Baseline Fracture Research Articles

Effect of Discordant Hip Bone Density on Incident Fracture Risk: A Registry-Based Cohort Study.

The Fracture Risk Assessment Tool (FRAX®) combines clinical risk factors and optionally femoral neck bone density to estimate major osteoporotic fracture (MOF) and hip fracture probability. Hip dual-energy X-ray absorptiometry (DXA) simultaneously measures the trochanter and total hip, but these regions are not considered by FRAX. Our aim was to determine whether discordance in trochanter and total hip bone density (defined as ≥1 T-score difference from the femoral neck) affects fracture risk adjusted for fracture probability. Using the Manitoba bone density registry, we identified 84,773 women and men age 40 years or older undergoing baseline hip DXA. The outcomes were incident MOF and hip fracture. Cox regression hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for baseline fracture probability were used to test the association between hip T-score discordance and incident fractures. Hip T-score discordance affected more than one in five subjects (trochanter lower in 3.9%, higher in 14.2%; total hip lower in 0.3%, higher in 14.9%). After mean 8.8 years there were 8444 incident MOF including 2664 hip fractures. Discordantly lower trochanter and lower total hip T-score (≥1 below femoral neck) was associated with increased risk for MOF (adjusted HRs 1.47 and 1.60) and hip fracture (HRs 1.85 and 2.12), while discordantly higher trochanter and total hip T-score (≥1 above femoral neck) was associated with lower risk for MOF (HRs 0.83 and 0.71) and hip fracture (HRs 0.79 and 0.68). In models that examined the trochanter and total hip simultaneously, discordantly lower trochanter T-score was associated with increased incident MOF and hip fracture risk (HRs 1.43 and 1.79) whereas discordantly higher total hip T-score was associated with lower risk (HRs 0.73 and 0.75). In conclusion, trochanter and total hip regions frequently show T-scores that are discordant with the femoral neck. This information strongly affects incident fracture risk independent of fracture probability scores computed with femoral neck bone density. © 2022 American Society for Bone and Mineral Research (ASBMR).

Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

ObjectivesEmerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. MethodThe Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. ResultsFull-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. ConclusionThe bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis.

Contemporary Population-Based Analysis of Bone Mineral Density Testing in Men Initiating Androgen Deprivation Therapy for Prostate Cancer.

Androgen deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer (PCa); however, it accelerates the loss of bone mineral density (BMD), which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to assess baseline fracture risk properly. The objective of this study was to examine the proportion of BMD testing in men initiating ADT in Quebec and to identify factors associated with receipt of this testing. The study cohort consisted of men extracted from Quebec public healthcare insurance administrative databases who initiated continuous ADT from 2000 to 2015 for >12 months. The primary study outcome was receipt of BMD testing in the period from 6 months before through 12 months after ADT initiation. Multivariable generalized linear mixed regression modeling with a logit link was performed to identify variables associated with BMD testing. We identified 22,033 patients, of whom 3,910 (17.8%) underwent BMD testing. Rates of BMD testing increased from 4.1% in 2000 to 23.4% in 2015. After multivariable analyses, prior history of osteoporosis (odds ratio [OR], 1.84; 95% CI, 1.32-2.57; P<.001), rheumatoid arthritis (OR, 1.64; 95% CI, 1.15-2.34; P=.006), use of bisphosphonates (OR, 1.47; 95% CI, 1.25-1.73; P<.001), and long-term corticosteroid use (OR, 1.63; 95% CI, 1.15-2.31; P=.006) were associated with higher odds of BMD testing. Patient age >80 years (OR, 0.67; 95% CI, 0.59-0.76; P<.001), metastases (OR, 0.79; 95% CI, 0.70-0.89; P<.001), higher Charlson comorbidity score (OR, 0.65; 95% CI, 0.51-0.81; P<.001), and rural residence (OR, 0.77; 95% CI, 0.68-0.87; P<.001) were associated with lower odds of BMD testing. In our study population, BMD testing rates in men initiating ADT were low, although they increased over the years especially in the years after the publication of recommendations for BMD testing in these patients. Potential gaps identified include being older, more comorbid, and rural areas. Overall, additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.

