Prior Fracture Research Articles

Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank.

Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population. This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37-73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre-existing cardiovascular disease were conducted. Mediation analyses using the g-formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk. Over a median follow-up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL-C had linear associations. There were also nonlinear associations of Apo A and HDL-C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL-C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL-C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL-C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality. Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL-C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification.

Association between dietary vitamin E and osteoporosis in older adults in the United States

BackgroundIncreased oxidative stress due to aging can lead to increased bone loss. The most abundant form of vitamin E, namely α-tocopherol, has high antioxidant properties and biological activity; however, its effect on osteoporosis has not been well studied in humans. We aimed to investigate the association between dietary vitamin E (α-tocopherol) and osteoporosis among older adults in the United States.MethodsThis cross-sectional study analyzed data on older adults in the United States aged ≥50 years from the 2007–2010, 2013–2014 and 2017–2020 pre-pandemic cycles of the National Health and Nutrition Examination Survey. Sample-weighted multivariate regression models were used, with adjustments for relevant confounders.ResultsThis study comprised 5,800 individuals with available data on dietary intake and bone mineral density of hip and spine. The mean participant age was 61.4 (standard deviation, 8.7) years, and approximately 9.9% had osteoporosis. High vitamin E intake was significantly associated with a reduced risk of osteoporosis (odds ratio, 0.96, 95% confidence interval, 0.93–0.98). In addition, there was evidence of interaction between dietary vitamin E and prior fracture on preventing osteoporosis.ConclusionsOur study indicated a linear association between dietary vitamin E levels and osteoporosis in an older population in the United States. Further research is required to explore the potential effects of different forms of vitamin E on osteoporosis.

Falls and fall-related injuries: prevalence, characteristics, and treatment among participants of the Geelong Osteoporosis Study

BackgroundFalls are a significant public health challenge, especially among older adults. In Australia, falls and related injuries incur an annual cost of $2.3 billion. However, there is a scarcity of prevalence data on falls among population-based groups. This study aimed to report the characteristics, circumstances, and treatment for falls and fall-related injuries in a population-based sample of Australian men and women.MethodsParticipants from the Geelong Osteoporosis Study provided cross-sectional data: baseline for men (2001–2006) and 10-year follow-up for women (2004–2008). Falls over the previous 12 months were self-reported by 2,631 participants aged 20–97 years (1,533 men and 1,098 women). The study described the timing, location, cause, and treatment of falls. Fall prevalence was standardized to the 2006 Australian population. Data collection included self-reported prior fractures, medication, disease conditions, anthropometry, and biochemical tests. Binary logistic regression identified factors linked to fall-related injuries.ResultsFall rates by age group: 20–29 (24.4%), 30–39 (21.5%), 40–49 (18.7%), 50–59 (24.9%), 60–69 (25.0%), 70–79 (34.6%), 80+ (40.5%). The age-standardized prevalence of falls was 25.0% (95% CI: 23.4–26.7%). In adults ≥65 years, the age-standardized prevalence of falls was 32.4% (95% CI: 29.3–35.5%). Fallers were typically older, less mobile, had higher BMI and cholesterol levels, and were more likely to have musculoskeletal conditions, cancer, and polypharmacy. Men had a higher fall risk, but fewer fall-related fractures compared to women. Most falls occurred outdoors (62.1%), were due to extrinsic cause (58.5%), and were on the same level (78.5%). Factors associated with fall-related injuries included being female, elevated falls and falls outside the home. Nearly half (45.7%) of those injured sought medical attention, primarily from general practitioners (25.7%) and emergency departments (12.6%).ConclusionFalls are common, occurring in approximately one quarter of adults in this study, with a greater prevalence among those ≥65 years. Women experienced fewer multiple falls than men. Many participants sought medical attention, primarily from general practitioners. This research identifies fall characteristics and circumstances, informing targeted prevention strategies to reduce occurrences and alleviate burdens on healthcare systems and individuals.

