ResearchPad - osteoporosis:-diagnosis-and-clinical-aspects https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-LB73 Is It Possible to Optimize Resources in Bone-Alkaline Phosphatase Medical Request?]]> https://www.researchpad.co/article/elastic_article_8670 INTRODUCTION: Bone metabolism assessment includes total alkaline phosphatase (ALP) and more specifically the bone-alkaline phosphatase (BAP) as markers of bone formation. Its measurement is important for diagnosis and in bone pathology treatment following-up. In our setting, a ten-fold price for BAP has raised the necesity to review in how many cases its request has been justified. AIM: Establish through an appropiate statistical analysis, cut-off values of ALP that could guarantee to perform BAP measurements. Its analysis would allow us to make a demand adequacy. MATERIALS AND METHODS: A retrospective study was carried out on laboratory analysis orders of 405 adult women. We separate them into the following groups: (G1): 48 premenopausal womens (pre) and 357 post menopausal women (pos): (G2)133 <60 years-old, (G3)135: 60-69 years-old and (G4)89: >70 years-old. All patients had measurements of both analytes; ALP (colorimetric method, Roche Cobas, Reference value (RefV)=40-130 UI/L) and BAP (QLIA, Liaison Diasorin, RefV pre=3-19 ug/mL, pos=6-26 ug/mL). Statistic analysis: ROC-Plot to define cut-off value (we define as true positive BAP values over RefV). Kruskal Wallis, Dunn test to compare all the groups. RESULTS: (median and range): ALP(UI/L) G1: 81(38-265) G2: 88(47-211)*, G3: 85(39-213) y G4: 80(40-138) (*p<0.05 G2vsG4). BAP (ug/L) G1: 13.6(5.1-106), G2: 14.3(3.5-61.5)*, G3: 13.9(2.9-52.5) and G4: 11.6(2.0-29.6), (*p<0.05 G2vsG4). We observe that 73% of G1, 93.5% of G2, 92.6% of G3, 97.7% of G4 has showed normal values. The ROC plot analysis showed the best cut-off for ALP in G1=87 (S=92%,Sp=85%,AUC=0.955). If, using this cut off we had processed 18 BAP which 6 patients would have been normal (33.4%). In G2=127 (S=100%, Sp=97.6%, AUC=0.996) using this cut off we had processed 13 BAP, which 4 patients would have been normal (30.8%). Meanwhile in G3=102(S=100%, Sp=85.6%, AUC=0.97) we had processed 30 BAP and G4=120 (S=100%, Sp=96.5%, AUC=0.966) we had processed only 6 BAP. CONCLUSIONS: Application of the calculated cut-off allowed us to investigate 97% of the pathological BAPs. The measurement of ALP first, would guarantee to process only 17% of the requested BAPs. This suggestion would result in a significant saving of our resources, maintaining the quality of care. It is necessary to apply cut-off according to age to justify the BAP assesment. Physicians must define the appropriate exceptions.

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<![CDATA[SUN-LB74 Radiofrequency Echographic Multi-Spectrometry (REMS) for the Assessment of Bone Strength and Fracture Risk Prediction]]> https://www.researchpad.co/article/elastic_article_8596 Introduction Fragility bone fractures impact patient’s quality of life and worldwide healthcare systems: accurate technologies and device are required in order to early diagnose and monitor the effect of osteoporosis on a mass-population basis. Several studied have analysed the pros and cons of the numerous technologies available nowadays for the diagnosis and monitoring of bone health, highlighting the need of further tools able to better define and estimate bone strength and to predict the risk of fracture [1].

Objectives The aim is to assess the state of the art about Radiofrequency Echographic Multi-Spectrometry (REMS).

Methods A review of the available literature was performed, considering full papers, reviews and abstracts on REMS published before January 31th 2020.

Results REMS has been recently presented by an ESCEO consensus paper as a valuable technology for osteoporosis diagnosis and fracture risk estimation [1]. It is based on the automatic processing of the raw unfiltered signals obtained with an ultrasound scan, thus overcoming the main drawback of dual-energy X-ray absorptiometry (DXA) and computed tomography (CT)-based technologies [2]. Moreover, REMS scans are performed at axial skeleton reference sites, i.e. lumbar spine [3] and femoral neck [4], differently from quantitative ultrasound (QUS) technology, which is usually applied to peripheral sites [3]. Clinical performance has been confirmed by a multicentre clinical trial enrolling over 1900 Caucasian women, demonstrating a high correlation between bone mineral density (BMD) estimated by REMS and DXA. In addition, high performance in terms of precision and intra- and inter-operator repeatability of REMS have been assessed [6]. Prospective studies have demonstrated the predictive ability of incident fragility fractures [7] and the high concordance with DXA in terms of measured BMD in patients with rheumatoid arthritis and pre/post-menopause [8, 9].

Conclusions REMS is an innovative approach for the early diagnosis, short-term monitoring of osteoporosis and risk fracture prediction. The available data envisaged for further applications in paediatric patients, pregnant women and patients at risk of secondary osteoporosis (e.g., diabetic, nephropathic, oncological patients). The EchoS system, a device implementing the REMS technology, has recently received the approval from the U.S. Food and Drug Administration (FDA).

