Baseline Bone Mineral Density Research Articles

Achieving osteoporosis treat-to-target goals with teriparatide or alendronate: sub-analysis of Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk. Participants received sequential therapy with once-weekly TPTD for 72weeks, followed by ALN for 48weeks (TPTD-ALN group) or ALN monotherapy for 120weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD. A total of 559 participants were selected. BMD ≥ -2.5 SD at 120weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD. During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.

Long-Term Bone Mineral Density Changes in Kidney Transplant Recipients Treated with Denosumab: A Retrospective Study with Nonequivalent Control Group.

Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60mg/6 months for 4years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.

Risk factors for treatment-related bone loss and osteoporosis in patients with follicular lymphoma

The survival rate of non-Hodgkin lymphoma (NHL) has steadily improved. However, osteoporosis introduced by treatment is prevalent and associated with increased mortality and disability for patients with NHL. We aimed to investigate factors impacting bone mineral density (BMD) reduction and osteoporosis, and the trend of BMD after chemotherapy. Overall, 97 newly diagnosed patients with follicular lymphoma (FL) were retrospectively enrolled. CT attenuation values were measured to assess BMD levels. Although 73.2% of patients received calcium and vitamin D supplements, 44.3% showed significant BMD reduction, and baseline BMD and hemoglobin levels were the risk factors. 26.6% of patients newly developed osteoporosis post-chemotherapy where age and cumulative dose of glucocorticoid were risk factors. The results of 20 patients with consecutive follow-up showed that BMD continued to decline for 6 months post-chemotherapy and did not return to baseline values. Therefore, BMD evaluation and more positive anti-resorption treatments should be administered for high-risk patients.

Abstract PO1-12-10: Zoledronic acid to prevent rebound fractures after stopping adjuvant denosumab: a randomized controlled sub-study of the ABCSG-18 trial

Abstract Introduction ABCSG-18 trial showed that 60mg denosumab subcutaneously every 6 months halves fracture risk in postmenopausal patients with early breast cancer, who are treated with adjuvant aromatase inhibitors. However, it has been reported that stopping denosumab may lead to overactivation of osteoclasts resulting in so called rebound vertebral fractures. As shown previously, zoledronic acid (ZA), when given to patients of the ABCSG-18 trial after stopping denosumab prevents a high bone turnover state that can occur in some patients. Here we report the impact of a single ZA dose on bone mineral density (BMD) and fractures after stopping denosumab. Methods ABCSG-18 trial patients, who had received adjuvant denosumab were re-randomized to receive a single dose of ZA 5mg i.v. or not, 8 months +- 4 weeks after their last denosumab dose. DXA scans, lateral spine X-rays and bone turnover markers (CTX and osteocalcin) were assessed at baseline and at 6, 12 and 18 months thereafter. New clinical fractures were assessed until 18 months after randomization. Results 50 patients were randomized to either ZA (24pts) or control (26pts). All patients of the ZA arm and 25 out of 26 patients of the control arm had received 7 doses of denosumab within the ABCSG 18 trial before re-randomization. Baseline bone health factors were well balanced between the 2 arms: Baseline BMD did not differ between the two arms with regard to femoral neck (ZA: 0.817 g/cm2; SOC: 0.816g/cm2), total hip (ZA: 0.918g/cm2; SOC: 0.921g/cm2) and lumbar spine (ZA: 1.128 g/cm2; SOC 1.142 g/cm2), respectively. Relative changes in BMD differed significantly between both arms for femoral neck after 12 months (ZA: 0.5%; control: -4.98%, p 0.004) and for total hip after 6 months (ZA: -0.73%; control: -4.61%, p&amp;lt; 0.001) and after 12 months (ZA: -0.13%; control: -5.62%; p&amp;lt; 0.001). There was a trend towards a greater decline in BMD at lumbar spine after 6 months in the control arm versus the ZA arm (-3.35% vs 0.67%, p=0.052). After randomization, 3 asymptomatic fractures (lumbar vertebral and thoracic vertebral in one patient and thoracic vertebral in a second patient) occurred in the ZA arm, whereas 2 clinical fractures (one radius fracture and one lumbar vertebral fracture) occurred in the SOC arm. Conclusion A single dose of Zoledronic acid prevents high bone turnover state resulting in loss of BMD in some patients after stopping denosumab. ZA may therefore be offered to breast cancer patients with aromatase inhibitor after stopping denosumab. Citation Format: Georg Pfeiler, Christian F. Singer, Dominik Hlauschek, Manfreda Diether, Ferdinand Haslbauer, Paul Sevelda, Kristin Köck, Karl Tamussino, Arno C. Reichenauer, Florian Fitzal, Dietmar Heck, Richard Greil, Claudia Pasterk, Sonja Heibl, Walter Herz, Marija Balic, Daniel Egle, Lidija Sölkner, Michael Gnant. Zoledronic acid to prevent rebound fractures after stopping adjuvant denosumab: a randomized controlled sub-study of the ABCSG-18 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-10.