7473 Mortality following Hip Fracture among Black and White Women in a Western US Healthcare System

Abstract Disclosure: J.C. Lo: None. M. Chandra: None. W. Yang: None. U. Ozomaro: None. M.D. Sharma: None. J.A. Darbinian: None. C. Lee: None. A.L. Wheeler: None. M.M. Khan: None. Background: Prior studies using US Medicare data demonstrate that Black women have higher mortality after hip fracture than White women. However, few studies have examined findings specific to the Western US. We previously found that 1-year mortality after hip fracture (in 2000-2010) was similar among Black and White women in a Western US healthcare system. We now examine 6-month and 1-year mortality in an expanded cohort of Black and White women with hip fracture in the same healthcare system. Methods: This retrospective study includes data from non-Hispanic White and Black women aged ≥65y in a Western US healthcare system who were hospitalized with hip fracture during 2000-2019. The outcome was all-cause mortality, within 6-months and 1-year after hip fracture. Covariates included age at hip fracture, femoral neck vs pertrochanteric (hip) fracture, year of fracture, prior clinical fracture (diagnosed in the prior 5 years), Charlson-Deyo Comorbidity index (CCI based on inpatient/outpatient data in the prior year and during hip fracture hospitalization) and diabetes (diagnosed in the prior 5 years or during hip fracture hospitalization). Modified Poisson regression was used to examine mortality after hip fracture (Black vs White women), adjusting for (a) age, fracture type, year and (b) age, fracture type, year, CCI, prior fracture and diabetes. Results: The cohort included 691 Black women (age 82.9 ± 8.0y; 43.4% age ≥85y) and 20,450 White women (age 82.8 ± 7.7y; 44.2% age ≥85y) with hip fracture in 2000-2019. Black women had a similar proportion with femoral neck fracture (58.2% vs 55.2%) but were more likely to have prior fracture (23.0% vs 33.5%), diabetes (35.2% vs 18.2%), and higher CCI vs White women. For Black vs White women, respectively, group differences in 6-month (18.4% [95% confidence interval 15.7-21.4%] vs 16.4% [15.9-16.9%], p=0.12) and 1-year mortality (23.2% [20.2-26.5%] vs 22.1% [21.4-22.6%], p=0.49) were not significant. In multivariable analyses, the relative risk of death at 1-year for Black (vs White) women was 1.03 [0.90-1.19] adjusting for age, year, fracture type and 0.97 [CI 0.84-1.11] adjusting for age, year, fracture type, CCI, prior fracture, and diabetes. The relative risk of death at 6-months for Black (vs White) women was 1.05 [0.89-1.23] adjusting for covariates. Conclusions: In a Western US healthcare system, differences in 6-month and 1-year mortality post-hip fracture were small and not significant for Black and White women aged ≥65y, after accounting for age and comorbidity burden. However, the number of Black women was small, and data on social factors, frailty, post-fracture morbidity, and other health factors were not available. Nonetheless, these results suggest that racial and ethnic differences in mortality after hip fracture may vary by geographic region. Hip fracture outcomes in larger populations of Black women in the Western US should be examined. Presentation: 6/3/2024

7334 Changing Trends In Oral Bisphosphonate Therapy: A 25-Year Surveillance In A US Healthcare System

Abstract Disclosure: J.C. Lo: None. M. Chandra: None. M.M. Khan: None. L.D. Carbone: None. E.A. Garcia: None. G.H. Tabada: None. D. Low: None. R.L. Hui: None. Introduction: Bisphosphonate (BP) drugs remain one of the first line therapies for fracture prevention, but treatment patterns have changed since BPs were first approved for osteoporosis. This study examines trends among adults initiating oral BP in a large US healthcare system over a 25-year period (1988-2022) and in each successive 5-year period. Methods: The study cohort comprised adults aged 50-89y who initiated alendronate, risedronate or oral ibandronate during 1998-2022 in an integrated healthcare delivery system, excluding those with select bone disorders, multiple myeloma, secondary metastatic cancer, end stage renal disease, and receipt of intravenous BP. Covariates included age (proportion age <65y), sex, race and ethnicity, and prior fracture (diagnosed within 5 years) using electronic health record data. Demographic trends and fracture status were examined across time periods. The chi-squared test and Cochrane-Armitage test for trend were used to examine differences and trends. This report extends findings from an earlier report of women initiating oral BP during 2004-2012 in the same healthcare population. Results: Among 208,780 adults (86% women) who initiated BP, including 26,646 (1998-2002, 35% <65y), 44,726 (2003-2007, 35% <65y), 34,005 (2008-2012, 24% <65y), 35,248 (2013-2017, 19% <65y), and 38,743 (2018-2022, 17% <65y) women and 2348 (1998-2002, 28% <65y), 4895 (2003-2007, 26% <65y), 5172 (2008-2012, 17% <65y), 5331 (2013-2017, 13% <65y), and 11,666 (2018-2022, 5% <65y) men in each 5-year period. Over time, an increasing proportion were age ≥65y (p<0.001 for trend), with larger numbers of older adults in later years partly reflecting initiatives targeting secondary fracture prevention (since 2008 for women, 2015 for men) and BMD screening (since 2011 for women, 2017 for men). Among women initiating BP, the proportion with prior fracture increased from 24-30% (pre-2008) to 43-45% (post-2008), partly reflecting secondary fracture prevention initiatives for women. For men, this proportion increased from 33% (1998-2002) to 42% (2003-2007), 47% (2008-2012), and 54% (2013-2017), but fell to 36% (2018-2022) after BMD screening initiatives began in 2017 for older men (primary prevention efforts). Racial and ethnic diversity in treatment also increased, comparing 1988-2002 (75.2% White, 2.5% Black, 8.6% Hispanic, 12.7% Asian/Pacific Islander) to 2018-2022 (61.5% White, 2.9% Black, 12.2% Hispanic, 21.1% Asian/Pacific Islander, p<0.001 for overall differences and % non-White). Conclusions: In a primary care population of adults initiating oral BP, a larger proportion in later years were age >65y, including larger numbers both with and without fracture coinciding with initiatives for fracture prevention. Among those initiating BP, the relative proportions with prior fracture in each period were likely influenced by primary or secondary prevention efforts. Presentation: 6/2/2024

