Hip Bone Mineral Density Research Articles

P-547. Efficacy and Safety of B/F/TAF in Treatment-Naïve People With HIV Aged ≥ 50 Years: 5-Year Follow-Up From Two Phase 3 Studies

Abstract Background An increasing proportion of people with HIV (PWH) are aged ≥ 50 years, with a greater burden of age-related comorbidities; however, long-term analyses of this population are limited. We present key treatment outcomes through 5 years of first-line therapy with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in PWH ≥ 50 vs < 50 years. Methods Studies 1489 (NCT02607930; B/F/TAF vs dolutegravir/abacavir/lamivudine [DTG/ABC/3TC]) and 1490 (NCT02607956; B/F/TAF vs DTG+F/TAF) were randomized, double-blind, multicenter Phase 3 studies in adult PWH. This pooled analysis reports outcomes for participants ≥ 50 vs < 50 years who received B/F/TAF in the 144-week (W) randomization phase and the 96W open-label extension. Baseline demographics and clinical characteristics; proportion of participants with HIV-1 RNA < 50 copies/mL (missing=excluded); adherence; changes in CD4 cell count and metabolic, renal, and bone parameters; and treatment-emergent adverse events (TEAEs) are presented. Results Overall, 634 participants received B/F/TAF up to W240; 96 (15.1%) were ≥ 50 years and 538 (84.9%) were < 50 years. Baseline demographics, clinical characteristics, and outcomes are shown in the Table. Higher rates of baseline comorbidities were observed in those aged ≥ 50 vs < 50 years. Both groups had high rates of HIV suppression at W240. A greater proportion of participants aged ≥ 50 vs < 50 years had ≥ 95% adherence (82.8% vs 66.3%; P=0.0015). Changes in CD4 count, weight, eGFR, fasting total cholesterol to high-density lipoprotein ratio, and hip and spine bone mineral density were similar between groups. Proportions of participants with study drug-related TEAEs were similar between groups, with few participants experiencing a TEAE leading to study drug discontinuation. Proportions of TE hypertension and diabetes were modestly higher in the ≥ 50 group vs the < 50 group. Conclusion Over 5 years, participants ≥ 50 years were more likely to have high adherence to B/F/TAF treatment vs those < 50 years, with low rates of discontinuations due to AEs in both groups. B/F/TAF maintained high rates of virologic suppression, was well tolerated, and resulted in similar changes in metabolic, renal, and bone parameters in both groups, supporting its use for long-term management of HIV in older PWH. Disclosures Cissy Kityo, MD, MSc, PhD, Gilead Sciences, Inc.: Medical writing support provided by Aspire Scientific (Bollington, UK)|Janssen Pharma: Grant/Research Support Samir K. Gupta, MD, Gilead Sciences, Inc.: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Princy N. Kumar, MD, Gilead Sciences, Inc.: Advisor/Consultant|Gilead Sciences, Inc.: Board Member|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Public Company)|Johnson & Johnson: Stocks/Bonds (Public Company)|Merck: Advisor/Consultant|Merck: Board Member|Merck: Grant/Research Support|Merck: Stocks/Bonds (Public Company)|Moderna: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Theratechnologies: Grant/Research Support|ViiV/GSK: Advisor/Consultant|ViiV/GSK: Board Member|ViiV/GSK: Grant/Research Support|ViiV/GSK: Stocks/Bonds (Public Company) Amy Weinberg, DNP, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Bhumi Gandhi-Patel, PharmD, Gilead Sciences, Inc.: Employee; Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Hui Liu, PhD, Gilead Sciences, Inc.: Employee; Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Jason Hindman, PharmD, MBA, Gilead Sciences, Inc.: Employee; Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Jürgen Rockstroh, Prof, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Boehringer: Advisor/Consultant|Boehringer: Honoraria|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Gilead Sciences, Inc.: Medical writing support provided by Aspire Scientific (Bollington, UK)|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV: Advisor/Consultant|ViiV: Honoraria

Testosterone Modulation of Muscle Transcriptomic Profile During Lifestyle Therapy in Older Men with Obesity and Hypogonadism