Interim Analysis of a Phase 2 Open-Label Trial Assessing Burosumab Efficacy and Safety in Patients With Tumor-Induced Osteomalacia

ABSTRACTPatients with tumor‐induced osteomalacia (TIO), an acquired paraneoplastic condition characterized by osteomalacia due to hypophosphatemia, exhibit a similar clinical picture to those with X‐linked hypophosphatemic rickets/osteomalacia (XLH). The human monoclonal anti‐fibroblast growth factor 23 (FGF23) antibody burosumab (KRN23) increases serum phosphate and improves bone turnover, fracture healing, pain, and physical function in XLH patients by inhibiting circulating FGF23; thus, burosumab is expected to be an effective treatment for TIO. We report here an interim analysis of a multicenter, open‐label, intraindividual dose‐adjustment study of burosumab (0.3 to 2.0 mg/kg every 4 weeks) in Japanese and Korean TIO patients. The primary endpoint was the fasting serum phosphate level at each visit. Key secondary endpoints were changes over time in bone biomarkers, pharmacodynamic markers, bone histomorphometric parameters, motor function, and patient‐reported outcomes. Safety was assessed based on treatment‐emergent adverse events (TEAEs). Thirteen patients received burosumab treatment, of whom 4 underwent bone biopsy. The mean dose after week 112 was approximately 1.0 mg/kg. After the first burosumab administration, mean serum phosphate levels increased and remained above the lower limit of normal and in the normal range from weeks 14 to 112. Bone biomarkers initially increased, reaching maximum values at week 16 or 24, and then gradually decreased. After burosumab treatment, patients were able to walk further (evaluated by the 6‐minute walk test), reported decreased pain levels, and showed a tendency toward healing of baseline fractures and pseudofractures. Two patients discontinued, one each due to disease progression and consent withdrawal. Burosumab was generally well tolerated, with no treatment‐related TEAEs of grade ≥3 and no treatment‐related serious AEs. In conclusion, the interim results of this first study of burosumab to treat TIO patients indicate that this drug has the potential to provide clinical benefit for patients with unresectable tumors. The full study results are eagerly anticipated. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Fracture prediction from FRAX for Canadian ethnic groups: a registry-based cohort study.

FRAX® is calibrated using population-specific fracture and mortality data. The need for FRAX to accommodate ethnic diversity within a country is uncertain. We addressed this question using the population-based Manitoba Bone Mineral Density (BMD) Program registry and self-reported ethnicity. The study population was women aged 40years or older with baseline FRAX assessments (Canadian and other ethnic calculators), fracture outcomes, and self-reported ethnicity (White N = 68,907 [referent], Asian N = 1910, Black N = 356). Adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to MOF and hip fracture were estimated. We examined candidate variables from DXA that might contribute to ethnic differences including skeletal size, hip axis length (HAL), trabecular bone score (TBS), and estimated body composition. Adjusted for baseline risk using the Canadian FRAX tool with BMD, Asian women compared with White women were at much lower risk for MOF (HR 0.46, 95% CI 0.35-0.59) and hip fracture (0.16, 95% CI 0.08-0.34). Black women were also at lower MOF risk (HR 0.58, 95% CI 0.32-1.00); there were no hip fractures. The US ethnic-specific FRAX calculators accounted for most of the between-ethnicity differences in MOF risk (86% for Asian, 92% for Black) but only partially accounted for lower hip fracture risk in Asian women (40%). The candidate variables explained only a minority of the effect of ethnicity. Gradient of risk in analyses was similar (p-interactions ethnicity*FRAX non-significant). We identified significant ethnic differences in performance of the Canadian FRAX tool with fracture probability overestimated among Asian and Black women. The US ethnic calculators helped to address this discrepancy for MOF risk assessment, but not for hip fracture risk among Asian women.

Identification of non-Hodgkin lymphoma patients at risk for treatment-related vertebral density loss and fractures

SummaryInformation on bone loss in treated non-Hodgkin’s lymphoma patients is limited. In this study, we used CT to analyze bone loss as well as prevalent and incident fractures. We found severe bone loss, a high rate of fractures, and a novel association between bone loss and the international prognostic index.IntroductionTo investigate bone loss and fracture risk in non-Hodgkin-lymphoma (NHL) patients by (i) comparing treatment-related vertebral density (VD) loss in NHL patients with control subjects and (ii) investigating associations of VD loss versus fracture risk. Further, associations of VD loss and clinical parameters were investigated.MethodsVD of 123 NHL patients was measured pre- and post-treatment in the L1, L2, and L3 vertebrae in routine computed tomography (CT) scans, performed between Jan 2016 and Mar 2017. Control measurements (n = 52) were obtained from CT colonographies between Sept 2003 and Sept 2017 and their subsequent follow-up-exams (10–137 months).Prevalent and incident (between baseline and follow-up) fractures were assessed in all subjects, and VD loss per year was calculated. Linear regression models were used to (i) compare VD loss between patients and controls and (ii) identify associations between VD loss and clinical parameters. Using logistic regression models, ORs for fractures per SD change in VD were assessed in patients. Analyses were adjusted for age, sex, and contrast application.ResultsNHL patients experienced significantly greater VDL1–3 loss than controls (P = 0.003), and greater VDL1–3 loss was associated with a greater likelihood of incident fractures (OR, [95%-CI], P 1.90, [1.03, 3.51], 0.04). Patients with an initial international prognostic index (IPI) of 5 suffered significantly greater VD loss compared with an IPI of 0 (P = 0.01).ConclusionUsing VD measurements in routine CT scans, substantial vertebral bone loss in NHL patients could be documented with a high incidence of fractures.

