Risk Factors for Bone Microarchitecture Impairments in Older Men with Type 2 Diabetes - The MrOS Study.

CONTEXT: Impaired bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), may contribute to bone fragility in type 2 diabetes (T2DM) but data on men are lacking. OBJECTIVE: To investigate the association between T2DM and HR-pQCT parameters in older men. METHODS: HR-pQCT scans were acquired on 1794 participants in the Osteoporotic Fractures in Men (MrOS) study. T2DM was ascertained by self-report or medication use. Linear regression models, adjusted for age, race, BMI, limb length, clinic site, and oral corticosteroid use, were used to compare HR-pQCT parameters by diabetes status. RESULTS: Among 1777 men, 290 had T2DM (mean age 84.4 years). T2DM men had smaller total cross-sectional area (Tt.AR) at the distal tibia (p=0.028) and diaphyseal tibia (p=0.025), and smaller cortical area at the distal (p= 0.009) and diaphyseal tibia (p= 0.023). Trabecular indices and cortical porosity were similar between T2DM and non-T2DM. Among men with T2DM, in a model including HbA1c, diabetes duration, and insulin use, diabetes duration ≥ 10 years, compared with <10 years, was significantly associated with higher cortical porosity but with higher trabecular thickness at the distal radius. Insulin use was significantly associated with lower cortical area and thickness at the distal radius and diaphyseal tibia and lower failure load at all three scan sites. Lower cortical area, cortical thickness, total BMD, cortical BMD, and failure load of the distal sites were associated with increased risk of incident non-vertebral fracture in T2DM. CONCLUSIONS: Older men with T2DM have smaller bone size compared to non-T2DM, which may contribute to diabetic skeletal fragility. Longer diabetes duration was associated with higher cortical porosity and insulin use with cortical bone deficits and lower failure load.

Fast dual-echo estimation of apparent long T2 fraction using ultrashort echo time magnetic resonance imaging in tibialis tendons and its osteoporosis-related differences in women.

Background: Tendon and bone comprise a critical interrelating unit. Bone loss, including that seen with osteopenia (OPe) or osteoporosis (OPo), may be associated with a reduction in tendon quality, though this remains incompletely investigated. Clinical magnetic resonance imaging (MRI) sequences cannot directly detect signals from tendons because of the very short T2. Clinical MRI may detect high-graded abnormalities by changes in the adjacent structures like bone. However, ultrashort echo time MRI (UTE-MRI) can capture high signals from all tendons. To determine if the long T2 fraction, as measured by a dual-echo UTE-MRI sequence, is a sensitive quantitative technique to the age- and bone-loss-related changes of the lower leg tendons. Methods: This is a cross-sectional study conducted between January 2018 to February 2020 in the lower legs of 14 female patients with OPe [72±6 years old, body mass index (BMI) =25.8±6.2 kg/m2] and 31 female patients with OPo (73±6 years old, BMI=22.0±3.8 kg/m2), as well as 30 female subjects with normal bone (Normal, 35±18 years old, BMI =23.2±4.3 kg/m2), were imaged on a 3T clinical scanner using a dual-echo 3D Cones UTE sequence. We defined the apparent long T2 signal fraction (aFrac-LongT2) of tendons as the ratio between the signal at the second echo time (TE =2.2 ms) to the UTE signal. The average aFrac-LongT2 and the cross-sectional area were calculated for the anterior tibialis tendons (ATTs) and the posterior tibialis tendons (PTTs). The Kruskal-Wallis rank test was used to compare the differences in aFrac-LongT2 and the cross-sectional area of the tendons between the groups. Results: The aFrac-LongT2 of the ATTs and PTTs were significantly higher in the OPo group compared with the Normal group (22.2% and 34.8% in the ATT and PTT, respectively, P<0.01). The cross-sectional area in the ATTs was significantly higher for the OPo group than in the Normal group (Normal/OPo difference was 28.7, P<0.01). Such a difference for PTTs did not reach the significance level. Mean aFrac-LongT2 and cross-sectional area in the OPe group were higher than the Normal group and lower than the OPo group. However, the differences did not show statistical significance, likely due to the higher BMI in the OPe group. Conclusions: Dual-echo UTE-MRI is a rapid quantification technique, and aFrac-LongT2 values showed significant differences in tendons between Normal and OPo patients.

Ultrashort echo time MRI detects significantly lower collagen but higher pore water in the tibial cortex of female patients with osteopenia and osteoporosis.

