Evaluation of the association between osteoporotic vertebral compression fractures and psoas major/paraspinal muscle mass and ADC measured on MRI.

OBJECTIVE: Evaluate magnetic resonance imaging factors associated with osteoporotic vertebral compression fractures. MATERIALS AND METHODS: We retrospectively reviewed 457 patients' records. Age, sex, and body mass index were recorded. Two blinded readers measured psoas major and paraspinal muscle areas at the L3 vertebral body level on transverse T2-weighted magnetic resonance images and the mean apparent diffusion coefficient values of the non-fractured vertebrae from Th12 to L5. Inter-reader reliability for continuous variables was assessed by intraclass correlation coefficients. RESULTS: We evaluated 210 patients (103 [49.0%] men). The osteoporotic vertebral compression fractures group was older and had lower BMI and smaller psoas major and paraspinal muscle areas than the group without vertebral compression fractures (p < 0.001). The mean apparent diffusion coefficient was weakly correlated with paraspinal muscle area in the osteoporotic vertebral compression fractures group. The intraclass correlation coefficient value was 0.83, and the intraclass correlation coefficients of the psoas major and paraspinal muscles were 0.94 and 0.97, respectively. Multivariate analysis revealed that decreased psoas major and paraspinal muscle areas and increased mean apparent diffusion coefficient values were significantly associated with the presence of osteoporotic vertebral compression fractures (all p < 0.05). Psoas major and paraspinal muscle areas showed relatively high predictive accuracy (57%, 61%). CONCLUSION: Psoas major and paraspinal muscle areas at the L3 level and the mean apparent diffusion coefficient value of non-fractured vertebrae from the Th12 to L5 level were associated with osteoporotic vertebral compression fractures. This may contribute to detecting the potential risk of healthy individuals developing osteoporotic vertebral compression fractures.

Investigation of taurine and aqueous garlic extract diet supplementation effect on the healing of rat osteoporotic fractures.

BACKGROUND: We have evaluated the effects of taurine and aqueous garlic extract (AGE) as a dietary supplement on osteoporotic fracture (OPF) healing in the ovariectomized rat femur fracture model. METHODS: In this experimental animal study,twenty-four osteoporosis-remodeled female Wistar albino rats were randomly divided into 3 groups (n: 8) according to their supplemented diet; control, taurine, and AGE groups. Unilateral femur middiaphysis mini-open osteotomy was stabilized with Kirschner wires. Six weeks after osteotomy, the rats were sacrificed before the femurs were harvested and OPF healing was evaluated with biochemical, histologic, microcomputed-tomography, and scintigraphic methods. RESULTS: As an indicator of the antiosteoporotic effect, the calcium levels of the taurine group were significantly lower than the AGE and control groups in biochemical analyzes (p < 0.01). In histological studies, the new bone diameter and new bone volume values of the taurine group were significantly higher than the control group (p = 0.002 and p = 0.032, respectively), while higher trabecular-compact callus was observed in the taurine and AGE groups, respectively, compared to the control group. In morphological analyses, taurine and AGE groups had significantly higher bone volume/tissue volume, trabecular number, bone surface density, and lower trabecular separation than the control group (p < 0.05). The scintigraphic imaging showed a significant increase in osteoblastic activity of the taurine group compared to the control group (p = 0.005). DISCUSSION: Taurine and AGE have positive anabolic effects, respectively, on the healing of OPFs, demonstrated by biochemical, histological, morphological, and scintigraphic methods.

Evaluation of the relationship between abdominal fat distribution and osteoporotic vertebral compression fracture with MRI.

