Skeletal fluorosis: an uncommon cause, yet a rescue treatment?

PURPOSE: Skeletal fluorosis (SF) results from chronic exposure to fluoride (F-) causing excessive aberrantly mineralized brittle bone tissue, fractures, and exostoses. There is no established treatment other than avoiding the source of F-. Still, excess F- can persist in bone for decades after exposure ceases. CASE PRESENTATION: A 50-year-old woman presented with multiple, recurrent, low AQ2 trauma fractures yet high radiologic bone mineral density. Serum F- was elevated, and osteomalacia was documented by non-decalcified transiliac biopsy. She reported intermittently "huffing" a keyboard cleaner containing F- (difluoroethane) for years. Following cessation of her F- exposure, we evaluated the administration of the parathyroid hormone analog, abaloparatide, hoping to increase bone remodeling and diminish her skeletal F- burden. CONCLUSION: Due to the prolonged half-life of F- in bone, SF can cause fracturing long after F- exposure stops. Anabolic therapy approved for osteoporosis, such as abaloparatide, may induce mineralized bone turnover to replace the poorly mineralized osteomalacic bone characteristic of SF and thereby diminish fracture risk. Following abaloparatide treatment for our patient, there was a decrease in bone density as well as a reduction in F- levels.

Periprosthetic fractures are osteoporotic fractures: missed opportunities for osteoporosis diagnosis.

Joint replacement surgery is common in older adults, leading to increasing periprosthetic fracture (PPFx) occurrence. We reviewed all PPFx seen over a 4-year period at an academic hospital. Clinical osteoporosis could be diagnosed based on existing data in 104 (67%) at the time of PPFx. Periprosthetic fractures are generally osteoporosis-related. PURPOSE: Periprosthetic fractures (PPFx) cause morbidity, mortality, and cost. This study's purpose was to describe osteoporosis-related data available at the time of PPFx. METHODS: The electronic medical record (EMR) of PPFx patients seen over 4 years in a university orthopedic practice were reviewed. Demographic data and osteoporosis relevant parameters were collected. Prior DXA studies were reviewed, and L1 Hounsfield unit (HU) measurements were performed on CT scans obtained within 2 years before PPFx. Clinical osteoporosis was defined as prior diagnosis, prescribed osteoporosis treatment, T-score ≤ - 2.5, HU ≤ 100, or prior fracture. RESULTS: Records of 156 PPFx patients (115 F/41 M), mean (SD) age 75.4 (11.9), were reviewed. Almost all 153/156 (98%) of these fractures were femoral. Falls caused 139 (89%); 12 (8%) were spontaneous. Mean time post-arthroplasty was 7.9 (6.3) years. Prior fragility fracture(s) occurred in 72 (46%); 14 were PPFx. Osteoporosis was previously diagnosed in 45 (29%) and medications prescribed in 41 (26%). Prior to PPFx, DXA data were available in 62, mean (SD) lowest T-score was - 1.9 (0.9) and was ≤ - 2.5 in 19. CT data were available in 46; mean (SD) L1 HU was 79.0 (29.4) and was ≤ 100 in 35. Based on existing data, clinical osteoporosis could have been diagnosed in 104 (67%) at the time of PPFx. CONCLUSION: Periprosthetic fractures are osteoporosis-related. They occur in older adults, often female, and result from falls; BMD, when assessed, is low. Data available at the time of PPFx often allows osteoporosis diagnosis; this should prompt evaluation and pharmacologic treatment consideration.

Dual-energy X-ray Absorptiometry Trends Among US Medicare Beneficiaries: 2005-2019.