References 1. Diez-Perez et al. Aging Clin Exp Res 2019;31(10):1375–89 2. Iwaszkiewicz & Leszczyński. Forum Reumatol 2019;5(2):81–8 3. Hans & Baim. J Clin Densitom 2017;20(3):322-3 4. Conversano et al. Ultrasound Med Biol 2015;41:281–300 5. Casciaro et al. Ultrasound Med Biol 2016;42:1337–56 6. Di Paola et al. Osteoporos Int 2018;30:391–402 7. Adami et al. Ann Rheum Dis, vol.78, supp.2, 2019, p.A928 8. Bojincă et al. Exp Ther Med 2019;18(3):1661-68 9. Kirilova et al. Clin Cases Miner Bone Metab 2019; 16(1):14-17

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<![CDATA[SUN-371 Hyponatremia Correction Normalizes Bone Mineral Density and Bone Fragility in Rats]]> https://www.researchpad.co/article/elastic_article_7114 Multiple epidemiologic studies have associated chronic hyponatremia with both osteoporosis and bone fractures. Studies in experimental animals and cultured cells have demonstrated that reducing the extracellular sodium concentration ([Na+]) causes bone loss primarily by increasing osteoclast formation and bone resorbing activity. In osteoclastic cell cultures, reducing [Na+] activated biochemical and functional changes in osteoclast activity, which appear to occur by direct sodium-sensing mechanisms on osteoclasts that are independent from changes in osmolality. Whether the pathological changes in bones induced by hyponatremia can be reversed by correction of hyponatremia has not been studied. The present studies were initiated to address this question. 22-month-old F344BN F1-hybrid rats were made hyponatremic using a desmopressin continuous infusion while fed a liquid diet. After 3 months of chronic sustained hyponatremia, a cohort of the hyponatremic rats were corrected to a normal [Na+] by removal of the desmopressin minipumps and allowed to recover for 2 months. Both bone density measurements by DXA and biomechanical testing were performed on excised bones from normonatremic control rats (NN, [Na+]=145±5.6 mmol/L, n=9), chronically hyponatremic rats (HN, [Na+]=114±4.7 mmol/L, n =9) and hyponatremic corrected rats (HC, [Na+]=139±1.4 mmol/L, n =9). The results confirm that chronic hyponatremia caused significant decreases in bone mineral density (BMD, g/cm2) in the L4 vertebra (NN=0.166±0.003, HN=0.151±0.002, P=0.002) and femur (NN=0.229±0.004, HN=0.213±0.005, P=0.024). Bone fragility as measured by ultimate load to fracture (UL, Newtons) was also increased in the L5 vertebra (NN=369.8±51.1, HN=262.9±29.4, P=0.0001), but only slightly in the femur (NN=295.4±57.5, HN=286.0±35.4, P=0.682). Following correction of hyponatremia, both BMD and UL recovered after 2 months to levels not significantly different than the normonatremic controls: L4 BMD (NN=0.166±0.003, HC=0.167±0.002, NS); femur bone density (NN=0.229±0.004, HC=0.226±0.003, NS); UL in the L5 vertebra (NN=369.8±51.1, HC=384.1±63.5, NS). These results show that bone fragility parameters are adversely affected by chronic hyponatremia in addition to the previously reported decreases in BMD in rats. Consistent with the BMD results, the trabecular bone in the spine was more severely affected than the cortical bone in the femur. Our results show that much of the bone pathology of hyponatremia-induced osteoporosis can be reversed following correction of the hyponatremia without using specific antiresorptive therapy. Our findings therefore raise the possibility that correction of hyponatremia may be effective as a therapy for treatment of hyponatremia-induced osteoporosis in selected patients.

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<![CDATA[SUN-392 Bone Mineral Density and Body Mass Index in Men with Cystic Fibrosis]]> https://www.researchpad.co/article/elastic_article_7077 Osteoporosis is an important endocrine complication of cystic fibrosis (CF). Low bone mass in CF patients has multiple contributing causes including vitamin D deficiency, calcium malabsorption, pulmonary infection and cytokine production, malnutrition, a sedentary life style, cumulative steroid dose, delayed puberty, and hypogonadism. The objective of this study was to examine the relationship between BMI and bone density of the hip and spine in adult men with CF. We conducted a retrospective chart review of adult men with CF receiving care at an academic medical center. Medical records of 43 men ages 19-60 (32.1±9.8) years were reviewed. 8 men with lung transplant, or receiving chronic glucocorticoid or androgen treatment were excluded. One subject was excluded as his BMI was >3SD above the mean. BMD was measured by dual-energy x-ray absorptiometry at the lumbar spine (LS) and hip. The mean ± SD BMI of the study population was 24.10 ± 5.24 kg/m2, mean LS BMD was 0.96 ± 0.204 g/cm2 and mean hip BMD was 0.701 ± 0.382 g/cm2. Men were divided into three groups: normal BMD, osteopenia, or osteoporosis, based on current guidelines. 8 (24%) men were found to have normal bone density (Z=0.40±0.60), 19 (56%) had osteopenia (Z= -1.57±0.67) and 7 (20%) had osteoporosis (Z= -3.27±0.83). Of these 7, 6 had osteoporosis of the LS only, and one patient had osteoporosis of the hip; 5 were being treated with a bisphosphonate. The three groups of men were similar in age (P=0.93). 25OH-vitamin D levels were 22.6±4.4, 35.6±12.7 and 27.0±13.4 ng/mL, respectively (p=0.03). There was a significant (p=0.023) difference in BMI among these three groups (26.33±4.80 vs 23.25 ± 3.01 vs 20.96±3.64 kg/m2). BMI was strongly positively correlated with LS BMD (r = 0.54, P<0.001) but not with BMD of the hip (r = 0.11, p=0.55). Moreover, LS BMD was highly predicted by body weight (r = 0.90, P<0.0001) but not significantly by height (r = 0.26, p=0.16). These findings indicate that CF-related bone disease (CF-RBD) affecting the LS is common in adult men, and that body weight is a major determinant of LS BMD in men with CF. Possible mechanisms for this association include signaling pathways related to nutritional status and sex steroids.

