Rapid bone microarchitecture decline in older men with high bone turnover-the prospective STRAMBO study.

Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60-87 yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD). Bone microarchitecture and strength (distal radius and distal tibia) were estimated by high-resolution pQCT (XtremeCT, Scanco Medical) at baseline and then after 4 and 8 yr. Thirty-seven men took medications affecting bone metabolism. Statistical models were adjusted for age and BMI. At the distal radius, the decrease in the total bone mineral density (Tt.BMD), cortical BMD (Ct.BMD), cortical thickness (Ct.Thd), and cortical area (Ct.Ar) and failure load was faster in the highest vs the lowest CTX-I quartile (failure load: -0.94 vs -0.31% yr-1, P < .001). Patterns were similar for distal tibia. At the distal tibia, bone decline (Tt.BMD, Ct.Thd, Ct.Ar, Ct.BMD, and failure load) was faster in the highest vs the lowest tDPD quartile. At each skeletal site, the rate of decrease in Tb.BMD differed between the extreme OC quartiles (P < .001). Men in the highest BAP quartile had a faster loss of Tt.BMD, Tb.BMD, reaction force, and failure load vs the lowest quartile. The link between PINP and bone decline was poor. The BTM score is the sum of the nos. of the quartiles for each BTM. Men in the highest quartile of the score had a faster loss of cortical bone and bone strength vs the lowest quartile. Thus, in the older men followed prospectively for 8 yr, the rate of decline in bone microarchitecture and estimated bone strength was 50%-215% greater in men with high bone turnover (highest quartile, CTX-I above the median) compared to the men with low bone turnover (lowest quartile, CTX-I below the median).

Fracture risk based on HR-pQCT measures does not vary with age in older adults - the bone microarchitecture international consortium (BoMIC) prospective cohort study.

Fracture risk increases with lower areal BMD (aBMD); however, aBMD-related estimate of risk may decrease with age. This may depend on technical limitations of 2-dimensional (2D) DXA which are reduced with 3D high-resolution peripheral quantitative computed tomography (HR-pQCT). Our aim was to examine whether the predictive utility of HR-pQCT measures with fracture varies with age. We analyzed associations of HR-pQCT measures at the distal radius and distal tibia with two outcomes: incident fractures and major osteoporotic fractures. We censored follow-up time at first fracture, death, last contact or 8 years after baseline. We estimated hazard ratios (HR) and 95%CI for the association between bone traits and fracture incidence across age quintiles. Among 6835 men and women (ages 40-96) with at least one valid baseline HR-pQCT scan who were followed prospectively for a median of 48.3 months, 681 sustained fractures. After adjustment for confounders, bone parameters at both the radius and tibia were associated with higher fracture risk. The estimated HRs for fracture did not vary significantly across age quintiles for any HR-pQCT parameter measured at either the radius or tibia. In this large cohort, the homogeneity of the associations between the HR-pQCT measures and fracture risk across age groups persisted for all fractures and for major osteoporotic fractures. The patterns were similar regardless of the HR-pQCT measure, the type of fracture, or the statistical models. The stability of the associations between HR-pQCT measures and fracture over a broad age range shows that bone deficits or low volumetric density remain major determinants of fracture risk regardless of age group. The lower risk for fractures across measures of aBMD in older adults in other studies may be related to factors which interfere with DXA but not with HR-pQCT measures.

Decline in muscle strength and physical function after fracture in men - the prospective STRAMBO study.

