A comprehensive review on glucocorticoids induced osteoporosis: A medication caused disease.

Glucocorticoids (GCs) are steroid hormones that are extensively used in the treatment of autoimmune diseases, inflammation, and cancer. The major ill effect of administering GCs is that it has a deleterious effect on bone, which leads to GC-induced osteoporosis. GC therapy induces bone loss and is associated with the risk of nonvertebral and vertebral fractures, as it works in combination by increasing bone reabsorption and suppressing bone formation during the initial phase of therapy. It is seen and established that GC in excess or in low dose for 3 months or more can be a risk factor for fracture, and the risk increases with an increase in dose and duration of usage. The most common cause of secondary osteoporosis is the administration of GC inside the body to treat various diseases. The degree of bone loss is directly proportional to the GC dose and the exposure duration. The first step is to evaluate the patients' risk factors for the development of glucocorticoids that induce osteoporosis, which include the dose, duration of use, patient age, sex, previous fractures, and other medical conditions.

Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo.

OBJECTIVE: Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress. METHODS: Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels. RESULTS: After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p-ERK. CONCLUSION: ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

Societal costs before and up to 1 year after the first fracture liaison service visit in patients requiring anti-osteoporosis treatments.

This study aimed to estimate societal and healthcare costs incurred before and 1 year after the first fracture liaison services (FLS) visit and to explore differences in fracture type. All costs after 1 year significantly decreased compared to costs preceding the first visit. Fracture type did not significantly affect costs. INTRODUCTION: Limited literature is available on resource utilization and costs of patients visiting fracture liaison services (FLS). This study aimed to estimate the societal and healthcare costs incurred by patients with a recent fracture requiring anti-osteoporosis medication before and 1 year after the first FLS visit and to explore differences according to fracture type. METHODS: Resource utilization was collected through a self-reported questionnaire with a 4-month recall on health resource utilization and productivity losses immediately following the first FLS visit, and 4 and 12 months later. Unit costs derived from the national Dutch guideline for economic evaluations were used to compute societal and healthcare costs. Linear mixed-effect models, adjusted for confounders, were used to analyze societal and healthcare costs over time as well as the effect of fracture type on societal and healthcare costs. RESULTS: A total of 126 patients from two Dutch FLS centers were included, of whom 72 sustained a major fracture (hip, vertebral, humerus, or radius). Societal costs in the 4 months prior to the first visit (€2911) were significantly higher compared to societal costs 4 months (€711, p-value = 0.009) and 12 months later (€581, p-value = 0.001). Fracture type did not have a significant effect on total societal or healthcare costs. All costs 12 months after the initial visit were numerically lower for major fractures compared to others. CONCLUSION: Societal and healthcare costs in the year following the first FLS visit significantly decreased compared to those costs preceding the first visit.

[Chinese expert consensus on treatment of osteoporotic fractures with teriparatide (2024 edition)].

Osteoporotic fracture is the most serious complication of osteoporosis, which is a special type of pathologic fracture of the skeleton that occurs because of osteoporosis. It is characterized by delayed fracture healing, high risk of re-fracture, high rate of disability and death, difficulty in treatment and long treatment time, and re-fracture has a"cascade effect". Guidelines in different countries recommend that patients with osteoporotic fractures and those at very high risk of fracture should consider anabolic agents as first treatment choice. Teriparatide is the only anabolic agent approved by National Medical Products Administration (NMPA), and it has the clinical efficacy of improving fracture healing, reducing the risk of re-fracture, and improving bone microstructure in the treatment of osteoporotic fracture. Due to deficiencies in the current standardization of clinical use of teriparatide, Committee of Accelerated Rehabilitation After Osteoporotic Fractures of China Association of Rehabilitation Technology Transformation and Promotion, Bone and Joint Group of Chinese Society of Osteoporosis and Bone Mineral Research and Osteoporosis Working Committee of Chinese Association of Orthopedic Surgeons developed this consensus. The development of this consensus follows the modified Delphi method and forms 8 evidence-based medical recommendations, aiming to propose methods and precautions for standardizing the application of teriparatide, and to emphasize the importance of teriparatide application for the treatment of patients with osteoporotic fracture.

Association of two geriatric treatment systems with anti-osteoporotic drug treatment and second hip fracture in patients with an index hip fracture: retrospective cohort study.

