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How should a DEXA scan be used to evaluate bisphosphonate therapy for osteoporosis?
If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years (strength of recommendation [SOR]: B, based on case series of dual energy X-ray absorptiometry [DEXA] scanning precision and bisphosphonate efficacy). Currently no prospective, randomized trials investigate the impact of bone density follow-up testing on osteoporotic patients receiving bisphosphonate therapy.
Evidence summary
Testing the effectiveness of therapy for osteoporosis by measuring changes in bone mineral density (BMD) is difficult because changes are often small and occur slowly, and a decrease in BMD does not necessarily mean treatment failure. Testing patients after starting bisphosphonate therapy has been part of many drug trials to assess the effectiveness of therapy. Follow-up testing in clinical practice has not been the focus of a prospective trial and therefore remains controversial.1
DEXA is considered the gold standard because it is the most extensively validated test for predicting fracture outcomes.2 Understanding the rate of bone density response to therapy, and the precision error of DEXA, helps to determine monitoring intervals. The larger the responses in BMD to therapy and the more precise the DEXA scan result, the shorter the period between testing in which clinically relevant differences can be found. Precision error rates are estimated at <1% for the anterior-posterior spine and 1% to 2% for the hip.3 The BMD change after the initiation of treatment must escape the precision error of the testing device or exceed the least significant change (LSC) value.4 The LSC—roughly analogous to a 95% confidence interval—is 2.8 times the precision error of the test on a specific machine and site of measurement. If the precision error for DEXA of the femoral neck BMD is 2%, then the LSC is 5.6%.5 Changes in BMD of <2%–4% in the vertebrae and 3% to 6% at the hip could be due to inherent measurement error.6
A clinician must also understand the anticipated response to the prescribed therapy. It is not clinically useful to retest BMD before a therapy would have time to affect bone turnover. Alendronate and risedronate increase lumbar spine BMD by 5% to 7% and hip BMD by 3% to 6% when used for approximately 3 years.7,8 These increases in BMD are associated with 30% to 50% reductions in vertebral and hip fractures.6 Alendronate continues to increase BMD: following 10 years of treatment, it increased BMD by 13.7% in the lumbar spine, 6.7% in the total hip, and 5.4 % in the femoral neck.9
Frequent testing, as seen in bisphosphonate clinical trials, demonstrates the phenomenon of regression to the mean. One analysis of the FIT trial, which compared alendronate with placebo in postmenopausal women with low BMD and at least 1 vertebral fracture, focused on the early evaluation of BMD. The study found a high degree of variability in BMD when tested after 1 year of treatment. This wide variety of response in the first year normalized in the second year.10 A second analysis showed that when women were divided into 8 groups, the group with the greatest increase in BMD in the first year (10.4%) also had the greatest decrease (1.0%) in year 2. In addition, the group with the greatest decrease in year 1 (6.6%) had the greatest increase in year 2 (4.8%). The variability in response among the 8 groups was approximately 17% (+10.4% and –6.6%) in year 1 and narrowed to a 6% difference in year 2 This regression to the mean leads to a normalization of bone density results.11,12 This patient variability in BMD response to the prescribed therapy should be considered when deciding to retest.
In summary, limitations in DEXA precision mean any changes in BMD of less than 5.6% at the femoral neck may be due to measurement error, and BMD response to bisphosphonates vacillates in the first few years of use but can be expected to increase femoral neck BMD 3% to 6% over 3 years. Therefore, if serial DEXA scanning is preformed on patients prescribed bisphosphonate therapy, it should be considered no earlier than 2 to 3 years after therapy begins. When monitoring osteoporosis therapy, a BMD change within the LSC should be interpreted as “no change” and should not lead to changes in patient management. If the BMD has decreased beyond the LSC there is cause for concern and reevaluation of diagnosis and treatment are warranted.4
Recommendations from others
Guidelines on monitoring the clinical response to osteoporosis therapy with DEXA are available from numerous groups ( TABLE ). In clinical practice, it is common for a BMD difference of 3% to 5% at the spine or 4% to 6 % at the hip to be considered clinically significant.13
TABLE
Recommendations on monitoring the clinical response to DEXA in osteoporosis therapy
| Organization | Method used to formulate responses recommendation | Recommendations for monitoring treatment to anti-resorptive therapy |
|---|---|---|
| AHRQ Evidence Report (Osteoporosis in Postmenopausal Women)14 | Systematic review | Advises against repeating bone density tests within the first year of treatment. Insufficient evidence to determine whether repeating tests 2 years after starting therapy is useful |
| American Association of Clinical Endocrinologists13 | Rating scheme (Statement not rated) | Yearly for 2 years and if bone mass has stabilized, follow-up measurements are recommended every 2 years |
| Canadian Panel of Clinical Densitometry15 | Not stated | Repeat scan should be considered after 1 to 3 years if concerned about progressive bone loss or with new intervention |
| Institute for Clinical Systems Improvement1 | Not stated | Controversy exists as to whether follow-up testing is necessary in all patients, but if performed, it should be done after 1 to 2 years of therapy |
| National Institute of Health16 change | Expert consensus | Monitoring has not been shown to improve compliance. Physicians should not stop or therapies because of modest bone density loss |
| National Osteoporosis Foundation6 | Expert consensus | Recommended 1 to 2 years following initiation of therapy |
| North American Menopause Society17 | Expert consensus | Monitoring before 2 years of treatment would not be useful |
| Osteoporosis Society of Canada18 | Not stated | Suggests at least 1 follow-up measurement is necessary. Central bone densitometry 1 to 2 years following initiation of bisphosphonate therapy. For patients receiving hormone therapy, repeat BMD is recommended at 2 to 4 years |
| University of Michigan19 | Evidence rating scheme | For most persons an interval of >2 years between DEXAs provides the most meaningful information |
If follow-up is needed, rescan in 2 to 3 years
Ann B. Gotschall, MD
Baylor College of Medicine, Houston, Tex
Rates of vertebral and hip fractures are significantly reduced by alendronate and risedronate, making them important in the prevention and treatment of osteoporosis. Despite controversies over the timing and necessity of monitoring bisphosphonate therapy with DEXA scans, they may be useful clinically if their limitations are recognized. It is necessary to wait 2 to 3 years to repeat the DEXA after initiating therapy to account for the slow rate of change of bone density and compensate for the regression-to-the-mean phenomenon seen in clinical trials.
