Changes In Bone Quality Research Articles

Pharmacological Treatment of Obesity in Older Adults.

Obesity is a complex health issue with growing prevalence worldwide. It is also becoming more prevalent in the population of older adults (i.e., 65 years of age and older), affecting frequency and severity as well as other comorbidities, quality of life and consequently, life expectancy. In this article we review currently available data on pharmacotherapy of obesity in the population of older adults and its role in obesity management. Even though there is growing evidence, in particular in the general population, of favourable efficacy and safety profiles of glucagon-like peptide-1 (GLP-1) receptor agonists liraglutide and semaglutide, and recently dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide, concise guidelines for older adults are not available to this day. We further discuss specific approaches to frequently represented phenotype of obesity in older adults, in particular sarcopenic obesity and rationale when to treat and how. In older adults with obesity there is a need for more drug trials focusing not only on weight loss, but also on geriatric endpoints including muscle mass preservation, bone quality and favourable fat distribution changes to get enough data for evidence-based recommendation on obesity treatment in this growing sub-population.

Presence and Progression of Changes in Bone Mass, Bone Quality, and Vascular Calcifications in Patients with Moderate to Advanced Reduction in Kidney Function

Presence and Progression of Changes in Bone Mass, Bone Quality, and Vascular Calcifications in Patients with Moderate to Advanced Reduction in Kidney Function

Correlation of Vertebral Bone Quality and Paraspinal Muscle Changes With Adjacent Segment Degeneration After Transforaminal Lumbar Interbody Fusion Operation

To investigate the correlation of vertebral bone quality (VBQ) and paraspinal muscle changes with adjacent segment degeneration (ASD) after transforaminal lumbar interbody fusion (TLIF) through a retrospective analysis of patients who have undergone TLIF for lumbar degenerative diseases (LDD). A total of 98 patients who underwent TLIF surgical treatment for LDD between January 2016 and December 2022 at Shenzhen People's Hospital were selected. Well-established follow-up imaging data were available for all subjects who were divided into two groups, the ASD group (n=43) and the non-ASD (N-ASD) group (n=55), according to whether they met the ASD evaluation criteria. Data on the basic characteristics of the patients in both groups were collected, and the relevant parameters, including VBQ and the total cross-sectional area (TCSA) and the functional cross-sectional area (FCSA) of psoas major (PM), erector spinae (ES), and multifidus (MF), were measured by magnetic resonance imaging of the lumbar spine performed preoperatively and at the last follow-up. Then, the relative fat infiltration (RFI) was calculated from the above metrics accordingly. Logistic regression analysis was conducted to investigate the risk factors for ASD. The incidence of ASD was 43.9% (n=43) at the final follow-up. The mean follow-up time was (27.23±4.15) months. The age, body mass index (BMI), preoperative bone mineral density (BMD), preoperative VBQ, ΔRFIPM, and ΔRFIES+MF showed significant differences between the ASD and N-ASD groups (P<0.05). According to the results of the logistic regression analysis, BMI (odds ratio [OR]=1.450, 95% confidence interval [CI]: 1.081-1.945, P=0.013), preoperative VBQ (OR=6.191, 95% CI: 1.692-22.657, P=0.006), and ΔRFIES+MF (OR=1.117, 95% CI: 1.007-1.238, P=0.037) were independent risk factors for ASD. The incidence of postoperative ASD in patients who have undergone TLIF for LDD was found to be associated with higher BMI, preoperative VBQ, and increased postoperative relative fat infiltration of the ES and MF muscles. Consequently, it is advisable to prioritize the intraoperative protection of the paraspinal muscles during TLIF. In the postoperative period, it is essential to strengthen exercises of the lower back muscles and to optimize bone mass and weight management, which is conducive to reducing the risk of ASD in the postoperative period.

Titanium patient-specific scaphoid replacement for unreconstructable nonunions: a case series study.

