The field of research on osteoporosis has grown in recent years. This has resulted in significant advances in determining the causes of osteoporosis, assessing risk factors, and creating new treatment methods. Several initiatives that are focused on skeletal biology should help in developing strategies to maintain and enhance bone density in childhood.
An Overview of Osteoporosis Research
Significant advances in preventing and treating osteoporosis are available today as the direct result of research focused on:
- Determining the causes and consequences of bone loss at the cellular and tissue levels
- Assessing risk factors for osteoporosis
- Developing strategies to maintain and enhance bone density
- Exploring the roles of such factors as hormones, calcium, vitamin D, drugs, and exercise on bone mass.
Research Studies on Osteoporosis
The following research studies have led to significant advances in understanding the causes of osteoporosis, the specific effects on the body, and potential new diagnostic, treatment, and prevention options:
- Identification of a gene essential for the formation of bone. Through a convergence of efforts by investigators around the world, research has shown that normal skeletal development in both mice and humans requires two active copies of the gene Cbfa1. This discovery is expected to open up a number of exciting new research areas.
- Discovery that estrogen causes "programmed cell death" in the cells responsible for degradation of bone (osteoclasts). By paving the way for future assessment of whether drugs can also affect the programmed cell death of osteoclasts (thereby making them potentially useful as bone-protecting treatments), this discovery represents an exciting link between basic research and tangible patient benefit.
- Discovery of a collection of molecules created by researchers (called peptidomimetics) that successfully blocks part of the bone resorption process. This is the first clear indication that a particular synthetic antagonist may be effective in the prevention of osteoporosis. The finding may hold promise for combating bone loss in women who cannot tolerate estrogen therapy.
- Patient-based research finding with clear implications for developing and targeting new preventive strategies. A recent research study on elderly women (who already had several spine fractures at the start of the study) determined that they experienced the greatest health benefit from calcium supplementation (both in terms of reducing the rate of new spine fractures and stopping bone loss).
- Low-dose estrogen study. A recent study supported by NIAMS (National Institute of Arthritis and Musculoskeletal and Skin Diseases) tested the usefulness of daily low-dose estrogen plus progesterone in women over age 65 and found that these women showed significant increases in spine, forearm, and total body bone mineral density. This study provides proof that low-dose estrogen can be an effective preventive and therapeutic option.
- Study of osteoporotic fractures (SOF). The development of risk-prediction models for osteoporotic fractures that incorporate clinical risk factors, along with bone mineral density measurements, is an important advance in identifying persons at greatest risk for fractures and for whom intervention measures may be suitable. The SOF, a study of postmenopausal Caucasian women, led to the identification of 14 clinical risk factors. Possession of five or more of these factors greatly increased the risk of fracture in the women in the study.
- Secondary osteoporosis. Information regarding the diseases, physical states, medical treatments, and drugs that can lead to the development of secondary osteoporosis is now available to physicians. The information alerts physicians to the appropriate use of treatment, the monitoring of patients at risk, and, where possible, the use of intervention measures to prevent the development of osteoporosis. For example, it is generally agreed that patients on glucocorticoid therapy for 2 months or longer and patients whose conditions place them at high risk for osteoporotic fractures should be considered for bone density measurement.
- Screening in the general population. Because there is a lack of sufficient evidence regarding the cost-effectiveness of routine screening or the effectiveness of early initiation of preventive drugs, an individualized approach is recommended for testing for bone loss.
- Testosterone study. Circulating levels of testosterone are known to decline in men as they age, which can lead to bone loss. A recent clinical trial of testosterone supplementation in a group of older men with low hormone levels revealed little difference in bone mineral density between the placebo-treated and testosterone-treated men, indicating that hormone therapy to replace bone mass is not necessary for most older men.
- Gene for osteoporotic fractures. A recent study showed that women 65 and older with the apolipoprotein E (APOE e4) gene on chromosome 19 were nearly twice as likely as those without the gene to suffer hip and wrist fractures. Women with this gene experience weight loss that contributes to bone loss and may have reduced levels of vitamin K, which stimulates bone formation and reduces bone-cell loss.
- Body mass index. Suboptimal bone growth in childhood and adolescence is as important as bone loss to the development of osteoporosis. Growth hormone and insulin-like growth factor-I, which are secreted the most during puberty, play a role in acquiring and maintaining bone mass and in determining body composition into adulthood. Children and youth with low body mass index (BMI) are likely to have a lower-than-average peak bone mass. There is a direct association between BMI and bone mass throughout the adult years, and several studies of fractures in older persons have shown an inverse relationship between fracture rates and BMI.
- Nutritional studies. It is known that calcium is essential for building strong bones and reducing fracture risk. Vitamin D is required for optimal calcium absorption by the body. Both substances should be part of any osteoporosis treatment. Recent studies have shown that while some substances, such as high dietary protein, caffeine, phosphorus, and sodium, can adversely affect calcium balance, their effects appear not to be important in individuals who have an adequate calcium intake.
- Gender/ethnicity. Caucasian postmenopausal women experience almost three quarters of hip fractures. However, women of other age, racial, and ethnic groups, as well as men and children, are also affected by osteoporosis. Much of the difference in fracture rates among these groups appears to be explained by differences in peak bone mass and rate of bone loss. Differences in bone geometry, frequency of falls, and presence of other risk factors also appear to play a role.
- New drugs. Bisphosphonates and selective estrogen receptor modulators (SERMs) are fairly recent prevention and treatment options for osteoporosis. Randomized placebo-controlled trials and meta-analysis of bisphosphonates (etidronate, alendronate, and risedronate) show that all increase bone mineral density at the spine and hip in a dose-dependent manner and reduce the risk of vertebral fractures by 30 percent to 50 percent. In large clinical trials, raloxifene, a SERM recently approved by the Food and Drug Administration (FDA), reduced the risk of vertebral fracture by 36 percent.
- Exercise and falls. There is some evidence that childhood exercise, particularly resistance and high-impact exercise (such as weight training), contributes to higher peak bone mass. While there are health benefits to low-impact exercise, such as walking, it has minimal benefit for bone mineral density. Acknowledging that falls are a major risk factor for osteoporotic fractures, researchers conducted randomized clinical studies of exercise during adulthood and later in life which showed that the conditioning, balance-enhancing, and muscle-building effects of exercise reduce falls by approximately 25 percent.
- Ultrasound. Clinical trials of drug therapy for osteoporosis have most often used dual energy x-ray absorptiometry (DEXA) to measure bone mineral density. Studies of the less cumbersome and less expensive quantitative ultrasound (QUS) of the heel show that QUS predicts hip fracture and other nonvertebral fractures nearly as well as DEXA at the femoral neck.
- Biomarkers. Biomarkers of bone remodeling (formation and breakdown), such as alkaline phosphatase and osteocalcin (serum markers) and pyridinolines and deoxypyridinolines (urinary markers), are of limited usefulness in evaluating individual patients because they do not predict bone mass or fracture risk. However, research studies show that biomarkers correlate with changes in indexes of bone remodeling, and may provide insights into the mechanisms of bone loss.