Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 1. Introduction.
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OBJECTIVE: To determine the best method of diagnosing osteoporosis and determining fracture risk and to promote standards in the use of bone densitometry and the reporting of results. OPTIONS: Methods of bone mineral density measurement: dual-energy x-ray absorptiometry (DXA), radiographic absorptiometry, single-photon absorptiometry, dual-photon absorptiometry, quantitative computed tomography, quantitative ultrasound, neutron activation analysis. The options of using bone densitometry in individual patient management and as a mass screening tool are also considered. OUTCOMES: Appropriate use of densitometry to promote accurate diagnosis and assessment of fracture risk and timely, appropriate treatment. EVIDENCE: Relevant clinical studies and reports were examined. Clinical practice in Canada was also considered. VALUES: Accurate assessment of osteoporotic fracture risk and diagnosis of osteoporosis and assuring low exposure to medical radiation were given a high value. BENEFITS, HARMS AND COSTS: Early diagnosis through bone density measurement allows proper management of osteoporosis to minimize injury and disability, improve quality of life and reduce the personal and social costs associated with the condition. Potential harms include radiation exposure and cost. The harms and costs of appropriate use of DXA are minimal compared with the harms and costs associated with osteoporosis. RECOMMENDATIONS: Bone mineral density should be measured only to assist in making a clinical management choice. DXA is the best method of measuring bone density and, thus, the best available indicator of osteoporotic fracture risk. Plain radiographs may supplement DXA if there is a specific reason for their use. Measurement of the lumbar spine and femoral neck is standard, but a different site or a single measurement is recommended in specific cases. Unless accelerated bone loss is suspected, DXA should be repeated every 2 to 4 years for patients receiving ovarian hormone therapy and 1 to 2 years for patients undergoing bisphosphonate therapy. Measurements and reporting of results must be standardized. Reports should refer to the World Health Organization's recommended definitions of osteopenia and osteoporosis and provide actual measurement and its relation to peak bone mass.
OBJECTIVE: To present recent evidence on the use of ovarian hormone therapy (OHT) for osteoporosis and outline safe and effective regimens. OPTIONS: Estrogen alone, estrogen and progestins, progestins alone; various treatment regimens. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with OHT. EVIDENCE: Relevant clinical studies and reports, including the Nurses' Health Study and the Post-menopausal Estrogen/Progestin Interventions (PEPI) Trial, were studied with emphasis on recent prospective, randomized, controlled trials. Current clinical practice was determined by survey. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Proper management of osteoporosis minimizes injury and disability, improves quality of life and reduces the personal and social costs associated with the condition. OHT is the front-line pharmaceutical therapy for prevention and treatment of osteoporosis in post-menopausal women. In those who are able and willing to comply with therapy, OHT prevents bone loss and fractures. Hormone therapy may also decrease risk of coronary artery disease. Cyclic progestin protects against endometrial cancer in patients receiving estrogen. Potential harms include breast cancer and endometrial cancer related to dosage and duration of therapy. Mastalgia and especially resumption of menstrual bleeding affect compliance. RECOMMENDATIONS: Use of OHT should be considered as early as possible in the perimenopausal period for women at increased risk of osteoporosis. Guidelines are provided for assessment of osteoporosis risk. Physicians and their patients should take into account the absolute and relative contraindications to OHT. Women with a uterus should be given estrogen in combination with a progestin. Ideally, therapy would be continued for a minimum of 10 years beyond menopause for maximum bone protection. Women using OHT should be carefully monitored and evaluated for possible adverse events. This should include regular screening mammography, breast examination and, for some, endometrial surveillance. Specific dosages and treatment regimens are outlined.
OBJECTIVE: To recommend appropriate levels of calcium intake in light of the most recent studies. OPTIONS: Dietary calcium intake, calcium supplementation, calcium and vitamin D supplementation; ovarian hormone therapy in postmenopausal women. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with osteoporosis prevention. EVIDENCE: Relevant clinical studies and reports were examined, in particular those published since the 1988 Osteoporosis Society of Canada position paper on calcium nutrition. Only studies in humans were considered, including controlled, randomized trials and prospective studies, using bone mass and fractures as end-points. Studies in early and later phases of skeletal growth were noted. The analysis was designed to eliminate menopause as a confounding variable. VALUES: Preventing osteoporosis and maximizing quality of life were given a high value. BENEFITS, HARMS AND COSTS: Adequate calcium nutrition increases bone mineral density during skeletal growth and prevents bone loss and osteoporotic fractures in the elderly. Risks associated with high dietary calcium intake are low, and a recent study extends this conclusion to the risk of kidney stones. Lactase-deficient patients may substitute yogurt and lactase-treated milk for cow's milk. True milk allergy is probably rare; its promotion of diabetes mellitus in susceptible people is being studied. RECOMMENDATIONS: Current recommended intakes of calcium are too low. Revised intake guidelines designed to reduce bone loss and protect against osteoporotic fractures are suggested. Canadians should attempt to meet their calcium requirements principally through food sources. Pharmaceutical calcium supplements and a dietician's advice should be considered where dietary preferences or lactase deficiency restrict consumption of dairy foods. Further research is necessary before recommending the general use of calcium supplements by adolescents. Calcium supplementation cannot substitute for hormone therapy in the prevention of postmenopausal bone loss and fractures. Adequate amounts of vitamin D are necessary for optimal calcium absorption and bone health. Elderly people and those who use heavy sun screens should have a dietary intake of 400 to 800 IU of vitamin D per day.