Studies on muscle strength and physical function after fracture are focused on short follow-ups and adjacent anatomical region. We compared loss of muscle strength and physical function in men after fracture with normal ageing-related decline. In 823 men aged 60-87, measurements of grip strength and clinical tests (chair stands, balance) were performed every 4 years for 12 years. In 155 men with incident fracture, we compared the status after vs. before the fracture. In men without fracture (controls), we compared the status on the first follow-up (4 years) vs. baseline. In men with fracture, grip strength decreased more than in the controls (41%, 0.28SD, P < .01). Men with fracture had higher risk of incident deterioration on the five chair-stand test vs. the controls (OR = 2.45, P < .001). They had higher risk of incident inability to stand for 10s with closed eyes vs. the controls (OR = 4.80, P < .01). They also had higher risk of deterioration on the tandem walk than the controls: forwards (OR = 2.04, P < .01), backwards (OR = 2.25, P < .005). The rapid physical decline was not limited to the region of the fracture site. In men who had incident non-upper limb fractures, grip strength decreased more (32%, P < .05) vs. the controls. In men who had incident non-lower limb fractures, the risk of decline in the tests of the lower limbs was higher vs. controls (chair stands, OR = 2.73, P < .001). The risk of decline was higher in men with clinical fractures which occurred >1 year before the next visit vs. controls (tandem walk forwards, OR = 2.98, P < .005). Overall, in older men, fractures were associated with greater loss of muscle strength and physical function vs. normal ageing. This accelerated decline was also found in the anatomical regions remote from the fracture site. Thus, programs to decrease or reverse the post-fracture decline could have beneficial effects on subsequent fracture risk.

Studies on muscle strength and physical function after fracture are focused on short follow-ups and adjacent anatomical region. We compared loss of muscle strength and physical function in men after fracture with normal ageing. In 823 older men, we assessed physical function every 4 years for 12 years. In men with incident fracture, we compared the status after vs. before the fracture. In men without fracture (controls), we compared the status at 4 years vs. baseline. Men with fracture had significantly greater loss of muscle strength (grip, thighs) as well as greater decline in static balance (standing with closed eyes) and dynamic balance (tandem walk) than the controls. The rapid physical decline was not limited to the region of the fracture site. In men who had non-upper limb fractures, grip strength decreased more than in the controls. In men who had non-lower limb fractures, lower limb physical function decreased more than in the controls. Thus, in older men, fractures were associated with greater loss of muscle strength and physical function vs. normal ageing. This rapid decline was also found in the anatomical regions remote from the fracture site. Therefore, programs to decrease the post-fracture decline could have beneficial effects.

Machine-Learning Assessed Abdominal Aortic Calcification is Associated with Long-Term Fall and Fracture Risk in Community-Dwelling Older Australian Women.

Abdominal aortic calcification (AAC), a recognized measure of advanced vascular disease, is associated with higher cardiovascular risk and poorer long-term prognosis. AAC can be assessed on dual-energy X-ray absorptiometry (DXA)-derived lateral spine images used for vertebral fracture assessment at the time of bone density screening using a validated 24-point scoring method (AAC-24). Previous studies have identified robust associations between AAC-24 score, incident falls, and fractures. However, a major limitation of manual AAC assessment is that it requires a trained expert. Hence, we have developed an automated machine-learning algorithm for assessing AAC-24 scores (ML-AAC24). In this prospective study, we evaluated the association between ML-AAC24 and long-term incident falls and fractures in 1023 community-dwelling older women (mean age, 75 ± 3 years) from the Perth Longitudinal Study of Ageing Women. Over 10 years of follow-up, 253 (24.7%) women experienced a clinical fracture identified via self-report every 4-6 months and verified by X-ray, and 169 (16.5%) women had a fracture hospitalization identified from linked hospital discharge data. Over 14.5 years, 393 (38.4%) women experienced an injurious fall requiring hospitalization identified from linked hospital discharge data. After adjusting for baseline fracture risk, women with moderate to extensive AAC (ML-AAC24 ≥ 2) had a greater risk of clinical fractures (hazard ratio [HR] 1.42; 95% confidence interval [CI], 1.10-1.85) and fall-related hospitalization (HR 1.35; 95% CI, 1.09-1.66), compared to those with low AAC (ML-AAC24 ≤ 1). Similar to manually assessed AAC-24, ML-AAC24 was not associated with fracture hospitalizations. The relative hazard estimates obtained using machine learning were similar to those using manually assessed AAC-24 scores. In conclusion, this novel automated method for assessing AAC, that can be easily and seamlessly captured at the time of bone density testing, has robust associations with long-term incident clinical fractures and injurious falls. However, the performance of the ML-AAC24 algorithm needs to be verified in independent cohorts. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Dysregulation of MicroRNAs in Adult Osteogenesis Imperfecta: The miROI Study.