Ultrashort echo time (UTE) MRI can quantify the major proton pool densities in cortical bone, including total (TWPD), bound (BWPD), and pore water (PWPD) proton densities, as well as the macromolecular proton density (MMPD), associated with the collagen content, which is calculated using macromolecular fraction (MMF) from UTE magnetization transfer (UTE-MT) modeling. This study aimed to investigate the differences in water and collagen contents in tibial cortical bone, between female osteopenia (OPe) patients, osteoporosis (OPo) patients, and young participants (Young). Being postmenopausal and above 55 years old were the inclusion criteria for OPe and OPo groups. The tibial shaft of fourteen OPe (72.5 ± 6.8 years old), thirty-one OPo (72.0 ± 6.4 years old), and thirty-one young subjects (28.0 ± 6.1 years old) were scanned using a knee coil on a clinical 3 T scanner. Basic UTE, inversion recovery UTE, and UTE-MT sequences were performed. Investigated biomarkers were compared between groups using Kruskal-Wallis test. Spearman's correlation coefficients were calculated between the total hip dual-energy x-ray absorptiometry (DXA) T-score and UTE-MRI results. MMF, BWPD, and MMPD were significantly lower in OPo patients than in the young group. Whereas T1, TWPD, and PWPD were significantly higher in OPo patients. The largest OPo/Young average percentage differences were found in MMF (41.9%), PWPD (103.5%), and MMPD (64.0%). PWPD was significantly higher (50.7%), while BWPD was significantly lower (16.4%) in OPe than the Young group on average. MMF was found to be significantly lower (27%) in OPo patients compared with OPe group. T1, MMF, TWPD, PWPD, and MMPD values significantly correlated with the total hip DXA T-scores (provided by the patients and only available for OPe and OPo patients). DXA T-score showed the highest correlations with PWPD (R = 0.55) and MMF (R = 0.56) values. TWPD, PWPD, and MMF estimated using the UTE-MRI sequences were recommended to evaluate individuals with OPe and OPo.

Ultrashort echo time (UTE) is an MRI technique that can quantify the water and collagen content of cortical bone. Water in the bone can be found residing in pores (pore water) or bound to the bone matrix (bound water). We investigated the differences in water and collagen contents of tibial cortical bone, between female osteopenia patients, osteoporosis patients, and young participants. Bound water and collagen contents were significantly lower in osteoporosis patients than in the young group. Whereas total water and pore water contents were significantly higher in osteoporosis patients. Pore water was significantly higher, while bound water was significantly lower in osteopenia than in the Young group. Collagen content was found to be significantly lower in osteoporosis patients compared with the osteopenia group. The estimated water and collagen contents were significantly correlated with the total hip bone densitometry measures in the patients.

Shared-Medical Appointment for Screening and Risk Assessment for Fall Prevention.

Background: The median age of Americans is rising and fall risk increases with age. While the causes of falls are multifactorial, falls risk can be reduced. Only a small percentage of older-adults report being asked about fall risk or falls. The CDC has initiated a Stopping Elderly Accidents, Deaths and Injuries (STEADI) toolkit, but penetration into practice has been slow. To address this, we implemented a Falls Prevention Shared Medical Appointment (SMA) at an academic internal medicine clinic. Methods: Patients were referred to the SMA and scheduled per their preference virtually or in-person. Patients attended a nurse visit for appropriate fallrisk related screening, followed by the SMA with two physicians for review of medical history, fall screening results and implementation of fall reduction strategies. Follow-up survey of the patients assessed program effectiveness. Results: Fifty-two patients were seen/assessed between November 2021 and February 2023 with SMAs ranging from 3 to 5 patients with an average age of 77 (=/- 6.7). Questionnaire self-reported risk factors, self-reported strength, and polypharmacy were associated with objective markers of increased fall risk. Survey results indicate acceptability of this model. Conclusion: Falls prevention SMAs can be effective. More work is needed to further delineate and refine cohort selection.

MRI-based porosity index (PI) and suppression ratio (SR) in the tibial cortex show significant differences between normal, osteopenic, and osteoporotic female subjects.

