Bisphosphonate Therapy Research Articles

Bone Augmentation With Alloplastic Graft Material in a Patient Under Bisphosphonate Therapy: A Case Report and Literature Review.

Cases of relatively safe dental implant treatment in patients with low-volume bisphosphonate (BP) have been gradually reported. Although bone augmentation is commonly used when the bone volume is insufficient for implant placement, the studies and case reports regarding the safety of bone augmentation in patients treated with BP remain insufficient. Herein, we report a case wherein bone augmentation was performed after BP treatment with bone healing realized according to imaging, and we review the literature regarding BP and bone augmentation. A 67-year-old Japanese woman requested implant treatment for a hopeless lower right second molar. She had been taking minodronic acid hydrate (50 mg/4 wk) for 18 months to treat steroid-induced osteoporosis. After obtaining informed consent, tooth extraction and bone augmentation within the extraction socket were performed. The tooth was extracted atraumatically to preserve the surrounding alveolar bone, and the extraction socket was intensely curetted. Subsequently, the socket was filled with carbonate apatite granules and covered with a biodegradable membrane, and the wound was sutured without tension. Although protracted wound healing without any symptoms of infection was observed, the wound healed completely. No clinical symptoms were observed, the color of the mucosa at the site was healthy, and imaging findings at 6 months postoperation indicated that osteogenesis had progressed uneventfully.

Disease Activity and Bone Microarchitectural Phenotype in Patients With Axial Spondyloarthritis

Background: Axial spondyloarthritis (AxSpA) is a chronic rheumatic disease characterized by spine inflammation, abnormal bone growth, and paradoxically osteoporosis and vertebral fractures. The pathogenesis of skeletal deficits in this disease is poorly understood. Purpose: We sought to evaluate volumetric bone mineral density (vBMD) and bone microarchitecture in patients with AxSpA and to identify disease-related factors associated with skeletal abnormalities. Methods: We enrolled patients between 2018 and 2021 as part of a 2-year prospective study at a single institution investigating skeletal health and the skeletal effects of interleukin-17 (IL-17) treatment. Patients with AxSpA who met Assessment in SpondyloArthritis International Society (ASAS) classification criteria by X-ray or had evidence of active inflammation on magnetic resonance imaging suggestive of sacroiliitis were referred to the study by their rheumatologists. We excluded those with a history of fragility fracture, multiple myeloma, Cushing’s disease, primary hyperparathyroidism, osteomalacia, untreated vitamin D deficiency, secondary osteoporosis, or other systemic rheumatic diseases, as well as use of oral steroids for 2 or more weeks in the 6 months prior or current use of hormone replacement therapy, current oral bisphosphonate, past or current intravenous bisphosphonate, teriparatide, or denosumab therapies. A total of 1606 patients were screened for eligibility. Of these, 30 participants were enrolled (mean age 43 years, 50% male). Patients with AxSpA had dual-energy X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) and high-resolution peripheral quantitative computed tomography (HR-pQCT) measurements of vBMD microarchitecture and failure load by finite element analysis. Standardized disease assessment tools used included the Bath Ankylosing Spondylitis Disease Activity (BASDAI), Metrology Index (BASMI), and Functional Index (BASFI). Results: In the 30 included patients, mean DXA and HR-pQCT Z-scores were within 1 standard deviation (SD) of normal for all indices, except for total vBMD in males (–1.2 SD below mean). Mean symptom duration was 11.7 years and mean scores for BASDAI, BASFI, and BASMI were 4.6, 3.6, and 2.7, respectively (range 1–10, 10 = severe limitation). Longer disease duration was associated with more severe skeletal deficits at the hip and tibia—specifically, lower hip aBMD, lower meta- and inner-trabecular vBMD, lower trabecular number, and higher trabecular separation and heterogeneity. Conclusion: This study of 30 patients with AxSpA found that abnormalities in bone density and microarchitecture at weightbearing sites were associated with longer disease duration. Because of its small sample size, larger studies are needed to better characterize the pathogenic disease factors that govern skeletal damage in AxSpA.

