Bone Mineral Research Articles

Associations between bone material strength index and FRAX scores.

Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. However, its ability to predict fractures is still uncertain. This study aimed to determine the association between BMSi and 10year fracture probability, as calculated by the FRAX algorithm. BMSi was measured using the OsteoProbe in 388 men (ages 40-90yr) from the Geelong Osteoporosis Study. The probabilities for a major osteoporotic fracture (MOF) and hip fracture (HF) were calculated using the Australian FRAX tool. Hip (HF) and major osteoporotic (MOF) fracture probabilities were computed with and without the inclusion of femoral neck bone mineral density (BMD). For each participant, four 10year probability scores were therefore generated: (i) HF-FRAXnoBMD; (ii) HF-FRAXBMD; (iii) MOF-FRAXnoBMD; (iv) MOF-FRAXBMD. BMSi was negatively correlated with age (r = -0.114, p = 0.025), no associations were detected between BMSi and femoral neck BMD (r = + 0.035, p = 0.507). BMSi was negatively correlated with HF-FRAXnoBMD (r = -0.135, p = 0.008) and MOF-FRAXnoBMD (r = -0.153, p = 0.003). These trends held true for HF-FRAXBMD (r = -0.087, p = 0.094) and MOF-FRAXBMD (r = -0.111, p = 0.034), but only the latter reached significance. BMSi captures the cumulative effect of clinical risk factors in the FRAX algorithm, suggesting that it could provide additional information that may be useful in predicting risk of fractures. Further studies are warranted to establish its efficacy in predicting fracture risk.

Evaluation of Bone Mineral Metabolism in Pre-Dialysis Chronic Kidney Disease: Quantitative Computed Tomography vs. Dual-Energy Absorptiometry and Correlation with Bone Turnover Markers

Background and Objectives: Bone and mineral disease (BMD) is a prevalent complication of advanced chronic kidney disease (CKD). The risk of fractures can be assessed via dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). This study aims to evaluate the effectiveness of two imaging modalities in identifying bone mineral status in individuals with pre-dialysis chronic renal disease and to assess their correlation with bone turnover markers. Materials and Methods: This controlled cross-sectional study, conducted at a single center from 2019 to 2022, assessed two groups of individuals aged 18 to 50. The patient cohort consisted of individuals with stage 4–5 chronic kidney disease, whereas the control cohort consisted of healthy participants. The participants’ bone and mineral status was evaluated using both QCT and DXA methods. Diagnostic measurements of the lumbar spine and femoral neck, obtained using DXA and QCT, were compared. Z-scores were utilized to evaluate low bone mineral density, with low Z-scores identified in either lumbar spine or femoral neck measures being seen as indicative of low bone mineral density. Results: Data from 38 participants (patient group: 18; control group: 20) who underwent QCT and/or DXA were evaluated. Thirty-three subjects were assessed using both QCT and DXA (patient group: 14; control group: 19). The median age of the patient cohort was 44 (range: 22–50), whereas the median age of the control cohort was 42 (range: 27–48) (p = 0.72). Women constituted 33% of the patient cohort and 50% of the control cohort (p = 0.23). In the patient cohort, low bone mineral density was detected in four individuals (28%) through QCT, and in just two patients (14%) through DXA. Compared to DXA, QCT identified a higher number of cases of low bone mineral density in the CKD cohort; however, no statistically significant difference was observed (p = 0.06). In addition, our study found that TRACP5b had a strong negative correlation with the DXA L1–L4 Z-score. Conclusions: This study revealed that QCT may be more sensitive than DXA for detecting low bone density in pre-dialysis CKD patients. Additionally, DXA may overestimate lumbar spine BMD in this population, and the strong negative correlation between TRACP5b levels and the DXA L1–L4 Z-score highlights the potential role of biochemical markers in assessing bone status in CKD

Bone cell differentiation and mineralization in wild-type and osteogenesis imperfecta zebrafish are compromised by per- and poly-fluoroalkyl substances (PFAS)

