Bisphosphonates. Making intelligent drug choices

Transcription

1 Making intelligent drug choices Bisphosphonates are a first choice for treating osteoporosis, according to Kedrin E. Van Steenwyk, DO, an obstetrician/gynecologist at Sycamore Women s Center, Miamisburg, Ohio. They are also first-line drugs for osteoporosis prevention. But not all bisphosphonates are created equal, observes Melicien A. Tettambel, DO, professor and chair, Maternal and Child Health, Still University, Kirksville College of Osteopathic Medicine, Kirksville, Mo. December 2005 AOA Health Watch 13

2 It is important for osteopathic physicians to individualize osteoporosis treatments and become familiar with the various treatment options their use, risks and side effects. Etidronate, for example, has a track record of increasing bone mineral density and decreasing vertebral fractures. However, the Food and Drug Administration never approved the drug for this indication. In fact, other bisphosphonates surged in popularity when providers questioned etidronate s role in causing osteomalacia. Taken daily, weekly or monthly depending on the formulation (see treatment box, pages 16-17), bisphosphonates are approved for the prevention and treatment of osteoporosis. On deck, says Dr. Tettambel, are other bisphosphonates including zoledronic acid, which would be taken once annually. Selective estrogen receptor modulators (SERMs), such as raloxifene and tamoxifen, generate estrogen-like effects while apparently decreasing possible effects that can lead to breast cancer. Approved by the FDA for the prevention and treatment of osteoporosis, raloxifene is probably less effective than bisphosphonates or estrogen in preventing bone loss. While Dr. Van Steenwyk believes hormone therapy is an excellent treatment for osteoporosis in the postmenopausal woman, she believes that each woman must be counseled on the risks and benefits of HT therapy, including the possible increased risks for cardiovascular events and breast cancer. Candidates for combined estrogen-progestin therapy include postmenopausal women with serious menopausal symptoms and women who need medication for osteoporosis but who can t tolerate other drugs, adds Dr. Tettambel. How does estrogen therapy compare with bisphosphonates and SERMS in reducing fracture risk? The jury is still out. However, the Women s Health Initiative (WHI) discovered that combined estrogen-progestin treatment reduces hip and vertebral fracture risk by 34%. Reduced fracture risk was also observed in the WHI trial of unopposed estrogen. Together with parathyroid hormone, calcitonin helps to regulate calcium concentrations in the body. Physicians who recommend calcitonin for treating osteoporosis typically suggest administration through an easy-to-use nasal spray. This serves as an alternative to injections, which can lead to nausea, vomiting and flushing in patients. Physicians often recommend other drugs over calcitonin (since no one is completely sure that calcitonin increases bone density and decreases fractures outside the spine.) would change this to read... data does not support calcitionins ability to decrease nonvertebral fractures. However, many physicians find the analgesic effects of calcitonin are useful in treating patients who experience sudden, acute pain from a vertebral fracture. Physicians change the treatment when the acute pain subsides or when the pain fails to subside within four weeks, says Dr. Tettambel. Produced by the parathyroid glands, parathyroid hormone (PTH) stimulates resorption and new bone formation. Administered intermittently, the drug stimulates formation more than resorption, while it also works to prevent and treat osteoporosis. One preparation, teraperitide has earned FDA approval as the first anabolic agent for the treatment of osteoporosis. While this preparation is more effective than other treatments in building spine bone density, it calls for daily injections and comes at a high price, says Dr. Van Steenwyk. For this reason, physicians reserve it for treating the most severe cases of osteoporosis. How do physicians evaluate the effectiveness of a hormone or drug therapy? They measure a patient s bone mineral density, while evaluating biochemical markers that signal bone turnover. Typically, physicians measure bone density and biochemical markers at the onset of therapy and follow up with a second series of biochemical marker tests within three months. If the hormone or drug therapy generates beneficial effects, physicians tend to continue it, scheduling a repeat bone density measurement within two years. 14 AOA Health Watch December 2005

3 To test or not to test Physicians should consider bone density testing for women who are age 65 or older; women who are 60 with an increased risk of osteoporosis; postmenopausal women who have recently fractured a bone; and younger postmenopausal women with other risk factors for osteoporosis. A woman s risk of osteoporosis increases if she is white; has a history of falls or bone fractures as an adult; smokes; has an early onset of menopause; is alcoholic; has low calcium and vitamin D intake; has low body weight; does not get enough physical activity; had a late onset of first menstrual cycle; has low estrogen levels; has muscle weakness; consumes a lot of caffeine; or has a family history of osteoporosis. If your patient is Medicare eligible, the Bone Mass Measurement Act of 1998 provides Medicare reimbursement of bone density testing. Repeat measurements can be done every two years and more often for patients on steroid therapy or further medical indications. The US government has ordered Medicare to pay for bone density testing in the following instances: If your patient is postmenopausal and at risk of osteoporosis. If your patient has primary hyperparathyroidism. If your patient has certain spinal abnormalities that might indicate a fracture. If your patient is on long-term corticosteroid therapy, such as prednisone. If you are assessing a patient s response to osteoporosis medications. Final notes Testing for osteoporosis no longer means just informing your patients about their fates. Test results now provide a framework so physicians can work with patients to build a treatment strategy. The best defense against osteoporosis is a healthy lifestyle: a diet rich in calcium, regular exercise, limited alcohol intake and no smoking; but for patients who have one or more risk factors, there are other preventative measures that can be considered. Breakthroughs in the prevention and treatment of osteoporosis continue as do the technological advances in testing. In addition, several drugs have been shown to stop and even reverse bone loss. Osteopathic physicians must continue to work with their patients to determine the best path of treatment and to educate them about preventing and treating osteoporosis. December 2005 AOA Health Watch 15

