Bone Health and Osteoporosis Foundation

Abstract Introduction Osteoporosis affects approximately 3.5 million individuals in the UK, resulting in over 500,000 fragility fractures annually. An initial fracture significantly increases the risk of subsequent fractures, particularly in very high-risk patients. Current clinical guidelines advocate a ‘treat-to-target’ strategy, recommending anabolic treatment for individuals at very high risk of fracture. The objective of this study was to evaluate biochemical safety, service delivery efficiency, and imminent fracture risk among osteoporosis patients receiving anabolic agents. Methods We conducted a retrospective review of Aneurin Bevan Fracture Liaison Service (AB-FLS) between August 2023 and June 2025. Of the initial 71 patients identified, 62 patients who received Romosozumab were included in the final analysis. Three Romosozumab patients were excluded due to disengagement from follow-up or declining treatment. Patients treated with Teriparatide (n = 5) and Abaloparatide (n = 1) were excluded due to small sample sizes. Data collected included patient demographics, fracture types, T-scores at the spine and femoral neck, biochemical markers (serum calcium, alkaline phosphatase (ALP), 25-hydroxyvitamin D [Vit D]), service metrics (waiting times from initial consultation to treatment initiation), incidence of hypocalcaemia (calcium <2.20 mmol/L), ALP elevation (>25% from baseline), vitamin D deficiency (<50 nmol/L), re-fracture incidence, and mortality. Results Mean age for all women (n = 62) was 72 years (range 40–83), 58% were vertebral, 24% were wrist/arm. Mean T-score at spine and femoral neck were − 3.20 (range − 5.39 to −0.70) and − 2.65 (range − 4.40 to −0.90) respectively. Median treatment initiation time post-initial consultation was 42 days (interquartile range 35–78 days). Biochemically, hypocalcaemia occurred in only 1 patient (1.6%) at the 4-month follow-up. Significant ALP elevations (>25%) were most common at 2 months (45%, 28/62) and gradually declined over subsequent follow-ups. Pre-treatment vitamin D deficiency was present in nine patients, all of whom received supplementation. Four patients (6.5%) experienced re-fracture between 84 to 275 days (mean 167 days). No mortality was recorded post initiation of anabolic. Conclusion Romosozumab treatment demonstrated good biochemical safety profiles and a low incidence of hypocalcaemia. We observed delays of nearly 6 weeks in treatment initiation for very high-risk patients. Given the observed imminent fracture risk of 6.5% whilst on treatment, efforts to reduce treatment delays by introducing stronger partnerships working with a dedicated FLS Pharmacists could be tested.

ABSTRACTBackgroundType 2 diabetes is associated with an increased risk of fragility fractures. While obesity may protect against fractures, individuals with type 2 diabetes often exhibit other metabolic syndrome (MetS) traits and albuminuria. We evaluated their roles and synergistic implications on incident fractures, stratified by obesity status.MethodsPatients with type 2 diabetes were identified from territory‐wide electronic health records in Hong Kong (2000–2018). MetS‐related traits included albuminuria and individual MetS traits (obesity, hypertension, low HDL‐cholesterol and hypertriglyceridemia). Outcomes were hip and major osteoporotic fractures (MOF). Patients were followed until fracture, death or 31 December 2020. Adjusted hazard ratios (aHRs) were estimated using multivariable Cox models.ResultsAmong 165 289 patients with type 2 diabetes (median age: 60.0 years; 54.2% men), 1583 (0.96%) experienced hip fractures, and 3393 (2.05%) had MOF over a median follow‐up of 5.3 years. Albuminuria was the strongest risk factor for hip fractures (obese: aHR 1.33, 95% CI 1.11–1.60; non‐obese: 1.54, 1.33–1.78) and MOF (obese: 1.13, 1.01–1.26; non‐obese: 1.28, 1.15–1.43). Hypertension was a significant risk factor only in non‐obese patients. In the non‐obese group, each additional MetS‐related trait was associated with an increased risk of hip fracture and MOF. When stratified by diabetes duration, albuminuria remained a significant risk factor across different diabetes durations, while suboptimal glycaemic control became a significant risk factor particularly when diabetes duration ≥ 5 years.ConclusionsIn this large population‐based cohort of patients with type 2 diabetes predominantly of Asian descent from Hong Kong, albuminuria emerged as an important predictor of fracture risk. MetS traits compound this risk, especially in non‐obese individuals. These findings could be instrumental in shaping screening initiatives for fracture risk optimization in type 2 diabetes.

