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An abundance of medical data and enhanced computational power have led to a surge in artificial intelligence (AI) applications. Published studies involving AI in bone and osteoporosis research have increased exponentially, raising the need for transparent model development and reporting strategies. This review offers a comprehensive overview and systematic quality assessment of AI articles in osteoporosis while highlighting recent advancements. A systematic search in the PubMed database, from December 17, 2020 to February 1, 2023 was conducted to identify AI articles that relate to osteoporosis. The quality assessment of the studies relied on the systematic evaluation of 12 quality items derived from the minimum information about clinical artificial intelligence modeling checklist. The systematic search yielded 97 articles that fell into 5 areas; bone properties assessment (11 articles), osteoporosis classification (26 articles), fracture detection/classification (25 articles), risk prediction (24 articles), and bone segmentation (11 articles). The average quality score for each study area was 8.9 (range: 7-11) for bone properties assessment, 7.8 (range: 5-11) for osteoporosis classification, 8.4 (range: 7-11) for fracture detection, 7.6 (range: 4-11) for risk prediction, and 9.0 (range: 6-11) for bone segmentation. A sixth area, AI-driven clinical decision support, identified the studies from the 5 preceding areas that aimed to improve clinician efficiency, diagnostic accuracy, and patient outcomes through AI-driven models and opportunistic screening by automating or assisting with specific clinical tasks in complex scenarios. The current work highlights disparities in study quality and a lack of standardized reporting practices. Despite these limitations, a wide range of models and examination strategies have shown promising outcomes to aid in the earlier diagnosis and improve clinical decision-making. Through careful consideration of sources of bias in model performance assessment, the field can build confidence in AI-based approaches, ultimately leading to improved clinical workflows and patient outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

We found that a standardized order set after hip fracture increased initiation of anti-osteoporosis medication and increased persistence at 1 year, but did not reduce secondary fractures., Background: A treatment gap exists after osteoporosis-related fractures. Introducing standardized care can improve treatment. We evaluated the impact of a hip fracture order set (OS) on anti-osteoporosis medication (AOM) initiation, persistence, and secondary fracture prevention., Methods: In 2015, one hospital in Manitoba, Canada, introduced a hip fracture OS including recommendations for the initiation of AOM (OS group). A control group was identified from the other hospitals in the same region. A retrospective cohort study was conducted using linked administrative health data. All individuals 50 + years with surgical treatment for low-energy hip fracture between 2010 and 2019 were included and followed for AOM initiation, medication persistence at 1 year, and secondary fractures. Between-group differences for each year were assessed using chi-square tests. Logistic regression models tested the impact of socio-demographic and clinical factors on initiation, persistence of AOM. Cox regression tested the risk of secondary fracture., Results: No baseline differences between OS group (813 patients) and control group (2150 patients) were observed in demographics, socioeconomic factors, or comorbidities. An increase in post-fracture AOM initiation was seen with OS introduction (OS group year before 16.7% versus year after 48.6%, p < 0.001). No change was seen in the control group. Persistence on AOM also increased (OS group year before 17.7% versus year after 28.4%, p < 0.001). No difference in secondary fractures was observed (OS group 19.8% versus control group 18.8%, p = 0.38)., Conclusion: Introduction of a hip fracture OS significantly increased AOM initiation and persistence at 1-year post-fracture. There was no significant difference in secondary fractures., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Introduction: Only change in bone mineral density (BMD) on repeat DXA that exceeds the 95% least significant change (LSC) should be considered clinically meaningful. Frequently lumbar spine DXA must be reported after omitting vertebrae with localized structural artifact, which reduces measurement precision. Previous reports have raised concerns of higher least significant change (LSC) when spine BMD is based on non-contiguous rather than contiguous vertebrae. The current study was performed to compare lumbar spine LSC and BMD response to intervening anti-osteoporosis medication use from non-contiguous versus contiguous vertebrae., Methodology: LSCs for lumbar spine DXA based on L1-L4 and all combinations of non-contiguous and contiguous vertebrae were calculated using 879 scan-pairs from the Manitoba BMD Program. We compared BMD change from these regions, overall and in relation to intervening anti-osteoporosis medication use, in 11,722 patients who had 2 DXA examinations., Results: LSCs were slightly greater when calculated from combinations of fewer than 4 vertebrae, but there was no meaningful difference between contiguous versus non-contiguous vertebrae. There were consistently high correlations between lumbar spine BMD change from L1-L4 and all combinations of continuous and non-contiguous vertebrae (all Pearson r≥ 0.9, p<0.001). Percentage changes in spine BMD and the fraction with treatment-concordant change exceeding the LSC were similar using contiguous or non-contiguous vertebrae., Conclusions: Lumbar spine BMD change can be assessed from 2 or 3 non-contiguous vertebrae when clinically necessary, and precision in such cases is similar to using contiguous vertebrae. Non-contiguous vertebrae can detect treatment-concordant changes similar in spine BMD to contiguous vertebrae., (Copyright © 2024 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Osteoporosis Canada 2023 clinical practice guidelines increase the number of individuals recommended or suggested for anti-osteoporosis pharmacotherapy by refining treatment guidance for those who fell within the 2010 guidelines' moderate-risk category., Purpose: In 2023, Osteoporosis Canada updated its 2010 clinical practice guidelines based upon consideration of fracture history, 10-year major osteoporotic fracture (MOF) risk, and BMD T-score in conjunction with age. The 2023 guidelines eliminated risk categories, including the moderate-risk group that did not provide clear treatment guidance. The current study was performed to appreciate the implications of the shift from 2010 risk categories to 2023 treatment guidance., Methods: The study population consisted of 79,654 individuals age ≥ 50 years undergoing baseline DXA testing from January 1996 to March 2018. Each individual was assigned to mutually exclusive categories based on 2010 and 2023 guideline recommendations. Treatment qualification, 10-year predicted and 10-year observed MOF risk were compared., Results: Treatment reclassification under the 2023 guidelines only affected 33.8% of individuals in the 2010 moderate-risk group, with 13.0% assigned to no treatment, 14.4% to suggest treatment, and 6.4% to recommend treatment. During the mean follow-up of 7.2 years, 6364 (8.0%) individuals experienced one or more incidents of MOF. The observed 10-year cumulative incidence of MOF in the study population was 10.5% versus the predicted 10.7% (observed to predicted mean calibration ratio 0.98, 95% CI 0.96-1.00). Individuals reclassified from 2010 moderate risk to 2023 recommend treatment were at greater MOF risk than those in the 2010 moderate-risk group assigned to 2023 suggest treatment or no treatment, but at lower risk than those in the 2010 high-risk group., Conclusions: Osteoporosis Canada 2023 clinical practice guidelines affect individuals within the 2010 moderate-risk category, increasing the number for whom anti-osteoporosis pharmacotherapy is recommended or suggested. Increased treatment could reduce the population burden of osteoporotic fractures, though moderate-risk individuals now qualifying for treatment have a lower predicted and observed fracture risk than high-risk individuals recommended for treatment under the 2010 guidelines., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: Human evidence on the association between oxidative stress and osteoporosis is inconsistent. Fluorescent Oxidation Products (FlOPs) are global biomarkers of oxidative stress. We examined the associations of FlOPs (excitation/emission wavelengths 320/420 nm for FlOP&#95;320, 360/420 nm for FlOP&#95;360, and 400/475 nm for FlOP&#95;400) with osteoporosis, bone microstructure, and bone turnover markers in humans and rats., Methods: In humans, we conducted a 1:2 age, sex, hospital, and specimen-matched case-control study to test the association between FlOPs and osteoporosis diagnosed from dual-energy X-ray absorptiometry. In eight-week-old male Wistar rats, we administrated D-galactose and 0.9 % saline for 90 days in treatment and control groups (n = 8/group); micro-CT was used to determine bone microstructure., Results: In humans, higher levels of FlOP&#95;320 (OR for per 1 SD increase = 1.49, 95 % CI: 1.01-2.20) and FlOP&#95;360 (OR for per 1 SD increase = 1.59, 95 % CI: 1.07-2.37) were associated with increased odds of osteoporosis. FlOP&#95;400 were not associated with osteoporosis. D-galactose treated rats, as compared with control rats, showed higher levels of FlOP&#95;320 and MDA, and lower P1NP levels during 90 days of experiment (all P < 0.05). The D-galactose group had lower trabecular bone volume fraction (0.07 ± 0.03 vs. 0.13 ± 0.05; P = 0.008) and volumetric BMD (225.4 ± 13.8 vs. 279.1 ± 33.2 mg HA/cm 3 ; P = 0.001) than the control group., Conclusion: In conclusion, higher FlOP&#95;320 levels were associated with increased odds of osteoporosis, impaired bone microstructure and decreased bone formation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Osteoporosis and cardiovascular disease (CVD) are highly prevalent in older women, with increasing evidence for shared risk factors and pathogenesis. Although FRAX was developed for the assessment of fracture risk, we hypothesized that it might also provide information on CVD risk. To test the ability of the FRAX tool and FRAX-defined risk factors to predict incident CVD in women undergoing osteoporosis screening with DXA, we performed a retrospective prognostic cohort study which included women aged 50 yr or older with a baseline DXA scan in the Manitoba Bone Mineral Density Registry between March 31, 1999 and March 31, 2018. FRAX scores for major osteoporotic fracture (MOF) were calculated on all participants. Incident MOF and major adverse CV events (MACE; hospitalized acute myocardial infarction [AMI], hospitalized non-hemorrhagic cerebrovascular disease [CVA], or all-cause death) were ascertained from linkage to population-based healthcare data. The study population comprised 59 696 women (mean age 65.7 ± 9.4 yr). Over mean 8.7 yr of observation, 6021 (10.1%) had MOF, 12 277 women (20.6%) had MACE, 2274 (3.8%) had AMI, 2061 (3.5%) had CVA, and 10 253 (17.2%) died. MACE rates per 1000 person-years by FRAX risk categories low (10-yr predicted MOF <10%), moderate (10%-19.9%) and high (≥20%) were 13.5, 34.0, and 64.6, respectively. Although weaker than the association with incident MOF, increasing FRAX quintile was associated with increasing risk for MACE (all P-trend <.001), even after excluding prior CVD and adjusting for age. HR for MACE per SD increase in FRAX was 1.99 (95%CI, 1.96-2.02). All FRAX-defined risk factors (except parental hip fracture and lower BMI) were independently associated with higher non-death CV events. Although FRAX is intended for fracture risk prediction, it has predictive value for cardiovascular risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporosis can currently be diagnosed by applying the WHO classification to bone mineral density (BMD) assessed by dual-energy x-ray absorptiometry (DXA). However, skeletal factors other than BMD contribute to bone strength and fracture risk. Lumbar spine TBS, a grey-level texture measure which is derived from DXA images has been extensively studied, enhances fracture prediction independent of BMD and can be used to adjust fracture probability from FRAX® to improve risk stratification. The purpose of this International Society for Clinical Densitometry task force was to review the existing evidence and develop recommendations to assist clinicians regarding when and how to perform, report and utilize TBS. Our review concluded that TBS is most likely to alter clinical management in patients aged ≥ 40 years who are close to the pharmacologic intervention threshold by FRAX. The TBS value from L1-L4 vertebral levels, without vertebral exclusions, should be used to calculate adjusted FRAX probabilities. L1-L4 vertebral levels can be used in the presence of degenerative changes and lumbar compression fractures. It is recommended not to report TBS if extreme structural or pathological artifacts are present. Monitoring and reporting TBS change is unlikely to be helpful with the current version of the TBS algorithm. The next version of TBS software will include an adjustment based upon directly measured tissue thickness. This is expected to improve performance and address some of the technical factors that affect the current algorithm which may require modifications to these Official Positions as experience is acquired with this new algorithm., (Copyright © 2023 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX., Introduction: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD)., Methods: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients., Results: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination., Conclusion: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

