Among people on osteoporosis medication, loss of appendicular or total body lean mass is an independent risk factor for hip and major osteoporotic fractures.

People with prior lean mass loss had a ~ 10% higher risk of MOF and ~ 22-26% higher risk of hip fracture, and the results were similar in people on anti-osteoporosis medications. Loss of lean mass is associated with increased fracture risk. Patients should be encouraged to pursue strategies to prevent loss of lean mass. BACKGROUND: Sarcopenia increases fracture risk. If the risk persists after starting osteoporosis medication, patients may need to be encouraged to pursue strategies to prevent loss of lean mass. OBJECTIVE: To estimate the effects of loss in appendicular lean mass (ALM) or total body lean mass (TBLM) on subsequent fracture risk and effect modification with anti-osteoporosis medication use. METHODS: We conducted a registry-based cohort study linked to population-based data. We identified individuals ≥ 40 years of age with two DXA assessments ≥ 1 year apart and minimum 0.5 years of observation. ALM and TBLM were estimated from weight, sex, and percent fat from DXA (R2 = 0.91 and 0.84 vs total body DXA, respectively). We report hazard ratios (HR) from Cox regression models estimating time to first incident major osteoporotic fracture (MOF) and hip fracture, adjusted for fracture risk; osteoporosis medication was included as an interaction term and used to stratify analyses. RESULTS: We included 21,249 individuals (mean 67 [SD 10] years, 95% female, 37% on osteoporosis medication). The mean follow-up was 7 years (SD 4). A total of 1868 and 548 people had incident MOF and hip fracture, respectively. People with prior ALM loss (HR per SD 1.09, 95% CI 1.04-1.15) or TBLM loss (HR per SD 1.09, 95% CI 1.42-1.14) had a higher risk of MOF. Hip fracture risk was greater in people with prior ALM loss (HR per SD 1.22, 95% CI 1.12-1.33) and TBLM loss (HR per SD 1.26, 95% CI 1.16-1.38). There were no interactions with anti-osteoporosis medication use (all p > 0.3). When restricted to people on anti-osteoporosis medication, each SD in ALM or TBLM loss was associated with 8-9% increased MOF risk and 18-23% increased hip fracture risk. CONCLUSIONS: Loss of lean mass is associated with increased fracture risk among individuals on anti-osteoporosis medication. Patients should be encouraged to pursue strategies to prevent sarcopenia.

Introduction of an order set after hip fracture improves osteoporosis medication initiation and persistence: a population-based before-after analysis.

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.

Secular Trends in Peak Bone Mineral Density: The National Health and Nutrition Examination Survey 1999-2018.

Peak bone mineral density (BMD) is one of the most important factors influencing the development of osteoporosis. It was predicted that a 10% increase in peak BMD will delay the onset of osteoporosis by 13 years. However, changes in peak BMD over time are unknown. This study aimed to investigate secular trends in peak BMD among young adults in the United States. Based on the National Health and Nutrition Examination Survey from 1999-2018, 3,975 males aged 19-28 years and 2370 females aged 31-40 years were our target population for estimating peak lumbar spine BMD. BMD was measured by dual-energy X-ray absorptiometry. Generalized linear models adjusted for multiple covariates were used to examine the secular trends in peak BMD in males and females, respectively. Secular trends for peak lumbar spine BMD from 1999-2000 to 2017-2018 were not statistically significant in males or females (all Plinear and Pquadratic > 0.05). Similar results were observed in race/ethnicity subgroups (all Plinear and Pquadratic > 0.05). However, in stratified analyses by obesity category, peak lumbar spine BMD in obese males and females increased from 1999-2000 to 2009-2010 and then decreased until 2017-2018, while peak lumbar spine BMD in non-obese females decreased from 1999-2000 to 2005-2006 and then increased until 2017-2018 (all Pquadratic < 0.05). Peak lumbar spine BMD was greater in obese males and females than in non-obese males and females up to 2009-2010, but not from 2011-2012 onwards. Overall, there were no significant secular trends in peak lumbar spine BMD. However, secular trends differed between obese and non-obese groups.