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<![CDATA[SUN-377 Efficacy of Low Dose Denosumab in Maintaining Bone Mineral Density in Postmenopausal Women with Osteoporosis: A Real World, Prospective Observational Study]]> https://www.researchpad.co/article/elastic_article_6997 Introduction: Denosumab, a fully human monoclonal antibody to RANK-ligand, has been shown to increase bone mineral density (BMD) and reduce the risk of hip, vertebral and non-vertebral fractures in postmenopausal women with osteoporosis (1-3). Varying doses of denosumab including 30mg/3months have demonstrated a decrease in bone remodelling in a dose-dependent manner (2,4-6). The primary objective of this study is to evaluate the efficacy of low dose denosumab (30mg/6 months) in postmenopausal women with osteoporosis who are reluctant to consider or continue the full dose of denosumab due to adverse events (AE) or concerns of potential AE. Methods: Following informed consent, postmenopausal women with a T-score of ≤ -2.5 at the lumbar spine (LS) or at the total hip (TH) received denosumab 30mg/6months. Patients with an additional skeletal disorder, prior fragility fracture, or on oral steroids (daily in the past 12 months) were excluded. The primary endpoint was the percent change in BMD at the lumbar spine (LS), total hip (HP), femoral neck (FN) and 1/3 radius (1/3R) at 12 months. Secondary outcomes were 1) percent change in BMD at the LS, TH, FN, and 1/3R at 24 months and 2) AE. Results: We enrolled 183 patients. The mean age was 69 years (SD= 7.07), 80% of patients had a moderate fracture risk (CAROC tool), 3% were current smokers and 9% consumed alcohol daily. 14.4% of patients were on SSRI/SNRI, 9.6% were on PPI, and no patient was on an aromatase inhibitor. At 12 months (n=125), the mean BMD significantly increased by +2.0% (95% CI 2.8%-1.3%) at the LS (p<0.001). There was no significant change in BMD at the FN, TH, AND 1/3R. At 24 months (n=65), the percent change in BMD was +3.4% (95% CI 4.8%-2.0%: p<0.001) at the LS, +1.5% (95% CI 2.9%-0.15%: p=0.031) at the FN, +1.9% (95% CI 3.5%-0.24%: p=0.025) at the 1/3R. There was no significant change in BMD at the TH. Conclusion: Low dose denosumab appears to be effective in maintaining BMD in postmenopausal women with a moderate fracture risk and may be of benefit in individuals who are experiencing side effects or concerns of side effects. This may also be of value following 10 years of therapy in order to maintain BMD.

References 1.Bekker, PJ, Holloway DL, Rasmussen AS, Murphy R, Martin SW, Leese PT... Depaoli AM. A Single-Dose Placebo-Controlled Study of AMG 162, a Fully Human Monoclonal Antibody to RANKL, in Postmenopausal Women. JBMR, 2004;19(7), 1059-1066. 2.Kumagai Y, Hasunuma T, Padhi D. A randomized, double-blind, placebo-controlled, single-dose study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of denosumab administered subcutaneously to postmenopausal Japanese women. Bone, 2011;49(5), 1101-1107. 3.Lewiecki EM, Miller PD, Mcclung MR, Cohen SB, Bolognese MA, Liu Y, . . . Fitzpatrick LA. Two-Year Treatment With Denosumab (AMG 162) in a Randomized Phase 2 Study of Postmenopausal Women With Low BMD. JBMR, 2007;22(12), 1832-1841.

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<![CDATA[SUN-389 Trends in Osteoporosis Treatment Uptake and Persistence Among Postmenopausal Women in the U.S., 2010–2015]]> https://www.researchpad.co/article/elastic_article_6978 Background: Over the last several years, the approval of new pharmacotherapies, changes to health plan formularies limiting treatment access, the emergence of new evidence related to medication safety and effectiveness, and updates to clinical practice guidelines may have influenced osteoporosis treatment patterns. Sankey visualizations were used to depict postmenopausal (PM) women’s osteoporosis treatment journeys, from treatment uptake, patterns of transition, to persistence. Methods: We conducted a retrospective analysis of all PM women (aged 55+) who newly initiated five antiresorptive treatments between October 1, 2010 and September 30, 2015 using patient and prescription data from the Truven Health Analytics MarketScan Commercial Claims and Encounters and Medicare Supplemental databases. We identified women who were continuously enrolled in the health plan for one year prior to the date of treatment initiation (index date) and were treatment-free during this period. Treatment states were evaluated cross-sectionally at six-month time points; treatment switches and gaps in therapy between time points were not captured. Persistence was defined as a patient being on the same treatment at a given follow-up time point as compared to the treatment they were on at the index date. Results: Among women newly initiating any of the five antiresorptive therapies, alendronate (53%) remained the most commonly prescribed therapy, followed by ibandronate (13 %), zoledronic acid-ZA (12%), risedronate (11 %), and denosumab (11%). New initiation of alendronate was high across all age, prior fracture history, and osteoporosis diagnosis subgroups (range: 45–68%). From 2010 to 2015, new uptake of denosumab increased by 13%, while ZA uptake declined by 10%. A higher proportion of denosumab users were ≥ 65 years (denosumab: 59%; ZA: 54%; alendronate: 46%) and had a prior history of fracture (denosumab: 30%, ZA: 25%; alendronate: 19%) compared to bisphosphonate users. Two-year persistence was highest among women initiating denosumab (58%), followed by ZA (48%), alendronate (32%), ibandronate (30%), and risedronate (25%). Persistence was lowest for oral bisphosphonate users (alendronate range: 30–33%), irregular among ZA users (range: 29–49%) and higher for denosumab users across all subgroups (range: 46–59%). From 2010 to 2014, persistence improved for all therapies, except among ZA users, which declined by 9%. Conclusions: Little has changed in the prescribing patterns and patient profiles of PM women newly initiating antiresorptive therapies over five years from 2010–2015. Alendronate remained the most commonly prescribed therapy despite lower rates of persistence, with similarly high uptake regardless of risk for fracture. Denosumab was primarily prescribed to women at higher risk for fracture, and persistence was higher compared to other therapies across all subgroups.