Pre-treatment bone mineral density (BMD) and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). This study used data from a large set of randomised controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into femoral neck (FN) BMD T-score subgroups (≤ -2.5, > -2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ -2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ -2.5 and > -2.5 subgroups. Compared to those with FN BMD T-score > -2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ -2.5, but only the all fracture outcome reached statistical significance (interaction p = 0.001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all and all clinical fractures in the lower BMD quintiles (all interaction p ≤ 0.03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above -2.5, though effects tended to be larger and more significant in those with baseline T-scores <-2.5.

High content omega-3 fish oil co-treatment maintains proper bone physiology in glucocorticoid treated autoimmune mice

Despite the known side effects of glucocorticoid therapy, such as a higher risk of osteoporosis, fractures, and reduced bone density, it remains a frequently prescribed treatment for autoimmune disorders due to its strong anti-inflammatory and immunosuppressive properties. If strategies could be identified to reduce the side effects commonly associated with glucocorticoid use, it could lead to more frequent and safer use of this treatment option for autoimmune diseases. In this work, the combined effects of high content omega-3 fish oil (HCW3FO) and a synthetic glucocorticoid, methylprednisolone (MP) medication are investigated in relation to bone mineral density (BMD) reduction in arthritis prone female MRL-lpr/lpr mice. Two treatment groups were introduced to the mice when they were 4 months old: one group was given weekly injections of PBS, while the other group was given either 5 mg/kg MP or 20 mg/kg MP. Additionally, both groups were provided with the AIN93M diet, supplemented with either 4% corn oil or 4% HCW3FO daily, for a duration of 8 weeks. Prior to initiating the drug injections and dietary modifications, the mice underwent dual energy x-ray absorptiometry (DXA) scans to establish their baseline BMD values. To find out their ultimate BMD values, the mice underwent another DXA scan eight weeks later, right before being sacrificed. Over the course of eight weeks, the MP treatment did not lead to a significant reduction in BMD across various bone regions, except for the lumbar regions. Similarly, the HCW3FO treatment alone did not offer protection against BMD loss in MRL-lpr/lpr mice. However, when MP and HCW3FO were combined, it resulted in a remarkable preservation of BMD in different bone regions. This enhanced protection against BMD loss was associated with a reduced number of tartrate-resistant acid phosphatase (TRAP) positive areas and an increased number of alkaline phosphatase (ALP) positive areas in tibial sections as revealed by immunohistochemistry. Our findings provide compelling evidence that the combination of MP and HCW3FO maintains bone health in arthritis-prone MRL-lpr/lpr mice by promoting a balance between bone resorption and bone formation. Co-treatment with HCW3FO may hold promise as a potential strategy for preventing bone deterioration induced by long-term glucocorticoid therapy. Before moving on to clinical trials, more in vitro research into the mechanisms should be carried out alongside preclinical studies in mice with inflammatory diseases. QUCG-CAS-2122-2. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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

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

Analyzing the factors associated with efficacy among teriparatide treatment in postmenopausal women with osteoporosis

