Introduction: Osteoporosis is a progressive bone disease characterised by a decrease in bone mass and density. It is a major public health problem and a significant risk factor for fractures, especially among elderly women. Additionally, longterm Glucocorticoid (GC) therapy is associated with a significant reduction in bone density and is one of the most common causes of secondary osteoporosis. Need of the study: Conventional medical management of osteoporosis typically involves calcium supplementation, Hormone Replacement Therapy (HRT), and the use of drugs such as bisphosphonates, which reduce osteoclast activity and, atleast in the short term, increase bone density. However, these interventions slow overall bone turnover. The present study aims to investigate the effectiveness of the Ayurvedic medicine Lakshadi Guggulu and its modified form, Pravalyukta Lakshadi Guggulu, in managing osteoporosis. According to Ayurvedic classics, Lakshadi Guggulu is a highly effective calcium formulation for correcting bone metabolic disorders, facilitating fracture repair, treating joint dislocations, and providing analgesic and anti-inflammatory effects. Aim: To conduct a pharmaceutico-analytical study of Lakshadi Guggulu and Pravalyukta Lakshadi Guggulu, and to evaluate their comparative anti-osteoporotic activity in vivo. Materials and Methods: The present experimental study will be conducted from June 2025 to November 2025 in the animal house at Datta Meghe College of Pharmacy (DMCP), Datta Meghe Institute of Higher Education and Research (DMIHER) Deemed University (DU) Wardha, Maharashtra, India. Raw materials will be collected from the local market and verified and authenticated by the Taxonomist/Dravyaguna Department. The medicines will be prepared, standardised, and analysed at Mahatma Gandhi Ayurved College Hospital and Research Centre (MGACH and RC) as per the Ayurvedic Pharmacopoeia of India (API). Analytical studies will be conducted for both Lakshadi Guggulu and Pravalyukta Lakshadi Guggulu. The animal study will adhere to Organisation for Economic Cooperation and Development (OECD) guidelines 423 and include a total of 78 female Wistar rats: 24 rats will be used for the acute toxicity study, and the remaining 54 rats will be divided into nine groups for the efficacy study. General clinical observations, biochemical and haematological parameters, and histopathological examinations will be conducted. Data will be statistically analysed using the Student’s t-test and Analysis of Variance (ANOVA) as appropriate. A p-value <0.05 will be considered statistically significant.

Rheumatoid arthritis (RA) is commonly complicated by secondary osteoporosis (OP), affecting up to 80% of patients. Although dual-energy X-ray absorptiometry (DEXA) is the diagnostic gold standard, its limited accessibility highlights the need for alternative tools. In this retrospective cohort study of 396 hospitalized RA patients, we developed machine learning models using demographic and routine laboratory data to identify concomitant OP. Five classifiers were evaluated and combined via a soft-voting ensemble. The support vector machine achieved the highest area under the curve (AUC) (86.5%), while the random forest showed the highest accuracy (81.5%). The ensemble model demonstrated balanced performance (AUC 83.2%; accuracy 81.1%). SHapley Additive exPlanations (SHAP) analysis indicated age, sex, and body mass index (BMI) as major contributors, whereas albumin and inflammatory markers-including platelet-to-lymphocyte ratio (PLR), neutrophil percentage/albumin ratio (NPAR), white blood cell count (WBC), and neutrophil-to-lymphocyte ratio (NLR)-showed modest but heterogeneous influences on model predictions. These findings suggest that machine learning models incorporating routinely collected clinical data offer a practical and interpretable approach for preliminary OP risk assessment in RA. However, given the single-center design and limited sample size, the results should be considered exploratory, and larger external validation studies are warranted.

