Good Bones, Good Health, Good Life A Look at Osteoporosis

Transcription

1 Good Bones, Good Health, Good Life A Look at Osteoporosis By Monique Camerlain, MD, FRCPC Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone strength reflects the integration of two main features: bone density and bone quality. Currently, there is no accurate measure of overall bone strength. While BMD is used as a proxy measure and accounts for approximately 70% of bone strength, there is no casual way to assess bone quality. The World Health Organization (WHO) defines osteoporosis as a bone density 2.5 standard deviations below the mean for young, white adult women. The patient is assigned a T-score of -2.5, which is the number of standard deviations below the mean. Normal BMD is defined as a T-score between +2.5 and -1. Osteopenia is associated with a T- score between -1 and The WHO group has added a fourth category, severe osteoporosis, to describe a patient whose T-score is below -2.5 and who has suffered a fragility fracture. A fragility fracture could be defined as fracture caused by an injury that would be insufficient to fracture normal bone. In this article: 1. What is osteoporosis? 2. What treatments are available? 3. What is the physician s role? The case of Molly Molly, 65, suffered a wrist fracture when she tripped over her grandson s skateboard eight months ago. She was seen at the emergency department and received proper analgesia and orthopedic management of her fracture. Molly is a healthy, post-menopausal woman who is very active in the community. She plays bridge and enjoys travelling with her recently retired husband. Her history reveals that she has recently quit hormone replacement therapy (HRT), though her mother has sustaind a hip fracture (following the Women s Health Initiative study results). She thinks she can now tolerate her mild menopausal symptoms. Her mother has also suffered from breast cancer. Molly has not had a bone mineral density study and is no longer on a bone-active medication. The SCORE test is also a useful decision tool that can assist physicians in selecting patients for BMD testing (Table 1). The 112

2 Table 1 SCORE * test Osteoporosis evaluation SCORE TM sheet If you are a post-menopausal woman aged 50 to 70, answering the following questions can help you determine whether you may be at risk for osteoporosis. How it works: After you have answered each question below, you will see a numerical "final SCORE," which is a calculation of your overall risk status for osteoporosis. This section also explains the action that should be taken depending on your total score. As found at 1. What is your current age? (years) 2. What is your race or ethnic group? (check one) Black Caucasian Hispanic Asian Native Canadian/First Nation Other 3. Have you ever been treated for, or told you have rheumatoid arthritis? Yes No 4. Since the age of 45, have you experienced a fracture (broken bone) at any of the following sites? Yes No Hip Rib Wrist 5. Do you currently take or have you ever taken estrogen? (Examples include: Premarin, Estraderm, Estring, Estrace, Ogen ) Yes No 6. What is your current weight in pounds? If you are between the age of 50 and 59 and your final SCORE is 6 or greater, you should be evaluated further for osteoporosis. If you are between the age of 60 and 70 and your final SCORE is 8 or greater, you should be evaluated further for osteoporosis. Take your SCORE assessment to your doctor at your next visit. Note: While this questionnaire is not 100% predictive of osteoporosis, it may strongly indicate the need for appropriate evaluation. *SCORE is a registered trademark of Merck & Co., Inc. Used under license. Reproduced with permission. 114

