Search Results (63)

Background. Glucocorticoid-induced osteoporosis represents a well-known type of secondary osteoporosis (SOp). While the most prevalent sub-category includes corticotherapy, another important contributor is represented by Cushing’s syndrome. In this traditional landscape, adrenal incidentalomas do not involve a standard cause of SOp, since most of them are non-functioning adrenal tumours (NFATs). Yet, 30–40% of them are not entirely “non-functioning”, due to mild autonomous cortisol secretion (MACS). Despite not being a guideline-based diagnosis, a lower ACTH might point to various NFATs/MACS complications. Objective. This study aimed to determine the relationship between the bone health status of post-menopausal women with NFATs/MACS and their baseline morning ACTH level. The bone health indicators were DXA, FRAX, and bone remodelling markers. Methods. This was a retrospective, real-life, transversal study in adult females who were hospitalized in a single tertiary centre of endocrinology. They were all anti-osteoporotic drug-naïve. The subjects underwent CT and DXA scanning and a 1 mg dexamethasone suppression test (DST). Results. The cohort (sample size of N = 84 patients, 61.49 ± 7.86 years) had a type 2 diabetes rate of 18%, arterial hypertension rate of 75%, and a dyslipidemia rate of 78%. Median ACTH was 11.89 pg/mL. The prevalence of MACS was 30.95%. The mean largest tumour diameter (LTD) was 2.25 ± 0.99 cm. ACTH correlated with second-day cortisol after the 1 mg DST (r = −0.301, p = 0.024), and LTD (r = −0.434, p < 0.001). ROC analysis for the bone resorption marker CrossLaps showed an AUC of 0.647 (p = 0.05), with the highest Youden index for the cut-off at 0.32 ng/mL (sensitivity 87.50%, specificity 39.50%). Bone impairment (osteoporosis + osteopenia) was found in 65% of patients, with an osteoporotic fracture prevalence of 4.76%. The lowest mean T-score (−1.12 ± 1.00) showed osteopenia, and the median trabecular bone score pointed a partially degraded microarchitecture [median (interquartile interval): 1.320 (1.230, 1.392)]. FRAX and FRAXplus estimations correlated with bone mineral density (BMD) at all three central DXA sites, regardless of the ACTH cut-off. Patients with a low ACTH (<10 pg/mL) displayed similar bone/adrenal features when compared to those with normal ACTH, except forbut they had a higher MACS rate (45.45% versus 21.57%, p = 0.021) and a larger LTD (2.67 ± 0.98 versus 1.98 ± 0.92 cm, p = 0.003). Fracture estimation showed that only in patients with a low ACTH, the 10-year fracture risk for major osteoporotic fractures (MOF) adjusted for lumbar BMD was lower than the risk for MOF adjusted for diabetes (p = 0.036), and the 10-year hip fracture risk was lower when adjusted for lumbar BMD (p = 0.007). ACTH correlated with lumbar BMD (r = 0.591, p = 0.002) only in the group with an ACTH < 10 pg/mL, suggesting its potential usefulness as a bone biomarker in these cases. On the other hand, MACS-negative subjects with a low ACTH versus those with a normal ACTH showed higher CrossLaps (0.60 ± 0.27 versus 0.42 ± 0.21 ng/mL, p = 0.022), indicating an elevated bone resorption even in patients with tumours that are regarded as true non-secretors. Conclusions. A subgroup of patients diagnosed with NFATs/MACS might be prone to skeletal damage, and biomarkers such as ACTH (specifically, suppressed ACTH) might serve as a surrogate pointer to help refine this higher risk in daily practice. Further research to address other ACTH cut-offs will place ACTH assays in the overall bone status evaluation in these patients, most probably not as a single biomarker, but in addition to other assays. Full article

