Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

OBJECTIVES: Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). METHODS: Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). RESULTS: Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (ß, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. CONCLUSIONS: In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. KEY POINTS: • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Incidental 68Ga-Prostate-Specific Membrane Antigen Uptake in Compression Fracture of a Vertebral Body.

ABSTRACT: Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein, which is overexpressed in prostate cancer cells. With its wide use, there is a growing number of case reports describing non-prostate cancer-related benign and malignant lesions showing increased 68Ga-PSMA uptake. We herein present the case of an 89-year-old man with prostate cancer who was referred for 68Ga-PSMA PET/CT for restaging, which revealed incidental 68Ga-PSMA uptake in compression fracture of a vertebral body. This case demonstrates that PSMA expression may occur in acute compression fractures, and it can be a potential pitfall when reporting 68Ga-PSMA PET/CT images.

Assessment of non-traumatic vertebral fractures in Cushing's syndrome patients.

PURPOSE: Hypercortisolism has detrimental effects on bone metabolism with the consequences of bone loss and bone fractures. We aimed to evaluate the frequency of vertebral fragility fractures and to determine the factors associated with Cushing's syndrome (CS). METHODS: A total of 135 patients diagnosed with Cushing's syndrome [108 patients with Cushing's disease and 27 patients with adrenocortical adenoma] and 107 healthy controls were included in this cross-sectional study. The available clinical, laboratory, and radiologic data of patients with CS were recorded, retrospectively. Lateral vertebral radiograms were evaluated for vertebral fragility fractures according to Genant's semi-quantitative method. Bone mineral density (BMD) was determined using a Dual-energy X-ray absorptiometry (DEXA). RESULTS: Vertebral fragility fractures (VFs) were observed in 75.3% (n = 61) of the patients. The median number of VFs was six (min-max: 2-12). All patients with vertebral fractures had thoracic VF, and 50.7% of the patients had lumbar fragility fractures. Thirty-three (40.7%) patients with vertebral fractures had normal bone densitometry values. Osteoporosis and osteopenia were observed in 16.2% and 40.7% of the patients, respectively. The duration of active disease, the presence of ACTH-secreting pituitary adenoma, and 24-h urinary cortisol did not influence the presence of vertebral fractures. Vertebral fractures were independently associated with age, FSH, LH levels, and lumbar BMD (R2 = 68.18%, p = 0.028). The femoral neck BMD (but not lumbar BMD) was independently associated with age, BMI, and PTH levels (R2 = 48.48%, p < 0.001). CONCLUSION: Vertebral fracture frequency was higher in CS patients. Most of the patients with vertebral fractures had multiple fractures. Although low lumbar BMD was associated with VF, patients with CS with normal bone densitometry could experience VF. Vertebral radiograph evaluations as a part of routine evaluation for silent vertebral fractures may help to prevent further fractures in patients with CS.

Vertebral compression fractures: Still an unpredictable aspect of osteoporosis

Vertebral compression fracture is a hallmark of osteoporosis (OP) and by far the most prevalent fragility fracture. It is well proven that patients who develop a vertebral compression fracture are at substantial risk for additional fractures. Diagnosis is based on adequate clinical evaluation, imaging, and laboratory tests. The imaging of OP and fragility fractures includes conventional radiology to evaluate spinal fractures, bone mineral density (BMD) testing by dual energy x-ray densitometry, quantitative computerized tomography, magnetic resonance imaging, bone scintigraphy (if necessary), and ultrasound. Screening and treatment of individuals with high risk of osteoporotic fracture are cost-effective, but approximately two-thirds of the vertebral compression fractures (VCF) that occur each year are not accurately diagnosed and, therefore, not treated. Evaluation of VCFs, even though they may be asymptomatic, seems essential to health-related and/or clinical research on OP.

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.

High Expression of Acid-Sensing Ion Channel 2 (ASIC2) in Bone Cells in Osteoporotic Vertebral Fractures.

Little is known about the function of acid-sensing ion channels (ASICs) in bone cells or osteoporotic vertebral fractures (OVF). This study delineated ASICs expression in adult human bone marrow-mesenchymal stem cells- (BM-MSC-) derived osteoblasts and in OVF bone cells. Adult BM-MSC-derived osteoblasts were isolated and cultured in different pH values. Osteogenic markers as alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OC) mRNA were assessed. Western blots method was applied to analyze ASICs protein expression in different pH values. Amiloride was added into the osteogenic media to analyze the Na+/K+ ATPase change. We harvested the vertebral cancellous bone through a bone biopsy needle in 26 OVF patients when performing percutaneous vertebroplasty. Six vertebral bone specimens obtained from 4 patients with high-energy vertebral fractures were used as the control. The reverse transcription polymerase chain reaction was performed to analyze the quantitative mRNA expression of ASICs. Osteogenic markers as ALP, OPN, and OC mRNA were higher expressed in increasing pH values throughout osteoblastogenesis. ASIC proteins were higher expressed in lower pH media, especially ASIC3, and ASIC4. The highest protein expression at days 7, 14, and 21 was ASIC2, ASIC4, and ASIC3, respectively. Expression of Na+/K+ ATPase was significantly decreased in cultured osteoblasts by addition of amiloride into the pH 6.9 osteogenic media. ASIC2 mRNA was most highly expressed with a 65.93-fold increase in the biopsied vertebral bone cells in OVF compared with the control. In conclusion, we found osteoblastogenesis was reduced in an acidic environment, and ASIC2, ASIC3, and ASIC4 were most highly expressed in turn during osteoblastogenesis within acidic media. ASIC2 was the most abundantly expressed gene in human bone cells in OVF compared with the control. ASIC2 could be crucial in the pathogenesis of osteoporosis and could serve as a therapeutic target for antiosteoporotic therapies.

Combined intravoxel incoherent motion diffusion-weighted MR imaging and magnetic resonance spectroscopy in differentiation between osteoporotic and metastatic vertebral compression fractures.

PURPOSE: Our purpose was to combine intravoxel incoherent motion diffusion-weighted MR imaging (IVIM-DWI) and magnetic resonance spectroscopy (MRS) to differentiate osteoporotic fractures from osteolytic metastatic vertebral compression fractures (VCFs). METHODS: A total of 70 patients with VCFs were included and divided into two groups, according to their causes of fractures based on pathological findings or clinical follow-up. All patients underwent conventional sagittal T1WI, T2WI, STIR, IVIM-DWI, and single-voxel MRS. The diffusion coefficient (D), pseudo diffusion (D*), and perfusion fraction (f) parameters from IVIM-DWI and the lipid water ratio (LWR) and fat fraction (FF) parameters from MRS were obtained and compared among groups. Furthermore, the diagnostic performance of MRS, IVIM-DWI, and IVIM-DWI combined with MRS for differentiation between osteoporotic and osteolytic metastatic VCFs was assessed by using receiver operating characteristic (ROC) curve analysis. RESULTS: Compared with the osteoporotic group, the metastatic group had significantly lower values for f, D, and FF, but higher D* (all P < 0.05). The area under the receiver operating characteristic (ROC) curve of MRS, IVIM-DWI, and IVIM-DWI combined with MRS were 0.73, 0.88, and 0.94, respectively. Among these, the IVIM-DWI combined with MRS showed the highest sensitivity, specificity, and accuracy, which are 90.63% (29/32), 97.37 % (37/38), and 94.29% (66/70), respectively. CONCLUSIONS: IVIM-DWI combined with MRS can be more accurate and efficient for differentiation between osteoporotic and osteolytic metastatic VCFs than single MRS or IVIM-DWI.

Histochemical and histological changes of paraspinal muscles in patients with thoracic and lumbar spine fractures treated with open and minimally invasive stabilisation.