We read with interest the article by Bobelyak and colleagues and the accompanying Editorial.However, we have serious concerns about the article's methodology and conclusions.The authors reported REMS-BMD measurements at the proximal femur in patients before and after hip arthroplasty and, based on minimal changes in BMD and variations observed with different anthropometric inputs, concluded that REMS-BMD is essentially derived from age, sex, and BMI rather than from ultrasound spectral data.This conclusion is not supported by the evidence provided, which highlight instead technical errors and misinterpretations of REMS operating principles, as detailed below.

Targeted mitochondrial-based therapeutic strategies for tumors have emerged as a significant research focus in the field of cancer treatment in recent years. Mitochondria, often referred to as the "energy factory" of cells, play a crucial role in the metabolic reprogramming of tumor cells, as well as in oxidative stress and immune evasion. In this study, we utilized a mitochondria-targeted photosensitizer, IR780, to engineer Celastrol (Cela)-loaded lipid nanoparticles, designed as Cela@Lip-IRH, for the synergistic therapy of chemotherapy and photodynamic therapy (PDT) against glioma. Cela@Lip-IRH could respond to the weakly alkaline environment of tumor cell mitochondria for rapid Cela release. Leveraging the mitochondrial targeting capacity and PDT property of IR780, Cela@Lip-IRH nanoparticles showed enhanced cellular uptake and mitochondria targeting distribution in vitro, as well as obvious tumor accumulation in vivo. Cela@Lip-IRH nanoparticles exhibited prominent intracellular reactive oxygen species (ROS) generation upon NIR laser irradiation, which was accompanied by pronounced photocytotoxicity and cell apoptosis, finally producing remarkable tumor growth suppression efficacy in vivo. We further verified that the potential antitumor molecular mechanism was triggered by the release of Cytochrome C, leading to an activated mitochondrial apoptosis pathway, alongside an immune response characterized by enhanced recruitment of CD4+ T cells and CD8+ T cells in tumor tissues. Currently, this mitochondria-targeted nanoplatform presents an ideal method to enhance the synergistic performance of chemotherapy and PDT in glioma, and it is anticipated that such a strategy will provide a promising alternative to optimize the tumor-targeted therapies.

