Higher Rates Of Bone Loss Research Articles

RANK signaling in osteoclast precursors results in a more permissive epigenetic landscape and sexually divergent patterns of gene expression.

Sex is an important risk factor in the development of osteoporosis and other bone loss disorders, with women often demonstrating greater susceptibility than men. While variation in sex steroids, such as estradiol, accounts for much of the risk, there are likely additional non-endocrine factors at transcriptional and epigenetic levels that result in a higher rate of bone loss in women. Identification of these factors could improve risk assessment and therapies to preserve and improve bone health. Osteoclast precursors were isolated male and female C57Bl/6 mice and cultured with either MCSF alone or MCSF and RANKL. Following the culture period RNA was isolated for RNA sequencing and DNA was isolated for tagmentation and ATAC sequencing. RNA-Seq and ATAC-seq were evaluated via pathway analysis to identify sex- and RANKL-differential transcription and chromatin accessibility. Osteoclasts demonstrated significant alterations in gene expression compared to macrophages with both shared and differential pathways between the sexes. Transcriptional pathways differentially regulated between male and female cells were associated with immunological functions with evidence of greater sensitivity in male macrophages and female osteoclasts. ATAC-Seq revealed a large increase in chromatin accessibility following RANKL treatment with few alterations attributable to sex. Comparison of RNA-Seq and ATAC-seq data revealed few common pathways suggesting that many of the transcriptional changes of osteoclastogenesis occur independently of chromatin remodeling.

Volumetric Evaluations of Full-Arch Implant Supported Restorations and Their Role on Patients’ Quality of Life: A Mixed-Model Analysis

Introduction Full-arch, implant-supported hybrid restorations, employing tilted implants, can offer an efficient way of treating edentulous patients. Several factors, such as the timing of implant placement and the inclination of the fixture, can have a detrimental effect on their stability. This retrospective study is aimed at discerning the role played by those factors. Materials and Methods Patients treated with full-arch, implant supported restorations were selected for this study; cone-beam computed tomography (CBCT) images, taken 3 months and 3 years after delivery of the final restoration, as well as peri-implant values, were obtained and compared; bone loss was measured on four sites for each implant and then averaged. These patients were recalled, and the OHIP-5 questionnaire was administered. Results 21 patients, with a mean age of 53 years, were included in the present analysis. 108 implants were placed, and 25 Toronto prostheses were delivered. According to a mixed-model analysis, tilted implants (0.51, p < 0.001) had a higher rate of bone loss, while implants placed in a healed ridge suffered less bone loss than immediate implants (-0.21, p < 0.001). Patient-level variables have a significant effect on this variable, as implants coming from the same subject share a similar risk of bone loss. The mean response to the self-administered OHIP-5 questionnaire was 1.53 ± 0.29; other variables did not have a statistically significant effect on this outcome. Discussion/Conclusions. The results of the present study show that Toronto bridges prostheses are an efficient procedure for treating edentulous patients, as their oral-related quality of life is reported as satisfactory even 7 years after delivery of the restoration. Tilted and immediate implants are more at risk of bone loss. Implants coming from the same subject share a similar risk of bone loss.

First Molars-Incisors Rate and Pattern of Bone Loss: A Cross-Sectional Analysis of CBCT Images.

Background: Periodontitis causes attachment and alveolar bone loss; hence, this study aimed to determine the prevalence, frequency, and pattern of bone loss at first molar–incisor areas using Cone Beam Computed Tomography (CBCT) images. Methods: A retrospective, cross-sectional analysis was conducted of 250 randomly selected CBCT images of clearly defined full arches of patients aged from 18 to 70 years who were divided into six age groups and into male and female groups. Four sites around each tooth were scanned at several accesses for bone loss detection. Distance beyond 2 mm apical to the cementoenamel junction to the level of the remaining bone was considered to indicate bone loss. The Shapiro–Wilk test was used to test the normality of the data, and statistical tests were applied for data analysis at the 0.05 p-value level. Results: The rate and amount of bone loss within the examined sample were relatively high. The examined images generally revealed a higher rate of bone loss on proximal than on labial/buccal and lingual/palatal surfaces of the first upper and lower molars. The highest amount of bone loss among all the teeth scanned in this study was seen on the mesial and distal bone of mandibular incisors, 4.36 mm and 4.31 mm, respectively, exceeding that in the labial and lingual bone, 3.23 mm and 1.89 mm, respectively, and it was highly horizontal rather than vertical in pattern. Conclusions: Based on 250 randomly selected CBCT images of clearly defined, full upper and lower arches scanned for this study, it was concluded that the rate and amount of horizontal bone loss were less than vertical bone loss and was focused mainly in the interproximal areas of the first molars. However, the highest recorded amount of bone loss was at the proximal and labial aspects of the mandibular incisors. Furthermore, younger age groups displayed significantly higher rates and amounts of bone loss than older groups, with a slight predilection for males.