Middle East experience from the Asia And Latin America Fracture Observational Study (ALAFOS): Baseline characteristics of postmenopausal women with osteoporosis using teriparatide.

ObjectiveWe aimed to describe the baseline clinical characteristics and fracture history of patients taking teriparatide in routine clinical practice in the Middle East (ME) subregional cohort of the Asia and Latin America Fracture Observational Study (ALAFOS).MethodsHerein, we report baseline clinical characteristics of patients who were prescribed teriparatide (20 µg/day, subcutaneous injection) in four participant ME countries (Saudi Arabia, United Arab Emirates, Kuwait, and Lebanon).ResultsThe ME cohort included 707 patients mean (SD) age 69.3 (11.6) years. Mean (SD) bone mineral density (BMD) T-scores at baseline were −3.13 (1.28) for lumbar spine, −2.88 (0.94) for total hip, and −2.65 (1.02) for femoral neck. Osteoporotic fractures after age 40 years were reported in 45.8% (vertebral fracture 14.4%, hip fracture 18.4%) and comorbidities in 57.4% of patients. Before starting teriparatide, 19.9% of patients took other osteoporosis medications. The median (Q1; Q3) EuroQoL 5-Dimension 5-Level visual analog scale score for perceived overall health status was 70 (50; 80). Mean (SD) worst back pain in the previous 24 hours was 4.0 (3.2) using a 10-point numeric rating scale.ConclusionThis analysis indicated that in ME countries, teriparatide is usually prescribed to patients with low BMD and high comorbidities, with prior fractures.

Different fracture risk profile in patients treated with anti-osteoporotic drugs in real-life.

In this retrospective study, we intended to investigate the baseline fracture risk profile in patients who started treatment with different anti-osteoporotic medications. We analyzed retrospectively the fracture risk calculated with DeFRA, a validated FRAX derived tool, in women who started an anti-osteoporotic treatment from 2010 to 2017. We analyzed baseline data of 12,024 post-menopausal women aged over 50 years. Teriparatide initiators had a baseline 10-year risk of major osteoporotic fracture of 82.1% with a Standard Deviation (SD) of 66.5%. Denosumab initiators and zoledronic acid initiators had a greater 10-year baseline risk of fracture (54.3%, SD 46.5% and 47.0%, SD 42.0 respectively) than patients initiated on alendronate (24.9%, SD 34.6%) and patients initiated on risedronate (23.9%, SD 24.1%). Using DeFRA, a FRAX™ derived tool, we showed significantly different fracture risk profiles in women who were started on various therapeutic agents for the treatment of osteoporosis in routine clinical practice.

Assessment of baseline bone turnover marker levels and response to risedronate treatment: Data from a Japanese phase III trial

BackgroundRisedronate increases bone mineral density (BMD) and reduces fracture risk, but treatment response may depend on the baseline state of bone turnover. Data regarding the selection of therapeutic drugs or the prediction of therapeutic effects with baseline levels of bone turnover markers (BTMs) as a reference are insufficient. We hypothesized that when the baseline levels of BTMs are higher, baseline BMD might be lower, changes in BMD at 12 months after risedronate treatment might be higher, and the reduction of fracture incidence might be greater. This study aimed to analyze the data of a phase III clinical trial of risedronate from Japan to investigate the relationships between baseline BTM levels and (1) baseline BMD, (2) changes in BMD at 12 months after the start of treatment, and (3) the incidence of new vertebral fractures. MethodsThis post-hoc analysis included 788 postmenopausal women with osteoporosis whose baseline BTM levels as well as baseline and endpoint BMDs were measured. Relationships between baseline BTM levels and BMD at baseline and 12 months after risedronate treatment and new vertebral fractures were examined. One-way analysis of variance, two-tailed Student's t-test, and Fisher's exact test were used to analyze the data. ResultsBaseline BMD showed a significant upward trend when baseline BTM levels were lower in the analysis by tertiles. New vertebral fractures tended to occur in patients with prevalent vertebral fractures, but the relationship between new fractures and BTM levels was not statistically significant. Regardless of BTM types, BMD percentage increments (%) and increments (g/cm2) with the 12-month treatment were high when pretreatment BTM levels were high (P < 0.0001), and a >5.0% increase in BMD was observed even if baseline BTM levels were within the normal range. A new vertebral fracture occurred in only six patients (0.77%), and there was not enough statistical power to clarify the relationship between baseline BTM levels and fracture risk reduction. ConclusionsWhen pretreatment BTM levels increased, baseline BMD tended to be lower and the increase in BMD with 12-month risedronate treatment was higher. However, BMD could still be increased even if the baseline BTM levels are within the normal range. Combined with available evidence, baseline BTMs may not have an important role in deciding the optimal therapy. To elucidate the relationship between baseline BTM levels and long-term fracture risk, it will be necessary to conduct more large-scale studies with a longer follow-up period in severe osteoporotic patients with a high fracture risk. Mini abstractWe evaluated the significance of baseline bone turnover markers in the response to risedronate treatment. The increase in the bone mineral density (BMD) with the 12-month treatment may be higher when the state of bone turnover at baseline is higher, and BMD could still be increased even if the baseline bone turnover is within the normal range.