Disclosure: D. Sturite: None. I. Rasa: None.Background: . Primary hyperparathyroidism (PHPT) can present a wide range of clinical symptoms, varying from asymptomatic to those with significant involvement of multiple organs. The literature shows variability in the prevalence of organ involvement and related conditions. Methods: . This LATVPHPT study included 177 PHPT patients diagnosed between January 1, 2021, and January 1, 2024. Using IBM SPSS 29.0 software, we conducted a detailed retrospective analysis of medical records, laboratory data, radiologic findings, surgical outcomes, and histopathology reports. Results: . 177 patients (mean age 63.8±11.9 years), 89% were females. 65% (n=115) of patients underwent parathyroidectomy, 14.7% (n=26) had surgery postponed due to unknown adenoma location, 1.1% (n=2) declined, 19.2% (n=34) - awaiting surgery, 3 - needed reoperation due to negative histopathology. Hungry bone syndrome occurred in 3 patients. 2 patients had MEN1 syndrome. Histopathological analysis and imaging in patients who underwent surgery identified a single adenoma in 94.0% (n=108), double adenomas - 1.7% (n=2), hyperplasia - 2.6% (n=3), carcinoma - 1.7% (n=2), and ectopic adenomas in 6.1% (n=7), with locations including intrathyroidal (n=3), anterior mediastinum (n=2), para jugular (n=1), superior posterior mediastinum (n=1). Among imaging modalities, contrast-enhanced ultrasonography (CEUS) showed superior performance compared to ultrasonography (b = −1.68, p = 0.020), scintigraphy (b = −1.70, p = 0.026), and 3D-CT (b = −1.66, p = 0.046). While SPECT/CT demonstrated a similar trend, the results did not reach statistical significance (b = −1.2, p = 0.099). The mean preoperative calcium was 2.9±0.3mmol/L, intact parathyroid hormone (iPTH) - 251.2±242.1pg/mL, phosphorus - 0.8±0.2mmol/L, 25-OH vitamin D - 27.6±13.3ng/mL. The mean postoperative calcium was 2.4±0.1mmol/L, iPTH - 59.9±36.5pg/mL, phosphorus - 1.1±0.2mmol/L, 25-OH vitamin D - 43.4±16.1ng/mL. Comorbid conditions included osteoporosis in 35% (n=62), osteopenia in 54% (n=95), and osteoporotic fractures in 15% (n=26). 17.5% (n=31) of patients received oral bisphosphonates, 4.0% (n=7) - intravenous bisphosphonates, 8.5% (n=15) - denosumab, 1.1% (n=2) - medication holidays. 25% (n=44) had kidney stones, 23% (n=41) - gallstones. Thyroid conditions included thyroid nodules in 81% (n=143), nontoxic goitre in 53% (n=93), and autoimmune thyroiditis in 29% (n=51). Other associated conditions included hypertension 43% (n=76), type 2 diabetes 14% (n=24), and malignancies 20% (n=36), most commonly breast and thyroid cancers. Conclusions: High rates of skeletal complications and malignancies in PHPT emphasize its clinical impact. Precise imaging, timely diagnosis, and appropriate treatment are essential for managing its complex manifestations.Presentation: Saturday, July 12, 2025

The present study focused on the culture medium of induced pluripotent stem cells (iPSCs) prior to the use of cardiomyocytes differentiation induction medium (pre-culture medium). Seven types (Nos. 1-7) of StemFit AK03 medium (Ajinomoto) for clinical iPSCs with varying compositions were prepared as pre-culture medium. The cardiac muscle troponin T (cTnT) positivity of No. 1 (StemFit AK03 medium) was 84%, No. 3 (similar to E8 medium) was 89%, No. 2 (similar to E8 medium) was 91%, No. 5 (similar to EB Formation medium) was 95%, when using differentiation induction medium prepared with known components available for clinical cell production. The formation of cardiac tissues was assessed by evaluating the expression levels of specific markers, including cTnT, atrial natriuretic peptides (ANP), and pro-B-type natriuretic peptide (proBNP). The results demonstrated that cardiac tissue with high protein expression levels of cTnT and ANP was formed when similar to E8 medium as pre-culture medium.

Radiometal-labeled porphyrin derivatives have emerged candidates for targeted brain tumor imaging and therapy. In this study, we synthesized a boronic-acid-conjugated porphyrin and radiolabeled it with 64Cu to evaluate its dual-function potential for PET imaging and boron neutron capture therapy (BNCT). The 64Cu-labeled 5,10,15,20-(tetra-4-dihydroxyborylphenyl)-porphyrin ([64Cu]-Cu-TDBP) exhibited excellent serum stability and significant uptake in U87MG cells. PET imaging in both xenograft and orthotopic models demonstrated time-dependent tumor accumulation, with selective localization in the brain tumor at 18 h post-injection (p.i.). The tumor-to-brain ratio increased from 7.2 at 4 h p.i. to 26.3 at 18 h p.i., alongside a rise in tumor boron concentration from 0.79 to 1.83 ppm over the same period. These results highlight the potential of [64Cu]-Cu-TDBP as a promising theranostic agent for precise brain tumor imaging and effective BNCT.