INTRODUCTION: Bone density measured using dual-energy X-ray absorptiometry (DXA) volume, performance site and interpreters have changed in the US since 2005. The purpose of this report is to provide updated trends in DXA counts, rates, place of service and interpreter specialty for the Medicare fee-for-service population. METHODS: The 100 % Medicare Physician/Supplier Procedure Summary Limited Data Set between 2005-2019 was used. DXA counts and annual rates per 10,000 Medicare beneficiaries were calculated. Annual distributions of scan performance location, provider type and interpreter specialty were described. Place of service trends (significance assigned at p < 0.05) of the mean annual share of DXA utilization were identified using linear regression. RESULTS: Annual DXA use per 10,000 beneficiaries peaked in 2008 at 832, declined to 656 in 2015 then increased (p < 0.001) by 38 per year to 807 in 2019. From 2005 to 2019 DXA performance in office settings declined from 70.7 % to 47.2 %. Concurrently, outpatient hospital (OH) DXA increased from 28.6 % to 51.7 %. In 2005, 43.5 % of DXAs were interpreted by radiologists. This increased (p < 0.001) in the office and OH, averaging 0.3 and 2.0 percentage points per year respectively, reaching 73.5 % in 2019. Interpretation by most non-radiologist specialties declined (p < 0.001). CONCLUSIONS: From 2005-2019, total DXA use among Medicare beneficiaries declined reaching a nadir in 2015 then returned to 2005 levels by 2019. Office DXA declined since 2005 with 51.7 % of all scans now occurring in an OH setting. The proportion of DXAs interpreted by radiologists increased over time, reaching 73.5 % in 2019.

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.

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.

Periprosthetic fractures: an unrecognized osteoporosis crisis.

Total joint replacement is common and increasing. Many of these patients have low bone mineral density preoperatively, and arthroplasty leads to bone loss. As falls are common before and after arthroplasty, it is unsurprising that periprosthetic fractures, defined as those associated with an orthopedic device, whether a joint replacement or other internal fixation devices, are not rare. These fractures engender morbidity and mortality comparable to osteoporosis-related hip fractures but remain largely unrecognized and untreated by osteoporosis/metabolic bone disease clinicians. Indeed, recent osteoporosis guidelines are silent regarding periprosthetic fractures. The purposes of this clinical review are to briefly describe the epidemiology of arthroplasty procedures and periprosthetic fractures, raise awareness that these fractures are osteoporosis-related, and suggest approaches likely to reduce their occurrence. Notably, bone health evaluation is essential following the occurrence of a periprosthetic fracture to reduce subsequent fracture risk. Importantly, in addition to such secondary fracture prevention, primary prevention, i.e., bone health assessment and optimization prior to elective orthopedic procedures, is appropriate.

MRI-based vertebral bone quality score: relationship with age and reproducibility.

Vertebral bone quality (VBQ) score is an opportunistic measure of bone mineral density using routine preoperative MRI in spine surgery. VBQ score positively correlates with age and is reproducible across serial scans. However, extrinsic factors, including MRI machine and protocol, affect the VBQ score and must be standardized. PURPOSE: The purposes of this study were to determine whether VBQ score increased with age and whether VBQ remained consistent across serial MRI studies obtained within 3 months. METHODS: This retrospective study evaluated 136 patients, age 20-69, who received two T1-weighted lumbar MRI within 3 months of each other between January 2011 and December 2021. VBQ(L1-4) score was calculated as the quotient of L1-L4 signal intensity (SI) and L3 cerebral spinal fluid (CSF) SI. VBQ(L1) score was calculated as the quotient of L1 SI and L1 CSF SI. Regression analysis was performed to determine correlation of VBQ(L1-4) score with age. Coefficient of variation (CV) was used to determine reproducibility between VBQ(L1-4) scores from serial MRI scans. RESULTS: One hundred thirty-six patients (mean ± SD age 44.9 ± 12.5 years; 53.7% female) were included in this study. Extrinsic factors affecting the VBQ score included patient age, MRI relaxation time, and specific MRI machine. When controlling for MRI relaxation/echo time, the VBQ(L1-4) score was positively correlated with age and had excellent reproducibility in serial MRI with CV of 0.169. There was excellent agreement (ICC > 0.9) of VBQ scores derived from the two formulas, VBQ(L1) and VBQ(L1-4). CONCLUSION: Extrinsic factors, including MRI technical factors and age, can impact the VBQ(L1-4) score and must be considered when using this tool to estimate bone mineral density (BMD). VBQ(L1-4) score was positively correlated with age. Reproducibility of the VBQ(L1-4) score across serial MRI is excellent especially when controlling for technical factors, supporting use of the VBQ score in estimating BMD. The VBQ(L1) score was a reliable alternative to the VBQ(L1-4) score.

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.

Proposed bone health screening protocol to identify total knee arthroplasty patients for preoperative DXA.

