Notes

Outline

DEFINITION

Osteoporosis Definition: NIH Consensus Conference

Prevalence and Epidemiology In  the US, 8 million women and 2 million men have osteoporosis1 An additional 34 million Americans currently have low bone mass1 In the US approximately half of women and one-fourth of men aged 50 years or older will suffer an osteoporosis – related fracture within their lifetime2 Osteoporotic fractures account for:3 ~$14 billion in direct medical costs >400,000 hospital admissions ~2.5 million physician visits >180,000 nursing home admissions Projected annual direct costs of osteoporosis by 2040: ~$50 billion4

Osteoporosis Fracture Incidence vs Incidence of Heart Attack, Stroke, Breast Cancer

Risk Factors for Osteoporotic Fracture Being a Caucasian or Asian postmenopausal woman Personal history of fracture as an adult History of low trauma fracture in a first-degree relative Low body weight (<127 lbs) Current smoking Use of oral corticosteroid therapy ³ 7.5 mg of prednisone or its equivalent for more than 3 months Long-term use of inhaled steroids also may affect bone health Advancing age

Risk Factors for Osteoporotic Fracture (continued) Impaired vision despite correction Estrogen deficiency at an early age (<45 yrs) Dementia Poor health/frailty Recent falls Lifelong low calcium intake Low physical activity Alcohol consumption in amounts >2 drinks per day

Fracture Risk with Aging*

Increased Risk Based on Gender and Hypogonadism

Risk Factors: Men Low testosterone levels Use of corticosteroid therapy > 7.5 mg of prednisone for more than 3 months Alcohol consumption Smoking Between 50 and 60% of men with osteoporosis have disorders known to produce bone loss including  hyperparathyroidism, intestinal disorders, malignancies, and conditions resulting in immobilization Orwoll, E. Osteoporosis in Men. NOF Osteoporosis Report 1999; Summer.

Bone Loss Following Menopause Women can lose up to 20% of their bone mass during the first 5 to 7 years following menopause1 Researchers have shown that an average annual bone loss of 3-5% occurs during the first 5 postmenopausal years compared to a loss not significantly different from zero during postmenopausal years 6 through 82 1NOF, 2002 2Mazzuoli G, Acca M, Pisani D, et al. Bone 2000;26(4):381-6.

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Estrogen Discontinuation and Rapid loss of HRT bone sparing effect 140,584 women from NORA 61% of women had used estrogen at some point 48% users at baseline 269 new hip fractures Current estrogen users had reduced risk of hip fracture 0.1% of 67,000 vs 0.28% of 53,000 OR 0.49 Women who had stopped estrogen in past 5 years had increased risk of hip fracture  0.26%     OR 1.73 95% CI: 1.08-2.66 Barrett Conner E. Recency and Duration of of Postmenopausal hormone therapy: effects on bone mineral density and fracturte risk in the National Osteoporosis Risk Assessment (NORA) Study Menopause 2003, 10:412-419

Parathyroid Physiology

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Pathophysiology of Glucocorticoid induced Osteoporosis

Medical Conditions that May Increase Risk for Osteoporosis Insulin-dependent diabetes mellitus Malabsorption syndromes, sprue, eating disorders (anorexia nervosa) inadequate diet, weight loss Hyperparathyroidism Hypogonadism, primary and secondary Rheumatoid arthritis Inflammatory bowel disease There are less common medical conditions know to result in bone loss

Medications Associated with Reduced Bone Mass in Adults Anticonvulsants (phenobarbital, phenytoin) Cytotoxic drugs Glucocorticoids and adrenocorticotropin Gonadotropin-releasing hormone agonists Immunosuppressants Lithium Long-term heparin use Progesterone, long-acting Total parenteral nutrition

Glucocorticoid-Induced Osteoporosis Common form of secondary osteoporosis Associated with long-term use of cortisone/prednisone-like oral medications Evaluate bone mineral density at the hip and spine Consider prescribing an FDA-approved medication Alendronate (see medication options) Risedronate (see medication options)