4 Currently, FDA-approved therapies are divided into two groups: antiresorptive therapy and anabolic therapy. Antiresorptive Therapies Alendronate, Fosamax Reduce fractures at the spine, hip and forearm. Increase and maintain bone density for 10 years. Indication: Prevention and treatment of osteoporosis in postmenopausal women and treatment of glucocorticoid induced osteoporosis in men and women, treatment of men with osteoporosis and Paget s disease. Anabolic Therapies Parathyroid Hormone: Teriparatide, Forteo Decrease vertebral and non-vertebral fractures. Indicated for postmenopausal women, men at high risk for fracture and women with osteoporosis who have multiple risk factors for fracture or who have fractured previously. Given as a daily injection of 20 mg subcutaneously. Forteo should be refrigerated when not in use. Prevention dose 35 mg once a week or 5 mg daily. Treatment dose 70 mg once a week or 10 mg daily. New formulation Fosamax with vitamin D once weekly. Should be taken on an empty stomach with a full glass of water. Patients must be able to sit upright or stand for at least 30 minutes after ingesting medication. nausea, heartburn, musculoskeletal pain and very rarely esophageal or gastric ulcers. Contraindicated in patients with hypocalcemia. Fosamax.com The FDA has limited its use to two years due to an increased incidence of osteosarcoma that was seen in earlier animal studies. No such tumors have been seen in human trials. Side effects include nausea, leg cramps, hypotension and transient hypercalcemia. Contraindicated in patients with Paget s disease, boney metastases, skeletal malignancy, hypercalcemia, and unexplained elevations in alkaline phosphatase Risedronate, Actonel Reduce fractures at the spine and hip-within six months, with antifracture, efficacy demonstrated to five years. Increase and maintain bone density for seven years. 5 mg daily or 35 mg once a week. New formulation Actonel with calcium is FDA approved. Indicated for the prevention and treatment of osteoporosis in postmenopausal women and prevention and treatment of glucocorticoid induced osteoporosis in men and women and treatment of Paget s disease. Should be taken in the morning on an empty stomach with a full glass of water. Patients must sit up or stand for 30 minutes after ingesting medication. nausea, heartburn, musculoskeletal pain, and very rarely esophageal or gastric ulcers. Contraindicated in patients with hypocalemia. Actonel.com Ibandronate, Boniva Reduce vertebral fractures in postmenopausal women. 16 AOA Health Watch December 2005

5 2.5 mg oral daily tablet or a 150 mg oral tablet monthly. Should be taken on an empty stomach with a full glass of water. Do not crush or suck tablet. Patients must be able to sit up or stand for 60 minutes after ingesting the medication. nausea, heartburn, musculoskeletal pain and esophageal irritation. Contraindicated in patients with hypocalcemia. 4boniva.com wwwnlm.nih.gov/medlineplus Calcitonin: Miacalcin Fortical Reduce vertebral fractures in women five years post menopause with osteoporosis. Given as a single daily nasal spray of 200 IUs or a daily subcutaneous injection. ET (estrogen therapy) HT(menopausal hormone therapy) Prevent osteoporosis in postmenopausal women. Hormone therapy needs to be individualized to the patient. In 2003 the FDA issued the following recommendations: Consider all nonestrogen preparations first; prescribe the smallest dose for the shortest amount of time to achieve treatment goals; prescribe ET/HT products only when the benefits outweigh the risks. A May 2002 Women s Health Initiative study showed that if 10,000 women were prescribed Conjugated Equine Estrogen/Medroxyprogesterone Acetate (CEE/MPA) at a dose equivalent to.625 to 2.5 mg daily, there would be seven more cardiac events, eight more strokes, 18 more venous thromboembolic events, eight more invasive breast cancers, six fewer colorectal cancers, five fewer hip fractures, and five fewer vertebral fractures. Selective Estrogen Receptor Modulators: Raloxifene, Evista Acts as an estrogen agonist on bone but as an estrogen antagonist on both the breast and uterus. Indicated for the prevention and treatment of osteoporosis in postmenopausal women. Reduces vertebral fractures in patients with and without history of vertebral fracture. Taken as a 60 mg tablet once a day with or without meals. Side effects include hot flashes, leg cramps and increased incidence of venous thromboembolism (VTE). Contraindicated in patients with a history of or active thrombotic disease and in women who may become pregnant; Raloxifene should be discontinued 72 hours prior to prolonged immbolization, such as sugery, bed rest or long flights. Evista has had positive effect on lipid profiles lowering total and LDL cholesterol. Side effects to the nasal spray include nasal irritation and runny or bloody nose. Side effects to the injection include nausea, headache and vomiting. Maicalcin nasal spray is recommended with adequate calcium (1000 mg elemental calcium)per day and vitamin D (400 IU) per day. nia.nih.gov/nr/rdonlyres Resources Internet Drug News.com (Osteoporosis and Paget s Disease Drug Database) Osteoporosis: Drugs Used to Treat Osteoporosis raloxifene.drugs.com HW Osteoporosis Drug Therapy Osteoporosis Treatment December 2005 AOA Health Watch 17