If after 2 or 3 years the bone density remains stable or has increased, reassurance can be given that fracture risk has decreased. If bone density has decreased more than the LSC, consider the following questions. Is the medicine is being taken first thing in the morning on an empty stomach? Is weight-bearing exercise performed routinely, tobacco avoided, and caffeine limited? Is the patient continuing adequate calcium and vitamin D supplements? The physician should also consider secondary causes of osteoporosis, such as hyperthyroidism and hyperparathyroidism.
1. Institute for Clinical Systems Improvement (ICSI). Diagnosis and Treatment of Osteoporosis. Bloomington, Minn: ICSI; 2002:1-67. Last updated July 31, 2002. Available at: www.icsi.org/knowledge/detail.asp?catID=29&itemID=547. Accessed on December 8, 2004.
2. Nelson HD, Helfand M, Woolf SH, Allan JD. Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services task force. Ann Intern Med 2002;137:529-541.
3. Mazees R, Chestnut CH 3rd, McClung M, Genant H. Enhanced precision with dual-energy X-rat absorptiometry. Calcif Tissue Int 1992;51:14-17.
4. Lenchik L, Kiebzak GM, Blunt BA. International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. What is the role of serial bone mineral density measurements in patient management? J Clin Densitom 2002;5 Suppl:S29-S38.
5. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry scientific review. JAMA 2002;288:1889-1897.Erratum in: JAMA 2002; 288:2825.
6. National steoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 2003. Available at: www.nof.org. Accessed on December 8, 2004.
7. Cranney A, Wells G, Willan A, et al. Meta-analysis of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002;23:508-516.
8. Cranney A, Tugwell P, Adachi J, et al. Meta-analysis of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:517-523.
9. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004;350:1189-1199.
10. Bonnick SL. Monitoring osteoporosis therapy with bone densitometry: a vital tool or regression toward mediocrity. J Clin Endocrinol Metabl 2000;85:3493-3495.
11. Cummings SR, Palermo L, Browner W, et al. Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group. JAMA 2000;283:1318-1321.
12. Hochberg MC, Ross PD, Black D, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. Arthritis Rheum 1999;42:1246-1254.
13. Hodgson SF, Watts NB, Bilezikian JP, et al. American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis. Endocr Pract 2000;7:293-312.
14. Nelson HD, Morris CD, Kraemer DF, et al. Osteoporosis in Postmenopausal Women: Diagnosis and Monitoring. Evidence Report/Technology Assessment No. 28 (Prepared by the Oregon Health & Science University Evidence-based Practice Center under Contract No. 290-97-0018). AHRQ Publication No. 01-E032. Rockville, Md: Agency for Healthcare Research and Quality. January 2001. Available at: www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View.Show Section&rid=hstat1.chapter.39885. Accessed on December 8, 2004.
15. Khan AA, Brown J, Faulkner K, et al. Standards and guidelines for performing central dual X-ray densitometry from the Canadian Panel of International Society for Clinical Densitometry. J Clin Densitom 2002;5:435-445.
16. Osteoporosis Prevention Diagnosis and Therapy. NIH Consensus Statement 2000; 17:1-36. Available at: consen-sus.nih.gov/cons/111/111_statement.htm. Accessed on December 8, 2004.
17. North American Menopause Society. Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Menopause 2002;9:84-101.
18. Sturtridge W, Lentle B, Hanley DA. Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 2. The use of bone density measurement in the diagnosis and management of osteoporosis. CMAJ 1996;155:924-929.
19. University of Michigan Health System. Osteoporosis: Prevention and Treatment. Ann Arbor: University of Michigan Health System; 2002:1-12. Available at: cme.med.umich.edu/pdf/guideline/osteoporosis.pdf. Accessed on December 8, 2004.