The next frontier in postmenopausal osteoporosis management lies not in novel pharmacological agents, but in the systematic integration of mechanism-guided drug selection, fall prevention, and long-term adherence strategies into a unified patient-centered care model. This review is intended for clinicians and clinical researchers involved in the diagnosis, treatment, and long-term management of postmenopausal osteoporosis. We provide a mechanism-to-practice framework that explicitly maps each therapeutic class to the specific molecular pathway it targets: bisphosphonates inhibit osteoclast function downstream of RANKL activation; denosumab blocks RANKL directly at the cytokine level; romosozumab inhibits sclerostin to restore Wnt-mediated bone formation. This mechanistic foundation supports a risk-stratified treatment paradigm in which antiresorptives address accelerated remodeling in moderate-risk patients, while patients at very high fracture risk—characterized by severe bone deficit or recent fragility fractures—benefit from an anabolic-first approach followed by consolidation. Beyond drug selection, we examine the persistent treatment gap in which fewer than 20% of post-fracture patients receive therapy, arguing that fall prevention—responsible for >90% of hip fractures—and medication adherence deserve equal priority in clinical practice. We further analyze key controversies, including T-score- versus FRAX-based intervention thresholds, limitations of the trabecular bone score, cost-effectiveness constraints on anabolic-first sequencing, and evidence gaps in post-denosumab transition strategies. By synthesizing mechanistic insights, guideline recommendations, and critical appraisal of current limitations, this review offers not only an overview of existing knowledge but a coherent decision-support model aimed at improving fracture prevention through comprehensive, individualized care. Full article

The aim of this study was to assess bone health in individuals over 60 years of age in Kazakhstan, focusing on the relationship between osteoporosis, body mass index (BMI), body composition, and nutritional factors. This study included 1961 participants, consisting of 1620 women and 341 men, aged 60 to 89. Bone strength was assessed using quantitative ultrasound of the calcaneus, while fracture risk was assessed with the FRAX tool. Osteoporosis was detected in 20.2% of women and 15.2% of men, and osteopenia affected 59.8% of women and 58.4% of men. A total of 73.7% of the participants were overweight, 38.2% were pre-obese, and 35.5% were obese. The results of the study emphasise that, in addition to classic nutrients (calcium, vitamin D, protein), a number of trace elements and vitamins (selenium, iodine, zinc, vitamin B6, phytosterols) also play a significant, possibly indirect, role in bone metabolism. An inverse correlation was observed between BMI and osteoporosis prevalence; with a decrease in BMI, the incidence of osteoporosis increased (women: χ² = 26.0, df = 2, p < 0.001; men: χ² = 4.29, df = 2, p < 0.014; total sample: χ² = 32.3, df = 2, p < 0.001), thus confirming that excess body fat exerts a protective effect on bone health. Significant risk factors for osteoporosis included age, height, and weight. A link was found between the age of first osteoporosis onset and BMI (from 65 to 72.14 years). This confirms the value of FRAX for accurately assessing fracture risk and developing personalised recommendations based on anthropometric and dietary characteristics. Future longitudinal research is warranted to validate these results and further elucidate the underlying mechanisms, including the predictive power of novel anthropometric parameters such as the Body Roundness Index and Body Shape Index. Full article