OBJECTIVE: To describe the mechanisms of action of bisphosphonates in the treatment of osteoporosis and compare bisphosphonate therapy with other treatments. OPTIONS: The bisphosphonates, etidronate, alendronate, clodronate, pamidronate, tiludronate, ibandronate and risedronate; combined bisphosphonates and estrogen; combined bisphosphonates and calcium supplements. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with bisphosphonate treatment. EVIDENCE: Relevant clinical studies and reports were examined with emphasis on recent controlled trials. The availability of treatment products in Canada was also considered. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Treatment with bisphosphonates may be an acceptable alternative to ovarian hormone therapy in increasing bone mass and decreasing fractures associated with osteoporosis. Compared with estrogens, bisphosphonates are bone-tissue specific, have equal or greater antiresorptive effect and have few side effects and no known risk for carcinogenesis. They also hold promise in treating male osteoporosis and steroid-induced bone loss. Prolonged, continuous treatment with etidronate may lead to impaired calcification of newly formed bone; therefore, etidronate is administered cyclically. This risk is not present in newer generations of bisphosphonates. RECOMMENDATIONS: Bisphosphonate therapies may be considered as an alternative to ovarian hormone therapy in postmenopausal osteopenic or osteoporotic women who cannot or will not tolerate ovarian hormone therapy. They should also be considered in treating male osteoporosis and steroid-induced bone loss. Combination therapy with estrogen may be effective, although more research is needed. Combination therapy with calcium supplements is recommended. Bisphosphonate therapies should be restricted to postmenopausal patients with osteopenia or established osteoporosis and are not yet recommended for younger perimenopausal women as prophylaxis.
OBJECTIVE: To present the latest findings on the use of fluoride in the treatment of osteoporosis. OPTIONS: Plain sodium fluoride (NaF), enteric-coated sodium fluoride (EC-NaF), sodium monofluorophosphate (Na2FPO4), slow-release sodium fluoride (SR-NaF); fluoride with a calcium supplement. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with treatment. EVIDENCE: Relevant clinical studies and reports were examined, with an emphasis on recent prospective, randomized, controlled trials. Clinical practices in European countries were also considered. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: NaF therapy stimulates bone formation and may be effective in preventing osteoporotic fractures. It may be an acceptable alternative treatment to estrogen or bisphosphonate therapy and useful in premenopausal and corticosteroid-induced osteoporosis and in some patients with mild osteogenesis imperfecta. Toxic effects are dependent on formulation and dosage. They include a range of gastrointestinal and musculoskeletal conditions. EC-NaF is associated with less toxicity than plain NaF; its gastrointestinal toxicity is negligible. Na2FPO4 has no gastrointestinal toxicity, but can give rise to skeletal toxicity. SR-NaF appears to have no side effects when given intermittently. Carcinogenicity has not been found in vivo with fluoride therapy, despite in vitro results. RECOMMENDATIONS: New data indicate that fluoride therapy should be re-evaluated as a potentially effective treatment of osteoporosis with minimal side effects. More studies are needed of slow-release fluoride formulations, intermittent treatment schedules and calcium supplementation of fluoride. Studies should be undertaken to see if it is advantageous to initiate treatment with antiresorptive agents before or in combination with fluoride. Conclusive data have not been presented regarding the benefit of any specific type of calcium supplement. Further studies on the basic mechanism of action of fluoride on the skeleton are necessary to evaluate fluoride's potential to stimulate bone formation therapeutically.
OBJECTIVE: To review recent findings on the skeletal actions of vitamin D and to examine results of the latest clinical trials of vitamin D in the treatment of osteoporosis. OPTIONS: The vitamin D analog 1-alpha hydroxycholecalciferol (1 alpha-OH-D3); the vitamin D metabolite calcitriol. OUTCOMES: Fracture and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures and improved quality of life associated with vitamin D therapies. EVIDENCE: Relevant laboratory and clinical studies and reports were examined. Greatest reliance was placed on recent large-scale, randomized, controlled trials; others were noted and their methods critiqued. Clinical practice in Japan was also considered. VALUES: Reducing fractures, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Vitamin D maintains the dynamic nature of bone and so presumably helps to keep it healthy. Calcitriol and 1 alpha-OH-D3 may be effective in increasing bone mass and preventing fractures in osteoporosis. Calcitriol may be an alternative treatment in the prevention and management of corticosteroid-induced osteoporosis. Possible side effects of vitamin D analogs and metabolites are hypercalcemia, hypercalciuria, renal calcification and renal stones. RECOMMENDATIONS: The use of 1 alpha-OH-D3 for the treatment of osteoporosis in Canada cannot be supported without larger and longer randomized, controlled clinical trials. Calcitriol appears to prevent vertebral fractures in patients with osteoporosis. More information is needed on its mechanism of action and efficacy in preventing hip fractures. Future studies should focus on comparisons with other effective therapies and on determining whether its effect on fractures is greater than that achieved through improved vitamin D nutrition. Patients taking calcitriol at dose levels required for antifracture effects should be monitored for serum and urine calcium response to the drug. Calcitriol should not be given to patients whose calcium intake is at current generally recommended levels. At present, prescription of calcitriol for the treatment of osteoporosis should be reserved for physicians with a special interest in the treatment of metabolic bone disease.