The Santa Fe Bone Symposium (SFBS) held its 23rd annual event on August 5-6, 2023, in Santa Fe, New Mexico, USA. Attendees participated in-person and remotely, representing many states and countries. The program included plenary presentations, panel discussions, satellite symposia, a Project ECHO workshop, and a session on healthcare policy and reimbursement for fracture liaison programs. A broad range of topics were addressed, including transitions of osteoporosis treatments over a lifetime; controversies in vitamin D; update on Official Positions of the International Society for Clinical Densitometry; spine surgery and bone health; clinical applications of bone turnover markers; basic bone biology for clinicians; premenopausal-, pregnancy-, and lactation-associated osteoporosis; cancer treatment induced bone loss in patients with breast cancer and prostate cancer; genetic testing for skeletal diseases; and an update on nutrition and bone health. There were also sessions on rare bone diseases, including managing patients with hypophosphatasia; treatment of X-linked hypophosphatemia; and assessment and treatment of patients with hypoparathyroidism. There were oral presentations of abstracts by endocrinology fellows selected from those who participated in the Santa Fe Fellows Workshop on Metabolic Bone Diseases, held the 2 days prior to the SFBS. These proceedings of the 2023 SFBS present the clinical highlights and insights generated from many formal and informal discussions in Santa Fe., Competing Interests: Disclosure E. Michael Lewiecki: Amgen investigator, consultant, and speaker, Radius investigator and consultant, Kyowa Kirin consultant and speaker. Teresita Bellido: nothing to disclose. John P. Bilezikian: Amgen consultant and speaker, Amolyt consultant and speaker, Radius consultant, Ascendis consultant and speaker, Abiogen consultant. Jacques P. Brown: Amgen consultant and speaker, Mereo researcher, Radius researcher, Ultragenyx data monitoring committee, Gilead consultant, Pfizer consultant. Azeez Farooki: Novartis consultant, Johnson and Johnson stock ownership. Christopher S. Kovacs: Novo Nordisk consultant and speaker, Ipsen consultant and speaker. Brendan Lee: Biomarin data safety monitoring board, Pacira, Sanofi, Acer royalties. William D. Leslie: nothing to disclose. Michael R. McClung: AbbVie consultant, Alexion consultant, Amgen consultant and speaker, Myovant consultant, Theramax speaker. Mark L. Prasarn: Stryker speaker. Deborah E. Sellmeyer: nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Trabecular bone score (TBS) enhances fracture risk assessment in older adults; whether this is true in younger people is uncertain. In this registry-based study of adults aged 20-39 years, low BMD, but not low TBS, predicted fracture., Purpose: Trabecular bone score (TBS), a bone texture measurement, is associated with fracture risk independent of bone mineral density (BMD) in older adults. In adults aged 20-40 years, TBS remains stable and its role in fracture risk assessment is unclear. We utilized the Manitoba Bone Density Registry to explore the relationship of fracture risk with BMD and TBS in younger adults., Methods: Women and men aged 20-39 years referred for DXA testing were studied. Incident major and any fractures were captured from health records. Categories based on WHO BMD T-score classification and TBS tertile were considered using Cox regression models to estimate covariate-adjusted (including sex) hazard ratios (aHR, 95%CI) for incident fracture by category, and each SD decrement in BMD and TBS., Results: The study included 2799 individuals (77% female, mean age 32 years). Mean (SD) minimum T-score was - 0.9 (1.1) and TBS 1.355 (0.114); 7% had osteoporosis and 13% were in the lowest TBS tertile. Incident major osteoporotic fracture (MOF) and any fracture risk was elevated in those with osteopenia (aHRs 1.20/1.45) and osteoporosis (aHRs 4.60/5.16). Fracture risk was unrelated to TBS tertile. Each SD decrement in BMD was associated with increased MOF risk (aHR 1.64) and any fracture (aHR 1.71); lower TBS was unrelated to fractures., Conclusion: In young adults, low BMD, but not low TBS, was predictive of MOF and any fracture. Routine clinical TBS measurement is not recommended for young adults. Further study is indicated to evaluate whether TBS is beneficial in subsets of younger adults., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Introduction: T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use., Methods: Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline., Results: The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34-4.27)., Conclusions: Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Lumbar spine trabecular bone score (TBS), a gray-level texture measure derived from spine dual-energy X-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved question is whether TBS is sufficiently responsive to change over time or in response to widely used osteoporosis therapy at the individual level to serve as a useful biomarker. Using the Manitoba DXA Registry, we identified 11,643 individuals age 40 years and older with two fan-beam DXA scans performed on the same instrument within 5 years (mean interval 3.2 years), of whom 6985 (60.0%) received antiresorptive osteoporosis medication (majority oral bisphosphonate) between the scans. We examined factors that were associated with a change in lumbar spine TBS, lumbar spine BMD, and total hip BMD exceeding the 95% least significant change (LSC). Change exceeding the LSC was identified in 23.0% (9.3% increase, 13.8% decrease) of lumbar spine TBS, 38.2% (22.1% increase, 16.1% decrease) lumbar spine BMD, and 42.5% (17.6% increase, 24.9% decrease) total hip BMD measurement pairs. From regression models, the variables most strongly associated with significant change in TBS (decreasing order) were tissue thickness change, acquisition mode change, weight change, and spine percent fat change. Consistent with the insensitivity of TBS to oral antiresorptive therapies, use of these agents showed very little effect on TBS change. In contrast, for both spine BMD change and total hip BMD change, osteoporosis medication use was the most significant variable, whereas tissue thickness change, acquisition mode change, and weight change had relatively weak effects. In summary, change in spine TBS using the present algorithm appears to be strongly affected by technical factors. This suggests a limited role, if any, for using TBS change in untreated individuals or for monitoring response to antiresorptive treatment in routine clinical practice with the current version of the TBS algorithm. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Individuals with cancer face unique risk factors for osteoporosis and fractures. Clinicians must consider the additive effects of cancer-specific factors, including treatment-induced bone loss, and premorbid fracture risk, utilizing FRAX score and bone mineral densitometry when available. Pharmacologic therapy should be offered as per cancer-specific guidelines, when available, or local general osteoporosis guidelines informed by clinical judgment and patient preferences. Our objective was to review and summarize the epidemiologic burden of osteoporotic fracture risk and fracture risk assessment in adults with cancer, and recommended treatment thresholds for cancer treatment-induced bone loss, with specific focus on breast, prostate, thyroid, gynecological, multiple myeloma, and hematopoietic stem cell transplant. This narrative review was informed by PubMed searches to July 25, 2022, that combined terms for cancer, stem cell transplantation, fracture, bone mineral density (BMD), trabecular bone score, FRAX, Garvan nomogram or fracture risk calculator, QFracture, prediction, and risk factors. The literature informs that cancer can impact bone health in numerous ways, leading to both systemic and localized decreases in BMD. Many cancer treatments can have detrimental effects on bone health. In particular, hormone deprivation therapies for hormone-responsive cancers such as breast cancer and prostate cancer, and hematopoietic stem cell transplant for hematologic malignancies, adversely affect bone turnover, resulting in osteoporosis and fractures. Surgical treatments such as hysterectomy with bilateral salpingo-oophorectomy for gynecological cancers can also lead to deleterious effects on bone health. Radiation therapy is well documented to cause localized bone loss and fractures. Few studies have validated the use of fracture risk prediction tools in the cancer population. Guidelines on cancer-specific treatment thresholds are limited, and major knowledge gaps still exist in fracture risk and fracture risk assessment in patients with cancer. Despite the limitations of current knowledge on fracture risk assessment and treatment thresholds in patients with cancer, clinicians must consider the additive effects of bone damaging factors to which these patients are exposed and their premorbid fracture risk profile. Pharmacologic treatment should be offered as per cancer-specific guidelines when available, or per local general osteoporosis guidelines, in accordance with clinical judgment and patient preferences., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

