Spinal Trabecular Bone Research Articles

Targeting EP2 Receptor Improves Muscle and Bone Health in Dystrophin−/−/Utrophin−/− Double-Knockout Mice

Duchenne muscular dystrophy (DMD) is a severe genetic muscle disease occurring due to mutations of the dystrophin gene. There is no cure for DMD. Using a dystrophin−/−utrophin−/− (DKO-Hom) mouse model, we investigated the PGE2/EP2 pathway in the pathogenesis of dystrophic muscle and its potential as a therapeutic target. We found that Ep2, Ep4, Cox-2, 15-Pgdh mRNA, and PGE2 were significantly increased in DKO-Hom mice compared to wild-type (WT) mice. The EP2 and EP4 receptors were mainly expressed in CD68+ macrophages and were significantly increased in the muscle tissues of both dystrophin−/− (mdx) and DKO-Hom mice compared to WT mice. Osteogenic and osteoclastogenic gene expression in skeletal muscle also increased in DKO-Hom mice, which correlates with severe muscle heterotopic ossification (HO). Treatment of DKO-Hom mice with the EP2 antagonist PF04418948 for 2 weeks increased body weight and reduced HO and muscle pathology by decreasing both total macrophages (CD68+) and senescent macrophages (CD68+P21+), while increasing endothelial cells (CD31+). PF04418948 also increased bone volume/total volume (BV/TV), the trabecular thickness (Tb.Th) of the tibia trabecular bone, and the cortical bone thickness of both the femur and tibia without affecting spine trabecular bone microarchitecture. In summary, our results indicate that targeting EP2 improves muscle pathology and improves bone mass in DKO mice.

Impact of the visceral adipose tissue on bone quality in patients with untreated mild-to-severe obstructive sleep apnea.

Obstructive sleep apnea (OSA) predominantly affects patients who are obese and causes systemic organ damage. Little is known about the relationship between fat distribution and bone impairment in these patients. We aimed to evaluate the impact of the visceral adipose tissue (VAT) on the bone quality of patients with OSA. In our prospective study, 49 untreated patients with mild-to-severe OSA underwent dual-energy X-ray absorptiometry. Polygraphy data were also collected. According to the recent reference values for European adults, patients were divided by the sex-related threshold of the VAT index into two categories: VAT index within limits (normal VAT [nVAT]) and increased VAT (iVAT). In all, 63% of the patients were in the iVAT category. Compared to patients with nVAT, those with iVAT had a higher prevalence of arterial hypertension (52% versus 22%) and diabetes (32% versus 6%), and higher values of mean nocturnal desaturation. Patients with iVAT had, in comparison to those with nVAT, lower values of the lumbar spine trabecular bone score (TBS; mean 1.24 versus 1.39; p < 0.001), TBS T-score (mean -1.82 versus -0.52; p < 0.001) and TBS Z-score (mean -0.35 versus 0.75; p = 0.002). Moreover, a close association was present between the VAT index and TBS lumbar spine L1-L4 (r2 linear 0.573; p < 0.001), and altered values of the TBS Z-score were associated with the severity of vertebral fractures. Finally, in a linear regression-adjusted model, the VAT index predicted TBS lumbar spine L1-L4 (β -0.323; p < 0.001). In patients with OSA VAT impacts bone quality. In these patients, the role of VAT as a metabolically active tissue should be considered.

Bone strain index for fracture risk assessment in older men-the prospective STRAMBO study.

Bone strain index (BSI) is a noninvasive index of bone strength assessed on lumbar spine and femur dual energy X-ray absorptiometry scans using the finite-element method. In this study, we assess the link of the lumbar spine and hip BSI with fracture risk in older men. Prospective cohort study. A cohort of 825 men aged ≥60 was followed up for 12 years. Lumbar spine and hip bone mineral density, BSI, Fracture Risk Assessment Tool (FRAX) for major osteoporotic fractures (MOPFx), and lumbar spine trabecular bone score (TBS) were assessed at baseline. Overall, 159 men had 198 incident fractures. After adjustment for FRAX and prior falls, a higher BSI was associated with a higher fracture risk, eg, trochanter BSI: (HR = 1.34 per standard deviation (SD) increase, 95% CI: 1.14-1.58, P < .001). Patterns were similar for MOPFx, vertebral, nonvertebral, and multiple fractures. The fracture risk was higher in the highest vs the lowest BSI quartiles. The associations were the strongest for the BSI of the lumbar spine and trochanter. When the TBS and BSI were analyzed jointly, their respective contributions to fracture prediction varied according to the fracture and the site of the BSI, eg, both the TBS and the trochanter BSI contributed to the MOPFx prediction (TBS: HR = 1.38/SD decrease, 95%CI: 1.04-1.84, P < .05; BSI: HR = 1.49/SD increase, 95% CI: 1.16-1.91, P < .005). The BSI at both the lumbar and the femoral sites was associated with a higher fracture risk independently of FRAX and prior falls in older men followed prospectively for 12 years.