<p><strong>Aim</strong> Osteoporosis is a global health concern, characterized by reduced bone density, microarchitectural changes, and an increased risk of fractures. The prevalence of osteoporosis is rising, particularly in developing countries. In Indonesia, the incidence of upper femur fractures due to osteoporosis is notably high. As human studies are limited, animal models are crucial for investigating osteoporosis, with several methods used to induce the condition. This study proposes an alternative model using leuprolide acetate, gonadotropin-releasing hormone (GnRH) agonist, combined with a low-calcium diet and immobilization, to induce secondary osteoporosis in animals.</p> <p><strong>Methods</strong> This experimental study employed a post-test-only control group design with 12 groups of Wistar rats (<em>Rattus norvegicus</em>). Three control groups received no treatment, while nine experimental groups were administered leuprolide acetate along with a low-calcium diet and immobilization. The study measured tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen type 1 N-terminal propeptide (PINP) levels in rat bone tissue.</p> <p><strong>Results</strong> Significant increase in TRACP-5b and decrease in PINP levels were observed on days 21, 28, and 35 in the treated groups. Post hoc analysis revealed significant differences between treatment groups.</p> <p><strong>Conclusion</strong> The experimental model successfully demonstrated a reliable and reproducible method for inducing secondary osteoporosis. Elevated TRACP-5b and reduced PINP levels indicate increased osteoclast activity and decreased osteoblast activity resulting from excessive bone remodelling. The combination of leuprolide acetate, a low-calcium diet, and immobilization is an effective and alternative method for inducing secondary osteoporosis in experimental animals.</p>

To evaluate serum tartrate-resistant acid phosphatase 5b (TRACP5b) levels in patients with ankylosing spondylitis (AS) and primary osteoporosis (OP), and to assess its diagnostic value, correlations with bone mineral density (BMD) and disease activity, and its potential as a marker of secondary osteoporosis in AS. In this cross-sectional comparative study, 23 patients with AS, 24 patients with primary OP, and 20 healthy controls were recruited from Assiut University Hospitals. Demographic, clinical, laboratory, and dual-energy X-ray absorptiometry (DXA) data were collected. AS disease activity was assessed using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Serum TRACP5b was measured by ELIZA. Group differences, correlations, and ROC curve analysis were performed. AS patients were predominantly male and younger than OP patients. Primary OP patients had significantly lower DXA T-scores than AS patients (mean difference = 2.36, p < 0.001). TRACP5b levels were higher in AS patients than controls but not significantly different (p = 0.111). In AS, TRACP5b correlated with age (r = 0.534, p = 0.009) and disease activity (r = 0.427, p = 0.042) but not with BMD. ROC analysis showed moderate diagnostic performance for detecting secondary osteoporosis in AS (AUC = 0.653). No significant differences in TRACP5b or BMD were found across AS treatment groups. Serum TRACP5b may serve as a supplementary marker of osteoclast activity in AS and shows moderate diagnostic value for secondary osteoporosis, with levels more related to age and disease activity than BMD. Larger studies are needed to confirm its clinical utility. Key Points • Serum TRACP5b levels were higher in patients with AS than in healthy controls, though without consistent statistical significance, reflecting biological variability. • TRACP5b correlated positively with age and disease activity (BASDAI) in AS but not with BMD, disease duration, or ESR, highlighting its link to inflammatory bone resorption. • ROC analysis showed TRACP5b had moderate diagnostic performance for secondary osteoporosis in AS, but limited value in primary osteoporosis. • Our findings suggest that TRACP5b may serve as supplementary marker of bone turnover in AS, warranting further validation in larger, longitudinal studies.

Abstract Background Osteoporosis (OP) is a systemic bone condition, characterized by low bone mass and disturbed microarchitecture, that raises fracture risk susceptibility and lowers the quality of life. Tartrate-resistant acid phosphatase isoform 5b (TRACP-5b) is a biomarker that tracks the progression of bone resorption and monitors treatment effectiveness. Therefore, this work intended to assess TRACP-5b levels in two types of osteoporosis, postmenopausal primary OP and Rheumatoid Arthritis (RA)-related secondary OP, and to evaluate its potential as an alternative to bone mineral density (BMD) measurement when Dual-energy X-ray absorptiometry (DEXA) is unavailable. Methods A hospital-based single-center cross-sectional observational study, where demographic data, therapeutic history, Disease activity score 28 (DAS28), DEXA, Fracture risk assessment tool (FRAX), and TRACP-5b levels were evaluated in both types of OP (and the normal population as reference). Detection of relation and correlation between different parameters was calculated, and the ROC curve analysis was used to test the diagnostic performance of TRACP-5b. Results No differences between the two OP groups regarding TRACP-5b, BMD &amp; FRAX. TRACP-5b levels were significantly higher in the 1ry OP (all newly diagnosed &amp; untreated) group (Median 5.5 ng/mL). Most of the RA patients (85.7%) had moderate to severe DAS28 and positively correlated with TRACP-5b level ( r = 0.513). The ROC curve at a cut-off of 3.1 ng/mL, AUC of 0.740 ( p = 0.002), delivered a better diagnostic accuracy to differentiate the 1ry OP &amp; the control group. Conclusion This study substantiated that TRACP-5b is a relatively sensitive indicator for osteoclast activity and offers likely advantages in early tracking of the process of bone resorption and treatment response indicator before its detection by DEXA.