9212 Changing Trends In Oral Bisphosphonate Therapy: A 25-Year Surveillance In A US Healthcare System

Abstract Disclosure: J.C. Lo: None. M. Chandra: None. M.M. Khan: None. L.D. Carbone: None. E.A. Garcia: None. G.H. Tabada: None. D. Low: None. R.L. Hui: None. Introduction: Bisphosphonate (BP) drugs remain one of the first line therapies for fracture prevention, but treatment patterns have changed since BPs were first approved for osteoporosis. This study examines trends among adults initiating oral BP in a large US healthcare system over a 25-year period (1988-2022) and in each successive 5-year period. Methods: The study cohort comprised adults aged 50-89y who initiated alendronate, risedronate or oral ibandronate during 1998-2022 in an integrated healthcare delivery system, excluding those with select bone disorders, multiple myeloma, secondary metastatic cancer, end stage renal disease, and receipt of intravenous BP. Covariates included age (proportion age <65y), sex, race and ethnicity, and prior fracture (diagnosed within 5 years) using electronic health record data. Demographic trends and fracture status were examined across time periods. The chi-squared test and Cochrane-Armitage test for trend were used to examine differences and trends. This report extends findings from an earlier report of women initiating oral BP during 2004-2012 in the same healthcare population. Results: Among 208,780 adults (86% women) who initiated BP, including 26,646 (1998-2002, 35% <65y), 44,726 (2003-2007, 35% <65y), 34,005 (2008-2012, 24% <65y), 35,248 (2013-2017, 19% <65y), and 38,743 (2018-2022, 17% <65y) women and 2348 (1998-2002, 28% <65y), 4895 (2003-2007, 26% <65y), 5172 (2008-2012, 17% <65y), 5331 (2013-2017, 13% <65y), and 11,666 (2018-2022, 5% <65y) men in each 5-year period. Over time, an increasing proportion were age ≥65y (p<0.001 for trend), with larger numbers of older adults in later years partly reflecting initiatives targeting secondary fracture prevention (since 2008 for women, 2015 for men) and BMD screening (since 2011 for women, 2017 for men). Among women initiating BP, the proportion with prior fracture increased from 24-30% (pre-2008) to 43-45% (post-2008), partly reflecting secondary fracture prevention initiatives for women. For men, this proportion increased from 33% (1998-2002) to 42% (2003-2007), 47% (2008-2012), and 54% (2013-2017), but fell to 36% (2018-2022) after BMD screening initiatives began in 2017 for older men (primary prevention efforts). Racial and ethnic diversity in treatment also increased, comparing 1988-2002 (75.2% White, 2.5% Black, 8.6% Hispanic, 12.7% Asian/Pacific Islander) to 2018-2022 (61.5% White, 2.9% Black, 12.2% Hispanic, 21.1% Asian/Pacific Islander, p<0.001 for overall differences and % non-White). Conclusions: In a primary care population of adults initiating oral BP, a larger proportion in later years were age >65y, including larger numbers both with and without fracture coinciding with initiatives for fracture prevention. Among those initiating BP, the relative proportions with prior fracture in each period were likely influenced by primary or secondary prevention efforts. Presentation: 6/2/2024