Perfluorinated compounds (PFAS) are well recognized toxic pollutants for humans, but if their effect is equally harmful for healthy and fragile people is unknown. Addressing this question represents a need for ensuring global health and wellbeing to all individuals in a world facing the progressive increase of aging and aging related diseases. This study aimed to evaluate the impact of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA) exposure on development and skeletal phenotype using the osteogenesis imperfecta (OI) zebrafish model Chihuahua (Chi/+), carrying a dominant glycine substitution in the α1 chain of collagen I and their wild-type (WT) littermates. To this purpose Chi/+ and WT zebrafish expressing the green fluorescent protein under the early osteoblast marker osterix were exposed from 1 to 6 days post fertilization to 0.36, 1.5 and 3.0 mg/L PFOS, 0.005 and 0.5 mg/L PFOA and 0.01, 0.48 and 16.0 mg/L PFHxA, and their development and skeletal phenotype investigated. Morphometric measurements, confocal microscopy evaluation of operculum area delimited by the fluorescent preosteoblasts and mineral deposition analysis following alizarin red staining were employed. PFOS and the highest concentration of PFHxA significantly impaired standard length in both genotypes. Osteoblast differentiation was significantly compromised by PFOS and by PFOA only in Chi/+. Limited to WT exposed to PFOA a reduced mineralization was also observed. No effect was detected after PFHxA exposure. Apoptosis was only activated by PFOA, specifically in Chi/+ mutant operculum osteoblasts. Interestingly, an altered lipid distribution in both WT and mutant fish was revealed after exposure to both pollutants. In conclusion, our data demonstrate that PFAS impair operculum development mainly compromising cell differentiation in mutant fish whereas alter lipid hepatic distribution in both genotypes with a more severe effect on Chi/+ preosteoblast survival. These results represent a first warning sign of the negative impact of PFAS exposure in presence of genetically determined skeletal fragility.

Impact of age and body mass index on dual-energy X-ray absorptiometry scan results in postmenopausal women

<p><strong>Aim</strong> To analyse the impact of age and body mass index (BMI) on dual-energy X-ray absorptiometry (DXA) scan results in postmenopausal women. <br /><strong>Methods</strong> The study included 100 postmenopausal women who underwent the DXA procedure, out of which 50 had a normal BMI and 50 were overweight/obese. Data that were examined included age, BMI, T-score of the lumbar region and the femoral neck, as well as bone mineral density (BMD). Correlation results were presented as Pearson’s correlation coefficient (r). <br /><strong>Results</strong> The T2-score and BMD2 were significantly lower in older patients compared to younger ones (p=0.008 and p=0.007, respectively). Post hoc test results showed that the T2-score and BMD2 were significantly lower in patients ≥71 years of age compared to patients ≤59 years of age (p=0.006 and p=0.005, respectively). Also, T1- and T2-scores, as well as BMD1 and BMD2, were significantly higher in overweight/obese patients (p<0.001 and p=0.003; p<0.001 and p=0.002, respectively). The correlation between BMI and the T1-score was moderate (r=0.429), between BMI and the T2-score weak (r=0.348), between BMI and BMD1 moderate (r=0.431), and between BMI and BMD2 weak (r=0.344). <br /><strong>Conclusion</strong> Our study showed that both age and BMI are important factors affecting DXA procedures and should be taken into account with each postmenopausal woman individually in everyday practice.</p>

Estrogen Deficiency alters Vascularization and Mineralization dynamics: insight from a novel 3D Humanized and Vascularized Bone Organoid Model.

Osteoporosis is not merely a disease of bone loss but also involves changes in the mineral composition of the bone that remains. In vitro studies have investigated these changes and revealed that estrogen deficiency alters osteoblast mineral deposition, osteocyte mechanosensitivity and osteocyte regulation of osteoclastogenesis. During healthy bone development, vascular cells stimulate bone mineralization via endochondral ossification, but estrogen deficiency impairs vascularization. Yet, existing in vitro bone models overlook the role of vascular cells in osteoporosis pathology. Thus, here we (1) develop an advanced 3D vascularized, mineralized and humanized bone model following the endochondral ossification process, and (2) apply this model to mimic postmenopausal estrogen withdrawal and provide a mechanistic understanding of changes in vascularization and bone mineralization in estrogen deficiency. We confirmed the successful development of a vascularized and mineralized human bone model via endochondral ossification, which induced self-organization of vasculature, associated with hypertrophy (collagen X), and promoted mineralization. When the model was applied to study estrogen deficiency, we reported the development of distinct vessel-like structures (CD31+) in the postmenopausal 3D constructs. Moreover, during estrogen withdrawal vascularized bone demonstrated a significant increase in mineral deposition and apoptosis, which did not occur in non-vascularized bone. These findings reveal a potential mechanism for bone mineral heterogeneity in osteoporotic bone, whereby vascularized bone becomes highly mineralized whereas in non-vascularised regions this effect is not observed.