Introduction: Ultrashort echo time (UTE) MRI enables quantitative assessment of cortical bone. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques developed to reduce the time demand and cost in future clinical studies. The goal of this study was to investigate the performance of PI and SR in detecting bone quality differences between subjects with osteoporosis (OPo), osteopenia (OPe), and normal bone (Normal). Methods: Tibial midshaft of fourteen OPe (72 ± 6 years old), thirty-one OPo (72 ± 6 years old), and thirty-seven Normal (36 ± 19 years old) subjects were scanned using dual-echo UTE and IR-UTE sequences on a clinical 3T scanner. Measured PI, SR, and bone thickness were compared between OPo, OPe, and normal bone (Normal) subjects using the Kruskal-Wallis test by ranks. Spearman's rank correlation coefficients were calculated between dual-energy x-ray absorptiometry (DEXA) T-score and UTE-MRI results. Results: PI was significantly higher in the OPo group compared with the Normal (24.1%) and OPe (16.3%) groups. SR was significantly higher in the OPo group compared with the Normal (41.5%) and OPe (21.8%) groups. SR differences between the OPe and Normal groups were also statistically significant (16.2%). Cortical bone was significantly thinner in the OPo group compared with the Normal (22.0%) and OPe (13.0%) groups. DEXA T-scores in subjects were significantly correlated with PI (R=-0.32), SR (R=-0.50), and bone thickness (R=0.51). Discussion: PI and SR, as rapid UTE-MRI-based techniques, may be useful tools to detect and monitor bone quality changes, in addition to bone morphology, in individuals affected by osteoporosis.

Ultrashort Echo Time (UTE) MRI porosity index (PI) and suppression ratio (SR) correlate with the cortical bone microstructural and mechanical properties: Ex vivo study.

Ultrashort echo time (UTE) MRI can image and consequently enable quantitative assessment of cortical bone. UTE-MRI-based evaluation of bone is largely underutilized due to the high cost and time demands of MRI in general. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques (∼ 5 mins scan time each), which can potentially reduce the time demand and cost in future clinical studies. This study aimed to investigate the correlations of PI and SR measures with cortical bone microstructural and mechanical properties. Cortical bone strips (n = 135) from tibial and femoral midshafts of 37 donors (61 ± 24 years old) were scanned using a dual-echo 3D Cones UTE sequence and a 3D Cones IR-UTE sequence for PI and SR calculations, respectively. Average bone mineral density, porosity, and pore size were measured using microcomputed tomography (µCT). Bone mechanical properties were measured using 4-point bending tests. The µCT measures showed significant correlations with PI (moderate to strong, R = 0.68-0.71) and SR (moderate, R = 0.58-0.68). Young's modulus, yield stress, and ultimate stress demonstrated significant moderate correlations with PI and SR (R = 0.52-0.62) while significant strong correlations with µCT measures (R > 0.7). PI and SR can potentially serve as fast and noninvasive (non-ionizing radiation) biomarkers for evaluating cortical bone in various bone diseases.

Saturated and Unsaturated Bone Marrow Lipids Have Distinct Effects on Bone Density and Fracture Risk in Older Adults.

Greater bone marrow adiposity (BMAT) is associated with lower bone mineral density (BMD) and vertebral fractures; less is known about BMAT composition and bone. We studied BMAT composition and bone outcomes in 465 participants from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. BMAT saturation and unsaturation, measured with magnetic resonance spectroscopy, were defined as the ratio of saturated (1.3 ppm peak) or unsaturated (5.3 ppm peak) lipid to total marrow contents, respectively. At baseline and follow-up visits, spine and hip BMD were assessed with quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) and vertebral fractures were identified with DXA. Incident clinical fractures were identified through medical records for up to 8.8 years of follow-up. Associations between BMAT composition and BMD, bone loss, and fractures were evaluated in adjusted regression models. At baseline, mean ± standard deviation (SD) participant age was 81.7 ± 4.3 years, mean BMAT unsaturation was 3.5% ± 1.0%, and mean saturation was 46.3% ± 7.2% in the full cohort (47.7% women). Each SD increase in BMAT saturation was associated with lower trabecular BMD: -23.6% (spine) and -13.0% (total hip) (all p < 0.0001). Conversely, BMAT unsaturation (per SD increase) was associated with higher trabecular BMD: +17.5% (spine) and +11.5% (total hip) (all p < 0.001). BMAT saturation (per SD increase) was associated with greater risk for prevalent (odds ratio [OR] 1.46; 95% confidence interval [CI], 1.11-1.92) and incident (OR 1.55; 95% CI, 1.03-2.34) vertebral fracture. BMAT unsaturation (per SD increase) was associated with lower risk for incident vertebral fracture (OR 0.58; 95% CI, 0.38-0.89). In gender stratified analyses, BMAT saturation and unsaturation had opposite associations with incident clinical fracture among men. In general, saturated marrow lipids were associated with worse skeletal outcomes, whereas unsaturated lipids were associated with better outcomes. We recommend that future studies of marrow fat and skeletal health report measurements of saturated and unsaturated marrow lipids, rather than total marrow fat content alone. © 2022 American Society for Bone and Mineral Research (ASBMR).

FSH Level and Changes in Bone Mass and Body Composition in Older Women and Men.

