Osteoporosis: Diagnosis and Managements _ _____________________________________________________
POSTMENOPAUSAL OSTEOPOROSIS Postmenopausal osteoporosis causes most of the skeletal difficulties in the adult female population. Again, these molecular processes are not well understood. It is known that declining estrogen levels cause an increase in osteoclastic activity with a resulting imbalance between skeletal formation and resorption [23]. Estrogens act on nuclear receptors of both osteoblasts and osteoclasts. Deficiency of estrogen leads to, among other effects, the upregulation of osteoprotegerin ligand gene transcription and increased production of macrophage colony stimulating factor (M-CSF), both of which result in increased osteoclastic activity [30]. SECONDARY OSTEOPOROSIS The final category is osteoporosis due to secondary causes. This can be from many diseases, including liver disease, rheumatoid arthritis, celiac sprue or other malabsorption syndromes, inflammatory bowel disease, lymphoma, multiple myeloma, thalassemia, acromegaly, amyloidosis, leukemia, and thyrotoxicosis. Nutritional deficiencies or medications that have effects on calcium, sex steroids, or other factors related to bone formation or resorption also may cause secondary osteoporosis [23]. In men, 30% to 60% of osteoporosis cases have been associated with secondary causes [25]. In perimenopausal women, about half of the cases are due to secondary causes, such as hyperthyroidism and anticonvulsant treatment. The most common medications associated with osteoporosis are glucocorticoids. Even small doses (i.e., 2.5–7.5 mg prednisone per day) have been associated with an increase in fractures [23]. Patients with osteoporosis should have possible secondary causes explored, as many of the conditions are treatable. RISK FACTORS There are numerous risk factors that predict low BMD, the development of osteoporosis, and resulting fractures. Risk factors include advanced age, white race, tobacco use, female gender, low body weight, physical inactivity, and others ( Table 2 ). Each risk factor has a different impact on the development of osteoporosis. When evaluating risk factors, it is important to discuss with patients those risk factors that they can modify. Some modifiable risk factors directly impact bone biology and result in a decrease in BMD. Others increase the risk of fracture independently of their effect on bone [31]. For example, smoking is well correlated with an increase in postmenopausal bone loss and fracture risk [21; 31]. Alcohol use is also a consistent risk factor for osteoporosis and fracture, though its effects seem to be dose-related. Drinking some but less than one drink a day may be protective, perhaps because of an effect on estrogen, but larger amounts of alcohol (i.e., two or more drinks/day) increase the risk of osteoporosis and fracture by 40% [20; 31]. High caffeine intake also may increase the risk of fracture in older women [20].
RISK FACTORS FOR OSTEOPOROSIS
Advanced age Low body weight (<70 kg) Family history Low physical activity White race Medications Female gender Menopause/hysterectomy Tobacco use Previous fracture Low cognitive function Estrogen deficiency Low calcium intake Source: Compiled by Author
Table 2
Low physical activity is also an important risk factor that should be modified. Exercise is important for maintaining strong bones, physical ability, and independence throughout life and, depending on the individual’s age, may increase or preserve bone mass and help reduce the risk of falls and fractures [23]. Patients with nutritional deficiencies of calcium and vitamin D also are at increased risk of osteoporosis. Protein may also be important due to its synergistic action with vitamin D and calcium [31]. Building a maximal peak bone mass as a child and adolescent is very important, and continuing to receive adequate amounts of these nutrients also is necessary. Clinicians and patients should be aware of medications that may increase the risk of osteoporosis. As noted earlier, glucocorticoids are the most common cause. The list of medications that may increase the risk of osteoporosis includes [20; 23]: • Anticonvulsants • Anticoagulants (long-term use) • Thyroxine • Lithium • Tamoxifen (premenopausal use) • Immunosuppressants and cytotoxic drugs Many of these drugs have different mechanisms of action. For instance, some of the anticonvulsants (e.g., phenytoin, phenobarbital) increase hepatic metabolism of vitamin D, resulting in decreased calcium absorption in the intestine. The key is to be aware of these medications and their impact on osteoporosis. Patient D has numerous risk factors for osteoporosis, including older age, female gender, and low body weight. She may also have a family history, and this should be explored further. Upon review of her medications, she has been treated with steroids for exacerbation of asthma, but there have been no such episodes in the past year. In addition, she is not on estrogen replacement therapy. The use of steroids and estrogen deficiency may be additional risk factors. Her level of physical activity is encouraging, but it does not offset her numerous risk factors.
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