ABSTRACTBackgroundTestosterone replacement therapy (TRT) 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.ObjectiveTo investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high‐risk older population.MethodsAmong 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently < 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26‐week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.ResultsDespite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (−2% vs. −4%, respectively; p = 0.04). Hip BMD was preserved in LT+TRT compared with LT+Pbo (0.4% vs. −1.3%; p = 0.03). Muscle strength increased similarly in LT+TRT and LT+Pbo (23% vs. 24%; p = 0.95). Total testosterone increased more in LT+TRT than LT+Pbo (133% vs. 32%; p = 0.005). Based on Next Generation Sequencing, of the 39 160 and 39 115 genes detected in LT+TRT and LT+Pbo, respectively, 195 were differentially expressed in LT+TRT and 158 in LT+Pbo. Gene Ontology enrichment analyses revealed that in LT+TRT, just four muscle‐related pathways (muscle organ development, muscle organ morphogenesis, regulation of skeletal muscle contraction, muscle atrophy) were downregulated and one pathway (muscle system process) was upregulated. In contrast, in LT+Pbo, nine muscle‐related pathways (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 pathway related to bone (bone mineralization involved in bone maturation) were downregulated. Muscle system process was upregulated in LT+TRT but downregulated in LT+Pbo. RT‐PCR analyses showed that LT+TRT resulted in a higher expression of MYOD1 (p = 0.02) and WNT4 (p = 0.02), key genes involved in muscle and bone metabolism, respectively, compared with LT+Pbo. We also observed significantly higher mRNA expression of MYBPH (p = 0.006), SCN3B (p = 0.02) and DSC2 (p = 0.01), genes involved in the muscle system process, in response to LT+TRT compared with LT+Pbo.ConclusionThe addition of TRT 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.

Effects of femoral neck width and hip Axis length on incident hip fracture risk: a registry-based cohort study.

Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) is widely used in clinical practice to assess fracture risk and guide management. DXA can also assess hip geometry, including femoral neck width (FNW) and hip axis length (HAL), which have both been associated with increased risk for hip fracture independently from BMD. Our objective was to assess if FNW predicts hip fracture independently from other factors including HAL. We performed a retrospective cohort study using the Province of Manitoba BMD registry. The study population comprised 75 095 individuals (90.8% women), mean age 64.7years, with baseline hip BMD and hip geometry parameters. Linked health records were used to ascertain subsequent hospitalization with hip fracture as a primary diagnosis. During a mean follow up of 8.3 (SD 5.1) years, 2341 incident hip fractures were recorded. Each SD increase in age- and sex-adjusted FNW was associated with incident hip fracture (HR 1.15, 95% CI 1.10-1.19) which was unchanged after adjustment for height, weight, femoral neck BMD and clinical risk factors. However, FNW showed a significant positive correlation with HAL (r = 0.68). When further adjusted for HAL, FNW was no longer associated with increased risk for hip fracture (HR 0.98, 95% CI 0.94-1.03). A similar pattern was seen for femoral neck, intertrochanteric and non hip fractures. In contrast, increased risk of hip fracture was consistently seen with each SD increase in HAL even after adjustment for all covariates including FNW (HR 1.35, 95% CI 1.28-1.42). In conclusion, FNW is a risk factor for hip fracture before but not after adjustment for HAL. HAL, on the other hand, robustly and independently predicts hip fracture, including both femoral neck and trochanteric fractures.

Correlation between serum high-density lipoprotein cholesterol and bone mineral density in vitamin D-deficient populations.

To investigate the relationship between serum high-density lipoprotein (HDL) cholesterol and bone mineral density (BMD) in vitamin D-deficient population. This study was a cross-sectional study. From January to December 2020, 2583 middle-aged and older adult aged 40 and above were randomly selected in the Health Management Center of the Affiliated Hospital of Guizhou Medical University for health examination and questionnaire survey. The correlation was determined by Pearson correlation method, and the independent correlation was analyzed by multiple linear regression. The receiver Operating characteristic (ROC) curve estimates HDL-C cutoff levels for predicting osteoporosis risk. The prevalence of osteoporosis in the study population was 11.4%, the overall prevalence of 25 (OH) D deficiency was 78.2%. There was no correlation between HDL-C and BMD of lumbar spine, femoral neck and total hip in normal vitamin D group (P > 0.05). HDL-C in the deficient group was negatively correlated with BMD of lumbar spine and femoral neck (P < 0.05), but not with BMD of total hip. Serum HDL-C concentration increased with the progression of osteoporosis. When serum 25 (OH) D level was lower than normal level, HDL-C ≥ 1.215mmol/L was an independent predictor of osteoporosis (sensitivity = 75%, specificity = 53%, Area = 0.625). HDL-C was inversely associated with BMD in the lumbar spine and femoral neck in people aged 40years and older with vitamin D deficiency. When serum HDL-C concentration ≥ 1.215mmol/L, it can better predict the occurrence of osteoporosis.