7740 Adult-Onset Hypophosphatasia Presenting As Low Alkaline Phosphatase Level Following Denosumab Use For Osteoporosis

Abstract Disclosure: J. Ocampo Mascaro: None. P. Wax: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding. Background: Hypophosphatasia (HPP) is a genetic disease characterized by low activity of the tissue non-specific alkaline phosphatase. It has a broad range of clinical phenotypes, with adults usually presenting with an incidental low alkaline phosphatase (ALP) finding. Differentiating this from other causes of low ALP is challenging, especially when treating osteoporosis, as antiresorptive therapy such as denosumab and bisphosphonates may cause low ALP and carry the potential of increasing risk of atypical femoral fractures in patients with undiagnosed HPP. Clinical Case: A 64-year-old woman with history of nephrolithiasis, hypercalciuria, and osteoporosis (screening DXA lowest T-score -3.3 in femoral neck (FN)) but no prior fractures or dental issues was seen in clinic. Initial bloodwork showed normal range calcium, 25-OH vitamin D, and intact PTH. Pre-treatment ALP was 42 IU/L (N 39-117). Work up for secondary causes of osteoporosis was negative. Three yearly doses of IV zoledronic acid resulted in +4.2% BMD increase in lumbar spine (LS) but no changes in FN. She had no side effects but was found to have a decrease in ALP to 33 IU/L. This normalized back to 42 IU/L during a three-year drug holiday. Follow up DXA noted significant decline in BMD, hence denosumab was initiated. ALP decreased back to the 30-35 IU/L range. Fasting Vitamin B6 level (off B6 supplements for 1 week) was 23.4 ng/ml (N 2.1-21). Urine phosphoethanolamine was mildly elevated at 5 mmol/mol creatinine (N ≤4). Genetic testing evidenced a pathogenic ALPL variant (Exon 6, c.575T>C (p.Met192Thr), heterozygous) compatible with HPP. She had tolerated three doses of denosumab by then with BMD improvement of 5.0% in LS but no changes in FN and no atypical femoral fracture. Denosumab was stopped. Abaloparatide was started for osteoporosis with close monitoring for worsening hypercalciuria. Conclusion: This case demonstrates that adult HPP patients may present with subtle findings and lower range of normal ALP and may tolerate short courses of antiresorptive agents. There is a need for better screening and diagnostic criteria for adult HPP patients whose ALP levels may not be initially low before initiating antiresorptive drugs for osteoporosis. The risk of adverse effects from therapy will likely vary significantly based on the clinical severity/presentation of HPP as some adults with lower ALP ranges might be more susceptible to developing atypical femur fractures (1). Balancing atypical femur fracture risk with the benefits of antiresorptive treatment in decreasing risk of osteoporotic fractures highlights the need for better risk stratification to prevent undertreatment of osteoporosis. Reference: 1. Warren AM, Ebeling PR, Grill V, Seeman E, Sztal-Mazer S. Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia. Endocrinol Diabetes Metab Case Rep. 2021 Sep 1;2021:21-0096. Presentation: 6/2/2024

7999 Tumor Induced Osteomalacia Caused By Glomangiopericytoma

Abstract Disclosure: N. Kabir: None. E. Campbell: None. S. Singh: None. Introduction: Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by FGF-23 secreting tumors. Excessive production of FGF23 causes hypophosphatemia, decreased phosphate resorption in the gut, increased renal phosphate wasting, and decreased activation of Vitamin D. This leads to decreased bone density, bone pain, proximal muscle weakness, impaired gait, and recurrent fractures. Case Presentation: 44 year old male with a history of recurrent insufficiency fractures and weakness. At the time of evaluation, he reported fracture of tibial growth plate, sacral fracture, and metatarsal stress fracture. Other symptoms included bone pain, fatigue, muscle weakness, and intercostal muscle spasms with exertion. His pain was debilitating, requiring crutches to ambulate. Available labs at that time were significant for hypophosphatemia (1.3 mg/dL), elevated ALP (160 U/L), low 25OH-vitamin D (26 ng/mL), and normal calcium (8.7 mg/dL). Urine studies demonstrated phosphaturia (fractional excretion of phosphate, 62.4%). FGF23 level resulted at the upper limit of normal (210 RU/mL). Pending further evaluation, burosumab was started. Further work up included a 68Ga-PET-DOTATATE scan revealing a somatostatin receptor expressing soft tissue mass in the left sphenoid sinus and posterior left ethmoid sinus. The scan also demonstrated impending bilateral femur fractures, prior rib fractures, and sacral insufficiency fractures. Based on these findings, he was admitted to the hospital and underwent prophylactic, intramedullary nail fixation of his bilateral femur fractures. He underwent resection of skull base tumor with the final pathology revealing a sinonasal glomangiopericytoma. Immunohistochemical stain was positive for CD99 and cyclin D1, and focally positive for SMA, consistent with histopathologic diagnosis. Patient required prolonged inpatient rehabilitation to recover independent ambulation. Discussion: Sinonasal glomangiopericytoma (SNGP) is a mesenchymal tumor that accounts for <0.5% of all nasal and sinus tumors. TIO due to SNGP is extremely rare, with only a few cases reported since the 1990s. As seen with our patient, TIO from SNGP rarely presents with sinonasal symptoms, and can often be overlooked. Our patient hadb significant progression of disease and disability due to numerous delays in diagnosis and management. Definitive cure for TIO can be achieved with complete surgical resection of the tumor, but failure to diagnose in a timely manner can result in decline in quality of life. Our takeaway from this case is that providers should obtain FGF23 levels, especially in the setting of hypophosphatemia and phosphaturia, to complete the work up for osteomalacia. Presentation: 6/1/2024