OBJECTIVE: This study was carried out to investigate the effects of abdominal subcutaneous adiposity and visceral adiposity on osteoporotic compression fractures. MATERIAL AND METHODS: The study group consisted of a total of 152 individuals aged 50-80 years; 76 were included in the vertebral fracture group and 76 in the healthy control group, whose bone mineral density was calculated. In order to determine the distribution of abdominal fat in both groups, four different measurements, i.e., sagittal abdominal diameter (SAD), abdominal diameter (AD), ventral subcutaneous thickness (VST), and dorsal subcutaneous thickness (DST), were made using lumbar magnetic resonance imaging (MRI). The visceral fat ratio (VFR) was also calculated based on these measurements. RESULTS: There was a significant difference between the patient and control groups in VST and DST values, both when gender distribution was and was not taken into account (p < 0.006 for all cases). There was no significant difference between the patient and control groups in SAD and AS values, both when only female patients were considered, and gender distribution was not taken into account (p > 0.25 for all cases). On the other hand, in the analysis, when only male patients were considered, the SAD and AD values of the patient group were found to be significantly lower than those of the control group (p = 0.046 and p = 0.048, respectively). CONCLUSION: In conclusion, the study findings indicated that high SAD values in the male gender and high VST and DST values in both genders were associated with low lumbar vertebral fracture risk.

Bone architecture, bone material properties, and bone turnover in non-osteoporotic post-menopausal women with fragility fracture.

Macro- and microarchitectural, bone material property, dynamic histomorphometric, and bone turnover marker data were studied in normal bone mineral density (BMD) post-menopausal women with fragility fracture. Women with fracture had thinner iliac cortices and more homogeneous bone material properties in cortical bone than age/BMD-matched non-fracture women. Low cortical thickness and bone tissue heterogeneity in normal BMD women are associated with prevalent fragility fracture. INTRODUCTION: Bone mass (bone mineral density, (BMD)) of the spine and hip is today's best single measurement for evaluating future fragility fracture risk. However, the majority of fragility fractures occur in women with BMD T-score above the WHO osteoporotic BMD threshold of - 2.5, indicating that non-BMD endpoints may play a role in their fragility fractures. We hypothesize that in non-osteoporotic women, bone micoarchitecture, bone material properties, dynamic histomorphometric endpoints, and bone turnover markers are related to fragility fracture. METHODS: Two groups (N = 60 each) of post-menopausal women with total hip BMD T-score ranging from + 0.3 to -2.49 were recruited: fragility fracture and age/BMD-matched, non-fragility fracture women. Normal (T-score > - 0.99) and osteopenic (T-score ≤ - 1.0) BMD cohorts were designated within both the fracture and non-fracture groups. Transiliac biopsy specimens were obtained to evaluate dynamic histomorphometric and microarchitectural endpoints and bone material properties by static and dynamic nanoindentation testing. All variables for fracture and non-fracture women within each BMD cohort were compared by the Wilcoxon signed-rank test (P < 0.01). RESULTS: Compared to non-fracture/normal BMD women, fracture/normal BMD women display lower iliac cortical thickness (- 12%, P = 0.0041) and lower heterogeneity of hardness (- 27%, P = 0.0068), elastic modulus (- 35%, P = 0.0009), and storage modulus (- 23%, P = 0.0054) in the cortical bone tissue, and lower heterogeneity of hardness (- 13%, P = 0.0088) in the trabecular bone tissue. Osteopenic women had no abnormalities related to fracture status. CONCLUSION: Post-menopausal women with normal BMD and fragility fracture have low cortical thickness and heterogeneity of several bone material properties in cortical and trabecular mineralized bone tissue. These differences may explain a portion of the excess bone fragility in women with normal BMD and fragility fracture.

Factors Associated With Skeletal Muscle Mass Increase by Rehabilitation in Older Adults With Vertebral Compression Fractures.

Age-related sarcopenia and osteoporosis-related fractures are critical health issues. Therefore, this study aimed to assess skeletal muscle mass changes in older patients with vertebral compression fractures undergoing rehabilitation and to evaluate factors associated with muscle increases. This study included 179 patients aged ≥80 years in rehabilitation wards with vertebral compression fractures. Appendicular skeletal muscle index was significantly higher at discharge (5.22 ± 1.04 kg/m2, p < .001) than on admission (5.03 ± 1.00 kg/m2). Multiple logistic regression analysis showed that length of hospital stay was significantly associated with increased skeletal muscle index (odds ratios, 1.020; 95% confidence intervals [1.000, 1.032]), whereas age, sex, body mass index, functional independence measure, protein intake, and exercise therapy duration were not. Participants with vertebral compression fractures aged ≥80 years achieved significantly increased skeletal muscle mass in rehabilitation wards. In addition, length of hospital stay was the factor independently associated with increased skeletal muscle index.

Proximal Hip Geometry, Trabecular Bone Score, Bone Mineral Density and Bone Mineral Parameters in Patients With Cryptogenic and Hepatitis B Related Cirrhosis- A Study From the Indian Subcontinent.

The impact of cryptogenic cirrhosis on skeleton has not been studied in Indian context. So this study investigated bone health in male patients with early cryptogenic cirrhosis as defined by Child-Turcot-Pugh A (CTP-A) categorization and compared it with patients diagnosed to have hepatitis B related chronic liver disease (CLD) on treatment and age, sex-matched healthy controls. It was a cross-sectional study, in which thirty male subjects were recruited in each group. Bone mineral density (BMD), trabecular bone score (TBS), hip structural analysis (HSA) and bone mineral parameters were assessed. The mean ±SD age of the study subjects was 39.3 ± 9.2 years. The mean 25-hydroxy vitamin D was significantly lower in subjects with cryptogenic cirrhosis as compared to controls (p = 0.001). Subjects with cryptogenic cirrhosis had significantly lower (1.297 ± 0.099) TBS as compared to hepatitis-B related CLD (1.350 ± 0.094) control subjects (1.351 ± 0.088) (p = 0.04). BMD at the hip and lumbar spine was also significantly lower in subjects with cryptogenic cirrhosis as compared to hepatitis-B related CLD and healthy age matched controls (p < 0.05). Most components of HSA were significantly affected in subjects with cryptogenic cirrhosis as compared to control subjects (p < 0.05). Patients with cryptogenic cirrhosis had significantly low TBS and BMD lumbar spine and hip as well as poor proximal hip geometry which may be good predictor of future fragility fractures.

Role of nitric oxide in type 1 diabetes-induced osteoporosis.

Type 1 diabetes (T1D)-induced osteoporosis is characterized by decreased bone mineral density, bone quality, rate of bone healing, bone formation, and increased bone resorption. Patients with T1D have a 2-7-fold higher risk of osteoporotic fracture. The mechanisms leading to increased risk of osteoporotic fracture in T1D include insulin deficiency, hyperglycemia, insulin resistance, lower insulin-like growth factor-1, hyperglycemia-induced oxidative stress, and inflammation. In addition, a higher probability of falling, kidney dysfunction, weakened vision, and neuropathy indirectly increase the risk of osteoporotic fracture in T1D patients. Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of T1D-induced osteoporotic fracture. This review discusses the role of NO in osteoblast-mediated bone formation and osteoclast-mediated bone resorption in T1D. In addition, the mechanisms involved in reduced NO bioavailability and activity in type 1 diabetic bones as well as NO-based therapy for T1D-induced osteoporosis are summarized. Available data indicates that lower NO bioavailability in diabetic bones is due to disruption of phosphatidylinositol 3­kinase/protein kinase B/endothelial NO synthases and NO/cyclic guanosine monophosphate/protein kinase G signaling pathways. Thus, NO bioavailability may be boosted directly or indirectly by NO donors. As NO donors with NO-like effects in the bone, inorganic nitrate and nitrite can potentially be used as novel therapeutic agents for T1D-induced osteoporosis. Inorganic nitrites and nitrates can decrease the risk for osteoporotic fracture probably directly by decreasing osteoclast activity, decreasing fat accumulation in the marrow cavity, increasing osteoblast activity, and increasing bone perfusion or indirectly, by improving hyperglycemia, insulin resistance, and reducing body weight.

Role of paraspinal muscle degeneration in the occurrence and recurrence of osteoporotic vertebral fracture: A meta-analysis.

Purpose: Recently, the effects of paraspinal muscle degeneration on osteoporotic vertebral fractures (OVFs) have attracted the attention of researchers; however, studies are limited, and their results vary. Hence, this study aimed to determine the role of paraspinal muscle degeneration in the occurrence and recurrence of OVF. Methods: Following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guideline, the PubMed, Embase, Web of Science, Wanfang Data, China National Knowledge Infrastructure, and ClinicalTrials.gov databases were comprehensively searched for relevant studies. Studies comparing the cross-sectional area (CSA) or fatty infiltration (FI) of the paraspinal muscles (including the psoas (PS), erector spinae plus multifidus (ES+MF), quadratus lumborum) in patients with and without initial OVF, or with and without recurrent OVF were included and analyzed. Results: Eleven studies were included in the meta-analysis. Seven studies investigated the effects of paraspinal muscles on initial OVF, and the overall results revealed significantly lower CSAES+MF (SMD: -0.575, 95% CI: -0.866 to -0.285) and CSAPS (SMD: -0.750, 95% CI: -1.274 to -0.226), and higher FI (SMD: 0.768, 95% CI: 0.475 to 1.062) in the fracture group. Meanwhile, four studies evaluated the effects of the paraspinal muscles on recurrent OVF, and the pooled results demonstrated significantly higher FI (SMD:0.720, 95% CI: 0.258 to 1.182) in the refracture group, although no significant difference in CSAES+MF (SMD: -0.103, 95% CI: -0.395 to 0.189) was observed between the two groups. Conclusions: Paraspinal muscle degeneration plays a role in the occurrence and recurrence of OVF. Assessing the paraspinal muscles may be useful for identifying high-risk populations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42021276681).

Population-based Analysis for Risk of Suicide Death in Elderly Patients after Osteoporotic Fracture: a Nested Case-Control Study.

BACKGROUND: The purpose of study was to investigate the incidence rate of suicide in elderly patients with osteoporotic fractures in a nested case-control model and to analyze the change in the risk of suicide death over time after each osteoporotic fracture. METHODS: We used the National Health Insurance Service-Senior cohort of South Korea. Suicide cases and controls were matched based on sex and age at the index date. Controls were randomly selected at a 1:5 ratio from the set of individuals who were at risk of becoming a case at the time when suicide cases were selected. Conditional logistic regression analysis was performed to evaluate the association between each type of osteoporotic fracture and the risk of suicide death. RESULTS: Three thousand seventy suicide cases and 15,350 controls were identified. Patients with hip fracture showed an increased risk of suicide death within 1 year of fracture (adjusted odds ratio [aOR] = 2.64; 95% confidence interval [CI], 1.57-4.46; P < 0.001) compared to controls. However, the increased risk of suicide death in patients with hip fracture lasted up to 2 years (aOR = 1.59; 95% CI, 1.04-2.41; P = 0.031). Spine fracture increased the risk of suicide deaths for all observation periods. There was no evidence that humerus fracture increased the risk of suicide death during the observational period. Radius fracture increased only the risk of suicide death within 2 years of fracture (aOR = 1.43; 95% CI, 0.74-2.77; P = 0.282). CONCLUSION: There were noticeable differences in both degree and duration of increased suicide risks depending on the type of osteoporotic fracture. Mental stress and suicide risk in elderly patients after osteoporotic fracture should be assessed differently depending on the types of fracture.

Risk factor analysis of fragility fractures in rheumatoid arthritis: A 3-year longitudinal, real-world, observational, cohort study.

OBJECTIVES: To explore the risk factors for fragility fractures in rheumatoid arthritis (RA) patients using a 3-year longitudinal, observational cohort study. METHODS: This RA registry study included consecutive RA patients in the outpatient clinic of Chang Gung Memorial Hospital since September 1, 2014. The demographics, clinical characteristics, lifestyle, evidence of previous fracture, risk factors according to the Fracture Risk Assessment Tool (FRAX®), and the FRAX score of each participant were recorded. The participants were categorized into the new incident fracture (group A) and no incident fracture (group B) groups based on evidence or absence of new incident fractures and propensity score matching (age and gender, 1:2). RESULTS: Overall, 477 participants completed the 3-year observation period. After matching, 103 and 206 participants were allocated to groups A and B, respectively. The non-adjusted model revealed, presented as hazard ratio (HR) (95% confidence interval [CI]), that the presence of co-morbidity (1.80 [1.17-2.78], p = 0.008), Health Assessment Questionnaire Disability Index (1.35 [1.07-1.69], p = 0.010), lower baseline hip bone mineral density (0.11 [0.02-0.48], p = 0.004), longer disease duration (1.02 [1.00-1.04], p = 0.026), higher FRAX score of major fracture (1.03 [1.02-1.04], p<0.001) or hip fracture (1.03 [1.02-1.04], p<0.001), and previous fracture history (2.65 [1.79-3.94], p<0.001) were associated with new incident fracture. After adjustment, it was disclosed that a previous fracture is an independent risk factor for fragility fractures in RA patients (2.17 [1.20-3.90], p = 0.010). CONCLUSIONS: In addition to aging and disease-related factors, previous fracture history is the most important risk factor for fragility fractures in RA patients.

Clinical and imaging features of surgically treated low lumbar osteoporotic vertebral collapse in patients with Parkinson's disease.

Osteoporosis and Parkinson's disease (PD) are age-related diseases, and surgery for osteoporotic vertebral collapse (OVC) in PD patients become more common. OVC commonly affects the thoracolumbar spine, but low lumbar OVC is frequent in patients with lower bone mineral density (BMD). The aim of this study was to identify differences in clinical and imaging features of low lumbar OVC with or without PD and to discuss the appropriate treatment. The subjects were 43 patients with low lumbar OVC below L3 who were treated surgically, including 11 patients with PD. The main clinical symptoms were radicular pain in non-PD cases and a cauda equina sign in PD cases. Rapid progression and destructive changes of OVC were seen in patients with PD. The morphological features of OVC were flat-type in non-PD cases with old compression fracture, and destruction-type in PD cases without old compression fracture. Progression of PD was associated with decreased lumbar lordosis, lower lumbar BMD, and severe sarcopenia. High postoperative complication rates were associated with vertebral fragility and longer fusion surgery. Progression of postural instability as a natural course of PD may lead to mechanical stress and instrumentation failure. Invasive long-fusion surgery should be avoided for single low lumbar OVC.

Osteoporotic Fractures and Vertebral Body Reshaping in Children With Glucocorticoid-treated Rheumatic Disorders.

CONTEXT: Osteoporotic fractures are an important cause of morbidity in children with glucocorticoid-treated rheumatic disorders. OBJECTIVE: This work aims to evaluate the incidence and predictors of osteoporotic fractures and potential for recovery over six years following glucocorticoid (GC) initiation in children with rheumatic disorders. METHODS: Children with GC-treated rheumatic disorders were evaluated through a prospective inception cohort study led by the Canadian STeroid-induced Osteoporosis in the Pediatric Population (STOPP) Consortium. Clinical outcomes included lumbar spine bone mineral density (LS BMD), vertebral fractures (VF), non-VF, and vertebral body reshaping. RESULTS: A total of 136 children with GC-treated rheumatic disorders were enrolled (mean age 9.9 years, SD 4.4). The 6-year cumulative fracture incidence was 16.3% for VF, and 10.1% for non-VF. GC exposure was highest in the first 6 months, and 24 of 38 VF (63%) occurred in the first 2 years. Following VF, 16 of 19 children (84%) had complete vertebral body reshaping. Increases in disease activity and body mass index z scores in the first year and declines in LS BMD z scores in the first 6 months predicted incident VF over the 6 years, while higher average daily GC doses predicted both incident VF and non-VF. LS BMD z scores were lowest at 6 months (mean -0.9, SD 1.2) and remained low by 6 years even when adjusted for height z scores (-0.6, SD 0.9). CONCLUSION: VF occurred early and were more common than non-VF in children with GC-treated rheumatic disorders. Eighty-four percent of children with VF underwent complete vertebral body reshaping, whereas vertebral deformity persisted in the remainder of children. On average, LS BMD z scores remained low at 6 years, consistent with incomplete recovery.

Serum Glycine Levels Are Associated With Cortical Bone Properties and Fracture Risk in Men.

CONTEXT: In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD). OBJECTIVE: To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk in men. METHODS: In the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n = 965) and 5-year follow-up (n = 546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high-resolution peripheral quantitative computed tomography. Urinary (n = 2682) glycine was analyzed at baseline. X-ray-validated fractures (n = 594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures). RESULTS: Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n = 7543) combining MrOS Sweden data with data from 3 other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (P = 7.7 × 10-9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (P = 0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum: hazard ratio [HR] per SD increase = 1.22, 95% CI, 1.05-1.43; urine: HR = 1.13, 95% CI, 1.02-1.24). These fracture associations were only marginally reduced in models adjusted by FRAX with BMD. CONCLUSIONS: Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.

The Association Between Cholecystectomy and the Risk for Fracture: A Nationwide Population-Based Cohort Study in Korea.

Objectives: To evaluate the risk of fracture in individuals with a history of cholecystectomy in Korean population. Methods: Individuals (n = 143,667) aged ≥ 40 y who underwent cholecystectomy between 2010 and 2015 and the controls (n = 255,522), matched by age and sex, were identified from the database of the Korean National Health Insurance Services. The adjusted hazard ratio (aHR) and 95% confidence interval (CI) of fracture were estimated following cholecystectomy, and a Cox regression analysis was performed. Results: The incidence rates of all fractures, vertebral, and hip fractures were 14.689, 6.483 and 1.228 cases per 1000 person-years respectively in the cholecystectomy group, whereas they were 13.862, 5.976, and 1.019 cases per 1000 person-years respectively in the control group. After adjustment for age, sex, income, place of residence, diabetes mellitus, hypertension, dyslipidemia, smoking, alcohol drinking, exercise, and body mass index, patients who underwent cholecystectomy showed an increased risk of all fractures, vertebral fractures, and hip fractures (aHR [95% CI]: 1.095 [1.059-1.132], 1.134 [1.078-1.193], and 1.283 [1.139-1.444] for all fractures, vertebral fractures, and hip fractures, respectively). The risk of vertebral fractures following cholecystectomy was more prominent in the young age group (40 to 49 y) than in the old age group (≥ 65 y) (1.366 [1.082-1.724] vs. 1.132 [1.063-1.206], respectively). However, the incidence of hip fractures following cholecystectomy was not affected by age. Conclusion: Individuals who underwent cholecystectomy have an increased risk of fracture. In the younger population, the risk of vertebral fractures may be further increased following cholecystectomy.

Potential Role of Perilacunar Remodeling in the Progression of Osteoporosis and Implications on Age-Related Decline in Fracture Resistance of Bone.

PURPOSE OF REVIEW: We took an interdisciplinary view to examine the potential contribution of perilacunar/canalicular remodeling to declines in bone fracture resistance related to age or progression of osteoporosis. RECENT FINDINGS: Perilacunar remodeling is most prominent as a result of lactation; recent advances further elucidate the molecular players involved and their effect on bone material properties. Of these, vitamin D and calcitonin could be active during aging or osteoporosis. Menopause-related hormonal changes or osteoporosis therapies affect bone material properties and mechanical behavior. However, investigations of lacunar size or osteocyte TRAP activity with age or osteoporosis do not provide clear evidence for or against perilacunar remodeling. While the occurrence and potential role of perilacunar remodeling in aging and osteoporosis progression are largely under-investigated, widespread changes in bone matrix composition in OVX models and following osteoporosis therapies imply osteocytic maintenance of bone matrix. Perilacunar remodeling-induced changes in bone porosity, bone matrix composition, and bone adaptation could have significant implications for bone fracture resistance.

