Infusion Of Zoledronic Acid Research Articles

313 STREAMLINING A ZOLEDRONIC ACID SERVICE TO A LEVEL TWO HOSPITAL

Abstract Background Approximately, 350-400 patients are admitted to a level 4 hospital for hip-fractures yearly (2019). According to the Irish Hip Fracture Database (2020) the average age for a hip-fracture is 81 years old. Patients post-hip fractures are commenced on Zoledronic acid; a bisphosphonate which is given intravenously 10 days post-surgery and then annually in year two and three. Zoledronic acid is a first line choice of bisphosphonate for the ≥65 population with a fragility fracture. Methods 274 patients were transferred from the level 4 Hospital waiting list to a level 2 hospital waiting list to streamline the service. Meetings occurred to establish a pathway for the transition of services. A rapid improvement of the level 2 Day Hospital (DH) was commenced. Essential resources, training and information leaflets were developed in order to begin the service. A policy review, procedure guidelines and referral pathway were implemented. An excel database of patient information was transferred between organisations. The 274 patients were triaged by the DH. Pre-assessment phone calls were conducted determining if patients were still eligible for Zoledronic acid. Results Of the 274 referrals; 24 had died; 30 refused; 37 were on other bone treatments and another 7 patients haven’t made creatinine clearance, leaving 176. All 176 patients were allocated an appointment for 2022. Of the 176 patients; currently 57 patients have received their Zoledronic acid infusion in the DH. 69 of these referrals had an indicative date for their next Zoledronic acid infusion for dates after April 2022. There are 50 patients yet to receive their treatment which is overdue. Conclusion With the prospect of service demands increasing due to Irelands aging population inevitably placing extra pressures on infusion suites in a level 4 hospital. The level 2 hospital has effectively managed to focus on tackling the backlog, streamlining referrals to the bone health service and thus reducing the risk of subsequent hip fractures.

101 UTILITY OF BONE TURNOVER MARKERS IN GUIDING ZOLEDRONIC ACID THERAPY AFTER STOPPING DENOSUMAB

Abstract Background Denosumab is commonly used to treat osteoporosis, but drug holidays are not an option, with a risk of rebound bone loss and vertebral fractures on stopping. However, data on therapy safety and efficacy is lacking beyond 10-years and switching treatment to bisphosphonates may be appropriate for some patients. Recent guidelines suggest treatment with Zoledronic Acid if stopping Denosumab, with consideration for a second dose based on subsequent Bone Turnover Markers (BTM). We aimed to assess BTM of older patients transitioned to Zoledronic acid after stopping Denosumab. Methods Patients who received Zoledronic acid 6 months after their last and final Denosumab injection were identified at our bone health clinic. We compared BTM on Denosumab therapy versus at 3 months post Zoledronic acid administration. BTM measured was cross linked C-Telopeptide of type I collagen (CTX ) (ng/ml). Results 48 patients were included (mean age 70.6 years and 90% female, mean Denosumab treatment 4.6 years). Mean CTX at baseline was 0.09 and 0.29 at 3-months post Zoledronic acid (mean difference 0.20, P <0.001). 40% of patients (19) had a CTX >0.30 (above the therapeutic range) at 3 months and in those, mean CTX was 0.45. Duration of prior Denosumab therapy, baseline CTX or age did not predict either change in CTX or CTX rises above 0.30. Conclusion All patients had a significant elevation in BTM at 3-months after transitioning to Zoledronic acid. However, a high proportion (40%) had a rise in CTX above the therapeutic range. Recent guidelines suggest treatment of such patients with a second infusion of Zoledronic acid to suppress bone resorption and bone loss. This highlights the value of using BTM in guiding therapy post Denosumab cessation. We did not find any predictors of greater rebound bone turnover but sample size was small and likely to be underpowered.

