
• All women age 65
• Postmenopausal women with a fragility
fracture
• Initiation of long-term glucocorticoid or
other drug therapy causing bone loss
ACR. Arthritis Rheum 2001;44:1496–1503.
National Osteoporosis Foundation. 2003.
Principles of Osteoporosis Prevention
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Adequate calcium and vitamin D
Regular exercise
Limit alcohol
Avoid smoking
Fall prevention
Pharmacologic intervention
Calcium Supplement Options
ACOG Educational Bulletin No. 246 Int J Gynaecol Obstet 1998;62:193–201.
Pharmacologic Intervention:
NOF Indications
• Postmenopausal women with T-score
<–2.0 and no risk factors
• Postmenopausal women with T-score
<–1.5 + risk factor(s)
• Postmenopausal women with prior
vertebral or hip fracture
The National Osteoporosis Foundation. 2003.
Pharmacologic Intervention Options
for Prevention and Treatment
*Used in combination with progestins in women with an intact uterus; combination agents available with
indications for postmenopausal osteoporosis prevention; †treatment indication is for women >5 years
postmenopause; ‡treatment indication is for women at high risk of fracture; SERM = selective estrogen
receptor modulator.
Bisphosphonates:
Mechanisms of Action
• Potent inhibition of osteoclasts
• Reduced formation rate of new bone
remodeling units
• Increased bone mass
• Improvement in bone architecture
(preservation of horizontal trabeculae,
bone strength)
Candidates for Bisphosphonates
Looker et al. J Bone Miner Res 1995;10:796–802.
Schott et al. Osteoporosis Int 1998;8:247–254.
Effects of Alendronate on New Vertebral
Fractures: Fracture Intervention Trial (FIT)
Black et al. Lancet 1996;348:1535–1541.
Effects of Alendronate on Fracture Risk in
Women with Pre-existing Fracture: FIT
Watts. Endocrinol Metab Clin North Am 1998;27:419–439.
Black et al. Lancet 1996;348:1535–1541.
Effect of Risedronate on Fractures: Vertebral
Efficacy with Risedronate Therapy (VERT) Study
Harris et al. JAMA 1999;282:1344–1352.
Glucocorticoid-induced
Osteoporosis Management
• Prevention
– Risedronate 5 mg/d or 35 mg/wk
• Treatment
– Risedronate 5 mg/d or 35 mg/wk
– Alendronate 5 mg/d, 10 mg/d or 70 mg/wk
Bisphosphonate Dosing
• Assess patient’s swallowing ability
• Take at least 30 minutes before food or
beverage
• Take with full 8-oz glass of water
• Remain upright (sitting or standing)
Raloxifene and Vertebral Fractures: Multiple
Outcomes of Raloxifene Evaluation (MORE)
Ettinger et al. JAMA 1999;282:637–645.
Effects of Raloxifene on
Cardiovascular Events: MORE
Barrett-Connor et al. JAMA 2002;287:847–857.
Effects of Raloxifene on
Breast Cancer: MORE
Hormone Therapy (HT):
Reduction in Fracture Risk
WHI = Women’s Health Initiative; RR = relative risk; CI = confidence interval; HERS = Heart and
Estrogen/Progestin Replacement Study I and II.
Hulley. JAMA 2002;288:58–66. WHI. JAMA 2002;288:321–333.
HT: Other Clinical Outcomes
CHD = coronary heart disease; WHI = Women’s Health Initiative; CI = confidence interval; RR = relative risk; HERS = Heart and
Estrogen/Progestin Replacement Study I and II; VTE = venous thromboembolism. Hulley. JAMA 2002;288:58–66. WHI. JAMA
2002;288;321–333.
Effects of 200 IU Calcitonin vs.
Placebo on Vertebral Fracture
Chesnut. Am J Med 2000;109:267–276.
Effects of Teriparatide on Fractures
PTH = parathyroid hormone.
Neer et al. N Engl J Med 2001;344:1434–1441.
Effects of Calcium on BMD
Reid et al. Am J Med 1995;98:331–335.
Therapeutic Monitoring
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Calcium/vitamin D intake
Medication compliance
Safety review
BMD testing
Height
Fracture Management
• Vertebral fracture
– Acute: bed rest, analgesics, ice packs
– Chronic pain: muscle relaxants
– Vertebroplasty/kyphoplasty
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Physical therapy
NSAIDs (degenerative arthritis)
Fall prevention strategies
Hip pads
Indications for Referral
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T-score <–3.0
Osteoporosis at a young age
Fractures + borderline/normal BMD
Secondary disease, eg, endocrinopathies
Candidates for combination therapies
Intolerance of approved therapies
Treatment of nonresponders
Hodgson et al. Endocr Pract 2001;7:293–312.