BACKGROUND: In Germany, geriatricians deliver acute geriatric care during acute hospital stay and post-acute rehabilitation after transfer to a rehabilitation clinic. The rate patients receive acute geriatric care (AGC) or are transferred to post-acute rehabilitation (TPR) differs between hospitals. This study analyses the association between the two geriatric treatment systems (AGC, TPR) and second hip fracture in patients following an index hip fracture. METHODS: Nationwide health insurance data are used to identify the rate of AGC and TPR per hospital following hip fracture surgery in patients aged ≥ 80 years. Outcomes are a second hip fracture after surgery or after discharge within 180 or 360 days and new specific anti-osteoporotic drugs. Cox proportional hazard models and generalised linear models are applied. RESULTS: Data from 29,096 hip fracture patients from 652 hospitals were analysed. AGC and TPR are not associated with second hip fracture when follow-up started after surgery. However, during the first months after discharge patients from hospitals with no AGC or low rates of TPR have higher rates of second hip fracture than patients from hospitals with high rates of AGC or high rates of TPR (Hazard Ratio (95% CI) 1.35 (1.01-1.80) or 1.35 (1.03-1.79), respectively). Lower rates of AGC are associated with lower probabilities of new prescriptions of specific anti-osteoporotic drugs. CONCLUSIONS: Our study suggests beneficial relationships of geriatric treatment after hip fracture with a) the risk of second hip fractures during the first months after discharge and b) an improvement of anti-osteoporotic drug treatment.

[Pharmacolgic osteoporosis treatment of nursing home residents]. / Medikamentöse Osteoporosetherapie bei Altersheimbewohner/-innen.

INTRODUCTION: Fragility fractures in older people are common and are often associated with nursing home admission in frail people. Only few institutionalized residents with documented osteoporosis receive pharmacologic osteoporosis treatment. Studies demonstrating the benefit of osteoporosis drug therapy in this multimorbid and vulnerable population are lacking.

[Osteoporosis - implications of the new guidelines in practice]. / Osteoporose ­ Implikation der neuen Leitlinie in die Praxis.

In September 2023, the guideline on the prophylaxis, diagnosis, and treatment of osteoporosis in postmenopausal women and men was published as a completely revised guideline. The implications for practice include a change in the justifying indication for performing a bone density measurement, the time interval over which the fracture risk is determined, the level and number of therapy thresholds, and the recommendations for the therapeutic approach that are adapted to the individual fracture risk present. Risk assessment for the prediction of spine and hip fractures is essential in the context of osteoporosis diagnostics. In addition to age and gender, there are a total of 33 risk factors to determine the individual risk of fracture. Much more attention is paid to the assessment of the risk of falls and, depending on the result, combined with recommendations for muscle training and protein intake from the age of 65. Risk indicators must also be taken into account when determining the indication for osteoporosis diagnosis, as well as the risk factors of the imminent risk of fracture. The indication for baseline diagnostics has changed from the >20% 10-year fracture risk to diagnostics in postmenopausal women and in men aged 50 years and older, depending on the fracture risk factor profile. This eliminates a specific fracture risk threshold for basic diagnostics. Thus, in the young patient group (50-60 years), the risk factors considered medically relevant for the indication for osteoporosis diagnosis must be taken into account. New thresholds as an indication for initiating therapy is the determination of fracture risk using a risk calculator over 3 years instead of 10 years. The indication for drug therapy should be based on the threshold values of the DVO risk model. The data clearly suggests a significantly faster and more effective fracture risk-reducing effect of anabolic therapy. This is recommended in the first sequence in cases of a very high risk of fracture from 10%/3 years with osteoanabolic active substances (teriparatide or romosozumab). Such a therapy sequence should be initiated directly and not delayed due to upcoming dental procedures. Follow-up therapy to consolidate the reduction of fracture risk should be chosen individually.

Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Water-soluble biopolymers calcium polymalate derived from fermentation broth of Aureobasidium pullulans markedly alleviates osteoporosis and fatigue.