Trabecular Bone Score in Individuals with Chronic Spinal Cord Injury: A Cross-Sectional Study.

To describe lumbar spine (LS) trabecular bone score (TBS) values after SCI, and to explore the differences in fractures risk assessment between FRAX® and TBS-adjusted FRAX® in individuals living with chronic SCI. Baseline dual-energy x-ray absorptiometry (DXA) scans from an established cohort were acquired using a Hologic Discovery QDR 4500. TBS measurements were performed using the TBS iNsightTM software version 2.1.2.0. A Welch's t-test was performed to explore differences in TBS, FRAX®, and TBS-adjusted FRAX® between men and women, between participants ≤49 years and ≥50 years, and between subgroups with and without history of fracture and with complete and incomplete injury. We analyzed 37 scans; the mean TBS was 1.336 ± 0.107. The mean 10-year fracture risk was 8.8% ± 11.4% for major osteoporotic fracture and 4.0% ± 10.8% for hip fracture according to FRAX®, and 6.6% ± 2.8% for major osteoporotic fracture and 2.8% ± 6.7% for hip fractures according to TBS-adjusted FRAX®. The 10-year fracture risk for major osteoporotic fractures was higher in individuals with a prior fragility fracture compared to those without, according to FRAX® (p = .033) and TBS-adjusted FRAX® (p = .001). Over a half of our sample presented a partially degraded bone microarchitecture based on TBS. TBS was not different between people with motor complete and motor incomplete injury or with and without prior fragility fracture. Future studies are needed to define the clinical relevance of TBS and TBS-adjusted FRAX® in people with chronic SCI.

Predictors of lumbar spine trabecular bone score in women with postsurgical hypoparathyroidism

Hypoparathyroidism is a rare disease that markedly reduces bone remodeling, leading to increased bone mineral density and changes in bone microarchitecture. However, it is currently unclear how these changes affect fracture risk. In this study, we investigated bone mass by dual-energy x-ray absorptiometry, the occurrence of morphometric vertebral fractures, and bone microarchitecture by assessing trabecular bone score in women with postsurgical hypoparathyroidism. We included 67 women with hypoparathyroidism aged 52.9 ± 12.3 years and 63 age- and body mass index-matched controls, which were assessed for femoral and lumbar spine bone mineral density, trabecular bone score, and vertebral fractures by dual-energy x-ray absorptiometry. Women with hypoparathyroidism had significantly higher bone mineral density at the lumbar spine, femoral neck, and total hip compared with controls despite similar trabecular bone score values. Vertebral fracture assessment indicated that two women with hypoparathyroidism presented vertebral fractures, both aged over 65 years. Conversely, no vertebral fractures were detected in control women. In a multivariate linear regression model, we found that older age, diabetes, and lower lumbar spine mineral density were significant predictors of lower trabecular bone score values. Our findings indicate that vertebral fractures are not common among women with postsurgical hypoparathyroidism aged under 65 years. Moreover, trabecular bone score values were similar in women with hypoparathyroidism and age-matched controls and were associated with traditional risk factors for fractures, such as older age, type 2 diabetes, and lower spine bone mineral density. Lay summaryChronic parathyroid hormone deficiency decreases bone turnover and modifies skeletal properties, although the impact of these changes on fracture risk remains unclear. We studied 67 women with postsurgical hypoparathyroidism and 63 age and body mass index-matched healthy controls and found that bone mineral density is increased in women with hypoparathyroidism despite similar trabecular bone score values and a low occurrence of morphometric vertebral fractures. This suggests that the low bone turnover in hypoparathyroidism increases bone mass, but this is not accompanied by improved bone microarchitecture, indicating that trabecular bone score may be a valuable tool to complement the assessment of skeletal health and the risk of fractures in this condition.

Increase in lumbar spine but not distal radius bone mineral density in adults after pancreas kidney transplantation

Osteoporosis occurs in every third individual after simultaneous pancreas kidney transplantation (SPKT). Currently used bone measures insufficiently predict their fracture risk. Lumbar spine Trabecular bone score (TBS) and distal radius areal and volumetric bone mineral density (BMD) were monitored for the first time in patients with type 1 diabetes and chronic renal failure after SPKT with steroid-sparing protocol. In 33 subjects (mean age 43.4 ± 9.8 years), dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were performed just after SPKT (baseline) and one and three years later. While TBS Z-scores increased (−1.1 ± 1.2 and −0.3 ± 1.0; p˂0.001, at baseline and year three, respectively), trabecular volumetric BMD Z-scores at distal radius metaphysis did not change during the study (−1.3 ± 1.3 and −1.3 ± 1.0; p = 0.38). Similarly, areal BMD Z-scores increased at lumbar spine, total hip and femoral neck (all p < 0.01), but not at the distal radius. SPKT induced bone measures' improvement at lumbar spine and hip but not at distal radius. Before suggesting changes in current clinical care, predictive value of individual bone measures or its combination for fracture risk assessment remains to be elucidated.

FRAX® Adjustment Using Renormalized Trabecular Bone Score (TBS) from L1 Alone may be Optimal for Fracture Prediction: The Manitoba BMD Registry

Lumbar spine trabecular bone score (TBS) used in conjunction with FRAX® improves 10-year fracture prediction. The derived FRAX risk adjustment is based upon TBS measured from L1-L4, designated TBSL1-L4-FRAX. In prior studies, TBS measurements that include L1 and exclude L4 give better fracture stratification than L1-L4. We compared risk stratification from TBS-adjusted FRAX using TBS derived from different combinations of upper lumbar vertebral levels renormalized for level-specific differences in individuals from the Manitoba Bone Density Program aged >40 years with baseline assessment of TBS and FRAX. TBS measurements for L1-L3, L1-L2 and L1 alone were calculated after renormalization for level-specific differences. Corresponding TBS-adjusted FRAX scores designated TBSL1-L3-FRAX, TBSL1-L2-FRAX and TBSL1-FRAX were compared with TBSL1-L4-FRAX for fracture risk stratification. Incident major osteoporotic fractures (MOF) and hip fractures were assessed. The primary outcome was incremental change in area under the curve (ΔAUC). The study population included 71,209 individuals (mean age 64 years, 89.8% female). Before renormalization, mean TBS for L1-3, L1-L2 and L1 was significantly lower and TBS-adjusted FRAX significantly higher than from using TBSL1-L4. These differences were largely eliminated when TBS was renormalized for level-specific differences. During mean follow-up of 8.7 years 6745 individuals sustained incident MOF and 2039 sustained incident hip fractures. Compared with TBSL1-L4-FRAX, use of FRAX without TBS was associated with lower stratification (ΔAUC = −0.009, p < 0.001). There was progressive improvement in MOF stratification using TBSL1-L3-FRAX (ΔAUC = +0.001, p < 0.001), TBSL1-L2-FRAX (ΔAUC = +0.004, p < 0.001) and TBSL1-FRAX (ΔAUC = +0.005, p < 0.001). TBSL1-FRAX was significantly better than all other combinations for MOF prediction (p < 0.001). Incremental improvement in AUC for hip fracture prediction showed a similar but smaller trend. In conclusion, this single large cohort study found that TBS-adjusted FRAX performance for fracture prediction was improved when limited to the upper lumbar vertebral levels and was best using L1 alone.

Romosozumab is associated with greater trabecular bone score improvement compared to denosumab in postmenopausal osteoporosis.