12478 A Pilot Evaluation Of Automated Morphometry Performance On Vertebral Fracture Assessment (vfa) And Its Impact On Interpretation

Abstract Disclosure: S. Syed: None. N. Binkley: None. Introduction: Prevalent vertebral fractures convey increased fracture risk but are often clinically silent; thus, imaging is required for their detection. Vertebral fracture assessment (VFA) can be performed at the time of DXA. We hypothesized that VFA automated morphometry does not accurately identify the number of vertebrae visualized nor the number of fractures present and sought to begin exploring if morphometry impacted the formal interpretation. Methods: Patients seen by an Orthopedic bone health provider were studied. Their VFA images were independently assessed by two physicians, after which a consensus “gold standard” (GS) reading was reached. The number of vertebral bodies able to be assessed and the number of fractures identified by morphometry (M), the formal interpretation (I) and the GS result were compared by one way ANOVA. Results: The study cohort included 100 patients with mean (SD) age 77.6 (8.6) years, 81% female with BMI 26.7 (5.0) kg/m2, 91 of whom had prior clinical fracture. M reported visualizing more vertebral bodies than I and GS; 1243, 1168 and 1063 respectively. I identified numerically more (13) fractures than did M (150 vs. 137) but was lower than GS (167). The automated and formal reports were identical in 52 patients; in this subgroup, 8 patients (15%) had vertebral fractures that were not identified on the formal interpretation. In this same group of 52 patients, an additional 7 (13%) with vertebral fractures had 9 vertebral fractures missed. Conclusion: In this pilot study assessing VFA, automated vertebral morphometry reports identifying more vertebrae than are actually able to be evaluated while missing almost 18% of vertebral fractures that were actually present. That the formal interpretation is identical to that of morphometry in over 50% of patients, while missing vertebral fractures over 12% of the time, implies that morphometry is adversely impacting the formal interpretation and thereby potentially patient care. Further study with larger datasets is indicated. Presentation: 6/3/2024

7474 Demographic Patterns In Early Vertebral Fracture Diagnoses Among Women After Initiation Of Bisphosphonate Therapy

Abstract Disclosure: J.C. Lo: None. G.H. Tabada: None. M. Chandra: None. L.D. Carbone: None. T.C. Tan: None. J. Yang: None. E. Garcia: None. Introduction: Vertebral fractures (VFX) are a major osteoporotic fracture that identify women at high risk for subsequent fracture. However, less is known about demographic patterns in VFX diagnoses among women initiating osteoporosis therapy, including prior and subsequent VFX diagnoses. In this study, we examined racial and ethnic variation in VFX diagnoses among older women who initiated oral BP therapy in a large healthcare system. Methods: The study cohort included women aged 65-85y who initiated oral bisphosphonate (BP) therapy in 2008-2017, excluding those with selective bone disorders, metastatic cancer, multiple myeloma, kidney dialysis or transplant. Prior VFX diagnosis was based on ICD-9/10-CM diagnosis codes in the 5 years prior to or at BP initiation, excluding fracture codes related to open fracture or spinal cord injury. In the 2 years after BP initiation, new or initial encounter diagnoses of VFX were examined among those without prior VFX diagnoses. Findings were compared by race and ethnicity, overall and within age strata (65-74y, 75-85y). New VFX diagnoses after BP initiation were examined using Cox proportional hazard analyses, reporting hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 50,870 women aged 65-85y (56.5% age <75y) who initiated BP (66.9% White, 16.7% Asian/PI, 11.9% Hispanic, 3.2% Black), 2819 (5.5%) had prior VFX diagnosis. By race and ethnicity, 4.5% of White, 2.3% of Asian/PI, 3.5% of Hispanic, and 4.1% of Black women aged 65-74y had prior VFX diagnosis, increasing to 7.9% of White, 6.6% of Asian/PI, 7.9% of Hispanic, and 6.3% of Black women aged 75-85y. During 2 years follow-up after BP initiation and stratified by age, the incidence of new VFX diagnosis (per 1000 person-years) was 8.9 (7.9-9.9) for White, 3.2 (2.3-4.5) for Asian/PI, 7.1 (5.3-9.5) for Hispanic, and 6.8 (3.8-12.3) for Black women aged 65-74y, and 17.4 (15.9-19.0) for White, 13.0 (10.2-16.6) for Asian/PI, 14.2 (11.2-18.1) for Hispanic, and 6.1 (3.1-12.2) for Black women aged 75-85y. Adjusting for age, prior clinical fracture, and BP initiation year, the risk of new VFX diagnosis among women aged 65-74y (White as reference) was much lower for Asian/PI women (HR 0.40, CI 0.28-0.57) but not Black (HR 0.70, CI 0.38-1.29) and Hispanic (HR 0.80, CI 0.59-1.10) women. For older women aged 75-85y, the risk was much lower for Black women (0.36 (CI 0.18-0.72) but not Asian/PI (0.78, CI 0.60-1.02) and Hispanic (0.83, CI 0.64-1.07) women. Conclusion: Compared to White women, much lower VFX diagnosis among younger but not older Asian/PI women and among older but not younger Black women were seen in the 2 years after BP initiation. While new VFX diagnoses may represent prevalent or incident VFX and underlying fracture risk and continuation of BP may differ by group, these pilot findings support the need for more studies examining ethnic variation in VFX among older women, including differences by age. Presentation: 6/3/2024