Cementation: for better or worse? Interim results of a multi-centre cohort study using a fenestrated spiral blade cephalomedullary device for pertrochanteric fractures in the elderly.

Cephallomedullary nail fixation is currently the most popular treatment for pertrochanteric fractures. Despite continuous improvement in implant design, fixation failures still occur in a concerning number of cases. This study aims to evaluate the effect of cement augmentation of the new-generation Trochanteric Femoral Nail Advanced (TFNA) perforated spiral blade on complications including fixation failure in the elderly population. We retrospectively evaluated 107 patients aged 65 + treated for pertrochanteric fractures via TFNA between 2015 and 2019 based on whether cementation was used. Baseline demographics, fracture classifications, and reduction quality were compared. Patients with a follow-up of at least 6months were analyzed for the primary outcome of fixation failure. All patients, regardless of loss to follow-up within 6months, were analyzed for other complications including mortality. Seventy-six patients (47 cemented, 29 non-cemented) had a minimum follow-up of 6months (mean 13months). There were no statistically significant differences between the two treatment groups in terms of patient demographics, ASA or AO/OTA fracture classification, reduction quality, or length of follow-up. There was a lower rate of fixation failure in the cement-augmented (CA) group versus the non-cement-augmented (NCA) group (2.1% vs 13.8%; p = 0.047). No cut-out or cut-through was observed in the CA group. Seven patients had adverse intraoperative events, with a significantly higher rate of fixation failure in these patients (40% vs 2.8%; p = 0.00). There were no statistically significant differences in 30-day mortality (6.3% CA vs 4.3% NCA; p = 0.632) or 3-month mortality (9.5% CA vs 12.8% NCA; p = 0.589). Cementation of TFNA blades may decrease risk of fixation failure, however, the surgeon must be aware of potential complications such as cement leakage into the hip joint and be able to manage them as they arise.

Underevaluation of fractures by self-report: an analysis from the FRISBEE cohort.

Most fracture cohort studies rely on participant self-report of fracture event. This approach may lead to fracture underreporting. The purpose of the study was to assess the rate of non-reported fractures in a well-characterized population-based cohort of 3560 postmenopausal women, aged 60-85years, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) study. Incident low-traumatic or non-traumatic fractures were registered annually during phone calls. In 2018, we reviewed the medical files of 67.9% of our study participants and identified non-reported fractures ("false negatives fractures (FN)"). We also evaluated whether the rate of FN was influenced by baseline patients' characteristics and fracture risk factors. Generalized estimating equation (GEE) was used to calculate odds ratio (OR) and 95% CI. Over a median follow-up period of 9.2years, we registered 992 fractures (781 by self-report, confirmed by a radiological report and 211 unreported). The global false negative rate for all fractures was 21.3%, including 22% for MOFs (major osteoporotic fractures), 13.1% for other major fractures, and 25.8% for minor fractures. The rate of non-reported fractures varied by fracture site: for MOFs, it was 2.7% (n = 2/73) at the hip, 5.3% at the proximal humerus (n = 5/94), 7.1% at the wrist (n = 11/154), and 46.5% at the spine (n = 100/215). For "other major" fractures, the highest rate of false negatives fractures was found at the pelvic bone (21%, n = 13/62), followed by the elbow (17.9%, n = 5/28), long bones (10.5%, n = 2/19), ankle (6.2%, n = 4/65), and knee (5.9%, n = 1/17). Older subjects (OR 1.7; 95% CI, 1.2-2.4; P = 0.003), subjects with early non-substituted menopause (OR 1.8; 95% CI, 1.0-3.3; P = 0.04), with a lower education level (OR 1.5; 95%CI, 1.1-2.2; P = 0.01), and those under drug therapy for osteoporosis (OR 1.5; 95% CI, 1.0-2.2; P = 0.05) were associated with a higher rate of FN. In conclusion, underreporting of a substantial proportion of fracture events will influence any model of fracture risk prediction and induce bias when estimating the associations between candidate risk factors and incident fractures.