If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years (strength of recommendation [SOR]: B, based on case series of dual energy X-ray absorptiometry [DEXA] scanning precision and bisphosphonate efficacy). Currently no prospective, randomized trials investigate the impact of bone density follow-up testing on osteoporotic patients receiving bisphosphonate therapy.
Evidence summary
Testing the effectiveness of therapy for osteoporosis by measuring changes in bone mineral density (BMD) is difficult because changes are often small and occur slowly, and a decrease in BMD does not necessarily mean treatment failure. Testing patients after starting bisphosphonate therapy has been part of many drug trials to assess the effectiveness of therapy. Follow-up testing in clinical practice has not been the focus of a prospective trial and therefore remains controversial.1
DEXA is considered the gold standard because it is the most extensively validated test for predicting fracture outcomes.2 Understanding the rate of bone density response to therapy, and the precision error of DEXA, helps to determine monitoring intervals. The larger the responses in BMD to therapy and the more precise the DEXA scan result, the shorter the period between testing in which clinically relevant differences can be found. Precision error rates are estimated at <1% for the anterior-posterior spine and 1% to 2% for the hip.3 The BMD change after the initiation of treatment must escape the precision error of the testing device or exceed the least significant change (LSC) value.4 The LSC—roughly analogous to a 95% confidence interval—is 2.8 times the precision error of the test on a specific machine and site of measurement. If the precision error for DEXA of the femoral neck BMD is 2%, then the LSC is 5.6%.5 Changes in BMD of <2%–4% in the vertebrae and 3% to 6% at the hip could be due to inherent measurement error.6
A clinician must also understand the anticipated response to the prescribed therapy. It is not clinically useful to retest BMD before a therapy would have time to affect bone turnover. Alendronate and risedronate increase lumbar spine BMD by 5% to 7% and hip BMD by 3% to 6% when used for approximately 3 years.7,8 These increases in BMD are associated with 30% to 50% reductions in vertebral and hip fractures.6 Alendronate continues to increase BMD: following 10 years of treatment, it increased BMD by 13.7% in the lumbar spine, 6.7% in the total hip, and 5.4 % in the femoral neck.9
Frequent testing, as seen in bisphosphonate clinical trials, demonstrates the phenomenon of regression to the mean. One analysis of the FIT trial, which compared alendronate with placebo in postmenopausal women with low BMD and at least 1 vertebral fracture, focused on the early evaluation of BMD. The study found a high degree of variability in BMD when tested after 1 year of treatment. This wide variety of response in the first year normalized in the second year.10 A second analysis showed that when women were divided into 8 groups, the group with the greatest increase in BMD in the first year (10.4%) also had the greatest decrease (1.0%) in year 2. In addition, the group with the greatest decrease in year 1 (6.6%) had the greatest increase in year 2 (4.8%). The variability in response among the 8 groups was approximately 17% (+10.4% and –6.6%) in year 1 and narrowed to a 6% difference in year 2 This regression to the mean leads to a normalization of bone density results.11,12 This patient variability in BMD response to the prescribed therapy should be considered when deciding to retest.
In summary, limitations in DEXA precision mean any changes in BMD of less than 5.6% at the femoral neck may be due to measurement error, and BMD response to bisphosphonates vacillates in the first few years of use but can be expected to increase femoral neck BMD 3% to 6% over 3 years. Therefore, if serial DEXA scanning is preformed on patients prescribed bisphosphonate therapy, it should be considered no earlier than 2 to 3 years after therapy begins. When monitoring osteoporosis therapy, a BMD change within the LSC should be interpreted as “no change” and should not lead to changes in patient management. If the BMD has decreased beyond the LSC there is cause for concern and reevaluation of diagnosis and treatment are warranted.4
Recommendations from others
Guidelines on monitoring the clinical response to osteoporosis therapy with DEXA are available from numerous groups ( TABLE ). In clinical practice, it is common for a BMD difference of 3% to 5% at the spine or 4% to 6 % at the hip to be considered clinically significant.13
TABLE
Recommendations on monitoring the clinical response to DEXA in osteoporosis therapy
| Organization | Method used to formulate responses recommendation | Recommendations for monitoring treatment to anti-resorptive therapy |
|---|---|---|
| AHRQ Evidence Report (Osteoporosis in Postmenopausal Women)14 | Systematic review | Advises against repeating bone density tests within the first year of treatment. Insufficient evidence to determine whether repeating tests 2 years after starting therapy is useful |
| American Association of Clinical Endocrinologists13 | Rating scheme (Statement not rated) | Yearly for 2 years and if bone mass has stabilized, follow-up measurements are recommended every 2 years |
| Canadian Panel of Clinical Densitometry15 | Not stated | Repeat scan should be considered after 1 to 3 years if concerned about progressive bone loss or with new intervention |
| Institute for Clinical Systems Improvement1 | Not stated | Controversy exists as to whether follow-up testing is necessary in all patients, but if performed, it should be done after 1 to 2 years of therapy |
| National Institute of Health16 change | Expert consensus | Monitoring has not been shown to improve compliance. Physicians should not stop or therapies because of modest bone density loss |
| National Osteoporosis Foundation6 | Expert consensus | Recommended 1 to 2 years following initiation of therapy |
| North American Menopause Society17 | Expert consensus | Monitoring before 2 years of treatment would not be useful |
| Osteoporosis Society of Canada18 | Not stated | Suggests at least 1 follow-up measurement is necessary. Central bone densitometry 1 to 2 years following initiation of bisphosphonate therapy. For patients receiving hormone therapy, repeat BMD is recommended at 2 to 4 years |
| University of Michigan19 | Evidence rating scheme | For most persons an interval of >2 years between DEXAs provides the most meaningful information |
If follow-up is needed, rescan in 2 to 3 years
Ann B. Gotschall, MD
Baylor College of Medicine, Houston, Tex
Rates of vertebral and hip fractures are significantly reduced by alendronate and risedronate, making them important in the prevention and treatment of osteoporosis. Despite controversies over the timing and necessity of monitoring bisphosphonate therapy with DEXA scans, they may be useful clinically if their limitations are recognized. It is necessary to wait 2 to 3 years to repeat the DEXA after initiating therapy to account for the slow rate of change of bone density and compensate for the regression-to-the-mean phenomenon seen in clinical trials.
