Thesis Nurs. 1997 H396g c.2 Hawley, Tina. Guidelines for the treatment of 1997. GUIDELINES FOR THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS by TINA HAWLEY Submitted in Partial Fulfillment of the Requirements for the Master of Science in Nursing Degree Approved by: Judith Schilling, CR T>, PHD Committee Chairperson of of Pennsylvania Edinboro University c_ V ---- Mary Lou Keller, CRNP, PHD Committee Member Edinboro University of Pennsylvania 7 D?te C •>" TABLE OF CONTENTS Acknowledgements Chapter ii Page Introduction 2 Background 2 Theoretical Framework 5 Definition of Terms 7 Summary 8 Review of Literature 10 Pathophysiology of Osteoporosis.. 10 Diagnostic Testing 12 Estrogen Therapy 13 Alendronate 16 Intranasal Calcitonin 19 Sodium Fluoride 21 Calcium 21 Summary 23 Methodology 24 26 References Appendix A. Guidelines for the Treatment of Postmenopausal Osteoporosis 32 ii Acknowledgement I would like to express my appreciation to my thesis committee and to Usha Mohandas MD for their support with this project. A very special thank you to my family, and good friend Peter Raimondo, for their encouragement throughout this time. I hope that these guidelines serve to improve the medical care of women. 2 CHAPTER 1 Introduction As under of treated (Miller, of 1994, 1994) . osteoporosis patient. osteoporosis was one of the most illnesses in the United States This chapter discusses the impact on society and the individual Advances in early detection and treatment of osteoporosis are discussed. Background Osteoporosis, heart disease, and cancer are the three most serious chronic conditions affecting United States women (Chung & Maroulis, 1996). Osteoporosis currently affects more than 20 million individuals in this country, accounting for about 1.5 million fractures annually (Chung & Maroulis, 1 996) . It is estimated that as many as 40% of women over 50 years of age will experience an osteoporotic fracture during their lifetime (Rupee, 1996). Osteoporosis causes 250,000 hip fractures and 500,000 vertebral fractures each year (Murray & O’Brien, 1995) . Fractures caused by osteoporosis often result in chronic pain related to poor healing and deformity. Disability and death are additional complications of hip fractures. The statistics for 20% die within 1 women with hip fractures show th^t 3 year of the injury, and 50% of the survivors never walk independently again (Chung & Maroulis, 1996). In the United. States, 60,000 nursing home admissions yearly are attributed to hip fractures, and more than 8% of all nursing home residents have had a hip fracture (Butler, Ghrischilles, Davis, & Wallace, 1991). As of 1994, osteoporosis was one of the most under treated illnesses in the United States (Miller, 1994). Estrogen and subcutaneous calcitonin were the only treatment for osteoporosis until 1995. Not all women are candidates for estrogen therapy and some women choose not to take estrogen therapy. Subcutaneous calcitonin requires a weekly injection that many patients object to (Gray,1994). In the fall of 1995, two new medications were released for the treatment of osteoporosis, alendronate and intranasal calcitonin. Alendronate is a bisphosphonate that inhibits bone resorption by indirectly interfering with osteoclast activity, stopping the accelerated bone loss of osteoporosis (Fleisch, 1992). The exact mechanism for alendronate’s effect on increasing bone density has not been determined. Calcitonin has a direct inhibiting the bone effect on the osteoclasts osteoporosis (Re^inster, 1993). resorption of 4 These new medications replace estrogen therapy. are not intended to Alendronate and calcitonin are indicated for the treatment of osteoporosis when estrogen therapy is contraindicated, or when the patient refuses estrogen therapy (Chung & Maroulis, 1996). Estrogen is the drug of choice for the treatment and prevention of osteoporosis (Murray & O’Brien, 1995). Many physicians have not been utilizing estrogen therapy to the fullest extent and little emphasis has been placed on osteoporosis prevention. Fewer than 15% of U.S. women over 65 are using hormone replacement therapy (Chung & Maroulis, 1996). A study conducted in Philadelphia found that only 37% of gynecologists would recommend hormone replacement therapy for the prevention of postmenopausal osteoporosis and that only 7% of general internist would do so (Kroll, Rozenberg, & Vandromme, 1996). Early diagnosis is another important aspect in the treatment of osteoporosis. Until recently, early diagnosis was not feasible because the only a plain x-ray. tool to diagnose bone loss was Osteoporosis was usually not identified until a x-rays do not show fracture occured because plain is lost osteoporosis until 30% of bone mass diagnostic technique is now (Miller, 1990) . A new 5 available that identifies bone loss earlier, before fractures occur. Dual energy x-ray absorptiometry exposes the patient to only low doses of radiation and diagnoses early bone loss with a high degree of accuracy (Chung & Maroulis, 1996). Early diagnosis allows the health care provider to identify patient's at risk for osteoporosis, and to begin treatment to stop the accelerated bone loss. The incidence of osteoporosis is increasing with the aging of the population. In 1990, 11% of the population of the U.S. was 65 years or older. By the year 2050, it is estimated that 22% of that population will be over 65 (Miller, 1990). By the year 2050 over 6 million people are expected to fracture a hip (Gray, 1994). Health care costs for osteoporosis are currently at least $6-10 billion annually (Edwards, Finch, & Kirkpatrick, 1991). This cost will increase as the incidence of osteoporosis increases. The prevention and treatment of osteoporosis is a growing health care concern in the United States. Theoretical Framework The theoretical framework for this project is (Orem,1995). The Orem's theory of self-care self-care agent is key to the patient's role as a As a prevention and treatment of osteoporosis. 