Age-related trends in trabecular bone scores and bone mineral density in Chinese men with type 2 diabetes mellitus: a cross-sectional study

Patients with Type 2 diabetes mellitus(T2DM) typically have an average or higher bone mineral density (BMD) but are at a significantly higher risk of fracture than patients without diabetes. Trabecular bone score (TBS) is a textural index derived from pixel gray-level variations in lumbar spine DXA image, which has been introduced as an indirect measure of bone quality. This study aimed to discuss the trends and annual rates of change in BMD and TBS with age in Chinese men with T2DM and men without diabetes mellitus. Lumbar spine(LS) TBS was significantly lower in males with T2DM compared to men without diabetes(1.279 ± 0.117 vs. 1.299 ± 0.090, P = 0.005). However, TBS in men with T2DM peaked around age 60, which occurred later and was lower than the peak observed in men without diabetes, who reached their peak TBS around age 50 (1.294 ± 0.126 vs. 1.328 ± 0.088). Femoral neck, total hip, and lumbar spine BMD in men with T2DM were not significantly different from those in men without diabetes. The results showed that both men with or without T2DM exhibited the lowest annual rates of change in TBS at 66–75 years of age, with values of -1.05%(P < 0.001) and − 0.90%(P < 0.001), respectively. Patients with great glycemic control demonstrated higher TBS and BMD. Men with T2DM have later and lower peak TBS and faster bone loss, suggesting that diabetes may negatively impact bone microarchitecture and mineralization.

Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use.

Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab's sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

Effect of a High-Impact Exercise Program on Hip Strength Indices in a Group of Obese Women after Bariatric Surgery.

The purpose of this study was to explore the influence of a 12-month high-impact physical training program (descending stairs) on bone health in a group of young obese women who had undergone bariatric surgery (type sleeve). Fifty-two premenopausal women with a body mass index (BMI) > 35 kg/m2 (range: 35.06-60.97 kg/m2), aged 19-47 years old were included in this study. Patients were randomized to either exercise group (EG), control group (CG) or observational group (OG). 2 to 3 weeks post-bariatric surgery (BS), EG underwent a 12-month semi-supervised high impact (descending stairs) exercise program, CG performed a 12-month oriental dance activity while the third OG received only standard medical care. Patients were assessed before BS and 12 months post-BS for body composition, bone mineral density (BMD) and femoral neck geometry. Bone parameters were evaluated by DXA. At baseline, there were no significant differences among the three groups in the clinical characteristics and the bone variables. 12 months after the surgery, there were some group*time interactions. The 3 groups showed significantly lower whole body BMD (-1.8; -2.9; -4.2 % respectively for EG; CG and OG). The EG showed a significant increase of the femoral neck BMD (+1.4 %; p < 0.05), the femoral neck cross-sectional area (+4.6 %; p < 0.05), and the femoral neck cross-sectional moment of inertia (+15.7 %; p < 0.01) while all these values decreased significantly in the 2 other groups. The total hip BMD decreased in all groups, but the EG showed less significant total hip variation, and lumbar spine BMD decreased significantly only in the OG. This study mainly shows that the stair descent can be considered as an effective high-impact physical exercise for obese women who have undergone bariatric surgery. This kind of exercise has significant effects in maintaining or reducing the loss of BMD at the femoral neck and the total hip. Finally, since the EG group showed significant increases in femoral neck geometry variables, this study suggests that this kind of training could be efficient at reducing the hip fracture risk.