Age-Related Changes in Bone Density, Microarchitecture, and Strength in Postmenopausal Black and White Women: The SWAN Longitudinal HR-pQCT Study.

Higher fracture risk in White versus Black women is partly explained by lower BMD and worse bone microarchitecture in White women. However, whether rates of decline in bone density, microarchitecture and strength differ between postmenopausal Black and White women is unknown. Further, factors that influence rates of age-related bone microarchitecture deterioration remain ill-defined. Thus, over 6.7 years, longitudinal changes were measured in peripheral volumetric bone mineral density (vBMD), microarchitecture, and strength at the distal radius and tibia using HR-pQCT in postmenopausal Black (n=80) and White (n=137) women participating in the Study of Women's Health Across the Nation. It was assessed whether age-related changes in vBMD and microarchitecture were influenced by body weight, body composition, and/or weight change. It was found that at the radius, where White women appeared to have slightly greater rates of loss in total vBMD, cortical bone volume, and porosity than Black women, those differences were attenuated after adjusting for clinical covariates. At the tibia, Black and White women had similar rates of bone loss. Independent of race and other clinical covariates, women with the lowest baseline body weight experienced the greatest decline in total and trabecular vBMD at the radius. Furthermore, women who lost weight over the follow-up period had higher rates of bone loss, particularly at the tibia, compared with those who maintained or gained weight. Higher baseline total body fat mass was also protective of bone loss at both the radius and tibia. In conclusion, these findings indicate that lower fracture risk among postmenopausal Black women is not caused by slower rates of bone deterioration, and highlight the importance for postmenopausal women to avoid lower body weight and excessive weight loss to avert rapid bone loss and subsequent fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Results of study of biochemical markers of bone metabolism in men with coronary heart disease

The development of atherosclerosis is closely related to the calcification of the vessel intima and fibrous plaques, being a complex and multifactorial process, in which the markers of bone formation and resorption play an important role. Objective. To study the biochemical markers of bone metabolism in men with stable coronary heart disease (CHD). Material and methods. The study included 102 men with verified CHD. Data were evaluated by densitometry, coronary angiography, multispiral computed tomography, color duplex scanning of brachiocephalic arteries, serum lipids (total cholesterol, triglycerides [TG], high-density [LHD] and low-density lipoprotein cholesterol), concentrationsin the blood of osteocalcin (OC), bone alkaline phosphatase (BAP), cathepsin K and C-telopeptides (CTx). Results. Concentrations of BAP, cathepsin K and CTx in patients with CHD were significantly higher than in men without CHD. The concentration of OC in men with normal bone mineral density was significantly lower than in patients with osteopenic syndrome. There was a direct correlation between OC and antiatherogenic HDL cholesterol and the inverse correlation between OC and TG, CTx and TG. There was no correlation between the level of bone remodeling markers and coronary artery (CA) lesion variant and the severity of coronary atherosclerosis on SYNTAX scale. The correlation analysis did not reveal the connection of biochemical markers of bone metabolism with the severity of coronary atherosclerosis and calcification and thickness of intima-media complex of carotid arteries. Absolute values of bone formation indices (BAP, OC) were significantly higher in patients with severe СA calcification than in patients without signs of calcification. Summary. Increased rates of osteogenesis and osteoresorption characterize the accelerated process of bone metabolism and indicate in favor of high rates of bone loss in men with CHD, which confirms the likelihood of common pathophysiological mechanisms of bone resorption and arterial calcification.