6 self-care agent the patient performs activities of health promotion. This involves activities that are beyond those that are life sustaining. As a selfcare agent, the patient with osteoporosis has health-deviation self-care requisites related to medication compliance, risk reduction, and pain control. The patient may also have self-care deficits related to universal self-care requisites such as prevention of hazards to human functioning and adequate rest. The role of the primary care provider is to work with patients to determine their health care needs and to assist patients in meeting those needs. The treatment plan must be individualized according to the self-care deficits of each patient. The menopausal woman has primary prevention self-care demands related to education about risk factor reduction for osteoporosis. Prevention and early detection of osteoporosis will decrease the patient’s self-care deficits and increase her ability as a self-care agent. The patient with tertiary self-care osteoporosis has secondary or demands related to education about diagnosis and treatment. The results of this project is the development of clinical guidelines for the treatment of 7 osteoporosis. Clinical guidelines are a tool for primary care providers to use in planning quality patient care. The guidelines are based on a review of the literature and input from experts in the treatment of osteoporosis. Definitions of Terms 1 . Primary Care Provider - A physician, nurse practitioner, or physician assistant providing primary care to patients. 2. Postmenopausal The time period in a women’s life that begins 12 months after menstruation ceases. 3. Clinical Practice Guidelines A set of diagnosis-specific guidelines developed by an interdisciplinary team to assist clinicians in providing quality patient care (Freed & Pare, 1995). 4. Risk Factors Factors that identify persons who are at risk of developing a disease. Risk factors for osteoporosis are postmenopausal, premature menopause, Caucasian or Asian race, positive family history, small frame, leanness, low calcium intake, inactivity, history of atraumatic fractures , nulliparity, long-term glucocorticoid therapy, long-term hyperthyroidism or anticonvulsant therapy, excessive thyroxine, cigarette smoking, alcohol abuse, and gastrlo/small bowel 8 bowel resection (Chung & Maroulis, 1996). 5. Osteoporosis Skeletal state of decreased bone mass that may result in pathologic bone fracture(s). Osteopenia is a precursor for osteoporosis (Edwards, Finch, & Kirkpatrick, 1991). 6. Osteoclasts Cells located on the bone surface that break down bone in the remodeling process (Miller, 1994). 7. Osteoblasts Cells located on the bone surface that build back the bone broke down by the osteoclasts (Miller, 1994). Summary Osteoporosis is one of the most serious chronic conditions affecting women and is one of the most under treated illnesses (Chung & Maroulis, 1996). Osteoporosis results in fractures that cause disability, chronic pain, and loss of self-esteem. Osteoporosis uses $6-10 billion annually in health care costs, and this figure will increase with the growing population over age 65 years (Edwards, Finch, & Kirkpatrick, 1991). There are three medications for the treatment intranasal of osteoporosis: alendronate, calcitonin, and estrogen. the rapid bone loss These medications inhibit of osteoporosis and increase bone density in varying degrees. Diagnostic tools 9 are also now available for identifying early bone loss before fractures occur. Orem’s theory of self-care is the theoretical framework for developing these clinical practice guidelines. The patient with osteoporosis is a self-care agent with health-deviation requisites related to medication compliance, risk reduction, and pain control. 10 CHAPTER 2 Review of Literature The pathophysiology, the diagnosis, and the treatment of osteoporosis are the topics included in this literature review. The review of literature also includes results of studies using medications for osteoporotic treatment. This information was the basis for the osteoporotic treatment guidelines. Pathophysiology of Osteoporosis The skeleton of the human body undergoes a continuous process of remodeling. This remodeling process is the body’s mechanism for obtaining free calcium and phosphate, in addition to responding to bone stress (Ramamureti, 1979). The remodeling process consists of osteoclasts that break down bone, and osteoblasts that rebuild bone (Riis, 1996). In osteoporosis, osteoclast activity exceeds osteoblast activity, resulting in a net loss of bone mass (Ramamureti, 1979). Osteoporosis can be described as primary or secondary, depending upon its etiology. Primary and is divided into two osteoporosis is idiopathic Secondary categories, senile and postmenopausal. an identified underlying osteoporosis is caused by 11 disease (Gray, 1994) Postmenopausal osteoporosis is related to estrogen deficiency (Barzel, 1990). There are estrogen receptors located on the bone’s osteoblasts that trigger osteoblastic activity (Lane, McDonnell, & Zimmerman, 1987). Decreased estrogen levels result in less triggering of the osteoblasts and, as a result, less bone is rebuilt. Since estrogen also stimulates the release of calcitonin, which inhibits bone resorption, an estrogen deficiency results in less circulating calcitonin (Lane et al., 1987). The end result of estrogen deficiency is excessive bone resorption and a loss of bone