BackgroundTeriparatide (TPTD) is a widely used anabolic agent for the treatment of osteoporosis. Several factors have been identified to be related to bone mineral density (BMD) increase in anti-osteoporosis treatment with other agents; however, there has been no systematic analysis to summarize the associated determinants of BMD reaction to daily teriparatide treatment.MethodsIn this retrospective study, we performed a comprehensive investigation involving not only clinical data but also several relevant lifestyle factors to be examined for their potential contribution to BMD response. This post-hoc analysis included 258 post-menopaused patients with osteoporosis who received TPTD at 20 µg/day for 12 months. Univariate and multivariate analyses were conducted to distinguish the response variables of lumbar spine (LS) BMD transformation, the principal outcome measure of efficacy, from the baseline at 12 months.ResultsTwelve months of TPTD treatment resulted in an absolute 0.39 ± 0.37 increase in T-score of LS BMD. Gastrointestinal disease, prior bisphosphonate or glucocorticoid treatment, no vitamin K2 supplementation, low levels of serum 25(OH)D and PINP, weak increment of PINP and β-CTX at 3 months, unhealthy lifestyle (excessive smoking, tea, coffee, and drinking), vegetarian diet pattern, low ALT level, and high BMD at baseline were determined by univariate analyses to be related to the weak reaction of TPTD treatment (P < 0.10). In the multiple regression model, postmenopausal women with vitamin K2 supplementation, higher baseline serum 25(OH)D level, and higher PINP concentration at 3 months indicated a good reaction of LS BMD at 12 months (P < 0.05). Patients with gastrointestinal disease, prior bisphosphonate and glucocorticoid treatment, vegetarian diet pattern, and higher baseline BMD were significantly more likely to have a lower absolute LS BMD response compared to patients without these characteristics (P < 0.05). Further analysis confirmed the negative effect of unhealthy lifestyle on TPTD treatment.ConclusionOur results emphasize the significance of a comprehensive assessment of clinical or lifestyle-related characteristics of postmenopausal women with osteoporosis in the management of TPTD therapy in routine care.

Implication of Bone Mineral Density and Body Composition Parameters for Length of Hospital Stay in Patients with COVID-19.

Multisystem information, including musculoskeletal information, can be captured from chest CT scans of patients with COVID-19 without further examination. This study aims to assess the relationship between chest CT-extracted baseline bone mineral density (BMD) and body composition parameters and the length of hospital stay in these patients. A retrospective analysis was performed in a cohort of 88 patients with COVID-19. Correlation analysis and a generalized linear model (GLM) were used to assess the associations between the length of hospital stay and covariates, including age, sex, body mass index (BMI), BMD and body composition variables. The mean length of hospital stay was 27.4±8.7 days. The length of hospital stay was significantly positively associated with age (r=0.202, p=0.046) and the paraspinal muscle fat ratio (r=0.246, p=0.021). The GLM involving age, sex, BMD, paraspinal muscle fat ratio, subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and liver fat fraction (LFF) showed that the length of hospital stay was positively correlated with VAT area (β coefficients, 95% CI: 9.304, 1.141-17.478, p=0.025). The musculoskeletal features extracted from chest CT correlated with the prognosis of COVID-19 patients. Factors including old age, a higher paraspinal muscle fat ratio and a larger VAT area in patients with COVID-19 were associated with longer hospital stays.

Bone mineral density as an individual prognostic biomarker in NSCLC patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have left a deep impression in the treatment of non-small cell lung cancer (NSCLC), however, not all patients benefit from it. The purpose of this study was to investigate the prognostic value of baseline bone mineral density (BMD) derived from chest computed tomography (CT) scans in NSCLC patients treated with ICIs. This study included patients with advanced NSCLC who underwent ICI treatment at the Wuhan Union Hospital from March 2020 to October 2022. Baseline BMD was evaluated at non-contrast chest CT at the level of first lumbar vertebra. Patients were divided into BMD-lower group and BMD-higher group according to the optimal cutoff value calculated by X-tile software. Baseline characteristics of the two groups were compared and variables between the two groups were balanced by propensity score matching (PSM) analysis. We calculated the objective response rate (ORR) and disease control rate (DCR) of the two groups and analyzed overall survival (OS) and progression-free survival (PFS) using BMD and other clinical indexes through Cox regression models and Kaplan-Meier survival curves. A total of 479 patients were included in this study, and all patients were divided into BMD-lower group (n=270) and BMD-higher group (n=209). After PSM analysis, each group consisted of 150 patients. ORR (43.3% vs. 43.5% before PSM, P = 0.964; 44.7% vs. 44.7% after PSM, P = 1.000) and DCR (91.1% vs. 94.3% before PSM, P = 0.195; 93.3% vs. 96.7% after PSM, P =0.190) were similar in two groups. There was no statistically significant relationship between BMD degree and PFS before (16.0 months vs. 18.0 months, P = 0.067) and after PSM analysis (17.0 months vs. 19.0 months, P = 0.095). However, lower BMD was associated with shorter OS both before (20.5 months vs. 23.0 months, P< 0.001) and after PSM analysis (20.0 months vs. 23.0 months, P = 0.008). Lower baseline BMD is associated with worse clinical outcomes in NSCLC patients treated with ICIs. As a reliable and easily obtained individual prognostic biomarker, BMD can become a routine detection indicator before immunotherapy.

