Hip Bone Mineral Density Research Articles

Denosumab for osteoporosis in older adults in long-term care: A randomized trial.

In long-term care (LTC), the incidence of hip or vertebral fractures are eight times that in the community. Despite the wide availability of osteoporosis therapy, LTC residents are omitted from pivotal trials and not treated. Denosumab is a relatively new, monoclonal antibody therapy for osteoporosis treatment. Via a randomized trial, we sought to determine the safety and efficacy of denosumab in LTC residents. We conducted a 2-year, double-blind, placebo-controlled, randomized clinical trial in 201 osteoporotic men and women aged ≥ 65 years, living in LTC communities. Participants with multimorbidity, dysmobility, and cognitive impairment were not excluded. The intervention was denosumab 60 mg subcutaneous every 6 months or placebo. Our primary outcome measures were hip and spine bone mineral density (BMD) improvement at 24 months. Secondary outcomes included BMD at other skeletal sites, function, and safety. We included 123 women and 78 men with a mean ± standard error age of 81.5 ± 0.6. Overall, 83% and 71% completed 12 and 24 months, respectively. Compared with placebo, the women receiving denosumab had a greater 24-month percent increase in spine (7.41 ± 0.93 vs. 2.15 + 0.56; p = 0.014), and total hip BMD (4.62 ± 0.62 vs. -0.19 ± 0.79; p = 0.007); and men in spine (7.91 ± 0.96 vs. 1.12 ± 1.13; p = 0.002) and total hip (3.74 ± 0.55 vs. 0.48 ± 0.74; p = 0.018). There were no significant differences in safety metrics. Denosumab was a safe and effective therapy for improving BMD in osteoporotic older men and women with multiple comorbidities in LTC.

F2-Isoprostanes Are Associated With Increased Fracture Risk in Type 2 Diabetes.

Fracture risk is higher in type 2 diabetes (T2D) for a given bone mineral density (BMD) level. Increased oxidative stress in T2D induces diabetic complications and may affect T2D bone fragility. To investigate whether the levels of plasma F2-isoprostanes, a reliable oxidative stress marker, are associated with incident clinical fracture risk in older adults with diabetes. An observational cohort study was conducted in a well-characterized cohort from Health, Aging, and Body Composition study. Older black and white ambulatory adults with baseline plasma F2-isoprostanes measurements (baseline age 70-79 years, T2D: N=132; non-diabetes: N=571) were selected from the study cohort of 3075 individuals. Incident clinical fractures. In the Cox proportional hazard model with multivariate adjustments (including BMD, medications, and other risk factors), a 93% increase in incident clinical fracture risk was significantly associated with each SD increase in log plasma F2-isoprostanes in the T2D group (HR: 1.93, 95% CI 1.26-2.95, p=0.002), but there was no evidence of an association in the non-diabetes group (HR: 0.98, 95% CI 0.81-1.18, p=0.79, p for interaction < 0.001). Log plasma F2-isoprostanes were moderately correlated with a decline in baseline total hip BMD (r=-0.25, p=0.003), and with a 4-year decrease in total hip BMD (r=-0.28, p=0.008) in T2D. There was no evidence of correlation between log plasma F2-isoprostanes and circulating glycoxidation markers or bone turnover markers in either group. Plasma F2-isoprostanes levels in individuals with diabetes are associated with increased incident clinical fracture risk independently of baseline BMD.

Hip structure and incident fracture: a time-updating survival analysis over 20 years of data from the Geelong Osteoporosis Study.

Hip structural analysis (HSA) uses dual X-ray absorptiometry (DXA) hip scans to calculate geometries of narrow neck (NN), intertrochanter (IT), and shaft (S), which may complement bone mineral density (BMD) for assessing fracture risk. We aimed to determine whether HSA parameters were associated with fracture. Participants were women (n = 986, ages 40-94 year) from the Geelong Osteoporosis Study. HSA was calculated from Lunar DPX-L scans. Low-trauma incident fractures were identified radiologically. Participants were followed from baseline to first fracture, death, or end of follow-up period (31/12/16) (13,487 person-years follow-up). Time-updating Cox-proportional hazards modelling investigated associations between HSA parameters and fracture. Three hundred thirty-five participants reported fractures (rate: 24.99/1000 person-years [95% CI 22.46-27.80]). Higher NN BMD (HR:0.12, 95% CI:0.05-0.29), cross-sectional area (CSA) (0.37, 0.26-0.52), cross-sectional moment of inertia (CSMI) (0.66, 0.50-0.89), section modulus (SM) (0.40, 0.24-0.68) and cortical thickness (CT) (0.00, 0.00-0.01 due to rounding) were associated with decreased risk. IT BMD (0.08, 0.04-0.20), CSA (0.58, 0.49-0.69), CSMI (0.90, 0.85-0.94), and SM (0.69, 0.59-0.81) were similarly associated. Decreased risk was observed at increased values of S BMD (0.20, 0.10-0.38), CSA (0.60, 0.47-0.76), SM (0.60, 0.43-0.83), and CT (0.03, 0.01-0.14). Higher S endocortical diameter (1.81, 1.29-2.53), and buckling ratio (BR) at all sites (NN: 1.07, 1.04-1.11; IT: 1.08, 1.05-1.11, S: 1.31, 1.19-1.46) were associated with increased risk. After adjustment for total hip BMD, the associations with BR at the shaft (1.14, 1.00-1.30) were sustained. Other associations were attenuated. A greater shaft buckling ratio was associated with an increased risk for fracture, independent of total hip BMD.