Although reconstruction is the preferred treatment option for symptomatic scaphoid nonunions, this may not be an option due to inadequate bone quality or degenerative changes. Existing salvage procedures tend to compromise function. This study introduces an alternative approach through the utilisation of a 3-D-printed titanium patient-specific scaphoid implant. In this retrospective case series, the outcomes of 12 patients treated for an unreconstructable scaphoid nonunion with a 3-D-printed prosthesis were evaluated. Patient-reported outcomes, range of motion, grip strength and plain radiographs were assessed pre- and postoperatively. The mean follow-up was 2 years and 8 months. Range of movement and patient-reported outcome scores improved postoperatively, although improvement in movement was not significant. Except for one, all implants showed satisfactory alignment on radiographs without any further degenerative changes. 3-D-printed titanium scaphoid replacement may be an alternative to salvage procedures for unreconstructable scaphoid nonunion.Level of evidence: IV.

Beyond bone volume: Understanding tissue-level quality in healing of maxillary vs. femoral defects

Currently, principles of tissue engineering and implantology are uniformly applied to all bone sites, disregarding inherent differences in collagen, mineral composition, and healing rates between craniofacial and long bones. These differences could potentially influence bone quality during the healing process. Evaluating bone quality during healing is crucial for understanding local mechanical properties in regeneration and implant osseointegration. However, site-specific changes in bone quality during healing remain poorly understood. In this study, we assessed newly formed bone quality in sub-critical defects in the maxilla and femur, while impairing collagen cross-linking using β-aminopropionitrile (BAPN). Our findings revealed that femoral healing bone exhibited a 73 % increase in bone volume but showed significantly greater viscoelastic and collagen changes compared to surrounding bone, leading to increased deformation during long-term loading and poorer bone quality in early healing. In contrast, the healing maxilla maintained equivalent hardness and viscoelastic constants compared to surrounding bone, with minimal new bone formation and consistent bone quality. However, BAPN-impaired collagen cross-linking induced viscoelastic changes in the healing maxilla, with no further changes observed in the femur. These results challenge the conventional belief that increased bone volume correlates with enhanced tissue-level bone quality, providing crucial insights for tissue engineering and site-specific implant strategies. The observed differences in bone quality between sites underscore the need for a nuanced approach in assessing the success of regeneration and implant designs and emphasize the importance of exploring site-specific tissue engineering interventions. Statement of significanceAccurate measurement of bone quality is crucial for tissue engineering and implant therapies. Bone quality varies between craniofacial and long bones, yet it's often overlooked in the healing process. Our study is the first to comprehensively analyze bone quality during healing in both the maxilla and femur. Surprisingly, despite significant volume increase, femur healing bone had poorer quality compared to the surrounding bone. Conversely, maxilla healing bone maintained consistent quality despite minimal bone formation. Impaired collagen diminished maxillary healing bone quality, but had no further effect on femur bone quality. These findings challenge the notion that more bone volume equals better quality, offering insights for improving tissue engineering and implant strategies for different bone sites.

Transmenopausal changes in cortical bone quality

Bone's resistance to fracture depends on its amount and quality, the latter including its structural and material/compositional properties. Bone material properties are dependent on bone turnover rates, which are significantly elevated immediately following menopause. Previously published data reported that following menopause, the amount of organic matrix synthesized at actively forming surfaces is significantly decreased, while glycosaminoglycan content was also modulated at resorbing surfaces, in the cancellous compartment.In the present study, we used Raman microspectroscopic analysis of paired iliac crest biopsies obtained before and shortly after menopause (1 year after cessation of menses) in healthy females to investigate changes in material/compositional properties due to menopause, in the cortical compartment. Specifically, the mineral/matrix ratio, the relative proteoglycan content, the mineral maturity/crystallinity, and the relative pyridinoline collagen cross-link content were determined at actively forming intracortical surfaces (osteons) as a function of tissue age, as well as in interstitial bone.Results indicated that it is the freshly synthesized organic matrix content that significantly declines following menopause, in agreement with what was previously reported for the cancellous compartment. This decline was not evident in the freshly deposited mineral content. None of the compositional/quality properties were altered following menopause either. Finally, no differences in any of the monitored parameters were evident in cortical interstitial bone.