Introduction/Background: Most adrenal incidentalomas (AIs) are non-functioning adrenal tumors (NFATs) without clinically overt hormonal hypersecretion; one-third show subtle endocrine over-activity and mild autonomous cortisol secretion (MACS). One out of ten NFATs involves not a unilateral (UTs), but bilateral tumors (BTs). Bone health, as opposed to cardio-metabolic complications, is less studied in NFAs/MACS, particularly in BTs. Hence, we aimed to analyze (blood) mineral metabolism assays (MMAs), including bone turnover markers (BTMs), central Dual-Energy X-ray Absorptiometry (DXA), and 10-year fracture risk estimation (FRAX/FRAXplus) in menopausal patients with UTs vs. BTs. Methods: This was a retrospective, single-center study. The inclusion criteria were women aged ≥50 y and CT-based AI detection. The exclusion criteria were medication against osteoporosis, malignancies, bone metabolic disorders, and cs-1mg-DST >5 µg/dL. Results: The cohort [N = 129; mean age: 62.39 ± 7.9 y; and y since menopause (YSM): 13.7 ± 8] included UT (62.22%) and BT (31.78%) groups with a similar age, YSM, type 2 diabetes rate (35.23% vs. 36.59%), arterial hypertension (73.6% vs. 75.5%), BMI, fasting glycemia, and glycated hemoglobin A1c (p > 0.5 for each). The borderline significance for morning cortisol was higher in UTs vs. BTs [median (interquartile interval): 13.9 (11.16, 15.00) vs. 10.10 (8.88, 12.95) µg/dL; p = 0.05] and the MACS-positive rate (24.45% vs. 36.59%; p = 0.051). The largest tumor diameter was similar (2.26 ± 0.97 vs. 2.51 ± 0.87 cm; p = 0.175), as was cs-1mg-DST [1.27 (1.01, 1.95) vs. 1.52 (0.92, 2.78) µg/dL; p = 0.357]. MMAs, BTMs, and DXA-BMD/T scores were similar in the UT vs. BT groups. The most prevalent DXA categories were osteopenia (50.82%) and normal (41.38%). The rate of DXA bone impairment (osteoporosis + osteopenia) was 72.13% vs. 58.62%. A generally low prevalence of fragility fractures was found (3.88%; N = 5, 3/2 between the groups). Out of the 25.58% (N = 33) females who were found to be MACS-positive, 54.55% were in the UT group and 45.45% were in the BT group. Age, YSM, the rate of analyzed comorbidities, BMI, biochemical parameters, DXA/BMDs, and FRAX/FRAXplus (lumbar BMD adjustment)-based probabilities were similar between the UT and BT groups, regarding MACS-positive vs. MACS-negative groups. Diabetic patients were all MACS-positive. A higher PTH level in the MACS-positive UT vs. MACS-positive BT groups (36.32 ± 9.21 vs. 51.65 ± 9.58 pg/mL; p = 0.01) was found, with the mean 25-hydroxyvitamin D showing mild deficiency (24.21 ± 12.73 vs. 26.16 ± 9.89 ng/mL; p = 0.694). In UTs, the largest tumor diameter statistically significantly correlated with baseline ACTH (r = −0.391; p < 0.001) and cs-1mg-DST (r = 0.306; p < 0.001), while in BTs, the largest diameter of the two tumors showed a positive correlation with cs-1mg-DST (r = 0.309; p = 0.012). Conclusions: The findings from this real-life setting (similar age, YSM, and diabetes and MACS-positive rates) could help us to better understand the bone features in UTs vs. BTs, noting that ACTH/cs-1mg-DST measurements showed no difference. The study population was associated with a generally low fracture prevalence and 10-year fracture risk probabilities, which might act as a bias in this distinct clinical exploration. Whether a multifactorial algorithm is needed to provide a 360-degree perspective of the bone health assessment in these patients remains an open matter. So far, starting from the current guidelines, a patient-centered approach is mandatory. To our best knowledge, this study adds to the limited number of prior studies regarding bone impairment in bilateral tumors. Full article

Background/Objectives: Comparison between the 10-year probability of major osteoporotic fracture (MOF) calculated with FRAX (pFRAX) and the actual MOF rate was conducted, and the availability of pFRAX was evaluated with a one-center cohort study. Methods: Eligible patients were followed up for 10 years. Risk factors listed as items in the FRAX, and presence of lifestyle-related diseases (LS-RDs), escalated ability to fall (Fall-ability), cognitive impairment (CI), etc., were evaluated concerning MOF. The 10-year probability and actual MOF rate were compared. Risk factors contributing to the discrepancy between the probability and the actual rate were evaluated after dividing subgroups. Results: The study included 931 patients. Factors that contributed to the significantly higher ratio for incident MOF besides items in the FRAX were LS-RD, Fall-ability, CI, and anti-osteoporotic drug intervention. The higher the number of factors presented, the higher the actual MOF prevalence compared to the probability rise. Presenting LS-RD, Fall-ability, and CI are independent of the items in the FRAX. pFRAX was overestimated in the low-risk groups and underestimated in the high-risk group compared to the actual MOF rate. These phenomena are caused by the lack of consideration of these three comorbidity risks. Conclusions: A discrepancy between pFRAX and the actual MOF rate exists. LS-RD, Fall-ability, and CI should be listed in the items of the FRAX for more concision. Full article

Inflammaging has been implicated in age-related bone loss and fragility fractures through immune-mediated effects on bone turnover. We aimed to explore the relationship between systemic inflammatory markers and bone health in older adults, focusing on the differences between patients with osteoporotic fractures and non-fractured controls. We retrospectively analyzed 40 older patients (20 with hip fractures and 20 with osteoarthritis without prior fragility fractures). We compared routine inflammatory markers, including red cell distribution width (RDW), C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and the composite CRP–albumin–lymphocyte index (CALLY), between groups. Bone mineral density (BMD) at the hip, lumbar spine, and wrist, as well as the FRAX score, were assessed. Correlations between inflammatory markers, BMD, and FRAX scores were evaluated using Spearman’s coefficient. Patients with fractures exhibited significantly elevated CRP (66.2 ± 70.3 vs. 3.8 ± 4.0 mg/L, p = 0.0008) and SII (1399.7 ± 1143.4 vs. 751.4 ± 400.8, p = 0.025) compared to controls. RDW, NLR, and CALLY scores did not differ significantly between the groups. Higher CRP levels were associated with lower BMD at all sites (hip: r ≈ −0.63, p = 0.002; spine: r ≈ −0.60, p = 0.005; wrist: r ≈ −0.60, p = 0.005). No significant correlations were observed between the SII and BMD or FRAX values. Elevated systemic inflammation, particularly indicated by CRP and SII, was associated with osteoporotic fracture status and low bone density in our cohort. These findings support the concept that inflammatory pathways may contribute to osteoporosis and fracture risk and suggest that inflammatory markers could serve as adjunctive tools in fracture risk assessment. Further studies are required to clarify the causality and evaluate whether targeting chronic inflammation can improve bone health in older adults. Full article

Background/Objectives: Sarcopenia is characterized by a decline in muscle mass and function. Its association with osteoporosis—referred to as osteosarcopenia—is linked to increased risks of falls, fractures, frailty, and mortality. Therefore, there is a growing need for accurate and accessible tools to assess muscle mass. Ultrasonography has emerged as a promising modality in recent years. The aim of our study was to compare rectus femoris ultrasound parameters in postmenopausal women with osteoporosis to healthy controls and to evaluate its diagnostic performance against a reference method. Materials and Methods: A cross-sectional prospective study was conducted including 88 postmenopausal women with a mean age of 65.7 ± 7.5 years. Functional status was evaluated using handgrip strength and gait speed. Rectus femoris ultrasonography was performed, measuring muscle thickness (MT), cross-sectional area (CSA), pennation angle (PA), and echo intensity (EI). Body composition was analyzed using bioelectrical impedance analysis, and appendicular skeletal muscle mass (ASM) was estimated using a validated predictive equation. All participants had undergone dual-energy X-ray absorptiometry within the previous year, and FRAX scores were calculated. Results: Women with osteoporosis had significantly lower muscle thickness compared to controls after adjusting for age and BMI. Rectus femoris MT and CSA were significantly correlated with predicted ASM (r = 0.428, p < 0.01; r = 0.462, p < 0.01). The area under the curve (AUC) for MT in identifying low muscle mass was 0.732 (95% CI 0.601 to 0.862, p = 0.001) at a cut-off value of 1.38 cm. CSA had an AUC of 0.789 (95% CI 0.678 to 0.901, p < 0.001) at a cut-off value of 4.48 cm². CSA, MT, and PA were significant independent predictors of osteoporosis regardless of bone mineral density but not of FRAX parameters. Conclusions: Rectus femoris ultrasonography is a potentially reliable and rapid method for assessing muscle mass. Rectus femoris ultrasound parameters may serve as predictors of osteoporosis, independent of bone mineral density. Full article

Osteoporosis is a chronic metabolic disease characterised by reduced bone mineral density (BMD) and increased susceptibility to fractures. Its development is influenced by both environmental and genetic factors that regulate bone metabolism. Among the genes involved in bone metabolism, COL1A1 and TNFRSF11B (OPG) are particularly important. The COL1A1 gene encodes the alpha-1 chain of type I collagen, a major component of the bone matrix, and plays a key role in maintaining bone mechanical strength. The TNFRSF11B gene encodes osteoprotegerin (OPG), a protein that inhibits bone resorption by binding the RANKL ligand and blocking osteoclast activation. Therefore, the aim of this study was to determine the association between the rs1107946 and rs1800012 polymorphisms of the COL1A1 gene and the rs2073617 polymorphism of the TNFRSF11B (OPG) gene and bone mineral density in postmenopausal women. The study included 590 postmenopausal women: 350 healthy controls, 105 with osteopenia, and 135 with osteoporosis. Genotyping was performed using real-time PCR and LightSNiP probes. Associations between genetic variables and BMD were assessed, taking into account environmental factors (BMI, smoking). The presence of the T allele of the rs1800012 variant was initially associated with lower BMD and an increased risk of osteopenia, but this association lost significance after adjustment for BMI and smoking. For rs1107946 and rs2073617,no statistically significant associations were observed. These findings suggest that the studied SNPs have, at most, modest effects on BMD, with environmental influences playing a stronger role. Further research in larger and more diverse cohorts, including FRAX-based risk estimation, is warranted. Full article

Background: Type 2 diabetes (T2D) has been placed among the risk factors for fragility (osteoporotic) fractures, particularly in menopausal women amid modern clinical practice. Objective: We aimed to analyze the bone status in terms of mineral metabolism assays, blood bone turnover markers (BTM), and bone mineral density (DXA-BMD), respectively, to assess the 10-year fracture probability of major osteoporotic fractures (MOF) and hip fracture (HF) upon using conventional FRAX without/with femoral neck BMD (MOF-FN/HF-FN and MOF+FN/HF+FN) and the novel model (FRAXplus) with adjustments for T2D (MOF+T2D/HF+T2D) and lumbar spine BMD (MOF+LS/HF+LS). Methods: This retrospective, cross-sectional, pilot study, from January 2023 until January 2024, in menopausal women (aged: 50–80 years) with/without T2D (group DM/nonDM). Inclusion criteria (group DM): prior T2D under diet ± oral medication or novel T2D (OGTT diagnostic). Exclusion criteria: previous anti-osteoporotic medication, prediabetes, insulin therapy, non-T2D. Results: The cohort (N = 136; mean age: 61.36 ± 8.2y) included T2D (22.06%). Groups DM vs. non-DM were age- and years since menopause (YSM)-matched; they had a similar osteoporosis rate (16.67% vs. 23.58%) and fracture prevalence (6.66% vs. 9.43%). In T2D, body mass index (BMI) was higher (31.80 ± 5.31 vs. 26.54 ± 4.87 kg/m²; p < 0.001), while osteocalcin and CrossLaps were lower (18.09 ± 8.35 vs. 25.62 ± 12.78 ng/mL, p = 0.002; 0.39 ± 0.18 vs. 0.48 ± 0.22 ng/mL, p = 0.048), as well as 25-hydroxyvitamin D (16.96 ± 6.76 vs. 21.29 ± 9.84, p = 0.013). FN-BMD and TH-BMD were increased in T2D (p = 0.007, p = 0.002). MOF+LS/HF+LS were statistically significant lower than MOF-FN/HF-FN, respectively, MOF+FN/HF+FN (N = 136). In T2D: MOF+T2D was higher (p < 0.05) than MOF-FN, respectively, MOF+FN [median(IQR) of 3.7(2.5, 5.6) vs. 3.4(2.1, 5.8), respectively, 3.1(2.3, 4.39)], but MOF+LS was lower [2.75(1.9, 3.25)]. HF+T2D was higher (p < 0.05) than HF-FN, respectively, HF+FN [0.8(0.2, 2.4) vs. 0.5(0.2, 1.5), respectively, 0.35(0.13, 0.8)] but HF+LS was lower [0.2(0.1, 0.45)]. Conclusion: Type 2 diabetic menopausal women when compared to age- and YSM-match controls had a lower 25OHD and BTM (osteocalcin, CrossLaps), increased TH-BMD and FN-BMD (with loss of significance upon BMI adjustment). When applying novel FRAX model, LS-BMD adjustment showed lower MOF and HF as estimated by the conventional FRAX (in either subgroup or entire cohort) or as found by T2D adjustment using FRAXplus (in diabetic subgroup). To date, all four types of 10-year fracture probabilities displayed a strong correlation, but taking into consideration the presence of T2D, statistically significant higher risks than calculated by the traditional FRAX were found, hence, the current model might underestimate the condition-related fracture risk. Addressing the practical aspects of fracture risk assessment in diabetic menopausal women might improve the bone health and further offers a prompt tailored strategy to reduce the fracture risk, thus, reducing the overall disease burden. Full article