Unveiling the Metabolic Challenges in Pulmonary Arterial Hypertension: Insights into Thyroid, Glycemic, Lipid, and Bone Disorders

This study aimed to evaluate the prevalence of thyroid, glycemic, lipid and metabolic bone disorders among adult patients with pulmonary arterial hypertension (PAH). MethodsThis was an observational cross-sectional clinical study with patients with PAH, matched by sex and age with a control group without PAH. All individuals were enrolled into a clinical assessment, metabolic workup, thyroid ultrasound, and bone densitometry protocol. ResultsThe PAH group included 35 participants (34 females, 46 ± 15.5 years), and the control group, 40 (39 females, 41.8 ± 13.1 years). There was no difference in body mass index (BMI) between PAH and control group (27.5 ± 5.9 and 26.9 ± 4.3 kg/m2, respectively; p = 0.63; 95% CI = -1.8, 2.94), neither in physical activity time per week (60.3 ± 103.3, 98.9 ±137.6, respectively; p = 0.17; 95% CI = -95.23, 18.06). Although there was no difference in the prevalence of insulin resistance between the PAH (51.4%) and the control group (47.5%), p=0.74, patients with PAH had a higher median of glycated hemoglobin (A1c) than the control group (6.1% and 5.57%, respectively), p=0.006; 95% CI = -0.14, 1.22. PAH group presented lower mean total cholesterol (170.46 ± 35.51 mg/dL) and median LDL-cholesterol [105 (46) mg/dL, median (interquartile range)] levels than the control group [192.1 ± 34.44 mg/dL, p = 0.009; 95% CI = -37.76, 5.52; 121.6 (35.02) mg/dL, p=0.012; 95% CI = -34.08, 0.77, respectively]. It was found a higher prevalence of hypothyroidism (22.9%) in PAH group than in control group (2.5%), p = 0.007. We found hyperparathyroidism (HPT) among 8 patients of PAH group (23%), but none in the control group. Considering bone mineral density disorders, 12 patients from PAH group presented low bone mass, osteopenia, or osteoporosis (34%), and 8 individuals in the control group (20%), p =0.032, which represented a 2.13 higher relative risk for those conditions for the former group. The patients with HPT presented a higher creatinine level (0.98 ± 0.12 mg/dL) than the PAH patients with normal parathyroid hormone (0.76 ± 0.14 mg/dL), p = 0.0004; 95% CI = 0.12, 0.33. The PAH group also presented lower total hip (-0.15 ± 1.25) and femoral neck (-0.14 ± 1.07) bone mineral density (BMD) Z-scores than the control group (0.50 ± 1.13, p = 0.021; 95% CI = -0.18, -0.027; 0.35 ± 0.94, p = 0.038; 95% CI = -0.16, -0.01, respectively). ConclusionIn this cohort, the findings of higher A1c levels, hypothyroidism prevalence, lower LDL and total cholesterol levels, and a higher prevalence of hyperparathyroidism, as well as lower total hip and femoral neck BMD Z-scores in the PAH group, compared to the control group and highlighting the dysregulation of various metabolic pathways in patients with HAP, suggesting the need for targeted interventions to enhance patient care. Additionally, they underscore the importance of gaining a deeper understanding of the mechanisms driving these changes and their potential pathophysiological connections to the disease.

Romosozumab following denosumab improves lumbar spine bone mineral density and trabecular bone score greater than denosumab continuation in postmenopausal women.