7077 A Rare Case Of Hypophosphatasia Presenting With Osteoporosis In A Young Female Patient- Diagnostic Delay In Hypophosphatasia

Abstract Disclosure: R. Abdelmasih: None. I. Ali: None. Introduction: Hypophosphatasia is a rare hereditary cause of secondary osteoporosis that affects 1/100.000 individuals. The rate of osteoporosis due to hypophosphatasia is probably underestimated as it likely goes undiagnosed in heterogeneous or milder cases. We present a case of Hypophosphatasia that presented initially with osteoporosis and went misdiagnosed for years with intermittent treatment of Bisphosphonate, luckily with no atypical fractures that prompted different course of management for osteoporosis. Case Presentation: A 44-year-old female with a history of rheumatoid arthritis and osteoporosis diagnosed 7 years prior and treated with intermittent bisphosphonate which was discontinued due to side effects including muscle aches and bone pains, presented to our endocrinology clinic to establish care for osteoporosis. Patient denied prior fractures. She reported jaw pain that is being evaluated by otolaryngology and a dentist. Family history is negative. DEXA scan showed Z scores of -1.1, -1.8, and -2.2 of the lumbar spine, femoral neck, and total femur respectively. Laboratory workup showed consistently low alkaline phosphatase (ALP) 25, 20, <20 U/L (ref range 34-123), elevated Vitamin B6 of 167 nmol/L (ref range 20-125), normal parathormone, calcium, phosphate, Vit D, magnesium, and liver enzymes. Genetic testing was sent for Tissue non-specific alkaline phosphatase (TNALP). Hypophosphatasia was diagnosed based on clinical and laboratory findings, patient was started on Asfotase alfa. Clinical course is to be followed. Discussion: Hypophosphatasia is a rare hereditary disorder due to mutation of (TNALP). In normal induvial, TNALP breaks down pyrophosphate to phosphate. It also plays a role in transferring Vit B6 into the tissues. Hence, clinical presentation due to impaired calcium-phosphate hemostasis is broad including musculoskeletal pain, pseudofractues, dental abscess, and neurological symptoms (due to accumulation of Vit B6). The clinical picture varies depending on the heterogenicity of ALPL mutation. Genetic testing is not mandated to establish diagnosis, clinical presentation and laboratory testing including low ALP and elevated Vit B6 are sufficient. However, genetic testing and counseling are recommended for the patient’s sake and their family members. Antiresorptive bone therapy is contraindicated due to a further decrease of bone turnover with reported cases of increased risk of atypical femur fracture, Bone density is reported to improve with enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase (Asfotase Alpha), if further treatment is needed, anabolic treatment is preferred. We present this case to shed light on such a rare disease to decrease rates of underdiagnosis or delayed diagnosis in young patients presenting with osteoporosis for prompt treatment and improved quality of life of these patients. Presentation: 6/2/2024

Prior fragility fractures are associated with a higher risk of 8-year complications following total shoulder arthroplasty.

As the population ages, more patients with osteoporosis are undergoing total shoulder arthroplasty (TSA), including those who have sustained a prior fragility fracture. Sustaining a fragility fracture before TSA has been associated with increased risk of short-term revision rates, periprosthetic fracture (PPF), and secondary fragility fractures but long-term implant survivorship in this patient population is unknown. Therefore, the purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision TSA, periprosthetic fracture, and secondary fragility fracture. Patients aged 50years and older who underwent TSA were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3years prior to TSA. Patients who had a prior fragility fracture (7631) were matched 1:1 to patients who did not based on age, gender, Charlson Comorbidity Index (CCI), smoking, obesity, diabetes mellitus, and alcohol use. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, periprosthetic fracture, and secondary fragility fracture within 8years of index surgery. The 8-year cumulative incidence of revision TSA (5.7% vs. 4.1%), periprosthetic fracture (3.8% vs. 1.4%), and secondary fragility fracture (46.5% vs. 10.1%) were significantly higher for those who had a prior fragility fracture when compared to those who did not. On multivariable analysis, a prior fragility fracture was associated with higher risks of revision (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.24-1.74; p < 0.001), periprosthetic fracture (HR, 2.98; 95% CI, 2.18-4.07; p < 0.001) and secondary fragility fracture (HR, 8.39; 95% CI, 7.62-9.24; p < 0.001). Prior fragility fracture was a significant risk factor for revision, periprosthetic fracture, and secondary fragility fracture within 8years of primary TSA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications. III.