Background/Objectives: Bisphosphonates may influence vascular calcification and atheroma formation via farnesyl pyrophosphate synthase inhibition in the mevalonate pathway regulating bone and lipid metabolism. However, the clinical impact of NCB use on cardiovascular outcomes remains uncertain, largely due to methodological heterogeneity in prior studies. We aimed to evaluate the association between nitrogen-containing bisphosphonate (NCB) therapy and coronary artery calcium (CAC) progression, as well as the incidence of cardiovascular disease (CVD) and coronary heart disease (CHD) events. Methods: From 6814 participants in MESA Exam 1, we excluded males (insufficient male NCB users in the MESA cohort), pre-menopausal women, baseline NCB users, and users of hormone replacement therapy, raloxifene, or calcitonin. Among 166 NCB initiators and 1571 non-users with available CAC measurements, propensity score matching was performed using the available components of FRAX, namely age, race, BMI, LDL cholesterol, alcohol, smoking, and steroid use, and baseline CAC yielded 165 NCB initiators matched to 473 non-users (1:3 ratio). Linear mixed-effects models evaluated CAC progression, and Cox models analyzed incident CVD and CHD events. Results: In the overall cohort, NCB use was not significantly associated with CAC progression (annual change: −0.01 log Agatston units; 95% CI: −0.05 to 0.01). However, among participants with a baseline estimated glomerular filtration rate (eGFR) < 65 mL/min/1.73 m², NCB use was associated with attenuated CAC progression compared with non-users (−0.06 log Agatston units/year; 95% CI: −0.12 to −0.007). No significant association was observed between NCB use and incident CVD events in the overall cohort (HR: 0.90; 95% CI: 0.60−1.36) or within kidney function subgroups. Conclusions: Incident NCB use among postmenopausal women with mild or no CAC at baseline was associated with reduced CAC progression only in women with impaired kidney function. However, this association did not correspond to a decreased risk of subsequent cardiovascular events, suggesting that the observed imaging benefit may not translate into meaningful clinical association. Full article