Fracture Risk Associated with Different Numbers and Combinations of Lumbar Vertebrae: The Manitoba BMD Registry.

Bone mineral density (BMD) is widely used for assessment of fracture risk. For the lumbar spine, BMD is typically measured from L1-L4 as it provides the largest area for assessment with the best measurement precision. Structural artifact often confounds spine BMD in clinical practice, and the International Society for Clinical Densitometry (ISCD) recommends removing vertebrae with artifact when reporting spine BMD. In its most recent position statements, the ISCD recommended against the use of a single vertebra when reporting spine BMD but stated that further studies should be done. The current analysis was performed to compare the performance of BMD from different numbers and combination of vertebral levels on fracture prediction in a large clinical registry of DXA tests for the Province of Manitoba, Canada. The study population comprised 39,727 individuals aged 40 years and older (mean age 62.7 years, 91.0 % female) with baseline DXA after excluding those with evidence of structural artifact. Mean follow-up for ascertaining fracture outcomes was 8.7 years. Area under the curve (AUC) for incident fracture risk stratification was statistically significant regardless of the BMD measurement site or fracture outcome. AUC differences with the various numbers and combinations of vertebral levels including a single vertebral body were small (less than or equal to 0.01). More substantial AUC differences were seen for femoral neck and total hip BMD versus L1-L4 BMD, approaching 0.1 for hip fracture stratification. In summary, we found that using combinations of fewer than 4 vertebrae including individual lumbar vertebrae predicted incident fractures. Importantly, differences between these different combinations were small when compared with L1-L4. Spine BMD was a better predictor of incident spine fracture compared to the hip, whereas the hip was better for hip fracture and overall fracture prediction.

The Effect of Smoking Cessation versus Current Smoking on Fracture Risk: The Manitoba BMD Registry.

Current tobacco smoking is included in FRAXTM calculator for fracture risk assessment. It is unknown whether previous smoking increases the risk of fracture. The current analysis was performed to compare incident fracture risk associated with current smoking, smoking cessation and non-smoking. The study population comprised 18,115 individuals aged 40 years and older (mean age 68.8 years, 95.1% female) from a large clinical registry of DXA tests for the Province of Manitoba, Canada, with two consecutive visits (mean interval 4.4 years) where current smoking was recorded. Smokers (N=1620) were defined as those reporting current smoking at visit 2 (index date), non-smokers (N=15,942) as answering no to current smoking at both visits, and ex-smokers (N=553) as answering yes to current smoking at visit 1 but no at visit 2. Incident fractures were identified through healthcare data linkage. Compared with non-smokers, risk for any incident fracture (primary outcome) was significantly greater in current smokers (hazard ratio [HR] 1.41, 95% CI 1.19-1.67 adjusted for age/sex; HR 1.22, 95% CI 1.03-1.44 full adjusted) and ex-smokers (HRs 1.56, 95% CI 1.19-2.024 and 1.42, 95% CI 1.09-1.86, respectively). Similar directions and magnitudes of effect were seen for incident major osteoporotic fractures and hip fractures (secondary outcomes), with point estimates for ex-smokers that were close to current smokers. In summary, recent smoking cessation was associated with ongoing increased short-term fracture risk similar to current smoking. Larger studies are needed to better define the time course of fracture risk after smoking cessation.

Estimating Lumbar Spine Least Significant Change for Fewer than Four Vertebrae: The Manitoba BMD Registry.

INTRODUCTION: The International Society of Clinical Densitometry recommends omitting lumbar vertebrae affected by structural artifact from spine BMD measurement. Since reporting fewer than 4 vertebrae reduces spine BMD precision, least significant change (LSC) needs to be adjusted upwards when reporting spine BMD change based on fewer than 4 vertebrae. METHODOLOGY: In order to simplify estimating LSC from combinations of vertebrae other than L1-L4 (denoted LSCL1-4 ), we analyzed 879 DXA spine scan-pairs from the Manitoba BMD Program's ongoing precision evaluation. The additional impact on the LSC of performing the second scan on the same day vs different day was also assessed. RESULTS: LSC progressively increased when fewer vertebrae were included, and also increased when the scans were performed on different days. We estimated that the LSCL1-4 should be adjusted upwards by 7 %, 24 % and 65 % to approximate the LSC for 3, 2, or 1 vertebral body, respectively. To additionally capture the greater LSC when the precision study was done on different days, LSCL1-4 derived from a precision study where scans were done on the same day should be adjusted upwards by 39 %, 60 % and 112 % for 3, 2, or 1 vertebral body, respectively. CONCLUSION: LSCL1-4 derived from a precision study where scans are performed on the same day can be used to estimate LSC for fewer than 4 vertebrae and for scans performed on different days.