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<![CDATA[SUN-381 Cortical Porosity Is Associated with Peripheral Small Vessel Disease in Adult Patients with Type 2 Diabetes]]> https://www.researchpad.co/article/elastic_article_6917 Patients with Type 2 Diabetes (T2D) are at higher fracture risk despite having relatively normal or even increased BMD by DXA. Increased cortical porosity has emerged as a potential factor contributing to fragility fractures in T2D. However, there is conflicting evidence whether T2D patients have increased cortical porosity. We hypothesized that microvascular complications have an important role in cortical porosity. Thus, we performed high-resolution peripheral quantitative computed tomography imaging at the distal radius and tibia to evaluate bone microarchitecture in men with T2DM age ≥ 50 yrs or postmenopausal women with T2DM and nondiabetic controls. Comprehensive diabetic complications were assessed in all patients including urine microalbuminuria, retinopathy, neuropathy (touch, temperature, and vibration sensation), ankle brachial index (ABI) and transcutaneous oxygen tension (TcPO2). Percent differences between groups were obtained from linear regression models adjusting for age, BMI, and sex. Relationships between variables were assessed using adjusted Spearman correlations. A total of 164 T2D patients (mean age 68.9 ±7.8 yrs.; 56.7% men; HbA1C=7.7 ±0.9%; mean diabetes duration 15.2 yrs.) and 107 nondiabetic controls (mean age 67.3±8.8 yrs.; 42.1% men; HbA1C =5.4 ±0.3%) were recruited to the study. Overall, there was a trend for increased cortical porosity at the distal tibia in the T2D group (+12.2%; p=0.063) compared with nondiabetic controls. Of note, TcPO2 was negatively correlated with cortical porosity at the distal radius (r= -0.17; p= 0.039) and distal tibia (r= -0.15; p= 0.073). In particular, the Low TcPO2 (≤40 mmHg) group (n=29) had greater cortical porosity at the distal tibia (+19.6 %; p=0.037) compared with the High TcPO2 (>40 mmHg) group (n=133). In addition, the low TcPO2 group had a significant increase in cortical porosity in the distal tibia (+24.8% p=0.020) compared with nondiabetic controls. In conclusion, this is the first evidence in humans indicating that TcPO2, a measure of microvascular blood flow, is linked to cortical porosity in the distal radius and tibia in T2D patients. Our findings may explain the conflicting findings regarding cortical porosity in T2D because only T2D patients with impaired microvascular blood flow have increased cortical porosity. Collectively, our data indicate that cortical porosity is a microvascular complication of longstanding T2D.

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<![CDATA[SUN-397 The Osteosee System Measurements, Based on Parametric Electrical Impedance Tomography, Correlate with Dual X-Ray Absorptiometry Results for the Diagnosis of Osteoporosis]]> https://www.researchpad.co/article/elastic_article_6867 Introduction: Dual X-Ray Absorptiometry (DXA) is the gold standard for the diagnosis of osteoporosis, but it has its pitfalls. The OsteoSee @Clinic is a novel portable and user-friendly system, which uses parametric Electrical Impedance Tomography (pEIT), being developed to allow screening and diagnosis of osteoporosis at the primary care clinic

Aim: To test the new system and compare its results to those of the DXA system.

Methods and Subjects: This prospective study was conducted between 01/01/2019 and 01/06/2019. Subjects who presented for a routine DXA scan (lumbar spine and proximal femur with Lunar Prodigy GE healthcare system) were enrolled. After signing an informed consent form, they were scanned with the OsteoSee @Clinic system (OsteoSee Ltd., Israel) using 5 electrodes placed around the left distal forearm and around the pelvis.

Results: OsteoSee @Clinic data were compared to DXA total hip bone mineral density (BMD). Correlations were examined between pEIT-index of the pelvis versus DXA total hip BMD. Sensitivity and specificity were calculated according to the diagnosis obtained by DXA based on the total hip T-score. An analysis based on 182 subjects (35 healthy, 115 osteopenia, 32 osteoporosis) scanned on the wrist showed an R-value of 0.795 (p-value < 0.001) representing the correlation between the pEIT-wrist index and DXA results. From the ROC plot, we obtained a sensitivity of 84% and specificity of 71% to diagnose osteoporotic vs osteopenic & normal subjects, and a sensitivity of 82% and specificity of 86% for identifying osteopenic & osteoporotic vs normal subjects. An analysis of 98 subjects (17 healthy, 66 osteopenic, 15 osteoporosis) scanned on the pelvis showed an R-value of 0.740 (p-value < 0.001), representing the correlation between the pEIT-pelvis index and DXA BMD. From the ROC plot, we obtained a sensitivity of 80% and specificity of 81% to diagnose osteoporotic vs osteopenic & normal subjects, and a sensitivity of 70% and specificity of 76% for identifying osteopenic & osteoporotic Vs normal subjects.