Modulation of Bone Mineral Density and Its Response to Menopausal Hormone Therapy according to the Apolipoprotein E Genotype in Postmenopausal Korean Women.

Genetic factors are a major cause of osteoporosis. The present study evaluated the association of the apolipoprotein E (ApoE) genotype with bone mineral density (BMD) and its response to menopausal hormone therapy (MHT) in postmenopausal Korean women. This retrospective cohort study included 172 postmenopausal women with no endocrine diseases, medications, or lifestyles that would affect bone metabolism and who were continuously treated with MHT for at least 2 years. BMDs were measured at baseline and periodically. Linear regression analysis demonstrated similar baseline BMDs at the lumbar spine, but significantly lower at the femur neck and total hip in the ApoE ε4 carrier than in the noncarrier group, after controlling for age, body mass index, and history of MHT usage. Overall, the Wilcoxon signed rank test demonstrated that MHT increased the BMD percentage change at all three regions, and the Generalized Estimating Equation (GEE) demonstrated significant time trends at the lumbar spine and femur neck. ApoE ε4 noncarriers exhibited a significant time trend in BMD changes at the femur neck, whereas ε4 carriers exhibited a time trend at the lumbar spine. However, BMD changes at each time point were comparable at all regions between the groups. Notably, GEE adjusted for baseline characteristics and BMD revealed a significant interaction effect of time and ApoE ε4 allele in BMD changes at the femur neck. Postmenopausal Korean women carrying the ApoE ε4 allele demonstrated a lower hip BMD compared with ε4 noncarriers. Furthermore, the ε4 allele may modulate hip BMD responses to MHT.

Bone mineral density fall during aromatase inhibitor treatment may predict lower breast cancer recurrence.

Aromatase inhibitors (AIs) are associated with reduction in bone mineral density (BMD). The use of bone strengthening agents zoledronic acid and denosumab are associated with improved breast cancer outcomes for post-menopausal patients treated with AIs. This study investigates whether change in BMD with AI therapy is associated with breast cancer recurrence. A cohort of patients treated at a single institution diagnosed with hormone receptor-positive breast cancer with baseline BMD and subsequent BMD test while receiving adjuvant aromatase inhibitor therapy were studied. Demographic, treatment and outcome data was obtained. Simple and multiple linear regression analysis was performed to investigate predictors of annual percent BMD change at the LS and hip. Univariate and multivariate Cox proportional hazards modelling were undertaken to investigate predictors of breast cancer recurrence. 353 patients eligible patients were identified. In multivariate analysis of lumbar spine BMD change, the difference between those in quartile 1, which showed the greatest reduction in BMD, and quartile 3, with substantially less reduction, was significant (HR = 3.02, 95% CI 1.15-7.90 p = 0.025). Hip BMD reduction was also not significantly associated with breast cancer recurrence. The two quartiles with the least reduction in hip BMD showing a non-significant reduced risk of recurrence relative to the quartile with the greatest (p = 0.10). The findings suggest an association may exist between lumbar spine BMD change and breast cancer recurrence for patients treated with adjuvant AI. Further research is required to determine whether BMD change can be utilised as a biomarker.