Case Report: Acute Unilateral Uveitis Induced by Infusion of Zoledronic Acid

Case Report: Acute Unilateral Uveitis Induced by Infusion of Zoledronic Acid

SAPHO—a diagnosis to consider in patients with refractory costochondritis

BackgroundSAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis) is a rare, heterogeneous, self-limited disease of unknown etiology. It involves progressive bone and joint damage, and skin and bone lesions may occur at different times in the course of the disease. Skin lesions are characterized by neutrophil dermatosis. Its management is empirical and mainly symptomatic, and nonsteroidal anti-inflammatory drugs are the first-line treatment.Case presentationForty-seven-year-old female presented with a 7-year history of costochondral pain. It had progressive onset, chronical course, with no other associated symptoms, and no other joint involvement. She was treated with intermittent NSAID (nonsteroidal anti-inflammatory drugs), which provided only partial pain relief; there was bilateral tender swelling of the sternoclavicular region, the skin over the sternoclavicular area was slightly erythematous, but there were no other skin lesions, and based on imaging findings, a diagnosis of SAPHO syndrome was established. The patient received an infusion of zoledronic acid with subsequent complete resolution of her chest wall symptoms, and completely improved after 3 days.ConclusionsThis case is considered atypical presentation of SAPHO syndrome, without skin changes, long-term persistence of refractory symptoms, and the diagnosis was established by imaging, with complete resolution after zoledronic acid infusion. SAPHO is a differential diagnosis in patients with chronic costochondritis. Therapeutic failure to NSAID is a key to its diagnostic suspicion. Also, early diagnostic suspicion is associated with better outcomes.

Renal safety of zoledronic acid for osteoporosis in adults 75years and older.

Zoledronic acid (ZA) is used for the treatment of osteoporosis (OP). Renal impairment is a known risk factor for the rare occurrence of nephrotoxicity after ZA infusions, leading to use being contraindicated below creatinine clearance (CCr) of 35mL/min. Our aims are to examine changes in serum creatinine (SCr) after infusions, capture frequency of acute kidney injury (AKI), and describe baseline kidney function estimates in adults 75years and older being treated for OP. This was a retrospective, cross-sectional, pre-post analysis that examined change in SCr before and after ZA infusions. The primary outcome was assessed using a paired Student t-test. Incidence of AKI within 1year following infusions was noted and patient-specific factors were collected. Five hundred fifty-eight ZA infusions in 327 patients met criteria. Mean SCr decreased by 0.01mg/dL in the year following ZA infusions (p = 0.005). AKI occurred in 1.4% of patients and all had CCr > 45mL/min. 4.5% of patients had CCr < 35mL/min and none experienced an AKI. There was no clinically relevant change in SCr after ZA infusions. Risk of nephrotoxicity was low and similar to risk seen in randomized trials occurring in younger patients. Kidney function estimates were dramatically lower using the Cockcroft-Gault (CG) equation in comparison to CKD-EPI. We believe use of the CG equation in this population may be inappropriately limiting our ability to use ZA for treatment of OP in older adults but more evidence is necessary.

Effect of zoledronic acid with or without methylprednisolone on 3D bone area and bone shape in patients with symptomatic knee osteoarthritis: A post-hoc analysis of the ZAP2 trial

ObjectiveTo evaluate the effect of annual infusions of zoledronic acid (ZA) with or without a single injection of methylprednisolone, compared to placebo, on quantitative magnetic resonance imaging 3-D bone area and bone shape in participants with symptomatic knee osteoarthritis (OA). MethodsThis was a post-hoc analysis of the ZAP2 trial. Active appearance modelling was used to assess bone area (mm2) and femur bone shape (B-score) in 262 participants (mean 61.8 ± 8.0 years, 51% female) at baseline, 6, and 24 months. Radiographic joint space narrowing (JSN) was measured at baseline. An ‘OA shape’ was defined as a B-score of >1.96. ResultsAt baseline 65% of participants demonstrated an OA shape. Treatment with ZA plus methylprednisolone but not ZA alone, compared to placebo, was associated with significantly slower expansion in bone area at the medial femoral (-33.9 mm2, 95% confidence interval [CI] -61.8 to -6.0) and lateral femoral (-22.0 mm2, 95%CI -40.7 to -3.4) compartments over 24 months. B-score increased in all groups, with no significant between-group differences. There were significant interactions of JSN (grade 0 vs grade 1–2) and B-score (≤1.96 vs >1.96) with treatment effect on bone area (p < 0.05), such that ZA plus methylprednisolone slowed the expansion of medial and lateral femoral bone area over 24 months in participants with JSN grade 1–2 or a B-score of >1.96. ConclusionsZA plus methylprednisolone may retard expansion of bone area over 24 months, but ZA alone may not. Neither ZA with or without methylprednisolone slowed progression of bone shape over 6 or 24 months.

Effects of zoledronic acid therapy in fibrous dysplasia of bone: a single-center experience.

