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

Easterling, Lisa

Koval, Peter G.

Mackler, Leslie

Pettus, Dawn

University of Missouri: MOspace

F R O M T H E F A M I L Y P R A C T I C E I N Q U I R I E S N E T W O R KClinical  InquiriesJANUARY 2005 / VOL 54, NO 1 · The Journal of Family Practice 65C O N T I N U E DHow should a DEXA scan be used to evaluatebisphosphonate therapy for osteoporosis?  ■ EVIDENCE-BASED ANSWERIf bone density is evaluated after initiating bispho-sphonate drug therapy, it should be tested no ear-lier than 2 years (strength of recommendation[SOR]: B, based on case series of dual energy x-ray absorptiometry [DEXA] scanning precisionand bisphosphonate efficacy). Currently noprospective, randomized trials investigate theimpact of bone density follow-up testing on osteo-porotic patients receiving bisphosphonate therapy. ■ EVIDENCE SUMMARYTesting the effectiveness of therapy for osteoporo-sis by measuring changes in bone mineral density(BMD) is difficult because changes are often smalland occur slowly, and a decrease in BMD does notnecessarily mean treatment failure. Testingpatients after starting bisphosphonate therapyhas been part of many drug trials to assess theeffectiveness of therapy. Follow-up testing in clin-ical practice has not been the focus of a prospec-tive trial and therefore remains controversial.1DEXA is considered the gold standard becauseit is the most extensively validated test for pre-dicting fracture outcomes.2 Understanding therate of bone density response to therapy, and theprecision error of DEXA, helps to determine mon-itoring intervals. The larger the responses inBMD to therapy and the more precise the DEXAscan result, the shorter the period between test-ing in which clinically relevant differences can befound. Precision error rates are estimated at <1%for the anterior-posterior spine and 1% to 2% forthe hip.3 The BMD change after the initiation oftreatment must escape the precision error of thetesting device or exceed the least significantchange (LSC) value.4 The LSC—roughly analo-gous to a 95% confidence interval—is 2.8 timesthe precision error of the test on a specificmachine and site of measurement. If the precisionerror 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 hipcould be due to inherent measurement error.6A clinician must also understand the antici-pated response to the prescribed therapy. It is notWhat are Clinical Inquiries?Clinical Inquiries answer recent questions from the practices offamily physicians. Practicing family physicians choose the mostrelevant questions submitted through a web-based voting systemoperated by the Family Physicians Inquiries Network (FPIN; onlineat www.fpin.org).FPIN is national, not-for-profit consortium of family medicinedepartments, community residency programs, academic healthsciences libraries, primary care practice-based research networks, and other specialists. Once questions are selected,FPIN editors then organize teams of clinicians and librarians toanswer them based on systematic review of the world literature.Answers are developed through an explicit, systematic method:• FPIN librarians and editors identify questions recentlyanswered in best evidence sources (e.g. Cochrane Reviews,Clinical Evidence, the US Preventive Services Task Force,Evidence Based Guidelines, a published systematic review).• FPIN librarians then conduct systematic and standardized literature searches of best evidence sources, Medline, and otherdatabases in collaboration with an FPIN clinician or clinicians. If abest evidence source has been identified, the search begins fromthe date of the search conducted for that source. Otherwise, thesearches are comprehensive.• FPIN clinician authors then choose the highest quality originalresearch sources, and critically appraise the research and integrate the findings in the Evidence Based Answer andEvidence Summary section of Clinical Inquiries. Authoritativesources are also quoted in the “Recommendations from Others”section of the Clinical Inquiry.• Each Clinical Inquiry is reviewed by 4 or more peers or edi-tors before publication in JFP.• FPIN medical librarians are accountable for the thorough-ness of the literature search, for recording the databasessearched, search hedges used and the search terms. Thedetails of each search is available to any interested reader (contact managingeditor@fpin.org).