CONTEXT: FSH may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes. OBJECTIVE: We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults. SETTING, DESIGN, PARTICIPANTS: We studied 162 women and 158 men (mean age 82 ± 4 years) from the Age, Gene/Environment Susceptibility (AGES)-Bone Marrow Adiposity cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later. MAIN OUTCOMES: Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels. RESULTS: There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7 to 3.3) mg/cm2/y in women, and -0.2 (-2.6 to 2.2) mg/cm2/y in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03 to 3.62) cm2/y in women, and -0.33 (-3.73 to 3.06) cm2/y in men. CONCLUSIONS: Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes.

Serum FSH Is Associated With BMD, Bone Marrow Adiposity, and Body Composition in the AGES-Reykjavik Study of Older Adults.

CONTEXT: Follicle-stimulating hormone (FSH) concentrations increase during the perimenopausal transition and remain high after menopause. Loss of bone mineral density (BMD) and gain of bone marrow adiposity (BMA) and body fat mass also occur during this time. In mice, blocking the action of FSH increases bone mass and decreases fat mass. OBJECTIVE: To investigate the associations between endogenous FSH levels and BMD, BMA, and body composition in older adults, independent of estradiol and testosterone levels. DESIGN, SETTING, AND PARTICIPANTS: Older adults from the AGES-Reykjavik Study, an observational cohort study. MAIN OUTCOME MEASURES: Areal BMD, total body fat, and lean mass were measured with dual-energy x-ray absorptiometry. Lumbar vertebral BMA was measured by 1H-magnetic resonance spectroscopy. Volumetric BMD and visceral and subcutaneous adipose tissue (VAT, SAT) areas were measured with quantitative computed tomography. The least squares means procedure was used to determine sex hormone-adjusted associations between quartiles of serum FSH and BMD, BMA, and body composition. RESULTS: In women (N = 238, mean age 81 years), those in the highest FSH quartile, compared with the lowest quartile, had lower adjusted mean spine integral BMD (-8.6%), lower spine compressive strength index (-34.8%), higher BMA (+8.4%), lower weight (-8.4%), lower VAT (-17.6%), lower lean mass (-6.1%), and lower fat mass (-11.9%) (all P < 0.05). In men, FSH level was not associated with any outcome. CONCLUSIONS: Older postmenopausal women with higher FSH levels have higher BMA, but lower BMD and lower fat and lean mass, independent of estradiol and testosterone levels. Longitudinal studies are needed to better understand the underlying mechanisms.

Factors Associated With Kyphosis and Kyphosis Progression in Older Men: The MrOS Study.

Hyperkyphosis (HK), or increased anterior curvature of the thoracic spine, is common in older persons. Although it is thought that vertebral fractures are the major cause of HK, only about a third of those with the worst degrees of kyphosis have underlying vertebral fractures. In older men, HK is associated with increased risk of poor physical function, injurious falls, and earlier mortality, but its causes are not well understood. We studied 1092 men from the Osteoporotic Fractures in Men (MrOS) Study aged 64 to 92 years (mean age 72.8 years) who had repeated standardized radiographic measures of Cobb angle of kyphosis to identify risk factors for HK (defined as ≥50 degrees) and kyphosis progression over an interval of 4.7 years. Specifically, we examined the associations with age, body mass index (BMI), weight, weight loss, health behaviors, family history of HK, muscle strength, degenerative disc disease (DDD), bone mineral density (BMD), prevalent thoracic vertebral fractures, and incident thoracic vertebral fractures (longitudinal analyses only). Men had an average baseline kyphosis of 38.9 (standard deviation [SD] 11.4) degrees. Fifteen percent had HK (n = 161) with a mean Cobb angle of 56.7 (SD = 6.0) degrees; these men were older (p < 0.01), had lower BMI (p < 0.01), lower BMD (p < 0.01), were more likely to have family history of HK (p = 0.01), and prevalent thoracic vertebral fracture (p < 0.01) compared with the men without HK. During follow-up, men experienced an average of 1.4 degrees of kyphosis progression with DDD (p = 0.04) and lower hip BMD (p < 0.01) being identified as statistically significant and incident vertebral fractures (p = 0.05) nearly significant factors associated with worse progression. These results suggest that in older men, HK results from not only low BMD and vertebral fractures but that DDD also may play a significant role in kyphosis progression. © 2020 American Society for Bone and Mineral Research (ASBMR).

Hyperkyphosis and self-reported and objectively measured sleep quality in older men.