Osteoporosis is a prevalent condition characterized by bone loss and decreased skeletal strength, resulting in an elevated risk of fractures. Calcium plays a crucial role in preventing and managing osteoporosis. However, traditional calcium supplements have limited bioavailability, poor solubility, and adverse effects. In this study, we isolated a natural soluble biopolymer, calcium polymalate (PMACa), from the fermentation broth of the fungus Aureobasidium pullulans, to investigate its potential as an anti-osteoporosis therapeutic agent. Characterization revealed that linear PMA-Ca chains juxtaposed to form a porous, rod-like state, in the presence of Ca2+. In vivo mouse models demonstrated that PMA-Ca significantly promoted the conversion of serum calcium into bone calcium, and stimulated bone growth and osteogenesis. Additionally, PMA-Ca alleviated exercise fatigue in mice by facilitating the removal of essential metabolites, such as serum lactate (BLA) and blood urea nitrogen (BUN), from their bloodstream. In vitro studies further showed that PMA-Ca strengthened osteoblast cell activity, proliferation, and mineralization. And PMA-Ca upregulated the expression of some genes involved in osteoblast differentiation, indicating a potential correlation between bone formation and PMACa. These findings indicate that soluble PMA-Ca has the potential to be a novel biopolymer-based calcium supplement with sustainable production sourced from the fermentation industry.

The screened compounds from Ligustri Lucidi Fructus using the immobilized calcium sensing receptor column exhibit osteogenic activity in vitro.

Calcium sensing receptor (CaSR) has become the novel target of treating osteoporosis with herbal medicine Ligustri Lucidi Fructus (LLF), however, the bioactive compounds responsible for anti-osteoporosis are hard to clarify due to the complexity and diversity of chemical constituents in it. Herein, the immobilized CaSR column was packed with stationary phase materials, which were derived from integrating CLIP-tagged CaSR directly out of crude cell lysates onto the surface of silica gels (5.83 mg/g) in a site-specific covalent manner. The column had a great specificity of recognizing agonists and kept a good stability for at least 3 weeks. The two compounds from LLF extract were screened and identified as olenuezhenoside and ligustroflavone using the immobilized CaSR column in conjunction with mass spectrometry. Molecular docking predicted that both compounds were bound in venus flytrap (VFT) domain of CaSR by the formation of hydrogen bonds. Cellular results showed that both compounds exhibited the distinct osteogenic activity by enhancing the proliferation, differentiation and mineralization of osteoblastic cells. Our study demonstrated that, the immobilized protein column enables to screen the bioactive compounds rapidly from herbal extract, and the newly discovered natural product ligands towards CaSR, including olenuezhenoside and ligustroflavone, will be the candidates for the treatment of osteoporosis.

Loading rutin on surfaces by the layer-by-layer assembly technique to improve the oxidation resistance and osteogenesis of titanium implants in osteoporotic rats.

The purpose of this study was to construct a rutin-controlled release system on the surface of Ti substrates and investigate its effects on osteogenesis and osseointegration on the surface of implants. The base layer, polyethylenimine (PEI), was immobilised on a titanium substrate. Then, hyaluronic acid (HA)/chitosan (CS)-rutin (RT) multilayer films were assembled on the PEI using layer-by-layer (LBL) assembly technology. We used scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy and contact angle measurements to examine all Ti samples. The drug release test of rutin was also carried out to detect the slow-release performance. The osteogenic abilities of the samples were evaluated by experiments on an osteoporosis rat model and MC3T3-E1 cells. The results (SEM, FTIR and contact angle measurements) all confirmed that the PEI substrate layer and HA/CS-RT multilayer film were effectively immobilised on titanium. The drug release test revealed that a rutin controlled release mechanism had been successfully established. Furthermore, thein vitrodata revealed that osteoblasts on the coated titanium matrix had greater adhesion, proliferation, and differentiation capacity than the osteoblasts on the pure titanium surface. When MC3T3-E1 cells were exposed to H2O2-induced oxidative stressin vitro, cell-based tests revealed great tolerance and increased osteogenic potential on HA/CS-RT substrates. We also found that the HA/CS-RT coating significantly increased the new bone mass around the implant. The LBL-deposited HA/CS-RT multilayer coating on the titanium base surface established an excellent rutin-controlled release system, which significantly improved osseointegration and promoted osteogenesis under oxidative stress conditions, suggesting a new implant therapy strategy for patients with osteoporosis.

Synthesis of Heterocyclic Ring-Fused Bisnoralcohol Derivatives as Novel Small-Molecule Antiosteoporosis Agents.

A series of heterocyclic ring-fused derivatives of bisnoralcohol (BA) were synthesized and evaluated for their inhibitory effects on RANKL-induced osteoclastogenesis. Most of these derivatives possessed potent antiosteoporosis activities in a dose-dependent manner. Among these compounds, 31 (SH442, IC50 = 0.052 µM) exhibited the highest potency, displaying 100% inhibition at 1.0 µM and 82.8% inhibition at an even lower concentration of 0.1 µM, which was much more potent than the lead compound BA (IC50 = 2.325 µM). Cytotoxicity tests suggested that the inhibitory effect of these compounds on RANKL-induced osteoclast differentiation did not result from their cytotoxicity. Mechanistic studies revealed that SH442 inhibited the expression of osteoclastogenesis-related marker genes and proteins, including TRAP, TRAF6, c-Fos, CTSK, and MMP9. Especially, SH442 could significantly attenuate bone loss of ovariectomy mouse in vivo. Therefore, these BA derivatives could be used as promising leads for the development of a new type of antiosteoporosis agent.

Targeted delivery of anti-osteoporosis therapy: Bisphosphonate-modified nanosystems and composites.

Osteoporosis (OP) constitutes a significant health concern that profoundly affects individuals' quality of life. Bisphosphonates, conventional pharmaceuticals widely employed in OP treatment, encounter limitations related to inadequate drug targeting and a short effective duration, thereby compromising their clinical efficacy. The burgeoning field of nanotechnology has witnessed the development and application of diverse functional nanosystems designed for OP treatment. Owing to the bone tissue affinity of bisphosphonates, these nanosystems are modified to address shortcomings associated with traditional drug delivery. In this review, we explore the potential of bisphosphonate-modified nanosystems as a promising strategy for addressing osteoporotic conditions. With functional modification, these nanosystems exhibit a targeted and reversible effect on osteoporotic remodeling, presenting a promising solution to enhance precision in drug delivery. The synthesis methods, physicochemical properties, and in vitro/in vivo performance of bisphosphonate-modified nanosystems are comprehensively examined in this review. Through a thorough analysis of recent advances and accomplishments in this field, we aim to provide insights into the potential applications and future directions of bisphosphonate-modified nanosystems for targeted and reversible osteoporotic remodeling.

Corticosteroid Injections and Risk of Fracture.

Importance: Corticosteroid injections (CSIs) are an important tool for pain relief in many musculoskeletal conditions, but the longitudinal effects of these treatments on bone health and fracture risk are unknown. Objective: To determine whether cumulative doses of corticosteroid injections are associated with higher risk of subsequent osteoporotic and nonosteoporotic fractures. Design, Setting, and Participants: This cohort study included adult patients receiving any CSI from May 1, 2018, through July 1, 2022. Eligible patients resided in Olmsted County, Minnesota, and were empaneled to receive primary care within the Mayo Clinic. Cox proportional hazards regression models were used to evaluate risk of fracture based on cumulative injected corticosteroid dose. Exposure: Receipt of any CSI during the study period. Main Outcomes and Measures: The primary outcome was risk of fracture by total triamcinolone equivalents received. Secondary outcomes consisted of risks of fracture based on triamcinolone equivalents received in subgroups of patients not at high risk for fracture and patients with osteoporosis. Results: A total of 7197 patients were included in the study (mean [SD] age, 64.4 [14.6] years; 4435 [61.6%] women; 183 [2.5%] Black and 6667 [92.6%] White), and 346 (4.8%) had a new fracture during the study period. Of these fractures, 149 (43.1%) were considered osteoporotic. In the adjusted Cox proportional hazards regression model, there was no association of higher fracture risk based on cumulative CSI dose (adjusted hazard ratio [HR], 1.04 [95% CI, 0.96-1.11]). There was also no associated higher risk of fracture in the non-high-risk (adjusted HR, 1.11 [95% CI, 0.98-1.26]) or osteoporosis (adjusted HR, 1.01 [95% CI, 0.90-1.11]) subgroups. Age, Charleson Comorbidity Index, and previous fracture were the only factors that were associated with higher fracture risk. Conclusions and Relevance: In this cohort study of cumulative injected corticosteroid dose and risk of subsequent fracture, no association was observed, including in patients with a preexisting diagnosis of osteoporosis. Treatment of painful conditions with CSI should not be withheld or delayed owing to concern about fracture risk.

Links among Obesity, Type 2 Diabetes Mellitus, and Osteoporosis: Bone as a Target.