International variations in osteoporosis and fracture rates have been reported, with temporal trends differing between populations. We observed higher BMD and lower fracture prevalence in a recently recruited cohort compared to that of a cohort recruited 20 years ago, even after adjusting for multiple covariates., Purpose: We explored sex-specific differences in femoral neck bone mineral density (FN-BMD) and in prevalent major osteoporotic fractures (MOF) using two Canadian cohorts recruited 20 years apart., Methods: We included men and women aged 50-85 years from the Canadian Multicentre Osteoporosis Study (CaMos, N = 6,479; 1995-1997) and the Canadian Longitudinal Study on Aging (CLSA, N = 19,534; 2012-2015). We created regression models to compare FN-BMD and fracture risk between cohorts, adjusting for important covariates. Among participants with prevalent MOF, we compared anti-osteoporosis medication use., Results: Mean (SD) age in CaMos (65.4 years [8.6]) was higher than in CLSA (63.8 years [9.1]). CaMos participants had lower mean body mass index and higher prevalence of smoking (p < 0.001). Adjusted linear regression models (estimates [95%CI]) demonstrated lower FN-BMD in CaMos women (- 0.017 g/cm 2 [- 0.021; - 0.014]) and men (- 0.006 g/cm 2 [- 0.011; 0.000]), while adjusted odds ratios (95%CI) for prevalent MOF were higher in CaMos women (1.99 [1.71; 2.30]) and men (2.33 [1.82; 3.00]) compared to CLSA. In women with prevalent MOF, menopausal hormone therapy use was similar in both cohorts (43.3% vs 37.9%, p = 0.076), but supplements (32.0% vs 48.3%, p < 0.001) and bisphosphonate use (5.8% vs 17.3%, p < 0.001) were lower in CaMos. The proportion of men with MOF who received bisphosphonates was below 10% in both cohorts., Conclusion: Higher BMD and lower fracture prevalence were noted in the more recently recruited CLSA cohort compared to CaMos, even after adjusting for multiple covariates. We noted an increase in bisphosphonate use in the recent cohort, but it remained very low in men., (© 2022. The Author(s).)