This study aimed to clarify trends in the incidence of secondary hip fractures and pharmacotherapy after primary fractures over time in Japan. Using Japan's National Database of Health Insurance Claims and Specific Health Checkups, we examined the number of hip fracture patients and their osteoporosis medication status from fiscal year (FY) 2012 to FY2023. A total of 1,289,333 females and 312,968 males had primary fractures. Among them, 42,835 females and 8,249 males had a secondary fracture within 1year following the primary fracture. The incidence rates averaged 3.44% annually, ranging from 3.26 to 3.57% by fiscal year. These rates showed an increasing trend from FY2012 to FY2018, followed by a decreasing trend until FY2020, but increased again in FY2021. The medication administration rate within the first year following the primary fracture progressively increased over time, from 39.1% in FY2012 to 49.6% in FY2021, followed by a notable increase to 65.5% in FY2022. Bisphosphonates were the most frequently administered medications, and the number of patients receiving bisphosphonates, eldecalcitol, denosumab, and romosozumab increased over time. The medication administration rate has consistently increased. The incidence of secondary fractures decreased from FY2019 but then increased in FY2021 due to the impact of the coronavirus disease 2019 (COVID-19) pandemic. However, in FY2022, this increase was mitigated by the introduction of management fees. It is anticipated that the incidence of secondary fractures will decline again due to a further increase in medication rates following the COVID-19 pandemic.

Ankylosing spondylitis (AS) significantly increases vulnerability to severe spinal injuries from minor trauma due to rigid "bamboo spine" morphology and secondary osteoporosis. Isolated intercostal artery rupture without rib fractures is extremely rare in general trauma populations. The concurrent occurrence of multilevel spinal fractures with complete spinal cord injury and occult intercostal artery hemorrhage following low-energy blunt trauma in AS patients has rarely been documented, and the underlying pathophysiological mechanisms remain unclear. A 43-year-old male with previously undiagnosed AS sustained a low-velocity bicycle collision, resulting in cervical and thoracic fracture-dislocation (C6-C7 and T11 bilateral laminae fractures) with complete spinal cord injury (ASIA Grade A, complete paraplegia), massive hemothorax, and active intercostal artery bleeding without significant rib fractures. Due to the patient's hemodynamic instability and altered consciousness on admission (hemorrhagic shock with SBP 63/40 mmHg), formal assessment of the bulbocavernosus reflex was not performed initially. The ASIA Grade A classification was based on complete absence of motor function (lower limbs 0/5) and sensory function below the T3 level, including absence of sacral sparing. Computed tomography angiography revealed active contrast extravasation from the right T10-level intercostal artery. Emergency transcatheter arterial angiography and embolization using coils and gelatin sponge particles successfully controlled the hemorrhage and stabilized the patient's hemodynamics. Following stabilization, staged posterior cervical (C5-C7) and thoracolumbar (T9-T12, L3-S1) pedicle screw-rod internal fixation with anterior cervical discectomy and fusion were performed. Despite postoperative complications including hospital-acquired pneumonia, pulmonary fungal infection (Candida albicans isolated from bronchoalveolar lavage, treated with intravenous fluconazole), and deep vein thrombosis, the patient demonstrated partial neurological recovery, with ASIA grade improving from Grade A (complete paraplegia) on admission to Grade C (incomplete paraplegia) at discharge on day 59. Serial neurological examinations documented the evolution from complete to incomplete injury (Table1). The patient was subsequently transferred to a specialized rehabilitation center for long-term functional training. This case illustrates the heightened and often unrecognized risk of complex, multisystem injuries in AS patients following seemingly minor trauma. Early recognition of hemothorax without rib fractures should raise high suspicion for intercostal artery injury, necessitating a lowered diagnostic threshold for computed tomography angiography. Transcatheter arterial embolization should be considered the first-line treatment for confirmed intercostal artery bleeding rather than a last resort. Prompt diagnosis, individualized multidisciplinary management, and early referral to specialized centers with interventional and spine surgical capabilities are essential for optimizing outcomes in these high-risk patients.

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, characterized by severe impairment of osteoblast function and increased bone fragility. Current therapeutic options inadequately address glucocorticoid (GC)-induced osteoblast apoptosis and suppress osteogenesis, highlighting the need for novel targeted interventions. To explore the molecular pathogenesis of GIOP and identify therapeutic targets, we performed integrated transcriptomic analysis, bioinformatics approaches, and multiple experimental validation methods. We demonstrate that dexamethasone (DEX), a prototypical GC, robustly upregulates osteoglycin (OGN) expression in both cellular and animal models. Crucially, the transcription factor ELF5 functions as a critical transcriptional repressor of OGN, counteracting DEX effects. ELF5-mediated OGN repression is essential for maintaining pro-survival PI3K/AKT/mTOR signaling integrity in osteoblasts. Molecular docking confirmed stable, high-affinity binding between the natural compound chrysophanol and OGN. Functionally, chrysophanol effectively antagonized DEX-induced OGN elevation and mitigated osteoblast apoptosis. This work is the first to define a role for the DEX-OGN-ELF5 axis in PI3K/AKT/mTOR signaling as critical for osteoblast survival in GIOP. Chrysophanol, as a novel natural compound targeting this OGN-centric axis, presents a promising and potentially safer therapeutic alternative to bisphosphonates, which are associated with risks like atypical femoral fractures and osteonecrosis of the jaw. Our findings offer novel insights into the molecular pathogenesis of GIOP, identify a potential druggable ELF5/OGN/PI3K/AKT/mTOR signaling axis, and establish a basis for future translational research in GC-induced bone diseases.

This review synthesises evidence on pharmacological interventions for secondary osteoporosis in older patients with hip fractures. A systematic review of five databases-Embase, Medline ALL, Cochrane Library, Web of Science Core Collection and Web of Science Preprint Citation Index-for articles published between January 2010 and July 2024. Abstracts and full texts were screened independently by multiple reviewers and critically appraised. Health outcomes, including refractures, follow-up bone mineral density (BMD) scans and treatment adherence, were synthesised, and adverse effects were examined in relation to study characteristics. A total of 60 articles met the inclusion criteria, and 40% were retrospective cohort studies. The median sample size within the included studies was 775 patients, with a median age of 78.7 years. Bisphosphonates (87%), anabolic agents (52%) and other antiresorptive agents (47%) were common pharmacological interventions. The average follow-up duration was 12 months. The cumulative refracture rate over 12 months was 3%, with a median incidence rate of 8%. Among patients who did not receive pharmacological treatment, the average refracture rate was 10%, compared with 4% in those who did receive treatment. Only 13 studies (22%) reported follow-up BMD. The implementation of fracture liaison services (FLS) was associated with an average of 44% increase in treatment initiation rates across four studies. Pharmacological treatment reduces refracture rates in older adults with hip fractures, especially when initiated through FLS. Although bisphosphonates are most commonly studied, anabolic and other antiresorptive agents also show benefits. Improved reporting on BMD follow-up and adherence is needed to guide long-term osteoporosis management.

ABSTRACT Secondary osteoporosis due to diabetes is a metabolic bone disorder where hyperglycemia impairs bone formation by suppressing osteoblast activity. Ocimum gratissimum L. has long been used in ethnomedicine and pharmacology for various illnesses. This study examines the osteogenic potential of Ocimum gratissimum leaf extract using both in vitro and in silico analysis. GC–MS analysis of OGLE confirmed the presence of flavonoids, polyphenols, terpenoids, sesquiterpenes, etc, and exhibited antioxidant potential (49.8 µg/mL). High glucose causes cytotoxic effects in MG‐63 cells with an IC 50 of approximately 45 mM. OGLE improved cell proliferation (p &lt; 0.0001) , restored alkaline phosphatase activity (p &lt; 0.05) , and significantly enhanced matrix mineralization (p &lt; 0.0001) under hyperglycemic conditions. Molecular docking was performed using AutoDock 4.2 to assess their binding interactions with osteogenic targets RUNX2 and osteocalcin, followed by in silico evaluation of their physicochemical properties, pharmacokinetics, lipophilicity, and drug‐likeness properties using PubChem and SwissADME. In silico analysis demonstrated favorable binding of γ‐tocopherol, copaene, and caryophyllene with RUNX2 (binding energies −5.4, −5.2, and −4.9 kcal/mol, respectively) and OCN (−4.7, −5.6, and −6.0 kcal/mol, respectively). Collectively, these results indicate that OGLE may mitigate high‐glucose‐induced osteoblast dysfunction through its antioxidant properties and modulation of osteogenic proteins, highlighting its potential as an anti‐osteoporotic agent.

Osteoporosis is characterized by an imbalance in bone remodeling, resulting in bone loss and increased fracture risk. Inflammatory diseases, such as rheumatoid arthritis, are strongly associated with secondary osteoporosis due to inflammation-induced bone loss. Pro-inflammatory cytokines, particularly TNF-α, disrupt bone homeostasis by promoting osteoclastogenesis and inhibiting osteoblast function. The Wnt signaling pathway is essential for bone formation and is suppressed in inflammatory conditions. WNT16, an osteoblast-derived ligand, increases bone mass mainly by inhibiting osteoclast differentiation but has also been found to stimulate osteoblast activity. Here we demonstrate that TNF-α downregulates Wnt16 mRNA expression in primary osteoblasts, suggesting that inflammation may impair WNT16 expression and thereby reduce bone mass. To evaluate whether pharmacological or genetical elevation of WNT16 levels can mitigate inflammation-induced bone loss, we examined the effect of WNT16 in three mouse models of local and systemic inflammation. In a knee arthritis model, intra-articular delivery of WNT16 liposomes failed to prevent local bone loss. Similarly, although osteoblast-specific WNT16 overexpression increased the overall bone mass, it did not protect against either local calvarial bone loss or systemic bone loss induced by Toll-like receptor 2 (TLR2) activation. Furthermore, in a model of systemic inflammation induced by Staphylococcus aureus, WNT16 overexpression did not preserve vertebral trabecular bone, despite increased baseline bone mass. These findings demonstrate that WNT16, although increasing the overall bone mass, is insufficient to counteract inflammation-driven bone loss.

Children with Medical complexity (CMC) and neuromuscular scoliosis (NMS) are prone to bone fragility and secondary osteoporosis due to immobility, chronic illness, nutritional deficiencies, and medication side effects. The resultant osteoporotic bone compounds operative challenges, contributing to complications such as implant failure by fracture, pedicle screw loosening and cut-out, proximal junctional kyphosis and pseudarthrosis. Pre-operative optimization of bone fragility has the potential to further improve surgical outcomes in the CMC population. Despite evidence for the safety and efficacy of zoledronate infusions in paediatric conditions (e.g. osteogenesis imperfecta), its tolerance, safety, and efficacy in medically complex children with neuromuscular scoliosis has not been established. The current investigation aims to establish the safety of pre-operative bisphosphonate therapy in children with CMC and NMS at a pediatric tertiary referral center as part of the implemented pre-operative optimization pathway. A retrospective review was conducted of patients who had undergone pre-operative zoledronate infusions as part of pre-operative optimization at a single tertiary pediatric referral center. The protocol included three infusions with an initial 0.0125mg/kg dose, a 0.0375mg/kg dose at 6 weeks, and 0.05mg/kg dose at 6 months. Surgery was scheduled no sooner than 6 weeks after infusion. Patient demographics, co-morbidities, medications, laboratory investigations, infusion protocol, and adverse events were collected. 47 patients received at least one pre-operative zoledronate infusion. Of these, 66% (31) completed the pre-operative optimization, receiving three infusions of zoledronate. The most common presenting etiology was cerebral palsy (70%), followed by Rett syndrome (9%), and congenital myopathy (9%). 66% of patients were GMFCS level 5 with 26% being GMFCS level 4. Minor adverse events were noted in 6 patients (13%), including 2 episodes of post-infusion hypocalcemia, 2 episodes of self-limited flu-like symptoms, 1 episode of nephrolithiasis and 1 episode of unspecified hypotension which resolved after receiving oral fluids. There were no major adverse events requiring hospital admission or emergency department presentation related to zoledronate infusions. 21 patients have reached 2 years follow up with signs of no clinical pseudarthroses. 1 patient was noted to have a broken pedicle screw at their 6 months follow-up but, to date, has had no further radiographic concerns that could indicate pseudarthrosis. Overall, no major adverse events were noted after pre-operative zoledronate infusions. The minor adverse events noted were self-resolving or resolved with minimal intervention. Zoledronate infusion can safely be included as part of a pre-operative optimization pathway in CMC with NMS. Further research is required to optimize patient selection, infusion dose and schedule, impact on screw pull-out, and long-term complications.