Romosozumab significantly increases bone mineral density (BMD) and rapidly reduces fracture risk. Whether romosozumab can improve the spinal trabecular bone score (TBS) as a bone quality indicator merits further investigation. Data for postmenopausal women starting romosozumab or denosumab treatment at Severance Hospital, Korea, were analyzed. Romosozumab and denosumab groups were 1:1 matched using propensity scores, considering relevant covariates. Good responders were defined as those with TBS improvement of 5.8% or greater. Overall, 174 patients (romosozumab, n = 87; denosumab, n = 87) were analyzed. Matched groups did not differ in age (64years), weight, height, previous fracture (38%), lumbar spine or femoral neck BMD (T-score, -3.4 and -2.6, respectively), or prior bisphosphonate or selective estrogen receptor modulator (SERM) exposure (50%). The romosozumab group exhibited a greater increase in lumbar spine BMD (15.2% vs. 6.9%, p < 0.001) and TBS (3.7% vs. 1.7%, p = 0.013) than the denosumab group. In patients transitioning from bisphosphonate or SERM, romosozumab users showed greater improvement in TBS compared to denosumab users (3.9% versus 0.8%, P = 0.006); the drug-naive group showed no significant difference (3.6% versus 2.7%, P = 0.472). The romosozumab group had a higher proportion of good responders than the denosumab group (33.3% vs. 18.4%, p = 0.024). Romosozumab therapy for 12months resulted in 3.8-fold higher odds of a good response in TBS than denosumab after covariate adjustment (adjusted odds ratio 3.85, p = 0.002). Romosozumab could improve bone mass and bone quality, measured by TBS, in postmenopausal osteoporosis, particularly as a subsequent regimen in patients previously taking anti-resorptive agents.

Changes in Bone Quality after Treatment with Etelcalcetide.

Secondary hyperparathyroidism is associated with osteoporosis and fractures. Etelcalcetide is an intravenous calcimimetic for the control of hyperparathyroidism in patients on hemodialysis. Effects of etelcalcetide on the skeleton are unknown. In a single-arm, open-label, 36-week prospective trial, we hypothesized that etelcalcetide improves bone quality and strength without damaging bone-tissue quality. Participants were 18 years or older, on hemodialysis ≥1 year, without calcimimetic exposure within 12 weeks of enrollment. We measured pretreatment and post-treatment areal bone mineral density by dual-energy X-ray absorptiometry, central skeleton trabecular microarchitecture by trabecular bone score, and peripheral skeleton volumetric bone density, geometry, microarchitecture, and estimated strength by high-resolution peripheral quantitative computed tomography. Bone-tissue quality was assessed using quadruple-label bone biopsy in a subset of patients. Paired t tests were used in our analysis. Twenty-two participants were enrolled; 13 completed follow-up (mean±SD age 51±14 years, 53% male, and 15% White). Five underwent bone biopsy (mean±SD age 52±16 years and 80% female). Over 36 weeks, parathyroid hormone levels declined 67%±9% ( P < 0.001); areal bone mineral density at the spine, femoral neck, and total hip increased 3%±1%, 7%±2%, and 3%±1%, respectively ( P < 0.05); spine trabecular bone score increased 10%±2% ( P < 0.001); and radius stiffness and failure load trended to a 7%±4% ( P = 0.05) and 6%±4% increase ( P = 0.06), respectively. Bone biopsy demonstrated a decreased bone formation rate (mean difference -25±4 µ m 3 / µ m 2 per year; P < 0.01). Treatment with etelcalcetide for 36 weeks was associated with improvements in central skeleton areal bone mineral density and trabecular quality and lowered bone turnover without affecting bone material properties. The Effect of Etelcalcetide on CKD-MBD (Parsabiv-MBD), NCT03960437.

The effect of body size and composition on lumbar spine trabecular bone score in morphologically diverse subjects.

The trabecular bone score (TBS) is a tool for assessing bone quality and health. Current TBS algorithm corrects for body mass index (BMI), as a proxy of regional tissue thickness. However, this approach fails to consider BMI inaccuracies due to individual differences in body stature, composition and somatotype. This study investigated the relationship between TBS and body size and composition in subjects with a normal BMI, but with large morphological diversity in body fatness and height. Young male subjects (n = 97; age 17.2±1.0 years), including ski jumpers (n = 25), volleyball players (n = 48) and non-athletes (controls n = 39), were recruited. The TBS was determined from L1-L4 dual-energy X-ray absorptiometry (DXA) scans using TBSiNsight software. TBS correlated negatively with height and tissue thickness in the L1-L4 area in ski jumpers (r = -0.516 and r = -0.529), volleyball players (r = -0.525 and r = -0.436), and the total group (r = -0.559 and r = -0.463), respectively. Multiple regression analyses revealed that height, L1-L4 soft tissue thickness, fat mass and muscle mass were significant determinants of TBS (R2 = 0.587, p<0.001). L1-L4 soft tissue thickness explained 27% and height 14% of the TBS variance. The negative association of TBS and both features suggests that a very low L1-L4 tissue thickness may lead to overestimation of the TBS, while tall stature may have the opposite effect. It seems that the utility of the TBS as a skeletal assessment tool in lean and/or tall young male subjects could be improved if tissues thickness in the lumbar spine area and stature instead of BMI were considered in the algorithm.

Trabecular Bone Score Vertebral Exclusions Affect Risk Classification and Treatment Recommendations: The Manitoba Bmd Registry

Lumbar spine trabecular bone score (TBS), a texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. Lumbar vertebral levels that show structural artifact are excluded from BMD measurement. TBS is relatively unaffected by degenerative artifact, and it is uncertain whether the same exclusions should be applied to TBS reporting. To gain insight into the clinical impact of vertebral exclusion on TBS, we examined the effect of lumbar vertebral exclusions in routine clinical practice on tertile-based TBS categorization and TBS adjusted FRAX-based treatment recommendations. The study population consisted of 71,209 individuals aged 40 years and older with narrow fan-beam spine DXA examinations and retrospectively-derived TBS. During BMD reporting, 34.3% of the scans had one or more vertebral exclusions for structural artifact. When TBS was derived from the same vertebral levels used for BMD reporting, using fixed L1-L4 tertile cutoffs (1.23 and 1.31 from the McCloskey meta-analysis) reclassified 17.9% to a lower and 6.5% to a higher TBS category, with 75.6% unchanged. Reclassification was reduced from 24.4% overall to 17.2% when level-specific tertile cutoffs from the software manufacturer were used. Treatment reclassification based upon FRAX major osteoporotic fracture probability occurred in 2.9% overall, but in 9.6% of those with baseline risk ≥15%. For treatment based upon FRAX hip fracture probability, reclassification occurred in 3.4% overall, but in 10.4% in those with baseline risk ≥2%. In summary, lumbar spine TBS measurements based upon vertebral levels other than L1-L4 can alter the tertile category and treatment recommendations based upon TBS-adjusted FRAX calculation, especially for those close to or exceeding the treatment cut-off. Manufacturer level-specific tertile cut-offs should be used if vertebral exclusions are applied.

Bone Marrow Adipose Tissue Is Increased in Postmenopausal Women With Postsurgical Hypoparathyroidism.

Suppression of bone turnover, greater trabecular volume, and normal-high normal all-site bone mineral density (BMD) are hallmarks of postsurgical hypoparathyroidism (HypoPT). Impairment in the trabecular microarchitecture with possible higher risk of vertebral fractures (VF) in women with postmenopausal HypoPT has also been described. Currently, no data on bone marrow adipose tissue (BMAT) are available in HypoPT. To assess BMAT by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) in postmenopausal women with chronic postsurgical HypoPT. This cross-sectional pilot study, conducted at an ambulatory referral center, included 29 postmenopausal women (mean age 66 ± 8.4 years) with postsurgical HypoPT and 31 healthy postmenopausal women (mean age 63 ± 8.5). Lumbar spine MRI was performed and BMAT was measured by applying PRESS sequences on the L3 body. Lumbar spine, femoral neck, and total hip BMD were measured by dual x-ray absorptiometry (DXA); site-matched spine trabecular bone score (TBS) was calculated by TBS iNsight (Medimaps, Switzerland); VF assessment was performed with lateral thoracic and lumbar spine DXA. Fat content (FC) and saturation level (SL%) were higher (P <.0001 and P <.001), while water content (W) was lower in HypoPT compared to controls (P <.0001). FC significantly correlated with years since menopause and body weight (P <.05) in HypoPT, while TBS negatively correlated with FC and SL% (P <.05) and positively with residual lipids (RL) and W (P <.05). We demonstrate for the first time that BMAT is increased in postmenopausal women with postsurgical hypoparathyroidism and negatively associated with trabecular microarchitecture.

Nupr1 deficiency downregulates HtrA1, enhances SMAD1 signaling, and suppresses age-related bone loss in male mice.

Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-βsignaling was markedly downregulated in Nupr1-KO osteocytes. Nupr1 deficiency also markedly reduced HtrA1 expression, but enhanced SMAD1 signaling in in vitro-cultured primary osteoblasts. In contrast, Nupr1 overexpression enhanced HtrA1 expression in osteoblasts, suggesting that Nupr1 regulates HtrA1 expression, thereby suppressing osteoblastogenesis. Since HtrA1 is also involved in cellular senescence and age-related diseases, we analyzed aging-related bone loss in Nupr1-KO mice. Significant spine trabecular bone loss was noted in WT male and female mice during 6-19 months of age, whereas aging-related trabecular bone loss was attenuated, especially in Nupr1-KO male mice. Moreover, cellular senescence-related markers were upregulated in the osteocytes of 6-19-month-old WT male mice but markedly downregulated in the osteocytes of 19-month-old Nupr1-KO male mice. Oxidative stress-induced cellular senescence stimulated Nupr1 and HtrA1 expression in in vitro-cultured primary osteoblasts, and Nupr1 overexpression enhanced p16ink4a expression in osteoblasts. Finally, NUPR1 expression in osteocytes isolated from the bones of patients with osteoarthritis was correlated with age. Collectively, these results indicate that Nupr1 regulates HtrA1-mediated osteoblast differentiation and senescence. Our findings unveil a novel Nupr1/HtrA1 axis, which may play pivotal roles in bone formation and age-related bone loss.

Trabecular Bone Score (TBS) Cross-Calibration for GE Prodigy and IDXA Scanners

Dual-energy X-ray absorptiometry (DXA) is used for osteoporosis diagnosis, fracture prediction and to monitor changes in bone mineral density (BMD). Change in DXA instrumentation requires formal cross-calibration and procedures have been described by the International Society for Clinical Densitometry. Whether procedures used for BMD cross-calibration are sufficient to ensure lumbar spine trabecular bone score (TBS) cross-calibration is currently uncertain. The Manitoba Bone Density Program underwent a program-wide upgrade in DXA instrumentation from GE Prodigy to iDXA in 2012, and a representative a sample of 108 clinic patients were scanned on both instruments. Lumbar spine TBS (L1-L4) measurements were retrospectively derived in 2013. TBS calibration phantoms were not available at our site when this was performed. We found excellent agreement for lumbar spine BMD, without deviation from the line of perfect agreement, and low random error (standard error of the estimate [SEE] 2.54% of the mean). In contrast, spine TBS (L1-L4) showed significant deviation from the line of identity: TBS(iDXA) = 0.730 x TBS(Prodigy) + 0.372 (p<0.001 for slope and intercept); SEE 5.12% of the mean with negative bias (r=-0.550). Results were worse for scans acquired in thick versus standard mode, but similar when the population was stratified as BMI < or > 35 kg/m2. In summary, it cannot be assumed that just because BMD cross-calibration is good that this applies to TBS. This supports the need for using TBS phantom calibration to accommodate between-scanner differences as part of the manufacturer's TBS software installation.

Ethnicity and Fracture Risk Stratification from Trabecular Bone Score in Canadian Women: The Manitoba BMD Registry

Lumbar spine Trabecular Bone Score (TBS), a grey-level texture measure derived from spine dual-energy x-ray absorptiometry (DXA) images, is a bone mineral density (BMD)-independent risk factor for fracture. An unresolved and controversial question is whether there are ethnic differences that affect the utility of TBS for fracture risk assessment. The current analysis examined whether self-identified ethnicity (White, Asian, Black) in women age 40 years and older referred for DXA testing affected fracture risk stratification from TBS using a large clinical registry. The study population comprised 63,078 White women, 1,915 Asian women and 329 Black women (n=329) with mean follow up 9.0±5.2 years. There were between group differences in BMI (Black>White>Asian), lumbar spine fat percentage (Asian>White>Black) and lumbar spine tissue thickness (Black>White>Asian). Despite this, lumbar spine TBS was not significantly different between the subgroups, though there was a significant difference in lumbar spine and total hip BMD (Black >White>Asian). TBS provided significant stratification for MOF and any fracture for all ethnicity subgroups, and for hip fracture in White and Asian subgroups (insufficient numbers for analysis in Black women). No significant difference in White vs. Asian or White vs. Black women were identified using a Bonferroni adjusted p-value. In summary, we found that lumbar spine TBS measurements were similar among White, Asian and Black women referred for DXA assessment in Manitoba, Canada. TBS and BMD measurements significantly stratified fracture risk in all three populations without a meaningful difference between groups. This suggests that TBS does not need to be used differently in White vs. non-White populations.