mass. Decreased bone mass causes bone fragility and can result in pathological fractures (Riis, 1996) . Senile osteoporosis is related to the physiological changes of aging (Ettinger, 1987). With aging there is often a decrease in active and a vitamin D, a decline in physical activity, 1987). decline in osteoblast activity (Lane et al., The loss of bone mass in osteoporosis effects two types of bone, trabecular and cortical, at Trabecular bone, different rates (Riis, 1996). the skeleton, is concentrated accounting for 20% and other flat bones, and in the vertebrae, pelvis, Trabecular bone is at the end of long bones - 12 effected first in postmenopausal osteoporosis because its surface area is greater (Madson, 1989). Cortical bone is found in the shafts of the long bones and comprises 80% of the skeleton. Trabecular and cortical bone are effected equally in senile osteoporosis. In osteoporosis, fractures can occur with normal activity or following minimal trauma. The most prevalent areas for fractures are the vertebrae, ribs, proximal femur, proximal humerus, and the distal radius (Kupec, 1996). The vertebrae are composed primarily of trabecular bone, therefore they fracture earlier than the highly cortical area of the femoral neck (Lane et al., 1987). The risk of fracture in osteoporosis relates to bone density or mass (Chung & Maroulis, 1996). Bone density correlates with bone strength and accounts for 75% to 85% of its variance (Riis, 1996). Diacmostic Testing Bone density measurement can be used to predict the risk of fractures (Murray & 0’Brien, 1995). In in bone density of postmenopausal women, a decrease below the mean indicates a one standard deviation 2.3 times higher than risk of vertebral fracture Osteoporosis is average (Bell et al-, 1• Health Organizatign as a value defined by the World 13 for bone mineral density that is 2.5 standard deviations or more below the young adult mean (Gold et al. , 1 996) . Dual energy x-ray absorptiometry (DEXA) is a new bone density test. It is an improvement over the older single energy x-ray absorptiometry (SXA). The SXA test measured bone density at the wrist and heel, and the heel site is less predictive of osteoporosis . The DEXA test images the spine and hip, which is more predictive of osteoporosis. The effective radiation dose of the DEXA is 1 (uSV) , and the SXA radiation dose is less than 1 (uSV) . A bone density result between 1 and 2.5 standard deviations below the mean indicates osteopenia; the DEXA should be repeated in 2 years (Gold et al. , 1996) . measures Quantitative computerized tomography (QCT) bone density using the spine site, but the effective (Gold et al., 1996). radiation dose is 60-100(uSV) of less than 1% The DEXA has a precision rate precision rate of 3% to variation, and the QCT has a For comparative value, 5% variation (Miller, 1994). used each time. the same test must be Estrogen Therapy In postmenopausal osteoporosis, the decrease in menses ceases and occurs at bone mass begins before 5 to 10 years after a higher rate the first 14 menopause (Bush, Ettinger, Lobo, Mishell, & Speroff, 1 995) . The rate of bone loss during the first 3 to 4 years postmenopausal is typically 2.5% annually. After that time, the rate of bone loss slows to an annual rate of 0.75% (Chung & Maroulis, 1996). Accelerated bone loss occurring in the early postmenopausal period can be prevented by the use of estrogen (Bush et al., 1995). Estrogen is the only medication currently FDA approved for the prevention of osteoporosis. In a study done at the University of California, San Francisco, 73 women who were started on estrogen therapy at the beginning of menopause showed no significant bone loss during a 2 year follow-up period. Other studies have also shown a beneficial effect on bone when estrogen was started within 3-5 years of menopause or oophorectomy (Barzel, 1990). Women who use estrogen therapy for 10 years after menopause, and then discontinue its use, reduce their relative fracture risk at the age of 80 by 15%. Women remaining on estrogen therapy longer than 10 years reduce their relative fracture risk by 50% by the age of 80 (Bush et al., 1995). Controversy exists concerning the long term use of estrogen therapy because of the increased risk of breast cancer with aging and its possible 15 association with estrogen therapy. Studies have come to conflicting conclusions concerning the risk of breast cancer with estrogen therapy. It is important to consider the risk in relationship to the benefit of hormone therapy. A 60 year old woman on hormone therapy has a 1-in-14 chance of breast cancer if she lives to be 80 years old; but she has an 8-in-14 chance of heart disease if she lives to age 80 without hormone therapy (Bush et al., 1995). There is even benefit for women who start estrogen therapy 5 or more years after menopause. A study done at Mayo Clinic showed a 5% to 7% increase in bone density, and a reduction in vertebral fractures , in postmenopausal women on estrogen therapy beginning more than 5 years after menopause (Bush et al., 1995). The greatest benefit of estrogen therapy in preventing osteoporosis, however, is gained when it is started early in menopause (Gambrell, 1991). The use of progesterone with estrogen does not alter the beneficial effect of estrogen therapy on bone mass (Barzel, 1990). The dose of estrogen that is effective in preventing and treating osteoporosis is 0.625 mg (Bush et al., 1995) . A transdermal form of estrogen is also approved (Miller, 1992) 16 Alendronate Alendronate is a new medication for the treatment of osteoporosis, released in the fall of 1 995. Alendronate is a bisphosphonate which is an alteration of a naturally occurring substance, pyrophosphonate (Compston, 1994). The phosphonate is altered by adding two carbons that make it resistant to hydrolysis. There have been other medications in this classification used to treat osteoporosis (Fleisch, 1992). Etridonate has been used in European countries in a cyclic pattern, but studies have shown alendronate to be 100 to 500 fold more potent (Bell, et al., 1995). Etridonate is given parenterally. Alendronate inhibits osteoclast-mediated bone resorption and has an indirect effect on osteoblast activity (Gertz, Kanis, Ortolani, & Singer, 1995). The decreased osteoclast activity results in fewer bone areas to refill, so the osteoblasts are able to keep pace with the osteoclasts and can even exceed osteoclastic activity. This results in an increase in bone density as well as a slowing of bone loss (Fleisch, 1992). There is no proven adverse effect on bone mineralization with alendronate (Papapoulos, 1993). Normal bone mineralization is important in 17 maintaining bone strength. Researchers believe that bone mineralization will not be effected because the osteoblast activity remains at a normal rate. Five clinical trials, involving 1,827 postmenopausal women aged 41 to 85 with osteoporosis, showed an increase in bone density of the hip and lumbar vertebrae with the use of alendronate. These trials were conducted in six countries and the women were followed for 2 years (Chung & Maroulis, 1996). The trials showed an average increase in bone mineral density of 8.2% at the spine and 7.2% at the hip, and also reported 48% fewer new spinal fractures (Lindsay, 1996). The dosing regime for alendronate that best balances efficacy and side effects is 10mg daily (Bell et al., 1995). In clinical trials the occurrence of side effects with alendronate, 10mg orally daily, was low (Chung & Maroulius, 1996). The most common side effect was gastrointestinal upset which occurred in less than 5% of patients. There was a rare occurrence of erosive esophagitis during the first few weeks of treatment. Alendronate is contraindicated in patients with dysphagia, gastritis, peptic ulcer disease, or esophageal irritation (Gold et al., 1996). Patients must be instructed to report to their health care 18 provider immediately should symptoms of dysphagia or esophageal irritation occur. Information from clinicians prescribing alendronate has shown a greater occurrence of gastrointestinal upset then expected from clinical trials (Nightingaler 1996). This may be related to patients’ nonadherance to instructions on how to take the drug. To prevent esophageal irritation, alendronate must be taken with a glass of water and the patient must not lie down for the next 30 minutes (Lindsay, 1996). Alendronate is absorbed poorly from the gastrointestinal tract, approximately 1% of the administered dose being absorbed. Absorption is markedly reduced further in the presence of food (Gertz et al., 1995). The medication therefore must be taken on an empty stomach and the patient must not eat for 30 minutes. Alendronate cannot be taken along with any other medications or liquid other than water (Lindsay, 1996) . Alendronate is excreted by the kidneys and is contraindicated in patients with a renal creatinine clearance less than 35ml/minute (Lindsay, 1996). The plasma half-life of alendronate is short, but its bone half-life is about 10 year. Alendronate is absorbed specifically by bone, and especially so in 19 areas of resorptive activity (Gertz et al., 1995). The long bone half-life has not been shown to have an adverse effect on bone mineralization (Compton, 1994) . Alendronate therapy, in clinical trials, resulted in an increased bone mineral density at the lumbar spine after 6 weeks of treatment (Gertz et al., 1995). Intranasal Calcitonin Nasal spray calcitonin was FDA approved for use in treating osteoporosis in the fall of 1995. Calcitonin is a natural occurring hormone produced by the thyroid gland (Reginister, 1993). Calcitonin directly inhibits osteoclast activity by interfering with the osteoclast precusor (Christiansen, Hansen, Jensen, & Overgaard, 1992). The medication also binds to receptors on the osteoclasts, causing the osteoclasts to move away from the bone resorptive surface (Reginister, 1993). The end result is to stop the rapid bone loss. Salmon calcitonin is used in the intranasal preparation because its potency is greater than human calcitonin (Attinger et al., 1987) . Calcitonin is not absorbed when taken orally. The biological effects obtained after intranasal administration are equivalent to those observed with parenteral administration (Reginister, 1995). 20 Tolerance to intranasal calcitonin is excellent with side effects occurring infrequently and transiently (Chung & Maroulis, 1996). Side effects with intranasal calcitonin include nausea, vomiting, and flushing, but rhinitis is the most common side­ effect (Gold et al., 1996). Two randomized, placebo controlled trials with intranasal calcitonin conducted with 325 postmenopausal females with osteoporosis showed a slowing of bone loss and a 1 % increase in bone mineral density of the lumber spine. The increase in bone density began as early as 6 months after treatment was started. These studies did not show a decrease in the fracture rate for the spine or hip, but the length of the study was only 2 years. A 2 year prospective study with elderly women having low forearm bone density showed a reduced fracture rate of 66% with nasal salmon calcitonin, as compared with oral calcium supplements alone (Reginister, 1995). The usual dose of nasal calcitonin is 200 I.U./day or one spray, alternating the nostril side used (Lindsay, 1996). Calcitonin has also been shown to relieve bone pain, but the exact mechanism is unknown (Chan & Pun, 1989). The use of calcitonin decreases the need for daily consumption 21 of analgesic drugs for bone pain. Sodium Fluoride Sodium fluoride has been studied for some years for its usefulness in treating osteoporosis. There is a significant increase in bone mass with sodium fluoride, but with abnormal bone mineralization. Recent clinical trials have shown that the abnormal mineralization with sodium fluoride is dose dependent and does not occur at doses less than 20 mg daily (Kanis, 1993). Extended release sodium fluoride has been shown not to effect bone mineralization (Meunier & Ringe, 1995) . Sodium fluoride has a bone-anabolic effect, and in patients with extensive bone loss would reduce the risk of bone fractures (Meunier & Ringe, 1995). The antiresorptive agents, alendronate and calcitonin, are not as effective in these cases. The effects of sodium fluoride on bone mass has not been consistent with up to 40% of patients showing little or no improvement. not clear (Kanis, 1993). The reason for this is Enteric coated forms decrease the gastointestinal upset that occurs with other forms of sodium fluoride. Calcium Calcium supplementation is not effective 22 treatment for established osteoporosis although calcium helps to build bone and low calcium intake contributes to low bone mass (Todd, 1985). A recent study of 118 healthy white women 3 to 6 years after menopause demonstrated that calcium augmentation alone retarded bone loss from the femoral neck, but that the effect was less pronounced compared to the group taking calcium combined with hormone replacement therapy (Chung & Maroulis, 1996). It is unclear whether calcium supplements actually decrease fractures (Todd, 1985). Calcium supplements are to be taken along with alendronate or calcitonin. The recommended dose of calcium is 1,000 mg per day for premenopausal women or women on hormone replacement therapy, and 1,500 mg after menopause without hormone replacement. Vitamin D increases the absorption of calcium but does not increase bone density independently (Todd, 1 985) . It is recommended that patients take 400 to 800 I.U. of Vitamin D along with calcium supplements (Chung & Maroulis, 1996). Vitamin D insufficiency is common among the frail elderly, especially those living in northern climates, or in institutions where they are exposed to little sunlight (Murray & O’Brien, 1995). 23 Summary Estrogen therapy is approved for use in preventing postmenopausal osteoporosis, and is effective in stopping the accelerated bone loss that occurs in the first 5 years of menopause. Alendronate slows the rate of bone loss and increases bone density. Alendronate increases bone density at the spine by 8.2% and at the hip by 7.2%, with 48% fewer new spinal fractures (Lindsay, 1996) . Intranasal calcitonin stops the accelerated bone loss of osteoporosis, and increases the bone density of the spine by 1%. The studies done with alendronate and intranasal calcitonin have extended over only a 2 year period. This is not long enough to determine the effect on hip fractures. Sodium fluoride is not FDA approved for use in the United States. supplementation should be taken by all postmenopausal women, along with vitamin D. Calcium 24 CHAPTER 3 Methodology- Written guidelines for treating medical conditions provide for standardized patient care that promotes quality. Guidelines serve as tools to use in determining the treatment plan for an individual patient. Research data, a review of the literature r and expert opinion are the basis for the development of treatment guidelines (Freed & Pare, 1995) . In order to develop guidelines for the treatment of postmenopausal osteoporosis, a review of the research data on alendronate, calcitonin, and estrogen was done. Information collected concerned the safety and efficacy, side effects, and contraindications for each medication. Effective dosage and indications for use were also studied. Risk factors for postmenopausal osteoporosis were also identified from the literature. Risk factor identification is an integral part of determining the need for diagnostic testing for osteoporosis. These guidelines, therefore, include screening patients for osteoporosis risk factors; indications for diagnostic testing are also included. 25 Patient education is an important aspect of the treatment of postmenopausal osteoporosis. Education involves information about taking the medication, side-effects, and other means of risk factor reduction. Intervention in osteopenia is included in the guidelines, because this can prevent the development of osteoporosis and the occurrence of fractures. Guidelines for the follow-up of osteoporotic treatment are included. The development of the guidelines involved the input from experts in the field who are experienced in using the medications. These experts were a board certified internal medicine physician and a pharmacist. The experts reviewed the guidelines, and appropriate corrections were then made in the wording of the guidelines. are in Appendix A. The revised guidelines 26 References Attinger, M., Azria, M., Buclin, T., Burckhardt, P•, Gomez, F., Jacquet, A., & Randin, J. (1987). The effect of rectal and nasal administration of salmon calcitonin in normal subjects . Calcified Tissue, 41, 252-25 Barzel, U. (1990). Estrogen therapy for osteoporosis: Is it effective? Hospital Practice, 2 (7), 95-198. Bell, N., Chesnut, C., Delmas, P., Ensrud, K., Genant, & Harris, H. (1995). Alendronate treatment of the postmenopausal woman: Effect of multiple dosages on bone mass and bone remodeling. American Journal of Medicine, 99(2), 144-151 . Bush, T., Ettinger, B., Lobo, R., Mishell, D., & Speroff, L. (1995) . New concepts in managing menopause. Symposium, Patient Care, 18-24. Butler, D., Chrischilles, E., Davis, C., & Wallace, R. (1991). A model of lifetime osteoporosis impact. Archives of Internal Medicine,151, 2026- 2032. Chan, L., & Pun, K. (1989). Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporosis vertebral fractures. Clinical Therapeutics^ 11(2), 205-208. Christiansen, C., Hansen, M., Jensen, S., & 27 Overgaard, K. (1992). Effect of calcitonin given intranasally on bone mass and fracture rates in established osteoporosis: A dose-response study. British Medical Journal, 305, 477-479. Chung, P., & Maroulis, G. (1996). Osteoporosis: An update on prevention and treatment. Physician Assistant , 12(4), 83-96. Compston, J. (1994). The therapeutic use of bisphosphonate. British Medical Journal, 309 (1 7) , 711-715. Edwards, M., Finch, N., & Kirkpatrick, M. (1991). Assessment and prevention of osteoporosis through use of a client self-reporting tool. Nurse Practitioner, 16(7) , 16-25. Ettinger, B. (1987). Estrogen and postmenopausal osteoporosis. American Association of Occupational Health Nursing, 35112), 543-546. Fleisch H. (1992). Editorial: Prospective use of bisphosphonates in osteoporosis. Journal of Clinical Endocrinology and Metabolism, 76(6), 1397- 1398. Freed, M., & Pare, S. (June, 1995). Clinical practice guidelines for quality patient outcomes. In P. A. Hickey (Ed.), Nursing Clinics of North America (pp- 183-196)- Philadelphia: W. B. Saunders Co. Gambrell, R- (1991)- Estrogen replacement therapy and osteoporosis. Hospital Practice, 26 28 (suppl. 1) 0-5. Gertz, B-, Kanis, J-, Ortolani, S., & Singer, F. (1995). Rationale for the use of alendronate in osteoporosis. Osteoporosis International, 5, 1-11. Gold, D., Lee, L., & Tresolini, C. (1996) . Working with patients to prevent, treat, and manage osteoporosis (Curriculum Guide For Health Professions). San Francisco, CA: National Fund for Medical Education. Gray, M. A. (1994). Osteopororsis medications: What’s your source of information? Orthopaedic Nursing, 13(5), 55-58. Kanis, J. (1993). Treatment of symptomatic osteoporosis with fluoride. The American Journal of Medicine, 95 (suppl. 5A) , 5 3 s-6 0 s. Kroll, M. , Rozenberg, S., & Vandromme, J. (1996) . Decision factors influencing hormone therapy. Journal of Obstetrics and Gynecology 1 0 3 (suppl. __1 3) t 92-98. Kupec, D. (1996). Alendronate for the treatment of osteoporosis. Nurse Practitioner, 21(1), 86. Lane, J.z McDonnellr J., & Zimmerman, P. (1987). Osteoporosis: Definition, risk factors, etiology, and diagnosis. American Association of Occupational Health Nursing^ 35112), 527-530. Lindsay, L. (1996) . The new treatment options for osteoporosis. Modern Medicine^ 64_l 6-7. 29 Madson, s. (1989). How to reduce the risk of postmenopausal osteoporosis. Journal of Gerontological Nursing, 1_5 (9) , 20-23. Meunier, p_, & Ringe, J. (1995). What is the future for fluoride treatment of osteoporosis? Osteoporosis International, 5, 71-73. Miller, C. (1992). Estraderm for osteoporosis. Geriatric Nursing, 13 L6) , 337-338. Miller, J. (1994). Clinical evaluation of osteoporosis. Physician Assistant, 18(3), 23-24. Miller, P. (1990). Osteoporosis: New developments in prevention and treatment. Physician Assistant, 14(6), 17-18. Murray, C., & O’Brien, K. (1995). Osteoporosis workup: Evaluating bone loss and risk of fractures. Geriatrics, 50(9)t Nightingale, 41-53. S. (1996). Important Information regarding alendronate adverse reactions. Journal of American Medical Association^ 275(20), 1534. Orem,D. (1995) . Nursing concepts of practice (5th ed.) St. Louis, MO: Mosby. Papapoulos, S. (1993). The role of and treatment of bisphosphonates in the prevention , osteoporosis. American Journal of Medicine, —------------------- 95(suppl. 5A), 48s-51s. Senile osteoporosis. In Ramamurti, C. (1979). R. V. Tinker (Ed-), Orthopaedics in Primary Care 30 (PP- 366-368). Baltimore: Williams & Wilkins. Riis, B. (1996) . The role of bone turnover in the pathophysiololgy of osteoporosis. British Journal of Obstetrics and Gynaecology, 103(suppl 13), 9-15. Reginister, J. (1993). Calcitonin for prevention and treatment of osteoporosis. The American Journal of Medicine, 95, 44s-46s. Todd, B. (1985). Can osteoporosis be treated? Geriatric Nursing, 6_L6) , 359-360. 31 Appendix A 32 Guidelines for the Treatment of Postmenopausal Osteoporosis Osteoporosis is defined as a metabolic disorder of bone in which decreased bone mass and strength lead to an increased incidence of fractures with minimal or no trauma [1] . In osteoporosis, osteoclast activity exceeds osteoblast activity, resulting in a net loss of bone mass. Osteoporosis can be described as primary or secondary, depending upon its etiology. Primary osteoporosis is idiopathic and is divided into two categories, senile and postmenopausal. Secondary osteoporosis is caused by an identified underlying disease [2]. The following guidelines are designed to assist the practitioner in planning the treatment of osteoporosis. These guidelines are based on a review of the literature and input from experts in the field. The guidelines include prevention, diagnosis, use of medications, patient education, and follow-up. It is hoped that these guidelines will promote quality patient care that meets the needs of the individual patient. 