Discordance Between Spine-Hip and Paretic-Nonparetic Hip Bone Mineral Density in Hemiplegic Stroke Patients: A Multicenter Retrospective Study

Objective: To identify the prevalence and factors associated with T-score discordance between the spine and hip, as well as between the paretic and non-paretic hips in hemiplegic stroke patients, this study investigated bone mineral density (BMD) patterns. Bone loss predominantly affects the paretic hip after a stroke, and typical clinical assessments using dual-energy X-ray absorptiometry (DXA) that scan the lumbar spine (LS) and a single hip may overlook an osteoporosis diagnosis. This oversight could potentially lead to suboptimal treatment for stroke patients.Methods: This study was a multicenter retrospective analysis of 540 patients admitted for stroke rehabilitation between October 2014 and February 2022, who underwent DXA of LS and bilateral hips.Results: The prevalence rates of concordance, low LS discordance, and low hip discordance between the LS and hips were 48.2%, 12.2%, and 39.6%, respectively. The discordance rate between bilateral hips was 17.0%. The paretic side had significantly lower total hip T-scores than the non-paretic side (p&lt;0.001). Notably low paretic hip discordance was more prevalent during the chronic phase. DXA scans of the LS and both hips revealed a 0.7%–0.9% higher major discordance compared to LS and single hip DXA scans. The multivariate analysis revealed a significant correlation between a low paretic hip discordance and cognitive impairment (adjusted odds ratio 0.071, 95% confidence interval 0.931–1.003, p&lt;0.05).Conclusion: Since stroke survivors are at high risk for hip fractures, comprehensive BMD assessments, which include LS and bilateral hips, should be considered for post-stroke osteoporosis care to enhance diagnostic accuracy and timely treatment.

Cumulative incidence and treatment effectiveness of low bone mineral density among people living with HIV in Iran (2021–2023)

BackgroundThe introduction of antiretroviral therapy (ART) has significantly improved the life expectancy of people living with HIV (PLHIV), leading to an increased prevalence of age-related comorbidities such as osteoporosis. This study investigates the incidence and characteristics of low bone mineral density (BMD) and the treatment effectiveness of low BMD participants among PLHIV in Kerman, Iran.MethodsA longitudinal study utilized dual-energy X-ray absorptiometry (DEXA) to screen 94 PLHIV in Kerman, Iran, for low BMD. Participants were aged 30 or older and had received antiretroviral therapy (ART) for at least 12 months. Those with low BMD were entered into a single-arm clinical trial and received the appropriate treatment. These people were checked to assess the treatment effectiveness 11 months after completion of the treatment. Those with normal BMD entered a cohort study and were checked to determine the cumulative incidence of low BMD. Data on demographics, medical history, and laboratory tests were collected. A chi-square test was used to assess the association between the categorical variables. A t-test (for normally distributed variables), or Mann-Whitney U (for non-normally distributed variables) was used to assess the differences of BMD between the two groups. Statistical significance was set at p ≤ 0.05, with analyses conducted in Stata 17.ResultsAmong 94 PLHIV at baseline, 48 participants (51%) had low BMD. During the follow-up, 11 participants (11.7%) missed the follow-up visits. In the follow-up, 83 PLHIV (40 with low BMD and 43 with normal BMD at baseline) were available. Among 40 participants who received treatment, 5 had normal BMD (treatment effectiveness: 12.5%). However, among 43 PLHIV with normal BMD at baseline, 7 PLHIV had low BMD at the follow-up visit (cumulative Incidence 16.3%). Those with lower body mass index (BMI) had a higher prevalence of low BMD than those with normal BMI during the follow-up (p-value: 0.003). Lumbar spine BMD increased modestly (0.005 g/cm2), while femoral neck and total hip BMD declined in total participants (0.011, 0.007 g/cm2, respectively). Osteocalcin and β-isomerized C-terminal telopeptides (β-CTx) levels were higher in the low BMD group in the follow-up, indicating increased bone turnover.ConclusionsThe study highlights the high cumulative incidence of 16.3% and treatment effectiveness of 12.5% of low BMD among PLHIV in Kerman, Iran, with implications for fracture risk. Despite a steady state in spine BMD decline, the risk of fracture remains elevated due to continued femoral neck and total hip BMD reduction. Gender-specific factors and BMI may influence susceptibility to low BMD.