Association of mental disorders and psychotropic medications with bone texture as measured with trabecular bone score.

Mental disorders and psychotropic medications are known to increase the risk of osteoporosis and fractures. However, current evidence is mostly limited to studies that used bone mineral density (BMD), which does not provide information about the texture of bone tissue and can underestimate fracture risk. We tested the association between bone texture, as measured with lumbar spine trabecular bone score (TBS), and both diagnosed mental disorders and psychotropic medication use in a large population-based BMD registry from Manitoba, Canada. General linear and logistic regression models were used to test the association of TBS with mental disorders (anxiety, depression, schizophrenia, and alcohol use disorder) and psychotropic medications use (selective serotonin reuptake inhibitors [SSRI], tricyclic antidepressants [TCA], other antidepressants, lithium, non‑lithium mood stabilizers, antipsychotics, and benzodiazepines), adjusted for comorbidities and confounding factors. The study population contained 45,716 women (mean age=64.1, SD=10.4), which included 21.1% with diagnoses for mental disorders and 18.7% using psychotropic medications. We observed significant negative covariate-adjusted effects on TBS from diagnosed alcohol use disorder (3.1% reduction in TBS, p<0.001) and exposure to SSRI (0.6% reduction, p<0.001), TCA (0.8% reduction, p<0.001), other antidepressants (0.8% reduction, p<0.001), and lithium (3% reduction, p<0.001). Logistic regression revealed that TBS in the lowest (versus highest) tertile was associated with alcohol use disorder (adjusted odds ratio [OR]=2.87, 95% confidence interval [CI]: 1.95, 4.21), exposure to SSRI (OR=1.21; 95% CI: 1.08, 1.35), TCA (OR=1.18, 95% confidence interval [CI]: 1.04, 1.35), other antidepressants (OR=1.26; 95% CI: 1.09, 1.45), and lithium (OR=1.97; 95% CI: 1.09, 3.57). Our results suggest that alcohol use disorder, antidepressants, and lithium are associated with poorer bone texture in women. These findings add to the current literature on the link of bone pathology with mental disorders and psychotropic medications.

Trabecular Bone Score as a Reliable Measure of Lumbar Spine Bone Microarchitecture in Acromegalic Patients.

Although GH and IGF-1 excess has a controversial impact on bone mineral density (BMD), acromegalic patients display variable degrees of bone structure impairment. In this study, we aim to investigate the usefulness of trabecular bone score (TBS), compared to BMD, in identifying acromegalic patients with impaired lumbar spine trabecular microarchitecture. Forty-four acromegalic patients were investigated for disease control, metabolic and gonadal status, bone metabolism parameters, and the presence of vertebral fractures (VFs). Patients and matched healthy controls underwent BMD and TBS examination. Mean TBS values were lower in patients than in controls (p &lt; 0.001), without significant differences in mean lumbar and femoral BMD. TBS values were significantly higher in controlled patients compared to the uncontrolled ones (p = 0.012). No significant differences were found in bone markers with respect to disease control. Mean TBS or lumbar BMD did not significantly differ in patients with or without VFs (prevalence 11.4%). TBS and BMD levels were lower in hypogonadal patients compared to the eugonadal ones (p = 0.030 and p &lt; 0.001, respectively). In conclusion, TBS values are significantly lower in patients than in controls, confirming the presence of impaired lumbar spine trabecular bone in acromegaly. Both uncontrolled disease and hypogonadism contribute to TBS deterioration in acromegaly.

Spine trabecular bone scores and bone mineral density of postmenopausal Taiwanese women.