If after 2 or 3 years the bone density remains stable or has increased, reassurance can be given that fracture risk has decreased. If bone density has decreased more than the LSC, consider the following questions. Is the medicine is being taken first thing in the morning on an empty stomach? Is weight-bearing exercise performed routinely, tobacco avoided, and caffeine limited? Is the patient continuing adequate calcium and vitamin D supplements? The physician should also consider secondary causes of osteoporosis, such as hyperthyroidism and hyperparathyroidism.
If bone density is evaluated after initiating bisphosphonate drug therapy, it should be tested no earlier than 2 years (strength of recommendation [SOR]: B, based on case series of dual energy X-ray absorptiometry [DEXA] scanning precision and bisphosphonate efficacy). Currently no prospective, randomized trials investigate the impact of bone density follow-up testing on osteoporotic patients receiving bisphosphonate therapy.
Evidence summary
Testing the effectiveness of therapy for osteoporosis by measuring changes in bone mineral density (BMD) is difficult because changes are often small and occur slowly, and a decrease in BMD does not necessarily mean treatment failure. Testing patients after starting bisphosphonate therapy has been part of many drug trials to assess the effectiveness of therapy. Follow-up testing in clinical practice has not been the focus of a prospective trial and therefore remains controversial.1
DEXA is considered the gold standard because it is the most extensively validated test for predicting fracture outcomes.2 Understanding the rate of bone density response to therapy, and the precision error of DEXA, helps to determine monitoring intervals. The larger the responses in BMD to therapy and the more precise the DEXA scan result, the shorter the period between testing in which clinically relevant differences can be found. Precision error rates are estimated at <1% for the anterior-posterior spine and 1% to 2% for the hip.3 The BMD change after the initiation of treatment must escape the precision error of the testing device or exceed the least significant change (LSC) value.4 The LSC—roughly analogous to a 95% confidence interval—is 2.8 times the precision error of the test on a specific machine and site of measurement. If the precision error for DEXA of the femoral neck BMD is 2%, then the LSC is 5.6%.5 Changes in BMD of <2%–4% in the vertebrae and 3% to 6% at the hip could be due to inherent measurement error.6
A clinician must also understand the anticipated response to the prescribed therapy. It is not clinically useful to retest BMD before a therapy would have time to affect bone turnover. Alendronate and risedronate increase lumbar spine BMD by 5% to 7% and hip BMD by 3% to 6% when used for approximately 3 years.7,8 These increases in BMD are associated with 30% to 50% reductions in vertebral and hip fractures.6 Alendronate continues to increase BMD: following 10 years of treatment, it increased BMD by 13.7% in the lumbar spine, 6.7% in the total hip, and 5.4 % in the femoral neck.9
Frequent testing, as seen in bisphosphonate clinical trials, demonstrates the phenomenon of regression to the mean. One analysis of the FIT trial, which compared alendronate with placebo in postmenopausal women with low BMD and at least 1 vertebral fracture, focused on the early evaluation of BMD. The study found a high degree of variability in BMD when tested after 1 year of treatment. This wide variety of response in the first year normalized in the second year.10 A second analysis showed that when women were divided into 8 groups, the group with the greatest increase in BMD in the first year (10.4%) also had the greatest decrease (1.0%) in year 2. In addition, the group with the greatest decrease in year 1 (6.6%) had the greatest increase in year 2 (4.8%). The variability in response among the 8 groups was approximately 17% (+10.4% and –6.6%) in year 1 and narrowed to a 6% difference in year 2 This regression to the mean leads to a normalization of bone density results.11,12 This patient variability in BMD response to the prescribed therapy should be considered when deciding to retest.