BACKGROUND: Histological and histochemical analyses of muscle samples were used to determine the intensity of paraspinal muscle injury during open (OPEN) and minimally invasive (MIS) procedures due to spinal trauma. OBJECTIVE: A randomised prospective study design was chosen. According to our hypothesis, OPEN procedures will lead to more intensive microscopic changes than MIS. METHODS: Muscle samples were collected during the primary surgery - fracture surgery (FRS) from the left and during material extraction (EXS) from the right side. Complete samples were acquired from 17 OPEN and 18 MIS subjects. We compared them histochemically and histologically; muscle fibre typing and statistical analysis were performed. RESULTS: We statistically confirmed that the increase in fibrosis in the OPEN EXS sample was significantly higher than in the MIS EXS sample, with p< 0.05 (p= 0.000322453). Fibre types in MIS did not differ almost at all in both samples; the changes were statistically insignificant.In OPEN samples, the number of type I fibres differed significantly. In EXS, it was significantly lower (46.23%) than in FRS (60.63%), at a statistically significant level, p< 0.05 (p= 0.0234375000) especially with the increase of the type IIA fibres, less in IIB fibres. CONCLUSIONS: These microscopic findings provide a statistically significant confirmation that OPEN procedures in spinal fracture lead, in most cases, to significant changes in the structure of the corset muscle at the fracture site and surgical access point than MIS procedures.

Elevated Microdamage Spatially Correlates with Stress in Metastatic Vertebrae.

Metastasis of cancer to the spine impacts bone quality. This study aims to characterize vertebral microdamage secondary to metastatic disease considering the pattern of damage and its relationship to stress and strain under load. Osteolytic and mixed osteolytic/osteoblastic vertebral metastases were produced in athymic rats via HeLa cervical or canine Ace-1 prostate cancer cell inoculation, respectively. After 21 days, excised motion segments (T12-L2) were µCT scanned, stained with BaSO4 and re-imaged. T13-L2 motion segments were loaded in axial compression to induce microdamage, re-stained and re-imaged. L1 (loaded) and T12 (unloaded) vertebrae were fixed, sample blocks cut, polished and BSE imaged. µFE models were generated of all L1 vertebrae with displacement boundary conditions applied based on the loaded µCT images. µCT stereological analysis, BSE analysis and µFE derived von Mises stress and principal strains were quantitatively compared (ANOVA), spatial correlations determined and patterns of microdamage assessed qualitatively. BaSO4 identified microdamage was found to be spatially correlated with regions of high stress in µFEA. Load-induced microdamage was shown to be elevated in the presence of osteolytic and mixed metastatic disease, with diffuse, crossed hatched areas of microdamage present in addition to linear microdamage and microfractures in metastatic tissue, suggesting diminished bone quality.

Osteoanabolic and dual action drugs.

Teriparatide (TPTD) and abaloparatide (ABL) are the only osteoanabolic drugs available, at this time, for treatment of osteoporosis. TPTD is a 34-amino acid fragment that is identical in its primary sequence to the 34 amino acids of full-length human parathyroid hormone [hPTH(1-84)]. ABL is identical to parathyroid hormone-related peptide (PTHrP) through the first 22 residues with significantly different amino acids inserted thereafter, between residues 22 and 34. The osteoanabolic actions of PTH are due directly to its effects on cells of the osteoblast lineage and indirectly by stimulating IGF-I synthesis and suppressing sclerostin and associated enhancement of Wnt signalling. Both TPTD and ABL are ligands that bind to and activate the PTH receptor type 1 (PTHR1) receptor but they appear to do so differently: ABL favours the transient, more anabolic configuration of the receptor. Both TPTD and ABL reduce the risk of vertebral fractures and non-vertebral fractures. Both drugs are administered for a maximum of 24 months, and should be followed by an antiresorptive agent to maintain gains in bone mineral density (BMD). Romosozumab, a monoclonal antibody that binds to and inhibits sclerostin, appears to have dual actions by stimulating bone formation and reducing bone resorption. In the pivotal clinical trial, romosozumab, administered as a 210 mg monthly subcutaneous dose, significantly reduced new vertebral fractures and in a subsequent study reduced both vertebral and non-vertebral fractures.

A retrospective analysis of bone mineral status in patients requiring spinal surgery.