Glucocorticoid Use and Fracture Risk in Users 18 Years and Older

Hip Fracture

World Health Organization (WHO) Osteoporosis Guidelines

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Who Should Have a BMD Test? All women aged 65 and older regardless of risk factors Younger postmenopausal women with one or more risk factors (other than being white, postmenopausal and female) Postmenopausal women who present with fractures (to confirm diagnosis and determine disease severity)

Universal Prevention/Treatment Strategies Counsel all patients on risk reduction Instruct all patients on adequate daily intake of calcium and vitamin D Provide guidelines for regular participation in  weight-bearing and muscle strengthening exercises to reduce risk of falls and fractures Provide strategies for fall prevention Counsel all patients on avoiding tobacco smoking and excessive alcohol intake

For Strong Bones: Calcium  Recommended Calcium Intake Infants                                                                      Amount in mg/day 0 to 6 Months 210 6 to 12 Months 270 Children and Adolescents 1 through  3 years 500 4 through  8 years 800 9 through 18 years                1300 Adult Women and Men 19 through 50 years 1000 > 50 years 1200-1500 Pregnant and Lactating Women 18 years 1300 19 through 50 years 1000 Source: National Academy of Sciences, 1997

For Strong Bones: Calcium

The Role of Exercise in Prevention and Treatment Benefits of exercise as they relate to osteoporosis: Decreased risk of falling Improved bone mass and strength Enhanced muscle strength Improved balance, better posture Increased flexibility of soft tissues Improved cardiovascular fitness Improved depression Recommend both weight-training exercises and    resistance-training exercises

NOF Recommendations for Initiation  of Pharmacologic Therapy Initiate therapy to reduce fracture risk in women with: BMD T-scores below –2.0 by central DXA with no risk factors BMD T-scores below –1.5 by central DXA with one or more risk factor History of a prior vertebral or hip fracture

US FDA-Approved Pharmacologic Options Bisphosphonates Alendronate Risedronate Calcitonin Estrogen/Hormone Therapy Parathyroid Hormone Therapy (PTH 1-34, teriparatide) Selective Estrogen Receptor Modulators (SERMs) Raloxifene

Alendronate In controlled clinical trials, Fracture Intervention Trial (FIT), FACET, FOSIT, use of  alendronate increased or maintained bone density and reduced the incidence of fractures at the hip, spine and wrist by 50% - 3 yr RCT assessing women with osteoporosis and osteopenia. Doses of 5mg day for 2 years, subsequently switched to 10 mg/day

Risedronate In controlled clinical trials, Vertebral efficacy risedronate trial (VERT), HIP  use of risedronate  increased or maintained bone density and reduced the risk of spine fractures by 40% and non-spine fracture by 30%

Estrogen: FDA Recommendations .

Parathyroid Hormone (1-34) (PTH) or Teriparatide PTH (1-34) is classified as an anabolic agent that builds new bone PTH (1-34) is administered daily by subcutaneous injection PTH (1-34) decreases the risk of vertebral fractures by 65% and non-vertebral fragility fractures by 53% after an average of 18 months of therapy

PTH (1-34) Teriparatide Fracture Results New vertebral fractures occurred in 14% of placebo patients, 5%of women taking 20 mcg (RR=0.35)1 New nonvertebral fragility fractures occurred in 6% of placebo patients and in 3% of those taking teriparatide (RR=0.46)1 Similar fracture reduction was observed regardless of the number of prevalent vertebral fractures present at baseline2 1Neer RM, Arnaud CD, Zanchetta JR, et al. N Engl J Med 2001;344(19):1434-41. 2Marcus R, Wang O, Satterwhite J, Mitlak B. J Bone Miner Res 2003 18 (1):18-23.

Teriparatide Adverse Effects Side effects are usually mild and may include: Nausea Leg cramps Dizziness Long-term effects are unknown Use currently limited to 2 years PTH trials were stopped early due to the finding of osteosarcoma in animal studies No osteosarcomas have been reported in humans FDA assigned a black box warning because of osteosarcoma findings in animal studies. US Food and Drug Administration. FDA. Talk Paper. November 26, 2002.

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