Obesity, type 2 diabetes mellitus (T2DM) and osteoporosis are serious diseases with an ever-increasing incidence that quite often coexist, especially in the elderly. Individuals with obesity and T2DM have impaired bone quality and an elevated risk of fragility fractures, despite higher and/or unchanged bone mineral density (BMD). The effect of obesity on fracture risk is site-specific, with reduced risk for several fractures (e.g., hip, pelvis, and wrist) and increased risk for others (e.g., humerus, ankle, upper leg, elbow, vertebrae, and rib). Patients with T2DM have a greater risk of hip, upper leg, foot, humerus, and total fractures. A chronic pro-inflammatory state, increased risk of falls, secondary complications, and pharmacotherapy can contribute to the pathophysiology of aforementioned fractures. Bisphosphonates and denosumab significantly reduced the risk of vertebral fractures in patients with both obesity and T2DM. Teriparatide significantly lowered non-vertebral fracture risk in T2DM subjects. It is important to recognize elevated fracture risk and osteoporosis in obese and T2DM patients, as they are currently considered low risk and tend to be underdiagnosed and undertreated. The implementation of better diagnostic tools, including trabecular bone score, lumbar spine BMD/body mass index (BMI) ratio, and microRNAs to predict bone fragility, could improve fracture prevention in this patient group.

Natural Compounds for Bone Remodeling: A Computational and Experimental Approach Targeting Bone Metabolism-Related Proteins.

Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome's influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment.

Aspirin use and changes in circulating tumor DNA levels in patients with metastatic colorectal cancer.

The study aimed to investigate the effects of aspirin on patients with metastatic colorectal cancer, focusing on circulating tumor DNA levels and bone tissue. Two groups (A and B) of ten patients with osteoporosis were selected for the study. Bone tissue samples were obtained from the patients and cultured under sterile conditions. The aspirin group showed a significant decrease in circulating tumor DNA levels and an increase in bone tissue density compared to the control group. Additionally, osteoblast apoptosis was reduced, while proliferation was enhanced in the aspirin group. The protein pAkt related to the PI3K/Akt signaling pathway was upregulated in the aspirin group. These results indicate that aspirin can effectively lower circulating tumor DNA levels, promote bone tissue proliferation, inhibit apoptosis, and activate the PI3K/Akt signaling pathway, thereby influencing bone cell function. These findings provide a basis for aspirin's potential application in treating metastatic colorectal cancer and encourage further research on its mechanism and clinical use.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Secondary fracture prevention in Spanish primary care: results of the PREFRAOS Study.

This study demonstrated a large treatment gap in elderly subjects experiencing fragility fracture in Spanish primary care, a low treatment persistence among subjects who do receive treatment, and more than one-quarter having no follow-up visits post-fracture. These data highlight the need to improve secondary fracture prevention in primary care. PURPOSE: To describe osteoporosis (OP) treatment patterns and follow-up in subjects with fragility fracture seen in Spanish primary care (PC). METHODS: This observational, retrospective chart review included subjects aged ≥ 70 years listed in the centers' records (November 2018 to March 2020), with ≥ 1 fragility fracture and prior consultation for any reason; subjects who had participated in another study were excluded. Outcomes included OP treatments and follow-up visits post-fragility fracture. RESULTS: Of 665 subjects included, most (87%) were women; overall mean (SD) age, 82 years. Fewer than two thirds (61%) had received any prior OP treatment (women, 65%; men, 38%); of these, 38% had received > 1 treatment (women, 25%; men, 13%). Among treated subjects, the most frequent first-line treatments were alendronate (43%) and RANKL inhibitor denosumab (22%), with a higher discontinuation rate and shorter treatment duration observed for alendronate (discontinuation, 42% vs 16%; median treatment duration, 2.5 vs 2.1 years). Over one-quarter (26%) of subjects had no follow-up visits post-fragility fracture, with this gap higher in women than men (35% versus 25%). The most common schedule of follow-up visits was yearly (43% of subjects with a fragility fracture), followed by half-yearly (17%) and biennial (10%), with a similar trend in men and women. Most OP treatments were prescribed by PC physicians, other than teriparatide and zoledronate. CONCLUSIONS: Across Spanish PC, we observed a large gap in the treatment and follow-up of elderly subjects experiencing a fragility fracture. Our data highlights the urgent need to improve secondary fracture prevention in PC.