Fracture union rates across a century of war: a systematic review of the literature

IntroductionFractures have been a common denominator of the injury patterns observed over the past century of warfare. The fractures typified by the blast and ballistic injuries of war lead to...

Surgical Outcomes In The Frequency, Etiology, Direction, Severity (feds) Classification System For Shoulder Instability

Objectives: The Frequency, Etiology, Direction, Severity (FEDS) system is a reliable and reproducible classification of glenohumeral instability. Frequency is defined as Solitary (1), Occasional (2-5), or Frequent (&gt;5) episodes per year; etiology as Traumatic or Atraumatic; direction as Anterior, Posterior, or Inferior; and severity as a Subluxation or Dislocation. 36 total combinations are possible, named by the first letter of each variable in order. The purpose of this descriptive study was to investigate epidemiology, surgical outcomes, and failure using FEDS in patients undergoing surgery in a large multicenter cohort of prospectively enrolled patients. Methods: 1204 patients undergoing surgery were assigned to FEDS categories. Two-year follow-up at time of analysis was available for 629 patients (85.7% of those eligible based on date of surgery). Those categories consisting of at least 5% of patients were further analyzed by patient reported outcomes (PROs) and failure rates for a total of 466 patients. PROs included American Shoulder and Elbow Surgeons score (ASES), Western Ontario Shoulder Instability index (WOSI), and Single Assessment Numeric Evaluation (SANE). Failure benchmarks included rates of recurrent subluxation, dislocation, and revision surgery. Results: Sixteen categories represented at least one percent of patients. Occasional Traumatic Anterior Dislocation (OTAD) was the most common category with 16.4% of patients. Five other anterior categories (STAS, OTAS, FTAS, STAD, FTAD) and one posterior category (STPS) represented at least 5%. PROs and failure rates for anterior categories are summarized in Figure 1. PROs improved significantly for each category. A downward trend in WOSI and ASES was noted in particular with increasing frequency of the dislocation groups. The highest rates of each type of failure occurred in the occasional and frequent groups for both dislocation and subluxation. Low rates of failure occurred in STPS, with 17.9% reporting subluxation, 3.6% dislocation, and no revisions. Conclusion: While overall success was good, different FEDS categories showed varying degrees of improvement and failure rates, indicating that the system can be used to provide prognostic insight for presurgical education. Overall, outcomes for traumatic anterior instability decreased with higher initial frequency, showing worse PROs and higher failure. Frequency appeared to have the greatest effect on outcomes. Early surgical intervention may be beneficial in preventing progression to more severe FEDS categories, with higher frequency having previously been associated with both higher rates of bone loss and greater time between initial event and surgical stabilization.

A comparison of exercise interventions from bed rest studies for the prevention of musculoskeletal loss

Musculoskeletal loss in actual or simulated microgravity occurs at a high rate. Bed rest studies are a reliable ground-based spaceflight analogue that allow for direct comparison of intervention and control participants. The aim of this review was to investigate the impact of exercise compared to no intervention on bone mineral density (BMD) and muscle cross-sectional area (muscle CSA) in bed rest studies relative to other terrestrial models. Eligible bed rest studies with healthy participants had an intervention arm with an exercise countermeasure and a control arm. A search strategy was implemented for MEDLINE. After screening, eight studies were identified for inclusion. Interventions included resistive exercise (RE), resistive vibration exercise (RVE), flywheel resistive exercise, treadmill exercise with lower body negative pressure (LBNP) and a zero-gravity locomotion simulator (ZLS). Lower limb skeletal sites had the most significant BMD losses, particularly at the hip which reduced in density by 4.59% (p < 0.05) and the tibial epiphysis by 6% (p < 0.05). Exercise attenuated bone loss at the hip and distal tibia compared to controls (p < 0.05). Muscle CSA changes indicated that the calf and quadriceps were most affected by bed rest. Exercise interventions significantly attenuated loss of muscle mass. ZLS, LBNP treadmill and RE significantly attenuated bone and muscle loss at the hip compared to baseline and controls. Despite exercise intervention, high rates of bone loss were still observed. Future studies should consider adding bisphosphonates and pharmacological/nutrition-based interventions for consideration of longer-duration missions. These findings correlate to terrestrial bed rest settings, for example, stroke or spinal-injury patients.