The relationship between baseline BMD and fracture incidence in the placebo groups of RCTs using individual patient data from the FNIH-ASBMR-SABRE Project.

We have proposed to the Food and Drug Administration (FDA) that treatment-related increases in total hip bone mineral density (TH BMD) at two years could be a surrogate endpoint for fracture risk reduction in clinical trials. The qualification of a surrogate includes a strong association of the surrogate with the clinical outcome. We compiled a large database of individual patient data (IPD) through the FNIH-ASBMR-SABRE project, and this analysis aimed to assess the relationship between baseline BMD and fracture risk in the placebo groups. We estimated the association of baseline TH, femoral neck (FN) and lumbar spine (LS) BMD with fracture risk using IPD from the combined placebo groups which included data from 46 666 placebo participants in 25 randomised controlled trials (RCTs). We estimated the relative risk (RR) of fracture per standard deviation (SD) decrease in baseline BMD using logistic regression models for radiographic vertebral fractures and proportional hazards models for hip, non-vertebral, "all" and "all clinical" fractures. Total person-years in the combined placebo groups was 250 662 (mean baseline age 70.2 ± 7.2years, mean TH BMD T-score -1.97 ± 0.90). We observed significant relationships between baseline TH BMD and vertebral (RR = 1.55/SD), hip (RR = 2.27), non-vertebral (RR = 1.31), all (RR = 1.43) and all clinical (RR = 1.35) fracture risk. Fracture risk estimates were similar for FN BMD and after adjustment for age, race and study. Fracture incidence increased with decreasing TH BMD quintile, confirming the strong graded association between TH BMD and fracture risk. There was a strong relationship between LS BMD and vertebral fracture risk (RR = 1.56/SD), but only a weak association with non-vertebral (RR = 1.07) and no association with hip (RR = 1.01) fracture risk. These data support the very strong relationship between hip BMD and fracture risk and provide supporting rationale for change in TH BMD as a surrogate for fracture risk reduction in future RCTs.

Sarcopenia-associated factors and their bone mineral density levels in middle-aged and elderly male type 2 diabetes patients.

Chronic hyperglycemia can damage the microcirculation, which impairs the function of various organs and tissues and predisposes individuals to chronic complications. Sarcopenia (SP) is the age-related decline in muscle mass and function that contributes to the sequelae of type 2 diabetes. In particular, diabetic patients are at higher risk of SP because of insulin resistance, chronic inflammation, and decreased physical activity. To identify SP-associated factors in middle-aged and elderly male type 2 diabetes mellitus (T2DM) patients and their correlation with bone mineral density (BMD). A retrospective analysis was conducted on 196 middle-aged and elderly male T2DM inpatients in the First Affiliated Hospital of Chongqing Medical University between June 2021 and June 2023, with 60 concurrent healthy individuals as the control group. Differences in general information, blood biochemistry, glycosylated hemoglobin, muscle strength, and detection rate of SP were compared between groups. The BMD, appendicular skeletal muscle (ASM), and fat mass, as well as grip strength and gait speed, were determined for each patient, and the ASM index (ASMI) was counted. The quantitative data were subjected to correlation and logistic regression analyses to identify risk factors for SP. Fifty-one of the 196 middle-aged and elderly male T2DM patients were diagnosed with SP, which accounted for 26.02%. The middle-aged and elderly T2DM patients with SP exhibited a longer diabetes mellitus (DM) course and a lower body mass index (BMI) and 25(OH)D3 compared with the non-SP patients. The T2DM + SP patients exhibited lower BMI, ASM, ASMI, left- and right-hand grip strength, gait speed, and muscle and fat mass of the upper and lower limbs compared with the diabetic non-SP patients. The femoral neck, total hip, and lumbar spine L1-4 BMD were markedly lower in T2DM + SP patients compared with those in the non-SP diabetics. Long-term DM course, low BMI, and low BMD of the femoral neck, lumbar spine L1-4, and total hip were identified as risk factors for the development of SP. T2DM patients are at risk for SP; however, measures can be taken to prevent the related risk factors.

The effect of denosumab on minimum 3-years BMD changes in patients with osteoporotic hip fractures: a propensity score matching analysis.