Combining anabolic loading and raloxifene improves bone quantity and some quality measures in a mouse model of osteogenesis imperfecta

Osteogenesis imperfecta (OI) increases fracture risk due to changes in bone quantity and quality caused by mutations in collagen and its processing proteins. Current therapeutics improve bone quantity, but do not treat the underlying quality deficiencies. Male and female G610C+/− mice, a murine model of OI, were treated with a combination of raloxifene and in vivo axial tibial compressive loading starting at 10 weeks of age and continuing for 6 weeks to improve bone quantity and quality. Bone geometry and mechanical properties were measured to determine whole bone and tissue-level material properties. A colocalized Raman/nanoindentation system was used to measure chemical composition and nanomechanical properties in newly formed bone compared to old bone to determine if bone formed during the treatment regimen differed in quality compared to bone formed prior to treatment. Lastly, lacunar geometry and osteocyte apoptosis were assessed. OI mice were able to build bone in response to the loading, but this response was less robust than in control mice. Raloxifene improved some bone material properties in female but not male OI mice. Raloxifene did not alter nanomechanical properties, but loading did. Lacunar geometry was largely unchanged with raloxifene and loading. However, osteocyte apoptosis was increased with loading in raloxifene treated female mice. Overall, combination treatment with raloxifene and loading resulted in positive but subtle changes to bone quality.

Adaptive enhancement of apatite crystal orientation and Young's modulus under elevated load in rat ulnar cortical bone

Functional adaptation refers to the active modification of bone structure according to the mechanical loads applied daily to maintain its mechanical integrity and adapt to the environment. Functional adaptation relates to bone mass, bone mineral density (BMD), and bone morphology (e.g., trabecular bone architecture). In this study, we discovered for the first time that another form of bone functional adaptation of a cortical bone involves a change in bone quality determined by the preferential orientation of apatite nano-crystallite, a key component of the bone. An in vivo rat ulnar axial loading model was adopted, to which a 3–15 N compressive load was applied, resulting in approximately 440–3200 μɛ of compression in the bone surface. In the loaded ulnae, the degree of preferential apatite c-axis orientation along the ulnar long axis increased in a dose-dependent manner up to 13 N, whereas the increase in BMD was not dose-dependent. The Young's modulus along the same direction was enhanced as a function of the degree of apatite orientation. This finding indicates that bone has a mechanism that modifies the directionality (anisotropy) of its microstructure, strengthening itself specifically in the loaded direction. BMD, a scalar quantity, does not allow for load-direction-specific strengthening. Functional adaptation through changes in apatite orientation is an excellent strategy for bones to efficiently change their strength in response to external loading, which is mostly anisotropic.

Rat bone responses to hindlimb unloading-reloading: Composition, BMD and mechanical properties

IntroductionBone loss in lower limbs under space microgravity condition can persist even after the astronauts return to Earth's gravitational environment. It is crucial to determine the extent and timing of bone recovery after spaceflight, especially for long-term flights. However, there is a lack of comprehensive descriptions of the recovery of various aspects of bone quality, particularly in terms of compositional characteristics that reflect changes in bone quality. Therefore, the objective of this study is to investigate the alterations in bone mineral density, composition characteristics, and mechanical properties of rat lower limbs during unloading (tail suspension) and the subsequent recovery loading period. MethodsRats were subjected to tail suspension for four weeks (TS4) followed by reloading for an additional four weeks. Bone mineral density (BMD) was measured by μ-CT and analyzed. The mechanical properties of the tibia were assessed by a three-point bending test, and the composition characteristics of bone tissue were evaluated using Raman spectroscopy. Regression analysis was performed to identify main component related to mechanical property. ResultsIn the metaphysis, BMD of the tibia significant decreased, particularly in trabecular bone. Upon reloading, only the cortical bone showed recovery. In the diaphysis, cortical bone remained unchanged during unloading but demonstrated delayed bone loss during the reloading period. Simultaneously, the mechanical properties of tibia experienced a substantial reduction after four weeks of unloading, The stiffness and maximum strength did not fully recover, though the elastic modulus and the ultimate strength were restored following the reloading process. Raman spectroscopy characterization found an increase in the carbonate substitution and crystal crystallinity of the diaphysis after 4 weeks of unloading. There was an intriguing alteration in the mineralized collagen ratio, that an increase was observed in the diaphysis while a decrease was observed in the metaphysis. During 4 weeks of reloading, the compositional characteristics of the diaphysis recovered earlier than those of the metaphysis, with the exception of crystallinity which remained unrecovered. Regression analysis indicated that carbonate replacement has a strong correlation to bone mechanical properties during the 4 weeks of unloading and subsequent 4 weeks of reloading. ConclusionsThe data obtained in this study highlight the incomplete recovery of bone mineral density, mechanical properties, and compositional characteristics during reloading in tail-suspended rats. These findings deepen our understanding of microgravity-induced bone loss and provide valuable information to develop interventions not only for astronauts but also for persons on earth during and after prolonged periods of unloading.