In summary, limitations in DEXA precision mean any changes in BMD of less than 5.6% at the femoral neck may be due to measurement error, and BMD response to bisphosphonates vacillates in the first few years of use but can be expected to increase femoral neck BMD 3% to 6% over 3 years. Therefore, if serial DEXA scanning is preformed on patients prescribed bisphosphonate therapy, it should be considered no earlier than 2 to 3 years after therapy begins. When monitoring osteoporosis therapy, a BMD change within the LSC should be interpreted as “no change” and should not lead to changes in patient management. If the BMD has decreased beyond the LSC there is cause for concern and reevaluation of diagnosis and treatment are warranted.4
Recommendations from others
Guidelines on monitoring the clinical response to osteoporosis therapy with DEXA are available from numerous groups ( TABLE ). In clinical practice, it is common for a BMD difference of 3% to 5% at the spine or 4% to 6 % at the hip to be considered clinically significant.13
TABLE
Recommendations on monitoring the clinical response to DEXA in osteoporosis therapy
| Organization | Method used to formulate responses recommendation | Recommendations for monitoring treatment to anti-resorptive therapy |
|---|---|---|
| AHRQ Evidence Report (Osteoporosis in Postmenopausal Women)14 | Systematic review | Advises against repeating bone density tests within the first year of treatment. Insufficient evidence to determine whether repeating tests 2 years after starting therapy is useful |
| American Association of Clinical Endocrinologists13 | Rating scheme (Statement not rated) | Yearly for 2 years and if bone mass has stabilized, follow-up measurements are recommended every 2 years |
| Canadian Panel of Clinical Densitometry15 | Not stated | Repeat scan should be considered after 1 to 3 years if concerned about progressive bone loss or with new intervention |
| Institute for Clinical Systems Improvement1 | Not stated | Controversy exists as to whether follow-up testing is necessary in all patients, but if performed, it should be done after 1 to 2 years of therapy |
| National Institute of Health16 change | Expert consensus | Monitoring has not been shown to improve compliance. Physicians should not stop or therapies because of modest bone density loss |
| National Osteoporosis Foundation6 | Expert consensus | Recommended 1 to 2 years following initiation of therapy |
| North American Menopause Society17 | Expert consensus | Monitoring before 2 years of treatment would not be useful |
| Osteoporosis Society of Canada18 | Not stated | Suggests at least 1 follow-up measurement is necessary. Central bone densitometry 1 to 2 years following initiation of bisphosphonate therapy. For patients receiving hormone therapy, repeat BMD is recommended at 2 to 4 years |
| University of Michigan19 | Evidence rating scheme | For most persons an interval of >2 years between DEXAs provides the most meaningful information |
If follow-up is needed, rescan in 2 to 3 years
Ann B. Gotschall, MD
Baylor College of Medicine, Houston, Tex
Rates of vertebral and hip fractures are significantly reduced by alendronate and risedronate, making them important in the prevention and treatment of osteoporosis. Despite controversies over the timing and necessity of monitoring bisphosphonate therapy with DEXA scans, they may be useful clinically if their limitations are recognized. It is necessary to wait 2 to 3 years to repeat the DEXA after initiating therapy to account for the slow rate of change of bone density and compensate for the regression-to-the-mean phenomenon seen in clinical trials.
If after 2 or 3 years the bone density remains stable or has increased, reassurance can be given that fracture risk has decreased. If bone density has decreased more than the LSC, consider the following questions. Is the medicine is being taken first thing in the morning on an empty stomach? Is weight-bearing exercise performed routinely, tobacco avoided, and caffeine limited? Is the patient continuing adequate calcium and vitamin D supplements? The physician should also consider secondary causes of osteoporosis, such as hyperthyroidism and hyperparathyroidism.
1. Institute for Clinical Systems Improvement (ICSI). Diagnosis and Treatment of Osteoporosis. Bloomington, Minn: ICSI; 2002:1-67. Last updated July 31, 2002. Available at: www.icsi.org/knowledge/detail.asp?catID=29&itemID=547. Accessed on December 8, 2004.
2. Nelson HD, Helfand M, Woolf SH, Allan JD. Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services task force. Ann Intern Med 2002;137:529-541.
3. Mazees R, Chestnut CH 3rd, McClung M, Genant H. Enhanced precision with dual-energy X-rat absorptiometry. Calcif Tissue Int 1992;51:14-17.
4. Lenchik L, Kiebzak GM, Blunt BA. International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. What is the role of serial bone mineral density measurements in patient management? J Clin Densitom 2002;5 Suppl:S29-S38.
5. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry scientific review. JAMA 2002;288:1889-1897.Erratum in: JAMA 2002; 288:2825.
6. National steoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 2003. Available at: www.nof.org. Accessed on December 8, 2004.
7. Cranney A, Wells G, Willan A, et al. Meta-analysis of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002;23:508-516.
8. Cranney A, Tugwell P, Adachi J, et al. Meta-analysis of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:517-523.
9. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004;350:1189-1199.