Denosumab, a potent antiresorptive agent, has been recognised to increase bone mineral density (BMD) and reduce fracture risk in vertebrae and hips. Despite its widespread use, no sequential follow-up studies have investigated its effects on BMD in patients with hip fractures. This study aimed to analyse the effect of denosumab on BMD gain in patients with hip fractures and investigate the incidence of subsequent hip fractures. This retrospective study analysed 371 patients treated with denosumab for at least 3years, including 122 patients with hip fractures. 1:1 propensity score matching was used to compare BMD changes in the lumbar spine, total hip, and femoral neck, as well as additional hip fracture incidence between the hip fracture and the other than hip fracture group. Ultimately, 122 patients in each group were compared. Subgroup analysis compared osteoporosis medication-naïve patients with those with prior medication use. The hip fracture and other than hip fracture group exhibited significant annual increases in lumbar spine and total hip BMD, with no significant differences between them after matching. The femoral neck BMD increased significantly only in the first year. The incidence of additional hip fractures did not differ significantly between the groups. Moreover, the effect of denosumab on BMD increase was more pronounced in patients without a previous medication history for anti-osteoporosis treatment than in those with such a history. Denosumab significantly increased lumbar spine and total hip BMD in patients with hip fractures, with comparable efficacy to that in other than hip fracture patients. Its effect was more pronounced in medication-naïve patients, suggesting its efficacy regardless of hip fracture status.

Biological Heterogeneity in Susceptibility to Glucocorticoid-Induced Bone Loss: Short- and Long-Term Hip BMD Trajectories.

Glucocorticoids (GCs) are widely used for their anti-inflammatory and immunosuppressive properties. Their effect on bone health is predominantly negative by decreasing bone formation and increasing risk of fractures. This work aimed to quantify the short- and long-term changes in total hip bone mineral density (THBMD) after initiating systemic GC treatment in previously GC treatment-naive adults without bone protective agents. An observational study was conducted using THBMD data from dual-energy x-ray absorptiometry (DXA). Individuals were stratified by sex and tertiles of GC exposure. Individuals not GC-exposed served as a reference group. Routine-care DXA scans were obtained from the main public hospitals servicing the Island of Funen in Denmark. A total of 15 099 adults underwent routine DXA at Odense University Hospital between 2006 and 2021. Data were enriched with Danish national registers. Intervention included systemic GCs (observational data). The short-term outcome included annualized THBMD changes between first 2 DXA scans. The long-term outcome included greater than 5% annualized THBMD loss over a 10-year follow-up. Strong associations between GC exposure and THBMD loss was found for both outcomes, with larger losses in the middle and upper tertiles of GC exposure. The risk of experiencing greater than 5% annualized THBMD loss was elevated, especially in the first 2 years of initiating GC treatment. There is significant heterogeneity in THBMD responses, with approximately 1 in 5 patients experiencing no nominal bone loss despite receiving upper tertile levels of GC exposure. The findings confirm the association between initial GC exposure and significant bone loss. The heterogeneity in individual responses emphasizes the need for early monitoring and personalized approaches in managing bone health for patients undergoing GC treatment.

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.

Age- and Sex-Related Volumetric Density Differences in Trabecular and Cortical Bone of the Proximal Femur in Healthy Population.

There are age- and sex-related increases in the prevalence of osteoporosis. Bone densitometry based on dual energy X-ray absorptiometry (DXA) is the gold standard for the assessment of bone mineral density (BMD). Three-dimensional (3D) analysis of the proximal femur (3D-DXA) allows discrimination between cortical and trabecular compartments, and it has shown a good correlation with computed tomography. We aimed to assess age- and sex-related volumetric density differences in trabecular and cortical bone using 3D-DXA and determine the reference intervals for integral volumetric (v)BMD within the Argentine population. Healthy female and male adult subjects (N=1,354) from Argentina were included. Hip BMD was measured using DXA, and 3D analysis was performed using 3D-Shaper software. The integral vBMD, cortical surface BMD, and trabecular vBMD (trab vBMD) were measured. The study population included 73.9% women (N=1,001) and 26.13% men (N=353). We found a significant decrease in integral vBMD between 20 and 90 years in both sexes (women, -23.1%; men, -16.6%). Bone loss indicated in the integral vBMD results was mainly due to a decrease in trabecular bone in both sexes (women, -33.4%; men, -27.7%). The age-related loss of cortical bone density was less and was limited to the female population, without no age-related differences in men. Moreover, 3D-DXA allowed us to propose reference intervals for integral vBMD. We found age- and sex-related bone loss between 20 and 90 years in an Argentine cohort via integral vBMD measurements using 3D-DXA, mainly due to decreases in trabecular bone in both sexes. The age-related loss of cortical bone density was less and was limited to the female population.

