Femoral Neck T-score Research Articles

Exercise Therapy For Bone Health: Translation To Clinical Practice

We previously reported that high-intensity resistance and impact training (HiRIT) is safe and improves risk factors for osteoporotic fracture in postmenopausal women and older men with low bone mass under trial conditions (LIFTMOR and LIFTMOR-M trials). We have now established a translational research Clinic implementing HiRIT in practice alongside systematic longitudinal monitoring of musculoskeletal and functional outcomes to determine effectiveness and feasibility as osteoporosis prevention and therapy in the ‘real world’. PURPOSE: The aim of the current report is to present 4 year outcomes from the Clinic. METHODS: All Clinic clients undergo testing for height, weight, spine (LS), total hip (TH) and femoral neck (FN) bone mineral density (BMD), lean and fat mass, back extensor strength (BES), and functional indices of fall risk at their baseline visit, and annually thereafter. Twice-weekly supervised HiRIT with balance training and a dietary consult is provided. Compliance and injuries are comprehensively monitored. In the absence of a control group, program effectiveness is determined from one-sample t-tests of percent change from baseline. RESULTS: We report outcomes from 275 clients (94.9% female) who have completed a minimum of 12 months HiRIT (63.6±7.1 yrs, 162.3±6.8 cm, 60.6±10.0 kg, LS T-score -2.0±1.1, FN T-score -2.0±0.7, compliance 69.1±39.6%). 70 clients were on bone medications at baseline but only 18 at follow-up. Improvement was observed in weight (0.8±3.8%, P<0.0001), LS (2.2±5.1%, P<0.0001), TH (1.0±3.7%, P<0.0001) and FN BMD (1.4±4.8%, P<0.0001), lean mass (2.3±5.5%, P<0.0001), fat percent (-4.5±10.7%, P<0.0001), functional reach (7.2±13.4%, P<0.0001), timed up and go (-9.8±12.0%, P<0.0001), tandem walk (-20.6±35.1%, P<0.0001), sit to stand (-9.9±15.9%, P<0.0001), BES (20.6±35.1%, P<0.0001), and kyphosis (5.1±54.8%, P<0.05). Clients increased daily dietary calcium (23±67%, P<0.0001) and total calcium (19±68%, P<0.0001). 20 injuries were sustained in a total of 31,483 training sessions, the majority being minor muscle strains. CONCLUSION: We show that, when supervised in clinical practice, an evidence-based, targeted, high-intensity resistance and impact training program is safe and highly effective osteoporosis therapy for older men and women with low bone mass.

Regular Supplementation With Resveratrol Improves Bone Mineral Density in Postmenopausal Women: A Randomized, Placebo-Controlled Trial.

ABSTRACTResveratrol, a naturally occurring polyphenol in red grapes and berries, can act as a phytoestrogen. It has been shown to improve both systemic and cerebral circulatory functions, possibly through activation of endothelial estrogen receptors. in vitro and in vivo studies in rodent models also indicate a bone‐protective role for resveratrol, particularly in ovariectomized rat models that mimic postmenopausal osteoporosis caused by estrogen deficiency. Hypothesizing a circulatory benefit of resveratrol in bone tissue, we investigated whether resveratrol supplementation could improve bone health in postmenopausal women. The Resveratrol for Healthy Aging in Women (RESHAW) trial was a 24‐month randomized, double‐blind, placebo‐controlled, two‐period crossover intervention conducted to evaluate the effects of resveratrol (75 mg twice daily) on cognition, cerebrovascular function, bone health, cardiometabolic markers, and well‐being in postmenopausal women. After 12 months of supplementation with resveratrol versus placebo, there were positive effects on bone density in the lumbar spine (+0.016 ± 0.003 g/cm2) and neck of femur (+0.005 ± 0.002 g/cm2), which were accompanied by a 7.24% reduction in C‐terminal telopeptide type‐1 collagen levels, a bone resorption marker, compared with placebo. The increase in bone mineral density in the femoral neck resulted in an improvement in T‐score (+0.070 ± 0.018) and a reduction in the 10‐year probability of major and hip fracture risk. The magnitude of improvement was higher in women with poor bone health biomarker status. Importantly, the improvement in femoral neck T‐score with resveratrol correlated with improvement in perfusion. Our subanalysis also revealed that the bone‐protective benefit of resveratrol was greater in participants who supplemented with vitamin D plus calcium. Regular supplementation with 75 mg of resveratrol twice daily has the potential to slow bone loss in the lumbar spine and femoral neck, common fracture sites in postmenopausal women without overt osteoporosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Low bone density and osteoporosis among older adults with Alzheimer's disease, vascular dementia, and mixed dementia: A Cross-sectional Study With Prospective Enrollment.