Conclusions: The OsteoSee @Clinic system results correlate well with DXA measurements, especially when taking into account clinical interpolations. Sensitivity and specificity values indicate that the OsteoSee @Clinic system can provide screening and diagnosis of osteoporosis. With the DXA system being costly to operate and inaccessible to many patients, the OsteoSee @Clinic system may address the unmet need for diagnosing and treating osteoporosis, and offer an alternative for a broader screening of the population at risk of fractures.

Disclosure: The study was funded by OsteoSee Ltd., Israel

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<![CDATA[SUN-380 Opportunistic Screening with Abdominal CT in Patients with Diabetes Can Identify Those at High Risk of Osteoporosis and Osteopenia]]> https://www.researchpad.co/article/elastic_article_6569 Background: Diabetes mellitus (DM) increases the risk of fracture at any given bone mineral density (BMD). However, the optimal strategy for osteoporosis screening with DXA is unknown in those with DM. A previously described strategy in the general population known as “Opportunistic Osteoporosis Screening” uses computer tomography (CT) images done for other reasons to assess the attenuation (density) of L1 in Hounsfield units (HU)—this was found to correlate with DXA-derived T-score. However, neither the methodology nor the cut-points have been specifically validated in those with DM. Thus, the goal of this study was to examine the performance of this methodology and define thresholds corresponding with low BMD in those with DM.

Methods: This was retrospective study using electronic medical record data. Patients with DM were identified by ICD code. Those with both abdominal CT and DXA within a 6-month period were included, excluding patients with CKD stage 5, solid organ transplantation, bariatric surgery, or L1 hardware. L1 attenuation, measured by 2 readers on sagittal view, were averaged. A different reader assessed for vertebral fractures. Fractures of the hip, forearm, humerus, and pelvis were identified by ICD code. The lowest T-score of lumbar spine, femoral neck, total hip, or forearm (available in 11 subjects) was used to compare to L1 attenuation. ROC curves were derived from univariate logistic regression.

Results: 320 subjects met study criteria; 10 (3.2%) had vertebral fractures, 8 (2.6%) had prior major non-vertebral fracture, and 33 (10.3%) had osteoporosis by BMD.

The 18 subjects with major fractures had lower T-scores (-2.3 ± 1.4 vs. -0.8 ± 1.4, p<0.001) and lower L1 attenuation (104 ± 46 vs. 149 ± 47 HU, p<0.001). T-score and L1 attenuation had similar discrimination for prior fracture by area under the ROC curve (0.77 vs. 0.76, p=NS). Moderate osteopenia (T-score -1.5 or less) and L1 attenuation of 130 HU or less had identical sensitivities (72.2% for both) and similar specificities (69.2% vs. 62.5%, respectively) for prior fracture.

In regards to L1 attenuation corresponding to DXA diagnosis of osteoporosis, 160 HU was 94% sensitive, while 110 HU was 80% specific. This is similar to the 90% sensitivity for 160 HU and 90% specificity for 110 HU previously reported in the general population. Given higher fracture risk in DM, moderate osteopenia (n=106) was also examined as an outcome: 130 HU was 61% sensitive and 71% specific. This threshold had similar or improved sensitivity and specificity among subgroups of insulin users, men, and women under age 65.

Conclusion: Our results validate the use of opportunistic osteoporosis screening in patients with DM, which could help clinicians decide on the need for screening DXA. Patients with diabetes and L1 attenuation below 130 HU on CT scan should be considered for DXA screening to formally assess the risk of fracture.

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<![CDATA[SUN-391 Denosumab Treatment of Patients with Osteoporosis and Idiopathic Hypercalciuria]]> https://www.researchpad.co/article/elastic_article_6499 Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and higher risk of osteoporotic fractures. Denosumab is a RANK-ligand inhibitor that prevents osteoporosis-related fractures. No previous published studies have specifically evaluated denosumab treatment of osteoporosis patients with IHC.

Methods: Retrospective chart review from a private endocrinology clinic identified 31 consecutive patients with osteoporosis (prior fragility fracture and/or t-score ≤-2.5 on bone density scan) with concomitant diagnosis of IHC (defined as urine calcium > 4.0 mg/kg weight/d when intaking low-moderate calcium amounts), who had received at least 3 denosumab injections. Comparisons were made for BMD measurements determined by dual-energy x-ray absorptiometry done before denosumab initiation, and after the latest dose.

Results: There were 28 women and 3 men, with average age of 71.9 ± 8.9 years. 20 subjects had prior total of 31 fragility fractures. Baseline 24-hr urine calcium was 331 ±65 mg/day. Average exposure to denosumab therapy was 9.0 ± 4.8 doses. 27 of these patients received concomitant thiazide diuretics during the course of their denosumab therapy. Baseline t-scores were -2.4 ± 0.8 at lumbar spine, -1.5 ± 0.7 at total hip and -1.8 ± 0.5 at femoral neck. After denosumab therapy, the t-scores were respectively -1.9 ± 0.9, -1.3 ± 0.8 and -1.6 ± 0.7. Mean increases in BMD were seen at the lumbar spine of 6.2 ± 8.4%, at the total hip of 3.2 ± 6.0%, and at the femoral neck of 2.5 ± 8.0%

19 patients were considered to have (+) BMD responses, based on consistent increases in BMD and/or t-scores across all spine and hip sites. 4 patients had (-) BMD responses, based on decreased BMD and/or t-scores across all sites. 6 patients had mixed responses and 2 did not have comparative BMD data. Baseline urine calcium did not seem to correlate with clinical responses. Those patients with longer duration of thiazide and/or denosumab use had higher likelihood of (+) BMD responses. However, during the course of follow-up, 4 subjects suffered 7 fragility fractures while treated with denosumab: 3 with (+) and 1 with (-) BMD responses.