BACKGROUND: Impaired bone quality is associated with poor outcome of spinal surgery. The aim of the study was to assess the bone mineral status of patients scheduled to undergo spinal surgery and to report frequencies of bone mineral disorders. METHODS: We retrospectively analyzed the bone mineral status of 144 patients requiring spinal surgery including bone mineral density by dual-energy X-ray absorptiometry (DXA) as well as laboratory data with serum levels of 25-hydroxyvitamin D (25-OH-D), parathyroid hormone, calcium, bone specific alkaline phosphate, osteocalcin, and gastrin. High-resolution peripheral quantitative computed tomography (HR-pQCT) was additionally performed in a subgroup of 67 patients with T-Score below - 1.5 or history of vertebral fracture. RESULTS: Among 144 patients, 126 patients (87.5%) were older than 60 years. Mean age was 70.1 years. 42 patients (29.1%) had suffered from a vertebral compression fracture. 12 previously undiagnosed vertebral deformities were detected in 12 patients by vertebral fracture assessment (VFA). Osteoporosis was present in 39 patients (27.1%) and osteopenia in 63 patients (43.8%). Only 16 patients (11.1%) had received anti-osteoporotic therapy, while 54 patients (37.5%) had an indication for specific anti-osteoporotic therapy but had not received it yet. The majority of patients had inadequate vitamin D status (73.6%) and 34.7% of patients showed secondary hyperparathyroidism as a sign for a significant disturbed calcium homeostasis. In a subgroup of 67 patients, severe vertebral deformities were associated with stronger deficits in bone microarchitecture at the distal radius compared to the distal tibia. CONCLUSIONS: This study shows that bone metabolism disorders are highly prevalent in elderly patients scheduled for spinal surgery. Vertebral deformities are associated with a predominant deterioration of bone microstructure at the distal radius. As impaired bone quality can compromise surgical outcome, we strongly recommend an evaluation of bone mineral status prior to operation and anti-osteoporotic therapy if necessary.

Osteoporosis Is the Most Important Risk Factor for Odontoid Fractures in the Elderly.

Traumatic odontoid fractures (TOFs) have been described as the most common injury affecting the C-spine in the elderly. Previous studies have identified degenerative changes and bone loss as important predisposing factors. However, their interaction and respective age-adjusted impact needs further clarification. We conducted a retrospective analysis of 5303 patients (aged ≥60 years) admitted to a level I trauma center between January 2008 and January 2016 who underwent CT imaging of the C-spine. Ninety-two patients with TOF and 80 patients with other cervical spine fractures (OCSF) were identified and a respective 3:1 age- and sex-matched control group without fractures after trauma was built. In all groups, cervical bone mineral density (cBMD) was determined using phantom calibration, and degenerative changes were evaluated in a qualitative manner. In all groups, the severity of degenerative changes of the C-spine increased with age (all p < 0.05) and was inversely correlated with cBMD (all p < 0.05). cBMD was the only significant predictor of a TOF in a multivariate logistic regression model (adjusted odds ratio [OR] = 3.066, 95% confidence interval [CI] 1.432-6.563 for cervical osteoporosis). An association between odontoid cysts and TOF reached significance only in Anderson and D'Alonzo (A&D) type II TOFs (aOR = 1.383; 95% CI 1.012-1.890). Patients with OCSFs, compared with patients with TOFs, were younger (median 74 versus 83 years) and had a higher cBMD (median 208 mg/mL versus 172 mg/mL). No differences were observable when comparing cBMD and grades of degenerative changes between OCSFs and their control group (all p >0.1). Decreased cBMD is the major predisposing factor for the occurrence of TOF but not for OCSF in the elderly. The severity of odontoid cysts was found to be a cBMD-independent factor associated with A&D type II TOFs. However, degenerative changes in the odontoid neighboring joints seem to be an epiphenomenon of bone loss and older age but do not independently predispose for TOF. © 2017 American Society for Bone and Mineral Research.

Sex Steroid Hormones and Fracture in a Multiethnic Cohort of Women: The Women's Health Initiative Study (WHI).

