Kenneth G. Saag, MD, MSc
Professor of Medicine
Department of Medicine, Division of Immunology/Rheumatology

Jeffrey R. Curtis, MD, MPH
Assistant Professor of Medicine
Department of Medicine, Division of Immunology/Rheumatology

The University of Alabama at Birmingham
Birmingham, Alabama

In accordance with the Accreditation Council for Continuing Medical Education Standards for Commercial Support the faculty disclose the following commercial affiliations:

Dr. Saag - research support from Sanofi-Aventis, Norvartis, Eli Lilly & Co., Amgen, Roche; is a consultant for Merck & Co., Eli Lilly & Co., Novartis, Amgen, Roche; receives an honorarium from Merck & Co., Eli Lilly & Co., Novartis and Roche.

Dr. Curtis - research support from Sanofi-Aventis, Novartis, Eli Lilly & Co., Amgen, Roche; consultant for Merck & Co., Eli Lilly & Co., Novartis, Amgen, Roche; receives an honorarium from Merck & Co., Eli Lilly & Co., Novartis, and Roche.

The University of Alabama School of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

The University of Alabama School of Medicine designates this educational activity for a maximum of 0.25 AMA PRA Category 1 credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The boards of nursing in many states, including Alabama, recognize Category 1 continuing medical education courses as acceptable activities for the renewal of license to practice nursing.

Osteoporosis is the world’s most common metabolic bone disease and contributes to more than 2 million fractures in the United States each year. Despite the substantial morbidity and excess mortality associated with osteoporotic fractures, a majority of postfracture patients remain untreated.

The National Osteoporosis Foundation (NOF) estimates 10 million Americans have osteoporosis and almost 34 million have osteopenia. “While white postmenopausal women have the highest risk for bone loss, minorities will experience the greatest increase in osteoporosis-related fractures during the next 15 years,” says UAB Professor of Medicine and Epidemiology Kenneth G. Saag, MD, MSc, director of the UAB Center for Education and Research on Therapeutics (CERT) of Musculoskeletal Disorders in the Division of Clinical Immunology and Rheumatology.

“Osteoporosis management guidelines have concentrated on diagnosing the condition with periodic bone mineral density [BMD] testing using dual energy X-ray absorptiometry [DXA]. In addition to

BMD and age, other clinical risk factors, including prior fracture, are critically important considerations when evaluating people with osteoporosis and assessing fracture risk,” says UAB rheumatologist and epidemiologist Jeffrey R. Curtis, MD, MPH, associate director of UAB’s CERT of Musculoskeletal Disorders.

“DXA results known as T-scores are measures of relative risk and have different prognostic significance at different ages. Using them without considering other clinical risk factors can lead to unnecessary drug intervention in younger patients and failure to properly treat 80% of older patients who are likely to fracture in the near future,” he says. “Additionally, recommendations regarding prescription therapies for patients with T-scores in the osteopenic range [less than -1 but more than -2.5 standard deviations below the mean peak value] are controversial. Because so many women are in this range, we must better integrate T-scores with clinical risk factors to identify the osteopenic patients most likely to benefit from medications that help prevent fractures.”

Emerging treatment paradigms focus on absolute fracture risk and quantify the absolute risk of fracture over a longer period, such as 10 years. By 2008, Curtis and Saag emphasize, this information will be available as a standard feature of DXA output, substantially reducing uncertainty regarding which patients in the osteopenic BMD range require treatment.

Risk factors for osteoporotic fractures include family history of osteoporosis, previous fractures, dementia, low body weight or weight loss, lack of weight-bearing exercise, cigarette smoking, excessive alcohol intake, and the use of certain drugs, including glucocorticoids, selective serotonin reuptake inhibitors, androgen deprivation therapy for prostate cancer, and aromatase inhibitors for breast cancer.

“Osteoporosis often goes undiagnosed until a fracture occurs,” Curtis says. “The best way to identify people with silent osteoporosis prior to their first complication is by measuring BMD, preferably with DXA, which is relatively inexpensive and exposes patients to minimal doses of radiation. In some clinical settings, such as nursing homes, DXA scans are not readily available, but detailed histories and physical examinations may reveal significant risk for future fractures.” Curtis and Saag recommend initiating medication in extremely high-risk patients if BMD scores are difficult to obtain.