As epigenetic regulators of gene expression, circulating micro-RiboNucleic Acids (miRNAs) have been described in several bone diseases as potential prognostic markers. The aim of our study was to identify circulating miRNAs potentially associated with the severity of osteogenesis imperfecta (OI) in three steps. We have screened by RNA sequencing for the miRNAs that were differentially expressed in sera of a small group of OI patients versus controls and then conducted a validation phase by RT-qPCR analysis of sera of a larger patient population. In the first phase of miROI, we found 79 miRNAs that were significantly differentially expressed. We therefore selected 19 of them as the most relevant. In the second phase, we were able to validate the significant overexpression of 8 miRNAs in the larger OI group. Finally, we looked for a relationship between the level of variation of the validated miRNAs and the clinical characteristics of OI. We found a significant difference in the expression of two microRNAs in those patients with dentinogenesis imperfecta. After reviewing the literature, we found 6 of the 8 miRNAs already known to have a direct action on bone homeostasis. Furthermore, the use of a miRNA-gene interaction prediction model revealed a 100% probability of interaction between 2 of the 8 confirmed miRNAs and COL1A1 and/or COL1A2. This is the first study to establish the miRNA signature in OI, showing a significant modification of miRNA expression potentially involved in the regulation of genes involved in the physiopathology of OI. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Accelerated Bone Loss in Older Men With Severe Abdominal Aortic Calcification-the Prospective MINOS Study.

CONTEXT: Data on the association between the severity of abdominal aortic calcification (AAC) and bone loss are discordant. OBJECTIVE: Our aim was to assess the association between baseline AAC and prospectively assessed bone loss in older men. METHODS: This prospective cohort study started in 1995 (MINOS). Men aged 50 to 85 years (n = 778) had AAC assessed on the lateral radiograph of the spine using Kauppila's semiquantitative score and was followed prospectively for 7.5 years. Bone mineral density (BMD) and bone mineral content (BMC) were measured by dual-energy x-ray absorptiometry every 18 months. Statistical analysis was performed using linear mixed models. RESULTS: In comparison to men without AAC (AAC = 0), severe AAC (>6) was associated with more rapid bone loss at the total hip (-0.62 ± 0.06 vs -0.32 ± 0.04%/year; P < .001), trochanter, and distal forearm (-0.72 ± 0.06 vs -0.45 ± 0.03%/year; P < .001). The highest decile (AAC >10) was associated with more rapid bone loss at the femoral neck, whole body, and ultradistal radius (-0.86 ± 0.12 vs -0.34 ± 0.05%/year; P < .001). The results were similar for BMD and for BMC. The patterns were similar in sensitivity analyses (eg, after excluding men with abdominal obesity, after excluding current smokers, after excluding men with ischemic heart disease or with diabetes mellitus, after excluding men with abnormal concentrations of lipids, bioavailable 17ß-estradiol or 25-hydroxycholecalciferol, after excluding men with glomerular filtration rate <60 mL/min). CONCLUSION: Severe AAC is associated with faster bone loss in older men and may contribute to the higher fracture risk observed in this population.

Machine learning for abdominal aortic calcification assessment from bone density machine-derived lateral spine images.