Coronary artery calcification is associated with smaller increases in femoral neck bone mineral density with anti-resorptive therapy

Abstract Introduction Patients with osteoporosis are at high cardiovascular risk, partly due to vascular calcification, such as in the coronary vessels. It is uncertain if the presence of coronary artery calcification (CAC) effects bone mineral density (BMD) response to anti-resorptive treatment – first line therapy for osteoporosis. We therefore assessed changes in BMD following initiation of anti-resorptive treatment for osteoporosis in patients with and without evidence of CAC. Methods Individuals dispensed at least one prescription for an anti-resorptive medication (bisphosphonates or denosumab) at Monash Health between 2009-2022 were identified. Unique record numbers for these individuals were then cross-matched against the cardiac CT imaging service at Monash Heart (HREC#73603). CAC was detected using a 320-slice CT coronary angiogram (CTCA). We included only those patients having a baseline BMD measurement within two years of CTCA. The annualised percentage change in femoral neck BMD was calculated and adjusted for age, sex, height, weight, and number of years on anti-resorptive treatment. Results 106 individuals were identified of which 85 (women=70 [85%], median age=73 years [interquartile range 64-79 years]) had a follow-up BMD measurement including 19 with, and 66 without, evidence of CAC. Those with CAC were older (76 years versus 64 years, p&amp;lt;0.001). There were 70 bisphosphonate users and 15 denosumab users. Individuals with evidence of CAC experienced, on average, a 1.2% lower increase [(0.345% (0.343 to 0.348) versus -0.881% (-0.883 to -0.879), mean difference -1.226% (-1.493 to -0.959; p&amp;lt;0.05)] in annualised femoral neck BMD with anti-resorptive therapy after adjusting for important clinical risk factors. Interpretation These preliminary data suggests that CTCA-determined CAC may negatively impact femoral neck BMD increases with anti-resorptive therapy. This is perhaps consistent with existing and evolving hypotheses of dysregulatory processes driving ectopic calcium deposition, which we surmise would partially counter the effects of anti-resorptive therapy and potentially manifest as CAC. Thus, of particular interest will be the comparison of cardiovascular outcomes of patients with known CAC with and without anti-resorptive therapy, with the hypothesis that anti-resorptive therapy may potentially have cardioprotective effects in context of CAC. Analysis of the full cohort is underway.Table 1

Bone mineral density and the risk of incident dementia: A meta-analysis.

It is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer's disease (AD). We performed a meta-analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow-up available. BMD was measured at the hip femoral neck using dual-energy X-ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline ("baseline BMD") and annualized percentage change in BMD prior to baseline ("prior bone loss") were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education. The combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta-analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23-0.96; p = 0.038) per increase in g/cm2 , or 0.91 (95% CI: 0.84-0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12-1.51; p < 0.001) per percent increase in prior bone loss only in the FHS cohort. Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three studies.

Quality improvement initiative to increase bone mineral density screening with DEXA scans among patients receiving aromatase inhibitors or androgen deprivation therapy at an urban safety-net hospital.

468 Background: Patients on aromatase inhibitors (AI) or androgen deprivation therapy (ADT) are at increased risk for osteopenia and osteoporosis. Guidelines recommend baseline and regular bone mineral density (BMD) assessment with dual-energy x-ray absorptiometry (DEXA) scans for these patients. Baseline data for BMD assessment for patients on either AI or ADT at our institution was reviewed and interventions were subsequently developed to improve screening rates. Methods: A retrospective chart review was performed for patients seen in the medical oncology clinic at Denver Health from 2018 through the first 2 quarters of 2020. Patients had a diagnosis of breast cancer or prostate cancer and were prescribed AI or ADT. The review evaluated whether DEXA scans had been ordered for this population. In September 2020, interventions were implemented including: an electronic reminder for ordering providers, education for pharmacists, and education for all nurses who worked in the clinic and the infusion center. Primary care providers who work outside of the oncology clinic were also contacted. An alert in Denver Health’s electronic medical software (EPIC) was launched successfully in September 2020. The alert reminded all providers ordering AI or ADT that a DEXA scan should be performed. The data for DEXA scan monitoring post-intervention was then tracked and measured through the second quarter of 2022. Results: A total of 282 patients were prescribed AI or ADT during the initial retrospective study, out of which 88 had baseline DEXA scans performed, accounting for 31.2% of the patients. After the intervention was implemented in 2020, the rate of DEXA scans performed increased to 44.2% in 2020, 59.4% in 2021 and 54.1% in 2022. The main barriers to the completion of DEXA scans were issues with transportation, multiple appointments leading to patient confusion and time constraints, and health literacy. Conclusions: Although BMD screening remains a very important part of cancer treatment and survivorship, it remains underutilized. In addition to the EPIC alert that was implemented, we are optimistic that continued education and reminders for all clinical staff will help ensure that the utilization of DEXA scans for BMD screening for patient on AI or ADT continues to increase. Community outreach is being planned to provide education about the importance of bone health.