33 Prevention of Osteoporosis Women during the transitional years before menopause should be evaluated for osteoporosis risk factors. Hormone replacement therapy should be discussed with women during this time, and they should be evaluated for contraindications to hormone therapy. Women that choose not to use hormone replacement therapy, or those in which it is contraindicated, may be at risk for osteoporosis. Bone density testing should be considered for these women at menopause and thereafter. Osteopenia is decreased bone density without the occurrence of fractures [2] . It is defined as a bone density between 1 and 2.5 standard deviations below the young adult mean [3] . Bone mineral density correlates highly with the risk of fractures, and osteopenia is a risk factor for osteoporosis. Identification of osteopenia, along with the presence of additional osteoporotic risk factors, allows for early intervention before the occurrence of a fracture. Determining the need for bone density testing should be based on the overall patient profile. Risk factors osteoporosisz health motivation, and financial status should be considered in of bone density determining the 34 testing. Refer to Figure 1 for an outline of the guidelines for prevention of postmenopausal osteoporosis. Risk factors for osteoporosis - Postmenopausal - Premature menopause Caucasian or Asian race - Positive family history Small frame Leanness Inactivity Low calcium intake - History of atraumatic fracture - Nulliparity - Long-term glucocorticoid therapy - Long-term anticonvulsant therapy _ Hyperthyroidism or excessive thyroxine - Cigarette smoking - Alcohol abuse - Gastric/small bowel resection 35 CD CO •4—» c o X— CD x— ■O c TD CD CD 25 C CD E c CD o co Q. 4—1 CO co o o ‘■O ID CD C 2 'CO—> CD s._ rs C o O _O < CD C c c O Q_ 5 o o LL n T Q < CD o CD Z) Io CO E C * CD E o <: CD CD ZJ ------> CO ­ CL O c 0 4—' CD O CL CD Q C CD CD CD VCL CD u. CO c CL CO i— CD CD C O 4-> CD Q CO c CD E To TD 0) C Q CO jCfl . •b c CD p q) clcC CD , > o cc 1c o ; CD CD U- H -»—» c CD E CD >jo CL CD O cc CD CD c cd o E x__ o c o o CD Ll 4 -C CD >s 4—■• 'cd o° o co 23 CD £ CD -+—• CO 0 *- CD C 2 CM C O — CD Q CD LO CM (fl O CL O 0) GO k_ o O o o I O v_ co cr c .E O co CD ‘cd £ CD 0 cc g r>(D -o CD co CD £ O T £ CM £ _C >% CD C CD Q > CD c o CD CL Z) § o o 36 Candidates for bonP ■density tie sting. - Postmenopausal women without hormone replacement Women concerned about osteoporosis - Women undecided concerning hormone replacement therapy Persons on long-term Presence of corticosteriods dowager’s hump” — Persons that have suffered a nontraumatic fracture after 40 years of age Estrogen therapy. Postmenopausal osteoporosis is related to estrogen deficiency. Osteoblasts have estrogen receptors that trigger osteoblastic activity, and with a decrease in estrogen there is a decrease in bone building [4] . When estrogen therapy is started in the first 3 to 5 years of menopause, bone loss can be prevented. The dose of estrogen that is effective in preventing osteoporosis is .625 mg daily. The use of progesterone with estrogen does not alter its effectiveness. estrogen is also approved. A transdermal form of The longer that estrogen is used after menopause the greater the reduction in fracture risk. The use of estrogen for 10 years discontinued, reduces the postmenopausally , then risk of fractures by 15% at the age of 80. Remaining on estrogen therapy beyond 10 years 37 postmenopausally reduces the risk of fractures by 50% at the age of 80 [5] . Alendronate LFosamax) Alendronate is another medication that effectively treats osteopenia. Alendronate is a bisphoshonate medication that stops bone loss by interfering with the osteoclasts. The recommended dose is 10 mg orally daily, to be taken on an empty stomach. The patient must then remain NPO for 30 minutes. Alendronate needs to be taken with a full glass of water and with no other medication, liquid, or food. Diagnosing Osteoporosis Osteoporosis is defined by the World Health Organization as a value for bone mineral density that is 2.5 standard deviations or more below the young adult mean. Dual energy x-ray absorptiometry (DEXA) measures bone density at the spine and hip. DEXA testing uses low dose radiation with a precision rate of less than 1% variation. Quantitative computerized tomography (QCT) measures bone density using the spine site with an effective DEXA and a precision rate radiation dose higher than For comparative value, of 3 to 5% variation [3] . the same test must be used each time. 38 Osteoporosis Treatment Estrogen therapy, alendronate, and intranasal calcitonin are the medications approved for treating osteoporosis. Which medication used depends on the individual patient. The practitioner needs to discuss various treatment options with the patient and decide which one best meets the patient's needs. Refer to figure 2 for an outline of the guidelines for treatment of postmenopausal osteoporosis. Estrogen therapy Estrogen therapy increases bone density by 5% to 7% and reduces the risk of vertebral fractures, even when started 5 or more years after menopause [5] . The dose is .625 mg daily and is used with progesterone if the patient has an intact uterus. The additional benefits of estrogen therapy, over and above bone density, need to be considered when deciding on treatment. The patient with a high risk of heart disease, for example, may obtain particular benefit from estrogen therapy. Estrogen therapy is not a treatment option for men. Alendronate therapy. (Fosamaxl Alendronate increases bone density by 8.2% at the spine and 7.2% at the hip, and there is a 48% reduction in new spinal fractures [6]- Alendronate after being started, increases bone density 6 weeks 39 and there is some effect for 2 years after it is Contraindications to alendronate are dysphagia, gastritis, peptic ulcer disease, stopped. esophageal irritation, and creatinine clearance less than 35 ml/min. Side effects of alendronate include gastrointestinal upset, and a rare occurrence of esophageal erosion which usually occurs in the first few weeks of therapy. Patients should be instructed to notify their