Romosozumab following anti-resorptive can be an effective sequential treatment strategy to improve bone strength. However, whether the transition to romosozumab after denosumab is associated with greater improvement in bone mineral density (BMD) and trabecular bone score (TBS) compared to denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020. Individuals who were transited to 12months of romosozumab after denosumab were 1:1 matched to those who continued an additional 12months of denosumab (n = 86 for each group; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). Mean BMD gain by denosumab treatment in matched DR and DD groups from denosumab initiation to transition (median 4 times [range 2 to 8]) was +4.8% and + 2.0% in the lumbar spine and total hip. DR group showed greater LS BMD gain compared to the DD group (+6.8 vs. +3.3% point, P<.001) for 12months post-transition independent of the duration of prior denosumab treatment, yielding greater overall LS BMD gain in DR compared to DD (+11.6% vs. +8.0%, P<.001). DD group showed continued improvement of hip BMD, whereas hip BMD was maintained but not improved in the DR group. DR group was associated with greater TBS improvement than the DD group (2.9% vs 1.0%, P=.042). One month after the transition to romosozumab from denosumab, P1NP immediately increased above the level of denosumab initiation with relatively suppressed CTx, creating a transient anabolic window. For 12months follow-up, one incident morphometric vertebral fracture and one patella fracture were observed in DD, whereas one ankle fracture was observed in the DR group. Romosozumab following denosumab improved lumbar spine BMD and TBS greater than denosumab continuation in postmenopausal women.

Picking a bone with fluoride – dose-response meta-analysis on exposure to fluoride and bone density

Abstract There are still uncertainties around the effects, beneficial and adverse, of water fluoride exposure on bone density and strength. We selected bone mineral density (BMD) for investigation as it is recognized as the major non-invasive indicator of bone strength, representing its clinical assessment standard. The aim of this systematic review and meta-analysis was to characterize for the first time the relation between fluoride exposure and BMD through a dose-response approach, using a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1201 potentially relevant literature records retrieved, after removing duplicates, title/abstract screening, and full-text evaluation, 16 studies were eligible for this review, 12 of which were also suitable for the dose-response meta-analysis. We observed an almost linear association between fluoride and BMD, yielding a mean difference of 2.60 (95% CI 0.17 to 0.40) at 4 mg/L of fluoride exposure. This pattern was also confirmed for hip BMD (MD = 2.83; 95% CI 0.11 to 0.40 at 4 mg/L). However, sex-specific analyses showed different patterns of association. In males, the relation between fluoride exposure and BMD was almost linear until 0.75 mg/L (MD = 0.24; 95% CI -0.22to 0.37), after which it plateaued. Females showed a slight increased BMD at 1 mg/L (MD = 0.05; 95% CI -0.02 to 0.16) but decreasing values above 2.5 mg/L (MD=-0.22; 95% CI -2.72 to 2.38 at 4 mg/L), with an indication of an inverted U-shaped association. This pattern was clearer when we restricted our analysis to hip BMD (MD=-0.56; 95% CI -2.98 to 1.85 at 4 mg/L). Sensitivity analyses examining both bone-specific BMD and conducting risk of bias assessments are currently underway. Moreover, imprecision of the estimates, especially in stratified analyses, and potential for residual confounding, underscore the need for further prospective studies, to more adequately assess the relation between fluoride exposure and bone density and strength. Key messages • At fluoride exposure below 1 mg/L, we observed a linear correlation between fluoride exposure and increase bone density in the overall pooled dose-response analysis of eligible studies. • Sex-specific patterns: males show positive response until certain exposure threshold; while females demonstrate an increase only at low doses of exposure and a downward trend at higher exposures.

Hip geometry and strength remain stable the first year after kidney transplantation – an ibandronate/placebo post hoc analysis

Abstract The sensitivity of bone mineral density (BMD) to identify patients with high fracture risk after kidney transplantation is low, wherefore alternative tools are needed. Hip Structure Analysis (HSA) provides an estimation of hip structural geometry and strength based on conventional DXA scans for hip analyses. We aimed to investigate the effect of antiresorptive therapy on hip geometrical and strength parameters by HSA. In a post hoc analysis of a 12-month randomized, double-blind, placebo-controlled trial evaluating the effect of ibandronate in addition to active vitamin D and calcium in kidney transplant recipients (KTR), we re-analyzed dual total hip and femoral neck DXA scans to measure cortical bone thickness (CBT) in the femoral neck (CBTNECK), calcar (CBTCALCAR), and shaft (CBTSHAFT), along with femur neck width, hip axis length, and to estimate Buckling Ratio and Strength Index. DXA measurements were performed within 5 weeks after transplantation and repeated at 10 weeks and 1-year post-transplant. The study included a total of 127 de novo KTR with eGFR &amp;gt;30 mL/min at baseline. The five geometrical and the strength and stability hip parameters remained stable over the first post-transplant year irrespective of antiresorptive therapy. We detected no statistically significant between-group differences in any of the HSA measures. Change in geometrical hip parameters and Buckling Ratio over the study duration was not correlated with change in plasma parathyroid hormone or change in dual total hip BMD. In this study, the so far largest of HSA in KTR, antiresorptive therapy with ibandronate for 12 months did not affect measures of hip geometry or strength. Clinical Trial Registration: www.clinicaltrials.gov as NCT00423384, EudraCT number 2006-003884-30.