10. Bonnick SL. Monitoring osteoporosis therapy with bone densitometry: a vital tool or regression toward mediocrity. J Clin Endocrinol Metabl 2000;85:3493-3495.
11. Cummings SR, Palermo L, Browner W, et al. Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group. JAMA 2000;283:1318-1321.
12. Hochberg MC, Ross PD, Black D, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. Arthritis Rheum 1999;42:1246-1254.
13. Hodgson SF, Watts NB, Bilezikian JP, et al. American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis. Endocr Pract 2000;7:293-312.
14. Nelson HD, Morris CD, Kraemer DF, et al. Osteoporosis in Postmenopausal Women: Diagnosis and Monitoring. Evidence Report/Technology Assessment No. 28 (Prepared by the Oregon Health & Science University Evidence-based Practice Center under Contract No. 290-97-0018). AHRQ Publication No. 01-E032. Rockville, Md: Agency for Healthcare Research and Quality. January 2001. Available at: www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View.Show Section&rid=hstat1.chapter.39885. Accessed on December 8, 2004.
15. Khan AA, Brown J, Faulkner K, et al. Standards and guidelines for performing central dual X-ray densitometry from the Canadian Panel of International Society for Clinical Densitometry. J Clin Densitom 2002;5:435-445.
16. Osteoporosis Prevention Diagnosis and Therapy. NIH Consensus Statement 2000; 17:1-36. Available at: consen-sus.nih.gov/cons/111/111_statement.htm. Accessed on December 8, 2004.
17. North American Menopause Society. Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Menopause 2002;9:84-101.
18. Sturtridge W, Lentle B, Hanley DA. Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 2. The use of bone density measurement in the diagnosis and management of osteoporosis. CMAJ 1996;155:924-929.
19. University of Michigan Health System. Osteoporosis: Prevention and Treatment. Ann Arbor: University of Michigan Health System; 2002:1-12. Available at: cme.med.umich.edu/pdf/guideline/osteoporosis.pdf. Accessed on December 8, 2004.
1. Institute for Clinical Systems Improvement (ICSI). Diagnosis and Treatment of Osteoporosis. Bloomington, Minn: ICSI; 2002:1-67. Last updated July 31, 2002. Available at: www.icsi.org/knowledge/detail.asp?catID=29&itemID=547. Accessed on December 8, 2004.
2. Nelson HD, Helfand M, Woolf SH, Allan JD. Screening for postmenopausal osteoporosis: a review of the evidence for the U.S. Preventive Services task force. Ann Intern Med 2002;137:529-541.
3. Mazees R, Chestnut CH 3rd, McClung M, Genant H. Enhanced precision with dual-energy X-rat absorptiometry. Calcif Tissue Int 1992;51:14-17.
4. Lenchik L, Kiebzak GM, Blunt BA. International Society for Clinical Densitometry Position Development Panel and Scientific Advisory Committee. What is the role of serial bone mineral density measurements in patient management? J Clin Densitom 2002;5 Suppl:S29-S38.
5. Cummings SR, Bates D, Black DM. Clinical use of bone densitometry scientific review. JAMA 2002;288:1889-1897.Erratum in: JAMA 2002; 288:2825.
6. National steoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation, 2003. Available at: www.nof.org. Accessed on December 8, 2004.
7. Cranney A, Wells G, Willan A, et al. Meta-analysis of therapies for postmenopausal osteoporosis. II. Meta-analysis of alendronate for the treatment of postmenopausal women. Endocr Rev 2002;23:508-516.
8. Cranney A, Tugwell P, Adachi J, et al. Meta-analysis of therapies for postmenopausal osteoporosis. III. Meta-analysis of risedronate for the treatment of postmenopausal osteoporosis. Endocr Rev 2002;23:517-523.
9. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004;350:1189-1199.
10. Bonnick SL. Monitoring osteoporosis therapy with bone densitometry: a vital tool or regression toward mediocrity. J Clin Endocrinol Metabl 2000;85:3493-3495.
11. Cummings SR, Palermo L, Browner W, et al. Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. Fracture Intervention Trial Research Group. JAMA 2000;283:1318-1321.
12. Hochberg MC, Ross PD, Black D, et al. Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis. Fracture Intervention Trial Research Group. Arthritis Rheum 1999;42:1246-1254.
13. Hodgson SF, Watts NB, Bilezikian JP, et al. American Association of Clinical Endocrinologists 2001 Medical Guidelines for Clinical Practice for the Prevention and Management of Postmenopausal Osteoporosis. Endocr Pract 2000;7:293-312.
14. Nelson HD, Morris CD, Kraemer DF, et al. Osteoporosis in Postmenopausal Women: Diagnosis and Monitoring. Evidence Report/Technology Assessment No. 28 (Prepared by the Oregon Health & Science University Evidence-based Practice Center under Contract No. 290-97-0018). AHRQ Publication No. 01-E032. Rockville, Md: Agency for Healthcare Research and Quality. January 2001. Available at: www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View.Show Section&rid=hstat1.chapter.39885. Accessed on December 8, 2004.