DXA In People Living With HIV

Abstract Background As people with HIV now live a near normal life-span, prevention of fractures is increasingly important. Alongside conventional risk factors for fractures, antiretrovirals and chronic inflammation are believed to contribute to their increased fracture risk compared to the general population. Methods We audited a 1-year series of consecutive DXA scans conducted on people living with HIV vs the European AIDS Clinical Society guidelines on bone health. These guidelines specify indications for DXA, for repeat DXA and for osteoporosis treatment. We recorded DXA results, any prior DXA, fracture history, fracture risks and drug treatment history. We assessed frequency of scanning and pharmacological management of low bone mass vs. guidelines. Results N=90 referred for DXA, of whom 18% did not attend, leaving n=74; 58% female, 42% male, median age 52 years [36-64] and 56 years [49-69] respectively. Of the 18% (n=14) who were aged under 50, 43% had no clear indication (fracture risk factor) for DXA. Of those aged &amp;gt;50 years (n=60), all scans were indicated as the guidelines advises this in those aged &amp;gt;50 years. Bone density was normal in n=32 (43%), osteopenic in 36 (49%) and osteoporotic in 7 (9%). Fifteen percent overall had a fragility fracture history, none of whom were taking osteoporosis treatment though it was indicated in at least 4 based on their DXA result. N=12 (16%) had a DXA in preceding years, and just 2 of the repeat scans were indicated according to guidelines. For the 12 with serial scans, there was no significant change in T score after a median three-year period. Conclusion Through an audit of consecutive DXA referrals, rather than consecutive individuals, low bone mass and fragility fractures are prevalent in people living with HIV. With advancing age, fracture incidence may rise sizeable in this group therefore due attention to bone health guidelines in required.

The Value of VFA (Vertebral Fracture Assessment) in Routine DXA Scanning

Abstract Background Low-trauma vertebral fractures are strongly predictive of future fracture risk so are generally given osteoporosis treatment regardless of bone density readings, and for every vertebral fracture presenting clinically, it is estimated that there are another two which are ‘silent’ or may have been ascribed to mechanical back pain. VFA (vertebral fracture assessment) during DXA scanning is a means of assessing the lateral spine for evidence of fractures which may have been undiagnosed prior. The International Society of Clinical Densitometry (ISCD) recommends a VFA in those with a T score &amp;lt;-1.0 plus one of: women ≥70 years, men ≥80 years, historical height loss &amp;gt;4cm, self-reported but undocumented prior vertebral fracture, regular use of steroids. Methods We developed a nurse-led DXA service in late 2021, conducting all scans in according with ISCD and HIQA guidelines however we do VFA on all patients aged over 50 years as it adds minimal time and negligible radiation exposure. In 2023 we commenced recording whether VFA fractures were previously diagnosed, in order to evaluate the benefits of VFA and so determine ongoing practice. To this end, we reviewed all DXA results since service launch for VFA evidence of fractures, and for patients from the calendar year 2023, we noted questionnaire responses and referral information as to whether any vertebral fracture was known of prior. Results There were 3,759 DXA scans conducted over the 24-month period 2022-2023 of whom n=3,299 had VFA performed. N=470/3,299 (14%) had a fracture identified on VFA. In the year 2023 only, of the n=289/1,795 (16%) who had a fracture on VFA, n=96 of these had not been diagnosed previously, representing a screening pick up rate of 5%. Conclusion VFA is a high-yield investigation for detecting undiagnosed vertebral fractures. As these fractures have definite treatment implications, wider use of VFA should be considered with routine DXA.

Similarities and differences between European guidelines for the management of postmenopausal osteoporosis