Hip fractures represent a significant public health challenge, particularly among the elderly, due to their high incidence, morbidity, and mortality rates. This review provides a comprehensive understanding of hip fractures through clinical, biomaterial, and biomechanical perspectives. Clinically, we examined key risk factors, including age, bone mineral density, and the high prevalence of falls, which account for over 95% of hip fractures. However, current clinical tools, such as FRAX, have notable limitations in accurately assessing fracture risk in individuals due to their reliance on statistical models, the treatment of interdependent risk factors as independent, and the omission of key variables like diabetes. From a biomaterial perspective, we analyzed bone composition—specifically the balance of inorganic minerals, organic proteins, and water—and its role in determining bone strength and fracture susceptibility. Various risk factors ultimately influence this composition balance, thereby affecting bone strength. Therefore, accurately measuring bone composition may provide a more reliable assessment of hip fracture risk. Although emerging imaging technologies such as dual-energy CT and MRI show promise for in vivo assessments of bone composition, these techniques still face significant challenges and remain an active area of research. Biomechanically, we explored the forces generated during falls, noting that impact forces can vastly exceed normal physiological loads and may exploit the anisotropic properties of bone, leading to fractures even in healthy individuals with strong bones. This understanding emphasizes the critical role of fall prevention in reducing fracture risk and highlights the limitations of using fall-induced fracture incidence as a validation metric for clinical assessment tools. Lastly, we discuss preventive strategies, including passive measures like environmental modifications for individuals diagnosed with low bone strength and proactive measures such as muscle strengthening and cognitive training. While passive measures are necessary for immediate protection, proactive strategies are more effective in the long term by addressing underlying risk factors for falls and promoting sustained bone health. This interdisciplinary review underscores the need to integrate clinical, biomaterial, and biomechanical factors to improve diagnostic accuracy, prevention, and treatment strategies for hip fractures, ultimately advancing public health outcomes in aging populations. Full article

Objectives: The study aims to evaluate adherence to Romosozumab treatment in osteoporotic patients after surgical fracture fixation and compare side effects with non-fractured controls on the same therapy. Methods: This retrospective case–control study was conducted at the Orthopaedic Department of Policlinico Universitario di Roma “Tor Vergata”, following the principles of the Declaration of Helsinki. It included postmenopausal women aged over 60, with the case group receiving Romosozumab after fracture fixation, and the control group consisting of women on Romosozumab therapy without fracture fixation. Exclusion criteria included psychiatric conditions, contraindications to Romosozumab, high-energy trauma, or other bone metabolism disorders. Data on fractures, surgeries, FRAX (Fracture Risk Assessment Tool) scores, BMD (Bone Mineral Densit) values, and follow-up details were collected. Side effects, including nasopharyngitis and severe events like hypocalcemia, stroke, and myocardial infarction, were recorded. Adherence was assessed via pharmacy records and patient interviews during routine clinical follow-up visits. Statistical analysis was performed using descriptive statistics, t-tests, and chi-square tests. Results: The study included 25 patients, with 12 in the surgical group and 13 in the conservative treatment group. The surgical group had a mean age of 67.3 years and a follow-up of 374 days, while the conservative group had a mean age of 76.4 years and a follow-up of 287 days. The surgical group underwent various fracture treatments, including femoral, humeral, and distal radius fractures, while the conservative group was treated with immobilization. There were no significant differences in FRAX scores or BMD values between the two groups. Vitamin D levels increased significantly in both groups after supplementation, but parathyroid hormone levels showed no difference. No new fractures occurred, and surgical patients had no delayed union or nonunion, though two had superficial wound infections. Conclusions: Both groups adhered well to Romosozumab therapy, with no severe side effects; minor side effects included myalgia in the surgical group and shoulder arthralgia in the conservative group. Romosozumab is well-tolerated and adherent in osteoporotic patients after osteosynthesis surgery, with adverse events similar to non-fractured individuals. While the study design is appropriate, multicenter trials would improve the sample size and allow for subgroup analysis based on fracture type and demographics. Full article