Bone strain index for fracture risk assessment in older men-the prospective STRAMBO study.

Bone strain index (BSI) is a noninvasive index of bone strength assessed on lumbar spine and femur dual energy X-ray absorptiometry scans using the finite-element method. In this study, we assess the link of the lumbar spine and hip BSI with fracture risk in older men. Prospective cohort study. A cohort of 825 men aged ≥60 was followed up for 12 years. Lumbar spine and hip bone mineral density, BSI, Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOPFx), and lumbar spine trabecular bone score (TBS) were assessed at baseline. Overall, 159 men had 198 incident fractures. After adjustment for FRAX and prior falls, a higher BSI was associated with a higher fracture risk, eg, trochanter BSI: (HR = 1.34 per standard deviation (SD) increase, 95% CI: 1.14-1.58, P < .001). Patterns were similar for MOPFx, vertebral, nonvertebral, and multiple fractures. The fracture risk was higher in the highest vs the lowest BSI quartiles. The associations were the strongest for the BSI of the lumbar spine and trochanter. When the TBS and BSI were analyzed jointly, their respective contributions to fracture prediction varied according to the fracture and the site of the BSI, eg, both the TBS and the trochanter BSI contributed to the MOPFx prediction (TBS: HR = 1.38/SD decrease, 95%CI: 1.04-1.84, P < .05; BSI: HR = 1.49/SD increase, 95% CI: 1.16-1.91, P < .005). The BSI at both the lumbar and the femoral sites was associated with a higher fracture risk independently of FRAX and prior falls in older men followed prospectively for 12 years.

Prevalence and risk factors of osteoporosis in lupus nephritis patients in China: a cross-sectional study

BackgroundOsteoporosis is a significant concern among individuals with lupus nephritis (LN), with reported prevalence rates exhibiting considerable variation. This study investigates the prevalence and identifies risk factors contributing to osteoporosis in premenopausal and postmenopausal LN patients, addressing the paucity of data specific to the Chinese population.MethodsThis cross-sectional study enrolled patients with renal biopsy-proven LN, who underwent bone mineral density (BMD) measurements using dual X-ray absorptiometry at the lumbar spine, total hip, and femoral neck. The study was conducted at Tongji hospital from May 2011 to June 2018.ResultsA total of 130 patients were evaluated, with a mean age of 46.2 ± 12.9 years, including 2 males and 128 females. A significant majority, 52.3% (n = 67) of the female patients, were identified as postmenopausal. BMD measurements revealed that 40.0% of patients had osteoporosis in at least one site. The spearman rank correlation of BMD with clinical characteristics indicated that age at menopause, weight, height, and body mass index were positively correlated with BMD, while age, age at diagnosis of LN, and menopause duration were negatively correlated with BMD in lumbar spine, total hip, and/or femoral neck. Multivariable linear regression analysis demonstrated that body mass index was positively associated with BMD, whereas disease duration and menopause duration were negatively associated with BMD in all and postmenopausal patients. Postmenopausal patients consistently had a higher prevalence of osteoporosis across all measured sites. Factors such as older age, lower weight, and the absence of bisphosphonates therapy were independently associated with an increased risk of osteoporosis in LN patients.ConclusionOur findings underscore a substantial prevalence of osteoporosis in LN patients, especially among postmenopausal individuals. The study identifies older age, lower weight, and absence of bisphosphonates treatment as risk factors for osteoporosis in this patient population.

High prevalence of osteoporosis among virally suppressed older people (≥60 years) living with HIV.