BACKGROUND: Lateral spine images for vertebral fracture assessment can be easily obtained on modern bone density machines. Abdominal aortic calcification (AAC) can be scored on these images by trained imaging specialists to assess cardiovascular disease risk. However, this process is laborious and requires careful training. METHODS: Training and testing of model performance of the convolutional neural network (CNN) algorithm for automated AAC-24 scoring utilised 5012 lateral spine images (2 manufacturers, 4 models of bone density machines), with trained imaging specialist AAC scores. Validation occurred in a registry-based cohort study of 8565 older men and women with images captured as part of routine clinical practice for fracture risk assessment. Cox proportional hazards models were used to estimate the association between machine-learning AAC (ML-AAC-24) scores with future incident Major Adverse Cardiovascular Events (MACE) that including death, hospitalised acute myocardial infarction or ischemic cerebrovascular disease ascertained from linked healthcare data. FINDINGS: The average intraclass correlation coefficient between imaging specialist and ML-AAC-24 scores for 5012 images was 0.84 (95% CI 0.83, 0.84) with classification accuracy of 80% for established AAC groups. During a mean follow-up 4 years in the registry-based cohort, MACE outcomes were reported in 1177 people (13.7%). With increasing ML-AAC-24 scores there was an increasing proportion of people with MACE (low 7.9%, moderate 14.5%, high 21.2%), as well as individual MACE components (all p-trend <0.001). After multivariable adjustment, moderate and high ML-AAC-24 groups remained significantly associated with MACE (HR 1.54, 95% CI 1.31-1.80 & HR 2.06, 95% CI 1.75-2.42, respectively), compared to those with low ML-AAC-24. INTERPRETATION: The ML-AAC-24 scores had substantial levels of agreement with trained imaging specialists, and was associated with a substantial gradient of risk for cardiovascular events in a real-world setting. This approach could be readily implemented into these clinical settings to improve identification of people at high CVD risk. FUNDING: The study was supported by a National Health and Medical Research Council of Australia Ideas grant and the Rady Innovation Fund, Rady Faculty of Health Sciences, University of Manitoba.

A Fracture Risk Assessment Tool for High Resolution Peripheral Quantitative Computed Tomography.

Most fracture risk assessment tools use clinical risk factors combined with bone mineral density (BMD) to improve assessment of osteoporosis; however, stratifying fracture risk remains challenging. This study developed a fracture risk assessment tool that uses information about volumetric bone density and three-dimensional structure, obtained using high-resolution peripheral quantitative compute tomography (HR-pQCT), to provide an alternative approach for patient-specific assessment of fracture risk. Using an international prospective cohort of older adults (n = 6802) we developed a tool to predict osteoporotic fracture risk, called µFRAC. The model was constructed using random survival forests, and input predictors included HR-pQCT parameters summarizing BMD and microarchitecture alongside clinical risk factors (sex, age, height, weight, and prior adulthood fracture) and femoral neck areal BMD (FN aBMD). The performance of µFRAC was compared to the Fracture Risk Assessment Tool (FRAX) and a reference model built using FN aBMD and clinical covariates. µFRAC was predictive of osteoporotic fracture (c-index = 0.673, p < 0.001), modestly outperforming FRAX and FN aBMD models (c-index = 0.617 and 0.636, respectively). Removal of FN aBMD and all clinical risk factors, except age, from µFRAC did not significantly impact its performance when estimating 5-year and 10-year fracture risk. The performance of µFRAC improved when only major osteoporotic fractures were considered (c-index = 0.733, p < 0.001). We developed a personalized fracture risk assessment tool based on HR-pQCT that may provide an alternative approach to current clinical methods by leveraging direct measures of bone density and structure. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Rapid Cortical Bone Loss at the Distal Radius Is Associated With Higher Risk of Fracture in Older Men - The STRAMBO Study.

Rapid loss of areal bone mineral density (aBMD) is associated with higher fracture risk after adjustment for confounders including initial aBMD. However, the link between bone microarchitecture decline and fracture is not clear. We studied the association between bone microarchitecture deterioration assessed prospectively over 4 years and the subsequent fracture risk in older men. Bone microarchitecture at the distal radius and tibia was assessed by high-resolution peripheral QCT (HR-pQCT; XtremeCT, Scanco Medical) (baseline, 4 years) in 732 men aged 60-87 years. During the 8-year follow-up, 109 men had fragility fractures. Areal BMD was assessed by dual-energy X-ray absorptiometry. After adjustment for age, weight, prior falls and fractures, distal radius aBMD (baseline, slope), and baseline distal radius total volumetric BMD (Tt.BMD), a faster decrease in distal radius Tt.BMD was associated with higher fracture risk (hazard ratio [HR] = 1.54/SD, 95% confidence interval: 1.20-1.95, p < .005). Rapid cortical bone loss was associated with higher fracture risk (cortical thickness: HR = 1.48; 1.15-1.90, p < .01; cortical BMD: HR = 1.38; 1.11-1.72, p < .01). The rate of trabecular bone loss at the distal radius and the rate of bone microarchitecture decline at the distal tibia were not associated with fracture risk. After adjustment for aBMD and distal radius HR-pQCT measures assessed after 4 years, changes in Tt.BMD were associated with higher fracture risk (e.g., Tt.BMD: HR = 1.37; 1.11-1.69, p < .005). Compared with the reference model (age, weight, prior fractures and falls, baseline and slope of aBMD, baseline HR-pQCT value), further addition of the slope of the HR-pQCT measure did not improve the fracture prediction. Thus, rapid cortical bone loss at the distal radius is associated with higher fracture risk in the multivariable models including baseline values of the HR-pQCT measure. However, repeated HR-pQCT measurements did not improve the assessment of the fracture risk in older men (compared with the reference model defined earlier). © 2023 American Society for Bone and Mineral Research (ASBMR).