Role of immunological and biochemical markers in bone turnover in type I diabetic patients in Karbala province, Iraq

Introduction &amp; Aim: Long-term diabetes mellitus (DM) is known to have a deleterious impact on bone health, resulting in change in bone mineral density, bone turnover, and bone quality, all of which increase the risk of fractures. The aim of. this study was to link immunological and pro-inflammatory cytokine (I.L-6, I.L-1, and TNF-alpha) markers in patients.with type 1 diabetes to Their connection to bones formation (sPINP) and bone resorption parameters (sCTX). Materials &amp; Methods: This study included 80 patients suffering from T1DM in the age range of 20-45 years. The patients were assayed for their biochemical (Vitamin D and HbA1c), Immunological (IL-6, IL-1 and TNF-alpha) parameters, as well as bone formation and resorption markers. Results: HbA1c values were observed to be 7.5 in 85% of individuals, while vitamin D levels were 16 ng/mL. Correlation in patients with HbA1c 7.5. The results of a linear regression between I.L-6 and sCTX showed that there was an increase in sCTX for each unit of IL-6. Conclusion: In patients with HbA1c levels 7.5, there is an association between IL-6, TNFalpha, and the bone resorption. TNF-alpha and IL-6 have been linked to metabolic control loss.

Is there a Correlation between Radiographic Absorptiometry of the Phalanges of the Hand and Radiomorphometric Indices of the Mandible?

Objectives: The aim of this study was to correlate the mandibular bone quality through radiomorphometric indices in panoramic radiograph with bone quality of non-dominant hand phalanges by radiographic absorptiometry phalanx (RA). Methods: The sample consisted of 167 patients (128 women and 39 men) with a mean age of 52.09 (± 11.5) divided into four groups according to RA test: (A) 92; (B) 36; (C) 25 and (D) with 14.9. A panoramic radiograph was taken of each patient and one observer made measurements of cortical thickness at the mental foramen (mental index, MI) and gonion (goniac index, GI) regions and fractal dimension (FD) analyze in mandibular ramus. In phalangeal radiograph was made measurements of cortical thickness at the intermediate (medial phalange index, MPI) and proximal (proximal phalange index, PPI) phalangeal. Results: The results showed correlation (p < 0.00037) between Klemetti index with RA. Variance analysis MI, GI, MPI, PPI shown significant differences (p < 0.05) between the two groups (normal and low bone mineral density - BMD). Area under the ROC curve was 0.74 (sensitivity = 97.4%, specificity = 78%) for MI, 0.79 (sensitivity = 94, specificity = 54%) for GI, 0.77 (sensitivity = 94.8%, specificity = 64%) for MPI, 0.76 (sensitivity = 93.1%, specificity = 62%) for PPI, 0.71 (sensitivity = 96.5%, specificity = 86%) for FD. Conclusions: Our results suggest that the analysis of radiomorphometric indices showed moderate accuracy for detecting changes in mandibular bone quality according to AR.

Fracture risk among children and adolescents with celiac disease: a nationwide cohort study.