Therapy with transitions from one bone-forming agent to another: a retrospective cohort study on Teriparatide and Romosozumab

Abstract This study aimed to evaluate the effectiveness of sequential therapy with a bone formation-promoting agent (either teriparatide or romosozumab) for osteoporosis treatment following prior treatment with the other bone-forming agent (teriparatide or romosozumab). This is a multicenter retrospective cohort study observing two groups for comparison: one with 69 patients transitioning from teriparatide to romosozumab (the T2R group) and the other with 25 patients transitioning from romosozumab to teriparatide (the R2T group), monitored for 12 months on the second drug. Key outcomes included changes in bone mineral density (BMD), bone turnover marker changes, and adverse events. The mean ages of each group were 72.3 years in the T2R group and 67.6 years in the R2T group, with the proportions of women being 91.3% and 80.0% respectively. The percent changes of BMD in the lumbar spine after 12 months of sequential therapy were + 10.78% in the T2Rgroup (P&amp;lt;.001 versus baseline) and − 0.02% in the R2T group (P=.875). The percent changes in BMD in the total hip and femoral neck were + 4.41% and + 4.41% in the T2R group, and -1.33% and -0.83% in the R2T group, respectively. When comparing the two groups, BMD changes at all sites in the T2R group were significantly higher than those in the R2T group (P&amp;lt;.001). Furthermore, when examining the changes in the proportion of patients who achieved the osteoporosis treatment goal of a T-score exceeding -2.5, no significant increase was observed in the R2T group, whereas a significant increase was observed in the lumbar spine in the T2R group. Regarding therapy switching between bone-forming agents, this study suggests that transitioning from teriparatide to romosozumab increases BMD more effectively than transitioning in the opposite sequence.

Alendronate preserves bone mineral density in adults with sickle cell disease and osteoporosis.

To describe the effects of alendronate in adults with sickle cell disease (SCD) and osteoporosis. We reviewed retrospective clinical data from adults with SCD and osteoporosis treated with alendronate at a single center in Brazil (2009-2019). Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and total hip. We analyzed BMD changes by alendronate treatment duration (months), stratified by sex, skeletal site, and SCD genotype. Sixty-four SCD adults with osteoporosis (69% females, 73% HbSS, mean age ± standard deviation 42.4 ± 10.9years) received alendronate for a median (interquartile range) of 48 (29, 73) months. Compared with males, females had significantly lower baseline BMD (g/cm2) at the femoral neck (0.72 vs 0.85, p = < 0.001) and total hip (0.79 vs 0.88, p = 0.009). The between-sex differences in BMD changes were insignificant. Mean lumbar spine BMD significantly changed by 0.0357g/cm2 (p = 0.028) in those on alendronate for > 5years. Four adults (6.3%) reported mild therapy-related side effects. An atypical femoral diaphysis fracture, attributed to alendronate, was incidentally noted in a 37-year-old man on treatment for 4years. In this retrospective cohort of adults with SCD and osteoporosis on alendronate for a median of 48months, we found no significant interactions between sex and changes in lumbar spine, femoral neck, or total hip BMD with alendronate. Lumbar spine BMD was stable in those on alendronate for < 5years. Side effects of alendronate were mild, though one patient developed an atypical femoral fracture.

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

Increased 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. This 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. This 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. Our 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.

Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women- a case-control study.

To investigate bone mineral density (BMD), osteoporosis prevalence and systemic sclerosis (SSc) specific associations of BMD in SSc patients compared with background population. In total, 211 SSc patients (182 women, 29 men; mean age 61.3 and 62.2 respectively) and 505 age and sex matched controls from the same geographic area participated. BMD and T-score at total hip and lumbar spine was measured by Dual-energy X-ray absorptiometry. Osteopenia was defined as T-score -1.0 to -2.5; osteoporosis as T-score ≤-2.5. Associates of low BMD were identified by multiple regression analysis. Women with SSc had lower BMD for total hip (p< 0.001) and spine (p= 0.011), equivalent to ΔT-score -0.56 and -0.35 compared with controls. Osteopenia was present in 51.6% and 16.5% had osteoporosis (p= 0.001, compared with controls). Already in women below age 45, differences in hip BMD were apparent (ΔT-score -0.93, p= 0.005). In addition to expected risk factors for osteoporosis (older age, lower BMI and menopause), finger ulcers (p= 0.009) and diffuse skin involvement (p= 0.027) were associated with lower hip BMD in women. In men with SSc, more than half displayed osteopenia or osteoporosis and had numerically lower hip BMD than their age matched counterparts. SSc patients, including men and younger women, have lower BMD than the background population. Finger ulcers and diffuse skin involvement, in addition to older age, lower BMI and being post-menopausal, are associated with lower BMD in women. The data emphasizes the importance of performing bone health assessment of all SSc patients, including men and young subjects.