This study aims to examine bone mineral density (BMD) and osteoporosis in older adults with dementia compared to those with a normal cognitive status and to evaluate the type, severity, and duration of dementia. Between May 2013 and May 2017, a total of 363 participants aged ≥65 years (136 males, 227 females; mean age 78.4±5.4 years; range 66 to 99 years) with and without Alzheimer's disease (AD), vascular dementia (VaD), or mixed dementia (AD-VaD) were included in this single-center, prospective, cross-sectional study. The dementia group included 93 patients with dementia and the control group included 270 age- and sex-matched healthy individuals. We used dual-energy X-ray absorptiometry (DXA) to measure BMD of the lumbar spine, total hip, and femoral neck. Controlled for age and sex, demented and non-demented participants had a similar BMD (g/cm2) at lumbar spine [F (1, 358):0.83, p=363], but lower BMD values of total hip [F (1, 359):10.26, p=0.001] and femoral neck [F (1, 359):15.21, p<0.001] in the patients with dementia. Adjusted percentage of osteoporosis and low bone mass based on total hip and femoral neck T-scores were also significantly higher in the patient group. The mean BMD values, frequency of osteoporosis, and low bone mass did not significantly differ according to the subtype of dementia, sex, and disease duration or severity. Our study results show that demented elders have a lower BMD and higher frequency of osteoporosis at the hip, but not at the lumbar spine, irrespective of sex and type of dementia. Based on these results, we can speculate that not only AD, but also VaD and AD-VaD may be associated with bone loss at the hip.

Impact of spine-hip discordance on fracture risk assessment and treatment qualification in Canada: the Manitoba BMD registry.

Discordance between lumbar spine and femoral neck T-score measurements are frequently encountered in clinical practice. The FRAX tool accepts femoral neck BMD as an optional input but does not consider lumbar spine BMD, though adjustments based upon T-score difference have been proposed. This analysis was undertaken to examine change in treatment qualification using the lumbar spine T-score adjustment to FRAX assuming an intervention threshold of 20% MOF. Women aged > 50 years with baseline FRAX MOF probability computed with femoral neck BMD of ≥ 20% but without previous high-risk fracture or high-risk medication use were identified in the province of Manitoba BMD registry. If lumbar spine T-score was lower than the femoral neck T-score, MOF probability was recalculated, and treatment qualification, reassessed. The study population consisted of 50,300 women (mean age 64.2 ± 8.6 years). During mean follow-up of 9.5 years, 4550 sustained incident MOF. The baseline mean T-score difference (femoral neck minus lumbar spine) was - 0.2 ± 1.1. Recalculated MOF probability using the T-score difference significantly improved overall net reclassification index for incident MOF prediction (+ 0.017, p < 0.001). A total of 561 (1.1%) of these women were reclassified from below to above 20% MOF probability based upon the T-score difference. No individuals with MOF probability less than 15% were reclassified to the higher risk category. Risk reclassification increased with lower lumbar spine T-score (15.6% reclassification for lumbar spine T-score of - 3.5 or lower, 4.0% of the study population) and larger T-score differences (9.7% reclassification for T-score difference of 2.5 or more, < 1% of the study population). Very few women showed risk reclassification based upon adjusting FRAX MOF probability for lumbar spine T-score. Reclassification occurred only in those with baseline MOF probability > 15%.

Association between Geriatric Nutrition Risk Index and Skeletal Muscle Mass Index with Bone Mineral Density in Post-Menopausal Women Who Have Undergone Total Thyroidectomy.

Background: Osteoporosis is highly prevalent in postmenopausal women and may result in fractures and disabilities. Total thyroidectomy has also been associated with loss of bone mass. The aim of this cross-sectional study was to evaluate associations among nutritional status, skeletal muscle index and markers of bone turnover to bone mineral density in postmenopausal women who had undergone total thyroidectomy. Methods: Fifty postmenopausal women who had undergone total thyroidectomy were included. Body composition was measured using dual-energy X-ray absorptiometry (DXA). The Geriatric Nutritional Risk Index (GNRI) was calculated using baseline body weight and serum albumin level. Skeletal muscle mass index was calculated as the appendicular skeletal muscle mass (ASM) divided by the height squared and assessed using DXA. Results. Multivariate stepwise linear regression analysis showed that a low GNRI was significantly associated with low lumbar spine bone mineral density (BMD) and T-score, and that a low ASM/height2 was significantly associated with low femoral neck BMD and T-score. A low vitamin D level was significantly associated with low femoral neck BMD and T-score and low total hip BMD and T-score. A high bone alkaline phosphatase (ALP) level was significantly associated with low femoral neck T-score and low total hip BMD and T-score. A low insulin-like growth factor-1 (IGF-1) was significantly associated with low total hip BMD and T-score. Conclusion: In the postmenopausal women who had undergone total thyroidectomy in this study, BMD was positively associated with GNRI, skeletal muscle mass index, and levels of vitamin D and serum IGF-1, and inversely associated with bone ALP level. Nutritional status, skeletal muscle mass index and bone turnover biomarkers can be used to early identify patients with a high risk of osteoporosis in this high-risk group.

SAT0455 RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS) FOR THE IDENTIFICATION OF FRAIL BONES

Background:Radiofrequency Echographic Multi Spectrometry (REMS) is the first clinically available approach for direct non-ionizing measurement of bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN). Available scientific evidences describe BMD estimated by REMS as an accurate parameter for the diagnosis of osteoporosis [1].Objectives:To investigate the effectiveness of the T-score values provided by REMS scans at FN and LS in the identification of frail patients at risk for osteoporotic fractures and to compare the performance of REMS with the dual-energy X-ray absorptiometry (DXA) one.Methods:The patients underwent DXA and REMS scans at FN and at LS. Five clusters of fractures occurred during a median 3.5-year follow-up were identified whether involving the upper limb (forearm, elbow, humerus, wrist, hand), lower limb (tibia, ankle, metatarsus), thorax (shoulder blade, shoulder, rib), hip (femur or pelvis bones), or vertebrae. The ability of REMS and DXA T-score values to assess the incidence and site of fractures was evaluated through an analysis of covariance.Results:Seven hundred twenty-one Caucasian women were enrolled. Ninety-five fractures occurred, in particular 41 at upper limb, 16 at hip, 15 at thorax, 14 at lower limb, 9 at vertebrae. Patients characteristics are reported in table. Considering subcategories of fractured patients, there were not statistically significant differences for age, height, weight and BMI.In the analysis of covariance including age and BMI as covariates, the difference of T-score values between fractured and non-fractured patients is statistically significant for REMS and DXA at both sites.Lower FN T-score values were found for patients with fractures at hip or vertebra with respect to non-fractured patients both for REMS and DXA (p&lt;0.001). Considering LS T-score, lower values were found for patients with fractures at hip, vertebra or upper limb with respect to non-fractured patients both for REMS and DXA (p&lt;0.001, Figure).Conclusion:REMS T-score measured at axial sites is an effective parameter for identification of patients at the risk of incident fragility fractures, in particular occurring at hip, vertebra or upper limb in a population-based sample of female subjects.

SUN-374 Decisions to Accept or Decline Pharmacologic Osteoporosis Therapy After Attending a Novel Patient-Centred Educonsult Program for Osteoporosis (PEP-OP)

Osteoporosis affects >200 million people, resulting in >8.9 million annual fragility fractures worldwide. Available medications can reduce fracture risk by 40–60%, although access to specialty osteoporosis services is limited, and many individuals remain unaware of their fracture risk and their treatment options. As the one-on-one ‘traditional consultation’ (TC) model of osteoporosis care is not time efficient (i.e. a single TC often requires >45 minutes), there is a need to identify innovative consultative models that can improve accessibility to osteoporosis care while maintaining quality. At our Osteoporosis Centre, we have implemented a group counseling model for this purpose: the Patient-Centred Educonsult Program for Osteoporosis (PEP-OP). Each two-hour PEP-OP session - co-facilitated by an osteoporosis physician and a nurse - provides up to 10 patients (the equivalent to 3–5 half-day physician clinics under the TC model) with a combined consultative and educational experience consisting of an individualized fracture risk assessment and extensive review of medications available to lower fracture risk. Patients are then encouraged to make an informed, autonomous decision about osteoporosis treatment initiation. Although the PEP-OP can accommodate a greater patient volume than the TC, and we have previously reported that the PEP-OP results in high patient satisfaction, it is not known whether PEP-OP produce similar results compared to TC in terms of treatment decisions. In this cohort study, we compared decisions to initiate osteoporosis therapy in PEP-OP (N=100) and TC (N=43) attendees. Ten-year risk of major osteoporotic fracture was estimated for each participant using the FRAX calculator, and participants were stratified based on whether their ten-year risk was ≥20% or <20%. Proportion of participants in each risk category who decided to initiate treatment were compared between the PEP-OP and TC groups. PEP-OP and TC groups were comparable in terms of age (63.3 vs 64.9 years), BMI (24.4 vs 24.9 kg/m2), previous fragility fractures (35 vs 25%), parental hip fractures (19 vs 23%), lumbar neck T-score (-2.5 vs -2.3), femoral neck T-score (-2.1 vs -2.1) and average FRAX estimate (13.1 vs 13.3%). The proportion of participants at high ten-year risk of major osteoporotic fracture (≥20%) who decided to initiate treatment was similar in both the PEP-OP (7/16, 44%) and TC (5/10, 50%) groups, according to the Chi Square Test (p=0.76). Among those with FRAX estimate of <20%, a similar proportion of patients in the PEP-OP (15/84, 18%) and TC (4/33, 12%) groups chose to undergo treatment (X2, p=0.45). In summary, decisions to initiate pharmacologic therapy were similar for the PEP-OP and the TC. Considering that the PEP-OP is acceptable to patients and is more efficient than the TC, this care model should be considered by other centers wishing to improve access to high-quality osteoporosis care.

SUN-380 Opportunistic Screening with Abdominal CT in Patients with Diabetes Can Identify Those at High Risk of Osteoporosis and Osteopenia

Background: Diabetes mellitus (DM) increases the risk of fracture at any given bone mineral density (BMD). However, the optimal strategy for osteoporosis screening with DXA is unknown in those with DM. A previously described strategy in the general population known as “Opportunistic Osteoporosis Screening” uses computer tomography (CT) images done for other reasons to assess the attenuation (density) of L1 in Hounsfield units (HU)—this was found to correlate with DXA-derived T-score. However, neither the methodology nor the cut-points have been specifically validated in those with DM. Thus, the goal of this study was to examine the performance of this methodology and define thresholds corresponding with low BMD in those with DM. Methods: This was retrospective study using electronic medical record data. Patients with DM were identified by ICD code. Those with both abdominal CT and DXA within a 6-month period were included, excluding patients with CKD stage 5, solid organ transplantation, bariatric surgery, or L1 hardware. L1 attenuation, measured by 2 readers on sagittal view, were averaged. A different reader assessed for vertebral fractures. Fractures of the hip, forearm, humerus, and pelvis were identified by ICD code. The lowest T-score of lumbar spine, femoral neck, total hip, or forearm (available in 11 subjects) was used to compare to L1 attenuation. ROC curves were derived from univariate logistic regression. Results: 320 subjects met study criteria; 10 (3.2%) had vertebral fractures, 8 (2.6%) had prior major non-vertebral fracture, and 33 (10.3%) had osteoporosis by BMD.The 18 subjects with major fractures had lower T-scores (-2.3 ± 1.4 vs. -0.8 ± 1.4, p<0.001) and lower L1 attenuation (104 ± 46 vs. 149 ± 47 HU, p<0.001). T-score and L1 attenuation had similar discrimination for prior fracture by area under the ROC curve (0.77 vs. 0.76, p=NS). Moderate osteopenia (T-score -1.5 or less) and L1 attenuation of 130 HU or less had identical sensitivities (72.2% for both) and similar specificities (69.2% vs. 62.5%, respectively) for prior fracture.In regards to L1 attenuation corresponding to DXA diagnosis of osteoporosis, 160 HU was 94% sensitive, while 110 HU was 80% specific. This is similar to the 90% sensitivity for 160 HU and 90% specificity for 110 HU previously reported in the general population. Given higher fracture risk in DM, moderate osteopenia (n=106) was also examined as an outcome: 130 HU was 61% sensitive and 71% specific. This threshold had similar or improved sensitivity and specificity among subgroups of insulin users, men, and women under age 65. Conclusion: Our results validate the use of opportunistic osteoporosis screening in patients with DM, which could help clinicians decide on the need for screening DXA. Patients with diabetes and L1 attenuation below 130 HU on CT scan should be considered for DXA screening to formally assess the risk of fracture.

Effects of supervised high-intensity resistance and impact training or machine-based isometric training on regional bone geometry and strength in middle-aged and older men with low bone mass: The LIFTMOR-M semi-randomised controlled trial.

Few data exist on the effects of bone-targeted exercise on geometric and biomechanical indices of bone strength in men. The Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men (LIFTMOR-M) trial was designed to compare the efficacy and safety of two novel, supervised, twice-weekly, high-intensity exercise programs in middle-aged and older men with osteopenia and osteoporosis on musculoskeletal health and risk factors related to falls and fractures. The current report includes secondary outcomes of the LIFTMOR-M exercise intervention trial. Our goal was to determine the effects of two supervised, twice-weekly, high-intensity exercise programs on bone geometry and strength of the proximal femur, and distal and proximal sites of the tibia and radius in middle-aged and older men with osteopenia and osteoporosis. Generally-healthy men (≥45years), with low lumbar spine (LS) and/or proximal femur areal bone mineral density (aBMD), were recruited from the community. Eligible participants were randomised to either eight months of twice-weekly supervised high-intensity progressive resistance and impact training (HiRIT) or supervised machine-based isometric axial compression (IAC) exercise training. Intervention group outcomes were compared at baseline and eight months with a matched but non-randomised control group (CON) who self-selected to usual activities. DXA scans (Medix DR, Medilink, France) of the skeletally non-dominant proximal femur were analysed using 3D hip software (DMS Group, France) to derive femoral neck (FN) and total hip (TH) bone mineral content (BMC), volume, and volumetric bone mineral density (vBMD) for total, trabecular and cortical bone compartments. Total FN cortical thickness was determined as well as anterior, posterior, lateral and medial subregions. pQCT scans (XCT-3000, Stratec, Germany) of the 4 and 38% sites of the tibia, and 4 and 66% sites of the radius were conducted to determine a range of geometric and bone structural strength indices. Intervention effects were examined using univariate ANCOVA of percent change, and repeated measures ANCOVA of raw baseline and follow-up data, controlling for initial values, using intention-to-treat and per-protocol approaches. Ninety-three men (67.1±7.5yrs, 175.2±6.7cm, 82.1±11.6kg, 26.7±3.5kg/m2) with lower than average aBMD (LS T-score -0.06±1.04, FN T-score -1.58±0.58, TH T-score -1.00±0.58) were recruited, and designated CON (n=26) or randomised to HiRIT (n=34) or IAC (n=33). Compliance to the supervised exercise programs did not differ (HiRIT 77.8±16.6% versus IAC 78.5±14.8%, p=0.872). HiRIT improved medial FN cortical thickness compared with CON (5.6±1.7% versus -0.1±1.9%, p=0.028) and IAC (5.6±1.7% versus 0.7±1.7%, p=0.044). Distal tibia total BMC, vBMD, area and bone strength index, and trabecular BMC and bone strength index all declined for CON compared with maintenance for both HiRIT and IAC (all p<0.05). HiRIT maintained distal tibia trabecular area compared with a loss in CON (0.2±0.5% versus -1.6±0.5%, p=0.013). HiRIT and IAC maintained distal radius total BMC compared with loss in CON (-0.1±0.7% versus -3.7±0.8%, p=0.001; 1.3±0.7% versus -3.7±0.8%, p<0.001, respectively). HiRIT and IAC maintained distal radius total bone strength index compared with loss in CON (1.4±1.4% versus -6.0±1.6%, p=0.001; 0.2±1.3% versus -6.0±1.6%, p=0.004, respectively). HiRIT reduced proximal radius cortical area compared with CON (-3.1±1.0% versus 1.1±1.2%, p=0.011) and IAC (-3.1±1.0% versus -0.2±1.0%, p=0.042). No between-group differences were detected in any pQCT-derived bone outcome at the diaphyseal tibia 38% site. Findings indicate that supervised HiRIT provides a positive stimulus to cortical bone at the medial FN compared with supervised IAC exercise, and both HiRIT and IAC preserve bone strength at the distal tibia and distal radius. These effects may translate into a reduced risk of lower and upper extremity fracture in middle-aged and older men with low bone mass.

New Zealand dietary patterns in relation to bone and nutritional health status among post-menopausal women

AbstractNutrients affect bone health status. However, dietary patterns advance insight into which particular foods influence bone and nutritional health status. The aim of this study was to explore the associations between dietary patterns, bone and nutritional health status in postmenopausal women. This cross-sectional study examined 127 postmenopausal women aged between 54–81 years. Body composition and bone health status were determined using dual-energy X-ray absorptiometry (DXA). The dietary composition was assessed by a validated food frequency questionnaire composed of 108 foods, of which 34 food groups were created. Dietary patterns (DP) were identified by principal component analysis. The bone and nutritional measures were regressed onto the dietary pattern. Five DPs were identified, two of which were associated with nutritional status. Fruit and carbohydrate DP was associated with decreased weight (r = -0.192, P = 0.038), body mass index (r = -0.184, P = 0.047) and body fat (r = -0.181, P = 0.050). Coffee and yoghurt/cream DP was associated with weight (r = 0.223, P = 0.015), body mass index (r = 0.245, P = 0.008) and body fat (r = 0.195, P = 0.036). Bone health status; spine T-score (r = 0.283, P = 0.002), hip T-score (r = 0.309, P = 0.001), femoral neck T-score (r = 0.317, P = 0.001) and whole-body bone mineral density (r = 0.261, P = 0.004) were also associated with coffee and yoghurt/cream DP. Milk products DP was associated with spine T-score (r = 0.304, P = 0.001). A dietary pattern characterized by high factor loadings of coffee, milk and yoghurt/cream was associated with higher BMD and T-scores. Although coffee intake has been associated with low bone mass, the impact of milk products appears to override the effects of coffee as an important determinant of bone health status in postmenopausal women.

The efficacy of pharmacotherapy in postmenopausal osteoporosis: a longitudinal observational study.

The aim of the study was an assessment of longitudinal changes in fracture probability in postmenopausal women. A group of 226 postmenopausal women at baseline mean age 66.46 ± 7.96 years were studied. There were 21 women without therapy, 102 taking calcium + vitamin D, and 103 women on antiresorptive therapy, in the study group. Data concerning clinical risk factors for osteoporosis and hip BMD were gathered. Fracture probability for major and hip fractures was established using FRAXTM. Mean follow-up time was 2.43 ± 0.59 years. Baseline FRAX value in the whole group for major fracture was 7.1 ± 4.18, and at follow-up it was 7.44 ± 4.04. Respective results for FRAX for hip fracture were 3.17 ± 2.69 and 3.02 ± 2.35. In the whole group the probability for major fractures significantly increased during follow-up (p < 0.05) and for hip fracture did not change. In non-treated patients and patients taking calcium + vitamin D the fracture probability increased significantly. In patients on antiresorptive therapy the fracture probability did not change, which was connected with an improvement in bone status assessed by DXA. Femoral neck T-score in the whole group did not change, in those not treated and taking calcium + vitamin D it decreased significantly (p < 0.05), while in treated women it increased significantly (p < 0.05). In patients with improved bone status the FRAX values for major and hip fractures decreased by 0.44 ± 1.62 and 0.36 ± 1.19, respectively. Conversely, in patients with worsening T-score value the FRAX values increased by 1.33 ± 1.42 and 0.66 ± 1.25, respectively. Antiresorptive therapy stabilises fracture probability in postmenopausal women due to improvement in bone status.

COPD as an independent risk factor for osteoporosis and fractures.

Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis and fractures, but screening and prophylactic measures to prevent both disorders are often neglected in this population. This case-control study assessed the prevalence of osteopenia, osteoporosis, and fractures in patients with COPD, and identified potential risk factors for fractures in this population. Overall, 91 patients with COPD (COPD group; COPDG) and 81 age- and sex-matched controls (control group; CG) were assessed with bone mineral density (BMD), thoracic/lumbar spine radiographs, and serum PTH and 25-hydroxyvitamin D (25[OH]D) levels. The occurrence of prior fractures was retrieved from clinical history. The prevalence of total fractures in the COPDG was 57.1% (odds of fracture 4.7 times greater compared with the CG), and the femoral neck T-score emerged as the best predictor of fractures. Compared with the CG, the COPDG had lower spine and femoral BMD (p ≤ 0.01) and 25(OH)D levels (p = 0.01) and 2.6 times greater odds of osteoporosis. Among men, vertebral fractures were more prevalent in the COPDG versus CG (25.9% vs. 6.5%, respectively, p = 0.01). The odds of fracture increased with femoral neck T-scores ≤ - 2.7 in the CG and ≤ - 0.6 in the COPDG. These results add robust evidence to an increased odds of osteoporosis and fractures in COPD. Fractures in the COPDG occurred at higher BMD values than expected, suggesting that COPD may be an independent marker of fracture risk, reinforcing a need for regular osteoporosis screening with BMD measurement and prophylaxis of fractures in patients with this disorder.

Obesity and leptin influence vitamin D metabolism and action in human marrow stromal cells

Obesity is associated with low serum 25-hydroxyvitamin D [s25(OH)D], high serum leptin, and generally high bone mineral density (BMD). Human Marrow Stromal Cells (hMSCs) differentiate to osteoblasts and are both a target and source of vitamin D metabolites in bone marrow. There is no information about the influence of obesity on vitamin D metabolism and osteoblastogenesis in hMSCs and little about direct effects of leptin on hMSCs. In this study, we tested the hypotheses that 1) obesity has an influence on the ex vivo constitutive expression of vitamin D-hydroxylase genes in hMSCs, and 2) recombinant human (rh) Leptin regulates the D-hydroxylases and promotes osteoblastogenesis in hMSCs. In a cohort of female subjects undergoing joint replacement surgery, the effects of Body Mass Index (BMI) and Fat Mass Index (FMI) on BMD T-scores and s25(OH)D were evaluated. hMSCs were isolated from bone tissues discarded during surgery. The direct effects of rh-Leptin on osteoblast differentiation and D-related genes in hMSCs were examined in vitro. There were positive correlations for BMD T-score of femoral neck and spine with BMI and FMI. Serum 25(OH)D levels in obese subjects were 71% of that in non-obese counterparts (p = 0.001). hMSCs from obese women had higher constitutive expression of CYP27A1/25-hydroxylase and vitamin D receptor. Those findings raised the mechanistic question of how obesity could influence vitamin D metabolism and osteoblast differentiation in hMSCs. Treating hMSCs with rh-Leptin in vitro significantly stimulated osteoblastogenesis. In addition, leptin downregulated CYP24A1 and upregulated CYP27B1, CYP27A1 and VDR, which play vital roles in vitamin D metabolism. Furthermore, co-treatment with leptin and vitamin D3 metabolites promoted ALP activity compared with either alone. This research demonstrates links between obesity, vitamin D metabolism, and osteoblastogenesis by which leptin's direct effects on D-metabolism and osteoblast differentiation in hMSCs may protect bone from low s25(OH)D in obese subjects.

Novel MRI-based score for assessment of bone density in operative spine patients

BackgroundGood bone quality is key in avoiding a multitude of afflictions, including osteoporotic fragility fractures and poor outcomes after spine surgery. In patients undergoing instrumented spine fusion, bone quality often dictates screw pullout strength, insertional torque, and vertebral body loading properties. While dual-energy X-ray absorptiometry (DEXA) screening is the current method of assessing bone mineral density, the majority of patients do not have DEXA measurements available before undergoing surgical instrumentation. PurposeTo create a simple magnetic resonance imaging (MRI)-based score to evaluate bone quality and evaluate the degree to which it correlates with conventional DEXA scores. Study Design/SettingRetrospective cohort. Patient SamplePatients ≥18 years of age undergoing spine surgery for degenerative conditions between 2013 and 2018. Outcome MeasuresCorrelation of the vertebral bone quality (VBQ) score with DEXA T-scores, and association between VBQ score and presence of osteopenia/osteoporosis. MethodsUsing noncontrast T1-weighted MRIs of the lumbar spine, the novel VBQ score was calculated for each patient. DEXA T-scores of the femoral neck and total hip were obtained and were compared with patient VBQ scores using linear regression and Pearson's correlation. ResultsAmong 68 patients included in this study, 37 were found to have osteopenia/osteoporosis (T-score < −1.0) based on DEXA. A greater VBQ score was significantly associated with the presence of osteopenia/osteoporosis with a predictive accuracy of 81%. VBQ scores correlated moderately with femoral neck T-scores, the lowest overall T-scores of each patient, and correlated fairly with total hip T-scores. ConclusionsThis is the first study to correlate the novel VBQ score obtained from MRIs with DEXA T-score. We found this score to be a significant predictor of healthy versus osteopenic/osteoporotic bone with an accuracy of 81%, and found that VBQ score was moderately correlated with femoral neck and overall lowest T-score.

Odanacatib for the treatment of postmenopausal osteoporosis: results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between -2·5 and -4·0 if no previous radiographic vertebral fracture, or between -1·5 and -4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than -4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43-40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45-60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40-0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39-0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68-0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42-0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40-0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66-0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95-1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90-1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02-1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58-1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98-1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02-1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10-1·71; p=0·0051). Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis. Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA.

Teriparatide treatment increases Hounsfield units in the lumbar spine out of proportion to DEXA changes.

The authors sought to assess whether Hounsfield units (HU) increase following teriparatide treatment and to compare HU increases with changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DEXA). A retrospective chart review was performed from 1997 to 2018 across all campuses at our institution. The authors identified patients who had been treated with at least 6 months of teriparatide and compared HU and BMD as measured on DEXA scans before and after treatment. Fifty-two patients were identified for analysis (46 women and 6 men, average age 67 years) who underwent an average of 20.9 ± 6.5 months of teriparatide therapy. The mean ± standard deviation HU increase throughout the lumbar spine (L1-4) was from 109.8 ± 53 to 133.9 ± 61 HU (+22%, 95% CI 1.2-46, p value = 0.039). Based on DEXA results, lumbar spine BMD increased from 0.85 to 0.93 g/cm2 (+9%, p value = 0.044). Lumbar spine T-scores improved from -2.4 ± 1.5 to -1.7 ± 1.5 (p value = 0.03). Average femoral neck T-scores improved from -2.5 ± 1.1 to -2.3 ± 1.0 (p value = 0.31). Teriparatide treatment increased both HU and BMD on DEXA in the lumbar spine, without a change in femoral BMD. The 22% improvement in HU surpassed the 9% improvement determined with DEXA. These results support some surgeons' subjective sense that intraoperative bone quality following teriparatide treatment is better than indicated by DEXA results. To the authors' knowledge, this is the first study demonstrating an increase in HU with teriparatide treatment.

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Case Presentation: A 72 year-old woman with a history of osteopenia, atrial fibrillation, hypothyroidism on levothyroxine, and cholangiocarcinoma status post-radioembolization, currently receiving chemotherapy with gemcitabine, cisplatin, and high-dose dexamethasone was evaluated for osteopenia. The patient underwent a dual-energy X-ray absorptiometry (DXA) scan with T-scores of lumbar-spine, hip, and femoral neck, found to be -1.7, -2.2, and -1.9, respectively. Upon review of the DXA scan the patient was noted to have a new radiopaque lesion noted in the L2 lumbar vertebral body (Fig.

Incident Fracture Risk in Type 2 Diabetic Postmenopausal Women in Mainland China: Peking Vertebral Fracture Study.