Union Following Biological and Rigid Fixations of Distal Tibia Extra-articular Fractures.

Distal tibia fractures are among the most common bony injuries, with a significant rate of nonunion and delayed union. There are multiple methods for the management of distal tibia fractures. Among the plating methods, there are bridge plating and compression plating techniques. There is still a lack of evidence about whether one method has a higher rate of union than the other. The present study aimed to assess the union rate of extra-articular distal tibia fractures using biological fixation with bridge plating and rigid fixation with compression plating. This retrospective analysis was performed on 41 adult patients with distal tibia fractures. The subjects were divided into two groups based on the fixation method, namely bridge plating and compression plating. Baseline characteristics, fracture characteristics, and union status were analyzed and compared in this study. Baseline and fracture characteristics were similar between the groups. Only higher translation in any planes was noted in the bridge plating group (2.80±3.04 mm; P<0.001). As for union status, the rates of the union during 3 months and delayed/no union were similar between the two groups (P=0.18). During a 6-month follow-up, 92% and 93.8% of the patients achieved union in the bridge plating and compression plating groups, respectively. Rates of delayed union and nonunion are similar regarding extra-articular distal tibia fractures treated with either bridge plating or compression plating.

Evaluation of baseline fracture risk in younger postmenopausal women with breast cancer using different risk assessment methods

ObjectiveControversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC.MethodsOverall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively.ResultsLumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group.ConclusionPostmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.

Reassessment Intervals for Transition From Low to High Fracture Risk Among Adults Older Than 50 Years

Fracture risk scores are used to identify individuals at high risk of major osteoporotic fracture or hip fracture for antiosteoporosis treatment. For those not meeting treatment thresholds at baseline, the optimal interval for reassessing fracture risk is uncertain. To examine reassessment intervals for transition from low to high fracture risk under guidelines-defined treatment thresholds. This retrospective cohort study included persons aged 50 years or older with fracture risk below treatment thresholds at baseline who had fracture risk reassessed at least 1 year later. Data were obtained from a population-based bone mineral density registry (baseline assessment during 1996-2015; reassessment to 2016) in the Province of Manitoba, Canada. Primary analysis was performed from May to June 2019. Analysis for the revision was performed in October 2019. The primary outcome was time to transition from low (below the treatment threshold) to high fracture risk (treatment-qualifying risk score using osteoporosis clinical practice guidelines strategies for Canada, the United States, and the United Kingdom). The study population consisted of 10 564 individuals (94.1% women; mean [SD] age at baseline, 63.2 [8.2] years). At the time of reassessment (a mean [SD] interval of 5.2 [2.9] years between initial and subsequent fracture risk assessment), 690 (6.6%) had reached the fixed major osteoporotic fracture treatment threshold of 20%, 1546 (16.2%) had reached the fixed hip treatment threshold of 3%, and 932 (9.4%) had reached the age-dependent major osteoporotic fracture treatment threshold. Among those below 25% of the treatment threshold at baseline for each guideline, few (0%-3.0%) reached guidelines-defined high fracture risk at follow-up. In contrast, among those at the upper end of the scale for each guideline (75%-99% of the treatment threshold at baseline), 30.6% to 74.4% reached guidelines-defined high fracture risk. An increased number of clinical risk factors was associated with increased likelihood of reaching guidelines-defined high fracture risk (range for 3 guidelines, 17.1%-28.2%) compared with unchanged or decreased clinical risk factors (range for 3 guidelines, 3.3%-12.8%) (P < .001). Estimated time for 10% of the population to reach treatment-qualifying high fracture risk ranged from fewer than 3 years to more than 15 years. The findings suggest that baseline fracture risk (as a fraction of the treatment threshold) and change in clinical risk factors can identify individuals with low and high probability of guidelines-defined high fracture risk during follow-up, thereby potentially helping to inform the reassessment interval.