THU181 Evaluation Of Bone Mineral Density In A Cohort Of Children With ACH Participating In The PROPEL 2 Study Of Infigratinib

Abstract Disclosure: R. Savarirayan: Advisory Board Member; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Sanofi, Sanofi. Consulting Fee; Self; BioMarin. Grant Recipient; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Therachon. Research Investigator; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Therachon. J. De Bergua: None. P. Arundel: None. J. Salles: None. A. Leiva-Gea: None. M. Irving: Advisory Board Member; Self; Ascendis Pharma, BioMarin, QED Therapeutics, Sanofi, Therachon/Pfizer. Speaker; Self; BioMarin, QED Therapeutics. V. Saraff: None. H. McDevitt: None. M. Salcedo: None. M.P. Nicolino: None. V. Cormier-Daire: Advisory Board Member; Self; BioMarin. P. Kannu: Advisory Board Member; Self; Novartis, Ipsen. Grant Recipient; Self; CIHR. M. Skae: None. M. Bober: Advisory Board Member; Self; Biomarin. Consulting Fee; Self; Ascendis Pharma, Biomarin, Pfizer, QED Therapeutics. Grant Recipient; Self; Ascendis Pharma, BioMarin, Pfizer, QED Therapeutics. Research Investigator; Self; Ascendis Pharma, BioMarin, Pfizer, QED Therapeutics. J. Phillips III: None. T. Candler: None. P. Harmatz: Consulting Fee; Self; Audentes, Aeglea, Homology, JCR, Denali, Inventiva, Paradigm, Capsida, Chiesi, Avrobio. Grant Recipient; Self; BioMarin, Inventiva. Research Investigator; Self; BioMarin, Shire/Takeda, QED Therapeutics, RegenXbio, Denali, Ascendis, Amicus, Allievex, JCR, Orphazyme, Idorsia, Sangamo. H. Saal: Advisory Board Member; Self; Alexion. Grant Recipient; Self; Alexion, BioMarin, Pfizer, QED Therapeutics. Research Investigator; Self; Alexion, BioMarin, Pfizer, QED Therapeutics. J. Hoover-Fong: Consulting Fee; Self; Pfizer/Therachon, BioMarin, QED Therapeutics, Sanofi, Ascendis Pharma. Grant Recipient; Self; Pfizer/Therachon, BioMarin, Ascendis Pharma. Research Investigator; Self; Pfizer/Therachon, BioMarin, Ascendis Pharma. E. Muslimova: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. T. Cho: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. R. Weng: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. D. Rogoff: Employee; Self; QED Therapeutics. Stock Owner; Self; QED Therapeutics. Background: Achondroplasia (ACH) is the most common form of short-limbed skeletal dysplasias and is caused by an activating pathogenic variant of the fibroblast growth factor receptor 3 (FGFR3) gene. People with ACH are at risk for several significant co-morbidities, including foramen magnum stenosis, obstructive sleep apnea, chronic otitis media with conductive hearing loss, spinal stenosis, and a propensity towards obesity. Decreased bone mass has been observed previously in gain-of-function mutation Fgfr3 mice, and adults with ACH can have a decrease in bone mineral density (BMD). Here we describe baseline BMD of a cohort of children with ACH participating in PROPEL 2, a proof-of-concept study evaluating preliminary efficacy and safety of infigratinib, an oral FGFR-1-3 tyrosine kinase inhibitor in development for ACH. Methods: Dual energy X-ray absorptiometry (DXA) scans of the spine (L1-4) were collected at baseline in children participating in PROPEL 2 using a Hologic or GE Lunar scanner following a pre-specified image acquisition procedure. Images were evaluated by a single reviewer. Results are expressed as z-score for age and sex based on average-height children. Results: 52 children (mean±SD age: 7.97±1.9 years; 29 female; mean±SD height z-score: -5.4±1) were included in this analysis. BMD of the lumbar spine was -0.96±0.9 SDS (min -4.1; max 0.7 SDS). No statistical difference was found between males and females. 85% of children (n=44) had a BMD &amp;lt;0 SDS, from which 21 (40%) had a BMD between -2 and &amp;lt; -1 SDS, 18 (35%) presented a BMD between -1 and 0, and 5 (10%) presented a BMD &amp;lt; -2 SDS. Eight children (15%) had a BMD &amp;gt;0 SDS. No correlations were observed between BMD and age, height z-score or BMI. Conclusion: Our findings show that lumbar spine BMD is lower in children with ACH compared with normative data from children of average height. Low BMD in the context of short stature is difficult to interpret, raising the question of the degree to which low bone status can be attributed to smaller bone size relative to age. Even though our findings do not take into account children’s height, no correlation between BMD and baseline height z-score was identified in this cohort, suggesting that the findings may not be solely attributable to overall height. These findings reinforce the need to better understand how to circumvent this limitation in children with skeletal dysplasias in order to improve DXA interpretation and avoid misdiagnoses. Presentation: Thursday, June 15, 2023