Conclusion: Denosumab can effectively increase BMD in a cohort of osteoporosis patients with IHC, the majority of whom also received thiazide. However, increased BMD response did not necessarily predict lower risks of fragility fractures. Further research needs to evaluate the role of denosumab therapy in such high-risk patients.

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<![CDATA[SUN-372 Deterioration of Bone Microarchitecture in Prediabetes Is Partly Mediated Through Fibroblast Growth Factor 21]]> https://www.researchpad.co/article/elastic_article_6239 Introduction: Prediabetes has been reported to be associated with a worse trabecular bone score (TBS). Fibroblast growth factor 21 (FGF21) levels are raised in prediabetes and other insulin-resistant states, and FGF21 has been reported to be implicated in bone metabolism. We compared the bone mineral density (BMD) and TBS between prediabetes and normoglycemia, and studied the correlation of FGF21 with BMD and TBS. Method: Chinese postmenopausal women aged between 55 and 80 and without type 2 diabetes were recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study between November 2016 and October 2018. Participants were excluded if they were already on anti-osteoporosis therapy, had secondary causes of osteoporosis, had body mass index (BMI) <15 or >37 kg/m2 (when TBS measurement may not be accurate), or had an estimated glomerular filtration rate (eGFR) <30mL/min. They were divided into prediabetes (defined by fasting glucose ≥5.6mmol/L or HbA1c ≥5.7%) and normoglycemia. BMD and TBS were measured by dual-energy X-ray absorptiometry. Serum FGF21 levels were measured with an in-house ELISA kit. Results: 258 participants were included (130 prediabetes and 128 normoglycemia), with a mean age of 61.5±5.1years and mean BMI of 24.2±3.7kg/m2. BMD over lumbar spine, femoral neck and total hip were all comparable between prediabetes and normoglycaemia, while TBS was lower in prediabetes (1.27±0.07 vs 1.30±0.07, p=0.007), which remained significant after adjustment for age and BMI. Serum FGF21 levels did not correlate with BMD but inversely correlated with TBS. On multiple linear regression models, serum FGF21 levels showed an independent inverse correlation with TBS (standardized beta -0.13, p=0.031), which remained significant with the inclusion of homeostasis model assessment of insulin resistance (HOMA-IR) in the model. Conclusion: Among Chinese postmenopausal women, bone quality was worse in prediabetes despite comparable bone density. Serum FGF21 levels showed a significant independent correlation with TBS, suggesting the potential impact of FGF21 on the deterioration of the bone microarchitecture in prediabetes.

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<![CDATA[SUN-383 Potential Impact of Using Male vs Female T-Scores for BMD Classification in Men]]> https://www.researchpad.co/article/elastic_article_6168 BACKGROUND: Osteoporosis is traditionally associated with post-menopausal women, but up to up to one-third of osteoporosis-related fractures occur in elderly men. The International Society for Clinical Densitometry (ISCD), the World Health Organization, and the Fracture Risk Assessment Tool (FRAX) all recommend using a white female reference for BMD T-score for men. However, in clinical practice and previous clinical trials, a sex-specific white male reference T-score is used. This report examines the implications of using a female versus male reference for T-score calculation in men.

METHODS: We reviewed BMD findings in 703 men (age 70-85y) who experienced a proximal femur, humerus, or distal radius/ulna fracture. For this cohort, femoral neck BMD was used to calculate a BMD T-score using either the young adult male and young adult female peak values (mean BMD 0.930 ± 0.136 and 0.849 ± 0.111 g/cm2, respectively). Osteoporosis was defined by BMD T-score ≤ -2.5, and osteopenia by BMD T-score < -1.0 and > -2.5. We also calculated FRAX-estimated fracture risk for hypothetical men ages 60-85y, with and without prior fracture. We used the National Osteoporosis Foundation (NOF) recommendations for treatment based on BMD (osteoporosis by BMD, or osteopenia by BMD with a 10-year risk of hip fracture ≥ 3% or 10-year risk of major osteoporotic fracture ≥ 20%).

RESULTS: The mean BMD for this cohort was 0.670 g/cm2 and the median T scores were -2.0 (male reference) and -1.7 (female reference). Using the male T-score, 29% of men were classified as having osteoporosis, while using the female T-score, only 21% were so classified. 36% of men age 70-79y and 19% of men age 80-85y with osteoporosis (using the male T-score) would be reclassified from osteoporosis to osteopenia when a female T-score is used. Hypothetical cases of men age 60-85y (height 170 cm, weight 70 kg, BMD 0.590 g/cm2 equivalent to a male T -2.5 or female T -2.2) were used to calculate 10-year hip fracture risk using FRAX. For these hypothetical cases, the calculated 10-year risk of hip fracture exceeded the NOF treatment threshold of 3% (10-year hip fracture risk) for all cases, with or without prior fracture.

CONCLUSION: For elderly men with fracture with male-T osteoporosis and female-T osteopenia, the T-score reference population used does not alter treatment recommendations because the calculated hip fracture risk is already above the treatment threshold of 3%. This is also true for men age ≥70 without a prior fracture. Hence the debate pertaining to the appropriate T-score reference population for men has limited relevance for men age ≥ 70 years who are being screened for osteoporosis.