Primary ovarian insufficiency in Classic Galactosemia: a systematic review.

Galactosemia is a rare inborn error of galactose metabolism. There are several forms, the most severe being classic galactosemia (CG), which begins in the first few days of life. Nowadays, it is possible to screen CG at birth, averting acute decompensation or death through diet. Although early dietary interventions help manage acute symptoms, long-term complications still occur, particularly primary ovarian insufficiency (POI) in female patients. This systematic review aims to synthesize existing literature on the relationship between galactosemia and POI, exploring the underlying mechanisms of pathophysiology, hormonal balance, metabolic control, fertility, and management. We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and PROSPERO. We queried the SCOPUS and PubMed databases using individual keywords and MeSH terms. Despite various proposed mechanisms, such as FSH dysfunction and the accumulation of galactose-1-phosphate, the exact cause of POI remains unclear, with studies showing variable correlations between genotype, galactose levels, and ovarian function. Monitoring AMH in prepubertal galactosemia patients may predict POI. Early estrogen replacement therapy, calcium supplementation, and strategies to improve galactosylation should be considered to enhance bone mineralization, given the impact of hypogonadism and low calcium intake on bone density in these patients. The course of POI in women with CG is unpredictable, with recent studies showing that nearly 30% of those attempting to conceive succeeded within a year, a rate that increases to almost 50% after two years. Despite advancements in understanding and managing CG, POI remains a significant clinical challenge, necessitating ongoing research and a multidisciplinary approach to enhance the long-term health of affected individuals.

The Association of Bone Mineral Density with Distal Junctional Kyphosis and Distal Junctional Failure After Multilevel Spine Fusions: A Systematic Review and Meta-Analysis.

Distal junctional kyphosis (DJK) and distal junctional failure (DJF) are known complications of adult multilevel spinal fusion surgery. Previous literature has extensively investigated proximal junctional kyphosis and proximal junctional failure, but DJK and DJF are relatively understudied. This study investigates the association between bone mineral density (BMD) and DJK/DJF via a systematic review and meta-analysis. A literature search was conducted across PubMed, Cochrane, Web of Science, Embase, and Scopus to find studies reporting DJK, DJF, and BMD. A 12-month minimum follow-up and radiographic biomarker for BMD (Hounsfield units [HU] or a T-score) individually reported for each patient type were required for inclusion. Studies that did not report individualized biomarkers but provided averaged estimates of the effect of BMD on DJK/DJF development were used for systematic review. Our search yielded 12 unique studies with 1094 patients, of which 5 studies with a total of 519 patients were suitable for comparison by meta-analysis. Patients who developed DJK/DJF had significantly lower HUs (113.17±33.86) than patients who did not develop DJK/DJF (142.51±41.39). No significant difference was found with regard to dual-energy X-ray absorptiometry measurements, age, or body mass index between patients who did and did not develop DJK/DJF. Patients who developed DJK/DJF had significantly lower computed tomography-measured HU as compared to those without DJK/DJF. Our findings highlight the potential importance of BMD evaluation with computed tomography prior to multilevel spine fusion surgery, though further research would be helpful to evaluate the significance of dual-energy X-ray absorptiometry-based BMD measurements on DJK/DJF development.

Crispant analysis in zebrafish as a tool for rapid functional screening of disease-causing genes for bone fragility.