Low disease activity state associated with fewer incident vertebral fractures in Mestizo women with systemic lupus erythematosus.

Low disease activity state (LDAS) has been linked to a significant reduction in flares and damage accrual in patients with systemic lupus erythematosus (SLE); however, the effect of LDAS on the risk of vertebral fractures (VFs) in subjects with SLE is unknown, considering that low bone mineral density (BMD) and VF are frequent in SLE. to evaluate whether achieving LDAS ≥50% of the observation time prevents new VF and BMD changes in Mestizo women. We carried out a longitudinal, observational, and retrospective study. Mestizo women with SLE were included for a median of an 8-year follow-up. LDAS was described as Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≤4, prednisone ≤7.5mg/day, and stable immunosuppressive therapies. BMD measurements and lateral thoracic and lumbar radiographs for a semiquantitative analysis for VF were assessed at baseline and during the follow-up. Uni- and multivariable interval-censored survival regression models were carried out. We included 110 patients: 35 (31.8%) had new VF. A total of 56 patients (50.1%) achieved LDAS ≥50% of the time during the follow-up and achieved a significantly lesser risk of incident VF (HR = 0.16; 95% CI, 0.06-0.49). After adjusting by age, BMI, menopause, prevalent VF, baseline BMD, cumulative glucocorticoid use, and anti-osteoporotic therapy, LDAS-50 was significantly related to a decrease in the risk of a new VF (HR = 0.39; 95% CI, 0.16-0.98). There was no association between LDAS and BMD measurement changes. When only patients on LDAS but not in remission (n = 43) were evaluated for the risk of incident VF, both uni- and multivariate analyses were significant (HR = 0.12; 95 CI, 0.04-47; p = 0.001, and HR = 0.26; 95% CI, 0.7-0.88; p = 0.03). LDAS ≥50% of the time was significantly associated with a diminished risk of new VF in Mestizo women with SLE, even in patients not in remission. However, LDAS did not help modify BMD changes over time.

Incident vertebral fracture and longitudinal BMD change in Chinese postmenopausal women with early CKD: Peking Vertebral Fracture Study.