3 LIPITOR * :Hitting targets. Osteoporosis Society of Canada (OSC) recommends that all post-menopausal women and men over 50 be assessed for the presence of risk factors for osteoporosis (Table 2). 1 The OSC has also taken the position that BMD testing is appropriate for targeted case finding among people under 65 and for all women 65 or older because of the high risk of osteoporosis and fracture at that age. 1 Osteoporosis can be further characterized as either primary or secondary. Primary osteoporosis occurs in both genders at all ages, but often follows menopause in women and occurs later in men. In contrast, secondary osteoporosis is a result of medications, other conditions, or diseases. Limited biochemical testing may be required as part of a proper workup to exclude other conditions. 2 EFFICACY A powerful demonstrated effect across key lipid parameters 1 What do the studies say? In a large, retrospective, cohort study involving 1,162 women with new onset distal radius fractures, Freedman et al. found that only 5% had a bone mineral density (BMD) test performed and 235 (20%) were initiated on hormone replacement therapy (HRT), calcitonin, or bisphosphonate. 3 Khan et al. found that 30% of patients with wrist fractures at the emergency department were using estrogens or a bisphosphonate at the time of the fracture. After the fracture, the proportion increased only slightly to 38%. 4 Dr. Camerlain is a consultant member, services de rhumatologie, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec. LIPITOR is an HMG-CoA reductase inhibitor (statin). LIPITOR is indicated as an adjunct to lifestyle changes, including diet, for the reduction of elevated total cholesterol, LDL -C, TG and apolipoprotein B in hyperlipidemic and dyslipidemic conditions (including primary hypercholesterolemia, combined [mixed] hyperlipidemia, dysbetalipoproteinemia, hypertriglyceridemia and familial hypercholesterolemia) when response to diet and other nonpharmacological measures alone has been inadequate. LIPITOR also raises HDL -cholesterol and therefore lowers the LDL -C/HDL -C and Total-C/HDL -C ratios (Fredrickson Type IIa and IIb). These changes in HDL -C with HMG-CoA reductase inhibitors should be considered as modest when compared to those observed in LDL -C and do not play a primary role in the lowering of LDL -C/HDL -C and Total-C/HDL -C ratios. See Prescribing Information for complete warnings, precautions, dosing and administration. LIPITOR is contraindicated: During pregnancy and lactation; active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit of normal; hypersensitivity to any component of this medication.

4 Foundation s (NOF) Table 2 Risk factors for osteoporosis guidelines for initiating treatment. Major factors Minor factors However, fewer than Age > 65 Rheumatoid arthritis 10% of these women Vertebral compression fracture Low dietary calcium intake were taking boneactive medications at Fragility fracture after age 40 Chronic anticonvulsant therapy the time of the hip Family history of osteoporotic Weight loss > 10% of weight at fracture (especially maternal) age 25 fracture and only Systemic glucocorticoid therapy Past history of clinical 10% received any lasting longer than 3 months hyperthyroidism bone-active medication Malabsorption syndrome Smoking in the year fol- Primary hyperparathyroidism Excessive caffeine intake lowing hip fracture. 5 Propensity to fall Weight < 57 kg In the current cohort of patients in Osteopenia apparent on X-ray film Chronic heparin therapy the BHS trial, which Hypogonadism began in 1998, Early menopause (before age 45) results of the baseline BMD measurement Owing et al. reported on a cohort of 205 postmenopausal women from the Baltimore Hip Study (BHS) enrolled between 1992 and The women had a mean age of 81 and more than 87% were osteoporotic and met the National Osteoporosis and a copy of the NOF treatment guidelines were sent to both the patients and their primary care physicians. In the year following their hip fracture, only 13% were on bone-active medications. Table 3 Prevention and treatment of osteoporosis The following is a summary of the recommendations of the Osteoporosis Society of Canada. Higher intakes of calcium and vitamin D are recommended, particularly in adults over 50 (calcium, 1,500 mg/day, and vitamin D, 800 IU/day). Children, particularly those entering and going through puberty, should participate in impact exercise or sports (mainly field and court sports). Men and women throughout life should participate in exercise, particularly weight-bearing exercises, such as brisk walking, running, or dancing. Bisphosphonates (Didrocal, Fosamax, Actonel ) and raloxifene (Evista ) are first choice therapies for individuals without menopausal (vasomotor) symptoms. HRT is no longer the "gold standard" for the treatment of osteoporosis. Alternative treatments, such as ipriflavone and vitamin K, are not recommended for the treatment of post-menopausal women with osteoporosis. In addition, these therapies are not recommended in men or premenopausal women. However, ipriflavone may be considered as a second-line preventive therapy in post-menopausal women. HRT: Hormone replacement therapy 116