Most of the published epidemiology on osteoporosis is derived from White populations; still many countries have increasing ethno-culturally diverse populations, leading to gaps in the development of population-specific effective fracture prevention strategies. We describe differences in prevalent fracture and bone mineral density patterns in Canadians of different racial/ethnic backgrounds., Introduction: We described prevalent fracture and bone mineral density (BMD) patterns in Canadians by their racial/ethnic backgrounds., Methods: For this cross-sectional analysis, we used the Canadian Longitudinal Study on Aging baseline data (2011-2015) of 22,091 randomly selected participants of Black, East Asian, South or Southeast Asian (SSEA) and White race/ethnic backgrounds, aged 45-85 years with available information on the presence or absence of self-reported prevalent low trauma fractures and femoral neck BMD (FNBMD) measurement. Logistic and linear regression models examined associations of race/ethnic background with fracture and FNBMD, respectively. Covariates included sex, age, height, body mass index (BMI), grip strength and physical performance score., Results: We identified 11,166 women and 10,925 men. Self-reported race/ethnic backgrounds were: 139 Black, 205 East Asian, 269 SSEA and 21,478 White. White participants were older (mean 62.5 years) than the other groups (60.5 years) and had a higher BMI (28.0 kg/m 2 ) than both Asian groups, but lower than the Black group. The population-weighted prevalence of falls was 10.0%, and that of low trauma fracture was 12.0% ranging from 3.3% (Black) to 12.3% (White), with Black and SSEA Canadians having lower adjusted odds ratios (aOR) of low trauma fractures than White Canadians (Black, aOR = 0.3 [95% confidence interval: 0.1-0.7]; SSEA, aOR = 0.5 [0.3-0.8]). The mean (SD) FNBMD varied between groups: Black, 0.907 g/cm 2 (0.154); East Asian, 0.748 g/cm 2 (0.119); SSEA, 0.769 g/cm 2 (0.134); and White, 0.773 g/cm 2 (0.128). Adjusted linear regressions suggested that Black and both Asian groups had higher FNBMD compared to White., Conclusion: Our results support the importance of characterizing bone health predictors in Canadians of different race/ethnic backgrounds to tailor the development of population-specific fracture prevention strategies., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Fracture risk calculators may not be accurate for all ethnicity groups. The Manitoba bone density registry was used to test the Canadian CAROC tool for predicting fracture risk in Asian-Canadian women. The tool significantly over-estimated fracture risk, suggesting that it may not be ideal for Asian-Canadian patients., Purpose: Health risk prediction tools based on largely White populations may lead to treatment inequity when applied to non-White populations where outcome rates differ. We examined the calibration of the Canadian Association of Radiologists-Osteoporosis Canada (CAROC) fracture risk prediction tool in self-identified Asian-Canadian women., Methods: Retrospective cohort study of women over age 50 using the Manitoba BMD Registry. At first BMD, the intake questionnaire collected self-identification of ethnicity and fracture risk factors. 10-year fracture risk was estimated using CAROC and categorized into low, medium, or high fracture risk. Linked administrative databases identified incident osteoporotic fractures. Observed fracture rates were compared between White and Asian-Canadians and compared to the original CAROC risk stratification., Results: There were 63,632 and 1703 women who self-identified as White-Canadian or Asian-Canadian, respectively, covering approximately 600,000 patient-years follow-up. There were 6588 incident fractures; a similar percentage of patients were assigned to each risk stratum at baseline by CAROC. A progressive rise in 10-year observed fracture rates occurred for each CAROC stratum in the White-Canadian population but much lower fracture rates than predicted in Asian-Canadian patients (p &lt; 0.001). Fracture incidence rate ratios were 1.9-2.6 fold higher in White- vs Asian-Canadian patients for all strata (p &lt; 0.001). In the CAROC moderate and high-risk categories, observed fracture rates in Asian-Canadian patients were typically lower than predicted, indicating poor model calibration., Conclusion: In Asian-Canadian women, observed osteoporosis fracture rates are lower than predicted when using the CAROC tool. Over-estimation of fracture risk may influence shared decision-making discussions., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures., Introduction: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors., Methods: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible., Results: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed., Conclusions: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266))., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Epidemiological studies show an inconsistent association between cancer and osteoporosis. In this nationally representative population-based study, we found that a prior cancer diagnosis was not associated with osteoporosis. This finding may primarily apply to cancer survivors seen many years after their cancer diagnosis., Background: Epidemiological studies show an inconsistent association between cancer and osteoporosis. We examined the association between a prior cancer diagnosis and osteoporosis in population-based data., Methods: We performed an age- and sex-matched case-control study (1:2 matching ratio) using the National Health and Nutrition Examination Survey, 2011-2018. Cases were determined by self-reported prior diagnosis of cancer; all controls were free of cancer at the time of bone density measurement with dual-energy x-ray absorptiometry. We defined osteoporosis as a T-score ≤  - 2.5 at femoral neck, total hip, or lumbar spine. Unconditional multivariable logistic regression was used to test the association between a prior cancer diagnosis and osteoporosis., Results: We identified 246 prior cancer cases and 492 controls (mean age: 65.8 years) in females, and 243 prior cancer cases and 486 controls (mean age: 68.0 years) in males. The most common types of cancer in females and males were breast cancer and prostate cancer, respectively. Osteoporosis prevalences were comparable between cases and controls among females (19.1% in cases vs. 18.7% in controls; P = 0.894) and males (5.8% in cases vs. 6.8% in controls; P = 0.594). After adjusting for covariates, a prior cancer diagnosis was not associated with osteoporosis in females (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.54-1.29) or males (OR: 1.09; 95% CI: 0.51-2.30). Results were unaffected by cancer severity, cancer type, or time since cancer diagnosis., Conclusions: A prior cancer diagnosis was not associated with osteoporosis in this nationally representative population., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose of Review: Type 1 (T1D) and 2 diabetes (T2D) are associated with increased risk of fracture independent of bone mineral density (BMD). Fracture risk prediction tools can identify individuals at highest risk, and therefore, most likely to benefit from antifracture therapy. This review summarizes recent advances in fracture prediction tools as applied to individuals with diabetes., Recent Findings: The Fracture Risk Assessment (FRAX) tool, Garvan Fracture Risk Calculator (FRC), and QFracture tool are validated tools for fracture risk prediction. FRAX is most widely used internationally, and considers T1D (but not T2D) under secondary osteoporosis disorders. FRAX underestimates fracture risk in both T1D and T2D. Trabecular bone score and other adjustments for T2D-associated risk improve FRAX-based estimations. Similar adjustments for T1D are not identified. Garvan FRC does not incorporate diabetes as an input but does includes falls. Garvan FRC slightly underestimates osteoporotic fracture risk in women with diabetes. QFracture incorporates both T1D and T2D and falls as input variables, but has not been directly validated in individuals with diabetes., Summary: Further research is needed to validate and compare available fracture prediction tools and their performance in individuals with diabetes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The majority of the research on rank-based sampling designs in finite populations has been concerned with univariate situations. In this article, we study design-based estimation using a bivariate ranked set sampling (BIRSS) for finite populations when we have bivariate response variables. We derive the first and second-order inclusion probabilities associated with a BIRSS design. We show that the size of a BIRSS sample is random and propose using a conditional Poisson sampling (CPS) design to rectify this problem. We then use calculated inclusion probabilities to obtain design-based estimators of correlation coefficients between the bone mineral density (BMD) levels at the baseline and followup of a longitudinal BMD study in the province of Manitoba in Canada. We also study the problem of estimating the parameters of a regression model between the followup BMD and easy to obtain auxiliary information from the underlying population. Finally, we study the problem of classifying patients as those with or without osteoporosis using BIRSS and various CPS designs. We show that BIRSS designs are very flexible and can be used to obtain more efficient design-based estimators in sample surveys when dealing with response variables that are hard to measure or expensive to obtain., (© 2021 John Wiley & Sons Ltd.)

The prevalence of self-reported and DXA-confirmed osteoporosis was 7.8% (males 2.2%; females 12.7%), and 3.6% (males 1.2%; females 5.9%), respectively. We found that most community-dwelling older adults at high fracture risk are not taking osteoporosis medication, particularly males. There is a major opportunity for improved primary fracture prevention in the community., Purpose: To provide an up-to-date prevalence estimate of osteoporosis, fracture risk factors, fracture risk, and the proportion of older Canadians at high fracture risk who are not taking an osteoporosis medication., Methods: We included Canadian Longitudinal Study on Aging (CLSA) participants: a community-dwelling cohort aged 45 to 85 years who completed the baseline (2015) comprehensive interview and had dual-energy X-ray absorptiometry (DXA) scans (N = 30,097). We describe the age- and sex-stratified prevalence of (1) self-reported osteoporosis; (2) DXA-confirmed osteoporosis; (3) fracture risk factors and people who are at high risk (FRAX® major osteoporotic fracture probability ≥ 20%); and (4) people who are at high fracture risk not taking osteoporosis medications. Sampling weights, as defined by the CLSA, were applied., Results: The mean age of participants was 70.0 (SD 10.3). Overall, 7.8% had self-reported osteoporosis (males 2.2%; females 12.7%) while 3.6% had DXA-confirmed osteoporosis (males 1.2%; females 5.9%), and 2.8% were at high fracture risk (males 0.3%; females 5.1%). Of people who had osteoporosis and were at high risk, 77.3% were not taking an osteoporosis medication (males 92.3%; females 76.8%)., Conclusions: Our study provides an up-to-date prevalence estimate of osteoporosis for community-dwelling older Canadians. We found that most community-dwelling older adults at high fracture risk are not taking an osteoporosis medication, particularly males. There is a major opportunity for improved primary fracture prevention in the community., (© 2022. The Author(s).)