health care provider of symptoms of esophageal irritation. The patient must remain upright for 30 minutes after taking alendronate to reduce the incidence of esophageal irritation. Only 1 % of alendronate is absorbed orally, so the patient must take it on an empty stomach and not eat or drink for 30 minutes. No other medications can be taken with alendronate, and it should be taken with a full glass of water [7] . The primary care provider needs to assess the patient’s ability to comply with these instructions before ordering alendronate. The patient with difficulty obtaining an severe kyphosis may have benefit from a different upright position, so may with a poor memory may have treatment. The patient difficulty remembering consistently. Patient with the success the instructions motivation plays a big part of alendronate therapy- 40 Intranasal ■Calcitonin .therapy (Miacalcin) Calcitonin decrease osteoclast activity inhibiting the accelerated bone loss of osteoporosis. Administrated as an intranasal spray, calcitonin has been shown to increase bone density by 1% at the lumbar spine. An increase in bone density is seen 6 months after starting therapy, and there is some effect for 2 years after stopping intranasal calcitonin. The only contraindication to its use is an allergy to salmon calcitonin [8] . Side-effects include rhinitis, nausea, vomiting, and flushing. The effective dose is 200 I.U./day taken as one intranasal spray, alternating nostrils each day. Side-effects, when they do occur, are often transient. Intranasal calcitonin has an additional benefit of reducing bone pain. Patients suffering from pain associated with osteoporotic fractures may benefit from this medication. Intranasal calcitonin can be given along with hormone replacement therapy - Patient Education explained to the patient Osteoporosis should be started, and all treatment before treatment is discussed. It is important that options should be of osteoporosis the patient understand the role treatment. 41 Calcium All women after menopause, and men after 50 years of age, should be instructed on calcium supplementation. The recommended daily calcium requirement is 1000 mg with hormone replacement or 1500 mg without hormone replacement. It is recommended that the calcium be taken in divided doses. Vitamin D 400 I.U. to 800 I.U. should also be taken to aid calcium absorption [9] Exercise Weight bearing exercises, such as walking, are recommended to reduce the risk of osteoporosis. All people should begin a regular exercise routine as an adolescence and continue it throughout their adult lives. Fall prevention Instruct the elderly patient to avoid throw rugs in the home, to use a cane or walker as needed, to maintain good posture and body mechanics, and to avoid medications that may cause dizziness. Consultation with physical therapy may be beneficial with some patients for fall precautions. Follow-up should be done in 1 to A follow-up bone density receiving medication to 2 years for the patient 42 treat osteopenia. Dual energy X-ray absorptiometry may not be sensitive enough to detect therapeutic effects within the first year or so [10]. The patient receiving medication to treat osteoporosis should have a follow-up bone density in 3 years. The primary care provider may want to change medications after the follow-up bone densities. For example, the patient with osteopenia treated with alendronate may be able change to hormone therapy if bone density returns to normal. The patient with osteopenia or osteoporosis on hormone replacement who shows no improvement after 2-3 years may benefit from additional medication. 43 CD E £ CD C O z ^8 Z Q ° as > I-i -E Q .9 §-.9 "o^-u 0 x c 2> S> 'as TJ -C CD ' V“ ___ > E CD O 2£ as > O > CD CD 27 27 0 o £0 0-55 0) 0) £ Z o o p ^888 ac ci Ip®®? CD ■4= o CD C 15 O o c co c CD E CD x: <: o CD CD CD O o o CD o £ as T O < < < ■o e OS < o CL O CD "cD O C c E-9 £ 5 CCS a> ’ CD > O .. as c cl 'A -h* cc 2a as CD___ Q. c CD o—► O o C O o c | o E CD "O CD £ x O +± LU CL 6 ■> CD ZJ CD c o E r> o ® E CD CD CD O CD CO 2 a CD CD cc Ct w c Q .E c o ® ’o as O ■a 78 CD as <. c >> J co 4= S £ > CD E O CD Q. <£ C CM -LL — i CD £ Q c CD ECD CD (f) c CD CD O aS CL CD Ct CD C o E o T CD k- 2o LL -------- >Z O •43 c 2 o. 2- ‘as o cI o co O £ 5 O « X c CD OS ■p "5 a? E Ll C > 2 CD CD O k_ cd £D □ □) > CD CD aS c (n (a E CD CD c o CM CD u. CD O OS Q. CD cc CD c o > XE— o I CD □ C •4= C o O 44 References 1 - Stein J: Osteoporosis. In: Internal Medicine, 4th ed. St. Louis, MO: Mosby-Year Book, 1994:1515. 2. Ramamurti C: Senile osteoporosis. In: R. V. Tinker, ed. Orthopaedics in primary care, Baltimore : Williams & Wilkins, 1979:366-368. 3. Gold D, Lee L, & Tresolini C: Working with patients to prevent, treat, and manage osteoporosis: Curriculum Guide For Health Professions. San Francisco, CA: National Fund for Medical Education, 1996. 4. Lane J, McDonnell J, & Zimmerman P: Osteoporosis: Definition, risk factors, etiology, and diagnosis. American Association of Occupational Health Nursing 1 987; 35(12):527-530. 5. Bush T, Ettinger B, Lobo R, Mishell D, & Speroff L: New concepts in managing menopause. Symposium, Patient Care 1995;18-24. for 6. Lindsay L: The new treatment options osteoporosis. Modern Medicine 1996; 64:6 7. 7. Gertz B, Kanis J, Ortolani S, & Singer F: in osteoporosis. Rationale for use of alendronate 5:1-11Osteoporosis International 1995; 8. Reginister j: Calcitonin for prevention and The American Journal of treatment of osteoporosis. 45 Medicine 1993; 95:44s-46s. 9. Todd B: Can osteoporosis be treated? Geriatric Nursing 1985; 6(6):359-360. 10. Hall W: Osteoporosis: Best managed in the primary care setting. Contemporary Internal Medicine 1 997; 9 (1 ) :55-56.