Chronic illnesses and their treatments in childhood pose significant risks of bone fragility due to osteoporosis. Bisphosphonates (BP) are commonly used for treatment, yet evidence remains limited and heterogeneous. This systematic review aims to consolidate current empirical evidence on BP efficacy and safety in children, youth and young adults aged ≤ 21years with secondary osteoporosis. Ovid MEDLINE and EMBASE, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials were searched by May 29th, 2025. This review followed the PRISMA guidelines the GRADE approach. This review was registered at PROSPERO (CRD42021242156). Seventeen studies were included (fifteen randomized controlled trials (RCTs), two quasi-RCTs) evaluating BP. Meta-analysis indicated that BP improved lumbar spine bone mineral density (BMD) z-score (mean difference (MD): 0.67; 95% confidence interval (CI): 0.37, 0.97) and lumbar spine bone mineral content (BMC) (MD: 2.90g; 95% CI: 0.91, 4.90). There were no studies adequately powered to assess vertebral and non-vertebral fractures. Patient-reported outcomes showed no consistent results. Adverse events (AEs) were comparable between treatment and control groups (relative risk (RR): 1.08; 95% CI: 0.94, 1.23). When limited to short-term periods after the first infusion, AEs were more likely in the treatment group (RR: 2.24; 95% CI: 1.22, 4.11). BP treatment benefits pediatric secondary osteoporosis by improving lumbar spine BMD and BMC. However, small sample sizes and heterogeneity among the study methods continue to challenge the reliability of results, and larger RCTs are needed to assess fracture rates.

The administration of various medications can induce bone loss as an adverse effect and may result in drug-induced osteoporosis, an important and clinically relevant form of secondary osteoporosis associated with an increased fracture risk. This review summarizes the skeletal effects of selected commonly used drugs with respect to bone metabolism, bone mineral density, and fracture outcomes. Medications may exert direct effects on osteoblasts and/or osteoclasts, leading to impaired bone remodeling and reduced bone mass. Alternatively, indirect mechanisms may contribute to skeletal damage, including disturbances in calcium and vitamin D metabolism with subsequent secondary hyperparathyroidism, as well as therapy-induced hypogonadism. Drug classes frequently associated with drug-induced osteoporosis during long-term use include glucocorticoids, aromatase inhibitors, androgen-deprivation therapy, thyroxine, proton pump inhibitors, anticoagulants (heparin and vitamin K antagonists), antidepressants, neuroleptics, and thiazolidinediones. Importantly, this overview represents a selection of relevant agents and does not aim to provide an exhaustive list. When prescribing potentially bone-damaging medications over extended periods, particularly in older individuals, bone health should be proactively considered. Evaluation should include laboratory assessment, fracture risk estimation (e.g., FRAX®), and bone mineral density measurement when appropriate. Adequate calcium and vitamin D intake should be ensured, and guideline-based osteoporosis therapy initiated when indicated.

Aim: Pamidronate is the preferred treatment for osteoporosis and hypercalcemia in children. This study examined its safety and effectiveness. Material and Methods: Patients treated with pamidronate for osteoporosis and hypercalcemia were included in the study. Osteoporosis patients received 1 mg/kg/day every three months for three days, while hypercalcemia patients received a single 1 mg/kg dose. Evaluations of height, weight, body mass index, bone mineral density (BMD), fractures, biochemical data, and complications were performed before and at least six months after treatment. Results: Of the 31 patients included in the study, 21 (67.7%) were male and 10 (32.3%) were female, with a mean age of 12.20 ±4.31 years. Secondary osteoporosis was diagnosed in 20 (64.5%) patients, primary osteoporosis associated with osteogenesis imperfecta in seven (22.6%) patients, and hypercalcemia in four (12.9%) patients. The average follow-up period was 11.26 ±4.16 months. The mean BMD before treatment in patients treated with pamidronate for osteoporosis was -3.53 ±1.43, while after treatment it was -1.42 ±1.81 (p&amp;lt;0.001). When comparing the pre- and post-treatment periods, a decrease was observed in the total number of fractures, the number of vertebral fractures, and the number of fractures occurring more than once per year (p&amp;lt;0.001). Complications were observed in six (19,3%) patients but all these side effects were temporary. Conclusion: Pamidronate treatment was administered at varying doses and for differing durations to patients from multiple groups, with no significant differences in efficacy or safety observed. The low complication rates reported are consistent with the literature and substantiate the safety of the treatment.