Our objective was to evaluate bone mineral density (BMD) among older people living with HIV at the time of enrolment into a clinical trial in Kenya. The bictegravir/emtricitabine/tenofovir alafenamide (BFTAF) Elderly Study is a clinical trial among virally suppressed people living with HIV aged ≥60 years randomized to switch to BFTAF or continue their pre-enrolment regimen. At enrolment, dual-energy x-ray absorptiometry (DXA) of the lumbar spine, total hip, and femoral neck was performed and T-scores calculated for BMD. Osteoporosis was defined as T-score -2.5 or lower and osteopenia as T-score between -1 and -2.5. Fracture risk was calculated based on clinical risk factors (not including BMD), considering HIV as a secondary cause of osteoporosis, and the correlation between FRAX®-HIV and BMD assessed. Between February and May 2022, a total of 296 participants were enrolled. All were Black African, 147 (49.7%) were female, the median age was 64 years (range 60-77), and 280 (94.6%) were on tenofovir disoproxil fumarate. The median BMD of lumbar spine, total hip, and femoral neck was 0.87 g/cm2 (interquartile range [IQR] 0.78-0.99), 0.89 g/cm2 (IQR 0.79-1.01), and 0.75 g/cm2 (IQR 0.67-0.84), respectively, with median T-scores of -1.9 (IQR -2.8 to -0.7), -1.0 (IQR -1.9 to -0.3), and -1.5 (IQR -2.2 to -0.9), respectively. Osteoporosis and osteopenia were found in 37.5% and 47.3% of participants, respectively. Major osteoporotic fracture and hip fracture 10-year median probabilities using FRAX®-HIV were 3.4% (IQR 2.8-4.6) and 1.0% (IQR 0.7-1.3). Correlation coefficients between these FRAX®-HIV probabilities and femoral neck BMD were -0.204 for major osteoporotic fracture and -0.338 for hip fracture. The prevalence of osteoporosis is high among older people living with HIV in Kenya, where DXA is not readily available and risk calculation without BMD had low correlation with measured BMD values. Additional data are required on the impact of investment in fracture risk assessment and treatment, including population-specific risk calculators.

Sequential treatment from bisphosphonate to denosumab improves lumbar spine bone mineral density in postmenopausal osteoporosis patients: A meta-analysis of randomized controlled trials.

Bisphosphonates are effective in the treatment of postmenopausal osteoporosis. However, their prolonged use induces adverse events and may lead to a rapid decline in bone mineral density (BMD) after discontinuation. Denosumab, a human monoclonal antibody, is a widely used antiresorptive agent that is more effective than bisphosphonates in improving bone density. Whether sequential treatment with denosumab after bisphosphonate therapy can maintain or further increase BMD at all sites has not been conclusively demonstrated. Thus, we performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of this sequential therapy on BMD. We searched the PubMed, Embase, and Cochrane Library databases from December 1, 1986, to May 2, 2024, for all RCTs that assessed the efficacy of sequential therapy of bisphosphonate transition to denosumab in postmenopausal women with osteoporosis. BMD changes at the lumbar spine, femoral neck, and total hip were used as outcomes. We assessed methodological quality, extracted relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions, applied random-effects models for meta-analyses, performed heterogeneity analyses, and assessed publication bias. A total of 3290 patients from 4 RCTs were included in the meta-analysis. Forest plot analysis showed that sequential treatment with bisphosphonate-denosumab was associated with higher lumbar spine BMD gain than continuous bisphosphonate treatment [mean difference (MD) = 5.50, 95% confidence interval (CI) = 5.26-5.75, I2 = 32.88%). No risk of bias was observed for the 4 trials, but there was an increase in femoral neck and total hip BMD. Moreover, analyses could not be performed because of high heterogeneity (femoral neck BMD: MD = 3.85, 95% CI = 2.84-4.85, I2 = 97.88%; total hip BMD: MD = 5.65, 95% CI = 4.28-7.02, I2 = 97.91%). Sequential therapy that involves a transition from bisphosphonates to denosumab had a positive effect on lumbar spine bone density, and this type of therapy may be a potential treatment option for increasing lumbar spine bone density in postmenopausal women.

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 and 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 (83–129) mg/dL, median (P25–P75)] levels than the control group [192.1 ± 34.44 mg/dL, p = 0.009; 95 % CI = −37.76, 5.52 and 121.6 (97–145) 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 and 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.