Over the years, prosthetic surgery has seen improvements in materials, design, component fixation, and surgical techniques to optimize the bone-prosthesis interface. A prosthetic joint acquires a new normality, but may still develop joint pathology. Today, the pathogenetic mechanisms, clinical manifestations, and medical-surgical treatment of these complications are becoming increasingly well understood. In the last two decades, the concept of continuous implant monitoring has emerged, along with the potential for pharmacological protection if necessary. This begins with preoperative treatment of articular Bone Marrow Lesions (BMLs), followed by therapy addressing the postope-rative decrease in Bone Mineral Density (BMD) due to immediate stress shielding, and continues with constant bone remodeling over the years, ultimately addressing potential prosthetic joint pathologies. Thus, long-term prosthetic implant monitoring involves surveillance of bone metabolism and pharmacological treatment with antiresorptive agents, particularly bisphosphonates, as a prerequisite for implant longevity.

The 24th Annual Santa Fe Bone Symposium (SFBS) was held in Santa Fe, New Mexico, USA, on August 2-3, 2024. This was a "hybrid" meeting, with in-person and real-time remote participants representing a broad range of geographical locations and medical disciplines. The focus was on new developments in the care of patients with osteoporosis, other metabolic bone diseases, and inherited skeletal disorders. The most current medical evidence was presented and discussed with consideration of implications for patient management. Topics included an update on clinical uses of osteoanabolic agents, management of patients discontinuing denosumab, bone health optimization for orthopedic surgery, estrogen and testosterone in the management of osteoporosis, osteoporosis treatment in the very old, overview of rare bone diseases, treat-to-target for osteoporosis, and a progress report on global activities of Bone Health ECHO. There were two highly interactive faculty panel discussions - one with case presentations by attendees and another with open microphone for all topics of interest. Endocrinology fellows, selected from attendees of the Santa Fe Fellows Workshop on Metabolic Bone Diseases, held the two days preceding the SFBS, participated with presentations of oral abstracts. Ancillary events addressed modern approaches to menopause and bone health, case studies of management of patients at very high fracture risk, and management of patients with rare bone diseases, such as hypophosphatasia, fibrodysplasia ossificans progressiva, X-linked hypophosphatemia, and hypoparathyroidism. These proceedings of the SFBS present the clinical highlights of the plenary sessions and the discussions that followed.

Aim: In rheumatoid arthritis (RA), seropositivity for both anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) is associated with disease severity and therapeutic response. Biologic (b) disease-modifying antirheumatic drugs (DMARDs) such as abatacept are recommended after inadequate response or contraindication to conventional synthetic DMARDs. This retrospective cohort study aimed to describe changes in Clinical Disease Activity Index (CDAI) measures over 12months among patients with ACPA+ and RF+ RA with an inadequate response to methotrexate treated with abatacept as a first-line bDMARD. Patients & methods: Patient data were abstracted from medical records by treating rheumatologists. Analyses included McNemar tests for paired proportions or paired t-tests to assess longitudinal changes in CDAI scores, and Kaplan-Meier methods for time-to-event outcomes. Serious AEs and rationale for initiating treatment were recorded. Results: Overall, 296 patients were included. Mean CDAI scores improved (decreased) by 34.0, 61.0 and 74.0% (all p<0.001) from baseline to 3-6months, 6-12months and ≥12months after abatacept initiation, respectively. Of 279 patients not in CDAI low disease activity (LDA) or remission at baseline, 24.7% of patients achieved it within 6months, 56.3% within 12months and 71.0% at any point during follow-up after abatacept initiation. Median time to CDAI LDA/remission was 10.2months. Serious AEs were reported in 2.4% of patients. Common reasons reported by rheumatologists for initiating abatacept were effectiveness/efficacy (52.7%), safety (31.4%) and patient preference (25.3%). Conclusion: In this analysis of patients with ACPA+ and RF+ RA treated with abatacept as a first-line bDMARD in a clinical practice setting, clinical outcomes and remission rates were improved at all time points, providing real-world evidence to further support the use of abatacept in this patient population.