FES-rowing attenuates bone loss following spinal cord injury as assessed by HR-pQCT.

Neurologically motor complete spinal cord injury (SCI) presents a unique model of bone loss whereby specific regional sites are exposed to a complete loss of voluntary muscle-induced skeletal loading against gravity. This results in a high rate of bone loss, especially in the lower limbs where trabecular bone mass decreases by ~50-60% and cortical bone mass decreases by 25-34% before the rate of bone loss slows. These SCI-induced losses that are likely superimposed on continual age-related bone losses, increase the risk of low-impact fragility fracture. The fracture incidence 20 years post SCI is reported to be 4.6% per year. An intervention that effectively prevents, attenuates, or reverses bone loss is therefore highly desirable. We present a case study of an individual with chronic complete SCI, where bone loss has been attenuated following long-term functional electrical stimulation (FES)-rowing training. In this case study, we characterize the ultradistal tibia and ultradistal radius of the FES-rower with chronic complete SCI using high-resolution-peripheral quantitative computed tomography. These data are compared with a group of FES-untrained individuals with chronic complete SCI and to a normative non-SCI cohort. The evidence suggests, albeit from a single individual, that long-term FES-rowing training can attenuate bone loss secondary to chronic complete SCI. Indeed, key FES-rower's bone metrics for the ultradistal tibia more closely resemble normative age-matched values, which may have clinical significance since the majority of fragility fractures in chronic SCI occur in the lower extremities.

Plasma n-3 Polyunsaturated Fatty Acids and Bone Mineral Density in Renal Transplant Recipients

Renal transplant recipients (RTR) suffer high rates of bone loss and increased risk of fracture. Marine n-3 polyunsaturated fatty acids (n-3 PUFA), found mainly in fish and seafood, may have beneficial effects on bone and are positively associated with bone mineral density (BMD) in healthy elderly. The aim of this study was to investigate if this association prevails despite the more complex causes of bone loss in RTR. A total of 701 RTR were included in a cross-sectional analysis. BMD of lumbar spine, proximal femur, and distal forearm were measured by dual energy x-ray absorptiometry scan, and blood samples were drawn in the fasting state for measurement of plasma fatty acid composition 10weeks posttransplant. Multiple linear regression analysis was used to assess the association between plasma marine n-3 PUFA levels and BMD. Mean age was 52.2years, and two-thirds were men. Based on femoral neck T-scores, 26% of patients were osteoporotic and 52% osteopenic. Z-scores increased significantly across quartiles of marine n-3 PUFA levels, and marine n-3 PUFA was a positive predictor of BMD at total hip and lumbar spine after multivariate adjustment. No association was found between n-6 PUFA content and BMD. Plasma marine n-3 PUFA levels were positively associated with BMD at the hip and lumbar spine 10weeks posttransplant.

25-Hydroxyvitamin-D and Bone Turnover Marker Levels in Patients with Distal Radial Fracture.

Fragility fractures are a major public health issue with substantial socioeconomic cost. Vitamin-D deficiency and increased bone turnover are associated with higher rates of bone loss and an increased risk of fracture. We hypothesized that patients with a distal radial fracture would have lower levels of 25-hydroxyvitamin D (25[OH]D) and increased levels of serum bone turnover markers than controls without a fracture. Postmenopausal women with a recent distal radial fracture (fracture group, n = 105) were prospectively recruited and were compared with individuals without a fracture (control group, n = 150). Outcome variables included serum levels of 25(OH)D and markers of bone formation, including N-terminal extension propeptide of type-I collagen (P1NP), parathyroid hormone (PTH), bone-specific alkaline phosphatase (BSAP), and osteocalcin, as well as a marker of resorption (C-terminal telopeptide of type-I collagen [CTX-1]). Bone mineral density was measured with dual x-ray absorptiometry. The fracture group was slightly older than the control group (mean and standard deviation [SD], 66.8 ± 10.8 years versus 63.3 ± 9.0 years, p = 0.008), had a lower body mass index (26.4 ± 5.9 kg/m(2) versus 28.0 ± 6.2 kg/m(2), p = 0.05), and more commonly had had a prior fracture (52% versus 31%, p < 0.001). Bone mineral density at the hip was lower in the fracture group than in the control group (0.831 ± 0.130 g/cm(2) versus 0.917 ± 0.139 g/cm(2), p < 0.001). The mean 25(OH)D levels were similar in the fracture and control groups (44.4 ± 14.6 ng/mL versus 41.3 ± 14.5 ng/mL, p = 0.08). Levels of serum markers of bone formation were significantly higher in the fracture group than in the control group (P1NP: 70.4 ± 33.2 ng/mL versus 53.2 ± 25.6 ng/mL, p < 0.001; osteocalcin: 22.3 ± 9.9 ng/mL versus 20.2 ± 9.2 ng/mL, p = 0.017). Levels of BSAP, PTH, and CTX-1 were similar in the two groups. Multivariable logistic regression showed independent associations between a distal radial fracture and low total hip bone mineral density (odds ratio [OR] = 2.02 for each decrease of 1 SD, 95% confidence interval [CI] = 1.38 to 3.01, p < 0.001) and a high P1NP level (OR = 2.17 for each 1-SD increase, 95% CI = 1.52 to 3.06, p < 0.001). In this cohort, 25(OH)D levels were not associated with distal radial fracture and do not appear to affect the risk assessment for distal radial fracture in postmenopausal women. Patients with a distal radial fracture, however, had increased bone turnover as evidenced by high P1NP and osteocalcin levels. Women with both a high P1NP level and low bone mineral density were at particularly high risk for fracture.

Prediction of bone loss in elderly women using bone turnover markers

Osteoporosis related fractures are common in old age and over 40 % of the women above 50 years of age are at a risk of developing a fragility fracture. Biochemical markers of bone turnover (BTMs) have proven to be of some value in fracture predictability. There is also a correlation between rate of decrease of areal bone mineral density (aBMD) and incident fractures. In this series of studies, the correlation between BTMs and rate of bone loss (change of aBMD and ultrasound variables) over 5 years was investigated in a cohort of 75 year-old Swedish women. In addition, correlation of BTMs and bone metabolism, as assessed by scintigraphy, was tested in postmenopausal women. Finally, the effect of precision error on the longitudinal monitoring of change in aBMD was assessed in elderly women and in elderly men. There was a strong correlation between all bone turnover markers and the results of scintigraphy (total skeletal uptake of 99mTc-labelled methylene diphosphonate), with no significant difference between bone formation markers and bone resorption markers. BTMs correlated to the 5-year rate of change of aBMD, especially in the legs and the total body, and 5 year change in speed of ultrasound. When serial measurements of BTMs were analysed, the mean value of measurements correlated more strongly to aBMD change than single measurements, and women with constantly high levels of BTMs had higher rates of bone loss. Precision error of aBMD measurement by dual-energy X-ray absorptiometry has an influence on the detection of individuals with aBMD change exceeding the least significant level. The calculated follow-up interval for detection of aBMD change beyond the least significant level in more than 50% of elderly individuals ranged from 332 years, and was dependent on the equipment used and the skeletal site tested. These results indicate that BTMs are associated with future bone loss although the correlations may not be strong enough to predict bone loss at individual level. DXA also has some limitations when used in longitudinal follow up of elderly individuals. DXA is therefore of limited use in the longitudinal monitoring ofbone loss. Further studies with novel bone turnover markers may improve the ability of BTMs to predict bone loss.

C-reactive protein, bone loss, fracture, and mortality in elderly women: a longitudinal study in the OPRA cohort.

This longitudinal study investigates the association between C-reactive protein (CRP), osteoporosis, fractures, and mortality in 1044 elderly women. CRP was not an indicator for low bone mineral density (BMD), bone loss, or fracture in elderly women; however, women with elevated CRP levels over a prolonged period lost more bone over the 10-year follow-up, although fracture risk was not increased. Inflammation may contribute to the pathophysiology underlying impaired bone metabolism. This study investigates the association between CRP, BMD, bone loss, fracture risk, and mortality in women aged 75 and above. This longitudinal study is based on 1044 women, all age 75 at inclusion, reassessed at ages 80 and 85, with a mean follow-up time of 11.6 years (maximum 16.9 years). Women in the lowest CRP quartile (mean 0.63 mg/L) had lower BMD compared to those in the highest CRP quartile (mean 5.74 mg/L) at total hip (TH) (0.809 vs. 0.871 g/cm2, p<0.001) and femoral neck (FN) (0.737 vs. 0.778 g/cm2, p=0.007). A single measurement of CRP was not associated with bone loss; however, women with persistently elevated CRP, i.e., ≥3 mg/L at ages 75 and 80 had significantly higher bone loss compared to women with CRP<3 mg/L (TH -0.125 vs. -0.085 g/cm2, p=0.018 and FN -0.127 vs. -0.078 g/cm2, p=0.005) during 10 years of follow-up. Women in the highest CRP quartile had a lower risk of osteoporotic fractures (hazard ratios (HR) 0.76 (95% confidence intervals (CI) 0.52-0.98)) compared to those in the lowest, even after adjusting for weight and BMD. Mortality risk was only increased among women with the highest CRP levels. CRP was not an indicator for low BMD, bone loss, or fracture in elderly women in this study. Persistently elevated CRP however seemed to be detrimental to bone health and may be associated with a higher rate of bone loss. Only the highest CRP levels were associated with mortality.

AB0300 ACPA in Reduction of BMD in Premenopausal RA Patients

BackgroundBone strength depends on its structure, the material properties, and bone turnover; bone mineral density (BMD) loss results in micro-architectural deterioration and decreased mechanical strength of bone. In rheumatoid arthritis...

Similarities and differences between sexes in regional loss of cortical and trabecular bone in the mid-femoral neck: The AGES-Reykjavik longitudinal study

The risk of hip fracture rises rapidly with age, and is notably higher in women. After falls and prior fragility fractures, the main clinically recognized risk factor for hip fracture is reduced bone density. To better understand the extent to which femoral neck density and structure change with age in each sex, we carried out a longitudinal study in subjects not treated with agents known to influence bone mineral density (BMD), to investigate changes in regional cortical thickness, as well as cortical and trabecular BMD at the mid-femoral neck. Segmental quantitative computed tomography (QCT) analysis was used to assess bone measurements in two anatomic subregions, the superolateral (superior) and inferomedial (inferior). A total of 400 older individuals (100 men and 300 women, aged 66-90 years) who were participants in the Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik), were studied. Participants had two QCT scans of the hip over a median follow-up of 5.1 years (mean baseline age 74 years). Changes in bone values during follow-up were estimated from mixed effects regression models. At baseline women had lower bone values in the superior region than men. At follow-up all bone values were lower in women, except cortical volumetric bone mineral density (vBMD) inferiorly. The relative losses in all bone values estimated in the superior region were substantially (about threefold) and significantly greater compared to those estimated in the inferior region in both sexes. Women lost cortical thickness and cortical vBMD more rapidly than men in both regions; and this was only weakly reflected in total femoral neck dual-energy X-ray absorptiometry (DXA)-like results. The higher rate of bone loss in women at critical locations may contribute materially to the greater femoral neck fracture incidence among women than men.

Rapid cortical bone loss in patients with chronic kidney disease.

Chronic kidney disease (CKD) patients may have high rates of bone loss and fractures, but microarchitectural and biochemical mechanisms of bone loss in CKD patients have not been fully described. In this longitudinal study of 53 patients with CKD Stages 2 to 5D, we used dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HRpQCT), and biochemical markers of bone metabolism to elucidate effects of CKD on the skeleton. Median follow-up was 1.5 years (range 0.9 to 4.3 years); bone changes were annualized and compared with baseline. By DXA, there were significant declines in areal bone mineral density (BMD) of the total hip and ultradistal radius: -1.3% (95% confidence interval [CI] -2.1 to -0.6) and -2.4% (95% CI -4.0 to -0.9), respectively. By HRpQCT at the distal radius, there were significant declines in cortical area, density, and thickness and increases in porosity: -2.9% (95% CI -3.7 to -2.2), -1.3% (95% CI -1.6 to -0.6), -2.8% (95% CI -3.6 to -1.9), and +4.2% (95% CI 2.0 to 6.4), respectively. Radius trabecular area increased significantly: +0.4% (95% CI 0.2 to 0.6), without significant changes in trabecular density or microarchitecture. Elevated time-averaged levels of parathyroid hormone (PTH) and bone turnover markers predicted cortical deterioration. Higher levels of serum 25-hydroxyvitamin D predicted decreases in trabecular network heterogeneity. These data suggest that significant cortical loss occurs with CKD, which is mediated by hyperparathyroidism and elevated turnover. Future investigations are required to determine whether these cortical losses can be attenuated by treatments that reduce PTH levels and remodeling rates.

Diabetes and Change in Bone Mineral Density at the Hip, Calcaneus, Spine, and Radius in Older Women

Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) but also have higher rates of fracture compared to those without DM. Limited evidence suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed BMD data in the Study of Osteoporotic Fractures (SOF) between 1986 and 1998. SOF participants were women ≥65 years at baseline who were recruited from four regions in the U.S. DM was ascertained by self-report. BMD was measured with dual-energy x-ray absorptiometry (DXA) at baseline and at least one follow-up visit at the hip (N = 6624) and calcaneus (N = 6700) and, on a subset of women, at the spine (N = 396) and distal radius (N = 306). Annualized percent change in BMD was compared by DM status, using random effects models. Of 6,867 women with at least one follow-up DXA scan, 409 had DM at baseline. Mean age was 70.8 (SD 4.7) years. Baseline BMD was higher in women with DM at all measured sites. In models adjusted for age and clinic, women with prevalent DM lost bone more rapidly than those without DM at the femoral neck (−0.96 vs. −0.59%/year, p < 0.001), total hip (−0.98 vs. −0.70%/year, p < 0.001), calcaneus (−1.64 vs. −1.40%/year, p = 0.005), and spine (−0.33 vs. +0.33%/year, p = 0.033), but not at the distal radius (−0.97 vs. −0.90%/year, p = 0.91). These findings suggest that despite higher baseline BMD, older women with DM experience more rapid bone loss than those without DM at the hip, spine, and calcaneus, but not the radius. Higher rates of bone loss may partially explain higher fracture rates in older women with DM.

Comparison of strain generated in bone by "platform-switched" and "non-platform-switched" implants with straight and angulated abutments under vertical and angulated load: A finite element analysis study

The aim of this study was to evaluate the microstrain exhibited by bone around immediately loaded, platform-switched, and non-platform-switched implants under vertical and angled loading using a finite element analysis (FEA) and also to evaluate whether platform-switched implants evoke a better response than non-platform-switched implants on a mechanical basis. Three-dimensional finite element study was undertaken to model and analyze an immediate loaded situation. FEA was chosen for this study since it is useful in determining the stress and strain around the dental implant. Bone responses to vertical and angulated loads on straight and angulated abutments (platform-switched and non-platform-switched abutments) were evaluated. Non-platform-switched abutments tend to exhibit a lower tensile stress and compressive stress but higher microstrain value (conducive to higher chance of bone resorption) than platform-switched abutments. Ideal bone remodeling values of microstrain (50-3000 μm) were exhibited by platform-switched straight abutments under vertical load and angled load (with an abutment-implant diameter difference of 1 mm). In spite of the obvious advantages, the practice of immediate loading is limited due to apprehension associated with compromised bone response and a higher rate of bone loss around an immediately loaded implant. The mechanical basis for the concept of "platform switching" in immediately loaded situation is analyzed in this context. The results of this limited investigation indicated that the ideal values of microstrain (50-3000 microstrain) can be exhibited by platform switching of dental implants (with an abutment-implant diameter difference of 1 mm) and can be considered as a better alternative for prevention of crestal bone loss when compared to non-platform-switched implants.