SummaryWe conducted a review of 10 national guidelines from five EU countries to identify similarities or differences in recommendations for the management of patients with osteoporosis. We found general alignment of key recommendations; however, there are notable differences, largely attributed to country-specific approaches to risk assessment and reimbursement conditions.IntroductionThe classification of fracture risk is critical for informing treatment decisions for post-menopausal osteoporosis. The aim of this review was to summarise 10 national guidelines from five European countries, with a focus on identifying similarities or differences in recommendations for the management of patients with osteoporosis.MethodsWe summarised the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease-International Osteoporosis Foundation guidelines and reviewed guidelines from France, Germany, Italy, Spain and the UK.ResultsThe approach to risk assessment differed across the guidelines. In France, and Spain, risk assessment was based on DXA scans and presence of prior fractures, whereas UK, German and Italian guidelines recommended use of a validated risk tool. These differences led to distinct definitions of very high and high-risk patients. Guidelines aligned in recommending antiresorptive and anabolic agents as pharmacologic options for the management of osteoporosis, with sequential treatment recommended. There was agreement that patients at high or very high risk of fracture or with severe osteoporosis should receive anabolic agents first, followed by antiresorptive drugs. Variations were identified in recommendations for follow up of patients on anti-osteoporosis therapies. Reimbursement conditions in each country were a key difference identified.ConclusionsCriteria for risk assessment of fractures differ across European guidelines which may impact treatment and access to anabolic agents. Harmonisation across EU guidelines may help identify patients eligible for treatment and impact treatment uptake. However, country-specific reimbursement and prescribing processes may present a challenge to achieving a consistent approach across Europe.

Increase in major osteoporotic fractures after therapy with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) can cause severe and sometimes long-standing immune-related adverse events (irAEs). Enhanced immune activation from ICI can theoretically result in osteoclast activation, bone loss and fracture. The...

P20. Impact of prior fragility fractures on risk of revision and secondary fragility fracture after lumbar spine fusion: a matched cohort analysis

P20. Impact of prior fragility fractures on risk of revision and secondary fragility fracture after lumbar spine fusion: a matched cohort analysis

The relationship between serum monoterpene levels and bone health: a retrospective cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) data.

Monoterpenes, a subset of the terpene family composed of two isoprene units, have garnered significant attention in research circles owing to their potential medicinal benefits. Recent experimental studies indicate that they might exert positive effects on bone health. Nevertheless, the impact of monoterpenes exposure on bone health remains unexplored in humans. We examined 748 adults (age ≥ 40 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to explore the correlation between three monoterpenes (α-pinene, β-pinene, and limonene), bone mineral density (BMD) in the total lumbar spine and proximal femur, FRAX® scores, and prior bone fracture history. Our analysis unveiled a significant inverse association between a one-unit increase in the natural logarithm (ln) of α-pinene and limonene and total proximal femur BMD (ß = -0.027, S.E. = 0.008, P = 0.004 and ß = -0.019, S.E. = 0.007, P = 0.016, respectively). As serum α-pinene levels ascended across quintiles, there was a notable decrease in total proximal femur BMD (P for trend = 0.025). The inverse relationship between ln α-pinene levels and total proximal femur BMD was more pronounced in women, especially pre-menopausal women. Compared to subjects with α-pinene and limonene levels at or below the 50th percentiles, those exceeding this threshold exhibited the lowest mean value of total proximal femur BMD (0.8628 g/cm2, S.E. = 0.026, P = 0.009). However, the trend was not statistically significant (P = 0.070). Additionally, all three monoterpenes were linked to a higher prevalence of previous spine fractures, whereas β-pinene showed a reduced incidence of other types of fractures. In this comprehensive survey of American adults aged 40 and above, higher serum levels of α-pinene and limonene correlated with decreased total proximal femur BMD. Furthermore, our findings suggest a potential combined effect of α-pinene and limonene on total proximal femur BMD. Further investigation is essential to elucidate the clinical relevance and causative nature of our findings.

Goal-directed osteoporosis treatment: ASBMR/BHOF task force position statement 2024.

The overarching goal of osteoporosis management is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment and treatment sequence is selected for individual patients. Goal-directed treatment decisions require assessment of clinical fracture history, vertebral fracture identification (using vertebral imaging as appropriate), measurement of bone mineral density (BMD), and consideration of other major clinical risk factors. Treatment targets should be tailored to each patient's individual risk profile and based on the specific indication for beginning treatment, including recency, site, number and severity of prior fractures, and BMD levels at the total hip, femoral neck, and lumbar spine. Instead of first-line bisphosphonate treatment for all patients, selection of initial treatment should focus on reducing fracture risk rapidly for patients at very high and imminent risk, such as in those with recent fractures. Initial treatment selection should also consider the probability that a BMD treatment target can be attained within a reasonable period of time and the differential magnitude of fracture risk reduction and BMD impact with osteoanabolic versus antiresorptive therapy. This position statement of the ASBMR/BHOF Task Force on Goal-Directed Osteoporosis Treatment provides an overall summary of the major clinical recommendations about treatment targets and strategies to achieve those targets based on the best evidence available, derived primarily from studies in older postmenopausal women of European ancestry.

Non-osteoporotic fractures are associated with increased risk of subsequent major osteoporotic fractures

SummaryWe studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk.PurposePrevious studies demonstrated that osteoporotic fractures—minor and major—increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk.MethodsThe study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population.ResultsThe general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64–2.82), 2.43 (2.32–2.54), and 1.83 (1.74–1.92), respectively.ConclusionNon-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures.