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.

Promotion of Bone Formation in a Rat Osteoporotic Vertebral Body Defect Model via Suppression of Osteoclastogenesis by Ectopic Embryonic Calvaria Derived Mesenchymal Stem Cells.

Osteoporotic vertebral compression fractures (OVCFs) are the most prevalent fractures among patients with osteoporosis, leading to severe pain, deformities, and even death. This study explored the use of ectopic embryonic calvaria derived mesenchymal stem cells (EE-cMSCs), which are known for their superior differentiation and proliferation capabilities, as a potential treatment for bone regeneration in OVCFs. We evaluated the impact of EE-cMSCs on osteoclastogenesis in a RAW264.7 cell environment, which was induced by the receptor activator of nuclear factor kappa-beta ligand (RANKL), using cytochemical staining and quantitative real-time PCR. The osteogenic potential of EE-cMSCs was evaluated under various hydrogel conditions. An osteoporotic vertebral body bone defect model was established by inducing osteoporosis in rats through bilateral ovariectomy and creating defects in their coccygeal vertebral bodies. The effects of EE-cMSCs were examined using micro-computed tomography (µCT) and histology, including immunohistochemical analyses. In vitro, EE-cMSCs inhibited osteoclast differentiation and promoted osteogenesis in a 3D cell culture environment using fibrin hydrogel. Moreover, µCT and histological staining demonstrated increased new bone formation in the group treated with EE-cMSCs and fibrin. Immunostaining showed reduced osteoclast activity and bone resorption, alongside increased angiogenesis. Thus, EE-cMSCs can effectively promote bone regeneration and may represent a promising therapeutic approach for treating OVCFs.

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.

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.

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.

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.

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.

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.

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.

Cortical Bone Microarchitecture in Dialysis Patients.

BACKGROUND: The incidence of skeletal fractures is high in dialysis patients. Current available tools are insufficient to predict bone fragility. We analyzed the microarchitecture in patients on dialysis therapy using bone biopsies and peripheral microcomputed tomography. METHODS: We analyzed 12 trans-iliac bone biopsies of patients with recent fractures. Bone microarchitecture was assessed in the bone cores by histology (2D-), microcomputed tomography (3D-µCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia. RESULTS: Trabecular bone volume/tissue volume was similar in 2D histology and 3D-µCT (p = 0.40), while lower in HR-pQCT (p < 0.01). There was no correlation in trabecular microarchitectural indices between 2-histology and 3D-µCT, or HR-pQCT. The 3D-µCT cortical thickness (Ct.Th) were positively correlated with 2D (p < 0.05), but with HR-pQCT (p = 0.33). Ct.Th was lower in patients with ≥2 vertebral fractures than with one fracture. CONCLUSIONS: 3D-µCT is a reliable method for the measurement of cortical bone in bone biopsies. Prospective studies are awaited to address its value in discriminating fracture risk.

Trabecular Bone Score (TBS) Predicts Fracture in Ankylosing Spondylitis: The Manitoba BMD Registry.

INTRODUCTION: Ankylosing spondylitis (AS) is a chronic inflammatory disease of the spine characterized among other features by spinal boney proliferation, back pain, loss of flexibility, and increased fracture risk. Overlying bone limits the utility of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) in the spine. Trabecular bone score (TBS) is a bone texture measurement derived from the spine DXA image that indicates bone quality and fracture risk independent of BMD. METHODOLOGY: Using the Manitoba Bone Density Program database, patients with diagnosis codes for ankylosing spondylitis, baseline DXA and lumbar spine TBS were identified. Incident nontraumatic fractures (major osteoporotic [MOF], clinical spine, hip, and all fracture) were identified from population based databases. Cox-proportional hazard models are presented. RESULTS: We identified 188 patients with diagnosed AS. TBS was lower in those with incident MOF (1.278 ± 0.126, compared to 1.178 ± 0.136, p < 0.001). Unadjusted TBS and FRAX-MOF-BMD adjusted predicted major osteoporotic fracture (N = 19) (hazard ratio [HR] 2.04, 95% confidence interval [CI]: 1.28-2.26, p = 0.003; HR 1.81, 95% CI: 1.11-2.96, p = 0.018). TBS unadjusted and FRAX-MOF-BMD adjusted also predicted clinical spine fracture (N = 7) (HR 2.50, 95% CI: 1.17-5.37; p = 0.019; HR 2.40 95% CI: 1.1-5.25; p = 0.028). Higher HRs were observed for prediction of hip fracture (N = 6), but these did not achieve statistical significance (FRAX-adjusted HR 1.74, 95% 0.73-4.17; p = 0.211). Unadjusted models show TBS was predictive of all fracture (N = 27) (HR 1.60, 95% CI: 1.08-2.39; p = 0.020), which was borderline significant after adjustment for FRAX-MOF-BMD (HR 1.51, 95% CI: 1.00-2.29; p = 0.052). CONCLUSION: We report the first analysis of TBS for fracture prediction as an incident event in AS. TBS independently predicted major osteoporotic and clinical spine fracture in AS independent of FRAX.

Assessment of Bone and Muscle Measurements by Peripheral Quantitative Computed Tomography in Geriatric Patients.

The loss of bone and muscle mass increases the risk of osteoporotic fractures. Dual energy X-ray absorptiometry (DXA) loses sensitivity in older age. The purpose of this study was to evaluate bone and muscle measurements of peripheral quantitative computed tomography (pQCT) in a geriatric cohort with osteoporosis. Bone mineral density and muscle area of 168 patients aged 65 years and older (76.3 ± 6.5) were measured with pQCT at distal forearm additionally to an osteoporosis assessment consisting of anamnesis, blood test and DXA of lumbar spine and hip. Prior fractures were categorized in minor and major osteoporotic fractures. Logistic regression was used to show the association of bone mineral density and muscle area with major fractures. 54.8% of the participants had at least one major fracture. Bone mineral density measured with pQCT and muscle area were significantly associated with these fractures (total and trabecular bone mineral density OR 2.243 and 2.195, p < 0.01; muscle area OR 2.378, p < 0.05), whereas DXA bone mineral density showed no significant association. These associations remained after adjustment for age, sex, BMI, physical activity and other factors. In all models for patients >75 years only muscle area was significantly associated (OR 5.354, p < 0.05) with major fractures. Measurement of bone mineral density and muscle area with pQCT seems to have advantage over DXA in fracture association in geriatric patients. Measuring muscle area also adds useful information to estimate the presence of osteosarcopenia.

Changes of Bone Turnover Markers and Bone Tissue Content After Severe Osteoporotic Vertebral Compression Fracture.

BACKGROUND The incidence of osteoporotic vertebral fractures (OVCFs) has increased significantly in recent years. In order to assess osteoporotic fracture healing process, it is necessary to study the characteristics after this type of vertebral fracture. However, there are few researches on fracture healing process in severe OVCFs. We aim to investigate the histological healing process and the kinetics of bone turnover markers following severe OVCFs. MATERIAL AND METHODS There were 149 patients with severe OVCFs included in this study. Fasting blood samples were obtained to detect bone turnover markers levels. A transpedicular bone biopsy was performed to collect bone biopsy specimens during vertebroplasty surgery. Stratification of healing process was performed: stage I (1-3 days), stage II (4-10 days), stage III (11-20 days), stage IV (21-30 days), stage V (1-3 months), stage VI (3-6 months). RESULTS Quantitative analysis of bone histomorphometry showed that a large amount of necrotic bone tissue was observed in stage VI (12.92±3.66%). Bone turnover markers showed the concentration of ß-isomerized C-terminal telopeptide (ß-CTX) which reflects activity in osteoclast continued to increase in stage VI (0.9±0.33 ng/mL). These results differed from previous reports of other type vertebral fractures. CONCLUSIONS Bone histomorphometric analysis and bone turnover markers showed that severe osteoporotic vertebral compression fractures often associated with delayed union and nonunion during the healing process.

Cement augmentation of an angular stable plate osteosynthesis for supracondylar femoral fractures - biomechanical investigation of a new fixation device.

BACKGROUND: Implant anchorage in highly osteoporotic bone is challenging, since it often leads to osteosynthesis failure in geriatric patients with supracondylar femoral fractures. Cementation of screws is presumed to prevent such osteosynthesis failure. This study aimed to investigate the effect of a newly designed, cementable fenestrated condylar screw for plate fixation in a biomechanical setting. METHODS: Eight pairs of osteoporotic cadaver femora with an average age of 77 years, ranging between 62 and 88 years, were randomly assigned to either an augmented or a non-augmented group. In both groups an instable 33-A3 fracture according to the AO / OTA classification was fixed with an angular stable locking plate. All right samples received a cement augmentation of their fenestrated condylar screws with calcium phosphate bone cement (CPC). Mechanical testing was performed at a load to failure mode by cyclic axial loading, using a servohydraulic testing machine. RESULTS: With a mean of 2475 N (95% CI: 1727-3223 N), the pressure forces resulting in osteosynthesis failure were significantly higher in specimen with cemented condylar screws as compared to non-cemented samples (1875 N (95% CI: 1320-2430 N)) (p = 0.024). In both groups the deformation of the constructs, with the distal screws cutting through the condylar bone, were the most frequent cause for failure. Analysis of axial stiffness (p = 0.889) and irreversible deformity of the specimens revealed no differences between the both groups (p = 0.161). No cement leakage through the joint line or the medial cortex was observed. CONCLUSION: Based on the present study results, the newly introduced, cementable condylar screw could be an encouraging feature for the fixation of supracondylar femoral fractures in patients with reduced bone quality in terms of load to failure accuracy of the cement application.

Evaluation of baseline fracture risk in younger postmenopausal women with breast cancer using different risk assessment methods.

OBJECTIVE: Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC. METHODS: Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively. RESULTS: Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group. CONCLUSION: Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.

Insertion/deletion polymorphism in the 3' untranslated region of COL1A2 disrupts its interaction with microRNA-382 and leads to decreased susceptibility to osteoporotic fracture.

A growing body of evidence has proved that the expression of COL1A2 is associated with a reduced risk of osteoporotic fracture. One single-nucleotide polymorphism (rs3917) located within the 3'-untranslated region of COL1A2 may "alter" binding site of miR-382 and thereby associated with the risk of osteoporotic fracture. Bioinformatic analysis, luciferase reporter assay, site-directed mutagenesis, Western blot and real-time PCR were performed in this study. In this study, we validated COL1A2 as a target of miR-382 in osteoblast. In addition, bone tissue samples were genotyped as wild-type rs3917, heterozygous rs3917, and homozygous rs3917. The expression of miR-382 was comparable between the genotype groups, whereas the expression of COL1A2 mRNA and protein was much higher in heterozygous rs3917 and homozygous rs3917 than the wild-type rs3917 group. Furthermore, we transfected the wild-type rs3917 and heterozygous rs3917 cells with miR-382 mimics or inhibitors and found that the transfection with miR-382 mimics significantly increased the level of the miR-382 in the cells of both genotypes, and the introduction of miR-382 inhibitors substantially suppressed the level of miR-382 in both cells. In wild-type rs3917 cells, transfection of miR-382 mimics and COL1A2 small interfering RNA (siRNA) similarly and substantially downregulated the expression of COL1A2, while in heterozygous rs3917 cells, only COL1A2 siRNA notably reduced the expression of COL1A2, whereas introduction of miR-382 mimics left expression of COL1A2 intact. The findings showed rs3917 polymorphism interfered with the interaction between COL1A2 mRNA and miR-382, and minor allele is associated with a reduced risk of osteoporotic fracture.

Effects of anti-osteoporosis medications on radiological and clinical results after acute osteoporotic spinal fractures: a retrospective analysis of prospectively designed study.

Effects of anti-osteoporosis medications such as anti-resorptive and anabolic agents on healing of osteoporotic spinal fracture were retrospectively investigated. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented good pain relief. These findings suggest that proper selection of medication could improve initial management of acute osteoporotic spinal fractures (OSFs). INTRODUCTION: Although anti-osteoporosis medications have beneficial effects on prevention of osteoporotic spinal fractures (OSFs), few studies have compared effects of medications on fracture healing following OSFs. Therefore, the purpose of this study was to elucidate the effects of different anti-osteoporosis medications on radiological and clinical outcomes after acute OSFs. METHODS: A total of 132 patients diagnosed with acute OSFs were enrolled and allocated into three groups [group I (n = 39, no anti-osteoporosis medication), group II (n = 66, bisphosphonate), and group III (n = 27, parathyroid hormone (PTH)]. Radiological parameters including magnetic resonance (MR) classification, occurrence of intravertebral cleft (IVC), and clinical outcomes such as numerical rating scale (NRS) and Oswestry disability index were assessed. Risk analyses for IVC and progressive collapse were done along the related factors and medication type. RESULTS: IVC sign was observed in 30 patients. The rate of IVC sign was lower in group III (7.4%) than that in group I (20.5%) or group II (30.3%), although the difference was not statistically significant. Moreover, the degree of NRS improvement was better in group III than that in group I or group II (5.7 vs. 3.1 vs. 3.5, p < 0.001). On multiple regression analysis, mid-portion type fracture in MR classification was a significant risk factor for progressive OSFs. The use of PTH showed significant lower incidences of occurrence of IVC (odds ratio (OR) = 0.160) and increase in height loss (OR = 0.325). CONCLUSIONS: Different anti-osteoporosis medications presented different clinical and radiological results after acute OSFs. The use of anabolic agent significantly enhanced fracture healing, reduced progressive collapse, and presented better clinical outcomes. Proper selection of medication might improve initial management of acute OSFs.

Associations between radius low-frequency axial ultrasound velocity and bone fragility in elderly men and women.

An exploratory study in elderly women and men from the Geneva Retirees Cohort indicates that low-frequency quantitative ultrasound measurement at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk. INTRODUCTION: The contribution of distal radius bone mineral density (BMD) and cortical microstructure to fracture risk has recently been demonstrated. In this exploratory study, we investigated whether low-frequency quantitative ultrasound measurement at the distal radius may capture the peripheral determinants of bone fragility assessed with dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Low-frequency velocity (VLF) was measured at the radius using OsCare Sono®, a portable axial transmission ultrasonometer, in 271 community-dwelling postmenopausal women and men (age 71.5 ± 1.4 years) from the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius were assessed by HR-pQCT, in addition to areal (a) BMD by DXA, at the same time point. RESULTS: VLF was highly correlated with aBMD at the distal third radius (r = 0.72, p < 0.001). For microstructure parameters, the highest correlation was observed with cortical area (r = 0.59, p < 0.001). VLF also captured bone geometry (total area) and cortical tissue mineral density independently of aBMD. In models adjusted for age and sex, VLF was significantly associated with prevalent low-trauma fractures [OR 95%CI for one SD decrease of VLF 1.50 (1.05, 2.14), p = 0.024], with discrimination performance comparable to femoral neck or distal radius aBMD. CONCLUSION: Measurement of VLF at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk.

Proof of Concept on Functionality Improvement of Mesenchymal Stem-Cells, in Postmenopausal Osteoporotic Women Treated with Teriparatide (PTH1-34), After Suffering Atypical Fractures.

Osteoporosis long-term treatment with nitrogen-containing bisphosphonates, has been associated with uncommon adverse effects, as atypical femoral fractures (AFF). Thus, treatment with teriparatide (TPTD; fragment of human parathyroid hormone; PTH1-34) has been proposed for such patients. Besides its anabolizing effect on bone, TPTD may affect stem-cell mobilization and expansion. Bone marrow mononuclear cells (BMMNC) were isolated from five women that had suffered AFF associated to bisphosphonate treatment, before and after 6 months of TPTD therapy. The presence of mesenchymal stromal cells (CD73, CD90 and CD105 positive cells), gene expression of NANOG, SOX2 and OCT4, proliferation, senescence and capacity to differentiate into osteoblasts and adipocytes were analyzed. After TPTD treatment, BMMNC positive cells for CD73, CD90 and CD105 increased from 6.5 to 37.5% (p < 0.05); NANOG, SOX2 and OCT4 were upregulated, being statistically significant for NANOG (p < 0.05), and cells increased proliferative capacity more than 50% at day 7 (p < 0.05). Senescence was reduced 2.5-fold (p < 0.05), increasing differentiation capacity into osteoblasts and adipocytes, with more than twice mineralization capacity of extracellular matrix or fat-droplet formation (p < 0.05), respectively. Results show that TPTD treatment caused BMMNC "rejuvenation", increasing the number of cells in a more undifferentiated stage, with higher differentiation potency. This effect may favor TPTD anabolic action on bone in such patients with AFF, increasing osteoblast precursor cells. Such response could also arise in other osteoporotic patients treated with TPTD, without previous AFF. Furthermore, our data suggest that TPTD effect on stromal cells may have clinical implications for bone-regenerative medicine. Further studies may deepen on this potential.

Lumbar muscle volume in postmenopausal women with osteoporotic compression fractures: quantitative measurement using MRI.

OBJECTIVE: To investigate the relationship between paraspinal and psoas muscle volumes and acute osteoporotic or low-bone-mass compression fractures of the lumbar spine in postmenopausal women. METHODS: Patient data were retrieved retrospectively for postmenopausal women with L-spine magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry showing osteoporosis/low bone mass. Group 1 comprised eight women aged 60-80 years with MRI showing a single acute compression fracture. The age-matched group 2a (N = 12) and younger group 2b (N = 12) comprised of women whose MRIs showed no fractures. Cross-sectional MRIs of the paraspinal and psoas muscles and intramuscular fat volume for each muscle group were measured. Operator repeatability and reproducibility were obtained. RESULTS: Group 1 showed significantly smaller lean muscle volume for all muscle groups at L5/S1. Intramuscular fat volume was also smaller in most muscle groups in group 1, though only reaching statistical significance at variable muscle groups and levels. Measurements show both good intrarater repeatability and interrater reproducibility of lean muscle volume estimations (intraclass correlation coefficient (ICC), 0.999 for rater A and 0.997 for rater B; Cronbach's alpha 0.995) and intramuscular fat volume estimations (ICC, 0.995 for rater A and 0.982 for rater B; Cronbach's alpha was 0.981). CONCLUSIONS: This study provides the first quantitative evidence that compression fractures in postmenopausal women with underlying osteoporosis/low bone mass are associated with less paraspinal and psoas muscle volumes. Further longitudinal studies with larger cohorts are needed to verify this relationship. KEY POINTS: • The risk of osteoporotic compression fractures is higher in older women with smaller paraspinal muscle volume. • Older women show smaller paraspinal muscle volume and more intramuscular fat compared to younger controls.