A multifaceted role of bisphosphonates from palliative care to anti-cancer therapy in solid tumors.

Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors. Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted. This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

Differences in tissue-level properties as assessed by nano-scratching in patients with and without atypical femur fractures on long-term bisphosphonate therapy: a proof-of-concept pilot study.

Atypical femur fractures (AFFs) are a well-established complication of long-term bisphosphonate (BP) therapy, but their pathogenesis is not fully understood. Although many patients on long-term BP therapy have severe suppression of bone turnover (SSBT), not all such patients experience AFF, even though SSBT is a major contributor to AFF. Accordingly, we evaluated tissue level properties using nano-scratch testing of trans-iliac bone biopsy specimens in 12 women (6 with and 6 without AFF matched for age and race). Nano-scratch data were analyzed using a mixed-model ANOVA with volume-normalized scratch energy as a function of AFF (Yes or No), region (periosteal or endosteal), and a first-order interaction between region and AFF. Tukey post hoc analyses of the differences of least squared means of scratch energy were performed and reported as significant if p<.05. The volume-normalized scratch energy was 10.6% higher in AFF than in non-AFF patients (p=.003) and 17.9 % higher in the periosteal than in the endosteal region (p=.004). The differences in normalized scratch energy are suggestive of a higher hardness of the bone tissue after long-term BP therapy. The results of this study are consistent with other studies in the literature and demonstrate the efficacy of using Nano-Scratch technique to evaluate bone tissue that exhibits SSBT and AFF. Further studies using nano-scratch may help quantify and elucidate underlying mechanisms for the pathogenesis of AFF.

Severe atypical iliac wing fracture associated with long-term bisphosphonate use.

Bisphosphonate use is associated with atypical non-traumatic fractures, which are most commonly seen in the femur. We report a 63-year-old postmenopausal woman who presented acutely with progressively worsening lumbar pain radiating to her left hip for 10days. There was no antecedent trauma. On examination, the patient could not bear weight on her left leg due to the severity of the pain. Radiography and computed tomography of the pelvis demonstrated an iliac wing fracture which was treated conservatively. The patient had a significant past medical history of breast cancer and intense bisphosphonate use for several years which was discontinued 3years previously. No discrete bone lesion was seen at the fracture site on computed tomography, and there was no evidence of metastatic disease elsewhere. A dual-energy X-ray absorptiometry scan showed the lowest bone mineral density T-score of - 1.2. A diagnosis of an atypical fracture related to long-term bisphosphonate therapy was made. To the best of our knowledge, this is the first reported case of an isolated iliac wing fracture associated with long-term bisphosphonate therapy in the literature. Whilst the incidence of such fractures is exceedingly rare, it is an important differential in patients with atypical fractures on long-term bisphosphonates.

Hypercalcaemia in gastrointestinal stromal tumour and sarcoidosis: a case report

BackgroundHypercalcaemia is a common manifestation of sarcoidosis but is sparingly described in gastrointestinal stromal tumours (GISTs). We describe a case of acute kidney injury and hypercalcemia resulting from simultaneous diagnosis of GIST and sarcoidosis, the presentation of which has not yet been reported.Case PresentationA 61-year-old male presented with acute kidney injury and hypercalcemia, with elevated 1,25-dihydroxyvitamin D levels. Investigations demonstrated a large gastric antral mass which was resected and proven to be GIST. Histopathology of incidentally found liver nodules revealed non-necrotising epithelioid granulomas consistent with concomitant sarcoidosis. The hypercalcemia was successfully treated with bisphosphonate therapy, resection of the GIST and a four month course of corticosteroids, which was truncated due to a mycobacterial infection.ConclusionsOur case report is the first to describe hypercalcemia due to GIST and biopsy-proven sarcoidosis, thereby raising the possibility of a common pathophysiological pathway relating the two entities. We review the literature describing the mechanisms of hypercalcaemia in GIST and the association between GIST and sarcoidosis.

Clinical effects of teriparatide, abaloparatide, and romosozumab in postmenopausal osteoporosis.

In the management of osteoporosis, anti-resorptive agents serve as a primary therapeutic approach. However, in cases where individuals exhibit an increased susceptibility to fractures, such as those characterized by severe low bone mass or a history of vertebral or hip fractures that markedly diminish life expectancy, the immediate reduction of fracture risk through the administration of osteoanabolic agents could be beneficial. Teriparatide, available in daily, once-weekly, or twice-weekly dosages, along with abaloparatide and romosozumab, constitutes a trio of such agents. Each of these medications is defined by unique characteristics, distinct efficacy profiles, and specific adverse effects. There is growing evidence to suggest that these agents have a superior effect on enhancing bone mineral density and reducing fracture incidence when compared to traditional bisphosphonate therapies. Nonetheless, their employment demands thorough consideration of clinical indications, which includes evaluating economic factors, the frequency of injections required, and the potential for adverse effects. The objective of this review is to consolidate the current evidence focusing primarily on the efficacy of these agents, with the goal of enhancing understanding and aiding in making more informed treatment decisions, particularly for those individuals who are at an elevated risk of fractures.

Generalized arterial calcification of infancy due to mutations of the ENPP1 and ABCC6 genes: phenotype features, bisphosphonate therapy

Generalized arterial calcification of infancy due to mutations of the ENPP1 and ABCC6 genes: phenotype features, bisphosphonate therapy

Pamidronate Response in a Novel Biallelic CREB3L1 Gene Mutation-Associated Osteogenesis Imperfecta: A Case Report.

We report a 15-year-old adolescent boy being followed up for 6 years with osteogenesis imperfecta (OI). Genetic testing of this child revealed a novel missense variant c.925C>T p.Arg309Cys in the CREB3L1 gene. Treatment with regular pamidronate therapy showed increased bone mineral density and a reduced fracture rate. His lower limb rush rodding improved his mobility. His withdrawal from bisphosphonate therapy worsened his mobility status but started improving after he restarted treatment, suggesting a response to pamidronate therapy. We report a novel biallelic missense variant c.925C>T, p.Arg309Cys, in the CREB3L1 gene causing OI, which responded to bisphosphonate therapy and corrective surgery.

Combinatorial effects of hydroxyapatite and Tualang honey on medication-related osteonecrosis of the jaw (MRONJ): An in vitro study

BackgroundMedication-related osteonecrosis of the jaw (MRONJ) is a severe complication associated with prolonged bisphosphonate therapy. Increasing evidence shows that mucosal damage plays an important role in the pathogenesis of MRONJ. This study investigates the combinatorial effects of hydroxyapatite with Tualang honey on cell viability and wound healing in MRONJ. Materials and methodsThe incorporation of Tualang honey into hydroxyapatite was assessed using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and field emission scanning electron-energy dispersive X-ray analysis microscopy (FESEM-EDX). The effect of hydroxyapatite combined with Tualang honey on cell viability was determined by WST-1 assay and wound healing was assessed by scratch assay. ResultsThe incorporation of Tualang honey into hydroxyapatite altered the functional groups, structure, size, morphology, and components of the crystal as evidenced by FTIR, XRD and FESEM-EDX analysis. High concentrations of pamidronic acid inhibit oral fibroblast viability and wound healing. Low and high concentrations of hydroxyapatite demonstrate non-toxicity towards fibroblast cells. Furthermore, hydroxyapatite reversed the action of pamidronic acid on the cells; it increased fibroblast viability but did not close the wound. Tualang honey promotes fibroblast viability and wound closure. However, the addition of Tualang honey is unable to overcome the inhibitory effects of pamidronic acid on fibroblasts. The addition of Tualang honey and hydroxyapatite improved the cell viability and accelerated wound closure of fibroblast exposed to pamidronic acid. ConclusionThese findings demonstrated that the combination treatment protects oral fibroblasts by preventing bisphosphonate toxicity.

Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy and their association with age and estimated glomerular filtration rate (eGFR). This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over 1 year. Patients' clinical data were collected. The levels of BTMs and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decreased levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.

The Risk of Medication-Related Osteonecrosis of the Jaw in Children: Guidance for Antiresorptive Use in Pediatric Patients

Antiresorptive targeted cancer therapies, such as denosumab and bisphosphonates, are used in adults, but their application in pediatric cancer is more recent. Side effects such as osteonecrosis of the jaw (ONJ) observed in adults have curtailed use of these medications in the pediatric population. This study assesses the frequency of ONJ, other side effects, and the indications for use of denosumab versus bisphosphonates in pediatric subjects. A retrospective cohort study of pediatric subjects who underwent bisphosphonate or denosumab therapy at our institution from 2007-2023 was conducted. Subjects aged ≥ 18years at therapy initiation were excluded. The independent variable was antiresorptive therapy divided into 2 groups, treatment with intravenous bisphosphonates or denosumab. Primary outcomes were development of bisphosphonate-related and denosumab-related ONJ. Secondary outcomes included additional side effects. ONJ risk factors, subject demographics, indications for use, timing, duration, and cumulative dose of antiresorptive therapy were abstracted. Univariate and bivariate statistics were computed to describe the sample and measure associations between antiresorptive therapy and outcomes. P values < .05 conferred statistical significance. The sample was composed of 178 subjects with a mean age of 11.7±6.1years. There were 14 (7.9%) and 164 (92.1%) subjects treated with denosumab and bisphosphonate therapies, respectively. There were 0 cases of ONJ across all subjects. The most common indication for treatment was adjuvant targeted therapy for aggressive tumors and malignancy (39.3%) followed by osteoporosis (14.6%). Subjects treated with denosumab had higher frequencies of hypercalcemia and severe bone pain than subjects treated with bisphosphonates, 28.6% versus 1.2% (P<.001) and 14.3% versus 0.00% (P<.001), respectively. While invasive dental procedures are ideally performed before antiresorptive treatment, our data suggest that bisphosphonates may be used safely in the pediatric population with low concern for ONJ. Our data also demonstrated bisphosphonates may have a more tolerable side effect profile than denosumab. If the perceived benefits are similar, we recommend using bisphosphonates as first-line therapy in children while reserving denosumab for refractory cases. Future studies will help determine long-term side effects and differences in efficacies of these medications.

Barriers to osteoporosis management and adherence to Clinical Practice Guideline: a comparative study between tertiary East Coast hospitals and a Fracture Liaison Services (FLS)-accredited hospital in Malaysia.

Osteoporosis management poses a substantial healthcare challenge, necessitating effective strategies and Clinical Practice Guidelines (CPG) adherence. The study employed a self-administered online questionnaire via Google Forms. Orthopedic clinicians from all study sites were invited to participate via messaging platforms. A total of 135 participants completed the questionnaire and the data was proceeded to statistical analyses. The study identified significant barriers, including inadequate knowledge of current osteoporosis guidelines and medications (p = 0.014), limited choice of anti-osteoporosis medication (p < 0.001), insufficient post-fracture care staff (p < 0.001), patients' financial constraints due to socioeconomic status (p = 0.027), and lack of doctor-patient time (p = 0.042). FLS demonstrated superior performance in CPG adherence in areas such as clinical diagnosis of osteoporosis without BMD assessment (p = 0.046), timely treatment initiation (p < 0.001), treatment monitoring using BMD (p = 0.004), reassessment treatment after 3-5years of bisphosphonate therapy (p = 0.034) and considering anabolic agents in very high-risk patients (p = 0.018). The findings highlight an essential opportunity for improvement and emphasize the necessity for robust strategies and strict adherence to Clinical Practice Guidelines (CPG), especially within tertiary East Coast hospitals. The exemplary efficacy demonstrated by the FLS model strongly advocates for its broader integration across multiple hospitals, promising substantial advancements in osteoporotic patient care outcomes throughout Malaysia.

Systemic Osteoporosis and Osteopenia Among Periprosthetic Fractures After Total Hip Arthroplasty

BackgroundMost periprosthetic fractures following total hip arthroplasty (THA) are fragility fractures that qualify patients for osteoporosis diagnoses. However, it remains unknown how many patients were diagnosed who had osteoporosis before injury or received the proper evaluation, diagnosis, and treatment after injury. MethodsWe identified 171 Vancouver B2 (109) and B3 (62) periprosthetic femur fractures treated with a modular fluted tapered stem from 2000 to 2018 at 1 institution. The mean patient age was 75 years (range, 35 to 94), 50% were women, and the mean body mass index was 29 (range, 17 to 60). We identified patients who had osteoporosis or osteopenia diagnoses, a fracture risk assessment tool (FRAX), bone mineral density (BMD) testing, an endocrinology consult, and osteoporosis medications. Age-appropriate BMD testing was defined as no later than 1 year after the recommended ages of 65 (women) or 70 years (men). The mean follow-up was 11 years (range, 4 to 21). ResultsFalls from standing height caused 94% of fractures and thus, by definition, qualified as osteoporosis-defining events. The prevalence of osteoporosis diagnosis increased from 20% before periprosthetic fracture to 39% after (P < .001). The prevalence of osteopenia diagnosis increased from 13% before the fracture to 24% after (P < .001). The prevalence of either diagnosis increased from 24% before fracture to 44% after (P < .001). No patients had documented FRAX scores before fracture, and only 2% had scores after. The prevalence of BMD testing was 21% before fracture and 22% after (P = .88). By the end of the final follow-up, only 16% had received age-appropriate BMD testing. The proportion of patients who had endocrinology consults increased from 6% before the fracture to 25% after (P < .001). The proportion on bisphosphonate therapy was 19% before fracture and 25% after (P = .08). ConclusionsAlthough most periprosthetic fractures following THA are fragility fractures that qualify patients for osteoporosis diagnoses, there remain major gaps in diagnosis, screening, endocrinology follow-up, and treatment. Like nonarthroplasty fragility fractures, a systematic approach is needed after periprosthetic fractures. Level of EvidenceLevel III, retrospective cohort study.

Assessing our adherence to bone protection standards in metastatic prostate cancer in the largest Irish center: Are we falling behind?

e24145 Background: Prostate cancer ranks as the second most prevalent cancer in men globally, often necessitating androgen deprivation therapy (ADT) as part of its treatment. While ADT effectively diminishes testosterone levels, a vital factor in prostate cancer cell growth, it concurrently poses a notable side effect – an accelerated rate of bone loss. This heightened bone loss elevates the vulnerability of patients to osteoporosis and fractures. The optimization of bone health entails early identification of patients susceptible to osteoporosis and fractures, the implementation of preventative measures, and prompt interventions to mitigate bone loss and fracture risks. Methods: The audit aims to evaluate adherence to established guidelines, such as those outlined by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), concerning the assessment and optimization of bone health. A retrospective analysis was performed on the medical records of prostate cancer patients who underwent Androgen Deprivation Therapy (ADT) at St James Hospital in Dublin. Pertinent data, encompassing patient demographics, duration of ADT, documentation of bone health assessment, frequency of Bone Mineral Density (BMD) testing, utilization of preventive measures (e.g., calcium and vitamin D supplementation), and any interventions for bone health optimization (such as bisphosphonate therapy and denosumab), was systematically collected. Results: A comprehensive review encompassed 57 patients, revealing that 38 patients (67%) exhibited metastatic disease. Among them, 42 patients (74%) presented with castrate-sensitive disease. Out of the total, 24 patients (42%) underwent a baseline Dual-Energy X-ray Absorptiometry (DEXA) scan. Results indicated that 12 patients were diagnosed with Osteoporosis, 9 with Osteopenia, and 3 with normal Bone Mineral Density (BMD). At baseline, 26 patients (46%) initiated Calcium and Vitamin D supplements, while 12 patients (21%) commenced Bisphosphonates/Denosumab based on DEXA scan outcomes. Notably, 8 (14%) patients experienced a skeletal/bone-related event which is much higher than reported in literature. Conclusions: The findings are intended to guide healthcare professionals in optimizing bone health strategies, with the ultimate goal of improving patients' quality of life and minimizing the risk of fractures and related complications. Identified areas for improvement in clinical practices will be addressed by implementing recommended recommendations, aiming to enhance patient care, decrease the risk of osteoporosis and fractures, and overall improve patient outcomes. A re-audit is planned to monitor ongoing adherence to guidelines and assess the impact of interventions implemented as a result of this study.