This study evaluates a novel, simple bone health screening protocol composed of patient sex, age, fracture history, and FRAX risk to identify total knee arthroplasty patients for preoperative DXA. Findings supported effectiveness, with sensitivity of 1.00 (CI 0.92-1.00) and specificity of 0.54 (CI 0.41-0.68) when evaluating for clinical osteoporosis. PURPOSE: Bone health optimization is a process where osteoporotic patients are identified, evaluated via modalities such as dual-energy X-ray absorptiometry (DXA), and treated when indicated. There are currently no established guidelines to determine who needs presurgical DXA. This study evaluates the effectiveness of a simple screening protocol to identify TKA patients for preoperative DXA. METHODS: This prospective cohort study began on September 1, 2019, and included 100 elective TKA patients. Inclusion criteria were ≥ 50 years and primary TKA. All patients obtained routine clinical DXA. The screening protocol defining who should obtain DXA included meeting any of the following: female ≥ 65, male ≥ 70, fracture history after age 50, or FRAX major osteoporotic fracture risk without bone mineral density (BMD) adjustments ≥ 8.4%. Osteoporosis was defined by the World Health Organization (WHO) criteria (T-score ≤ - 2.5) or clinically (T-score ≤ - 2.5, elevated BMD-adjusted FRAX risk, or prior hip/spine fracture). Sensitivity and specificity were calculated. RESULTS: The study included 68 females and 32 males, mean age 67.2 ± 7.7. T-score osteoporosis was observed in 16 patients while 43 had clinical osteoporosis. Screening criteria recommending DXA was met by 69 patients. Screening sensitivity was 1.00 (CI 0.79-1.00) and specificity was 0.37 (CI 0.27-0.48) for identifying patients with T-score osteoporosis. Similar sensitivity of 1.00 (CI 0.92-1.00) and specificity of 0.54 (CI 0.41-0.68) were found for clinical osteoporosis. CONCLUSIONS: A simple screening protocol identifies TKA patients with T-score and clinical osteoporosis for preoperative DXA with high sensitivity in this prospective cohort study.

Intraoperative physician assessment of bone: correlation to bone mineral density.

This study evaluated the intraoperative physician assessment (IPA) of bone status at time of total knee arthroplasty. IPA was highly correlated with distal femur and overall bone mineral density. When IPA identifies poor bone status, formal bone health assessment is indicated. PURPOSE: Intuitively, intraoperative physician assessment (IPA) would be an excellent measure of bone status gained through haptic feedback during bone preparation. However, no studies have evaluated the orthopedic surgeon's ability to do so. This study's purpose, in patients undergoing total knee arthroplasty (TKA), was to relate IPA with (1) the lowest bone mineral density (BMD) T-score at routine clinical sites; and (2) with distal femur BMD. METHODS: Seventy patients undergoing TKA by 3 surgeons received pre-operative DXA. Intraoperatively, bone quality was assessed on a 5-point scale (1 excellent to 5 poor) based on tactile feedback to preparation. Demographic data, DXA results, and IPA score between surgeons were compared by factorial ANOVA. Lowest T-score and distal femur BMD were associated with IPA using Spearman's correlation. RESULTS: The mean (SD) age and BMI were 65.8 (7.6) years and 31.4 (5.1) kg/m2, respectively. Patient demographic data, BMD, and IPA (mean [SD] = 2.74 [1.2]) did not differ between surgeons. IPA correlated with the lowest T-score (R = 0.511) and distal femur BMD (R = 0.603-0.661). Based on the lowest T-score, no osteoporotic patients had an IPA above average, and none with normal BMD was classified as having poor bone. CONCLUSIONS: IPA is highly correlated with local (distal femur) and overall BMD. This study supports the International Society for Clinical Densitometry position that surgeon concern regarding bone quality should lead to bone health assessment. As IPA is comparable between surgeons, it is logical this can be widely applied by experienced orthopedic surgeons. Future studies evaluating IPA at other anatomic sites are indicated.

Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.

Clinical practice guideline for management of osteoporosis and fracture prevention in Canada: 2023 update.