5 A meta-analysis of epidemiologic studies and clinical trials concluded that people with a previous fracture at any skeletal site have two to five times greater risk of subsequent fracture compared with those without prior fracture. The relationship is consistent across studies. 6 We also know that a large proportion of patients who have experienced a vertebral fracture will sustain additional vertebral fractures within the following one to three years. Vertebral fractures are also indicators of increased risk of fragility fractures elsewhere, such as the hip. 7 Hip and vertebral fractures are a problem for women in their late 70s and 80s, wrist fractures are a problem in the late 50s to early 70s, and all other fractures (e.g., pelvic and rib) are a problem throughout post-menopausal years. 2 Osteoporotic fractures can be associated with chronic, disabling pain. Nearly one-third of patients with hip fractures are discharged to nursing homes within a year following a fracture and one in five patients is no longer living. Hip fracture has a profound impact on quality of life. The societal cost is also significant. In 1993, the total acute care cost for osteoporosis (admission to hospital, outpatient care, and drug therapy) was over $1.3 billion Cdn. 1 However, primary prevention of osteoporosis initiated in the immediate post-menopause stage is not yet considered a public health priority. Caregivers now face complicated situations with women seeking treatment for the first time at later stages of the disease, namely after diagnosis of osteoporosis has already been made, or after a clinical fracture. Clinical trials have established that two bisphosphonates (alendronate and risedronate) and the selective estrogen receptor modulator raloxifene, are very effective for reducing the risk of vertebral fractures. More importantly, alendronate and rise- LIPITOR * :Hitting targets. EFFICACY A powerful demonstrated effect across key lipid parameters 1 EXPERIENCE More than million patient-years of experience 2 Lipid levels should be monitored periodically and, if necessary, the dose of LIPITOR adjusted based on target lipid levels recommended by guidelines. Caution should be exercised in severely hypercholesterolemic patients who are also renally impaired, elderly, or are concomitantly being administered digoxin or CYP 3A4 inhibitors. Liver function tests should be performed before the initiation of treatment, and periodically thereafter. Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. The effects of atorvastatin-induced changes in lipoprotein levels, including reduction of serum cholesterol on cardiovascular morbidity, mortality, or total mortality have not been established. A patient-year represents the total time of exposure to LIPITOR as defined by the sum of each patient time on LIPITOR. 5

6 First choice Second choice Non-pharmacologic treatment: Calcium: 1,500 mg/day Vitamin D: 800 IU/day Physical activity: > 30 minutes at least 3 times/week Without fragility fracture* Vasomotor symptoms Yes HRT Alendronate, risedronate, raloxifene, calcitonin No Alendronate, risedronate, raloxifene Calcitonin, etidronate, HRT Figure 1. Optimal treatment for osteoporosis in post-menopausal women. *Mainly vertebral fractures. Only alendronate and risedronate (and recently, continuous estrogen/ progesterone) have been shown to decrease hip fracture risk. dronate have each been shown to reduce the risk of non-vertebral fractures, including those of the hip. 8 What are the treatments for osteoporosis? With fragility fracture* Alendronate, risedronate, raloxifene Calcitonin, etidronate, HRT HRT: Hormone replacement therapy The OSC launched the first evidence-based clinical practice guidelines for osteoporosis in the world in November Table 3 and Figure 1 summarize the recommendations for prevention and treatment. In terms of medications, a recent meta-analysis of therapies for post-menopausal osteoporosis concluded that only alendronate and risedronate reduce the risk of both non-vertebral and vertebral fractures. Other agents that reduced vertebral fractures included raloxifene, etidronate, vitamin D, and calcitonin. 8 New weekly formulations of both alendronate and risedronate are also preferred by patients and may improve compliance. More importantly, new data show that alendronate maintains and increases BMD in women who have discontinued HRT. 9,10 Finally, alendronate is the only approved treatment for male osteoporosis in Canada. New agents are also on the horizon. Preliminary results show that new agents, such as ibandronate and zoledronate, may modify the perspective of bisphosphonate treatments by offering potentially as efficient, but less frequent, dosing therapeutic regimens. Two agents, the parathyroid hormone fragment PTH (1-34) (with a potent anabolic action on bone) and strontium ranelate (an inducer of uncoupling between a decreased bone resorption and an increased bone formation) have demonstrated ability to reduce the risk of vertebral and non-vertebral fractures. They may correspond to a new paradigm in our treatment of osteoporosis. 11 What is the physician s role? New therapeutic approaches have emerged in the last decade which, combined with proper lifestyle modifications, can significantly alter outcomes in the management of osteoporosis. We know that a 50-year-old Caucasian woman has a remaining lifetime risk of 40% for hip, vertebral, or 118