15. Khan AA, Brown J, Faulkner K, et al. Standards and guidelines for performing central dual X-ray densitometry from the Canadian Panel of International Society for Clinical Densitometry. J Clin Densitom 2002;5:435-445.
16. Osteoporosis Prevention Diagnosis and Therapy. NIH Consensus Statement 2000; 17:1-36. Available at: consen-sus.nih.gov/cons/111/111_statement.htm. Accessed on December 8, 2004.
17. North American Menopause Society. Management of postmenopausal osteoporosis: position statement of the North American Menopause Society. Menopause 2002;9:84-101.
18. Sturtridge W, Lentle B, Hanley DA. Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 2. The use of bone density measurement in the diagnosis and management of osteoporosis. CMAJ 1996;155:924-929.
19. University of Michigan Health System. Osteoporosis: Prevention and Treatment. Ann Arbor: University of Michigan Health System; 2002:1-12. Available at: cme.med.umich.edu/pdf/guideline/osteoporosis.pdf. Accessed on December 8, 2004.
Evidence-based answers from the Family Physicians Inquiries Network
What are effective strategies for reducing the risk of steroid-induced osteoporosis?
Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs]). Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months). (Grade of recommendation: A, based on RCTs) Replacement of sex hormones in hypogonadal patients prevents bone loss and increases bone mineral density (BMD). (Grade of recommendation: A for women, based on RCTs; B for men, based on one randomized, crossover trial.) Calcitonin prevents bone loss for up to 1 year. (Grade of recommendation: A, based on systematic review.)
Evidence summary
A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500–1000 mg daily) and vitamin D (400–800 IU) daily.1 A systematic review found that patients receiving steroids longer than 3 months gained bone mass when placed on a bisphosphonate.2 A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P= .026), respectively.3 A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS).4 A 1-year RCT of 184 men on or off steroids using risedronate found an 82.4% decreased incidence of vertebral fractures compared with those who received placebo (NNT = 5; P= .008).5
In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3–4%; men 5%; all P< .05). Fracture reduction and risk of long-term use were not studied.6-8 In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months.9
Recommendations from others
The American College of Rheumatology recommends calcium and vitamin D be offered to all patients initiating a regimen of prednisone 5 mg/d or its equivalent with expected duration of longer than 3 months. Bisphosphonates should be prescribed for all patients starting steroids and for patients receiving steroids with a T-score less than -1.0; however they should be used with caution in pre-menopausal women.8 A leading researcher states the rank order for prevention is a bisphosphonate followed by a vitamin D metabolite or hormone replacement.10
Clinical Commentary by Michael Fisher, MD, at http://www.fpin.org.
1. Homik J, Suarez-Almazor ME, Shea B, Cranny A, et al. Cochrane Database Syst Rev. Issue 2, 2002.
2. Blair MM, Carson DS, Barrington R. J Fam Pract 2000;49:839-48.
3. Adachi JD, Saag KG, Delmas PD, Liberman UA, et al. Arthritis Rheum 2001;44:202-11.
4. Saag KG, Emkey R, Schnitzer TJ, Brown JP, et al. N Engl J Med 1998;339:292-9.
5. Reid DM, Adami S, Devogelaer JP, Chines AA. Calcif Tissue Int 2001;69:242-7.
6. Kung AW, Chan TM, Lau CS, Wong RW, et al. Rheumatology 1999;38:1239-44.
7. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Arch Intern Med 1996;156:1173-7.
8. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
9. Cranney A, Welch V, Adachi JD, Homik J, et al. Cochrane Database Syst Rev. Issue 2, 2002.
10. Sambrook PN. Ann Acad Med Singapore 2002;31:48-53.
Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs]). Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months). (Grade of recommendation: A, based on RCTs) Replacement of sex hormones in hypogonadal patients prevents bone loss and increases bone mineral density (BMD). (Grade of recommendation: A for women, based on RCTs; B for men, based on one randomized, crossover trial.) Calcitonin prevents bone loss for up to 1 year. (Grade of recommendation: A, based on systematic review.)
Evidence summary
A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500–1000 mg daily) and vitamin D (400–800 IU) daily.1 A systematic review found that patients receiving steroids longer than 3 months gained bone mass when placed on a bisphosphonate.2 A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P= .026), respectively.3 A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS).4 A 1-year RCT of 184 men on or off steroids using risedronate found an 82.4% decreased incidence of vertebral fractures compared with those who received placebo (NNT = 5; P= .008).5
In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3–4%; men 5%; all P< .05). Fracture reduction and risk of long-term use were not studied.6-8 In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months.9
Recommendations from others
The American College of Rheumatology recommends calcium and vitamin D be offered to all patients initiating a regimen of prednisone 5 mg/d or its equivalent with expected duration of longer than 3 months. Bisphosphonates should be prescribed for all patients starting steroids and for patients receiving steroids with a T-score less than -1.0; however they should be used with caution in pre-menopausal women.8 A leading researcher states the rank order for prevention is a bisphosphonate followed by a vitamin D metabolite or hormone replacement.10
Clinical Commentary by Michael Fisher, MD, at http://www.fpin.org.
