Osteoporosis Prevention, Diagnosis, and Therapy
Abstract & Commentary
Synopsis: Osteoporosis is now considered to be largely preventable, yet controversy over screening, diagnosis, and treatment continues. Prevention of fractures by enhancing bone mass, and reducing the risk and consequences of falls, is the primary treatment goal.
Source: NIH Consensus Development Panel. JAMA. 2001; 285:785-795.
The national institutes of health (nih) recently convened this expert consensus panel to review the literature on osteoporosis for the last 5 years and prepare this statement clarifying current issues. Thirteen physicians, scientists, and a dentist from multiple specialties heard testimony from 32 experts and reviewed a bibliography of 2449 references in front of an audience of 699 persons who were given an opportunity to comment on the statement before revisions were made.
Osteoporosis results when bone strength (an integration of bone density and bone quality) is compromised and leads to an increased risk of fracture. Usually this results from bone loss, but it also occurs if an individual does not reach their optimal peak bone mass in adolescence. Although the World Health Organization defines osteoporosis as a bone mineral density (BMD) 2.5 SD below the mean for young adult Caucasian women, there is controversy about applying this criterion to others, and furthermore, BMD only measures about 70% of total bone strength.
Both men and women have age-related decline in BMD, although women experience more rapid bone loss and, thus, have fractures earlier. Caucasian women at age 50 have a 14% chance of lifetime hip fracture, compared to 5-6% for men, and women have 3/4 of all hip fractures. Most of this gender difference is thought to be explained by lower peak bone mass and earlier onset of bone loss in Caucasian women, which may explain why African-American women with higher peak BMDs have less fractures (6% lifetime risk vs 14% for Caucasian women). However, some Japanese women have lower BMDs but also have lower rates of hip fractures.
Fracture risk is not only related to low BMD, but also to clinical factors such as history of falls and poor physical functioning (slow gait, decreased strength, impaired vision and cognition, and environmental hazards). Smoking and family history of osteoporosis are also important predictors of developing osteoporosis. While persons in these categories should be screened for low BMD, there is insufficient evidence at this point to advocate screening the entire population for osteoporosis. Clinicians must still make individual judgments on screening for persons with advancing age. More research is also needed to standardize different measurements of BMD, which tend to reflect risk mainly for the site on which they are performed and cannot reliably be compared between different devices.
Secondary osteoporosis can result from a large number of medical disorders and drugs, especially long-term glucocorticoid use. Only 2 months of glucocorticoids in a daily dose of 5 mg or more can result in excessive bone loss. In men, the most common cause of secondary osteoporosis is hypogonadism, followed by glucocorticoid use and alcoholism. Organ transplant recipients and those with excessive thyroid hormone are also at high risk for osteoporosis.
Adolescent girls with low body weight, emotional stress, and strenuous athletic training, which can produce delayed menarche, oligo- and amenorrhea, may not achieve adequate peak bone mass and are also at risk for increased fractures. Adolescent boys similarly need testosterone to achieve and maintain maximal bone mass. Since bone accumulation attained early in life is so critical to lifelong skeletal health (peak bone mass is completed with the cessation of linear growth), it is particularly important to maximize bone mass in children with adequate nutrition (calcium and vitamin D) and healthy lifestyles (exercise). Cigarette smoking, which usually starts in adolescence, may have a negative affect on achieving maximal bone density.
Effective treatments for established osteoporosis start with adequate calcium and vitamin D intake from diet or supplements, which increases spinal BMD and reduces fractures. The therapeutic effects of other drug treatments are seen when used in conjunction with calcium and vitamin D. Exercise is also necessary for bone acquisition during skeletal growth, and at other times may be important in improving muscle strength and balance, which can prevent falls.
Hormone replacement therapy has a positive effect on BMD and vertebral fracture reduction, but few studies have measured actual hip fracture reduction. Phytoestrogens from plant sources have weak estrogen-like effects but have not yet shown reduction in fracture risk in humans. Calcitonin will increase BMD in the lumbar spine but has weaker supporting research for reducing fractures. Bisphosphonates (etidronate, alendronate, and risendronate) will increase BMD at the hip and spine and reduce vertebral fractures by 30-50% in adults, but they have not been studied for safety in children. Selective estrogen receptor modulators (SERMs) are actively being studied; raloxifene is FDA approved and has been shown to reduce vertebral fracture risks. Tamoxifen can maintain bone mass but has not been proven yet to reduce fracture risk.
This report cautions against using follow-up BMD or other serum bone markers as indications of failed therapy. The Fracture Intervention Trial reported a statistical phenomenon of "regression to the mean" in successive BMD studies, such that larger bone loss in the first year was followed by greater gain in the next year.1
In the treatment of acute osteoporotic fractures, new minimally invasive procedures injecting polymethlmethacrylate bone cement into fractured vertebrae holds promise but has not been tested with controlled trials. Early surgical management of hip fractures remains the preferred treatment with the least perioperative morbidity.
COMMENT BY MARY ELINA FERRIS, MD
Osteoporosis is a huge public health problem affecting most of the elderly in the United States, estimated to cost $10-15 billion in hospital costs alone annually. Vertebral deformities and subsequent spine and hip fractures were once thought to be inevitable, but now are considered largely preventable with better attention to bone health at all ages.
Screening of all persons for osteoporosis should include history and physical examinations for specific risk factors, loss of height, and change of posture. Evaluation for secondary causes should be considered once the diagnosis is made. Measurement of bone density using various methods and skeletal sites is useful to predict fracture risk at the site that is being measured, but the cost-effectiveness of universal BMD screening has not been established in randomized controlled trials. This NIH panel recommends that BMD testing be considered on an individual basis when it would aid decisions about beginning treatments for fracture prevention, and that it be used cautiously to assess response to treatment.
The National Osteoporosis Foundation, with the support of multiple specialty societies, has issued recommendations that all women age 65 or older receive a screening BMD, although they acknowledge that this mainly applies to Caucasian women since research is lacking in other groups.2 Medicare coverage recently began for BMD screening once every 2 years. Additional drugs will likely be added to our choices (eg, risendronate was also recently shown to reduce hip fractures).3
This article reinforces the importance of building maximal bone mass in adolescents as a primary prevention for a subsequently common disease. Routine screening with BMD is not scientifically supported; our traditional skills for risk assessment and individualized treatment are still the preferred approach. Once osteoporosis is identified (often by the first fracture), drug treatment should be accompanied by calcium and vitamin D supplementation, along with attention to reducing the potential for future falls and fractures.
References
1. Cummings SR, et al. JAMA. 1998;280:2077-2082.
2. National Osteoporosis Foundation. http://www.nof.org. Accessed April 16, 2001.
3. McClung MR, et al. N Engl J Med. 2001;344:333-340.