Heritable fragile bone disorders (FBDs), ranging from multifactorial to rare monogenic conditions, are characterized by an elevated fracture risk. Validating causative genes and understanding their mechanisms remain challenging. We assessed a semi-high throughput zebrafish screening platform for rapid in vivo functional testing of candidate FBD genes. Six genes linked to severe recessive osteogenesis imperfecta (OI) and four associated with bone mineral density (BMD) from genome-wide association studies were analyzed. Using CRISPR/Cas9-based crispant screening in F0 mosaic founder zebrafish, Next-generation sequencing confirmed high indel efficiency (mean 88%), mimicking stable knock-out models. Skeletal phenotyping at 7, 14, and 90 days post-fertilization (dpf) using microscopy, Alizarin Red S staining, and microCT was performed. Larval crispants showed variable osteoblast and mineralization phenotypes, while adult crispants displayed consistent skeletal defects, including malformed neural and haemal arches, vertebral fractures and fusions, and altered bone volume and density. In addition, aldh7a1 and mbtps2 crispants experienced increased mortality due to severe skeletal deformities. RT-qPCR revealed differential expression of osteogenic markers bglap and col1a1a, highlighting their biomarker potential. Our results establish zebrafish crispant screening as a robust tool for FBD gene validation, combining skeletal and molecular analyses across developmental stages to uncover novel insights into gene functions in bone biology.

Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age

BackgroundZoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown.MethodsWe conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than −2.5 (scores of −1 or higher typically indicate normal bone mineral density) at the lumbar spine, femoral neck, or hip. Participants were randomly assigned to receive an infusion of zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate–zoledronate group), zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate–placebo group), or placebo at both baseline and 5 years (placebo–placebo group). Spinal radiographs were obtained at baseline, 5 years, and 10 years. The primary end point was morphometric vertebral fracture, which was assessed semiquantitatively and defined as at least a 20% change in vertebral height from that seen on the baseline radiograph. Secondary end points were fragility fracture, any fracture, and major osteoporotic fracture.ResultsOf 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up. A new morphometric fracture occurred in 22 women (6.3%) in the zoledronate–zoledronate group, in 23 women (6.6%) in the zoledronate–placebo group, and in 39 women (11.1%) in the placebo–placebo group (relative risk, zoledronate–zoledronate vs. placebo–placebo, 0.56 [95% confidence interval {CI}, 0.34 to 0.92; P=0.04]; and zoledronate–placebo vs. placebo–placebo, 0.59 [95% CI, 0.36 to 0.97; P=0.08]). The relative risk of fragility fracture, any fracture, and major osteoporotic fracture was 0.72 (95% CI, 0.55 to 0.93), 0.70 (95% CI, 0.56 to 0.88), and 0.60 (95% CI, 0.42 to 0.86), respectively, when zoledronate–zoledronate was compared with placebo–placebo and 0.79 (95% CI, 0.61 to 1.02), 0.77 (95% CI, 0.62 to 0.97), and 0.71 (95% CI, 0.51 to 0.99), respectively, when zoledronate–placebo was compared with placebo–placebo.ConclusionsTen years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women. (Funded by the Health Research Council of New Zealand; Australian New Zealand Clinical Trials Registry number, ACTRN12612000270819.)

The impact of body mass index on the relationship between psoriasis and Osteopenia: a mediating analysis based on NHANES (2003-2006).

The relationship between psoriasis and osteopenia remains undetermined. Patients with psoriasis tend to have a higher Body Mass Index (BMI) compared to those without the condition. While it appears plausible that BMI could mediate this association, further study is required to confirm this hypothesis. The objective of this study is to ascertain whether BMI plays a role in influencing the impact of psoriasis on osteopenia. This study encompassed 2,624 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2006. The condition of psoriasis was self-reported, while osteopenia was assessed based on bone mineral density (BMD) range and self-reported osteoporosis. BMI was derived from NHANES body measurement data. Weighted logistic regression analyses and mediation analysis were utilized to elucidate the relationship. Subgroup differences were further explored in the absence of a clear relationship. A positive correlation was observed between psoriasis and osteopenia. Furthermore, BMI was positively related to psoriasis and negatively related to osteopenia. Additionally, BMI served as a mediator in the relationship between psoriasis and osteopenia, accounting for 20.8% of the variance. Specifically, the mediating influence of BMI exhibited variations based on diabetes status and gender. In conclusion, Controlling BMI could potentially mitigate the impact of psoriasis on osteopenia. Therefore, we advocate for a rigorous focus on bone health in individuals with psoriasis, particularly among males and non-diabetic populations.

Mechanistic Insights into Kaempferol's Therapeutic Effects on Postmenopausal Osteoporosis: A Proteomic and Experimental Validation in Ovariectomized Rats.

Postmenopausal Osteoporosis (PMOP) is characterized by decreased bone mass and deterioration of bone microarchitecture, leading to increased fracture risk. Current treatments often have adverse effects, necessitating safer alternatives. Kaempferol, a flavonoid identified as a key active component of the traditional Chinese medicine Yishen Gushu formula, has shown promise in improving bone health, but its mechanisms in PMOP treatment remain unclear. The aim of this study was to investigate the therapeutic effects and underlying mechanisms of kaempferol in the treatment of PMOP. A bilateral ovariectomized (OVX) rat model was established to simulate PMOP. Sixty female Sprague-Dawley rats were divided into six groups: Sham operation, OVX control, OVX with alendronate (ALN), and OVX with kaempferol at doses of 10, 20, and 40 mg/kg. Treatments were administered orally once daily for 12 weeks. Assessments included Bone Mineral Density (BMD), trabecular microarchitecture via histopathology, organ morphology, organ indices, and serum levels of bone metabolism markers (TRACP-5b, BALP, ALP, Ca, P, and Fe) as well as liver and kidney function indicators (ALT, AST, CREA, and urea). Tandem Mass Tag (TMT) quantitative proteomics and bioinformatics analyses were conducted on femur samples to identify differentially expressed proteins (DEPs). Key DEPs were validated using parallel reaction monitoring (PRM), immunohistochemistry, and molecular docking. Kaempferol significantly improved BMD and enhanced trabecular microarchitecture in OVX rats in a dose-dependent manner, comparable to ALN, without causing hepatic, renal, or estrogen- like side effects. Serum bone metabolism markers were normalized with kaempferol treatment. Proteomic analysis identified 902 DEPs associated with kaempferol treatment, involved in processes such as bone remodeling, skeletal system development, and osteoclast function. Key signaling pathways affected included NF-κB, PI3K-AKT, and HIF-1. Notably, kaempferol downregulated five key DEPs-Rac2, Ddb1, Cdc42, Rpl19, and Hist2h4-in the femur, which are crucial for osteoclast resorptive activity, migration, adhesion, and cell cycle progression. Kaempferol exerts therapeutic effects on PMOP by inhibiting key proteins involved in osteoclast function, thereby reducing bone resorption and promoting bone health. These findings suggested that kaempferol is a potential safer alternative for PMOP treatment. Further research is recommended to explore its clinical applications and elucidate detailed mechanisms.

Impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in patients with postmenopausal osteoporosis: a case-control study.

To investigate the impact of switching from bisphosphonates (BP) to denosumab (DMAb), teriparatide (TPTD), or romosozumab (ROMO) in postmenopausal osteoporosis. This retrospective, case-controlled, multicenter study included 389 patients who switched from BP to DMAb, TPTD, or ROMO due to treatment inefficacy. Propensity score matching was used to align patient backgrounds, resulting in 45 patients per group. Baseline characteristics included a mean age of 73.8years, prior BP treatment duration of 37.1months, and bone mineral density (BMD) T-scores of -2.8 in the lumbar spine (LS), -2.5 in the total hip (TH), and -2.7 in femoral neck (FN). BMD and bone turnover markers were assessed over 12months. Following the switch from BP, the ROMO group demonstrated a dual effect of decreased bone resorption and increased bone formation markers. The TPTD group exhibited the highest increases in both markers, while the DMAb group suppressed both. After 12months, the ROMO group demonstrated significantly greater BMD increases in the LS (11.4%) compared to the DMAb (6.3%; p < 0.001) and TPTD (5.9%; p < 0.001) groups. Additionally, the ROMO group showed greater increases in the TH (3.3%) than TPTD group (0.8%; p < 0.01). Only the ROMO group showed a significant BMD increase in the FN (2.0%; p < 0.01 from baseline). Significant BMD increases were observed in the LS for all groups, in the TH for the ROMO and DMAb groups, and in the FN for the ROMO group. ROMO showed the most substantial BMD improvements following BP therapy.