Romosozumab versus denosumab in long-term users of glucocorticoids: A pilot randomized controlled trial.

To compare the efficacy of romosozumab (ROMO) and denosumab (DEN) in prevalent long-term glucocorticoid (GC) users. Adult patients receiving oral prednisolone (≥5mg/day) with high risk of fracture were randomized to receive subcutaneous ROMO (210mg monthly) or DEN (60mg 6-monthly) for 12 months, followed by DEN for two more doses. The primary end point was the change in spine bone mineral density (BMD) from Months 0 to 12. Secondary end points included changes in BMD of the spine/hip/femoral neck and bone turnover markers at various time points and adverse events. Seventy patients (age 62.6±9.1 years; 96% women; median prednisolone dose 5.0mg/day; duration of therapy 10.7±7.4 years) were enrolled, and 63 completed the study. At Month 12, the spine BMD increased significantly in both ROMO (+7.3%±4.5%; p<0.001) and DEN (+2.3%±3.1%; p<0.001) groups. The absolute spine BMD gain from Months 0 to 12 was significantly greater in ROMO-treated patients (p<0.001). Although the total hip BMD at Month 12 also increased significantly in the ROMO (+1.6%±3.3%; p=0.01) and DEN groups (+1.6%±2.6%; p=0.003), the absolute BMD gain was not significantly different between the groups. At Month 24, the spine BMD continued to increase in both the ROMO (+9.7%±4.8%; p<0.001) and DEN group (+3.0%±3.0%; p<0.001) compared to baseline, and the absolute BMD gain remained significantly greater in ROMO-treated patients. The total hip BMD continued to increase in both groups (ROMO +2.9%±3.7%; p<0.001; DEN +2.2%±3.4%; p=0.001), but the changes from baseline were similar. Injection site reaction was more frequently reported in ROMO-treated patients. ROMO was superior to DEN in raising the spine BMD at Month 12 in chronic GC users. After switching to DEN, ROMO-treated patients continued to gain spine BMD to a greater extent than DEN until Month 24.

9172 Contrasting Bone Profiles In Pcos Are Related To Bmi: A Systematic Review And Meta-analysis

Abstract Disclosure: M.O. Premaor: None. G. Risseti: None. J. Piovezan: None. F.V. Comim: None. Polycystic ovary syndrome (PCOS) is a complex and multifaceted disorder that may affect bone health. Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty. We conducted a systematic review and meta-analysis of published research on bone mineral density (BMD), bone markers, and the risk of fractures in individuals with PCOS. We searched MEDLINE, Embase, and conference s and preprints. Studies were eligible if the PCOS was defined according to the NIH criteria, the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group criteria, AE-PCOS society criteria, or ICD codes. The endpoints studied included fractures, bone mineral density (BMD), and bone markers. The study protocol is available at PROSPERO (CRD42016049664). From the 3322 studies identified in the databases, 111 had their full texts evaluated, and 31 studies met the inclusion criteria for qualitative analysis. Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30305 women with PCOS and 101907 controls. No differences were observed between individuals with PCOS and the control group in the pooled analysis for the whole group. Nevertheless, contrasting profiles emerged after stratification using a BMI cutoff of 27 kg/m2. Women with PCOS and a mean BMI &amp;lt;27 kg/m2 exhibited lower spine BMD (MD -0.060; 95% CI, -0.110 and -0.011) and total hip BMD (MD -0.042; 95% CI, -0.068 and -0.017), and increased bone resorption marker (CTX) levels (SMD 0.38; 95%CI 0.03 and 0.72). Conversely, women with PCOS and a mean &amp;gt;27 kg/m2 exhibited increased spine BMD (MD 0.029; CI 95%, 0.009 to 0.048) and total hip BMD (MD 0.036; CI 95%, 0.010 to 0.063), with no significant changes in bone resorption markers. Due to the limited number of longitudinal studies available, it was not possible to determine the risk of bone fractures in both groups. In conclusion, the findings of this systematic review show a negative impact of PCOS on bone health in women with a BMI &amp;lt;27 kg/m2, suggesting that increased surveillance and research for bone disease may be necessary for this particular group. Presentation: 6/3/2024

8455 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p&amp;lt;0.01), had longer diabetes duration (8.4 vs 7.2, p&amp;lt;0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p&amp;lt;0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024

9236 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p&amp;lt;0.01), had longer diabetes duration (8.4 vs 7.2, p&amp;lt;0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p&amp;lt;0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024