Context: We hypothesize that endogenous sex steroids are associated with fracture risk independent of race/ethnicity. Design and Setting: We performed a nested case-control study within the prospective Women's Health Initiative Observational Study. Incident nonspine fractures were identified in 381 black, 192 Hispanic, 112 Asian, and 46 Native American women over an average of 8.6 years. A random sample of 400 white women who experienced an incident fracture was chosen. One control was selected per case and matched on age, race/ethnicity, and blood draw date. Bioavailable estradiol (BioE2), bioavailable testosterone (BioT), and sex hormone-binding globulin (SHBG) were measured using baseline fasting serum. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence interval (CI) of fracture across tertiles of hormone. Results: In multivariable and race/ethnicity-adjusted models, higher BioE2 (>8.25 pg/mL) and higher BioT (>13.3 ng/dL) were associated with decreased risk of fracture (OR, 0.65; 95% CI, 0.50 to 0.85; P trend = 0.001 and OR, 0.76; 95% CI, 0.60 to 0.96; P trend = 0.02, respectively). The interaction term between race/ethnicity and either BioE2 or BioT was not significant. There was no association between SHBG and fracture risk. In models stratifying by race/ethnicity, higher BioE2 was associated with a lower risk of fracture in both white women (OR, 0.56; 95% CI, 0.36 to 0.87) and black women (OR, 0.61; 95% CI, 0.39 to 0.96). Higher BioT was associated with a significantly lower fracture risk in only black women (OR, 0.65; 95% CI, 0.43 to 1.00), P trend = 0.03. Conclusions: Serum BioE2 and BioT are associated with fracture risk in older women irrespective of race/ethnicity and independent of established risk factors for fracture.

Increased osteoclastogenesis in patients with vertebral fractures following discontinuation of denosumab treatment.

OBJECTIVE: To test the hypothesis that rebound of bone remodeling is responsible for clinical vertebral fractures reported in a few patients with osteoporosis after cessation of denosumab treatment. DESIGN: In this case-control study we compared clinical and biochemical characteristics of postmenopausal women with clinical vertebral fractures 8-16 months after the last injection of denosumab (Dmab/Fx+, n = 5) with those of treatment-naïve women with such fractures (Fx+, n = 5). In addition, 5 women who discontinued denosumab treatment but did not sustain vertebral fractures 18-20 months after the last injection were studied (Dmab/Fx-, n = 5). METHODS: We measured serum microRNAs, gene expression of mRNAs of factors regulating formation and activity of osteoclasts and biochemical markers of bone and mineral metabolism. In Dmab/Fx+ and Fx+ women, blood was taken 4-8 weeks after the fracture. RESULTS: Compared to Fx+ women, Dmab/Fx+ women had higher serum P1NP and CTx levels, and significantly lower serum miR-503 and miR-222-2 that downregulate osteoclastogenesis and osteoclast activity, and higher RANK (13-fold) and CTSK (2.6-fold) mRNA. The respective values of Dmab/Fx- women were in the same direction as those of Dmab/Fx+ women but of a lesser magnitude. CONCLUSIONS: Bone fragility in women with clinical vertebral fractures after stopping denosumab therapy is pathophysiologically different from that of treatment-naïve women with osteoporosis and clinical vertebral fractures and it is associated with upregulation of markers of osteoclast formation and activity. The small number of women with this rare event studied is a limitation.

Incidental PSMA Uptake in an Undisplaced Fracture of a Vertebral Body.

A 50-year-old man with recently diagnosed prostate cancer was referred for Ga-prostate-specific membrane antigen (PSMA) PET/CT with elevated prostate-specific antigen. PET/CT demonstrated increased PSMA uptake in an undisplaced transverse fracture of the L1 vertebral body. This case illustrates that PSMA uptake can occur in a transverse vertebral body fracture and is a benign cause of PSMA uptake.

Mineral metabolism disorders, vertebral fractures and aortic calcifications in stable kidney transplant recipients: The role of gender (EMITRAL study).

BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.

Effect of microRNA-21 on the proliferation of human degenerated nucleus pulposus by targeting programmed cell death 4.