Juvenile dermatomyositis (JDM) is the most common form of idiopathic inflammatory myopathy in children and adolescents. The exact pathogenesis is not clear; however, a combination of several factors, including genetics, immunological abnormalities and environmental factors, has been implicated in the pathogenesis of JDM. The role of Type I interferons in the pathogenesis of JDM has received a lot of attention recently. JDM is characterised by proximal muscle weakness, elevated muscle enzymes, and pathognomonic skin rashes such as heliotrope rash and Gottron’s papules. Main long-term complications include calcinosis, lipodystrophy, and secondary osteoporosis. With the advent of myositis-specific antibodies (MSA), important phenotypic subtypes of the disease are characterised. Treatment of JDM is multidisciplinary. Prolonged immunosuppression with physical and medical rehabilitation is the backbone of therapy. The outcome has improved over the years with early recognition and initiation of immunosuppressive treatment and increasing use of steroid-sparing immunomodulators.

Patients with immune-mediated inflammatory diseases (IMID) are characterized by increased vulnerability to spinal trauma and distinct fracture patterns. Inflammatory alterations of periosseous soft tissues, along with impaired bone metabolism, lead to reduced mechanical resilience with unfavorable spinal alignment and biomechanics. Acommon denominator across IMID is secondary osteoporosis, which predisposes patients to pathological or fragility fractures, often triggered by low-impact trauma. Due to the heterogeneity of postinflammatory changes, ranging from focal structural destruction to long-segment ankylosis, the fracture morphology within this patient group varies considerably. From both apathomechanical and therapeutic perspective, osteoporotic fractures must be clearly distinguished from fractures occurring in ankylosing diseases. Although reduced bone density and insufficient residual stability may endanger the spinal cord in the long run, fractures of afused spine carry an acute risk of displacement and spinal cord injury, potentially resulting in paraplegia. Despite these differences, the therapeutic goal remains the same: to achieve amechanically stable osseous bridging of the fractured segment. This article highlights the distinct challenges of fracture management in various IMID types compared to structurally healthy spines. This is illustrated based on two representative clinical cases.

IntroductionOsteoporosis is a metabolic bone disease characterized by decreased bone mineral density and deterioration of bone microarchitecture, leading to an increased risk of fractures. Antiresorptive drugs are the first choice for treatment. Atypical femoral fractures (AFF) are a rare complication that can occur after bisphosphonate or denosumab therapy, especially in patients at high risk for fracture. We present a case of atypical femur fracture that developed in the second year of denosumab treatment, which was initiated after bisphosphonate treatment in our clinic due to postmenopausal osteoporosis.Clinical CaseA 76-year-old female patient was followed in our clinic postoperative hypothyroidism after bilateral total thyroidectomy caused by multinodular goiter and postmenopausal osteoporosis. Between 2014 and 2022, she was treated with bisphosphonates (oral alendronic acid/cholecalciferol and ibandronic acid, intravenous ibandronic acid) for postmenopausal osteoporosis. She was receiving replacement therapy due to vitamin D deficiency. The bone mineral density (BMD) measurements taken during her follow-ups are summarized in Table 1. Hemogram, kidney and liver function tests, parathyroid hormone, calcium, phosphorus, and alkaline phosphatase values, as well as 24-hour urinary calcium levels, were within normal limits. Additionally, celiac autoantibodies, anterior pituitary hormones, and sedimentation rates were checked to rule out secondary osteoporosis due to her initial severe osteoporosis and were found to be normal. Due to the lack of regression in BMD after bisphosphonate treatment and the high risk of major osteoporotic fractures, a drug holiday could not be implemented, and treatment for osteoporosis continued with denosumab and calcium/vitamin D. In the second year of denosumab, the patient presented with sudden onset right thigh pain and inability to walk, and X-rays revealed an atypical shaft fracture of the right femur (Figure 1). Surgery was recommended by orthopedics, but the patient declined. The treatment of the patient, who is suspected to have an atypical femur fracture related to denosumab, is being continued with calcium and vitamin D.ConclusionAtypical femur fractures are stress-type fractures originating from the lateral shaft of the femur. They occur with minimal trauma or no trauma at all and have specific radiographic findings. It has been hypothesized that there may be a drug-gene interaction that could predispose patients who have been using long-term bisphosphonates or denosumab to AFF. To minimize the risk of AFF, it is recommended that patients with low risk of major osteoporotic fractures after 5 years of bisphosphonate use be given a drug holiday, or patients receiving denosumab should not discontinue the medication or continue treatment with bisphosphonates after stopping the drug.Figure 1:X-rayAn atypical shaft fracture on the lateral side of the right femur is seen in the area marked with the arrow. Table 1:Bone mineral density values