Tenofovir accelerates bone mass loss of the lumbar spine in the first years of menopause in HIV‐infected women

BackgroundHIV‐infected postmenopausal women have higher rates of bone loss than HIV negative women. We aimed to identify predictors of body mass density (BMD) in HIV infected women entering menopause and to evaluate the pre‐ and post‐menopausal BMD change, with regard to tenofovir (TDF) use.MethodsWomen with at least one DEXA measurement were enrolled. The observation period was divided into: “Reproductive period”, “Menopause transition period”, “Early menopause period”, “Late menopause period”. BMD of the lumbar spine (L1‐4) and femur neck were measured by DEXA. Lowess smoothing curves were drawn to analyze impact of menopause and TDF on BMD. Three different longitudinal linear regression models with random effects were built. Longitudinal regression analysis fits cross sectional time series regression models and allows to analyze repeated measures for each patient.ResultsFifty‐five women were included. Median age at enrollment was 46 years (IQ range 44–49). Median observation period was 16 months (IQ range 8; 23) and 33 months (IQ range 23; 72) for pre‐ and post‐menopausal respectively. At enrollment mean CD4 cell count was 553 cell/mL (±269.62) and HIV‐VL was undetectable in 77.5% of patients: 6 women were not undergoing ART. Most common backbone TDF/FTC (46.9%) and ABC/3TC (20.4%). At the time of inclusion in the cohort osteopenia and ostoeporosis were present in 60% and 3.64%, respectively. At the time of last DEXA evaluation osteopenia and osteoporosis were present in 78.18% and 36.36%, respectively. The impact of menopause on lumbar BMD was depicted (fig. 1) using a lowess smoothing analysis according to current TDF exposure (as treated model). Lumbar BMD change predictors were years from menopause and TDF current exposure in the “Early menopause period” and years from menopause, Baseline lumbar BMD, BMI and vitD supplementation in the “Late menopause period”.DiscussionThis is the first study analyzing BMD across menopause. BMD was stable in the pre‐menopause period while BMD loss characterized the post‐menopause period. Traditional risk factors contributed to BMD change in the post ‐menopause period. Current TDF exposure was independently associated with BMD change in the “Early menopause period” only, but not confirmed in the “Late menopause period”, suggesting a compensating mechanism occurring after the second year post‐menopause. image Transitional period Early menopause Late menopause β 95% CI p‐value β 95% CI p‐value β 95% CI p‐value Years to (from*) menopause −0.1 −0.03; 0.01 0.407 −0.01 −0.02; − 0.01 &lt;0.001 −0.1 −0.2; − 0.003 0.009 Baseline lumbar BMD 0.0002 −0.001; 0.003 0.078 0.0002 −0.0001; 0.0004 0.074 0.9 0.70−1.09 &lt;0.001 PTH −0.0005 −0.001; 0.0004 0.280 0.0001 −0.0004; 0.0002 0.535 −0.0001 −0.0002; 0.0002 0.800 BMI 0.003 −0.005; 0.010 0.489 0.004 −0.001; 0.010 0.142 0.008 0.002; 0.014 0.010 VitD supplementation −0.003 −0.05; 0.04 0.865 0.008 −0.010; 0.026 0.392 0.03 0.001; 0.054 0.038 TDF current exposure −0.03 −0.07; 0.01 0.125 −0.03 −0.05; −0.01 0.012 −0.04 −0.09; 0.01 0.129

High serum total homocysteine levels accelerate hip bone loss in healthy premenopausal women and men

IntroductionDespite extensive evidence demonstrating the direct, detrimental role of homocysteine on bone metabolism, the effects of serum total homocysteine (tHcy) on bone loss are still equivocal. In the present study, we performed a longitudinal study on healthy participants of various ages of both sexes in order to investigate the association between serum tHcy concentrations and annualized changes in bone mineral density (BMD). MethodsA total of 460 Koreans≥30years of age received comprehensive, routine health examinations for an average period of 3years. The BMD at proximal femur sites was measured with dual-energy X-ray absorptiometry using the same equipment at baseline and follow-up. ResultsAfter adjusting for potential confounders, the rates of bone loss at the proximal femur sites were significantly accelerated in a dose–response fashion across increasing tHcy concentrations in premenopausal women and men, but not in postmenopausal women. Consistently, compared with subjects in the lowest tHcy quartile, premenopausal women in the third and/or highest tHcy quartile and men in the highest tHcy quartile showed significantly higher rates of bone loss at all proximal femur sites (p=0.015–0.048) and at the total femur and femur neck (p=0.008–0.013), respectively. In contrast, there were no differences in terms of bone loss among the tHcy quartiles for postmenopausal women. ConclusionThese data provide the first clinical evidence that increased tHcy levels could be an independent risk factor for the future deterioration of bone mass in premenopausal women and men.