BACKGROUND: In Canada, more than 2 million people live with osteoporosis, a disease that increases the risk for fractures, which result in excess mortality and morbidity, decreased quality of life and loss of autonomy. This guideline update is intended to assist Canadian health care professionals in the delivery of care to optimize skeletal health and prevent fractures in postmenopausal females and in males aged 50 years and older. METHODS: This guideline is an update of the 2010 Osteoporosis Canada clinical practice guideline on the diagnosis and management of osteoporosis in Canada. We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework and quality assurance as per Appraisal of Guidelines for Research and Evaluation (AGREE II) quality and reporting standards. Primary care physicians and patient partners were represented at all levels of the guideline committees and groups, and participated throughout the entire process to ensure relevance to target users. The process for managing competing interests was developed before and continued throughout the guideline development, informed by the Guideline International Network principles. We considered benefits and harms, patient values and preferences, resources, equity, acceptability and feasibility when developing recommendations; the strength of each recommendation was assigned according to the GRADE framework. RECOMMENDATIONS: The 25 recommendations and 10 good practice statements are grouped under the sections of exercise, nutrition, fracture risk assessment and treatment initiation, pharmacologic interventions, duration and sequence of therapy, and monitoring. The management of osteoporosis should be guided by the patient's risk of fracture, based on clinical assessment and using a validated fracture risk assessment tool. Exercise, nutrition and pharmacotherapy are key elements of the management strategy for fracture prevention and should be individualized. INTERPRETATION: The aim of this guideline is to empower health care professionals and patients to have meaningful discussions on the importance of skeletal health and fracture risk throughout older adulthood. Identification and appropriate management of skeletal fragility can reduce fractures, and preserve mobility, autonomy and quality of life.

Advances in Osteoporosis Therapy: Focus on Osteoanabolic Agents, Secondary Fracture Prevention, and Perioperative Bone Health.

PURPOSE OF REVIEW: This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including those undergoing bone-related surgery. RECENT FINDINGS: Two osteoanabolic agents, abaloparatide and romosozumab, were recently approved for treatment of patients with osteoporosis at high fracture risk. These agents, along with teriparatide, are valuable for primary and secondary fracture prevention. Orthopedic surgeons are well positioned to facilitate secondary fracture prevention via referrals to fracture liaison services or other bone health specialist colleagues. This review aims to help surgeons understand how to identify patients with sufficiently high fracture risk to warrant consideration of osteoanabolic therapy. Recent evidence around the perioperative use and potential benefits of osteoanabolic agents in fracture healing and other orthopedic settings (e.g., spinal fusion and arthroplasty) in individuals with osteoporosis is also discussed. Osteoanabolic agents should be considered for patients with osteoporosis at very high fracture risk, including those with prior osteoporotic fractures and those with poor bone health who are undergoing bone-related surgery.

Ethnicity and Fracture Risk Stratification from Trabecular Bone Score in Canadian Women: The Manitoba BMD Registry.

Lumbar spine Trabecular Bone Score (TBS), a grey-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 and controversial question is whether there are ethnic differences that affect the utility of TBS for fracture risk assessment. The current analysis examined whether self-identified ethnicity (White, Asian, Black) in women age 40 years and older referred for DXA testing affected fracture risk stratification from TBS using a large clinical registry. The study population comprised 63,078 White women, 1,915 Asian women and 329 Black women (n=329) with mean follow up 9.0±5.2 years. There were between group differences in BMI (Black>White>Asian), lumbar spine fat percentage (Asian>White>Black) and lumbar spine tissue thickness (Black>White>Asian). Despite this, lumbar spine TBS was not significantly different between the subgroups, though there was a significant difference in lumbar spine and total hip BMD (Black >White>Asian). TBS provided significant stratification for MOF and any fracture for all ethnicity subgroups, and for hip fracture in White and Asian subgroups (insufficient numbers for analysis in Black women). No significant difference in White vs. Asian or White vs. Black women were identified using a Bonferroni adjusted p-value. In summary, we found that lumbar spine TBS measurements were similar among White, Asian and Black women referred for DXA assessment in Manitoba, Canada. TBS and BMD measurements significantly stratified fracture risk in all three populations without a meaningful difference between groups. This suggests that TBS does not need to be used differently in White vs. non-White populations.

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.

Trabecular Bone Score Vertebral Exclusions Affect Risk Classification and Treatment Recommendations: The Manitoba Bmd Registry.