OBJECTIVES: Hyperkyphosis is associated with restricted pulmonary function and posture, potentially contributing to poor sleep. A previous study reported older women with hyperkyphosis had worse self-reported sleep quality, but it is less clear if this association exists in men. We examined the association between hyperkyphosis and subjective and objective sleep quality in a cohort of older men. DESIGN: Longitudinal analysis of data from large cohort of older men participating in the Osteoporotic Fractures in Men Study (MrOS). SETTING: Community. PARTICIPANTS: We studied 754 men participants in MrOS who had kyphosis measured during the 3rd clinic visit (2007-2009) and future subjective and objective sleep quality assessed between 2009-2012 (an average of 2.9 years later). INTERVENTION: N/A. MEASUREMENTS: To measure kyphosis, 1.7 cm thick wooden blocks were placed under the participant's head to achieve a neutral spine position while lying supine on a DXA table. We collected data on both subjective (Pittsburgh Sleep Quality Index [PSQI], and Epworth Sleepiness Scale [ESS]) and objective (wrist actigraphy: Total Sleep Time [TST], Wake After Sleep Onset [WASO], Sleep Efficiency [SE], Sleep Onset Latency [SOL]; and polysomnography: Apnea Hypopnea Index [AHI]) sleep measurements. Those who required >3 blocks were considered hyperkyphotic (n = 145 or 19.2%). RESULTS: In unadjusted and multivariable analyses, men with hyperkyphosis did not report having worse self-reported sleep characteristics based on PSQI and ESS. Similarly, there were no significant associations between hyperkyphosis and objective sleep measures. When examined as a continuous predictor (blocks ranging from 0-8), results were no different. CONCLUSIONS: Although we hypothesized that poor posture in those with hyperkyphosis would interfere with sleep, in this sample of older men, worse kyphosis was not associated with self-reported or objectively measured poor sleep quality.

Greater Bone Marrow Adiposity Predicts Bone Loss in Older Women.

Bone marrow adiposity (BMA) is associated with aging and osteoporosis, but whether BMA can predict bone loss and fractures remains unknown. Using data from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study, we investigated the associations between 1 H-MRS-based measures of vertebral bone marrow adipose tissue (BMAT), annualized change in bone density/strength by quantitative computed tomography (QCT) and DXA, and secondarily, with incident clinical fractures and radiographic vertebral fractures among older adults. The associations between BMAT and annualized change in bone density/strength were evaluated using linear regression models, adjusted for age, body mass index (BMI), diabetes, estradiol, and testosterone. Cox proportional hazards models were used to evaluate the associations between baseline BMAT and incident clinical fractures, and logistic regression models for incident vertebral fractures. At baseline, mean ± SD age was 80.9 ± 4.2 and 82.6 ± 4.2 years in women (n = 148) and men (n = 150), respectively. Mean baseline BMAT was 55.4% ± 8.1% in women and 54.1% ± 8.2% in men. Incident clinical fractures occurred in 7.4% of women over 2.8 years and in 6.0% of men over 2.2 years. Incident vertebral fractures occurred in 12% of women over 3.3 years and in 17% of men over 2.7 years. Each 1 SD increase in baseline BMAT was associated with a 3.9 mg2 /cm4 /year greater loss of spine compressive strength index (p value = .003), a 0.9 mg/cm3 /year greater loss of spine trabecular BMD (p value = .02), and a 1.2 mg/cm3 /year greater loss of femoral neck trabecular BMD (p value = .02) in women. Among men, there were no associations between BMAT and changes in bone density/strength. There were no associations between BMAT and incident fractures in women or men. In conclusion, we found greater BMAT is associated with greater loss of trabecular bone at the spine and femoral neck, and greater loss of spine compressive strength, in older women. © 2019 American Society for Bone and Mineral Research.

Liposomal Bupivacaine Utilization in Total Knee Replacement Does Not Decrease Length of Hospital Stay.

Liposomal bupivacaine has reportedly been used as an adjunct for perioperative pain management in total knee replacement (TKR). The purpose of our single-blind, prospective study is to show that wound infiltration with long-acting liposomal bupivacaine during TKR will shorten length of stay (LOS) as compared with standard bupivacaine injection and spinal anesthetic with or without spinal narcotic. A total of 195 patients were randomized into three groups: wound infiltration with bupivacaine and a spinal with narcotic (Group 1, N = 65), wound infiltration with liposomal bupivacaine and a spinal without narcotic (Group 2, N = 67), and bupivacaine wound infiltration with a spinal without narcotic (Group 3, N = 64). The groups were then compared with look for any benefit in using the liposomal bupivacaine with regard to LOS, pain control, function, and complications. There was a trend toward a decreased LOS (days) in the liposomal bupivacaine (Group 2) with a mean LOS of 1.83 as compared with wound infiltration with bupivacaine with spinal narcotic LOS of 2.04 (Group 1) and without spinal narcotic LOS of 1.94 (Group 3). These results were not statistically significant (p = 0.37). Patient-reported pain scores were no different between the three groups. The daily narcotic usage (morphine equivalents) during the hospitalization was statistically highest in the liposomal bupivacaine group at 77.2 versus 55.0 in Group 1 and 68.1 in Group 3 (p = 0.025). Nausea or vomiting was most common in Group 1 at 42%, followed by 28% in Group 2 and 22% in Group 3. Pruritus was most common in the spinal narcotic group at 38% versus Group 2 at 14% and Group 3 at 11%.Liposomal bupivacaine showed a trend toward a decreased LOS, but this was not statistically significant. There was no difference in pain scores reported by these patients. In conclusion, we cannot justify the extra cost of liposomal bupivacaine as compared with plain bupivacaine as an adjunct for perioperative pain management in TKR patients.