Context: Fracture on therapy should motivate better antifracture medication adherence., Objective: This study aimed to describe osteoporosis medication adherence in women before and following a fracture., Methods: This retrospective cohort analysis of antifracture medication possession ratios (MPR) among women in the Manitoba BMD Registry (1996-2013) included menopausal women who started antifracture drug therapy after a dual-energy x-ray absorptiometry (DXA)-BMD assessment with follow-up for 5 years during which a nontraumatic fracture occurred at least 1 year after starting treatment. Linked prescription records determined medication adherence (estimated by MPR) in 1-year intervals. The variable of interest was MPR in the year before and after the year in which the fracture occurred, with subgroup analyses according to duration of treatment pre-fracture. We chose an MPR of ≥ 0.50 to indicate minimum adherence needed for drug efficacy., Results: There were 585 women with fracture on therapy, 193 (33%) had hip or vertebral fracture. Bisphosphonates accounted for 82.2% of therapies. Median MPR the year prior to fracture was 0.89 (IQR, 0.49-1.0) and 0.69 (IQR, 0.07-0.96) the year following the year of fracture (P < 0.0001). The percentage of women with MPR ≥ 0.5 pre-fracture was 73.8%, dropping to 57.3% post-fracture (P < 0.0001); when restricted to hip/vertebral fracture, results were similar (58.2% to 33.3%; P < 0.002). Among those with pre-fracture MPR < 0.5, only 21.7% achieved a post-fracture MPR ≥ 0.5., Conclusions: Although fracture on therapy may motivate sustained/improved adherence, MPR remains low or even declines after fracture in many. This could reflect natural decline in MPR with time but is paradoxical to expectations. Fracture on therapy represents an important opportunity for clinicians to reemphasize treatment adherence., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: The value of serial bone mineral density (BMD) monitoring while on osteoporosis therapy is controversial., Objective: We determined the percentage of women classified as suboptimal responders to therapy with antiresorptive medications according to 2 definitions of serial BMD change., Methods: This was a cohort study using administrative databases at a single-payer government health system in Manitoba, Canada. Participants were postmenopausal women aged 40 years or older receiving antiresorptive medications and having 3 sequential BMD measures. Women stopping or switching therapies were excluded. The percentage of women whose spine or hip BMD decreased significantly during the first or second interval of monitoring by BMD was determined. Suboptimal responder status was defined as BMD decrease during both monitoring intervals or BMD decreased from baseline to final BMD., Results: There were 1369 women in the analytic cohort. Mean BMD monitoring intervals were 3.0 (0.8) and 3.2 (0.8) years. In the first interval, 3.2% and 6.5% of women had a decrease in spine or hip BMD; 8.0% and 16.9% had decreases in the second monitoring interval; but only 1.4% showed repeated losses in both intervals. Considering the entire treatment interval, only 3.2% and 7.4% showed BMD loss at spine or hip. Results may not apply to situations of poor adherence to antiresorptive medication or anabolic therapy use., Conclusion: Among women highly adherent to antiresorptive therapy for osteoporosis, a very small percentage sustained BMD losses on repeated measures. The value of multiple serial BMD monitoring to detect persistent suboptimal responders should be questioned., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The role of mid-treatment monitoring dual-energy X-ray absorptiometry-bone mineral density (DXA-BMD) for bisphosphonate-treated patients with osteoporosis remains unsettled. A common reason for such monitoring is to encourage ongoing medication adherence. We sought to determine if a DXA-BMD treatment monitoring test was associated with improved medication adherence and whether improved adherence after a DXA-BMD treatment monitoring test was associated with subsequent reduction in fracture rates. Using linked administrative databases within Manitoba, Canada, we performed a retrospective cohort study of women starting and continuing antiresorptive therapy in whom a mid-treatment DXA-BMD monitoring test was performed. From the provincial pharmacy database, we estimated medication adherence by calculating annual medication possession ratio (MPR) and determining the change in MPR with respect to change (stable/decrease) in the DXA-BMD monitoring test, in addition to fracture rates before and after the test. The cohort comprised 3418 women, 90.7% treated with oral bisphosphonate, with pharmacy data for the 3 years before and after the mid-treatment DXA-BMD. Median (interquartile range) MPR was 0.84 (0.49-0.99) in the year before DXA-BMD and 0.84 (0.48-0.99) in the year after DXA-BMD (p = 0.37). Among those whose DXA-BMD declined, MPR in the prior year was 0.54 (0.04-0.92) but improved to 0.70 (0.31-0.92) in the year after DXA-BMD (p < 0.001). Among those whose DXA-BMD monitoring test was stable/improved, the fracture rate before the monitoring DXA-BMD was 10.1 per 1000 person-years and in those whose DXA-BMD monitoring test showed a decrease, the rate was 23.7 per 1000 person-years (p < 0.001). Despite improved adherence in those with DXA-BMD decline, the post DXA-BMD fracture rate was 22.4 per 1000 person-years versus 12.9 per 1000 person-years in those who had stable DXA-BMD (p < 0.001). A mid-treatment DXA-BMD reassessment strategy may be useful to focus attention upon adherence, but for optimal fracture outcomes, treatment adherence should be specifically addressed at the commencement of therapy. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Dual-energy X-ray absorptiometry (DXA) is the method of choice for assessing bone mineral density (BMD). Unfortunately, the performance and interpretation of DXA can be challenging and errors are common. In fact, it has been reported that up to 90% of BMD reports contain at least 1 error. Errors can be the result of technique or interpretative in nature or both and can result in inappropriate diagnosis and management. In this article, we review the various types of pitfalls frequently encountered by physicians interpreting DXA studies. Being aware of these pitfalls will help readers recognize and avoid them when encountered in clinical practice.

Diabetes-induced osteoporosis is characterized by an increase in fracture risk. FRAX, the most widely used tool, underestimates the risk of fracture in both type 1 and type 2 diabetes. Specific adjustments to FRAX can help to better identify patients with diabetes at increased risk of fracture and select those at high fracture risk for treatment. Although clinical trial data are limited, the available evidence indicates that the presence of diabetes does not alter antiosteoporotic treatment response in patients with diabetes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Both diabetes and osteoporosis are increasingly prevalent diseases, in part owing to aging populations worldwide. Epidemiologic data have shown that other organs may be adversely affected by diabetes, including the skeleton, in what has become known as diabetes-induced osteoporosis, which represents the combined impact of conventional osteoporosis with the additional fracture burden attributed to diabetes. There is an increased risk of fracture in patients with Type 1 and Type 2 diabetes, and some antidiabetic medications also may contribute to increased risk of fracture in diabetes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Osteoporosis and its clinical consequence, bone fracture, is a multifactorial disease that has been the object of extensive research. Recent advances in machine learning (ML) have enabled the field of artificial intelligence (AI) to make impressive breakthroughs in complex data environments where human capacity to identify high-dimensional relationships is limited. The field of osteoporosis is one such domain, notwithstanding technical and clinical concerns regarding the application of ML methods. This qualitative review is intended to outline some of these concerns and to inform stakeholders interested in applying AI for improved management of osteoporosis. A systemic search in PubMed and Web of Science resulted in 89 studies for inclusion in the review. These covered one or more of four main areas in osteoporosis management: bone properties assessment (n = 13), osteoporosis classification (n = 34), fracture detection (n = 32), and risk prediction (n = 14). Reporting and methodological quality was determined by means of a 12-point checklist. In general, the studies were of moderate quality with a wide range (mode score 6, range 2 to 11). Major limitations were identified in a significant number of studies. Incomplete reporting, especially over model selection, inadequate splitting of data, and the low proportion of studies with external validation were among the most frequent problems. However, the use of images for opportunistic osteoporosis diagnosis or fracture detection emerged as a promising approach and one of the main contributions that ML could bring to the osteoporosis field. Efforts to develop ML-based models for identifying novel fracture risk factors and improving fracture prediction are additional promising lines of research. Some studies also offered insights into the potential for model-based decision-making. Finally, to avoid some of the common pitfalls, the use of standardized checklists in developing and sharing the results of ML models should be encouraged. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Background: It is unknown as to what factors typically drive osteoporosis therapy decisions in real-world practice., Methods: Retrospective, 20-year cohort study within the government health system of Manitoba including all women having bone densitometry (BMD) tests between 1996 and 2017. Osteoporosis prescription data was linked to registry data on fractures, clinical risk factors and BMD tests. We defined 6 possible treatment decisions by prescription data: no treatment, starting, stopping, continuing, drug hiatus and re-starting. For each decision, we tested the association between salient patient factors (age, glucocorticoid use, recent fracture, BMD hip or spine T-score ≤ -2.5, FRAX major osteoporotic fracture probability ≥20%) using multivariable logistic regression. The factors were rank-ordered by decreasing Wald χ 2 statistic to determine the relative importance., Results: There were 64,181 women, 33.8% of whom started osteoporosis therapy. For patients who begin therapy after a first BMD, the rank-ordered multivariable logistic regression factor most strongly associated was the T-score ≤ -2.5 [OR of 7.59(95%CI 7.19-8.01, p < 0.001)]. This was followed by glucocorticoid use [OR 2.89(95%CI 2.59-3.22, p < 0.001)]. Increasing age and recent fracture (within 2 years) were weak predictors of therapy and high FRAX score associated with reduced odds of therapy [OR 0.80 (95%CI 0.74-0.88, p < 0.001)]. T-scores were the strongest factor predicting therapy stop/continuation/re-starting; age and prior fracture had weak or no associations., Conclusions: Despite recommendations for fracture-risk-based approach to osteoporosis therapy, BMD T-score continues to be the dominant factor in actual practice. Age, prior fracture or global fracture risk are much less associated; it is possible that BMD T-score categories are therefore acting as a clinically salient distracting factor., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Among 4238 cancer and 16,418 cancer-free individuals with incident major non-traumatic fractures (hip, clinical vertebral, forearm, humerus), post-fracture osteoporosis care was equally poor for both groups, whether assessed from bone mineral density (BMD) testing, initiation of osteoporosis therapy or either intervention (BMD testing and/or osteoporosis therapy)., Introduction: Most individuals sustaining a fracture do not undergo evaluation and/or treatment for osteoporosis. Cancer survivors are at increased risk for osteoporosis and fracture. Whether cancer survivors experience a similar post-fracture "care gap" is unclear. Using population-based databases, we assessed whether cancer patients are evaluated and/or treated for osteoporosis after a major fracture., Methods: From the Manitoba Cancer Registry, we identified cancer cases (first cancer diagnosis between 1987 and 2013) and cancer-free controls with incident major non-traumatic fractures (from provincial physician billing claims and hospitalization databases). The outcomes were performance of BMD testing (from the BMD Registry), initiation of osteoporosis therapy (from drug dispensation database) or either intervention (BMD testing and/or osteoporosis therapy) in the 12 months post-fracture., Results: There were 4238 cancer and 16,418 cancer-free individuals who sustained a fracture after the index date (cancer diagnosis) and were followed for at least 1 year post-fracture. Subsequent BMD testing was performed in 11.0% of cancer cases versus 11.5% non-cancer controls (P = 0.43), osteoporosis treatment in 22.9% cancer cases versus 21.8% non-cancer controls (P = 0.15), and either testing or treatment in 28.9% cancer cases versus 28.4% non-cancer controls (P = 0.53). Predictors of BMD testing and/or initiation of therapy were similar for non-cancer and cancer patients. Post-fracture interventions were consistently used more frequently among women, older patients (age 50 years or older), those who sustained fractures in a later calendar period, and (for treatment) after vertebral fracture. Cancer-specific variables (cancer type, years from cancer diagnosis to fracture, specialty of care provider) showed only weak and inconsistent effects., Conclusions: A large care gap exists among cancer patients who sustain a fracture, similar to the general population, whereby the evaluation or treatment for osteoporosis is seldom conducted. Care maps may need to be developed for cancer populations to improve post-fracture care.