Calcium, in combination with vitamin D, prevents bone loss and is recommended in all patients. (Grade of recommendation: A, based on systematic reviews of randomized controlled trials [RCTs]). Alendronate and risedronate prevent fractures and should be considered for all patients at increased risk of fracture (5 mg of prednisone or equivalent, daily for longer than 3 months). (Grade of recommendation: A, based on RCTs) Replacement of sex hormones in hypogonadal patients prevents bone loss and increases bone mineral density (BMD). (Grade of recommendation: A for women, based on RCTs; B for men, based on one randomized, crossover trial.) Calcitonin prevents bone loss for up to 1 year. (Grade of recommendation: A, based on systematic review.)
Evidence summary
A systematic review of 5 RCTs (N=274) confirmed clinically and statistically significant prevention of bone loss at the lumbar spine for patients receiving glucocorticoids who also received calcium (500–1000 mg daily) and vitamin D (400–800 IU) daily.1 A systematic review found that patients receiving steroids longer than 3 months gained bone mass when placed on a bisphosphonate.2 A two-year RCT of 208 patients receiving steroids who also received alendronate or placebo demonstrated an incidence of vertebral fracture of 0.7% and 6.8% (NNT=16; RRR=90%; ARR = 5.9%; P= .026), respectively.3 A 48-week RCT involving 477 patients receiving steroids who also received alendronate or placebo demonstrated a 2.3% and 3.7% in incidence of vertebral fracture, respectively (RRR = 38%; ARR = 1.4%; P= NS).4 A 1-year RCT of 184 men on or off steroids using risedronate found an 82.4% decreased incidence of vertebral fractures compared with those who received placebo (NNT = 5; P= .008).5
In hypogonadal patients, several small studies have shown that replacement of sex hormones (estrogen in women and testosterone in men) increases lumbar spine BMD (women 2% and 3–4%; men 5%; all P< .05). Fracture reduction and risk of long-term use were not studied.6-8 In a systematic review of 9 RCTs, including 441 patients, calcitonin preserved bone mass in the lumbar spine but not the femoral neck during the first year of steroid therapy. Lumbar spine BMD values with calcitonin were significantly higher than with placebo at 6 and 12 months, but were similar at 24 months.9
Recommendations from others
The American College of Rheumatology recommends calcium and vitamin D be offered to all patients initiating a regimen of prednisone 5 mg/d or its equivalent with expected duration of longer than 3 months. Bisphosphonates should be prescribed for all patients starting steroids and for patients receiving steroids with a T-score less than -1.0; however they should be used with caution in pre-menopausal women.8 A leading researcher states the rank order for prevention is a bisphosphonate followed by a vitamin D metabolite or hormone replacement.10
Clinical Commentary by Michael Fisher, MD, at http://www.fpin.org.
1. Homik J, Suarez-Almazor ME, Shea B, Cranny A, et al. Cochrane Database Syst Rev. Issue 2, 2002.
2. Blair MM, Carson DS, Barrington R. J Fam Pract 2000;49:839-48.
3. Adachi JD, Saag KG, Delmas PD, Liberman UA, et al. Arthritis Rheum 2001;44:202-11.
4. Saag KG, Emkey R, Schnitzer TJ, Brown JP, et al. N Engl J Med 1998;339:292-9.
5. Reid DM, Adami S, Devogelaer JP, Chines AA. Calcif Tissue Int 2001;69:242-7.
6. Kung AW, Chan TM, Lau CS, Wong RW, et al. Rheumatology 1999;38:1239-44.
7. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Arch Intern Med 1996;156:1173-7.
8. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
9. Cranney A, Welch V, Adachi JD, Homik J, et al. Cochrane Database Syst Rev. Issue 2, 2002.
10. Sambrook PN. Ann Acad Med Singapore 2002;31:48-53.
1. Homik J, Suarez-Almazor ME, Shea B, Cranny A, et al. Cochrane Database Syst Rev. Issue 2, 2002.
2. Blair MM, Carson DS, Barrington R. J Fam Pract 2000;49:839-48.
3. Adachi JD, Saag KG, Delmas PD, Liberman UA, et al. Arthritis Rheum 2001;44:202-11.
4. Saag KG, Emkey R, Schnitzer TJ, Brown JP, et al. N Engl J Med 1998;339:292-9.
5. Reid DM, Adami S, Devogelaer JP, Chines AA. Calcif Tissue Int 2001;69:242-7.
6. Kung AW, Chan TM, Lau CS, Wong RW, et al. Rheumatology 1999;38:1239-44.
7. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Arch Intern Med 1996;156:1173-7.
8. American College of Rheumatology Ad Hoc Committee on Glucocorticoid-Induced Osteoporosis. Arthritis Rheum 2001;44:1496-503.
9. Cranney A, Welch V, Adachi JD, Homik J, et al. Cochrane Database Syst Rev. Issue 2, 2002.
10. Sambrook PN. Ann Acad Med Singapore 2002;31:48-53.
Evidence-based answers from the Family Physicians Inquiries Network