Assessing Change in Spine Bone Density from Different Numbers and Combinations of Lumbar Vertebrae: The Manitoba BMD Registry.

INTRODUCTION: Change in bone mineral density (BMD) is considered significant when it exceeds the 95 % least significant change (LSC) derived from that facility's precision study. The lumbar spine is often affected by structural artifact such that not all four lumbar vertebrae are evaluable. Guidelines suggest using a site-matched LSC when omitting vertebrae from the BMD measurement. The current study describes significant BMD change related to intervening anti-osteoporosis treatment for different numbers and combinations of lumbar vertebrae using site-matched LSC values. METHODOLOGY: We identified 10,526 untreated adult women mean age 59.6 years with baseline and repeat spine BMD testing (mean interval 4.7 years) where all 4 lumbar vertebrae were evaluable. Change in spine BMD for different combinations of lumbar vertebrae was assessed in relation to intervening anti-resorptive treatment, contrasting women with high treatment exposure (medication possession ratio, MPR ≥ 0.8) versus women who remained untreated. Site-matched LSC values were derived from 879 test-retest precision measurements. RESULTS: There was consistent linear trend between increasing MPR and BMD change exceeding the LSC for all lumbar vertebral combinations, positive with BMD increase and negative with BMD decrease (all p-trend <0.001). In the high treatment exposure group, mean percent increases in spine BMD were similar for all vertebral combinations, from L1-4 to a single vertebra. In untreated women, mean percent decreases in spine BMD were also similar for all vertebral combinations. The net treatment response (proportion of women with treatment-concordant changes minus proportion with treatment-discordant changes exceeding the LSC) was 29.7 % for 4 vertebrae, 27.5-30.0 % for 3 vertebrae, 22.4-28.5 % for 2 vertebrae, and 18.1-21.9 % for a single vertebra. CONCLUSIONS: All numbers and combinations of lumbar vertebrae, when used in conjunction with site-matched LSC values, can provide clinically meaningful follow-up in treated and untreated patients, even when spine BMD is based on a single vertebral body.

Bone Mineral Density Monitoring in Contiguous versus Non-Contiguous Lumbar Vertebrae: The Manitoba BMD Registry.

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.

Effects of Lumbar Spine Vertebral Fractures on Trabecular Bone Score (TBS): The Manitoba BMD Registry.

Trabecular bone score (TBS) is a BMD-independent risk factor for fracture. During BMD reporting, it is standard practice to exclude lumbar vertebral levels affected by structural artifact. It is uncertain whether TBS is affected by lumbar spine fractures. The current study examined the effect of lumbar spine compression fractures on TBS measurements. We identified 656 individuals with vertebral fractures (mean age 75.8 ± 7.9 years, 90.9% female) who had lumbar spine DXA, TBS measurements from L1-L4 and vertebral fracture assessment (VFA) for identifying vertebral fractures. There were 272 cases with lumbar spine fractures and 384 controls with only thoracic spine fractures. L1 TBS and BMD were significantly greater in those with than without lumbar fractures (p< 0.001) but did not significantly differ for other vertebral levels or for L1-L4 combined. TBS and BMD measurements were then renormalized to remove level-specific differences (denoted rTBS and rBMD). The mean difference (all fractured minus all non-fractured vertebrae) was +0.040 (+3.3%) for rTBS and +0.088 g/cm2 (+9.5%) for rBMD (both p <0.001). The largest effect was for L1 with mean difference +0.058 (+4.9%) for rTBS and +0.098 g/cm2 (+10.6%) for rBMD (both p <0.001). The mean difference between fractured and non-fractured levels for rTBS was +0.028 (+2.4%) for grade 1, +0.036 (+3.0%) for grade 2 and +0.059 (+5.0%) for grade 3 fractures; for rBMD +0.051 (+5.5%), +0.076 (+8.2%) and +0.151 (+16.4%) g/cm2, respectively. The impact of excluding lumbar vertebral levels with fracture from the L1-L4 TBS measurement overall was small (-0.011 [-1.0%]; p<0.001) and was also small for grade 3 fractures (-0.020 [-1.7%]; p<0.001). In summary, TBS is mildly increased by VFA-confirmed lumbar vertebral fractures, but the percentage effect is much smaller (less than half) than seen for BMD and minimally affects TBS measured from L1-L4. This would support the use of L1-L4 without exclusions in individuals with lumbar vertebral fractures.