Lumbar spine trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. Lumbar vertebral levels that show structural artifact are excluded from BMD measurement. TBS is relatively unaffected by degenerative artifact, and it is uncertain whether the same exclusions should be applied to TBS reporting. To gain insight into the clinical impact of vertebral exclusion on TBS, we examined the effect of lumbar vertebral exclusions in routine clinical practice on tertile-based TBS categorization and TBS adjusted FRAX-based treatment recommendations. The study population consisted of 71,209 individuals aged 40 years and older with narrow fan-beam spine DXA examinations and retrospectively-derived TBS. During BMD reporting, 34.3% of the scans had one or more vertebral exclusions for structural artifact. When TBS was derived from the same vertebral levels used for BMD reporting, using fixed L1-L4 tertile cutoffs (1.23 and 1.31 from the McCloskey meta-analysis) reclassified 17.9% to a lower and 6.5% to a higher TBS category, with 75.6% unchanged. Reclassification was reduced from 24.4% overall to 17.2% when level-specific tertile cutoffs from the software manufacturer were used. Treatment reclassification based upon FRAX major osteoporotic fracture probability occurred in 2.9% overall, but in 9.6% of those with baseline risk ≥15%. For treatment based upon FRAX hip fracture probability, reclassification occurred in 3.4% overall, but in 10.4% in those with baseline risk ≥2%. In summary, lumbar spine TBS measurements based upon vertebral levels other than L1-L4 can alter the tertile category and treatment recommendations based upon TBS-adjusted FRAX calculation, especially for those close to or exceeding the treatment cut-off. Manufacturer level-specific tertile cut-offs should be used if vertebral exclusions are applied.

Vertebral Level Variations in Trabecular Bone Score and Effect on Fracture Prediction: The Manitoba BMD Registry.

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. TBS is reportedly insensitive to degenerative changes, and it is uncertain whether the same rules for excluding lumbar vertebral levels from BMD measurement should be applied to TBS. The current analysis was performed to explore inter-vertebral variation in TBS measurements from L1 to L4, how this relates to clinically identified structural artifact resulting in vertebral level exclusion from BMD reporting, and area under the curve (AUC) for incident fracture. The study population comprised 70,762 individuals aged 40 years and older at the time of baseline spine DXA assessment (mean age 64.1 years, 89.7% female), among whom 24,289 (34.3%) had one or more vertebral exclusions. Both TBS and BMD showed a similar cranial/caudal inter-vertebral gradient. Compared with L1-4, TBS from L1 alone was lower (mean difference -0.096; -7.6%) while TBS from L4 alone was 0.046 (3.6%) greater, similar in those without and with visual structural artifact. During mean follow-up of 8.7 years, 6744 (9.5%) individuals sustained incident major osteoporotic fractures. TBS from L1 alone gave significantly higher AUC for incident fracture than L1-4, which was in turn significantly higher than L2, L3 and L4 alone, seen in those without and with visual structural artifact. In contrast, AUCs for BMD showed minimal variation from L1 to L4, and was higher for L1-4 than for any individual lumbar vertebral level. In summary, we found inter-vertebral TBS variations within the lumbar spine are overall similar to BMD but are relatively unaffected by visual structural artifact. Fracture outcomes showed the strongest association with TBS measured from L1 alone. Further investigation is need to understand the cause and clinical application of these differences.

Adjusting Trabecular Bone Score (TBS) for Level-Specific Differences Reduces FRAX®-Based Treatment Reclassification in Patients with Vertebral Exclusions: The Manitoba BMD Registry.

Trabecular bone score (TBS) is a FRAX®-independent risk factor for fracture prediction. TBS values increase from cranial to caudal, with the following mean differences between TBSL1-L4 and individual lumbar vertebrae: L1 -0.093, L2 -0.008, L3 +0.055 and L4 +0.046. Excluding vertebral levels can affect FRAX-based treatment recommendations close to the intervention threshold. We examined the effect of adjusting for level-specific TBS differences in individuals with vertebral exclusions due to structural artifact on TBS-adjusted FRAX-based treatment recommendations. We identified 71,209 individuals aged ≥40 years with TBS and FRAX calculations through the Manitoba Bone Density Program. In the 24,428 individuals with vertebral exclusions, adjusting TBS using these level-specific factors agreed with TBSL1-L4 (mean difference -0.001). We compared FRAX-based treatment recommendations for TBSL1-L4 and for non-excluded vertebral levels before and after adjusting for level-specific TBS differences. Among those with baseline major osteoporotic fracture risk ≥15 %, TBS with vertebral exclusions reclassified FRAX-based treatment in 10.6 % of individuals compared with TBSL1-L4, and was reduced to 7.2 % after adjusting for level-specific differences. In 11,131 patients where L1-L2 was used for BMD reporting (the most common exclusion pattern with the largest TBS effect), treatment reclassification was reduced from 13.9 % to 2.4 %, respectively. Among individuals with baseline hip fracture risk ≥2 %, TBS vertebral exclusions reclassified 7.1 % compared with TBSL1-L4, but only 4.5 % after adjusting for level-specific differences. When L1-L2 was used for BMD reporting, treatment reclassification from hip fracture risk was reduced from 9.2 % to 5.2 %. In conclusion, TBS and TBS-adjusted FRAX-based treatment recommendations are affected by vertebral level exclusions for structural artifact. Adjusting for level-specific differences in TBS reduces reclassification in FRAX-based treatment recommendations.

FRAX® Adjustment Using Renormalized Trabecular Bone Score (TBS) from L1 Alone may be Optimal for Fracture Prediction: The Manitoba BMD Registry.

Lumbar spine trabecular bone score (TBS) used in conjunction with FRAX® improves 10-year fracture prediction. The derived FRAX risk adjustment is based upon TBS measured from L1-L4, designated TBSL1-L4-FRAX. In prior studies, TBS measurements that include L1 and exclude L4 give better fracture stratification than L1-L4. We compared risk stratification from TBS-adjusted FRAX using TBS derived from different combinations of upper lumbar vertebral levels renormalized for level-specific differences in individuals from the Manitoba Bone Density Program aged >40 years with baseline assessment of TBS and FRAX. TBS measurements for L1-L3, L1-L2 and L1 alone were calculated after renormalization for level-specific differences. Corresponding TBS-adjusted FRAX scores designated TBSL1-L3-FRAX, TBSL1-L2-FRAX and TBSL1-FRAX were compared with TBSL1-L4-FRAX for fracture risk stratification. Incident major osteoporotic fractures (MOF) and hip fractures were assessed. The primary outcome was incremental change in area under the curve (ΔAUC). The study population included 71,209 individuals (mean age 64 years, 89.8% female). Before renormalization, mean TBS for L1-3, L1-L2 and L1 was significantly lower and TBS-adjusted FRAX significantly higher than from using TBSL1-L4. These differences were largely eliminated when TBS was renormalized for level-specific differences. During mean follow-up of 8.7 years 6745 individuals sustained incident MOF and 2039 sustained incident hip fractures. Compared with TBSL1-L4-FRAX, use of FRAX without TBS was associated with lower stratification (ΔAUC = -0.009, p < 0.001). There was progressive improvement in MOF stratification using TBSL1-L3-FRAX (ΔAUC = +0.001, p < 0.001), TBSL1-L2-FRAX (ΔAUC = +0.004, p < 0.001) and TBSL1-FRAX (ΔAUC = +0.005, p < 0.001). TBSL1-FRAX was significantly better than all other combinations for MOF prediction (p < 0.001). Incremental improvement in AUC for hip fracture prediction showed a similar but smaller trend. In conclusion, this single large cohort study found that TBS-adjusted FRAX performance for fracture prediction was improved when limited to the upper lumbar vertebral levels and was best using L1 alone.

FRAX Adjustment by Trabecular Bone Score with or Without Bone Mineral Density: The Manitoba BMD Registry.

Trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a FRAX®-independent risk factor for fracture. The TBS adjustment to FRAX assumes the presence of femoral neck BMD in the calculation. However, there are many individuals in whom hip DXA cannot be acquired. Whether the TBS-adjustment would apply to FRAX probabilities calculated without BMD has not been studied. The current analysis was performed to evaluate major osteoporotic fracture (MOF) and hip fracture risk adjusted for FRAX with and without femoral neck BMD. The study cohort consisted of 71,209 individuals (89.8% female, mean age 64.0 years). During mean follow-up 8.7 years, 6743 (9.5%) individuals sustained one or more incident MOF, of which 2037 (2.9%) sustained a hip fracture. Lower TBS was significantly associated with increased fracture risk when adjusted for FRAX probabilities, with a slightly larger effect when BMD was not included. Inclusion of TBS in the risk calculation gave a small but significant increase in stratification for fracture probabilities estimated with and without BMD. Calibration plots showed very minor deviations from the line of identity, indicating overall good calibration. In conclusion, the existing equations for incorporating TBS in FRAX estimates of fracture probability work similarly when femoral neck BMD is not used in the calculation. This potentially extends the range of situations where TBS can be used clinically to those individuals in whom lumbar spine TBS is available but femoral neck BMD is not available.