7138 Testosterone Modulation of Muscle Transcriptome Profile During Intensive Lifestyle Intervention in Older Men With Obesity and Hypogonadism

Abstract Disclosure: V. Viola: None. T. Samanta: None. M. Duremdes Nava: None. A. Celli: None. R.C. Villareal: None. N.H. Nguyen: None. G. Colleluori: None. Y. Barnouin: None. N. Napoli: None. C. Qualls: None. B.A. Kaipparettu: None. D.T. Villareal: None. Background: We reported that testosterone replacement added to lifestyle therapy can mitigate weight loss-induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism (Barnouin et al., J Clin Endocrinol Metab, 2021). Objective: To investigate the molecular mechanisms underlying the mitigation of muscle and BMD loss in response to testosterone replacement therapy during intensive lifestyle intervention in this at-risk population. Materials and Methods: Among the 83 older (≥ 65 y) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently &amp;lt;300 ng/dl) associated with frailty (PPT score ≤ 31) who were randomized into 26-week lifestyle therapy plus testosterone (LT+Test) or placebo (LT+Pbo), 38 underwent serial muscle biopsies for the muscle transcriptomics substudy. Results: Despite a similar 9% weight loss, lean body mass and thigh muscle volume decreased less in LT+Test than LT+Pbo (both -2% vs -4%, respectively; p=0.04). Hip BMD was preserved in LT+Test compared with LT+Pbo (0.4% vs -1.1%; p=0.03). Muscle strength increased similarly in LT+Test and LT+Pbo (23% vs 24%; p=0.95). Total testosterone increased more in LT+Test than LT+Pbo (133% vs 32%; p=0.01). Based on Next Generation Sequencing, of the 39,160 and 39,115 genes detected in LT+Test and LT+Pbo, respectively, 151 genes were differentially expressed (DEGs) in LT+Test and 114 in LT+Pbo group. Gene Ontology enrichment analyses revealed that in the LT+Test group, just four muscle-related terms (muscle organ development, muscle organ morphogenesis, regulation of skeletal muscle contraction, muscle atrophy) were downregulated, and one term (muscle system process) was upregulated while in the LT+Pbo, nine terms related to muscle (muscle system process, muscle tissue development, muscle organ development, skeletal muscle tissue development, skeletal muscle organ development, skeletal muscle cell differentiation, muscle organ morphogenesis, response to stimuli involved in regulation of muscle adaptation, muscle atrophy), and one term related to bone (bone mineralization involved in bone maturation) were downregulated. Notably, muscle system process was upregulated in the LT+Test but downregulated in the LT+Pbo. The RT-PCR analyses showed that LT+Test resulted in a higher expression of MYOD1 (p=0.02) and WNT4 (p= 0.08), key genes involved in muscle and bone metabolism, respectively, compared to LT+Pbo. Furthermore, we observed significantly higher mRNA expression of MYBPH (p=0.01), SCN3B (p=0.02), and DSC2 (p=0.01), genes involved in the muscle system process, in response to LT+Test compared to LT+Pbo. Conclusion: The addition of testosterone replacement to lifestyle therapy mitigates the weight loss-induced reduction of muscle mass and BMD via countering the weight loss-induced downregulation of genes involved in muscle and bone anabolism. Presentation: 6/2/2024

7686 A Case Of A 66-Year-Old Male With Systemic Macrocytosis Complicated By Osteoporosis

Abstract Disclosure: J.M. Gri: None. M. Hillhouse: None. P. madhavan: None. Background: Osteoporosis in men is underestimated and warrants investigation for secondary causes of osteoporosis. Systemic mastocytosis is a rare secondary cause of osteoporosis. Clinical Case: This is a 66-year-old male with a past medical history of severe persistent asthma, eczema, hypertension, GERD with esophagitis, basal cell carcinoma, and systemic mastocytosis (diagnosed in 2010). Family history was significant for lung cancer in both of his parents. Patient was first noted to have hyperpigmented skin lesions on his legs, trunk and upper extremities in the early 1990s. The spots were biopsied and he was diagnosed with urticaria pigmentosa in 1998. Due to persistent symptoms of facial flushing and soft stool, he was referred to Hematology and was started on antihistamines. He later underwent a bone marrow biopsy in 2010 which showed multifocal mast cell aggregates but normal trilineage hematopoiesis. He endorsed back pain shortly after his diagnosis and a DXA scan was completed. The DXA scan showed osteopenia of the spine T score of -1.8, BMD 0.999 mg/mm3 and normal bone density in bilateral hips. He had no history of fractures. He was started on alendronate and remained on the medication from 2012 to 2015. It was stopped due to intolerable symptoms of acid reflux and he required proton pump inhibitors. DXA scan in 2017 showed normal bone density of the hips and osteopenia of the lumbar spine (T score -1.2). DXA scan in 2022 showed a decrease in spine BMD by 6% (T score -1.8) from 2017 to 2022 but unchanged from 2010. Hip bone mineral density was normal but decreased by 10% since 2010 and by 6% since 2017. Labs obtained in May 2022 showed normal serum electrophoresis, normal urine calcium and creatinine ratio, calcium and vitamin D level and urine NTX of 41 nM BCE/mM (21-83) and bone specific alkaline phosphatase level of 31.5 U/L (15-41.3). After discussion with the patient, conservative management with calcium, vitamin D and exercise has been implemented along with close follow up. Should the patient’s bone turnover markers increase or fracture risk increase, additional antiresorptive therapy will be initiated. Conclusion: This case study highlights the importance of screening for osteoporosis in patients with systemic macrocytosis. As this patient was diagnosed with osteopenia at age 53, this case also emphasizes the importance of early screening in both women and men with this rare condition. Presentation: 6/3/2024