Dental Implant Failure in Post-Menopausal Women on Oral Bisphosphonates: A Systematic Review and Meta-Analysis.

A systematic review was designed to investigate the effect of treatment with oral bisphosphonate (BP) on osseointegration of dental implants and the incidence of BP-related osteonecrosis of the jaw (BRONJ) in postmenopausal women. Multiple electronic databases, including MEDLINE (PubMed), EMBASE, and SCOPUS, were searched to find all eligible articles published since 1990. All titles and abstracts retrieved by searching information sources were evaluated independently by 2 authors against the eligibility criteria. The number of cases ranged from 11 to 235, and the number of controls ranged from 14 to 343. Alendronate was used in all other studies. Risedronate was used in 6 studies, while ibandronate was used in 4 studies. The number of implants in cases ranged from 25 to 1267, while in controls, the number of implants ranged from 28 to 1450. The time between the placement of implant and the follow-up visit ranged from 4-6 months to 8 years. The results show that out of 2582 placed implants, 50 (1.94%) failed in BP-treated patients. This is while out of 4050 placed implants, 188 (4.6%) failed in the non-BP group. The results from the meta-analysis demonstrated that BP therapy is significantly associated with increased implant failure rates (RR = 1.73 [95% CI, 1.03-2.83], P = .04). Overall, the qualitative assessment of this review suggests that oral treatment with BPs in postmenopausal women does not increase the rate of dental implant failure. Thus, further studies with larger sample sizes should compare BP and non-BP groups in regard to dental implants.

Dynamics of procollagen type 1 N-terminal propeptide in postmenopausal osteoporosis during bisphosphonate therapy and transcranial electrical stimulation

Dynamics of procollagen type 1 N-terminal propeptide in postmenopausal osteoporosis during bisphosphonate therapy and transcranial electrical stimulation

Randomised control trial on management of early avascular necrosis of femoral head by core decompression with bisphosphonate therapy versus core decompression in tertiary care hospital in central India

Background This study outlines a randomised control trial to assess the efficacy of Core Decompression with and without Bisphosphonate Therapy in managing early Avascular Necrosis of the femoral head. Avascular Necrosis, a debilitating condition, necessitates exploration of interventions to mitigate progression. The trial is conducted at Jawaharlal Nehru Medical College and Acharya Vinoba Bhave Rural Hospital, Sawangi, Wardha, focusing on clinical, radiographic, and patient-reported outcomes. Methods Skeletally mature participants diagnosed with stage 1 or 2 Avascular Necrosis of the femoral head will be randomly assigned to either Core Decompression with Bisphosphonate Therapy or Core Decompression Alone. Data collection from July 2022 to September 2024 will involve preoperative assessments, intraoperative details, postoperative care records, and followup evaluations at six weeks, three months, six months, and nine months. Statistical analyses will encompass primary outcomes assessed by Harris Hip Score, secondary outcomes including pain reduction and radiographic changes, and subgroup analyses. Expected Outcome Anticipated outcomes involve insights into the comparative effectiveness of the two interventions. Primary analyses will reveal variations in Harris Hip Score changes over time, while secondary analyses will shed light on pain reduction, radiographic changes, and potential complications. Subgroup analyses may discern nuances based on etiological factors. The results aim to inform clinical practice, guiding the optimal management of early Avascular Necrosis of the femoral head.

E009 An audit looking into bisphosphonate co-prescription and compliance in patients with giant cell arteritis

Abstract Background/Aims The treatment of giant cell arteritis includes glucocorticoid use to reduce inflammation. There are known drawbacks of long-term glucocorticoid use, including osteopenia and osteoporosis. The British Society for Rheumatology giant cell arteritis guidelines recommend that we should consider appropriate pharmacological bone protection at the time of presentation to counteract this. Glucocorticoid toxicity risks increases with both dosage and duration of steroid use. To reduce steroid burden, we consider introduction of the steroid sparing agents such as tocilizumab and methotrexate. This audit was to look into whether we were locally achieving bone protection consideration and to whether steroid sparing agents were helping in terms of compliance of bisphosphonates. Methods We retrospectively looked at the clinical letters of the patients locally diagnosed with giant cell arteritis in the previous 3 years to ascertain whether there was documentation of decisions around starting bisphosphonates at the time of diagnosis and whether the patients tolerated bisphosphonate therapy for the recommended duration. Patients were classified into 3 groups, as to whether their treatment was glucocorticoids with tocilizumab (TOC), glucocorticoids with methotrexate (MTX) or glucocorticoid monotherapy (MONO). Results 49 Patients were identified. 3 of these patients were excluded for various reasons. 17 were in the TOC group, 11 in the MTX group, and 18 in the MONO group. Documentation of consideration of bisphosphonates at diagnosis was 94% in TOC, 91% in MTX and 100% in MONO. Overall this was 96%. Compliance of bisphosphonate therapy for the recommended duration was 88% in TOC, 90% in MTX and 86% in MONO. Overall compliance was 88%. There was no statistically significant difference between the steroid sparing groups and the monotherapy group both in terms of consideration of initiation of bisphosphonate treatment and compliance of bisphosphonate treatment, with p values of 0.52 and 0.8 respectively. Conclusion Overall, we found that locally there was good consideration of bisphosphonate therapy at diagnosis and that compliance remained good throughout treatment. This can help reduce the side effect profile of glucocorticoid toxicity. Although, there was no statistically significant difference in our study of concordance of bisphosphonates between the two groups, steroid sparing agents are useful in our arsenal at reducing the risks of glucocorticoid toxicity. Disclosure A.A. Bolger: None. L. Hutton: None.

Surrogate markers in assessment of bisphosphonate effectiveness in osteoporosis treatment (bone mineral density, bone turnover markers)

A review of the literature which summarizes our knowledge on the use of surrogate markers of the osteoporosis treatment effectiveness when on bisphosphonate (BP) therapy. Bone mineral density (BMD) and markers of bone turnover, which have been shown to be associated with the clinical fracture end point, have been used as surrogate criteria for the effectiveness of treatment of osteoporosis in randomized controlled trials. When prescribing BP for the treatment of osteoporosis, BMD measurement every 12 months by dual-energy x-ray absorptiometry (DXA) is the well-described surrogate marker of BP efficacy. At the same time, stabilization of BMD is also a criterion for the treatment effectiveness since changes in BMD determined only 16% of the anti-fracture effectiveness of BP. Markers of bone remodeling can be used as surrogate markers after 3 (bone resorption) or 6 (bone formation) months from the start of BP therapy. A decrease of 30% or more is considered to be prognostically effective for both antifracture and BMD gain. There is a direct relationship between the degree of bone remodeling markers decrease and the antifracture effectiveness of BP therapy. The decrease in markers persists throughout the entire period of therapy and, accordingly, they can be used as surrogate markers of effectiveness and adherence to BP therapy throughout the entire treatment period. However, the presence of pathological fractures is a key clinical manifestation of osteoporosis and should be considered first in every decision making compared to any surrogate marker.Thus, when prescribing BP treatment, surrogate markers of changes in BMD and/or markers of bone remodeling can be used to monitor the effectiveness of treatment throughout the entire period of treatment and patients’ monitoring.