The atherogenic index of plasma is related to a degraded bone microarchitecture assessed by the trabecular bone score in postmenopausal women: The Camargo Cohort Study.

OBJECTIVE: To assess the association between the atherogenic index of plasma (AIP) and the trabecular bone score (TBS) in postmenopausal women. Furthermore, to analyze its relationship with bone mineral density (BMD), and serum concentrations of 25OHD, PTH, and bone turnover markers. STUDY DESIGN: Cross-sectional study nested in a population-based cohort of 1,367 postmenopausal women aged 44-94 years. Participants were classified according to TBS values (<1.230, between 1.230-1.310 and >1.310) and regarding a widely accepted cut-off point of ≥0.11 for AIP. We analyzed TBS, BMD, serum levels of 25OHD, PTH, P1NP, CTX, and clinical covariates. A multivariate analysis was performed to assess the adjusted association between AIP and TBS. RESULTS: The mean age of participants was 63±10 years. Women with TBS values <1.230 were older, had greater BMI, greater prevalence of fractures after the age of 40 years, more years since menopause, higher values of AIP, and significantly lower levels of HDL-C, serum phosphate, and 25OHD. AIP values ≥0.11 were not associated with the presence of densitometric osteoporosis (OR=0.83, 95%CI 0.58-1.18; p = 0.30) but, in multivariate analysis, AIP values ≥0.11 were related to a degraded microarchitecture after controlling for age, BMI, smoking, diabetes status, ischemic heart disease, statin use, GFR, a fragility fracture at over 40 years of age and lumbar osteoporosis by DXA, with an adjusted OR=1.61 (95%CI 1.06-2.46; p = 0.009). CONCLUSIONS: AIP is significantly and independently associated with a degraded bone microarchitecture as measured by TBS. In this sense, AIP might be a useful tool in the overall assessment of bone metabolism in postmenopausal women.

Low bone density, vertebral fracture and FRAX score in kidney transplant recipients: A cross-sectional cohort study.

BACKGROUND: Kidney transplantation (KT) recipients are at increased risk of low bone density (LBD) and fractures. In this retrospective study, we investigated bone mineral density (BMD), vertebral fractures, calculated risk for major osteoporotic fractures (MOF), and hip fractures in the KT recipients. PATIENTS-METHOD: Patients who completed at least one year after KT were included in the analysis. Demographic, clinical, and laboratory data were recorded. Measurements of BMD were performed by dual-energy X-ray absorptiometry. Vertebral fractures were assessed using semi-quantitative criteria with conventional radiography. The ten-year risk for MOF and hip fracture were calculated using the FRAX@ tool with BMD. RESULTS: One hundred fifty-three KT recipients were included in the study. The population included 77 women. The mean age at evaluation was 46,5±11,9 years. Seventy-eight (50.9%) patients had normal femoral neck BMD while osteoporosis and osteopenia at the femoral neck were present in 12 (7.8%) and 63 (41.1%) of the patients, respectively. Age at evaluation was the risk factor for LBD (OR 1.057; 95% CI 1.024-1.091; p = 0.001). In female KT recipients, LBD was principally affected by menopausal status whereas in males, mammalian target of rapamycin (mTOR) inhibitor use and lower BMI levels were the risk factors. The prevalent vertebral fracture was found in 43.4% of patients. In multivariate analysis, only steroid use (OR 0.121; 95% CI 0.015-0.988; p = 0.049) was found to be associated with prevalent fracture. Among all KT recipients, 1.9% had a high MOF probability (≥20% risk of fracture), and 23.5% had high hip fracture probability (≥3% risk of hip fracture) according to FRAX. CONCLUSION: Exploring the prevalence of LBD and vertebral fracture and the risk factors would help clinicians to modify long-term follow-up strategies. Furthermore, the high hip fracture risk probability in our cohort suggested that there is a need for longitudinal studies to confirm the validity of the FRAX tool in the transplant population.