This study aims to explore the effect of microRNA-21 (miR-21) on the proliferation of human degenerated nucleus pulposus (NP) by targeting programmed cell death 4 (PDCD4) tumor suppressor. NP tissues were collected from 20 intervertebral disc degeneration (IDD) patients, and from 5 patients with traumatic spine fracture. MiR-21 expressions were tested. NP cells from IDD patients were collected and divided into blank control group, negative control group (transfected with miR-21 negative sequences), miR-21 inhibitor group (transfected with miR-21 inhibitors), miR-21 mimics group (transfected with miR-21 mimics) and PDCD4 siRNA group (transfected with PDCD4 siRNAs). Cell growth was estimated by Cell Counting Kit-8; PDCD4, MMP-2,MMP-9 mRNA expressions were evaluated by qRT-PCR; PDCD4, c-Jun and p-c-Jun expressions were tested using western blot. In IDD patients, the expressions of miR-21 and PDCD4 mRNA were respectively elevated and decreased (both P<0.05). The miR-21 expressions were positively correlated with Pfirrmann grades, but negatively correlated with PDCD4 mRNA (both P<0.001). In miR-21 inhibitor group, cell growth, MMP-2 and MMP-9 mRNA expressions, and p-c-Jun protein expressions were significantly lower, while PDCD4 mRNA and protein expressions were higher than the other groups (all P<0.05). These expressions in the PDCD4 siRNA and miR-21 mimics groups was inverted compared to that in the miR-21 inhibitor group (all P<0.05). MiR-21 could promote the proliferation of human degenerated NP cells by targeting PDCD4, increasing phosphorylation of c-Jun protein, and activating AP-1-dependent transcription of MMPs, indicating that miR-21 may be a crucial biomarker in the pathogenesis of IDD.

Cost-Effectiveness of Osteoporosis Screening Strategies for Men.

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual-level state-transition cost-effectiveness model with a lifetime time horizon to identify the cost-effectiveness of different osteoporosis screening strategies for US men involving various screening tests (dual-energy X-ray absorptiometry [DXA]; the Osteoporosis Self-Assessment Tool [OST]; or a fracture risk assessment strategy using age, femoral neck bone mineral density [BMD], and Vertebral Fracture Assessment [VFA]); screening initiation ages (50, 60, 70, or 80 years); and repeat screening intervals (5 years or 10 years). In base-case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was "dominated" by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost-effective in base-case analyses and one-way sensitivity analyses when assuming willingness-to-pay of $50,000/quality-adjusted life-year (QALY) or $100,000/QALY included screening initiation at age 50 years with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 years with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 years with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for US men to initiate routine screening at age 50 or 60 years would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost-effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. © 2016 American Society for Bone and Mineral Research.

Subclinical hypercortisolism: a state, a syndrome, or a disease?

Subclinical hypercortisolism (SH), defined as alterations of the hypothalamus-pituitary-adrenal axis in the absence of clinical signs or symptoms related to cortisol secretion, is a common finding in patients with adrenal incidentalomas. The clinical correlates of this pathological condition have become clearer over the last few years. The aim of this review is to summarize the co-morbidities and the clinical outcomes of patients with SH. According to the analysis of the results of the studies published within the last 15 years, hypertension and type 2 diabetes are a common finding in patients with SH, occurring roughly in 2/3 and 1/3 of the patients respectively. Moreover, several additional cardiovascular and metabolic complications, like endothelial damage, increased visceral fat accumulation and impaired lipid metabolism have been shown to increase the cardiovascular risk of those patients. Accordingly, recent independent reports investigating the natural history of the disease in a long-term follow-up setting have shown that patients with SH have a higher incidence of cardiovascular events and related mortality. Moreover, longitudinal studies have also shown increased incidence of osteoporotic vertebral fractures. Future research is needed to improve the diagnostic performance of hormonal tests, by assessment of the complete steroid profile with more accurate assays, and to define the efficacy of surgical vs medical treatment in a randomized-controlled setting.

Vertebral compression fractures as the initial presentation of AL amyloidosis: case series and review of literature.

The clinical presentation of AL amyloidosis is highly variable. In this series, we describe five cases of AL amyloidosis with vertebral compression fractures as initial presentation. All five patients had evidence of bone marrow replacement on magnetic resonance imaging and bone marrow biopsies demonstrating diffuse interstitial amyloid deposition. Hepatomegaly and elevated liver enzymes, consistent with liver involvement with amyloidosis, were also seen in each case. All five patients responded well to anti-plasma cell chemotherapy, with normalization of serum free light chain levels, reduction in alkaline phosphatase and improvement in pain and functional status. Although rare, AL amyloidosis should be considered in the differential diagnosis of selected patients with spontaneous vertebral compression fractures. Moreover, there seems to be an association of vertebral compression fractures with liver involvement in AL amyloidosis.