Association between frailty and bone health in early-stage chronic kidney disease: a study from the population-based CARTaGENE cohort

Abstract Frailty is a clinical syndrome that is particularly prevalent in patients with chronic kidney disease (CKD). We aimed to assess the associations between renal function and the presence of frailty criteria and to assess the association between frailty and bone outcomes. We have conducted a retrospective study from a population-based cohort, which represents 1% of people aged 40 to 69 years in a Canadian province, excluding individuals with an estimated glomerular filtration rate (eGFR) lower than 30 ml/min/1,73m2. Frailty was defined with Fried's criteria. Bone density was estimated with Quantitative Ultrasound (QUS) at the calcaneus measuring Speed of Sound (SOS) and Broadband Ultrasound Attenuation (BUA). Time to first fracture event was assessed and analyses were conducted using logistic regressions, multiple linear regressions and Cox models. Overall, 19 973 individuals were included (mean age 54.2 ±7.8, women 51.6%, 47.0% CKD stage G2, 3.9% CKD stage G3, 34.8% with at least one frailty criterion. We observed a U-shaped association between eGFR and the Odds Ratio (OR) of presenting at least one frailty criterion, with a minimum OR around 77 ml/min/1.73m2 (per a 10 mL/min/1.73m2 increase, respectively for an eGFR&amp;lt;77 and &amp;gt;77, OR=0.93, 95%Confidence Interval (CI):0.86-1.01 and OR 1.09, 95%CI:1.06-1.13). After a median follow-up of 5.8 years, there were 837 fracture events. Having at least one frailty criterion was negatively associated with SOS (β=-3.97, p&amp;lt;0.0001) and BUA (β=-1.82, p&amp;lt;0.0001). Having at least one frailty criterion was associated with a higher fracture risk (Hazard Ratio=1.23, 95%CI: 1.07-1.42). In conclusion, having at least one frailty criterion was associated with a higher risk of fracture and a lower bone mineral density.

Dapagliflozin combined with metformin improves blood glucose, bone metabolism and bone mineral density in elderly patients with type 2 diabetes mellitus complicated with osteoporosis.

The incidence of type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP) (T2DM-OP) is growing. Dapagliflozin and metformin are commonly prescribed to manage glycemic levels in T2DM patients. We investigated the clinical efficacy of combining dapagliflozin with metformin in elderly patients with T2DM-OP. Totally 144 T2DM-OP patients were prospectively enrolled and allocated into two groups: the Metformin and Dapagliflozin + Metformin groups. Each group received treatment for 12 months. Fasting peripheral blood samples were collected before and after 12 months of treatment. Glycemic parameters and bone metabolic parameters were measured using oral glucose tolerance test, automatic biochemical analyzers, or liquid chromatography. Bone mineral density (BMD) changes at lumbar vertebrae (L1-4), femoral neck (FN) and total hip (TH) were assessed using dual-energy X-ray bone mineral densitometry. Pain severity was evaluated using the visual analog scale (VAS). The total effective rate, fracture incidence, and adverse reaction rate were also evaluated. After 12 months, both groups showed improvements in glycemic parameters, bone metabolic parameters, and BMD at L1-4, FN, and TH, and reductions in VAS scores. The Dapagliflozin + Metformin group exhibited more significant improvements. The overall effective rate was higher and fracture incidence, was lower in Dapagliflozin + Metformin group, with comparable rates of adverse reactions and safety profiles between the two groups. Taken together, treatment with a combination of dapagliflozin and metformin led to improvements in blood glucose levels, bone metabolism, and BMD in elderly patients with T2DM-OP, demonstrating superior efficacy and safety compared to metformin monotherapy.

Bone and Nerve Response to Sciatic Compression Neuropathy in a Rabbit Model.