Spondyloarthritis and Sarcopenia: Prevalence of Probable Sarcopenia and its Impact on Disease Burden: The Saspar Study.

To evaluate the prevalence of probable, confirmed, and severe sarcopenia in spondyloarthritis (SpA), according to the European Working Group on Sarcopenia in Older People 2019 (EWGSOP2) definition. A total of 103 patients (51% women) with SpA, mean age 47.1 ± 13.7 years, were included and compared to 103 age- and sex-matched controls. Grip strength was measured by dynamometry. Body composition was assessed by whole-body densitometry. In SpA patients gait speed was measured by the 4-m-distance walk test and quality of life was evaluated with a specific health-related questionnaire for sarcopenia (SaRQoL®). Twenty-two SpA patients (21%) versus 7 controls (7%) had a low grip strength, i.e., probable sarcopenia (p < 0.01), 15 SpA (15%) patients and 7 controls (7%) had low Skeletal Muscle mass Index (SMI) (ns), respectively, and 5 and 2% of SpA patients and controls had low grip strength and low SMI, i.e., confirmed sarcopenia (ns). All the sarcopenic SpA patients had a low gait speed, i.e., severe sarcopenia. Finally, probable sarcopenic SpA patients had significantly higher C-Reactive Protein (CRP, p < 0.001) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI score, p < 0.01), lower gait speed (p < 0.001), and SarQoL® score (p < 0.001) than SpA patients with normal grip strength. According to EWGSOP2 definition, the prevalence of probable sarcopenia was significantly higher in SpA patients compared to controls. Probable sarcopenia was associated with higher inflammation and disease activity, impaired muscle performance, and quality of life. These results suggest that muscle strength may be a salient hallmark in SpA.

C-reactive protein predicts endocortical expansion but not fracture in older men: the prospective STRAMBO study.

In older men, higher high-sensitivity C-reactive protein (hsCRP) concentrations were associated with faster prospectively assessed endocortical expansion (distal radius, distal tibia) and slightly higher cortical bone loss at distal tibia, but not with the fracture risk. High hsCRP level has a limited impact on bone decline in older men. PURPOSE: Data on the link of the high-sensitivity C-reactive protein (hsCRP) with bone loss and fracture risk are discordant. We studied the association of the hsCRP with the prospectively assessed decrease in areal bone mineral density (aBMD), bone microarchitecture decline, and fracture risk in older men. METHODS: At baseline, hsCRP was measured in 823 men aged 60-88. Areal BMD and bone microarchitecture (distal radius, distal tibia) were assessed by dual-energy X-ray absorptiometry and high-resolution peripheral QCT, respectively, at baseline and after 4 and 8 years. Data on incident fractures were collected for 8 years. RESULTS: Higher hsCRP concentration was associated with faster increase in aBMD at the whole body and lumbar spine, but not other sites. Higher hsCRP levels were associated with faster decrease in cortical area and more rapid increase in trabecular area at the distal radius (0.048 mm2/year/SD, p < 0.05) and distal tibia (0.123 mm2/year/SD, p < 0.001). At the distal tibia, high hsCRP level was associated with greater decrease in total and cortical volumetric BMD (vBMD) and in failure load. The hsCRP levels were not associated with the fracture risk, even after accounting for competing risk of death. CONCLUSION: Higher hsCRP levels were associated with greater endocortical expansion at the distal radius and tibia. Higher hsCRP was associated with slightly faster decrease in total and cortical vBMD and failure load at distal tibia, but not with the fracture risk. Thus, high hsCRP levels are associated with faster cortical bone loss, but not with fracture risk in older men.