12460 Bilateral Parietal Thinning: A Rare Condition Of Unclear Etiology

Abstract Disclosure: T.L. Madsen-Barbosa: None. M. Cheikh: None. I. Marcano: None. Background: Bilateral parietal bone thinning (BPT) is an infrequent and often underdiagnosed condition characterized by the external thinning of the skull's parietal bone. The pathophysiology is unclear, but some studies suggest a link to osteoporosis. We present a case of osteoporosis diagnosed on evaluation of BPT. Case Description: A 77-year-old woman with a history of chronic kidney disease (CKD stage IV) and type 2 diabetes was referred to the Bone Health Clinic for evaluation of low bone density. She initially presented to Neurosurgery clinic for evaluation of head indentations. A dual energy x-ray absorptiometry (DEXA) scan showed values in osteopenia range (left total hip bone mineral density (BMD) 0.678 and T-score of -2.2, left femoral neck BMD 0.272 and T-score of -1.6, and left 33% radius BMD 0.577 and T-score of -2.0), leading to the referral. The patient reported painless indentations in the parietal bones that had been progressing for four years, with no history of head trauma, inflammatory disease, or prolonged steroid use. A head computed tomography (CT) scan showed symmetric thinning of the skull’s parietal bones, with an average thickness of 2.34 mm (compared to 5.1 mm four years earlier). Review of prior images also revealed a T11 compression fracture on spine X-ray from 2019. Laboratory tests showed elevated parathyroid hormone (PTH) 155 pg/mL (reference range 15-65 pg/mL), low vitamin D 25-OH 10.6 ng/mL (reference range 30-100 ng/mL), elevated alkaline phosphatase 142 units/L (reference range 46-116 units/L), and high creatinine level 2.7 mg/dL (reference range 0.5-0.8 mg/dL), other laboratory tests were normal. After discussion with the patient and Nephrology, Denosumab therapy along with Calcium and Vitamin D supplementation were started in November 2023. The patient continues the treatment with antiresorptive medication every 6 months and head CT scan to monitor the skull thinning changes. Discussion: BPT is rare, with only approximately 150 cases reported. Crucial aspects such as its etiology, pathophysiology, treatment, and prognosis remain unknown. It can result from various conditions like trauma, systemic mastocytosis, diabetes mellitus, hereditary diseases, or idiopathic causes and mainly affects women of advanced age. Osteoporosis is suggested as a possible cause based on histological findings on prior studies that propose BPT may result from osteoporosis-induced decreased bone formation rather than increased bone destruction. The reason for excessive bone resorption in the skull of osteoporotic patients remains unclear. Our case highlights progressive and symmetric BPT possibly related to systemic conditions like osteoporosis, with a focus on treatment options. Conclusion: This case sheds light on the clinical presentation, imaging findings, pathogenesis, and treatment options for the rare condition of bilateral parietal bone thinning. Presentation: 6/3/2024