Chronic Kidney Disease Is Associated With Greater Bone Marrow Adiposity.

Bone marrow adiposity is associated with aging, osteoporosis, and reduced hematopoiesis, as well as anorexia nervosa, but little is known about the underlying mechanisms that affect marrow adiposity. Chronic kidney disease (CKD) may influence bone marrow adipose tissue (BMAT), possibly through loss of lean mass or higher circulating levels of sclerostin. To test these hypotheses, we investigated the cross-sectional association between estimated glomerular filtration rate (eGFR) as a measure of kidney function and 1 H-MRS-based measurement of vertebral BMAT (L1 to L4) in 475 older adults from the Age Gene/Environment Susceptibility (AGES)-Reykjavik study. Mean BMAT was compared in those with eGFR >60 (n = 297) versus those with eGFR 45 to 60 (n = 120) or eGFR <45 (n = 58) using linear regression models. Participants had a mean age of 81.5 (SD 4.1) years, mean eGFR of 64.3 (SD 16.1) mL/min/1.734 cm2 , mean BMAT of 54.5% (SD 8.5); 48.2% were women. In unadjusted and adjusted models (age, visit window, gender, diabetes and visceral adipose tissue), BMAT was higher in those with eGFR <45 (adjusted mean 58.5%; 95% CI, 56.2 to 60.7) compared with those with eGFR >60 (adjusted mean 53.8%; 95% CI, 52.8 to 54.8) (p = 0.0002). BMAT did not differ in those with eGFR 45 to 60 (adjusted mean 54.3%; 95% CI, 52.8 to 55.9) compared with those with eGFR >60 (p = 0.58). In a subgroup of participants with serum sclerostin available (n = 253), additional adjustment for sclerostin attenuated the difference in adjusted mean vertebral BMAT between those with eGFR <45 versus >60 from 3.7% (p = 0.04) to 2.4% (p = 0.20). CKD stage 3b or worse was associated with greater bone marrow adiposity; this association may be partially mediated by sclerostin. © 2018 American Society for Bone and Mineral Research.

Patterns of menopausal hormone therapy use and hyperkyphosis in older women.

OBJECTIVE: Hyperkyphosis, an exaggerated anterior curvature of the thoracic spine, is associated with poor physical function, falls, fractures, and earlier mortality. Low bone mineral density, bone loss, and vertebral fractures are strong risk factors for hyperkyphosis. Menopausal hormone therapy (HT) reverses bone loss, prevents vertebral fractures, and, therefore, we hypothesize, may reduce the risk for developing hyperkyphosis. METHODS: We evaluated the cross-sectional association between Cobb angle of kyphosis from lateral spine radiographs and pattern of self-reported HT use during the prior 15-year period in 1,063 women from the Study of Osteoporotic Fractures. RESULTS: Participants had a mean age of 83.7 ±â€Š3.3 years and a mean Cobb angle of 51.3 ±â€Š14.6°. Forty-six per cent of women were characterized as never-users of HT, 24% as remote past users, 17% as intermittent users, and 12% as continuous users. In minimally adjusted models, the mean Cobb angle was 4.0° less in continuous HT users compared with never-users (P = 0.01); however, in fully adjusted models, this association was attenuated to 2.8° (P = 0.06). Remote past HT users had 3.0° less kyphosis compared with never-users in minimally adjusted models (P = 0.01), attenuated to 2.8° less in fully adjusted models (P = 0.02). Intermittent users did not differ from never-users in degree of kyphosis. CONCLUSIONS: Women reporting continuous or remote past HT use had less pronounced kyphosis than never-users by their mid-eighties, suggesting a possible role for HT in the prevention of age-related hyperkyphosis.

Sex hormones are negatively associated with vertebral bone marrow fat.