Abdominal Aortic Calcification, Bone Mineral Density, and Fractures: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Abdominal aortic calcification (AAC) has been inconsistently associated with skeletal health. We aimed to investigate the association of AAC with bone mineral density (BMD) and fracture risk by pooling the findings of observational studies. METHODS: MEDLINE, EMBASE, Web of Science, and Google Scholar were searched (August 2021). All clinical studies that assessed the association between AAC and BMD or fracture were included. AAC was categorized into any/advanced (all higher reported groups) versus no/less advanced (lowest reported group). Pooled standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CI) were determined for BMD and fracture, respectively, using random-effects models. RESULTS: Of 2 192 articles screened, 86 (61 553 participants) were included in the review, while 42 provided data for meta-analysis. AAC was associated with lower BMD at the total hip (SMD = -1.05 [95%CI: -1.47 to -0.63]; 16 studies), femoral neck (-0.25 [-0.46 to-0.04]; 10), and lumbar spine (-0.67 [-1.21 to -0.12]; 20). AAC was associated with a greater risk of any fracture (RR = 1.73 [95%CI: 1.48-2.02]; 27). AAC was also associated with vertebral, non-vertebral, and hip fractures. In dose-response analysis, the highest AAC group had greater risks of any, vertebral and non-vertebral fractures. CONCLUSIONS: AAC is associated with lower BMD and increased fracture risk at multiple sites, underscoring the potential importance of vascular disease on skeletal health. Detection of AAC at the time of BMD testing may provide clinicians with prognostic information about bone health to enhance osteoporosis screening programs and fracture risk prediction.

Association of Vitamin D and Parathyroid Hormone Status With the Aging-Related Decline of Bone Microarchitecture in Older Men: The Prospective Structure of Aging Men's Bones (STRAMBO) Study.

Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years. At distal radius, total bone mineral density (Tt.BMD), cortical thickness (Ct.Thd ), cortical area (Ct.Ar), cortical BMD (Ct.BMD), and trabecular BMD (Tb.BMD) decreased, whereas trabecular area (Tb.Ar) increased more rapidly in men with 25OHD ≤20 ng/mL versus the reference group (>30 ng/mL). Men with 25OHD ≤10 ng/mL had faster decrease in reaction force and failure load than men with 25OHD >30 ng/mL. At the distal tibia, Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, failure load, and reaction force decreased, whereas Tb.Ar increased more rapidly in men with 25OHD between 10 and 20 ng/mL versus the reference group. The results were similar when 12 ng/mL was used as a threshold of severe vitamin D deficiency. At distal radius, men with PTH levels above the median (>44 pg/mL) had more rapid decrease in Tt.BMD, Ct.Ar, Ct.BMD, Ct.Thd , reaction force, and failure load, and more rapid increase in Tb.Ar versus the lowest quartile (≤34 pg/mL). At the distal tibia, men in the highest PTH quartile had faster decrease in Tt.BMD, Ct.Thd , Ct.Ar, Ct.BMD, reaction force, and failure load and faster increase in Tb.Ar versus the lowest quartile. The results were similar in men with glomerular filtration rate >60 mL/min. The results were similar in men who took no vitamin D or calcium supplements for 8 years. In summary, vitamin D deficiency and secondary hyperparathyroidism are associated with more rapid prospectively assessed cortical and trabecular bone decline in older men. © 2022 American Society for Bone and Mineral Research (ASBMR).

Elevated lipoprotein(a) as a predictor for coronary events in older men.