Metabolic bone disease is a common manifestation of celiac disease (CD). We aimed to assess fracture risk among children and adolescents with CD compared with a matched group. This registry-based cohort study included 2372 children with CD who were matched 1:5 to 11,860 children without CD. Demographic and clinical data were obtained from the electronic database of Meuhedet, a health maintenance organization. Fracture events at ages 1-18 years were identified by coded diagnoses. The overall fracture incidence rate was 256 per 10,000 patient-years (PY) in the CD group and 165 per 10,000 PY in the comparison group (p < 0.001). The hazard ratio (HR) to have a fracture was 1.57 (95% CI 1.43-1.73, p < 0.001) for the CD group compared to the matched group. The HR for multiple fractures was 1.67 (95% CI 1.38-2.01, p < 0.001). Analysis of the pre- and post-diagnosis periods separately showed that the HR for fractures in the pre-diagnosis period was 1.64 (95% CI 1.42-1.88, p < 0.001) for the CD group compared to the matched group, and 1.52 (95% CI 1.26-1.71, p < 0.001) in the period from diagnosis to the end of the follow-up period. Children with CD had increased fracture risk both preceding and following the diagnosis of CD. One manifestation of celiac disease (CD) is metabolic bone disease, including osteoporosis and impaired bone mineralization. We found increased fracture risk among children with CD, both preceding the CD diagnosis and during the years following the diagnosis. Recognition of the high risk of fractures in this population may help promote prevention. Further studies are needed to evaluate changes in bone quantity and quality after initiation of a gluten-free diet, and to identify those at risk for persistent metabolic bone disease.

Five-year change of panoramic radiomorphometric indices and fractal dimension values in type 2 diabetes patients.

Diabetes mellitus is a chronic disease characterized by dysregulation of glucose metabolism, with characteristic long-term complications accompanied by changes in bone quality. The purpose of this study is to compare the results with a control group by performing radiomorphometric analyses on panoramic radiographs obtained 5years apart to examine changes in the mandibular bone cortex and microstructures of type 2 diabetes mellitus (T2DM) patients. Two panoramic radiographs that were taken 5years (mean 5.26 ± 0.134) apart from 52 patients with T2DM (n:26) and a control group (n:26) were used. A total of 104 images were evaluated. Analyses were done from the condyle (FD1), angulus (FD2), distal second premolar apex (FD3), and anterior to the mental foramen (FD4) for fractal dimension (FD) in the mandible. Symphysis index (SI), anterior index (AI), molar index (MI), posterior index (PI), and panoramic mandibular index (PMI) measurements were taken for cortical analysis. Three-way ANOVA, three-way robust ANOVA, two-way ANOVA, and two-way robust ANOVA tests were used for statistical analysis (p < 0.05). After a 5-year period, there was a significant decrease in all FD measures of the mandible in both T2DM and control groups (p < 0.05). This resulted in a statistical difference in the main effect of time. After a 5-year period, no significant difference in mandibular cortical measures was identified between the T2DM and control groups (p > 0.05). According to panoramic radiography, the mandibular trabecular structure deteriorated after 5years, whereas cortical values remained the same. It concluded that T2DM had no effect on these results.

The myosin and RhoGAP MYO9B influences osteocyte dendrite growth and responses to mechanical stimuli.

Introduction: Myosin IXB (MYO9B) is an unconventional myosin with RhoGAP activity and thus is a regulator of actin cytoskeletal organization. MYO9B was previously shown to be necessary for skeletal growth and health and to play a role in actin-based functions of both osteoblasts and osteoclasts. However, its role in responses to mechanical stimulation of bone cells has not yet been described. Therefore, experiments were undertaken to determine the role of MYO9B in bone cell responses to mechanical stress both in vitro and in vivo. Methods: MYO9B expression was knocked down in osteoblast and osteocyte cell lines using RNA interference and the resulting cells were subjected to mechanical stresses including cyclic tensile strain, fluid shear stress, and plating on different substrates (no substrate vs. monomeric or polymerized collagen type I). Osteocytic cells were also subjected to MYO9B regulation through Slit-Robo signaling. Further, wild-type or Myo9b -/- mice were subjected to a regimen of whole-body vibration (WBV) and changes in bone quality were assessed by micro-CT. Results: Unlike control cells, MYO9B-deficient osteoblastic cells subjected to uniaxial cyclic tensile strain were unable to orient their actin stress fibers perpendicular to the strain. Osteocytic cells in which MYO9B was knocked down exhibited elongated dendrites but were unable to respond normally to treatments that increase dendrite length such as fluid shear stress and Slit-Robo signaling. Osteocytic responses to mechanical stimuli were also found to be dependent on the polymerization state of collagen type I substrates. Wild-type mice responded to WBV with increased bone tissue mineral density values while Myo9b -/- mice responded with bone loss. Discussion: These results demonstrate that MYO9B plays a key role in mechanical stress-induced responses of bone cells in vitro and in vivo.