People with osteoporosis risk recurrent fractures of the hips, vertebrae, ribs, and wrists. Fractures lead to significant pain, poor quality of life, depression, functional decline, and potential complications of immobility, including deep vein thrombosis and pressure ulcers. People with osteoporosis may develop spinal deformities or kyphosis and can lose inches of height. Patients with compression fractures may have no back pain but complain their height is shrinking.

“Untreated patients who experience a fracture are at high risk for recurrence. Once a fracture has occurred in an older patient, regardless of their gender, their fracture risk becomes equal to the risk of a first fracture in a woman 10 years older and remains persistently elevated for a decade. Fifty percent of patients who experience an osteoporotic fracture will have a second fracture within 10 years of the first event, and almost half of those fractures occur within the first 2 years,” Curtis says.

Glucocorticoids and vitamin D deficiency are important, treatable causes of secondary osteoporosis, says Saag, who, with Curtis and other UAB investigators, recently found more than 90% of individuals taking long-term glucocorticoids reported at least one adverse event, with 55% of those reporting that at least one event was very bothersome. Weight gain (70%), cataracts (15%), and fractures (12%) were the most common self-reported adverse events (Arthritis & Rheumatism. 2006;55[3]:420-426).

The study indicated glucocorticoid users older than 65 years who take >20 mg/day of prednisone for >2 years have the highest risk for osteoporotic fractures. Vertebral fractures may be asymptomatic; studies estimate two thirds of patients taking glucocorticoids live with undiagnosed fractures. “Even at low doses, adverse events have a dose-dependent association with cumulative glucocorticoid use and are significantly associated with increased duration of use,” Saag says.

“Certain chronic disease sufferers, including those with early rheumatoid arthritis, are likely to reap significant benefits from the sustained, disease-modifying effects of glucocorticoids, but therapies that minimize the risk of drug-related osteoporosis and related fractures in these patients are underutilized,” adds Curtis, who led a prospective randomized trial that found physicians engaged in a Web-based intervention incorporating personalized audit and feedback of glucocorticoid-induced osteoporosis management had higher rates of successful outcomes compared with controls (Arch Intern Med. 2007;167:591-596).

The NOF recommends older adults consume 1200 mg of calcium daily and take vitamin D supplements with physician supervision. Curtis recommends testing 25-hydroxy vitamin D levels in patients with suspected osteoporosis and prescribing ergocalciferol if vitamin D deficiency is found.

“Bisphosphonates, such as alendronate, ibandronate, and risedronate, are the most common prescription drugs for preventing and treating osteoporosis, producing modest bone mass increases and reducing fracture risk by up to 50% over 3 to 5 years,” he says. “Studies show the drugs may continue to yield benefits for an additional 5 years after patients stop taking them. Long-term adherence, however, is poor. Almost half of patients who begin osteoporosis therapy discontinue medication within 1 year. Patients need to understand their fracture risk and the benefits of treatment to reinforce the need for adherence.”

Newer bisphosphonate regimens, which include once-monthly oral ibandronate; twice-monthly risedronate; and 30-second intravenous ibandronate administration every 3 months, can provide convenient dosing options for some patients. Curtis says osteoporosis investigators are currently studying additional bisphosphonates, such as once-yearly zoledronate, that may soon provide attractive treatment choices.

Teriparatide, the newest osteoporosis medication, is an injectable anabolic agent that increases the number and action of osteoblasts. In a study of 1637 postmenopausal women, 2 years of daily 1000 mg calcium and 400 IU vitamin D supplementation plus teriparatide decreased spinal fracture risk by 65% and the risk for other osteoporotic fractures by 53% (Arch Intern Med. 2004; 164:2024-2030).

“Teriparatide increases BMD and decreases fracture risk. No fracture outcomes studies directly compare teriparatide with bisphosphonates, but based on its anabolic mechanism of action and the substantial gains in BMD and bone strength, it may be the most effective osteoporosis treatment currently available,” Curtis says. Teriparatide is most appropriate for high-risk patients and those who have not responded to previous osteoporosis therapies.

“We must comprehensively assess the risks and benefits of managing osteoporosis and osteopenia to reduce the occurence of fractures and the long-term costs and complications they can incur,” he says. “Clinicians can explain fracture risk by discussing it in the context of other health issues. For many patients, the risk of fracture exceeds that of heart disease, cancer, and stroke. Helping them consider how fracture risk compares with these other illnesses reinforces the seriousness of osteoporosis and the importance of prevention.”

For more information:

Dr. Kenneth Saag
Dr. Jeffrey Curtis
1-800-UAB-MIST
mist@uabmc.edu

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