7 Take-home message Diagnosis The OSC recommends that all postmenopausal women and men over 50 be assessed for the presence of osteoporosis risk factors. Treatment Alendronate and risedronate are the only medications that reduce risk of both vertebral and non-vertebral fractures. New agents on the horizon are ibandronate and zoledronate. They offer effective treatment with less frequent dosing. wrist fracture. We know that 80% of women over 75 would prefer death over a bad hip fracture resulting in nursing home placement. Yet, one year after a hip fracture a cohort study has shown that only 10% of patients were receiving a bone-active medication. Perhaps these numbers would improve if physicians reviewed their concept of health and illness in the elderly and reconsidered the value of their interventions. Since health and disease can coexist, and the presence of disease does not necessarily reflect a loss of function and wellbeing, it is suggested that the word disease be replaced with illness. Health and illness are not entirely separate concepts and we should consider them as ends of a continuum. Molly, and other elderly patients with osteoporosis, have a right to wellness. We have the tools to provide them with good bones, good health, and a good life. Perhaps, as we reflect on the meaning of quality time for active seniors and adequately use the treatments that are available, we can rewrite the statistics. D x Surf your way to Ostéoporose Québec: 2. The Osteoporosis Society of Canada: 3. The National Osteoporosis Foundation: References 1. Brown JP, Josse RG for the Scientific Advisory Council of the Osteoporosis Society of Canada: 2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada. CMAJ 2002; 167(10 suppl):s Osteoporosis prevention, diagnosis, and therapy. NIH Consensus Statement 2000; 17(1): Freedman KB, Kaplan FS, Bilker WB, et al: Treatment of osteoporosis: Are physicians missing an opportunity? J Bone Joint Surg Am 2000; 82- A(8): Khan SA, de Geus C, Holroyd B, et al: Osteoporosis follow-up after wrist fracture following minor trauma. Arch Intern Med 2001; 161(10): Rheumawire: Excess Bone loss after hip fracture. Oct 17, Klotzbuecher C, Ross PD, Landsman P, et al: Patients with prior fractures have an increased risk of future fractures: A summary of the literature and statistical synthesis. J Bone Miner Res 2000; 15(4): Nevitt MC, Ross PD, Palermo L, et al. for the Fracture Intervention Trial Research Group: The association of prevalent vertebral fractures, bone density and alendronate treatment with incident vertebral fractures: The effect of number and spinal location of fractures. Bone 1999; 25(5): Adachi J, Cranney A, Griffith L, et al: Meta-analyses of therapies for post-menopausal osteoporosis. Endoc Rev 2002; 23(4): Ascott-Evans BH, Guenebens N, Kivinens S, et al: Alendronate prevents loss of bone density associated with discontinuation of hormone replacement therapy: A randomized controlled trial. Arch Intern Med 2003; 163(7): Rheumawire: Alendronate prevents loss of BMD after HRT is stopped. May 6, Reginster JY: New agents for the treatment of osteoporosis. Medscape CME. For a quick-take on this article, go to our Frequently Asked Questions on page For an electronic version of this article, visit: The Canadian Journal of Diagnosis online. 120