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.

Strategies to reduce the onset of sleeve gastrectomy associated bone loss (STRONG BONES): Trial design and methods

BackgroundDespite recognized improvements in obesity-related comorbidities, mounting evidence implicates surgical weight loss in the onset of skeletal fragility. Sleeve gastrectomy (SG) is the most commonly performed bariatric procedure and is associated with 3–7% axial bone loss in the year following surgery. Bisphosphonates are FDA-approved medications for the prevention and treatment of age-related bone loss and may represent a strategy to reduce bone loss following SG surgery. MethodsThe Strategies to Reduce the Onset of Sleeve Gastrectomy Associated Bone Loss (STRONG BONES) trial (NCT04922333) is designed to definitively test whether monthly administration of the bisphosphonate, risedronate, for six months can effectively counter SG-associated bone loss. Approximately 120 middle-aged and older (≥40 years) SG patients will be randomized to six months of risedronate or placebo treatment, with skeletal outcomes assessed at baseline, six, and 12-months post-surgery. The primary outcome of the trial is 12-month change in total hip areal bone mineral density (aBMD), measured by dual energy x-ray absorptiometry (DXA). This will be complemented by DXA-acquired aBMD assessment at other skeletal sites and quantitative computed tomography (QCT) derived changes in bone quality. Change in muscle mass and function will also be assessed, as well as biomarkers of bone health, turnover, and crosstalk, providing mechanistic insight into intervention-related changes to the bone-muscle unit. DiscussionResults from the STRONG BONES trial have the potential to influence current clinical practice by determining the ability of bisphosphonate use to mitigate bone loss and concomitant fracture risk in middle-aged and older SG patients.

Micro-scale vertebral features in postmenopausal women with alcohol-associated and metabolic-associated fatty liver disease: ex vivo bone quality analyses.

Although epidemiological studies indicate increased fracture risk in women with alcohol-associated liver disease (AALD) and metabolic-associated fatty liver disease (MAFLD), data about their micro-scale bone features are still limited. We aimed to characterize bone quality changes in the anterior mid-transverse part of the first lumbar vertebral body collected from 32 adult postmenopausal females. Based on pathohistological assessment of the liver tissue, individuals were divided into AALD (n = 13), MAFLD (n = 9), and control group (n = 10). We analyzed trabecular and cortical micro-architecture (using micro-computed tomography), bone mechanical properties (using Vickers microhardness tester), osteocyte lacunar network and bone marrow adiposity morphology (using optic microscopy). Data were adjusted to elude the covariant effects of advanced age and body mass index on our results. Our data indicated a minor trend toward deteriorated bone quality in MAFLD women, presented in impaired trabecular and cortical micro-architectural integrity, which could be associated with bone marrow adiposity alterations noted in these women. Additionally, we observed a significant decline in micro-architectural, mechanical, and osteocyte lacunar features in lumbar vertebrae collected from the AALD group. Lastly, our data indicated that vertebral bone deterioration was more prominent in the AALD group than in the MAFLD group. Our data suggested that MAFLD and AALD are factors that could play a part in compromised vertebral strength of postmenopausal women. Also, our data contribute to understanding the multifactorial nature of bone fragility in these patients and highlight the necessity for developing more effective patient-specific diagnostic, preventive, and therapeutic strategies.

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study.

The impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART. HIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate. A total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF. A bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity.

MRI-based porosity index (PI) and suppression ratio (SR) in the tibial cortex show significant differences between normal, osteopenic, and osteoporotic female subjects.