CONTEXT: Higher bone marrow fat (BMF)1 is associated with osteoporosis and reduced hematopoiesis. Exogenous estradiol reduces BMF in older women, but effects of endogenous sex hormones are unknown. OBJECTIVE: To determine if endogenous sex hormones are associated with BMF in older men and women. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Participants using medications that may affect BMF were excluded. MAIN OUTCOME MEASURES: Vertebral BMF was measured with magnetic resonance spectroscopy. Estradiol, testosterone and sex hormone binding globulin were measured on archived serum. Linear regression models were adjusted for age, total percent body fat and visit window. RESULTS: Analyses included 244 men and 226 women, mean age 81.5 (SD 4.1) years. Mean BMF was 54.1% (SD 8.6) (men) and 54.7% (SD 8.1) (women). In adjusted models, per 1pg/ml increase in total estradiol, there was a statistically significant 0.26% decrease in BMF in men (95% CI: -0.41, -0.11) and a non-significant 0.20% decrease in women (95% CI: -0.55, 0.15), with no evidence of interaction by gender (p=0.88). Per 10ng/dl increase in total testosterone, there was a significant 0.10% decrease in BMF in men (95% CI: -0.17, -0.03) and a non-significant 0.13% (95% CI: -0.79, 0.53) decrease in women, with no evidence of interaction by gender (p=0.97). CONCLUSION: Higher bone marrow fat is associated with lower total estradiol and testosterone levels in older men, with a similar but statistically non-significant association in older women. Sex hormone levels appear to play a role in the regulation of bone marrow fat in older adults.

A comparison of MOVE! versus TeleMOVE programs for weight loss in Veterans with obesity.

BACKGROUND: Obesity is a leading contributor to disability. Treatment approaches incorporating telehealth technologies are becoming increasingly popular in treating obesity, but their benefits relative to established behavioural weight loss therapies are poorly understood. The objective of this study was to compare a new telehealth treatment (TeleMOVE) to an established behavioural treatment (MOVE!) among Veterans with obesity. METHODS: This was an observational study of Veterans in the TeleMOVE or MOVE! programs between October, 2011 and March, 2013. A total of 699 Veterans enrolled in these programs from 2011-2013. A secondary focus was on Veterans that were ≥90% adherent to their treatment. From this group, 72 (33.1%) TeleMOVE and 141 (29.3%) MOVE! participants met adherence criteria. The primary outcome criterion was changes in body weight. RESULTS: Both programs were associated with significant weight reductions, with MOVE! participants showing significantly less weight loss relative to those in TeleMOVE (MOVE! mean weight loss=4.5[7.1]lb/2.0[3.2]kg; 1.8% mean weight loss; 12.0% achieving ≥5% weight loss; TeleMOVE mean weight loss=8.6[9.9]lb/3.9[4.5]kg; 3.6% mean weight loss; 26.6% achieving ≥5% weight loss, p's<.01). Among highly adherent participants, patients in TeleMOVE versus MOVE! lost significantly more weight (TeleMOVE=11.1[9.9]lb/5.0[4.5]kg versus MOVE!=5.7[7.1]lb/2.6[3.2]kg; t=4.6, p<.001) and were significantly more likely to achieve clinically significant weight loss (% with ≥5% weight loss were 43.1% versus 13.5%, respectively, p<.001). CONCLUSIONS: In this observational study, TeleMOVE was at least as effective for weight loss as the more established multidisciplinary MOVE!

SHBG, Sex Steroids, and Kyphosis in Older Men: The MrOS Study.

Accentuated kyphosis is associated with adverse health outcomes, including falls and fractures. Low bone density is a risk factor for hyperkyphosis, and each vertebral fracture adds roughly 4° to forward spine curvature. Sex steroids, in particular low bioavailable estradiol and high sex hormone-binding globulin (SHBG), are associated with bone loss and high SHBG is associated with vertebral fractures in older men. We, therefore, hypothesized that low bioavailable estradiol and high SHBG would be associated with worse kyphosis. To test this hypothesis, we examined the cross-sectional associations between individual bioavailable sex hormones and SHBG with radiographically assessed kyphosis. Participants included 1500 men aged 65 and older from the Osteoporotic Fractures in Men (MrOS) Study, in whom baseline measures of kyphosis and sex hormones were available. Modified Cobb angle of kyphosis, calculated from T4 through T12, was assessed from supine lateral spine radiographs. Serum total estradiol and total testosterone were measured by mass spectrometry, and bioavailable sex steroids were calculated from mass action equations. After adjustment for age and other confounding variables, no association was found between bioavailable estradiol or testosterone and Cobb angle, either when kyphosis was analyzed as a continuous variable or dichotomized into highest versus lower three quartiles. In linear regression models adjusted for age and clinic site, there was a significant association between SHBG and kyphosis (parameter estimate = 0.76 per SD increase, p = 0.01). In the fully adjusted model, this association was weakened and of only borderline statistical significance (parameter estimate = 0.61 per SD, p = 0.05). Logistic models demonstrated similar findings. Although associated with bone loss, we did not demonstrate that low bioavailable estradiol translates into worse kyphosis in older men. High SHBG is associated with bone loss and vertebral fractures. Our results suggest that high SHBG may also be a risk factor for hyperkyphosis. © 2016 American Society for Bone and Mineral Research.