The aim of this 5-year longitudinal cohort study was to compare the risk of incident morphometric vertebral fracture (mVF) and longitudinal bone mineral density (BMD) change between individuals with early chronic kidney disease (CKD) and those without CKD. A total of 869 Chinese postmenopausal women were enrolled in the study. Serum creatinine levels were assessed using standard methods, and estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Incident mVF was confirmed through lateral radiographs of the thoracolumbar spine. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured using dual-energy X-ray absorptiometry. CKD was defined based on eGFR values: 60-89 mL/min/1.73m2 for stage 2 (n = 511) and 30-59 mL/min/1.73m2 for stage 3 (n = 92). The non-CKD group included individuals with an eGFR greater than or equal to 90 mL/min/1.73m2. The incidence of mVF was not statistically different between individuals with early CKD and those without CKD (4.1% in non-CKD, 6.3% in CKD stage 2, and 7.6% in CKD stage 3; p = 0.348). Neither eGFR nor CKD status was significantly associated with incident mVF in the multivariate logistic regression analysis. Baseline BMD T-scores were negatively associated with incident mVF (LS T-score, OR = 0.603, 95% CI = 0.468-0.777; FN T-score, OR = 0.511, 95% CI = 0.350-0.746). No evidence of interaction between BMD T-scores and CKD status were identified (p = 0.284-0.785) . The differences in longitudinal BMD changes between non-CKD and CKD groups were comparable (FN BMD: -6.31 ± 7.20% in non-CKD, -5.07 ± 8.20% in CKD stage 2, and -4.49 ± 8.40% in CKD stage 3, p = 0.556; LS BMD: -1.38 ± 8.18% in non-CKD, -0.32 ± 7.14% in CKD stage 2, and 1.5 ± 6.97% in CKD stage 3, p = 0.406). Individuals with a higher baseline FN BMD showed a greater longitudinal FN BMD loss (r = -0.185, p < 0.001) . Our study revealed that early CKD was not associated with an increased risk of incident mVF or greater longitudinal BMD loss. Moreover, CKD did not modify the association between BMD and the risk of incident mVF, suggesting that the management and prevention of fractures in early CKD should be approached similarly to those without CKD. Measurement of BMD appears to be crucial for predicting incident mVF risk and longitudinal bone loss in early CKD.

Dance/movement therapy for improving balance ability and bone mineral density in long-term patients with schizophrenia: a randomized controlled trial

Fractures are common accidents for long-term hospitalized patients with schizophrenia (SZ) in psychiatric hospitals, and once they occur, patients usually endure the pain of fractures for a long time. Accumulating evidence has supported the implementation of dance/movement therapy (DMT) as a promising intervention for patients with SZ. However, no research has been conducted to investigate its role in balance ability in SZ. This study was designed to investigate the efficacy of a 12-week DMT intervention in bone mineral density and balance ability in patients with SZ using a randomized, controlled trial design. A total of 58 veterans with SZ were randomly assigned to the DMT intervention group (n = 29) and the treatment-as-usual (TAU) group (n = 29). Bone mineral density (BMD) and balance ability were measured in both groups at two measurement points (at baseline and at the end of Week 12). We found that patients in the DMT intervention group had significant improvements in BMD and balance ability compared with the TAU group by using repeated measures analysis of variance. Treatment with DMT demonstrated a significant improvement in BMD from baseline to week 12 (0.03, 95% CI: 0.01–0.05). For the Berg total score and static and dynamic balance, the mean changes in the DMT group were 7.3 (95% CI: 5.6–9.0), 4.0 (95% CI: 0.9–7.1), and 3.7 (95% CI: 2.6–4.8), respectively. Regression analysis showed that baseline BMD was a significant predictor of improvement in BMD from baseline to week 12 in the DMT group (β = 0.58, p < 0.001). Our results suggest for the first time that DMT intervention may be effective in beneficially regulating BMD and balance ability in SZ patients.

Skeletal response to teriparatide in real-life setting: effects of age, baseline bone density and prior denosumab use

ABSTRACT Objectives Teriparatide (TPD) is an osteoanabolic agent used in patients with high osteoporotic fracture risk. Predictors of therapeutic response to TPD in real-life setting are not well characterised. This study investigated the influence of previous antiresorptive therapy, age and other patient characteristics on the skeletal response to TPD. Methods Retrospective study at the metabolic bone clinic, University Hospitals Leuven, Belgium. Patients with osteoporosis and a high fracture burden received TPD for 9–18 months. Bone mineral density (BMD) was measured at baseline, 9 and 18 months at lumbar spine (LS), femoral neck (FN) and total hip (TH). Results BMD at LS increased at 9 months (change mean (standard error) 6.8 % (0.7) p < 0.001) and at 18 months (8.0 % (0.9) p < 0.001), while BMD at FN and TH did not change significantly. Non-response in BMD change at the LS was seen with prior denosumab use (odds ratio 0.21, 95% confidence interval (CI) 0.049–0.912, p = 0.037). Changes in BMD at TH were significantly greater in younger patients and in patients with a lower baseline BMD. Conclusion TPD-induced changes in BMD at TH might depend on age and baseline BMD and at LS on prior denosumab use. The results suggest that these factors may be relevant for clinical decision making when initiating TPD treatment, although larger studies are needed to confirm these findings.