Core principles for fracture prevention address fundamental concepts for the evaluation and management of patients at risk for fracture. These are intended to form the foundation of clinical practice guidelines and represent a first step toward guideline harmonization., Introduction: The large number of clinical practice guidelines for osteoporosis and discordance of recommendations has led to confusion among clinicians and patients, and likely contributes to the large osteoporosis treatment gap. We propose that stakeholder organizations reach agreement on fundamental principles in the management of osteoporosis and prevention of fracture as a first step toward a goal of guideline harmonization., Methods: The best available evidence, as interpreted by an ad hoc working group of expert representatives from major osteoporosis societies in North America, was considered in the development of core principles for skeletal healthcare. These principles were subsequently endorsed by the USA National Osteoporosis Foundation, Osteoporosis Canada, and Academia Nacional de Medicina de Mexico (National Academy of Medicine of Mexico)., Results: Core principles are summarized here in bullet format. Categories include evaluation, lifestyle and nutrition, pharmacological therapy, and monitoring. A pathway forward to achieve guideline harmonization, at least in part, is proposed., Conclusion: Greater concordance of recommendations for the care of patients at risk for fracture are expected to lead to improved patient care across jurisdictions, with a narrowing of the osteoporosis treatment gap and reduced burden of fractures.

The role for bone mineral density (BMD) monitoring while on antiosteoporosis therapy remains controversial. The current study used population-based registries to identify factors associated with BMD monitoring in women within 5 yr of receiving antiosteoporosis treatment vs treatment without monitoring in routine clinical practice. The analytical dataset consisted of women age 40 yr and older at baseline receiving antiosteoporosis therapy: 6877 with BMD monitoring (mean interval 3.2 yr) and 6747 without BMD monitoring. There was a significant negative secular trend in BMD monitoring during the study period (p < 0.001). Multivariable logistic regression demonstrated that parental hip fracture, glucocorticoid and aromatase inhibitor use, and lower baseline BMD were independently and positively associated with BMD monitoring. Individuals with increasing age, greater body mass index, smoking, rheumatoid arthritis, later calendar year, diabetes, rural residency, lower income, and greater comorbidity score were less likely to undergo monitoring. A shorter monitoring interval (<23 mo) was strongly associated with glucocorticoid and aromatase inhibitor use. In conclusion, our study identifies factors associated with BMD monitoring over 5 yr in patients receiving antiosteoporosis therapy., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

In a global survey of fracture liaison services, most reported that DXA access met needs. However, adherence to basic DXA quality and reporting procedures was confirmed by only around 50% of institutions and many required education for operators/interpreters. Overall, there is significant variability in the access to, and quality of, DXA services worldwide., Introduction: While the use of dual-energy X-ray absorptiometry (DXA) has been widely adopted worldwide for the assessment of bone mineral density, the quality of DXA facilities is unknown. To address this, a global survey of fracture liaison services (FLS) was conducted by the International Society for Clinical Densitometry (ISCD) and the International Osteoporosis Foundation (IOF) to assess the quality of their DXA facilities., Methods: A questionnaire for the accessibility and quality of DXA services was co-created by representatives of the ISCD and the IOF and made available to institutions who participated in the Capture the Fracture Best Practice Framework. From a list of 331 contacted invitees, 124 FLS centres responded; analyses were based on 121 centres with suitable data., Results: Over 70% of institutions reported that, for over 90% of the time, DXA access met service needs, and the scanning/reporting quality was perceived as excellent. However, 25% of DXA facilities reported not being accredited by a professional/governmental organization, and adherence to some basic DXA quality assurance and reporting procedures was confirmed by < 50% of services. Importantly, in excess of 50% of institutions stated that they desired ongoing education in osteoporosis and DXA for operators and interpreters., Conclusion: There is significant variability in the access to and quality of DXA services for established FLS worldwide. Despite two decades of training initiatives in osteoporosis densitometry, many centres are falling short of the standards of the IOF-ISCD Osteoporosis Essentials criteria.

Among 39,475 women, age 65 years and older, use of fracture history, major osteoporotic fracture (MOF) probability from FRAX®, vertebral fracture assessment (VFA), and bone mineral density (BMD) T-score stratified women into different levels of risk. The majority of women identified as being at high risk from fracture history, FRAX MOF-BMD > 20%, or vertebral fracture on VFA had a BMD T-score in the osteoporotic range., Purpose: To inform criteria for pharmacologic treatment in women age 65 years and older, we examined subgroups defined from fracture history, MOF calculated with BMD (MOF-BMD), VFA, and BMD T-score using the population-based Manitoba BMD Program registry., Methods: The study population consisted of women age > 65 years was divided into mutually exclusive subgroups based upon fracture history, MOF-BMD ≥ 20%, vertebral fracture on VFA, and osteoporotic BMD T-score. Healthcare records were assessed for the presence of fracture diagnosis codes occurring after DXA assessment. For each subgroup, we estimated the proportion of individuals with BMD T-score in the osteoporotic range, predicted versus observed 10-year MOF probability, hazard ratio (HR) for MOF, and number needed to treat (NNT) for 3 years to prevent a fracture event., Results: The study population consisted of 39,475 women (median age 72 years). The majority of women (76.8%) selected as being at high risk based on fracture history, MOF-BMD > 20%, or vertebral fracture on VFA had a BMD T-score in the osteoporotic range. During a median follow-up of 8 years, 5169 (13.1%) sustained one or more incident MOF. Fracture rates and HRs generally paralleled the FRAX prediction, except in women with a positive VFA where predicted risk based upon clinical risk factors prior to VFA underestimated the observed risk. NNT differed by the risk subgroup, and showed a gradient of decreasing NNT (consistent with greater benefit) in individuals with the highest fracture risk., Conclusions: Fracture history, fracture probability from FRAX, targeted vertebral fracture assessment (VFA), and BMD T-score can stratify older women into different levels of risk and treatment benefit. These results are expected to inform clinical practice guidelines in Canada.

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health., Introduction: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk., Methods: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI)., Results: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ 2 (172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001)., Conclusions: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.

Purpose of Review: Identifying individuals at high fracture risk can be used to target those likely to derive the greatest benefit from treatment. This narrative review examines recent developments in using specific risk factors used to assess fracture risk, with a focus on publications in the last 3 years., Recent Findings: There is expanding evidence for the recognition of individual clinical risk factors and clinical use of composite scores in the general population. Unfortunately, enthusiasm is dampened by three pragmatic randomized trials that raise questions about the effectiveness of widespread population screening using clinical fracture prediction tools given suboptimal participation and adherence. There have been refinements in risk assessment in special populations: men, patients with diabetes, and secondary causes of osteoporosis. New evidence supports the value of vertebral fracture assessment (VFA), high resolution peripheral quantitative CT (HR-pQCT), opportunistic screening using CT, skeletal strength assessment with finite element analysis (FEA), and trabecular bone score (TBS). The last 3 years have seen important developments in the area of fracture risk assessment, both in the research setting and translation to clinical practice. The next challenge will be incorporating these advances into routine work flows that can improve the identification of high risk individuals at the population level and meaningfully impact the ongoing crisis in osteoporosis management.