Hip Fracture in Nonagenarians: Characteristics and Factors Related to 30-Day Mortality in 1177 Patients

BackgroundThe number of nonagenarian patients with hip fracture is increasing. The goals of this study were to describe the characteristics and in-hospital course of a cohort of 1177 nonagenarians admitted for hip fracture compared with younger patients and to identify risk factors for 30-day mortality after admission. MethodsThis is a retrospective observational cohort study including patients aged 65 years or older admitted for hip fracture during various periods from February 1997 to December 2016. We defined 3 age groups: 65-79, 80-89, and 90 years and older. We included sociodemographic variables, baseline functional status, comorbidities, fracture and surgical characteristics, postoperative complications, length of stay, and in-hospital and 30-day mortality. Multiple logistic regression analysis was used to study risk factors for 30-day mortality in surgically treated nonagenarians. ResultsNonagenarians were more likely to be women and to have dementia and heart disease. Some 72% walked independently before the fracture. The most relevant treatable risk factor for 30-day mortality in nonagenarians (in terms of higher odds ratio [OR]) was developing respiratory infection (OR: 4.56, 95% confidence interval [CI]: 2.73-7.63). Better prefracture functional status (higher Katz score; OR: 0.83, 95% CI: 0.74-0.92) and spinal anesthesia (OR: 0.19, 95% CI: 0.05-0.68) decreased risk of 30-day mortality. ConclusionsNonagenarian patients with hip fracture differ significantly from younger patients concerning clinical characteristics, medical complications, and in-hospital and 30-day mortality rates. We identified several variables on which we could act to reduce 30-day mortality, such as respiratory infection, electrolyte disorders, polypharmacy, cardiac arrhythmia, and spinal anesthesia.

POSSUM and P-POSSUM Scoring in Hip Fracture Mortalities.

Introduction:Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) and Portsmouth POSSUM (P-POSSUM) are general surgical tools used to efficiently assess mortality and morbidity risk. Data suggest that these tools can be used in hip fracture patients to predict morbidity and mortality; however, it is unclear what score indicates a significant risk on a case-by-case basis. We examined the POSSUM and P-POSSUM scores in a group of hip fracture mortalities in order to assess their accuracy in identification of similar high-risk patients.Materials and Methods:Retrospective analysis of all consecutive mortalities in hip fracture patients at a single tertiary care center over 2 years was performed. Patient medical records were examined for baseline demographics, fracture characteristics, surgical interventions, and cause of death. Twelve physiological and 6 operative variables were used to retrospectively calculate POSSUM and P-POSSUM scores at the time of injury.Results:Forty-seven hip fracture mortalities were reviewed. Median patient age was 88 years (range: 56-99). Overall, 68.1% (32) underwent surgical intervention. Mean predicted POSSUM morbidity and mortality rates were 73.9% (28%-99%) and 31.1% (5%-83%), respectively. The mean predicted P-POSSUM mortality rate was 26.4% (1%-91%) and 53.2% (25) had a P-POSSUM predicted mortality of >20%. Subgroup analysis demonstrated poor agreement between predicted mortality and observed mortality rate for POSSUM in operative (χ2 = 127.5, P < .00001) and nonoperative cohorts (χ2 = 14.6, P < .00001), in addition to P-POSSUM operative (χ2 = 101.9, P < .00001) and nonoperative (χ2 = 11.9, P < .00001) scoring.Discussion/Conclusion:Hip fracture patients are at significant risk of both morbidity and mortality. A reliable, replicable, and accurate tool to represent the expected risk of such complications could help facilitate clinical decision-making to determine the optimal level of care. Screening tools such as POSSUM and P-POSSUM have limitations in accurately identifying high-risk hip fracture patients.

Assessment of Aromatase Inhibitor-Induced Bone Loss and Appropriateness of Supportive Therapy in Postmenopausal Breast Cancer Patients at a Tertiary Care Center

Objective: To assess aromatase inhibitor-induced bone loss (AIBL) and its management in postmenopausal women (PMW) with breast cancer (BC). Materials and Methods: A cohort of 350 PMW with BC receiving aromatase inhibitors (AIs) during a span of 4 years was evaluated retrospectively. Bone mineral density (BMD) of the patients at lumbar spine (LS) and dual femur was monitored at baseline and annually for 2 years. Baseline fracture risk was evaluated using WHO fracture risk assessment tool. Results: At baseline, only 35.4% of the patients received supportive therapy such as calcium and Vitamin D supplements ± bisphosphonates. Significant decrease of mean BMD occurred at LS, left femur, and right femur (LF and RF) at 1 year (P

Risk of Fracture Following Front Line R-CHOP Immunochemotherapy in Older Patients with Diffuse Large B Cell Lymphoma Is Common