The aims of the study were to determine the mean trabecular bone score (TBS) of postmenopausal Taiwanese women and to analyze the value of TBS in predicting osteoporosis. A total of 1,915 postmenopausal women with lumbar spine and hip bone mineral density (BMD) and spine TBS were enrolled from a single medical center into this study. The women's BMD and TBS were measured using dual x-ray absorptiometry (Discovery Wi; Hologic, Bedford, Mass) and iNsight software (Med-Imaps SASU, Merignac, France), respectively. The women's demographic characteristics; lumbar spine, total hip, and femoral neck BMD; and lumbar spine TBS were recorded, and correlations among the parameters were identified using a 2-tailed Pearson test, in which a P value less than 0.05 was considered statistically significant. We developed simple linear regression models to represent changes related to TBS and performed an analysis of variance on the selected variables. The average age of the women was 62.5 ± 9.1 years (range, 25.7-93.7 years). The mean TBS was 1.300 ± 0.086 (range, 1.015-1.596). The TBS was weakly and negatively correlated with body mass index ( r = -0.078) and moderately and positively correlated with the lumbar spine BMD ( r = 0.619). The patients' lowest BMD values among those measured at multiple sites revealed a higher rate of osteoporosis (32.5%) than those measured at individual sites. Degraded TBS were noted in 21.2% of the participants, and a combination of BMD and TBS results predicted more individuals (7.8%) at a high risk of fracture than did the BMD result only. The rates of both osteoporosis and degraded TBS increased with age. Bone mineral density and TBS can be used in combination to predict osteoporosis in a greater number of postmenopausal Taiwanese women. Because the incidence of osteoporosis is the highest among older women, clinicians should pay careful attention to TBS degradation among older patients without low BMD.

Association of amino acid metabolites with osteoporosis, a metabolomic approach: Bushehr elderly health program

Amino acids are the most frequently reported metabolites associated with low bone mineral density (BMD) in metabolomics studies. We aimed to evaluate the association between amino acid metabolic profile and bone indices in the elderly population. 400 individuals were randomly selected from 2384 elderly men and women over 60years participating in the second stage of the Bushehr elderly health (BEH) program, a population-based prospective cohort study that is being conducted in Bushehr, a southern province of Iran. Frozen plasma samples were used to measure 29 amino acid and derivatives metabolites using the UPLC-MS/MS-based targeted metabolomics platform. We conducted Elastic net regression analysis to detect the metabolites associated with BMD of different sites and lumbar spine trabecular bone score, and also to examine the ability of the measured metabolites to differentiate osteoporosis. We adjusted the analysis for possible confounders (age, BMI, diabetes, smoking, physical activity, vitamin D level, and sex). Valine, leucine, isoleucine, and alanine in women and tryptophan in men were the most important amino acids inversely associated with osteoporosis (OR range from 0.77 to 0.89). Sarcosine, followed by tyrosine, asparagine, alpha aminobutyric acid, and ADMA in women and glutamine in men and when both women and men were considered together were the most discriminating amino acids detected in individuals with osteoporosis (OR range from 1.15 to 1.31). We found several amino acid metabolites associated with possible bone status in elderly individuals. Further studies are required to evaluate the utility of these metabolites as clinical biomarkers for osteoporosis prediction and their effect on bone health as dietary supplements.

Insulin resistance and skeletal health.

Bone fragility is a complication of type 2 diabetes (T2D), and insulin resistance is suspected to contribute to diabetes-related bone deficits. This article provides an overview of emerging clinical research involving insulin resistance and bone health by summarizing recent publications, identifying existing knowledge gaps, and suggesting 'next steps' for this evolving field of research. Clinical studies in children and adults report greater bone density in people with increased insulin resistance, but these associations are often attenuated when adjusting for body size. Advancements in bone imaging methods allow for assessment of nuanced characteristics of bone quality and strength that extend beyond standard bone mineral density assessment methods. For example, several recent studies focusing on lumbar spine trabecular bone score, a relatively new measure of trabecular bone quality from dual-energy X-ray absorptiometry, have reported generally consistent inverse associations with insulin resistance. Longitudinal studies using advanced imaging methods capable of evaluating trabecular bone microstructure and strength, such as high-resolution peripheral quantitative computed tomography, are lacking. Studies in younger individuals are sparse, but emerging data suggest that peak bone mass attainment might be threatened by diabetes progression, and increased visceral fat, suppressed muscle-bone unit, advanced glycation end-products, sedentary lifestyle, and poor diet quality might contribute to diabetes effects on bone. Prospective studies during the transition from adolescence to young adulthood are required. Insulin resistance is a main feature of T2D, which is suspected to contribute to subclinical diabetes-related threats to bone health. Future clinical studies should focus on the critical years surrounding peak bone mass and peak bone strength attainment using contemporary imaging techniques.