Patient engagement in clinical guidelines development is essential. The results of a self-administered online survey identified themes important to people living with osteoporosis and will inform the development of Osteoporosis Canada clinical guidelines recommendations., Introduction: Patient engagement is essential in the development of high-quality and relevant guidelines for osteoporosis management. Osteoporosis Canada (OC) is updating its national clinical practice guidelines in collaboration with people living with osteoporosis in the process., Methods: Using electronic mail, we contacted 6937 members of the Canadian Osteoporosis Patient Network (COPN) to provide input on the selection of relevant content, outcomes, and research questions via a self-administered online survey. Close-ended questions were analyzed using descriptive statistics, and conventional content analysis was conducted for open-ended questions., Results: A total of 1108 individuals completed the survey (97% women, 86% stated they lived with osteoporosis). Most participants considered it critical to have recommendations on physical activity and exercise (74%), fall prevention (69%), nutrition (68%), and initial bone mineral density testing (67%). In addition to preventing fractures, over 75% of respondents stated that consideration of preserving quality of life and ability to perform daily activities, preventing admission to long-term care and fracture-related death, and avoiding serious harms from medications were essential outcomes to consider in evaluating the evidence. In terms of selection of research questions, seven themes emerged from the content analysis including pharmacotherapy, screening and monitoring, diet and supplements, education, exercise, alternative therapies, and pain management., Conclusions: Patients emphasized that autonomy, mobility, and quality of life are highly valued outcomes and must be integral to practice guideline development. As expected, guidance on pharmacotherapy, screening and monitoring, and fracture prevention were priorities identified to be included in osteoporosis management guidelines.

Osteoporosis is a major public health problem worldwide. Lower peak bone mineral density (BMD) in youth may be the single most important factor leading to the development of osteoporosis in the elderly. Using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014, we included 18,713 individuals with complete and valid data on femoral neck, total hip and lumbar spine BMD. Generalized additive models were used to estimate the age at attainment of peak BMD and 95% confidence intervals (95%Cls); model covariates were sex, race, body mass index (BMI) and we also examine factors potentially affecting age at attainment of peak BMD. This study clearly stated that age at attainment of peak femoral neck, total hip and lumbar spine BMD were 20.5 years, 21.2 years and 23.6 years in males, and 18.7 years, 19.0 years and 20.1 years in females, respectively and age at attainment of peak BMD varied by skeletal sites and sex. The study also found that females achieved peak femoral neck, total hip and lumbar spine BMD earlier than males (all P < 0.001); race and BMI were not associated with the age at attainment of peak BMD (all P > 0.05). These results suggested that improving bone health among individuals before 20 years old may be useful for reducing future risk of osteoporosis and osteoporotic fractures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The fracture risk assessment tool, FRAX ® , was released in 2008 and provides country-specific algorithms for estimating individualized 10-year probability of hip and major osteoporotic fracture (hip, clinical spine, distal forearm, and proximal humerus). Since its release, 71 models have been made available for 66 countries covering more than 80% of the world population. The website receives approximately 3 million visits annually. Following independent validation, FRAX has been incorporated into more than 80 guidelines worldwide. The application of FRAX in assessment guidelines has been heterogeneous with the adoption of several different approaches in setting intervention thresholds. Whereas most guidelines adopt a case-finding strategy, the case for FRAX-based community screening in the elderly is increasing. The relationship between FRAX and efficacy of intervention has been explored and is expected to influence treatment guidelines in the future.

This comparison of osteoporosis treatment strategies and intervention thresholds highlights tradeoffs in terms of number of individuals qualifying for treatment and estimated fractures prevented., Purpose: The current analysis was performed to inform the following key question as part of the Osteoporosis Canada's Osteoporosis Guidelines Update: "What is the best strategy to identify those at high fracture risk for pharmacotherapy in order to prevent the most fractures, considering both population and patient perspectives?", Methods: The study population consisted of 66,878 women age 50 years and older (mean age 66.0 ± 9.7 years) with documented fracture probability assessment (FRAX) and fracture outcomes. Fractures over the next 5 years were identified through linked administrative healthcare data. We estimated the fraction of the population that would warrant treatment and the number of fractures avoided per 1000 person-years according to multiple strategies and thresholds. Strategies were then rank ordered using 19 metrics., Results: During mean 4.4 years, 863 (3.5%) sustained one or more major osteoporotic fractures (MOF), 212 (0.8%) sustained a hip fracture, and 1210 (4.9%) sustained any incident fracture. For woman age 50-64 years, the highest ranked strategy was treatment based upon total hip T score ≤ -2.5, but several other strategies fell within 0.5 overall ranking. For women age 65 years and older, MOF > 20% was the highest ranked strategy with no closely ranked strategies. Pooling both age subgroups gave MOF > 20% as the highest ranked strategy, with several other strategies within 0.5 overall ranking., Conclusions: Choice of treatment strategy and threshold for osteoporosis management strongly influences the number of individuals for whom pharmacologic treatment would be recommended and on estimated fracture rates in the population. This evidence-based approach to comparing these strategies will help to inform guidelines development in Canada and may be on interest elsewhere.

Purpose of Review: Despite the high prevalence and impact of osteoporosis, screening and treatment rates remain low, with few women age 65 years and older utilizing osteoporosis screening for primary prevention., Recent Findings: This review examines opportunities and challenges related to primary prevention and screening for osteoporosis at the population level. Strategies on how to identify individuals at high fracture risk and target them for treatment have lagged far behind other developments in the osteoporosis field. Most osteoporosis quality improvement strategies have focused on patients with recent or prior fracture (secondary prevention), with limited attention to individuals without prior fracture. For populations without prior fracture, the only quality improvement strategy for which meta-analysis demonstrated significant improvement in osteoporosis care was patient self-scheduling of DXA plus education Much more work is needed to develop and validate effective primary screening and prevention strategies and translate these into high-quality guidelines.

Background: Aromatase inhibitors (AIs) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk., Materials and Methods: Using a population-based BMD registry, we identified women aged at least 40 years initiating AIs for breast cancer with at least 12 months of AI exposure ( n = 1,775), women with breast cancer not receiving AIs ( n = 1,016), and women from the general population ( n = 34,205). Fracture outcomes were assessed to March 31, 2017 (mean, 6.2 years for AI users)., Results: At baseline, AI users had higher body mass index (BMI), higher BMD, lower osteoporosis prevalence, and fewer prior fractures than women from the general population or women with breast cancer without AI use (all p < .001). After adjusting for all covariates, AI users were not at significantly greater risk for major osteoporotic fractures (hazard ratio [HR], 1.15; 95% confidence interval [CI], 0.93-1.42), hip fracture (HR, 0.90; 95% CI, 0.56-1.43), or any fracture (HR, 1.06; 95% CI, 0.88-1.28) compared with the general population., Conclusion: Higher baseline BMI, BMD, and lower prevalence of prior fracture at baseline may offset the adverse effects of AI exposure. Although confirmatory data from large cohort studies are required, our findings challenge the view that all women with breast cancer initiating AI therapy should be considered at high risk for fractures., Implications for Practice: In a population-based observational registry that included 1,775 patients initiating long-term aromatase inhibitor therapy, risk for major osteoporotic fracture, hip fracture, or any fracture was similar to the general population. Higher baseline body mass index, bone mineral density, and lower prevalence of prior fracture at baseline may offset the adverse effects of aromatase inhibitor exposure., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Routine bone mineral density (BMD) monitoring of individuals during the initial 5 years of anti-osteoporosis treatment is controversial. Using a registry-based cohort from the Province of Manitoba, Canada, we compared anti-osteoporosis medication use and fracture outcomes in women with versus without BMD monitoring receiving anti-osteoporosis medication. We identified 4559 women aged 40 years and older receiving anti-osteoporosis therapy with serial BMD testing (monitoring) within 5 years (mean interval 3.2 years) and 4559 propensity score-matched women without BMD monitoring. We assessed anti-osteoporosis medication use over 5 years from a population-based retail pharmacy database. Incident fractures to 10 years from health services data. During median 10 years observation, 1225 (13.4%) women developed major osteoporotic fracture, including 382 (4.2%) with hip fractures. Monitored women had significantly better fracture-free survival for major osteoporotic fracture (p = 0.040; 10-year cumulative risk 1.9% lower, 95% confidence interval [CI] 0.3-3.6%) and hip fracture ( p = 0.001; 10-year cumulative risk 1.8% lower, 95% CI 0.7-2.8%) compared with women who were not monitored. Hazard ratios (HRs) were significantly lower in monitored versus not monitored women for major osteoporotic fracture (HR = 0.89, 95% CI 0.80-0.98) and hip fracture (HR = 0.74, 95% CI 0.63-0.87). Days of medication use, medication persistence ratio, and treatment switching over 5 years were greater in monitored versus not monitored women. At the end of 5 years, more women in the monitored group persisted on treatment and more switched treatment, with switching behavior associated with an observed interval reduction in BMD. In conclusion, our findings suggest a possible role for BMD monitoring after initiating anti-osteoporosis therapy in the routine clinical practice setting. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