Prediction of Fracture Risk From Early-Stage Bone Markers in Patients With Osteoporosis Treated With Once-Yearly Administered Zoledronic Acid.

The prevention of fractures is the ultimate goal of osteoporosis treatments. To achieve this objective, developing a method to predict fracture risk in the early stage of osteoporosis treatment would be clinically useful. This study aimed to develop a mathematical model quantifying the long-term fracture risk after 2 annual doses of 5 mg of once-yearly administered zoledronic acid or placebo based on the short-term measurement of bone turnover markers or bone mineral density (BMD). The data used in this analysis were obtained from a randomized, placebo-controlled, double-blind, 2-year study of zoledronic acid that included 656 patients with primary osteoporosis. Two-year individual bone resorption marker (tartrate-resistant acid phosphatase 5b [TRACP-5b]) and lumbar spine (L2-L4) BMD profiles were simulated using baseline values and short-term measurements (at 3 months for TRACP-5b and 6 months for BMD) according to the pharmacodynamic model. A new parametric time-to-event model was developed to describe the risk of clinical fractures. Fracture risk was estimated using TRACP-5b or BMD and the number of baseline vertebral fractures. As a result, the fracture risk during the 2 years was successfully predicted using TRACP-5b or BMD. The 90% prediction intervals well covered the observed fracture profiles in both models. Therefore, TRACP-5b or BMD is useful to predict the fracture risk of patients with osteoporosis, and TRACP-5b would be more useful because it is an earlier marker. Importantly, the developed model allows clinicians to inform patients of their predicted response at the initial stage of zoledronic acid treatment.

Antidiabetic Treatment, Level of Glycemic Control, and Risk of Fracture in Type 2 Diabetes: a Nested, Case-Control Study.

CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have an increased risk of low-trauma fractures. However, the effect of antidiabetic medication in relation to glycemic control on the risk of fracture is poorly understood. OBJECTIVE: This work aimed to evaluate the association between the level of glycemic control, use of antidiabetic medication, and risk of low-trauma fractures in patients with newly diagnosed T2DM. METHODS: We conducted a nested case-control analysis among individuals registered in the Clinical Practice Research Datalink. The base population consisted of patients with newly diagnosed T2DM from 1995 to 2017. Cases were patients with a low-trauma fracture after T2DM diagnosis. We matched 4 controls to each case. Exposures of interest were glycemic control (last glycated hemoglobin [HbA1c] level before fracture) and type of diabetes treatment. We conducted conditional logistic regression analyses adjusted for several confounders. RESULTS: We identified 8809 cases and 35 219 controls. Patients with current metformin use and HbA1c levels of less than 7.0% and between 7.0-8.0% had a reduced risk of fractures (adjusted odds ratio 0.89; 95% CI, 0.83-0.96 and 0.81; 95% CI, 0.73-0.90, respectively) compared with untreated patients. However, in patients receiving metformin plus 1 or 2 other antidiabetic drugs, or insulin (alone or in addition to other antidiabetic medication), the level of glycemic control was not associated with the risk of fracture compared with untreated patients. CONCLUSIONS: While patients with good or medium glycemic control receiving current metformin monotherapy had a lower risk of fracture compared with untreated patients, glycemic control in patients receiving treatment other than metformin was not associated with risk of fracture.

Pentosidine and carboxymethyl-lysine associate differently with prevalent osteoporotic vertebral fracture and various bone markers.

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22-2.07; P < 0.001), but not with lumbar BMD. In contrast, a significant negative correlation was found between CML and lumbar BMD (r = - 0.180; P < 0.001), and this relationship was significant after adjustment for confounders (OR 0.84, 95% CI 0.76-0.93; P < 0.01). Although patients with prevalent vertebral fracture had significantly higher CML levels, the association between CML and prevalent vertebral fracture did not reach significance in the multivariate regression model. Both PEN and CML may play important roles in bone health for postmenopausal women, possibly via different mechanisms.