***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: IMPORTANCE Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered , but methods to monitor fracture risk after discontinuation have not been established . OBJECTIVE To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years . DESIGN , SETTING , AND PARTICIPANTS The prospect i ve Fracture Intervention Trial Long-term Extension ( FLEX ) study r and omized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003 ; the present analysis includes only the placebo group .  Hip and spine dual-energy x-ray absorptiometry ( DXA ) were measured when placebo was begun ( FLEX baseline ) and after 1 to 3 years of follow-up . Two biochemical markers of bone turnover , urinary type 1 collagen cross-linked N-telopeptide ( NTX ) and serum bone-specific alkaline phosphatase ( BAP ) , were measured at FLEX baseline and after 1 and 3 years . MAIN OUTCOMES AND MEASURES Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover . RESULTS During 5 years of placebo , 94 of 437 women ( 22 % ) experienced 1 or more symptomatic fractures ; 82 had fractures after 1 year . One-year changes in hip DXA , NTX , and BAP were not related to subsequent fracture risk , but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk ( lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio , 2.17 [ 95 % CI , 1.38 - 3.41 ] ; total hip DXA relative hazard ratio , 1.87 [ 95 % CI , 1.20 - 2.92 ] ) . CONCLUSIONS AND RELEVANCE Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years , age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years . Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and can not be recommended . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00398931 ABBREVIATIONS AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval  DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial ( FIT ) Long-term Extension FRAX ® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R = recommendation RANK = receptor activator of nuclear factor kappa-B RANKL = receptor activator of nuclear factor kappa-B lig and RCT = r and omized controlled trial RR = relative risk S-CTX = serum C-terminal telopeptide SQ = subcutaneous VFA = vertebral fracture assessment WHO = World Health Organization Osteoporosis-related fractures are common and impose a large societal burden in terms of human and economic costs ( 1 ) . In the absence of a typical low-trauma fracture ( for example , vertebral compression fracture ) ( 2 ) , the diagnosis of osteoporosis is usually based on finding low bone mineral density ( BMD ) from dual-energy x-ray absorptiometry ( DXA ) ( 3 , 4 ) . Screening with DXA is recommended for women aged 65 years or older and in younger women with elevated fracture risk ( 5 ) . In appropriately selected women , approved treatments can reduce fracture risk in primary and secondary prevention setting s ( 6 , 7 ) . The role for repeated BMD testing  after initial evaluation is uncertain because prospect i ve studies have not shown that repeated BMD measurements or changes in BMD were more predictive of subsequent fractures than the baseline measurement ( 5 , 8) . The practice of repeated  BMD testing during pharmacotherapy also remains controversial ( 9 , 10 ) . Group-level clinical trial data suggest that greater increases in BMD are associated with greater fracture risk reduction ( 11 , 12 ) , but this may be more difficult to show in individuals as measurement error is typically 3 % to 5 % ( 1315 ) . In clinical trials in which good patients are selected for participation and their adherence is closely monitored , treatment failuredefined as detectable BMD lossis uncommon , particularly when the patients are receiving bisphosphonates , which is the most widely used class of drugs for osteoporosis ( 16 ) . Results from clinical trials are not always applicable to clinical practice in which patients are lost to follow-up , adherence and persistence with medications are difficult to monitor , and patients often have underlying conditions that would exclude many from trial participation . We used population -based registries from Manitoba , Canada , to assess the effectiveness of repeated  BMD testing in routine clinical practice as a predictor of treatment-related fracture risk reduction in women initiating treatment . Methods Patient Population In Manitoba , Canada ( population , 1.2 million persons ) , health services are provided to virtually all residents through a public health care system . Since 1997 , DXA testing has been managed as an integrated program ( the Manitoba Bone Density Program ) ; criteria for baseline testing include screening women at age 65 years and younger women with additional risk factors ( 17 ) . Consistent with national guidelines , the program 's recommended interval for initial follow-up is 3 years for most patients , 1 year for those receiving systemic glucocorticoid therapy or aromatase inhibitors , and at least 5 years for those previously reported as low-risk ( 18 ) . The program maintains a data base of all DXA results that can be linked with other population -based computerized health data bases through an anonymous personal identifier . The DXA data base has completeness and accuracy in excess of 99 % ( 19 ) . From this data base , we identified all women aged 40 years or older with baseline DXA measurements of the hip or lumbar spine obtained from 1 of the program 's cross-calibrated primary DXA instruments ( Prodigy ; GE Healthcare Lunar ) after 1 April 1998 . We then identified those with a follow-up DXA examination before 31 March 2013 ( minimum interval of 1 year ) for assessment of change in BMD in at least 1 measurement site ( total hip , femoral neck , or lumbar spine ) . Using linkage to the province-wide retail pharmacy network ( 20 ) , we identified women not receiving osteoporosis treatment during the year before baseline DXA testing ( defined as no pharmacy-dispensed bisphosphonate , calcitonin , systemic estrogen product , raloxifene , or teriparatide ) who initiated 1 of these same osteoporosis treatments between the first and second DXA scans ( defined as 1 or more prescription dispensations ) . Analyses did not consider subsequent medication switching . The study was approved by the Health Research Ethics Board of the University of Manitoba . BMD Measurements Lumbar spine and hip DXA scans were performed and analyzed in accordance with manufacturer recommendations . Femoral neck and total hip T-scores ( number of SDs above or below the mean BMD for young adults ) were calculated from NHANES III ( Third National Health and Nutrition Examination Survey ) reference values for white women ( 21 ) ; lumbar spine ( L1 to L4 ) T-scores were based on the manufacturer 's reference values for white women ( 22 ) . The program 's quality assurance is under strict supervision by a medical physicist ( 17 ) . The instruments used for this study exhibited stable long-term performance ( coefficient of variation , < 0.5 % ) . All reporting physicians and supervising technologists are required to maintain DXA certification with the International Society for Clinical Densitometry . The absolute BMD difference ( measured in g/cm2 ) between the 2 DXA tests was compared with 95 % least-significant change ( LSC ) values for assessment of change using accepted methods , where LSC is the least amount of change in BMD that can be considered statistically significant ( 2325 ) . The BMD measurement error of the Manitoba Bone Density Program used for computing the LSC is derived from more than 400 DXA scan pairs ( most performed on different days but within 28 days by different technologists ) . We have previously reported that this approach ( rather than same-day repositioning with the same technologist ) is more representative of measurement error encountered during clinical monitoring ( 26 ) . From these scan pairs , we obtained the following 95 % LSC values , which are within acceptable ranges ( 25 ) : total hip , 0.030 g/cm2 ; lumbar spine , 0.050 g/cm2 ; and femoral neck , 0.055 g/cm2 . An observed absolute difference less than these values would be considered to be within the range of measurement error ( stable ) , whereas an increase or decrease exceeding these values would be outside the range of measurement error ( detectable increase or decrease in BMD , respectively ) . The use of the absolute difference for BMD monitoring follows International Society for Clinical Densitometry recommendations and avoids errors that can arise when change is expressed as a percentage ( 27 , 28 ) . Baseline Fracture Probability Calculations The 10-year probability of the risk for major osteoporotic fracture was calculated by using the Canadian version of the World Health Organization Fracture Risk Assessment Tool ( FRAX ) , version 3.7 ( FRAX Desktop Multi-Patient Entry ) ( 29 , 30 ) . Age , body mass index , femoral neck BMD , and other data required for calculating fracture probability with FRAX were assessed through a combination of hospital discharge abstract s ( diagnoses and procedures coded using the International Classification of Diseases , Ninth Revision , Clinical Modification , before 2004 and International Statistical Classification of Diseases and Related Health Problems , 10th Revision , Canada thereafter ) , physician billing cl aims ( coded using International Classification of Diseases , Ninth Revision , Clinical Modification ) , and information collected directly from patients at the time of DXA scanning as previously described ( Appendix Table ) ( 31 ) . The Canadian FRAX was calibrated by using nationwide hip fracture data ( 30 ) . Predictions agreed closely with observed fracture risk in our population ( 31 , 32 ) . Appendix Table . Study Population Baseline Characteristics , by Variables Used in Fracture Probability Assessment and Incident Fracture Outcomes * Fractures Outcomes Records from Manitoba Health were assessed for the presence of incident nontraumatic hip , clinical vertebral , forearm , and humerus fracture diagnostic codes ( collectively design ated as major osteoporotic fractures ) using previously vali date d algorithms ( 33 , 34 ) . Fractures that were not associated with trauma codes were assessed through a combination of hospital discharge abstract s and physician billing cl aims . We required that hip and forearm fracture codes be associated with site-specific fracture reduction , fixation , or casting codes to enhance specificity for an acute fracture event . To minimize potential misclassification of prior incident fractures , we conservatively required that there be no hospitalization or physician visit for the same fracture type in the 6 months preceding an incident fracture diagnosis . Statistical Analysis Cumulative fracture incidence after the first DXA scan ( index date ) was studied using survival analysis . Observations were censored for death , migration out of province , or end of follow-up ( 31 March 2013 ) . Our primary analysis examined change in total hip BMD between DXA scans , which was the site with the smallest measurement error ; these scans were categorized as stable ( referent ) , detectable decrease , or detectable increase . Cumulative incidence curves , along with point estimates and 95 % CIs at 5 and 10 years , were directly adjusted for baseline fracture probability ( 35 ) . Average absolute differences in cumulative fracture risk were compared based on change in BMD ( detectable decrease or increase vs. stable BMD ) , and 95 % CIs were estimated . Analyses were conducted using SAS , version 9.3 ( SAS Institute ) . We did a series of secondary sensitivity analyses to test the robustness of our findings and explore potential interactions . First , we examined hip fractures as the outcome of interest given their large implication s on morbidity , mortality , and cost compared with other fractures . Second , we constructed separate models for change in femoral neck and lumbar spine BMD . Finally , we explored potential interactions in multiplicative Cox proportional hazards models stratified according to age ( 40 to 64 , 65 to 74 , and 75 years ) ; baseline BMD ( osteoporotic vs. nonost 
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You 'd think taking the Fosamax would be easy because you only take it once a week .
I would usually take it on Sundays but then I could n't lie down or eat or anything for 45 minutes , so I 'm thinking , Oh gee , I could go back to bed , but I did n't .
So , it was easy enough to take , and it did n't bother me .
I did n't have any reactions or side effects .
I stopped taking it in 2014 , but I continued with the vitamin D and the calcium .
What I understood about this most recent bone density in 2017 was that it was a little more serious than I thought .
I do n't knowprobably because I 'm getting older and I 'm starting to think about these things .
I 'd have to hear my options before I could make any decisions about how to treat itI mean , if I had to take medication again I certainly would .
I do n't know what other options there are , probably exercise more .
Moderate- quality evidence showed that women treated with antiresportive agents and the anabolic agent teriparatide had reduced fractures , even if BMD did not increase or if it decreased .
This suggests that large changes in BMD are often due to r and om error rather than true change .
Thus , it is unclear that monitoring BMD while taking an osteoporosis medication improves outcomes .
Consequently , yearly monitoring of BMD may not improve adherence .