• Finally, a practicing family physician or other clinician writesan accompanying commentary to provide a clinical perspective.C L I N I C A L  I N Q U I R I E SJANUARY 2005 / VOL 54, NO 1 · The Journal of Family Practice 69C O N T I N U E Din the first year normalized in the second year.10 Asecond analysis showed that when women weredivided into 8 groups, the group with the greatestincrease in BMD in the first year (10.4%) also hadthe greatest decrease (1.0%) in year 2. In addi-tion, the group with the greatest decrease in year1 (6.6%) had the greatest increase in year 2(4.8%). The variability in response among the 8groups was approximately 17% (+10.4% and–6.6%) in year 1 and narrowed to a 6% differencein year 2 This regression to the mean leads to anormalization of bone density results.11,12 Thispatient variability in BMD response to the pre-scribed therapy should be considered when decid-ing to retest. In summary, limitations in DEXA precisionmean any changes in BMD of less than 5.6% atthe femoral neck may be due to measurementerror, and BMD response to bisphosphonatesvacillates in the first few years of use but can beclinically useful to retest BMD before a therapywould have time to affect bone turnover.Alendronate and risedronate increase lumbarspine BMD by 5% to 7% and hip BMD by 3% to6% when used for approximately 3 years.7,8 Theseincreases in BMD are associated with 30% to50% reductions in vertebral and hip fractures.6Alendronate continues to increase BMD: follow-ing 10 years of treatment, it increased BMD by13.7% in the lumbar spine, 6.7% in the total hip,and 5.4 % in the femoral neck.9Frequent testing, as seen in bisphosphonateclinical trials, demonstrates the phenomenon ofregression to the mean. One analysis of the FITtrial, which compared alendronate with placeboin postmenopausal women with low BMD and atleast 1 vertebral fracture, focused on the earlyevaluation of BMD. The study found a highdegree of variability in BMD when tested after 1year of treatment. This wide variety of responseBone mineral density in osteoporosisF I G U R EDEXA scanning is useful if its limitations are understoodImprecision is a reality with the DEXA scan.Clinical experience has shown that, forpatients receiving biphosphonate therapy toincrease bone mineral density (BMD) in thefemoral neck, any change in BMD of lessthan 5.6% may be due to measurementerror and should not necessarily prompt achange in treatment. BMD response to bisphosphonates vacillates in the first fewyears of use but can be expected toincrease femoral neck BMD by 3% to 6%over 3 years. If serial DEXA scanning ismade part of the management plan, itshould be considered no sooner than 2 to 3years following the start of therapy.ILLUSTRATION BYJENNIFER FAIRMANC L I N I C A L  I N Q U I R I E S70 JANUARY 2005 / VOL 54, NO 1 · The Journal of Family Practice■ RECOMMENDATIONS FROMOTHERSGuidelines on monitoring the clinical response toosteoporosis therapy with DEXA are availablefrom numerous groups (Table). In clinical prac-tice, it is common for a BMD difference of 3% to5% at the spine or 4% to 6 % at the hip to be con-sidered clinically significant.13Peter G. Koval, PharmD, BCPS, Lisa Easterling,PharmD, Moses Cone Family Practice Residency, Greensboro,NC; Dawn Pettus, PharmD, CPP, Greensboro AHEC,Greensboro; Leslie Mackler, MSLS, Moses Cone HealthSystem Library, Greensboroexpected to increase femoral neck BMD 3% to6% over 3 years. Therefore, if serial DEXA scan-ning is preformed on patients prescribed bispho-sphonate therapy, it should be considered noearlier than 2 to 3 years after therapy begins.When monitoring osteoporosis therapy, a BMDchange within the LSC should be interpreted as“no change” and should not lead to changes inpatient management. If the BMD has decreasedbeyond the LSC there is cause for concern andreevaluation of diagnosis and treatment arewarranted.4TA B L ERecommendations on monitoring the clinical response to DEXA in osteoporosis therapyMethod used to formulate responses Recommendations for monitoring treatment Organization recommendation to anti-resorptive therapyAHRQ Evidence Report Systematic review Advises against repeating bone density tests (Osteoporosis in within the first year of treatment. Insufficient Postmenopausal evidence to determine whether repeating tests Women)14 2 years after starting therapy is usefulAmerican Association  Rating scheme Yearly for 2 years and if bone mass has of Clinical (Statement not rated) stabilized, follow-up measurements areEndocrinologists13 recommended every 2 yearsCanadian Panel of Not stated Repeat scan should be considered after 1 to 3 Int’l Society for years if concerned about progressive bone loss Clinical Densitometry15 or with new interventionInstitute for Clinical Not stated Controversy exists as to whether follow-up testing Systems Improvement1 is necessary in all patients, but if performed, it should be done after 1 to 2 years of therapyNational Institute Expert consensus Monitoring has not been shown to improve of Health16 compliance. Physicians should not stop orchange therapies because of modest bone density lossNational Osteoporosis Expert consensus Recommended 1 to 2 years following initiation Foundation6 of therapyNorth American Expert consensus Monitoring before 2 years of treatment would Menopause Society17 not be usefulOsteoporosis Society Not stated Suggests at least 1 follow-up measurement is of Canada18 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 yearsUniversity of Michigan19 Evidence rating scheme For most persons an interval of >2 years betweenDEXAs provides the most meaningful informationC L I N I C A L  I N Q U I R I E SJANUARY 2005 / VOL 54, NO 1 · The Journal of Family Practice 71C O N T I N U E D■ CLINICAL