Ultrashort echo time (UTE) MRI enables quantitative assessment of cortical bone. The signal ratio in dual-echo UTE imaging, known as porosity index (PI), as well as the signal ratio between UTE and inversion recovery UTE (IR-UTE) imaging, known as the suppression ratio (SR), are two rapid UTE-based bone evaluation techniques developed to reduce the time demand and cost in future clinical studies. The goal of this study was to investigate the performance of PI and SR in detecting bone quality differences between subjects with osteoporosis (OPo), osteopenia (OPe), and normal bone (Normal). Tibial midshaft of fourteen OPe (72 ± 6 years old), thirty-one OPo (72 ± 6 years old), and thirty-seven Normal (36 ± 19 years old) subjects were scanned using dual-echo UTE and IR-UTE sequences on a clinical 3T scanner. Measured PI, SR, and bone thickness were compared between OPo, OPe, and normal bone (Normal) subjects using the Kruskal-Wallis test by ranks. Spearman's rank correlation coefficients were calculated between dual-energy x-ray absorptiometry (DEXA) T-score and UTE-MRI results. PI was significantly higher in the OPo group compared with the Normal (24.1%) and OPe (16.3%) groups. SR was significantly higher in the OPo group compared with the Normal (41.5%) and OPe (21.8%) groups. SR differences between the OPe and Normal groups were also statistically significant (16.2%). Cortical bone was significantly thinner in the OPo group compared with the Normal (22.0%) and OPe (13.0%) groups. DEXA T-scores in subjects were significantly correlated with PI (R=-0.32), SR (R=-0.50), and bone thickness (R=0.51). PI and SR, as rapid UTE-MRI-based techniques, may be useful tools to detect and monitor bone quality changes, in addition to bone morphology, in individuals affected by osteoporosis.

Radiomorphometric Indicators, their Reliability in Detecting Early Signs of Osteoporosis in Menopausal Women

Background: The aim of this study was to evaluate the diagnostic value of panoramic radiography and the radiomorphometric indices in osteoporosis identification. Methods and Results: The research included 60 women (average age of 62,907,07 years) in the postmenopausal stage who were subjected to an assessment of bone density through the DEXA test and were divided into 2 groups based on the value of the DEXA test from the lumbar region (L1-L4): Main group (MG) included 30 women with osteoporosis (T-score&lt;-2.5) and Comparison group (CG) included 30 women without osteoporosis (T-score&gt;-2.5). Panoramic radiography were used to assess the mandibular cortical index (MCI), mental index (MI), panoramic mandibular index (PMI) Based on the porosity level, Klemetti et al.(1994) has categorized MCI into three categories (C1, C2, and C3). MCI–C1, which represents the normal appearance of the lower jaw cortex without changes in bone quality, was found only in CG in 63.33%. MCI-C2 and MCI-C3 were found in 70% and 30% of cases, respectively, in MG. In CG, MCI-C2 was found in 36.67% of cases and MCI-C3 in 0% of cases. There was a significant difference between the two study groups in the distribution of MCI (P=0.000). MI below 3 mm was found in 19(63.33%) of cases in CG and 27(90.00%) in MG (OR=5.211, 95% CI: 1.278-21.237, P=0.0213). PMI below 0.3mm was found in 7(23.33%) of cases in CG and 19(63.33%) in MG (OR=5.675 95% CI: 1.841-17.494, P=0.0025). MCI sensitivity and specificity for osteoporosis were 70% (95% CI: 50.60%-85.27%) and 63.33% (95% CI: 43.86%-80.07%), respectively; PPV, NPV, and accuracy were 65.62% (95% CI: 53.03%-76.35%), 67.86% (95% CI: 53.41%-79.54%) and 66.67% (95% CI: 53.31%-78.31%), respectively. MI sensitivity and specificity at a cutoff point of 3 mm for osteoporosis were 90% (95% CI: 73.47%-97.89%) and 36.67% (95% CI: 19.93%-56.14%), respectively; PPV, NPV, and diagnostic accuracy were 58.70% (95% CI: 51.35%-65.67%), 78.57% (95% CI: 53.18%-92.21%) and 63.33% (95% CI: 49.90%-75.41%), respectively. PMI sensitivity and specificity at a cutoff point of 0.3 mm for osteoporosis were 63.33% (95% CI: 43.86%-80.07%) and 76.67% (95% CI: 57.72%-90.07%), respectively; PPV, NPV, and diagnostic accuracy were 73.08% (95% CI: 57.32%-84.58%), 67.65% (95% CI: 55.66%-77.69%) and 70.00% (95% CI: 56.79%-81.15%), respectively. Conclusion: PR can be a useful tool to identify early signs of osteoporosis by using the evaluation of radiomorphometric indices. MCI, MI, and PMI can be potential screening tools for initial BMD loss.