Elevated circulating lipoprotein (a) [Lp(a)] is associated with an increased risk of first and recurrent cardiovascular events; however, the effect of baseline Lp(a) levels on long-term outcomes in an elderly population is not well understood. The current single-center prospective study evaluated the association of Lp(a) levels with incident acute coronary syndrome to identify populations at risk of future events. Lp(a) concentration was assessed in 755 individuals (mean age of 71.9 years) within the community and followed for up to 8 years (median time to event, 4.5 years; interquartile range, 2.5-6.5 years). Participants with clinically relevant high levels of Lp(a) (>50 mg/dl) had an increased absolute incidence rate of ASC of 2.00 (95% CI, 1.0041) over 8 years (P = 0.04). Moreover, Kaplan-Meier cumulative event analyses demonstrated the risk of ASC increased when compared with patients with low (<30 mg/dl) and elevated (30-50 mg/dl) levels of Lp(a) over 8 years (Gray's test; P = 0.16). Within analyses adjusted for age and BMI, the hazard ratio was 2.04 (95% CI, 1.0-4.2; P = 0.05) in the high versus low Lp(a) groups. Overall, this study adds support for recent guidelines recommending a one-time measurement of Lp(a) levels in cardiovascular risk assessment to identify subpopulations at risk and underscores the potential utility of this marker even among older individuals at a time when potent Lp(a)-lowering agents are undergoing evaluation for clinical use.

Role of sex steroids hormones in the regulation of bone metabolism in men: Evidence from clinical studies.

Sex steroids regulate bone metabolism in young men during growth and consolidation. Their deficit during growth compromises longitudinal and radial growth of bones and has a negative impact on body height, bone width, peak areal bone mineral density (aBMD) and bone microarchitecture. In older men, the deficit of sex steroid hormones (mainly 17ß-oestradiol) contributes to high bone turnover rate, low aBMD, poor bone microarchitecture, low estimated bone strength, accelerated bone loss and rapid decline of bone microarchitecture. The role of 17ß-oestradiol is confirmed by the case of men with congenital oestrogen receptor deficit and with congenital aromatase deficiency. 17ß-oestradiol inhibits bone resoption, whereas both hormones regulate bone formation. However, the associations are weak. Prospective data on the utility of blood 17ß-oestradiol or testosterone for fracture risk assessment are inconsistent. Men with hypogonadism have decreased aBMD and poor bone microarchitecture. In men with hypogonadism, testosterone replacement therapy increases aBMD and improves bone microarchitecture. In men with prostate cancer, androgen deprivation therapy (gonadoliberin analogues) induces rapid bone loss and severe deterioration of bone microarchitecture.

Body Composition in Patients With Psoriatic Arthritis and Changes During Interleukin-12/Interleukin-23 Inhibition.

OBJECTIVE: Little is known about body composition in patients with psoriatic arthritis (PsA). Our objective was to compare body composition parameters in PsA patients and healthy controls and then investigate the effects of ustekinumab (UST) on body composition in patients with PsA. METHODS: At baseline, 30 PsA patients were compared cross-sectionally with 60 healthy controls without PsA, matched for age, sex, menopausal status, and body mass index (BMI). Thirty active PsA patients treated with UST were included in a 6-month open follow-up study. Body composition parameters were measured at baseline and 6 months of treatment. RESULTS: Body composition parameters were different in PsA patients compared to healthy controls; in PsA patients, total and appendicular lean mass were lower (P = 0.013 and P = 0.010, respectively), whereas total fat mass was higher (P < 0.001). In 30% of the PsA patients, skeletal muscle mass was below the cutoff for low muscle quantity (men 7.26 kg/m2 , women 5.5 kg/m2 ), whereas no such change was observed in the control group. After 6 months of treatment with UST, there was no significant change in BMI in 18 of the PsA patients. Total lean mass decreased slightly (P = 0.046), whereas fat mass tended to increase, but not significantly. No significant changes in appendicular lean mass and skeletal muscle mass index were observed. CONCLUSION: In this study, we found that PsA patients had higher fat mass and lower lean mass than healthy controls. At 6-months of treatment, total lean mass decreased slightly, whereas fat mass tended to increase, but not significantly.

Abdominal aortic calcification, cardiac troponin I and atherosclerotic vascular disease mortality in older women.

