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SERMs

New agents have been developed that retain estrogen's positive effects on bone, while attempting to minimize the associated risks and side effects. This class of drugs is termed Selective estrogen receptor modulators (SERMs) and include raloxifene and tamoxifen. Raloxifene reduces the risk of vertebral fractures by approximately 40%, and produces increases in bone density of approximately 3% at the spine in its first three years. It also lowers total and LDL cholesterol, does not stimulate the endometrium, and probably reduces the risk of breast cancer.

Calcitonin

Salmon calcitonin has been used subcutaneously for many years. The recently released intranasal form is more acceptable for longterm use. Despite modest effects on bone density, vertebral fracture risk is reduced by approximately 40%. Intranasal calcitonin is well-tolerated and has minimal side-effects.

Figure 18. Independent interaction between clinical risk factors and bone mineral density. Risk factors were: age over 80, maternal history of hip fracture, any fracture since age 50, reduced self-rated health (fair or worse), previous hyperthyroidism, anticonvulsant therapy, current use of long-acting benzodiazepines, current weight less than at age 25, height at age 25 over 168 cm, caffeine intake more than the equivalent of two cups of coffee per day, on feet less than four hours per day, no walking for exercise, inability to rise from a chair without using arms, lowest quartile for visual depth perception, lowest quartile for visual contrast sensitivity, resting pulse rate greater than 80 beats per minute. (Adapted from Cummings SR et al. N Eng J Med 1995; 332:767-773.)

Figure 18. Independent interaction between clinical risk factors and bone mineral density. Risk factors were: age over 80, maternal history of hip fracture, any fracture since age 50, reduced self-rated health (fair or worse), previous hyperthyroidism, anticonvulsant therapy, current use of long-acting benzodiazepines, current weight less than at age 25, height at age 25 over 168 cm, caffeine intake more than the equivalent of two cups of coffee per day, on feet less than four hours per day, no walking for exercise, inability to rise from a chair without using arms, lowest quartile for visual depth perception, lowest quartile for visual contrast sensitivity, resting pulse rate greater than 80 beats per minute. (Adapted from Cummings SR et al. N Eng J Med 1995; 332:767-773.)

Bisphosphonates

This class of drugs inhibit osteoclast number and activity and have few extra-skeletal effects. Etidronate was the first available compound. It has low potency and inhibits bone mineralization when used continuously (though this is not seen with intermittent regimens). Alendronate is a potent aminobisphosphonate that is capable of increasing bone density at the lumbar spine by 8% over 3 years. More importantly, it has been proven to reduce hip and spine fractures by 50% in postmenopausal women with previous fractures. The main risk is erosive esophagitis, especially in patients with prior esophageal disease, gastroesophageal reflux or when directions are not carefully followed. Risedronate has also been demonstrated to produce similar

Figure 19. Risk for incident vertebral fractures (Vb Fx) based on current vertebral fracture status. (Adapted from Ross PD et al. Ann Intern Med 1991; 114:919.)

increases in bone density in postmenopausal osteoporosis and similar reductions in the incidence of vertebral and hip fractures.

Anabolic Agents

Strategies which directly stimulate osteoblast activity have the potential to produce larger increases in bone density and potentially larger effects on fracture prevention. One such strategy is the use of intermittent parathyroid hormone therapy which has been demonstrated to produce large increases in bone mineral density in various populations, and to reduce vertebral fractures by approximately 65% in postmenopausal women with previous fractures.

Who to treat?

General recommendations that apply to the entire population include ensuring adequate calcium and vitamin D intake, engaging in regular weight-bearing exercise, avoidance of smoking and limitation of alcohol use. Although whole population testing is not advocated, the National Osteoporosis Foundation (NOF) has defined guidelines for targeted screening(Fig. 20). In addition, the NOF has identified four clinical risk factors as being sufficiently common and predictive of osteoporosis in postmenopausal women to be useful in the clinical setting for guiding decisions on whether to recommend bone densitometry: (1) history of fracture after age 40; (2) history of hip, wrist or vertebral fracture in a first-degree relative; (3) being in the lowest quartile for body weight (less than 57.8 kg); and (4) current cigarette smoking.

The NOF established therapeutic cutpoints for antiresorptive therapy. According to these guidelines, therapy to reduce the risk of fracture should be initiated in the following groups: women with a T-score below -2; or women with a T-score -1.5 if any of the four risk factors given above are present. In addition, women over age 70

Figure 20. Guidelines for the targeted screening and treatment of osteoporosis. Major risk factors include (1) history of fracture over age 40; (2) history of hip, wrist or vertebral fracture in a first-degree relative; (3) being in the lowest quartile for body weight (less than 57.8 kg); and (4) current cigarette smoking. (Adapted from the National Osteoporosis Foundation's "Physician's Guide to Osteoporosis Prevention and Treatment".)

The Smoker's Sanctuary

The Smoker's Sanctuary

Save Your Lungs And Never Have To Spend A Single Cent Of Ciggies Ever Again. According to a recent report from the U.S. government. Centers for Disease Control and Prevention, more than twenty percent of male and female adults in the U.S. smoke cigarettes, while more than eighty percent of them light up a cigarette daily.

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