Using data from the Peking Vertebral Fracture Study, we conducted a longitudinal cohort study to investigate the association between type 2 diabetes mellitus (T2DM) and the risk of incident fractures, especially of vertebral fractures (VFs), and we also examined the modifying effect of body mass index (BMI) on this association and the effect of bone mineral density (BMD) T-score as a risk factor for incident fractures in T2DM. Chinese postmenopausal women were enrolled (n = 982), among whom 186 had T2DM. Incident VFs were confirmed by lateral radiographs of the thoracolumbar spine (T4-L5), while incident clinical non-VFs were self-reported. BMDs at the lumbar spine (LS) and femoral neck (FN) were measured by dual-energy X-ray absorptiometry. T2DM and non-DM women were at similar risk for VFs (OR 0.74, 95% CI 0.32-1.74), even adjusting for age, BMI, BMD, and previous fractures. Meanwhile, T2DM women had nearly twice the risk for non-VFs (HR 1.95, 95% CI 1.11-3.35) compared with non-DM women. After stratifying by BMI, the risk of VFs remained similar between diabetics and non-diabetics despite their BMI status (p for interaction = 0.470), and the risk of non-VFs was positively associated with T2DM only in women with BMI ≥ 25kg/m2 (HR 3.59, 95% CI 1.68-7.65) (p for interaction = 0.065). Although LS BMD T-score was similarly and negatively associated with incident VFs both in T2DM (OR 0.34, 95% CI 0.12-0.88) and non-DM women (OR 0.60, 95% CI 0.44-0.82) (p for interaction = 0.430), the FN BMD T-score was not found to be significantly associated with either non-VFs or VFs among T2DM women. Comparing T2DM and non-DM women with similar fracture risks, the mean difference in LS T-score was - 0.36 (95% CI - 1.77 to 1.04) for VF, and difference in FN T-score was 1.61 (95% CI - 0.11 to 3.34) for non-VF. In conclusion, Chinese postmenopausal women with T2DM had a similar risk of incident VFs, but a significantly higher risk of incident non-VF, compared to women without DM. Higher BMI did not modify the effect of T2DM on risk of VFs, but it increased the association between T2DM and risk of non-VFs. LS BMD T-score was similarly and negatively associated with VF risk in T2DM and non-DM women and appear to be useful for clinical evaluation of VF risk.

ESR1 Gene Variants Are Predictive of Osteoporosis in Female Patients with Crohn's Disease.

Decreased bone mass in patients with inflammatory bowel diseases (IBD) is a clinical problem with extremely severe consequences of osteoporotic fractures. Despite its increasing prevalence and the need for mandatory intervention and monitoring, it is often ignored in IBD patients’ care. Determining the biomarkers of susceptibility to bone mineral density disorder in IBD patients appears to be indispensable. We aim to investigate the impact of estrogen receptor gene (ESR1) gene polymorphisms on bone mineral density (BMD) in patients with ulcerative colitis (UC) and Crohn’s disease (CD), as they may contribute both, to osteoporosis and inflammatory processes. We characterised 197 patients with IBD (97 with UC, 100 with CD), and 41 controls carrying out vitamin D, calcium and phosphorus serum levels, and bone mineral density assessment at the lumbar spine and the femoral neck by dual-energy X-ray absorptiometry (DXA), ESR1 genotyping and haplotype analysis. We observed that women with CD showed the lowest bone density parameters, which corresponded to the ESR1 c.454-397T and c.454-351A allele dose. The ESR1 gene PvuII and XbaI TA (px) haplotype correlated with decreased femoral neck T-score (OR = 2.75, CI = [1.21–6.27], P-value = 0.016) and may be predictive of osteoporosis in female patients with CD.

FRAX-based intervention and assessment thresholds for osteoporosis in Iran.

The fracture risk assessment algorithm FRAX® has been recently calibrated for Iran, but guidance is needed on how to apply fracture probabilities to clinical practice. The age-specific ten-year probabilities of a major osteoporotic fracture were calculated in women with average BMI to determine fracture probabilities at two potential intervention thresholds. The first comprised the age-specific fracture probabilities associated with a femoral neck T-score of - 2.5 SD, in line with current guidelines in Iran. The second approach determined age-specific fracture probabilities that were equivalent to a woman with a prior fragility fracture, without BMD. The parsimonious use of BMD was additionally explored by the computation of upper and lower assessment thresholds for BMD testing. When a BMD T-score ≤ - 2.5 SD was used as an intervention threshold, FRAX probabilities in women aged 50years was approximately two-fold higher than in women of the same age but with an average BMD and no risk factors. The relative increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80years or more, a T-score of - 2.5 SD was actually protective. The 10-year probability of a major osteoporotic fracture by age, equivalent to women with a previous fracture rose with age from 4.9% at the age of 50years to 17%, at the age of 80years, and identified women at increased risk at all ages. Intervention thresholds based on BMD alone do not effectively target women at high fracture risk, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a "fracture threshold" target women at high fracture risk.