OBJECTIVE: Examine if two inexpensive measures of atherosclerotic vascular diseases (ASVD), abdominal aortic calcification (AAC) and high-sensitivity cardiac troponin I (hs-cTnI) provide complementary information for 10-year ASVD mortality and all-cause mortality risk in older women. METHODS: 908 community-dwelling women without prevalent ASVD (≥75 years) were followed-up between 2003 and 2013. AAC and plasma hs-cTnI measures were obtained in 2003. AAC was assessed on lateral spine images using a semiquantitative method (AAC24). Linked health records were used for mortality outcomes. RESULTS: Mean±SD age was 79.9±2.6 years. 276 (30.4%) women died during follow-up, including 138 (15.2%) ASVD-related deaths. AAC24 and hs-cTnI were independently associated with ASVD and all-cause mortality (p<0.001). The cohort was dichotomised into four groups: (1) low AAC24 (AAC24: 0 or 1) and 1) and

Dual-energy CT hybridation and kernel processing effects on the estimation of bone mineral mass and density: a calcination study on ex vivo human femur.

INTRODUCTION: Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS: DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS: QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION: BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.

Bone Microarchitecture Phenotypes Identified in Older Adults Are Associated With Different Levels of Osteoporotic Fracture Risk.

Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a "one-size-fits-all" approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured. In this study, we propose that there are common combinations of bone properties, referred to as phenotypes, that are predisposed to different levels of fracture risk. Using HR-pQCT data from a multinational cohort (n = 5873, 71% female) between 40 and 96 years of age, we employed fuzzy c-means clustering, an unsupervised machine-learning method, to identify phenotypes of bone microarchitecture. Three clusters were identified, and using partial correlation analysis of HR-pQCT parameters, we characterized the clusters as low density, low volume, and healthy bone phenotypes. Most males were associated with the healthy bone phenotype, whereas females were more often associated with the low volume or low density bone phenotypes. Each phenotype had a significantly different cumulative hazard of major osteoporotic fracture (MOF) and of any incident osteoporotic fracture (p < 0.05). After adjustment for covariates (cohort, sex, and age), the low density followed by the low volume phenotype had the highest association with MOF (hazard ratio = 2.96 and 2.35, respectively), and significant associations were maintained when additionally adjusted for femoral neck aBMD (hazard ratio = 1.69 and 1.90, respectively). Further, within each phenotype, different imaging biomarkers of fracture were identified. These findings suggest that osteoporotic fracture risk is associated with bone phenotypes that capture key features of bone deterioration that are not distinguishable by aBMD. © 2021 American Society for Bone and Mineral Research (ASBMR).

Risk Factors for the Incident Decline of Physical Performance in Older Men: The Prospective Strambo Study.

Risk factors of physical performance decline in older men remain uncertain. We assessed risk factors of incident physical performance deterioration in older men followed up prospectively. In a cohort of 821 men aged 60-87, physical performance was assessed by four tests (five chair stands, standing with closed eyes, forward and backward tandem walk) at baseline, 4 and 8 years. Various predictive biological measurements were performed at baseline. Serum creatinine/ cystatin C (Cr/CysC) ratio was used as an index of muscle mass. In multivariate models, higher age, higher fat mass index (FMI = fat mass/height2), low physical activity, prior stroke and fracture were associated with poor physical performance at baseline. Higher age, low physical activity, low calcium intake, prior non-vertebral fractures, low apparent free testosterone concentration and poor health status were associated with higher risk of loss to follow-up. Low grip strength, Parkinson's disease and stroke were associated with higher risk of incident inability to do five chair stands. Low Cr/CysC ratio and high FMI were associated with high risk of incident inability to perform forward and backward tandem walk. Sarcopenic obesity (co-occurrence of lower tertile of Cr/CysC and upper tertile of FMI) was associated with higher risk of incident inability to perform forward (OR = 3.31, 95% CI 1.88-5.84, p < 0.001) and backward tandem walk and of incident inability to perform more than one test (OR = 5.82, 95% CI 1.29-26.27, p < 0.001). In conclusion, sarcopenic obesity and poor health are associated with higher risk of incident severe decline of physical performance.