Compression neuropathy is a prevalent medical condition, including common types such as carpal tunnel syndrome, cubital tunnel syndrome, sciatica, and many others. While the neurological consequences are well understood, the effects on bone properties and the potential downstream impact on fracture risk remain less clear. This study aimed to assess the influence of compressive neuropathy on bone properties using a rabbit model of sciatic nerve compression. We hypothesized that compressive neuropathy could adversely alter bone properties. Five New Zealand white rabbits underwent surgery to induce perineural scarring in the sciatic nerve, with the contralateral limb serving as a sham control. Bone mineral density (BMD), mechanical strength, and bone signaling proteins were evaluated through microcomputed tomography (μCT), four-point bending tests, and ELISA assays, respectively. Sciatic nerve histology was analyzed using VEGF and Nissl staining to assess axon and Schwann cell densities and quantified using image analysis software. The results showed no significant differences in BMD, biomechanical properties, or key bone signaling proteins (OPG and RANKL) between the affected and control tibias. These findings suggest that compression neuropathy does not significantly impact bone properties in the rabbit model.

Trends in screening and treatment of osteoporosis after periprosthetic fractures from 2010 to 2020.

Periprosthetic fractures (PPF) typically occur from low-energy mechanisms and are pathognomonic for osteoporosis. However, osteoporosis is often underrecognized and undertreated. The aim of this study was to examine trends in dual energy X-ray absorptiometry (DXA) scans and treatment of osteoporosis after PPF between 2010 and 2020. Patients older than 40 who experienced a lower extremity PPF between 2010 and 2020 and had no prior history of osteoporosis screening or treatment were identified utilizing a large national administrative database. Rates of bone mineral density (BMD) measurement using DXA and anti-osteoporotic treatment with pharmacotherapy, or either intervention within 1year following experiencing a PPF were determined. The rate of change for these interventions was calculated using the compounded annual growth rate (CAGR), with linear regression used to determine whether trends were statistically significant. In total, 5.7% and 3.6% of patients were screened and treated for osteoporosis, respectively. Between 2010 and 2020, there was no significant change in rates of osteoporosis screening (CAGR + 0.1%; p = 0.13), treatment (CAGR - 2.4%; p = 0.29), or either intervention (CAGR - 1.1%; p = 0.77) within 1year following PPF. Factors associated with intervention included older age, female sex, and increased comorbidities. Our study found that there has been no significant change in the rates of osteoporosis screening or treatment within 1year following PPF. Orthopedic surgeons and allied healthcare workers can play an integral role in helping to curtail the osteoporosis epidemic.

Risk factors for developing osteoporosis in diabetic kidney disease and its correlation with calcium-phosphorus metabolism, FGF23, and Klotho.

The progression of diabetic kidney disease (DKD) affects the patient's kidney glomeruli and tubules, whose normal functioning is essential for maintaining normal calcium (Ca) and phosphorus (P) metabolism in the body. The risk of developing osteoporosis (OP) in patients with DKD increases with the aggravation of the disease, including a higher risk of fractures, which not only affects the quality of life of patients but also increases the risk of death. To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices, fibroblast growth factor 23 (FGF23), and Klotho. One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People's Hospital from September 2019 to May 2021 were selected and divided into an OP group (n = 103) and a normal bone mass group (n = 55) according to their X-ray bone densitometry results. Baseline data and differences in Ca-P biochemical indices, FGF23, and Klotho were compared. The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed, and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis. The OP group had a higher proportion of females, an older age, and a longer diabetes mellitus duration than the normal group (all P < 0.05). Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone (iPTH), blood P, Ca-P product (Ca × P), fractional excretion of phosphate (FeP), and FGF23, as well as lower estimated glomerular filtration rate, blood Ca, 24-hour urinary phosphate excretion (24-hour UPE), and Klotho levels (all P < 0.05). In the OP group, 25-(OH)-D3, blood Ca, and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho. In contrast, iPTH, blood Ca, Ca × P, and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho (all P < 0.05). Moreover, 25-(OH)-D3, iPTH, blood Ca, FePO4, FGF23, Klotho, age, and female gender were key factors that affected the lumbar and left femoral neck bone mineral density. The Ca-P metabolism metabolic indexes, FGF23, and Klotho in patients with DKD are closely related to the occurrence and development of OP.