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<![CDATA[SUN-395 Pelvic Bone Density Is Lower Than Bone Density of Hip and Femoral Neck in Postmenopausal Women]]> https://www.researchpad.co/article/N943e3a1b-e978-4c23-9fc1-dd13ffabed51 Pelvic fractures represent 7% of all fragility fractures; they account for 5% of the cost of osteoporotic fracture care, and are commonly (> 50%) associated with loss of independence in the elderly. The incidence of pelvic fractures has increased significantly over the past 3 decades. However, little is known about the relationship between bone mineral density (BMD) and pelvic fractures. We have conducted a pilot cross-sectional study to establish a method of measuring pelvic BMD and to correlate BMD of the pelvis with BMD at other skeletal sites. Postmenopausal women without a history of pelvis and hip fragility fractures were enrolled. Hip, spine, and pelvis DXA scans were obtained using a Hologic DXA machine. Pelvic BMD was calculated using Hologic Research Software from 3 areas of the pelvis (R1: public symphysis, R2: inferior pubic ramus, and R3: superior pubic ramus), corresponding to common fracture locations. Pelvis BMD was the average of the 3 pelvis sites. Pelvic BMD measurement precision error was calculated using the root mean square method (Recommended by International Society of Clinical Densitometry (ISCD)). Statistical analysis was used to compare BMD at different sites. Alpha error was set at 0.05. Of 73 postmenopausal women who were enrolled in the study (average age 64 years, average 15 years postmenopausal), 3% had chronic kidney disease, 7% had type 2 DM, 3% were on corticosteroids and none were smokers. BMD of femoral neck assessed on pelvic DXA was not significantly different from femoral neck BMD measured on standard DXA (P=0.09). To assess pelvis BMD measurement precision, 15 patients underwent 3 separate pelvic DXA images after repositioning. BMD precision error was 0.011g/cm2 which is slightly lower than the precision total hip BMD at our center (0.007 g/cm2). BMD of R1, R2, and R3 pelvic areas were measured as 0.44±0.15, 0.41± 0.15, and 0.62 ±0.19 g/cm2, respectively. Notably, BMD of R3 was significantly higher than the other 2 areas (P<0.001, ANOVA). Average BMD (0.49±0.14 g/cm2) of pelvis was significantly lower than BMD of femoral neck (0.72± 0.16 g/cm2), total hip (0.86±17 g/cm2) and spine (0.97± 19 g/cm2)(P <0.001). Average BMD of pelvis was significantly lower in participants with osteopenia and osteoporosis of the hip and femoral neck compared to participants with normal BMD in those locations. In summary, we report a precise method of measuring BMD of commonly fractured areas of the pelvis. Pelvis BMD is lower than hip, femoral neck, and spine. Bone density of the pelvis correlates with hip and femoral neck bone density. The results of this pilot study can be used for future studies looking at pelvic low bone density in patients with pelvic fragility fractures which could help identify patients at risk for pelvic fragility fractures and change how osteoporosis is defined based on DXA images.

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<![CDATA[SUN-376 A Quality Improvement Project on Identification and Management of Primary Hyperparathyroidism in Patients Who Present with Osteoporosis to Reduce Morbidity from Bone Disease]]> https://www.researchpad.co/article/N1028434d-a6ff-4370-a4b6-6ea7868957c7 <![CDATA[SUN-385 Differential Effects of Abaloparatide and Teriparatide on Hip Cortical Volumetric BMD by DXA-Based 3d Modeling]]> https://www.researchpad.co/article/N3638afd1-b983-4003-b81f-633b47238874 <![CDATA[SUN-388 Role of QUS and Functional Tests in Evaluating Fracture Risk Based on Frax Tool]]> https://www.researchpad.co/article/N55246931-c6a5-459f-bbf8-d2d8e7c218c2 -1.05 (adequate) or ≤ -1.05 (inadequate);Sitting – rising test (SRT) (composite score): age-reference values at quartiles 3 and 4 (adequate); quartiles 1 and 2 (inadequate); best result 3 attempts of the dominant arm handgrip test, according to age and gender: percentile ≥50 (adequate) and <50 (inadequate); FRAX tool: suggests high risk for major osteoporotic fractures if > 20% and for hip fractures when > 3%; NOGG (complement to FRAX): patient′s risk for major and for hip fractures considered as low (green zone), medium (yellow zone) or high (red zone). Qui square test was used for associations. Results: We included 162 individuals: 118 females, mean age 66.8 years and 44 males, mean age 71.8 years. High risk of hip fractures by FRAX was observed in 51% of those patients with a QUS T-score ≤-1.05 while it was observed in 28% of those with a QUS T-score> -1.05 (p=0.005). An inadequate QUS T-score was also associated with a higher risk of hip fracture by NOGG (p=0.007). An inadequate SRT and HT were not associated with a high fracture risk. Conclusions: As densitometry, a method established in clinical practice for the diagnosis of osteoporosis, has limitations in its use, other tools are necessary for tracking the risk of fragility fractures in these events. Quantitative calcaneal ultrasound was a good predictor of hip fracture risk, while SRT and HT were not capable of evaluate for fracture risk stratification in our study, reinforcing the need for QUS for screening in large populations. Having strength and functional ability did not eliminate the need for investigation. ]]> <![CDATA[SUN-395 Pelvic Bone Density Is Lower Than Bone Density of Hip and Femoral Neck in Postmenopausal Women]]> https://www.researchpad.co/article/N3ffa96cb-cef8-4cb4-a9c2-b53b91dd97d6