OBJECTIVE: To describe potential therapeutic uses of calcitonin in the prevention and treatment of osteoporosis. OPTIONS: Parenterally and intranasally administered calcitonin (eel, salmon or human). OUTCOMES: Fracture, fracture pain and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures, reduction of pain and improved quality of life associated with calcitonin treatment. EVIDENCE: Relevant clinical studies and reports were examined, with an emphasis on recent randomized, placebo-controlled trials. In vitro and in vivo studies of osteoclast activity were also considered. VALUES: Reducing fractures and fracture pain, increasing bone mineral density and minimizing side effects of treatment were given a high value. BENEFITS, HARMS AND COSTS: Calcitonin reduces acute pain associated with osteoporotic fractures and has been found useful in treating chronic back pain following vertebral fractures in spinal osteoporosis. It can prevent bone loss and may be effective in preventing fractures. Side effects are dose related and generally mild; they include gastrointestinal, vascular and dermatologic conditions that can be treated symptomatically or by varying the dosage. Side effects are much rarer with nasal administration than with injection. True allergic reactions are rare. RECOMMENDATIONS: Calcitonin in both intramuscular and intranasal forms can reduce the pain of acute osteoporotic vertebral fractures and may be effective in treating that associated with chronic vertebral osteoporotic fractures. Calcitonin may also prevent postmenopausal bone loss and increase bone density in those with established osteoporosis. Current evidence for long-term prevention of fractures is limited and does not support the use of calcitonin as a first-line treatment for established osteoporosis. Most side effects can be avoided with nasal administration. Further trials are needed to assess fracture prevention and effective dose ranges for treating pain and increasing bone mineral density and to determine the long-term efficacy of calcitonin in secondary osteoporosis, in premenopausal women, in men and in elderly people.
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OBJECTIVE: To examine exercise as a therapy for people with osteoporosis. OPTIONS: Immobilization, standing low-load and high-load physical activities. OUTCOMES: Risk of injury, quality of life, risk of falls and fractures, strength and posture and pain management. EVIDENCE: Relevant epidemiologic studies, clinical trials and reviews were examined, including the large-scale FICSIT trial in the United States, a prospective 4-year study of women enrolled in an exercise program in Toronto and the large-scale Study of Osteoporotic Fractures. VALUES: Minimizing risk of injury and increasing quality of life were given a high value. BENEFITS, HARMS, AND COSTS: Moderate physical activity in people with osteoporosis can reduce the risk of falls and fractures, decrease pain and improve fitness and overall quality of life. It may also stimulate bone gain and decrease bone loss. Its positive effects are an adjunct to other interventions, such as hormonal therapy. It may give patients the confidence to resume regular activity and can provide social interaction and support. During exercise programs, proper nutrition is necessary to prevent excessive weight loss and impaired immune function resulting from inadequate protein, vitamin and mineral intake. RECOMMENDATIONS: Immobilization should be avoided if possible in anyone with osteoporosis or at increased risk for osteoporosis. Regular, moderate physical activity is recommended for those with osteoporosis. Elderly people should be assessed for risk of falling to identify those in greatest need of an exercise program. Community group exercise programs are beneficial. Younger people with osteoporosis also need exercise that will preserve or improve bone mass, muscular strength, endurance and cardiovascular fitness. Weight loss as a result of physical activity should be avoided and adequate intake of protein, vitamins and minerals assured. Because the benefits of physical activity are independent of the effect of other therapies, physical activity is an essential adjunct to appropriate nutrition and other therapies. VALIDATION: These recommendations were developed by the Scientific Advisory Board of the Osteoporosis Society of Canada at its 1995 Consensus Conference. They are in agreement with the position taken on osteoporosis and exercise by the United States Center for Disease Control and Prevention and the American College of Sports Medicine. SPONSORS: Sponsors of the 1995 conference included the Dairy Farmers of Canada, Eli Lilly Canada, Inc., Hoffmann-La Roche Canada Ltd., Merck Frosst Canada Inc. and Procter & Gamble Pharmaceuticals Canada Inc.
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