Clinical Use of Trabecular Bone Score: The 2023 ISCD Official Positions.

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.

Fracture prediction in rheumatoid arthritis: validation of FRAX with bone mineral density for incident major osteoporotic fractures.

OBJECTIVES: FRAX® uses clinical risk factors, with or without bone mineral density (BMD), to calculate 10-year fracture risk. Rheumatoid arthritis (RA) is a risk factor for osteoporotic fracture and a FRAX input variable. FRAX predates the current era of RA treatment. We examined how well FRAX predicts fracture in contemporary RA patients. METHODS: Administrative data from patients receiving BMD testing were linked to the Manitoba Population Health Research Data Repository. Observed cumulative 10-year Major Osteoporotic Fracture (MOF) probability was compared with FRAX-predicted 10-year MOF probability with BMD for assessing calibration. MOF risk stratification was assessed using Cox regression. RESULTS: RA patients (N = 2,099, 208 with incident MOF) and non-RA patients (N = 2,099, with 165 incident MOF) were identified. For RA patients, FRAX predicted 10-year risk was 13.2% and observed 10-year MOF risk was 13.2% (95% CI 11.6% to 15.1%). The slope of the calibration plot was 0.67 (95% CI 0.53-0. 81) in those with RA vs 0.98 (95% CI 0.61-1.34) in non-RA patients. Risk was overestimated in RA patients with high FRAX scores (>20%), but FRAX was well-calibrated in other groups. FRAX stratified risk in those with and without RA (hazard ratios 1.52, 95% 1.25-1.72 vs 2.00, 95% 1.73-2.31), with slightly better performance in the latter (p-interaction = 0.004). CONCLUSIONS: FRAX predicts fracture risk in contemporary RA patients but may slightly overestimate risk in those already at high predicted risk. Thus, the current FRAX tool continues to be appropriate for fracture risk assessment in RA patients.

Fracture risk and assessment in adults with cancer.

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.

Liver enzyme inducing anticonvulsant drug use is associated with prevalent vertebral fracture.

Among those who use of liver-enzyme inducing anticonvulsant medication for more than 2 years, 27% have a prevalent vertebral fracture on vertebral fracture assessment (VFA) lateral spine imaging. VFA imaging at the time of bone densitometry may be appropriate for older individuals who are chronic users of these medications. PURPOSE: It is unclear whether prevalent vertebral fractures are associated with use of anticonvulsant drugs, especially those that induce liver enzymes (LEI) that metabolize drugs and vitamin D. Our purpose was to estimate the prevalence of vertebral fracture on densitometric lateral spine images according to duration of prior anticonvulsant medication use. METHODS: Our study population was 11,822 individuals (mean [sd] age 76.1 [6.8] years, 94% female) who had bone densitometry with VFA between 2010 and 2018. Cumulative prior exposure to LEI anticonvulsants (carbamazepine, phenobarbital, phenytoin, valproic acid, n = 538), non-LEI anticonvulsants (clonazepam, gabapentin, levetiracetam, others, n = 2786), and other non-clonazepam benzodiazepines (n = 5082) was determined using linked pharmacy records. Prevalent vertebral fractures were identified on VFA images using the modified ABQ method. Logistic regression models were used to estimate the association of anticonvulsant drug exposure with prevalent vertebral fractures. RESULTS: Prevalence of one or more vertebral fractures was 16.1% for the entire analytic cohort, and 27.0%, 19.0%, and 18.5% for those with ≥ 2 years of prior LEI anticonvulsant use, non-LEI anticonvulsant use, and other benzodiazepine use, respectively. Adjusted for multiple covariates, use of prior LEI anticonvulsant medication for ≥ 2 years was associated with prevalent fracture on VFA (OR 1.48 [95% CI 1.04, 2.10]). CONCLUSION: LEI anticonvulsant use for ≥ 2 years is associated with higher vertebral fracture prevalence. Lateral spine VFA imaging at the time of bone densitometry may be appropriate for older individuals who have used LEI anticonvulsant medications for ≥ 2 years.