Abstract

Pelvic fractures represent 7% of all fragility fractures; they account for 5% of the cost of osteoporotic fracture care, and are commonly (> 50%) associated with loss of independence in the elderly. The incidence of pelvic fractures has increased significantly over the past 3 decades. However, little is known about the relationship between bone mineral density (BMD) and pelvic fractures. We have conducted a pilot cross-sectional study to establish a method of measuring pelvic BMD and to correlate BMD of the pelvis with BMD at other skeletal sites. Postmenopausal women without a history of pelvis and hip fragility fractures were enrolled. Hip, spine, and pelvis DXA scans were obtained using a Hologic DXA machine. Pelvic BMD was calculated using Hologic Research Software from 3 areas of the pelvis (R1: public symphysis, R2: inferior pubic ramus, and R3: superior pubic ramus), corresponding to common fracture locations. Pelvis BMD was the average of the 3 pelvis sites. Pelvic BMD measurement precision error was calculated using the root mean square method (Recommended by International Society of Clinical Densitometry (ISCD)). Statistical analysis was used to compare BMD at different sites. Alpha error was set at 0.05. Of 73 postmenopausal women who were enrolled in the study (average age 64 years, average 15 years postmenopausal), 3% had chronic kidney disease, 7% had type 2 DM, 3% were on corticosteroids and none were smokers. BMD of femoral neck assessed on pelvic DXA was not significantly different from femoral neck BMD measured on standard DXA (P=0.09). To assess pelvis BMD measurement precision, 15 patients underwent 3 separate pelvic DXA images after repositioning. BMD precision error was 0.011g/cm

which is slightly lower than the precision total hip BMD at our center (0.007 g/cm

). BMD of R1, R2, and R3 pelvic areas were measured as 0.44±0.15, 0.41± 0.15, and 0.62 ±0.19 g/cm

, respectively. Notably, BMD of R3 was significantly higher than the other 2 areas (P<0.001, ANOVA). Average BMD (0.49±0.14 g/cm

) of pelvis was significantly lower than BMD of femoral neck (0.72± 0.16 g/cm

), total hip (0.86±17 g/cm

) and spine (0.97± 19 g/cm

)(P <0.001). Average BMD of pelvis was significantly lower in participants with osteopenia and osteoporosis of the hip and femoral neck compared to participants with normal BMD in those locations. In summary, we report a precise method of measuring BMD of commonly fractured areas of the pelvis. Pelvis BMD is lower than hip, femoral neck, and spine. Bone density of the pelvis correlates with hip and femoral neck bone density. The results of this pilot study can be used for future studies looking at pelvic low bone density in patients with pelvic fragility fractures which could help identify patients at risk for pelvic fragility fractures and change how osteoporosis is defined based on DXA images.

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<![CDATA[SUN-378 Unilateral Primary Aldosteronism as an Independent Risk Factor for Vertebral Fracture]]> https://www.researchpad.co/article/N8f1f2fb7-af5a-4b9e-b69d-5caf8082266e <![CDATA[SUN-370 Validation of a Deep Learning Based Algorithm to Diagnose Vertebral Compression Fractures]]> https://www.researchpad.co/article/N13395673-b045-4176-98b9-4ade7a7cbdc8 <![CDATA[SUN-374 Decisions to Accept or Decline Pharmacologic Osteoporosis Therapy After Attending a Novel Patient-Centred Educonsult Program for Osteoporosis (PEP-OP)]]> https://www.researchpad.co/article/N978a6b10-a4c6-441e-8ff1-f81e490c0a19 200 million people, resulting in >8.9 million annual fragility fractures worldwide. Available medications can reduce fracture risk by 40–60%, although access to specialty osteoporosis services is limited, and many individuals remain unaware of their fracture risk and their treatment options. As the one-on-one ‘traditional consultation’ (TC) model of osteoporosis care is not time efficient (i.e. a single TC often requires >45 minutes), there is a need to identify innovative consultative models that can improve accessibility to osteoporosis care while maintaining quality. At our Osteoporosis Centre, we have implemented a group counseling model for this purpose: the Patient-Centred Educonsult Program for Osteoporosis (PEP-OP). Each two-hour PEP-OP session - co-facilitated by an osteoporosis physician and a nurse - provides up to 10 patients (the equivalent to 3–5 half-day physician clinics under the TC model) with a combined consultative and educational experience consisting of an individualized fracture risk assessment and extensive review of medications available to lower fracture risk. Patients are then encouraged to make an informed, autonomous decision about osteoporosis treatment initiation. Although the PEP-OP can accommodate a greater patient volume than the TC, and we have previously reported that the PEP-OP results in high patient satisfaction, it is not known whether PEP-OP produce similar results compared to TC in terms of treatment decisions. In this cohort study, we compared decisions to initiate osteoporosis therapy in PEP-OP (N=100) and TC (N=43) attendees. Ten-year risk of major osteoporotic fracture was estimated for each participant using the FRAX calculator, and participants were stratified based on whether their ten-year risk was ≥20% or <20%. Proportion of participants in each risk category who decided to initiate treatment were compared between the PEP-OP and TC groups. PEP-OP and TC groups were comparable in terms of age (63.3 vs 64.9 years), BMI (24.4 vs 24.9 kg/m2), previous fragility fractures (35 vs 25%), parental hip fractures (19 vs 23%), lumbar neck T-score (-2.5 vs -2.3), femoral neck T-score (-2.1 vs -2.1) and average FRAX estimate (13.1 vs 13.3%). The proportion of participants at high ten-year risk of major osteoporotic fracture (≥20%) who decided to initiate treatment was similar in both the PEP-OP (7/16, 44%) and TC (5/10, 50%) groups, according to the Chi Square Test (p=0.76). Among those with FRAX estimate of <20%, a similar proportion of patients in the PEP-OP (15/84, 18%) and TC (4/33, 12%) groups chose to undergo treatment (X2, p=0.45). In summary, decisions to initiate pharmacologic therapy were similar for the PEP-OP and the TC. Considering that the PEP-OP is acceptable to patients and is more efficient than the TC, this care model should be considered by other centers wishing to improve access to high-quality osteoporosis care. ]]>