Introduction Diffuse large B cell lymphoma (DLBCL) and osteoporotic fracture are commoner in older patients (pts). Steroids and chemotherapy are recognised as a risk factor (RF) for fragility-related fracture and its associated morbidity. A small randomised trial (RCT) (Westin 2013) showed bisphosphonates stabilize bone mineral density (including all ages / histologies) in NHL pts. Despite this, there is a lack of data defining the specific incidence and fracture risk in older DLBCL pts post R-CHOP. We aimed to better define this risk in this specific cohort. Methods Data on consecutive DLBCL pts ≥70 years (y) treated with R-CHOP were retrospectively collected across 7 UK centres (2009-2019). Follow up was censored in 07/2019. All pts had untreated, de novo DLBCL or untreated transformed (to DLBCL) indolent B cell NHL. PTLD, HIV and pre-treated NHL pts were excluded. All pts received 1-9 cycles of full or attenuated R-CHOP with curative intent. Pts were excluded if they had progressive disease (PD) or died &lt; 6 months (m) of cycle 1 R-CHOP (RCHOP1). A detailed anonymised database included ECOG performance status (PS), body mass index (BMI), history of osteoporosis / osteopenia, documented steroid pre-phase, vitamin D supplementation, calcium and alkaline phosphatase levels, and sites of bone DLBCL involvement. Fractures at diagnosis (DLBCL-related/unrelated) and pre diagnosis were collected. Fractures (including bone site) occurring during 18m from RCHOP1 were identified from radiology records. Pts were followed for a minimum of 6m and censored at 18m from RCHOP1, or at their last follow up if &lt; 18m or at PD or death if between 6-18m. Baseline pt characteristics were descriptive. Survival analyses were performed using Kaplan Meier methods and Cox regression with comparisons between categories using the log-rank test. Time to event analyses were measured from RCHOP1 until fracture event. Primary end point was 18m cumulative fracture incidence censoring pts at death or relapse. Univariable and multivariable analyses (UVA; MVA) of potential influencing RFs for fracture was assessed by Cox regression (Final stepwise model; p=0.1 for inclusion). Results Of 589 pts identified, 92 pts had PD or died prior to 6m and were excluded. 20 pts were excluded due to short follow up. Across 477 pts, the median age was 77 (range 70-93) y. 66% had an ECOG PS 0-1. The median cycles given was 6 (range 1-9). 27.3% received pre-phase steroids. The median BMI was 25.5 (range 14.2-48.1). 8.1% had a fracture prior to DLBCL, and 9.1% had a history of osteopenia or osteoporosis. 5.7% were current smokers, 3% had rheumatoid arthritis, 13.5% had type (T) 2 diabetes (DM), and 4.5% had a history of excess alcohol. At baseline, 25.2% had PET or CT-assessed cortical bone involvement. Overall, there were 52 fractures, including 50 within 18m follow up. Cumulative fracture incidence was 6.3% (95% confidence interval (CI) 4.4 - 8.9) at 6m, 9.5% (95% CI 7.1 - 12.6) at 12m and 11.5% (95% CI 8.8 - 14.9) at 18m (Fig A). 6 pts had multiple fracture sites (2; n=5, 3; n=1). 32 (62%) had vertebral fracture(s). Thoracic (34% 20/59) and lumbar vertebral (27% 16/59) were dominant sites (Fig C). 7/52 fractures were at the site of DLBCL involvement, 17/52 were at a different site from initial bone DLBCL involvement, 27/52 were in pts without bone involvement and 1/52 was unknown. Univariable RFs included female sex (hazard ratio (HR) 1.89 (95% CI 1.05 - 3.28)), known osteopenia or osteoporosis (HR 2.64 (95% CI 1.32 - 5.29)), DLBCL-related fracture at diagnosis (HR 4.05 (95% CI 2.07 - 7.92) (Fig B). Initial bone involvement was only associated with an increased risk in pts with a DLBCL-related baseline fracture (95% CI HR 4.56 (2.27 - 9.17)) (Table 1). MVA showed that DLBCL-related baseline fracture (HR 4.32 (1.97 - 9.47)) was the only significant independent RF for fracture with low BMI (p=0.051) and smoking history (p=0.052) of borderline significance (Table 2). Conclusions This is the largest series to date to show there is a clinically relevant fracture risk in older DLBCL pts specifically receiving R-CHOP in early follow up. Our data have limitations inherent to a retrospective study including the potential for unknown confounders, missing data, and medical record misinterpretation. Prospective data is required to validate RFs identified which could enable targeting a high-risk population. An RCT is needed to determine the value of prophylactic intervention(s) in high risk pts. Figure Disclosures Gibb: Takeda: Research Funding. Collins:Gilead: Consultancy, Honoraria. Eyre:Janssen: Honoraria; Abbvie: Honoraria; Gilead: Consultancy, Honoraria, Other: commercial research support; Roche: Honoraria.