COMMENTARYIf follow-up is needed, rescan in 2 to 3 yearsRates of vertebral and hip fractures are signifi-cantly reduced by alendronate and risedronate,making them important in the prevention andtreatment of osteoporosis. Despite controver-sies over the timing and necessity of monitoringbisphosphonate therapy with DEXA scans, theymay be useful clinically if their limitations arerecognized. It is necessary to wait 2 to 3 yearsto repeat the DEXA after initiating therapy toaccount for the slow rate of change of bone den-sity and compensate for the regression-to-the-mean phenomenon seen in clinical trials.If after 2 or 3 years the bone density remainsstable or has increased, reassurance can begiven that fracture risk has decreased. If bonedensity has decreased more than the LSC, con-sider the following questions. Is the medicine isbeing taken first thing in the morning on anempty stomach? Is weight-bearing exerciseperformed routinely, tobacco avoided, and caf-feine limited? Is the patient continuing ade-quate calcium and vitamin D supplements? Thephysician should also consider secondary caus-es of osteoporosis, such as hyperthyroidismand hyperparathyroidism. Ann B. Gotschall, MD, Baylor College of Medicine,Houston, TexREFERENCES1. Institute for Clinical Systems Improvement (ICSI). Diagnosisand 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 forpostmenopausal osteoporosis: a review of the evidence forthe 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 forClinical Densitometry Position Development Panel andScientific Advisory Committee. What is the role of serial bonemineral density measurements in patient management? J ClinDensitom 2002; 5 Suppl:S29–S38.5. Cummings SR, Bates D, Black DM. Clinical use of bone den-sitometry scientific review. JAMA 2002; 288:1889–1897.Erratum in: JAMA 2002; 288:2825.6. National Osteoporosis Foundation. Physician’s Guide toPrevention 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 thera-pies for postmenopausal osteoporosis. II. Meta-analysis ofalendronate for the treatment of postmenopausal women.Endocr Rev 2002; 23:508–516.8. Cranney A, Tugwell P, Adachi J, et al. Meta-analysis of ther-apies for postmenopausal osteoporosis. III. Meta-analysis ofrisedronate for the treatment of postmenopausal osteoporo-sis. Endocr Rev 2002; 23:517–523.9. Bone HG, Hosking D, Devogelaer JP, et al. Ten years’ experi-ence with alendronate for osteoporosis in postmenopausalwomen. N Engl J Med 2004; 350:1189–1199.10. Bonnick SL. Monitoring osteoporosis therapy with bone den-sitometry: a vital tool or regression toward mediocrity. J ClinEndocrinol Metabl 2000; 85:3493–3495.11. Cummings SR, Palermo L, Browner W, et al. Monitoringosteoporosis therapy with bone densitometry: misleadingchanges and regression to the mean. Fracture InterventionTrial Research Group. JAMA 2000; 283:1318–1321.12. Hochberg MC, Ross PD, Black D, et al. Larger increases inbone mineral density during alendronate therapy are associ-ated with a lower risk of new vertebral fractures in womenwith postmenopausal osteoporosis. Fracture InterventionTrial Research Group. Arthritis Rheum 1999; 42:1246–1254.13. Hodgson SF, Watts NB, Bilezikian JP, et al. AmericanAssociation of Clinical Endocrinologists 2001 MedicalGuidelines for Clinical Practice for the Prevention andManagement of Postmenopausal Osteoporosis. Endocr Pract2000; 7:293–312.14. Nelson HD, Morris CD, Kraemer DF, et al. Osteoporosis inPostmenopausal Women: Diagnosis and Monitoring. EvidenceReport/Technology Assessment No. 28 (Prepared by theOregon Health & Science University Evidence-basedPractice Center under Contract No. 290-97-0018). AHRQPublication No. 01-E032. Rockville, Md: Agency forHealthcare Research and Quality. January 2001. Availableat: www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=hstat1.chapter.39885. Accessed on December8, 2004.15. Khan AA, Brown J, Faulkner K, et al. Standards and guide-lines for performing central dual X-ray densitometry from theCanadian Panel of International Society for ClinicalDensitometry. J Clin Densitom 2002; 5:435–445. 16. Osteoporosis Prevention, Diagnosis, and Therapy. NIHConsensus Statement 2000; 17:1–36. Available at: consen-sus.nih.gov/cons/111/111_statement.htm. Accessed onDecember 8, 2004.17. North American Menopause Society. Management of post-menopausal osteoporosis: position statement of the NorthAmerican Menopause Society. Menopause 2002; 9:84–101.18. Sturtridge W, Lentle B, Hanley DA. Prevention and manage-ment of osteoporosis: consensus statements from theScientific Advisory Board of the Osteoporosis Society ofCanada. 2. The use of bone density measurement in the diag-nosis and management of osteoporosis. CMAJ 1996;155:924–929.19. University of Michigan Health System. Osteoporosis:Prevention and Treatment. Ann Arbor: University of MichiganHealth System; 2002:1–12. Available at:cme.med.umich.edu/pdf/guideline/osteoporosis.pdf.Accessed on December 8, 2004.

How should a DEXA scan be used to evaluate bisphosphonate therapy for osteoporosis?

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