We previously found that population-based postfracture notification, which informed primary care physicians of their patient's recent fracture and suggested assessment for osteoporosis, led to an improvement in postfracture care in the context of a randomized controlled trial ( ClinicalTrials.gov identifier NCT00594789, fractures from late 2007 to mid-2010). Since June 2010, a province-wide postfracture notification program was implemented. This study was to (1) determine whether this program has resulted in sustained improvement in postfracture care and (2) test factors associated with receiving osteoporosis care., Methods: A retrospective matched cohort study was performed using population-based health administrative data in Manitoba, Canada. We selected individuals aged 50+ years with an incident major osteoporosis fracture (MOF; N = 18,541) in fiscal years 2000/2001 to 2013/2014 and controls without a MOF (N = 92,705) matched (5:1) on age, sex, and residential area. The Cochran-Armitage test tested for a linear trend in osteoporosis care outcomes for cases and controls. Logistic regressions were used to test characteristics associated with the likelihood of receiving osteoporosis care., Results: The percentage of individuals receiving DXA testing and/or osteoporosis medication increased in fracture cases (p < 0.001), but decreased in controls (p < 0.001). Odds ratios for osteoporosis care in years following the postfracture notification program were approximately double of those prior to the clinical trial. In addition to prior MOF (OR 9.03, 95% CI 8.60-9.48), factors associated with osteoporosis care included lower income (OR   0.72, 95% CI 0.67-0.78), glucocorticoid use (OR   4.37, 95% CI 3.72-5.14), diabetes diagnosis (OR =  0.74, 95% CI 0.68-0.80), and Charlson Comorbidity Index (indexes 1-2: OR 1.27, 95% CI 1.20-1.34; indexes 3-5: OR 1.26, 95% CI 1.13-1.40)., Conclusions: Adopting a population-based postfracture notification program led to sustained improvements in postfracture care.

Purpose: To inform recommendations by the Canadian Task Force on Preventive Health Care by systematically reviewing direct evidence on the effectiveness and acceptability of screening adults 40 years and older in primary care to reduce fragility fractures and related mortality and morbidity, and indirect evidence on the accuracy of fracture risk prediction tools. Evidence on the benefits and harms of pharmacological treatment will be reviewed, if needed to meaningfully influence the Task Force's decision-making., Methods: A modified update of an existing systematic review will evaluate screening effectiveness, the accuracy of screening tools, and treatment benefits. For treatment harms, we will integrate studies from existing systematic reviews. A de novo review on acceptability will be conducted. Peer-reviewed searches (Medline, Embase, Cochrane Library, PsycINFO [acceptability only]), grey literature, and hand searches of reviews and included studies will update the literature. Based on pre-specified criteria, we will screen studies for inclusion following a liberal-accelerated approach. Final inclusion will be based on consensus. Data extraction for study results will be performed independently by two reviewers while other data will be verified by a second reviewer; there may be some reliance on extracted data from the existing reviews. The risk of bias assessments reported in the existing reviews will be verified and for new studies will be performed independently. When appropriate, results will be pooled using either pairwise random effects meta-analysis (screening and treatment) or restricted maximum likelihood estimation with Hartun-Knapp-Sidnick-Jonkman correction (risk prediction model calibration). Subgroups of interest to explain heterogeneity are age, sex, and menopausal status. Two independent reviewers will rate the certainty of evidence using the GRADE approach, with consensus reached for each outcome rated as critical or important by the Task Force., Discussion: Since the publication of other guidance in Canada, new trials have been published that are likely to improve understanding of screening in primary care settings to prevent fragility fractures. A systematic review is required to inform updated recommendations that align with the current evidence base.

FRAX was developed to predict 10-year probability of major osteoporotic fracture (MOF) and hip fracture in the general population. Aromatase inhibitors (AI) used in breast cancer induce loss in bone mineral density (BMD) and are reported to increase fracture risk. AI exposure is not a direct input to FRAX but is captured under "secondary osteoporosis". To inform use of FRAX in women treated with AI, we used a population-based registry for the Province of Manitoba, Canada, to identify women aged ≥40 years initiating AI for breast cancer with at least 12 months' AI exposure (n = 1775), women with breast cancer not receiving AI (n = 1016), and women from the general population (n = 34,205). Among AI users, fracture probability estimated without BMD (AI use coded as secondary osteoporosis) significantly overestimated risk (10-year observed/predicted ratio 0.56, 95% confidence interval [CI] 0.45-0.68; 10-year hip fracture observed/predicted ratio 0.33, 95% CI 0.18-0.49). However, when BMD was included in the fracture probability, there was no significant difference between observed and predicted fracture risk. In Cox proportional hazards models, FRAX stratified risk of MOF, hip, and any fracture equally well in all subgroups (p-interaction >0.1). When adjusted for FRAX score without BMD, with AI use coded as secondary osteoporosis, AI users were at significantly lower risk for MOF (hazard ratio [HR] = 0.78, 95% CI 0.64-0.95), hip fracture (HR = 0.46, 95% CI 0.29-0.73) and any fracture (HR = 0.75, 95% CI 0.63-0.89). AI use was no longer significantly associated with fractures when AI use was not entered as secondary osteoporosis in FRAX without BMD or when BMD was included in the FRAX calculation. In conclusion, FRAX scores stratify fracture risk equally well in women receiving AI therapy as in non-users, but including secondary osteoporosis as a risk factor for AI users overestimates fracture risk. Our results call this practice into question. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Objective: Finite element analysis (FEA) is a computational method to predict the behavior of materials under applied loading. We developed a software tool that automatically performs FEA on dual-energy X-ray absorptiometry hip scans to generate site-specific fracture risk indices (FRIs) that reflect the likelihood of hip fracture from a sideways fall. This longitudinal study examined associations between FRIs and incident fractures., Methods: Using the Manitoba Bone Mineral Density (BMD) Registry, femoral neck (FN), intertrochanter (IT), and subtrochanter (ST) FRIs were automatically derived from 13,978 anonymized dual-energy X-ray absorptiometry scans (Prodigy, GE Healthcare) in women and men aged 50 yr or older (mean age 65 yr). Baseline covariates and incident fractures were assessed from population-based data. We compared c-statistics for FRIs vs FN BMD alone and fracture risk assessment (FRAX) probability computed with BMD. Cox regression was used to estimate hazard ratios and 95% confidence intervals (95% CIs) for incident hip, major osteoporotic fracture (MOF) and non-hip MOF adjusted for relevant covariates including age, sex, FN BMD, FRAX probability, FRAX risk factors, and hip axis length (HAL)., Results: During mean follow-up of 6 yr, there were 268 subjects with incident hip fractures, 1003 with incident MOF, and 787 with incident non-hip MOF. All FRIs gave significant stratification for hip fracture (c-statistics FN-FRI: 0.76, 95% CI 0.73-0.79, IT-FRI 0.74, 0.71-0.77; ST-FRI 0.72, 0.69-0.75). FRIs continued to predict hip fracture risk even after adjustment for age and sex (hazard ratio per standard deviation FN-FRI 1.89, 95% CI 1.66-2.16); age, sex, and BMD (1.26, 1.07-1.48); FRAX probability (1.30, 1.11-1.52); FRAX probability with HAL (1.26, 1.05-1.51); and individual FRAX risk factors (1.32, 1.09-1.59). FRIs also predicted MOF and non-hip MOF, but the prediction was not as strong as for hip fracture., Summary: Automatically-derived FN, IT, and ST FRIs are associated with incident hip fracture independent of multiple covariates, including FN BMD, FRAX probability and risk factors, and HAL., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)