Background: Patients with myasthenia gravis (MG) are susceptible to fractures due to glucocorticoid (GC) use and disease-related functional impairment affecting activities of daily living (ADL). The Fracture Risk Assessment Tool (FRAX^®) estimates fracture probability but does not incorporate disease-specific functional status. We investigated whether combining FRAX^® with the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale improves fracture risk stratification in MG patients. Methods: This single-center prospective cohort study followed 53 MG patients for 10 years (2012–2022) at Toho University Ohashi Medical Center, Japan. Patients were categorized into four groups based on baseline FRAX^® probability (calculated with bone mineral density [BMD]) and MG-ADL scores using median splits: high FRAX^®/high MG-ADL (HH), high FRAX^®/low MG-ADL (HL), low FRAX^®/high MG-ADL (LH), and low FRAX^®/low MG-ADL (LL). The primary outcome was incident major osteoporotic fracture (MOF). Results: Over 10 years, nine MOFs occurred: seven in the HH group (43.8%), two in the HL group (16.7%), and none in the LH or LL groups. Fracture-free survival differed significantly among the groups (log-rank p < 0.001), with the HH group exhibiting the lowest survival rate. Baseline characteristics, including age, disease duration, MG severity scores, BMD, and FRAX^® scores, differed significantly among groups. Specific MG-ADL items reflecting greater impairment (impairment of ability to arise from a chair, double vision, and ptosis) were significantly more pronounced in the HH group at baseline. Conclusions: Combining baseline FRAX^® scores with the MG-ADL assessment effectively stratifies long-term MOF risk in patients with MG. Individuals with both high FRAX^® and high MG-ADL represent a particularly high-risk subgroup. This dual-assessment approach may improve the identification of patients requiring targeted preventive interventions. Full article

Background/Objective: Osteoporotic fractures may be prevalent, as expected, in patients with primary osteoporosis such as menopause-related or age-related bone loss, but a supplementary contribution to the risk may be added by less than common conditions, including a non-functioning adrenal tumor with or without mild autonomous cortisol secretion (MACS). Many of the standard fracture risk-related elements are captured by the FRAX model; yet, novel insights are brought by an improved algorithm, namely, FRAXplus. Our objective was to analyze the fracture risk in menopausal females diagnosed with low bone mineral density (BMD) and MACS-negative adrenal incidentalomas using FRAXplus (lumbar BMD adjustment). Methods: This as a retrospective, multi-center study of 66 menopausal women, where 50% of them had non-MACS adrenal tumors (group A), and 33 were controls (group B). They were put into four sub-groups, either group A1 (N = 14/33 subjects with normal DXA), or A2 (19/33 subjects with lowest T-score < −1), or group B1 (14/33) where subjects had normal DXA, or group B2 (19/33) for subjects with low BMD. Results: The sub-groups were matched on age, body mass index, and years since menopause, as well BMD matched (A versus B, A1 versus B1, A2 versus B2). FRAX analysis showed similar results for 10-year probability between groups A and B, and A2 and B2, while lumbar BMD adjustment showed statistically significant lower risk in group A1 versus B1 (p = 0.013), but not for hip fracture (p = 0.064). Conclusions: we introduced a pilot study in the FRAXplus model regarding adrenal tumors diagnosed in menopausal females with or without low BMD at central DXA assessment, a pilot study that to the best of our knowledge represents the first of this kind due to the novelty of using this fracture risk calculator with lumbar BMD adjustment. FRAXplus algorithm might be a better discriminator for fracture risk in these patients since we found that in age-, BMI-, and years since menopause-matched sub-groups, patients with normal DXA and MACS-free adrenal incidentalomas display a lower 10-year probability of major osteoporotic fractures than controls upon lumbar BMD adjustment. Full article

Inherited neurological disorders, such as spinocerebellar ataxia (SCA) and fragile X (FraX), are frequently caused by short tandem repeat (STR) expansions. The detection and assessment of STRs is important for diagnostics and prognosis. We tested the abilities of nanopore long-read sequencing (LRS) using a custom panel including the nine most common SCA-related genes and FraX and created raw data to report workflow. Using known STR lengths for 23 loci in 12 patients, a pipeline was validated to detect and report STR lengths. In addition, we assessed the capability to detect SNVs, indels, and the methylation status in the same test. For the 23 loci, 22 were concordant with known STR lengths, while for the last, one of three replicates differed, indicating an artefact. All positive control STRs were detected as likely pathogenic, with no additional findings after a visual assessment of repeat motifs. Out of 226 SNV and Indel variants, two were false positive and one false negative (accuracy 98.7%). In all FMR1 controls, a methylation status could be determined. In conclusion, LRS is suitable as a diagnostic workflow for STR analysis in neurological disorders and can be generalized to other diseases. The addition of SNV/Indel and methylation detection promises to allow for a one-test-fits-all workflow. Full article