IntroductionPrimary amenorrhea is a challenging presentation with diverse etiologies, including genetic, endocrine, structural, and chronic systemic diseases. Celiac disease (CD), an autoimmune enteropathy, may manifest with extraintestinal features such as delayed puberty or amenorrhea. We present a case of primary amenorrhea due to CD, diagnosed at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC), Basrah, south of Iraq.Clinical CaseA 21-year-old female presented in October 2021 with primary amenorrhea. She was the eldest sibling; her mother and sister had normal menarche at 13 years. She denied chronic illness, gastrointestinal symptoms, galactorrhea, or prolonged drug use. Examination revealed a thin female (40 kg, 150 cm, BMI 17.7 kg/m²) with breast Tanner stage II, scant pubic and axillary hair, and otherwise normal systemic findings.Initial investigations showed hypogonadotropic hypogonadism: FSH 0.2 mIU/mL, LH 0.1 mIU/mL, estradiol 2.5 pg/mL. MRI pelvis revealed an infantile uterus, pituitary MRI was normal. Other labs included TSH 3.2 µIU/mL, free T4 1.3 ng/dL, cortisol 17 µg/dL, ACTH 23.4 pg/mL, DHEA-S 272.2 µg/dL, prolactin 9.2 ng/mL, PTH 23.9 pg/mL. DEXA showed low bone mineral density (Z-score −2.8, BMD 0.744 g/cm²). Labs showed Hb 12.9 g/dL, MCV 79 fL, calcium 8.5 mg/dL, vitamin D 19 ng/mL. Anti-tTG (anti-tissue transglutaminase antibody) was negative. Hormone replacement therapy (HRT) with ethinyl estradiol was initiated and titrated for 18 months without improvement; uterine hypoplasia persisted.On reevaluation in October 2023, duodenal biopsy showed villous atrophy with lymphoid hyperplasia (Marsh IIIA), confirming CD. Genetic testing revealed HLA-DQ2 positivity (DQB102, DQA105). Pelvic ultrasound continued to show a hypoplastic uterus. A strict gluten-free diet was initiated alongside HRT due to low bone density.Within 3 months, she reported improved appetite and weight gain (to 50 kg), height increased to 153 cm, breast development advanced to Tanner stage III then stage IV, and vaginal discharge appeared. Spotting began in August 2024, with serial imaging showing progressive uterine growth, reaching near adult size by April 2025. She remains on full adult doses of estradiol with cyclic progesterone.This case highlights CD as an uncommon cause of primary amenorrhea and hypogonadotropic hypogonadism. Diagnosis may be difficult, especially in the absence of gastrointestinal symptoms and with negative serology, as seen in our patient. Biopsy and HLA typing were critical. Extraintestinal manifestations may precede classical symptoms, and failure to respond to HRT should prompt further evaluation.ConclusionPrimary amenorrhea can be the first manifestation of CD. In young females with unexplained hypogonadotropic hypogonadism, CD should be considered—even with negative serology. Early recognition and a gluten-free diet may restore endocrine function, promote pubertal progression, and improve reproductive potential.Figure 1:DEXA scan showing low bone mineral density (left) and sagittal pelvic MRI demonstrating an infantile uterus (right) in a 21-year-old female with primary amenorrhea. Table 1:Densitometry DataLumbar spine Z-scores ranged from -2.3 to -2.9, falling below the expected range for age. This finding indicates low bone mass not attributable to physiologic aging and raises concern for secondary osteoporosis, likely related to hypogonadism secondary to celiac disease.”

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.