Fracture rate increases after immune checkpoint inhibitor treatment: a potential new immune related adverse event.

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.

Bone density and trabecular bone score to predict fractures in adults aged 20-39 years: a registry-based study.

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.

Adjusting conventional FRAX estimates of fracture probability according to the number of prior falls in the preceding year.

A greater propensity to falling is associated with higher fracture risk. This study provides adjustments to FRAX-based fracture probabilities accounting for the number of prior falls. INTRODUCTION: Prior falls increase subsequent fracture risk but are not currently directly included in the FRAX tool. The aim of this study was to quantify the effect of the number of prior falls on the 10-year probability of fracture determined with FRAX®. METHODS: We studied 21,116 women and men age 40 years or older (mean age 65.7 ± 10.1 years) with fracture probability assessment (FRAX®), self-reported falls for the previous year, and subsequent fracture outcomes in a registry-based cohort. The risks of death, hip fracture, and non-hip major osteoporotic fracture (MOF-NH) were determined by Cox proportional hazards regression for fall number category versus the whole population (i.e., an average number of falls). Ten-year probabilities of hip fracture and major osteoporotic fracture (MOF) were determined according to the number of falls from the hazards of death and fracture incorporated into the FRAX model for the UK. The probability ratios (number of falls vs. average number of falls) provided adjustments to conventional FRAX estimates of fracture probability according to the number of falls. RESULTS: Compared with the average number of falls, the hazard ratios for hip fracture, MOF-NH and death were lower than unity in the absence of a fall history. Hazard ratios increased progressively with an increasing number of reported falls. The probability ratio rose progressively as the number of reported falls increased. Probability ratios decreased with age, an effect that was more marked the greater the number of prior falls. CONCLUSION: The probability ratios provide adjustments to conventional FRAX estimates of fracture probability according to the number of prior falls.

Variation in bone mineral density and fractures over 20 years among Canadians: a comparison of the Canadian Multicenter Osteoporosis Study and the Canadian Longitudinal Study on Aging.

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/cm2 [- 0.021; - 0.014]) and men (- 0.006 g/cm2 [- 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.

Trabecular Bone Score (TBS) Cross-Calibration for GE Prodigy and IDXA Scanners.

Dual-energy X-ray absorptiometry (DXA) is used for osteoporosis diagnosis, fracture prediction and to monitor changes in bone mineral density (BMD). Change in DXA instrumentation requires formal cross-calibration and procedures have been described by the International Society for Clinical Densitometry. Whether procedures used for BMD cross-calibration are sufficient to ensure lumbar spine trabecular bone score (TBS) cross-calibration is currently uncertain. The Manitoba Bone Density Program underwent a program-wide upgrade in DXA instrumentation from GE Prodigy to iDXA in 2012, and a representative a sample of 108 clinic patients were scanned on both instruments. Lumbar spine TBS (L1-L4) measurements were retrospectively derived in 2013. TBS calibration phantoms were not available at our site when this was performed. We found excellent agreement for lumbar spine BMD, without deviation from the line of perfect agreement, and low random error (standard error of the estimate [SEE] 2.54% of the mean). In contrast, spine TBS (L1-L4) showed significant deviation from the line of identity: TBS(iDXA) = 0.730 x TBS(Prodigy) + 0.372 (p<0.001 for slope and intercept); SEE 5.12% of the mean with negative bias (r=-0.550). Results were worse for scans acquired in thick versus standard mode, but similar when the population was stratified as BMI < or > 35 kg/m2. In summary, it cannot be assumed that just because BMD cross-calibration is good that this applies to TBS. This supports the need for using TBS phantom calibration to accommodate between-scanner differences as part of the manufacturer's TBS software installation.