A Young Woman With Recurrent Gestational Hypercalcemia and Acute Pancreatitis Caused by CYP24A1 Deficiency.

The CYP24A1 gene encodes a mitochondrial 24-hydroxylase that inactivates 1,25(OH)2 D. Loss-of-function mutations in CYP24A1 cause hypercalcemia, nephrolithiasis and nephrocalcinosis. We describe a woman with CYP24A1 deficiency and recurrent gestational hypercalcemia. Her first pregnancy, at age 20, resulted with the intrauterine demise of twin fetuses. Postpartum, she developed severe hypercalcemia (14 mg/dL), altered mental status, and acute pancreatitis. Her PTH was suppressed (6 pg/mL) and her 1,25(OH)2 D was elevated (165 and 195 pg/mL on postpartum day 1 and 5, respectively). Between one and three months postpartum, her serum calcium decreased from 11.4 to 10.2 mg/dL while her 1,25(OH)2 D level decreased from 83 to 24 pg/mL. Her 24-hour urine calcium was 277 mg. Six months postpartum, she became pregnant again. At 14 weeks, her albumin-corrected calcium level was 10.4 mg/dL and her 1,25(OH)2 D level exceeded 200 pg/mL. To establish the diagnosis of CYP24A1 deficiency, we showed her 24,25(OH)2 D level to be undetectable (<2 ng/mL). Exon sequencing of the CYP24A1 gene revealed a homozygous, 8-nucleotide deletion in exon 8, causing an S334V substitution and premature termination due to a frame shift (c.999_1006del, p.Ser334Valfs*9). To prevent hypercalcemia, she was advised to discontinue prenatal vitamins, avoid sun exposure and calcium-rich foods, and start omeprazole and a calcium binder (250 mg K-Phos-neutral with meals). Despite these measures, both hypercalcemia (11.5 mg/dL) and acute pancreatitis recurred. Labor was induced and a healthy, normocalcemic boy was delivered. In the absence of lactation, maternal hypercalcemia resolved within 2 months. This report shows that CYP24A1-deficient subjects may be normocalcemic at baseline. Hypercalcemia may be unmasked by pregnancy through the routine use of calciferol-containing prenatal vitamins, increased 1-alpha hydroxylation of VitD by the placenta and maternal kidney, and production of PTHrP by the uteroplacental unit. CYP24A1 deficiency should be considered in patients with unexplained vitamin D-mediated hypercalcemia. © 2016 American Society for Bone and Mineral Research.

Spatial Cognition in Adult and Aged Mice Exposed to High-Fat Diet.

Aging is associated with a decline in multiple aspects of cognitive function, with spatial cognition being particularly sensitive to age-related decline. Environmental stressors, such as high-fat diet (HFD) exposure, that produce a diabetic phenotype and metabolic dysfunction may indirectly lead to exacerbated brain aging and promote the development of cognitive deficits. The present work investigated whether exposure to HFD exacerbates age-related cognitive deficits in adult versus aged mice. Adult (5 months old) and aged (15 months old) mice were exposed to control diet or HFD for three months prior to, and throughout, behavioral testing. Anxiety-like behavior in the light-dark box test, discrimination learning and memory in the novel object/place recognition tests, and spatial learning and memory in the Barnes maze test were assessed. HFD resulted in significant gains in body weight and fat mass content with adult mice gaining significantly more weight and adipose tissue due to HFD than aged mice. Weight gain was attributed to food calories sourced from fat, but not total calorie intake. HFD increased fasting insulin levels in all mice, but adult mice showed a greater increase relative to aged mice. Behaviorally, HFD increased anxiety-like behavior in adult but not aged mice without significantly affecting spatial cognition. In contrast, aged mice fed either control or HFD diet displayed deficits in novel place discrimination and spatial learning. Our results suggest that adult mice are more susceptible to the physiological and anxiety-like effects of HFD consumption than aged mice, while aged mice displayed deficits in spatial cognition regardless of dietary influence. We conclude that although HFD induces systemic metabolic dysfunction in both adult and aged mice, overall cognitive function was not adversely affected under the current experimental conditions.