Construction and validation of a prediction model for fall risk in hospitalized older adults with osteoporosis

ObjectiveThe aim of this study is to develop and validate a prediction model for fall risk factors in hospitalized older adults with osteoporosis.MethodsA total of 615 older adults with osteoporosis hospitalized at a tertiary (grade 3A) hospital in Nantong City, Jiangsu Province, China, between September 2022 and August 2023 were selected for the study using convenience sampling. Fall risk factors were identified using univariate and logistic regression analyses, and a predictive risk model was constructed and visualized through a nomogram. Model performance was evaluated using the area under the receiver operator characteristic curve (AUC), Hosmer-Lemeshow goodness-of-fit test, and clinical decision curve analysis, assessing the discrimination ability, calibration, and clinical utility of the model.ResultsBased on logistic regression analysis, we identified several significant fall risk factors for older adults with osteoporosis: gender of the study participant, bone mineral density, serum calcium levels, history of falls, fear of falling, use of walking aids, and impaired balance. The AUC was 0.798 (95% CI: 0.763–0.830), with a sensitivity of 80.6%, a specificity of 67.9%, a maximum Youden index of 0.485, and a critical threshold of 121.97 points. The Hosmer-Lemeshow test yielded a χ2 value of 8.147 and p = 0.419, indicating good model calibration. Internal validation showed a C-index of 0.799 (95% CI: 0.768–0.801), indicating the model’s high discrimination ability. Calibration curves showed good agreement between predicted and observed values, confirming good calibration. The clinical decision curve analysis further supported the model’s clinical utility.ConclusionThe prediction model constructed and verified in this study was to predict fall risk for hospitalized older adults with osteoporosis, providing a valuable tool for clinicians to implement targeted interventions for patients with high fall risks.

Validity of A-Mode Ultrasound for Estimating Body Fat Percentage of Young Adult Athletes: A Multicomponent Model Study.

This study compared %BFUS to %BF4C in young adult athletes. University club sport athletes (86 women, 138 men) from a variety of teams participated. ADP, DXA, and bioimpedance spectroscopy were used to measure body volume, bone mineral content, and total body water, respectively, for the 4C model. Ultrasound measurements were taken at three sites to estimate %BFUS. Comparisons between %BFUS and %BF4C were evaluated with Pearson correlation, paired t-test, linear regression, equivalence testing, and plots of individual errors. For the combined sample of men and women (N = 224), the two methods were highly correlated (r = 0.93) with a constant error (CE) of 0.8% BF (P < .001) and standard error of estimate (SEE) of 3.0% BF. The 90% confidence intervals of the mean difference (0.47 to 1.17) were well within the ±2% BF limits for equivalence testing, and no bias was evident from the error plot. However, equivalence testing failed to remain inside the ±2% BF range for women, and the prediction errors for women (CE = 1.9% BF, P < .001, SEE = 3.2% BF) were larger than for men (CE = 0.1% BF, P = .597, SEE = 2.8% BF). Overall, the %BFUS errors were low, suggesting that A-mode ultrasound is a valid field measure of %BF for young adult athletes. Accuracy is better for men than women.

Plasma levels of anti phosphocholine IgM antibodies are negatively correlated with bone mineral density in humans

Phosphatidylcholine is a ubiquitous phospholipid. It contains a phosphocholine (PC) headgroup and polyunsaturated fatty acids that, when oxidized, form reactive oxidized phospholipids (PC-OxPLs). PC-OxPLs are pathogenic in multiple diseases and neutralized by anti-PC IgM antibodies. The levels of anti-PC IgM increase as the levels of PC-OxPLs increase and, in humans, are inversely correlated with the incidence of cardiovascular diseases and steatohepatitis. PC-OxPLs also decrease bone mass in mice. Overexpression of anti-PC IgM ameliorates atherosclerosis and steatohepatitis, increases bone mass in young mice, and protects against high fat diet- and age-associated osteoporosis. We investigated the relationship between anti-PC IgM plasma levels and bone mineral density (BMD) in a cross-sectional study of 247 participants [mean age: 65.5 (± 8.6) years] without medical conditions known to influence BMD or antibody production. Anti-PC IgM levels negatively correlated with both T- and Z-scores at the lumbar spine, femur and, to a lesser extent, the forearm. These correlations were maintained after adjustment for age, race, and sex. These results raise the possibility that higher levels of anti-PC IgM in patients with lower BMD reflect exposure to higher levels of PC-OxPLs, which are known to affect bone mass, and could be a novel risk marker for osteoporosis.