Effects of Severe Lumbar Spine Structural Artifact on Trabecular Bone Score (TBS): The Manitoba BMD Registry.

Trabecular bone score (TBS) is a bone mineral density (BMD)-independent risk factor for fracture. During DXA analysis and BMD reporting, it is standard practice to exclude lumbar vertebral levels affected by structural artifact. Although TBS is relatively insensitive to degenerative artifact, it is uncertain whether TBS is still useful in the presence extreme structural artifact that precludes reliable spine BMD measurement even after vertebral exclusions. Among individuals aged 40 years and older undergoing baseline DXA assessment from September 2012 to March 2018 we identified three mutually exclusive groups: spine BMD reporting performed without exclusions (Group 1, N=12,865), spine BMD reporting performed with vertebral exclusions (Group 2, N=4867), and spine BMD reporting not performed due to severe structural artifact (Group 3, N=1541). No significant TBS difference was seen for Group 2 versus Group 1 (referent), whereas TBS was significantly greater in Group 3 (+0.041 partially adjusted, +0.043 fully adjusted). When analyzed by the reason for vertebral exclusion, multilevel degenerative changes significantly increased TBS (+0.041 partially adjusted, +0.042 fully adjusted), while instrumentation significantly reduced TBS (-0.059 partially adjusted, -0.051 fully adjusted). Similar results were seen when analyses were restricted to those in Group 3 with a single reason for vertebral exclusions, and when follow up scans were also included. During mean follow-up of 2.5 years there were 802 (4.2 %) individuals with one or more incident fractures. L1-L4 TBS showed significant fracture risk stratification in all groups including Group 3 (P-interaction >0.4). In conclusion, lumbar spine TBS can be reliably measured in the majority of lumbar spine DXA scans, including those with artifact affecting up to two vertebral levels. However, TBS is significantly affected by the presence of extreme structural artifact in the lumbar spine, especially those with multilevel degenerative disc changes and/or instrumentation that precludes reliable BMD reporting.

Fracture Prediction from Trabecular Bone Score is Unaffected by Anti-Resorptive Treatment: A Registry-Based Cohort Study.

Trabecular bone score (TBS) predicts osteoporotic fractures independent of bone mineral density (BMD) and clinical risk factors. The aim of this study was to explore whether anti-resorptive treatment affects fracture risk prediction from TBS using a large clinical registry that includes all dual-energy X-ray absorptiometry (DXA) tests for the Province of Manitoba, Canada. Cohort 1 included 53,863 individuals aged ≥ 40 years (11.4% men; mean age 64.1 years) who had not received any anti-resorptive therapy in the year prior the baseline DXA. Cohort 2 comprised 22,917 individuals aged ≥ 40 years (6% men, mean age 66.7 years) undergoing a second DXA visit. Anti-resorptive medication was initiated in the first year after DXA in 13,439 (25%) individuals from Cohort 1 (87.9% bisphosphonates); among Cohort 2 8,864 (38.7%) had received anti-resorptive medication in the year before DXA (77.8% bisphosphonates). Incident major osteoporotic fracture (MOF), hip fracture and any fracture were identified over mean follow up 8.6 and 7.0 years for Cohorts 1 and 2, respectively. Area under the curve showed significant risk stratification for all fracture types and treatment levels, whether treatment was initiated after TBS measurement (Cohort 1) or prior to TBS measurement (Cohort 2). In Cox regression models, without and with covariate adjustment, fracture prediction from TBS was unaffected by anti-resorptive medication use (p-interaction >0.5 for all analyses). In conclusion, TBS was a robust predictor of fracture in models adjusted for clinical risk factors and BMD. The use of anti-resorptive therapy, either in the year before or following TBS measurement, did not attenuate fracture risk prediction by TBS compared to untreated individuals.