Osteoporosis: Diagnosis and Managements _ _____________________________________________________
EXERCISE Exercise is beneficial for many reasons, including reduction in the risk of heart disease, improved glycemic control in diabetes, improved blood pressure, and reduction in cholesterol levels (total cholesterol and low-density lipoprotein [LDL]), as well as improved psychologic well-being. For patients with osteoporosis, exercise may specifically increase bone mass and total body calcium. Numerous studies have documented that consistently active individuals have higher bone density than inactive individuals [23]. The beneficial physiologic effects most likely result from imposing repetitive stress upon the muscular and skeletal systems. The mechanical strain and loading on bone may decrease the rate of bone loss as well as produce an actual increase in bone mass [23]. Exercises can basically be classified as either aerobic or anaerobic. Aerobic exercise is any activity that uses large muscle groups, is maintained continuously, and is rhythmic in nature. It strengthens the myocardium and improves overall fitness by increasing the body’s ability to use oxygen. It does so by increasing the inotropic and chronotropic activity of the heart along with increasing respiratory demand. Examples of aerobic exercise include running, biking, skating, brisk walking, and dancing. Anaerobic exercises typically involve major muscle groups and resistance training, which relate to muscular strength and muscular endurance. Muscular strength involves exerting a force for a brief period of time with repeat contractions until the muscle becomes fatigued. Weightlifting is a good example of an anaerobic muscular strength activity. Muscular endurance involves sustaining repeated contractions or the application of a continual force against a fixed object. Push-ups are an example of muscular endurance. The BHOF has recommended a combination of weight-bearing and resistance type (i.e., muscle strengthening) exercises [20]. The program prescribed will depend on the ability and interests of the individual patient. Patients should be encouraged to exercise at least 30 minutes per day, at least five days per week, eventually working up to 60 minutes per day, if tolerated. Ideally, patients should stretch for 10 minutes prior to exercise. Patients with a history of vertebral compression fracture, as well as those patients with significant musculoskeletal disease or serious degenerative joint disease, should initially participate in a monitored exercise program [11]. MEDICATION Medications may be divided into antiresorptives, which reduce bone loss, and anabolic, or bone-formation, agents. Antiresorptive therapies include estrogen, selective estrogen receptor modulators (SERMs), bisphosphonates, and calcitonin. The first U.S. Food and Drug Administration (FDA)-approved anabolic agent was teriparatide, which is a synthetic form of PTH. A second agent, abaloparatide, was approved by the FDA in 2017 for the treatment of osteoporosis in postmenopausal women at high risk for fracture [72; 73]. A third anabolic agent, romosozumab, was approved by the FDA in 2019 [74]. The effectiveness of these therapies, and combinations of them, is being studied [23].
Antiresorptives Hormone Replacement
Hormone replacement, either in the form of unopposed estrogen or estrogen-progestin combination agents, had commonly been used in postmenopausal patients for alleviation of postmenopausal symptoms and prevention of chronic diseases. Estrogen increases osteoblastic activity, which leads to greater pro-collagen and alkaline phosphatase production. As a result, it inhibits bone resorption. Deficiency in estrogen causes increased osteoclast formation. Studies conducted in the early 2000s have led to a change in the recommendations for hormone therapy in postmenopausal women [20; 36; 75]. The WHI, a large randomized control trial (and an observational study), showed the osteoporosis prevention benefit of combination therapy in healthy, postmenopausal women. Nearly 27,000 women were randomized to conjugated estrogen plus medroxyprogesterone (if they had an intact uterus), conjugated estrogen (if they had a hysterectomy), or placebo. The primary outcome measure was coronary heart disease, but hip fracture was one of the secondary outcomes measured. The results demonstrated a one-third decrease in hip fractures and a 24% to 30% decrease in total fractures among the treatment group [13; 23]. The reduction in total fracture risk was significant; however, reductions in vertebral and hip fractures were not statistically significant. The study was stopped before completion due to increases in invasive breast cancer in the treatment group. There was also an increased absolute risk of nonfatal stroke, cognitive impairment, venous thromboembolism, and nonfatal myocardial infarction. A reduced incidence in colon cancer was observed. The authors concluded that hormone replacement is not recommended unless the fracture risk benefit is greater than the risk of cardiovascular disease and breast cancer [13; 23]. Another trial, the Heart and Estrogen/Progestin Replacement Study (HERS) and its subsequent follow-up HERS II, studied more than 2,700 postmenopausal women with pre-existing coronary heart disease and an intact uterus. Patients were randomized to conjugated estrogen plus medroxyprogesterone daily versus placebo. The studies involved a mean follow-up of 4.1 years. No significant decrease in hip or total fracture rates was shown for the patients receiving daily combination therapy [76]. The HERS trial showed no protective cardiovascular effects of the treatment and actually showed a 50% increase in cardiovascular events in the treatment group in the first year of the trial. The HERS II trial supported the conclusion from the initial HERS study, which was that hormone replacement therapy does not reduce the risk of cardiovascular events in postmenopausal women with coronary heart disease. Prior to the studies, hormone replacement therapy was generally considered beneficial; however, recommendations have changed. The USPSTF has recommended against routine use of combination hormone therapy for prevention of chronic disease in postmenopausal women. The USPSTF also has
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