9342 Managing Osteoporosis In Patients With Phocomelia: Challenges And Strategies

Abstract Disclosure: M. Renzu: None. C. Hubers: None. V. Mehta: None. A.M. Qazi: None. A.M. Satei: None. D.K. Yerasuri: None. Introduction: Phocomelia, a rare congenital limb malformation, often results from disruptions in limb bud formation during embryonic stage, due to genetic mutations, teratogens, or environmental factors like thalidomide embryopathy. These disruptions pose unique challenges in bone health management, including an increased risk of osteoporosis.We present a case report of a 52-year-old patient with phocomelia who developed an early onset severe osteoporosis. This case stresses the need for specific measures and care to tackle bone health in individuals with congenital limb anomalies. Case Presentation: A 52-year-old white female with phocomelia, had absence of the left forearm and hand, as well as a transverse tibial deficiency with a prosthetic left lower leg since the age of 1. Osteoporosis was diagnosed after follow-up, with initial osteopenia noted at age 49. DEXA scan showed lumbar osteopenia, radial osteoporosis, and bilateral femoral neck osteopenia. FRAX score showed an 11.9% risk of osteoporotic fracture and 3.1% risk of a hip fracture.Risk factors to her osteoporosis included late menarche, early menopause due to hysterectomy, and a history of hormone replacement therapy without pregnancies. Also, chronic colitis and diarrhea caused malabsorption issues. Her left hip bone mineral density was disproportionately low due to chronic prosthesis use, necessitating close monitoring and treatment initiation with Denosumab, along with vitamin D3 and calcium supplementation.As of the latest follow-up, the patient is closely monitored, and improvement is noted in her condition. She has incorporated daily gym sessions into her routine, indicating proactive engagement in her well-being. Discussion: Managing osteoporosis in patients with phocomelia needs a personalized approach, considering the patient's unique anatomical challenges and the limitations of traditional osteoporosis management strategies. Bone tissue adapts its structure based on mechanical loading, with reduced loading in deformed limbs leading to increased resorption and elevated osteoporosis risk. Tailored treatment plans, including Denosumab, which is known as an effective pharmacological option for managing osteoporosis, complemented by dietary adjustments to enhance vitamin D and calcium intake. Physical therapy programs play a vital role in muscle strengthening and balance improvement, reducing fracture risk.Another challenge that patients with phocomelia face is barriers to accessing healthcare services, like limited specialized care providers, financial constraints, and transportation difficulties, leading to increased morbidity. Hence early screening and intervention are essential to prevent osteoporotic complications. Overall, a comprehensive approach to osteoporosis management in phocomelia patients is crucial for optimizing outcomes and enhancing quality of life. Presentation: 6/3/2024

7867 Treatment-Related Changes in Total Hip Bone Mineral Density and Fracture Risk Reduction for Drugs With Different Mechanisms of Action: The FNIH-ASBMR-SABRE Project

Abstract Disclosure: T. Vilaca: None. M.T. Schini: None. A.R. Thompson: None. E. Vittinghoff: None. L. Lui: None. S.K. Ewing: None. D.C. Bauer: None. D.M. Black: None. M. Bouxsein: None. R. Eastell: Consulting Fee; Self; Immunodiagnostic Systems, CL Bio, CureTeQ, Biocon, Takeda, UCB. Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Osteolabs. Speaker; Self; Pharmacosmos, Alexion Pharmaceuticals, Inc., Amgen Inc, UCB. Introduction: To date, trials of new anti-osteoporosis therapies have used fractures as primary endpoints. In the FNIH-ASBMR-SABRE project, we posited that the treatment-related change in total hip BMD (THBMD) could be used as a surrogate endpoint for fractures in future clinical trials of new osteoporosis therapies. To demonstrate this, we compiled a large dataset of individual patient data (IPD) from randomized trials and showed a strong association between the change in THBMD at 24 months and reduction in fracture risk. To further explore the use of THBMD as a surrogate endpoint, here we examine whether the association is robust across drugs with different mechanisms of action. Methods: We used IDP (n&amp;gt;120,000 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications (17 anti-resorptive, 3 PTH analogs, 1 odanacatib, and 1 romosozumab). We calculated the treatment-related difference (active-placebo) in mean % change in THBMD at 12, 18, and 24 months for each trial. We determined the treatment-related fracture risk reductions for the entire follow-up period, using logistic regression for radiologic vertebral fractures and Cox regression for all clinical fractures (a combination of non-vertebral and clinical vertebral fractures). We used meta-regression to estimate the study-level association (r2) between treatment-related differences in THBMD changes and fracture risk reduction, including only the 17 trials of anti-resorptive drugs and then using the entire set of 22 trials. Since there were only 3 trials of anabolic drugs, we did not perform separate analyses for the anabolic trials. Results: The r2 values were similar between all trials and antiresorptive trials only for both fracture outcomes at all time points. Specifically, for vertebral fractures, the r2 was 0.59 vs 0.70 at 12 mo, 0.69 vs 0.74 at 18 mo, and 0.73 vs 0.78 at 24 mo for all trials vs anti-resorptive trials only. For all clinical fractures, the r2 was 0.46 vs 0.51 at 12 mo, 0.64 vs 0.60 at 18 mo, and 0.71 vs 0.65 at 24 mo for all trials vs anti-resorptive trials only. Conclusion: These results demonstrate that the associations between treatment-related changes in THBMD and fracture risk reductions are robust across anti-osteoporosis therapies with varying mechanisms of action. We conclude that the treatment-related difference in THBMD change would predict fracture reduction equally well for drugs with different mechanisms of action. Presentation: 6/2/2024