Baseline characteristics of postmenopausal women with osteoporosis treated with teriparatide in a real-world setting in Latin America: a subregional analysis from the Asia and Latin America Fracture Observational Study (ALAFOS)

BackgroundOsteoporosis is a major healthcare concern in Latin America. Factors such as changing demographics, fragmented healthcare systems, and financial considerations may result in a huge increase in the burden of osteoporosis in this region. The aim of this article is to describe the baseline clinical characteristics and fracture history of patients who are prescribed teriparatide in normal clinical practice in Latin America.MethodsWe conducted a prospective, multinational, observational study (the Asia and Latin America Fracture Observational Study [ALAFOS]) in 20 countries worldwide to assess the incidence of fractures in postmenopausal women with osteoporosis receiving teriparatide as a part of routine clinical practice in a real-world setting. In this subregional analysis of the ALAFOS study, we report the clinical characteristics, fracture history, risk factors for osteoporosis, comorbidities, previous osteoporosis therapies and health-related quality of life measures at baseline for patients from the four participant Latin American countries: Argentina, Brazil, Colombia, and Mexico.ResultsThe Latin America subregional cohort included 546 postmenopausal women (mean [SD] age: 71.0 [10.1] years; range: 40–94 years), constituting 18% of the ALAFOS total population. The baseline mean (SD) bone mineral density T-scores were − 3.02 (1.23) at the lumbar spine and − 2.31 (0.96) at the femoral neck; 62.8% of patients had a history of low trauma fracture after the age of 40 years and 39.7% of patients had experienced ≥1 fall in the past year. Osteoporosis medications were used by 70.9% of patients before initiating teriparatide. The median (Q1, Q3) EQ-5D-5 L Visual Analog Scale (VAS) scores for perceived health status at baseline was 70 (50, 80). The mean (SD) worst back pain numeric rating scale score for the overall Latin American cohort was 4.3 (3.4) at baseline.ConclusionsThis baseline analysis of the Latin America subregion of the ALAFOS study indicates that patients who are prescribed teriparatide in the four participant countries had severe osteoporosis and high prevalence of fractures. They also had back pain and poor health-related quality of life. The proportions of patients with severe or extreme problems on the EQ-5D-5 L individual domains were lower than those in the overall ALAFOS study population.

857P - Baseline fracture risk in men with prostate cancer starting the STAMPEDE trial

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer (PC) increases fracture risk. In non-cancer populations, FRAX, a fracture risk assessment tool, is used routinely to calculate 10-year probability of major osteoporotic fracture (MOF; spine/hip/forearm/humeral fractures) and hip fracture alone to determine the need for bone density (BMD) assessment and/or treatment. We calculated FRAX using risk factors at entry to the large STAMPEDE PC study. MethodsSTAMPEDE includes men with newly diagnosed metastatic/high risk non-metastatic PC about to commence ADT, randomised to add or substitute other therapies. Our pre-planned analysis included 6379 men, 86% of enrolment at the time of analysis (2018) for whom FRAX clinical risk factors (excluding femoral neck BMD) were collected prospectively. Secondary osteoporosis in FRAX was set to ‘yes’ for all, as they were about to receive ADT. Glucocorticoid use was set to ‘yes’ for men allocated to abiraterone due to potentially long concomitant use, but not for those allocated shorter treatment with docetaxel. ResultsBaseline characteristics for this largest dataset of its kind, are shown below. The mean (SD) baseline FRAX 10-year probability was 3.06(2.96)% for hip fracture and 8.70(4.02)% for MOF. Risk increased with increased age at entry, eg MOF probability at age 50-54 years was 4.9% rising to 11.3% in those aged 75 years or older. Using UK National Osteoporosis Guideline Thresholds, 2221 (34.8%) men were classified as high/intermediate risk (meriting BMD scan).The need for BMD assessment varied across planned treatment arms (18.4% in men receiving ADT only to 80.0% in men also planned to receive abiraterone).Table857PTableCharacteristicRandomisation years2006- 2018Age (y)67.4±7.2Height (cm)174.7±6.9Weight (kg)85.6±14.8BMI (kg/m2)28.0±4.5Prevalence of FRAX risk factors (%) Previous fracture after age 50yr6.1Glucocorticoid use (≥4mo)27.4Parental hip fracture7.7Rheumatoid arthritis2.4Alcohol (≥3 units daily)15.5Current smoking11.5 ConclusionsFRAX fracture risk assessment in men starting ADT suggests 1 in 3 require BMD assessment to decide on the need for bone protection. Planned treatment in addition to ADT, rather than age, was the main determinant for consideration of bone health. Clinical trial identification2004-000193-31. Legal entity responsible for the studyUniversity of Sheffield. FundingUniversity of Sheffield. DisclosureJ.E. Brown: Honoraria (self), Research grant / Funding (institution): Amgen; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Research grant / Funding (institution): Bayer; Honoraria (self): BMS; Honoraria (self): Daiichi-Sankyo; Honoraria (self): Ipsen; Honoraria (self): Sandoz; Honoraria (self): Merck Sharpe Dome. All other authors have declared no conflicts of interest.