Fibrous dysplasia (FD) is a rare bone disorder that can involve any part of the skeleton, leading to bone pain, deformities, and fractures. Treatment with intravenous bisphosphonates has been used with variable results. Therefore, we aimed to evaluate the effects of zoledronic acid (ZA) therapy in patients with monostotic or polyostotic FD. The medical records of thirteen patients with FD evaluated between 2015 and 2020 were retrospectively analyzed. In the subgroup of patients treated with ZA (n = 7), data on pain relief, changes in bone turnover markers (BTMs), and adverse events following ZA infusions were retrieved. Moreover, radiological changes in response to treatment were recorded in patients who underwent radiological follow-up. Of the patients, 5 (38%) presented with monostotic whereas 8 (62%) had polyostotic FD. Bone pain was a common finding (69%), and most patients (62%) exhibited elevated baseline BTMs. Partial or complete pain relief was reported in 6 of 7 patients treated with ZA. BTMs, especially C-telopeptide of type I collagen (CTX), significantly decreased after therapy (change rate: -61.8% [IQR -71, -60%]), and median CTX levels were significantly lower than at baseline (0.296 ng/mL [0.216, 0.298] vs. 0.742 ng/mL [0.549, 0.907], respectively; P = 0.04). No radiological improvement was observed in cases with radiological follow-up (n = 3). No serious adverse effects of ZA were reported. ZA treatment was well tolerated and provided beneficial effects in relieving bone pain and reducing BTMs, especially CTX. Our data reinforce the role of ZA in the treatment of FD-related bone pain.

Эффективность применения золедроновой кислоты при лечении остеопороза у больных раком предстательной железы, получающих терапию агонистами ГнРГ

Introduction. It has been established that prolonged androgen-deprivation therapy (ADT) of prostate cancer leads to a decrease in bone mineral density (BMD) and increases the risk of fractures, which is an important medical and social problem. Zoledronic acid (ZA) is most often used for the prevention of osteoporosis against the background of ADT. The purpose of the study is to determine the efficacy and safety of ZA for the treatment and prevention of osteopo-rosis in non-metastatic prostate cancer against the background of ADT therapy with GnRH agonists. Materials and methods. The study included 45 men aged 54-81 years with morphologically verified prostate cancer (stages T2-4 N0-1 M0) who underwent surgical castration at least 6 months before inclusion or continuously received therapy with GnRH agonists. The blood level of CTX-1 was used as the main marker of bone resorption. To assess the BMD, the screening method of dual-band X-ray densitometry of the calcaneus with laser determination of the examination area – DXL using the CALSCAN apparatus and the DXL Calscan Workstation software was used. Patients were randomized into groups of 15 people each: Group 1 – received intravenous infusion of ZA at a dose of 4 mg at the beginning of the study and after 3 months of treatment; Group 2 received ZA at 2 mg in the same mode; Group 3 – control. For antire-sorptive therapy (ART), the drug Resorba (JSC «Pharm-Synthesis», Russia) was used. The duration of follow-up was 6 months. Results. In 13 out of 15 patients of Group 1, 3 months after the first administration of ZA, a decrease in the level of CTX-1 by 50% or more was observed, and after 6 months all 15 patients (100%) reached the age norm («complete answer»). Group 2 patients also responded to ART and by the 6th month 13 out of 15 (87%) had achieved a «complete response». In the control group by the 6th month the decrease in CTX-1 was not observed in any of the patients. Initially, the values of BMD in the studied groups did not differ. By the 3rd month of the study, the BMD index significantly increased only in Group 1. In Group 2 this indicator significantly increased by the 6th month of treatment. At the same time, in Group 1 after 6 months the BMD index reached higher values than in Group 2: an increase of 27% and 13%, respectively. In the control group, by the 6th month of observation, a significant decrease in BMD by 12% was noted. In Group 1, the number of patients with osteoporosis decreased to 6% and with a normal level of BMD – reached to 40%. Conclusion. High efficacy and sufficient safety of ZA in doses of 4 mg and 2 mg i/v one time in 3 months for anti-resorptive therapy in patients receiving long-term hormonal therapy with GnRH agonists has been demonstrated.

Tolerability of the first infusion of once-yearly zoledronic acid within one to two weeks after hip fracture surgery.

Once-yearly infusions of zoledronic acid (ZA) 5mg may be optimal for secondary fracture prevention after hip fracture (HF), but there are crucial side effects of ZA. This study assessed the tolerability of the first infusion of once-yearly ZA within one to two weeks after HF surgery and to identify risk factors for acute-phase reactions (APRs) and the decrease in serum calcium (Ca) concentration. We analyzed 84 patients (average age: 83years, 18 men and 66 women) who met the inclusion criteria. The patients underwent the first infusion of ZA one to two weeks after HF surgery and received antipyretic analgesics and active vitamin D analog. APRs occurred in ten patients (11.9%) and all these patients had pyrexia (>37.5°C) and/or other symptoms. The asymptomatic hypocalcemia (serum Ca<8.3mg/dL) incidence was 6.0% at 7days after ZA infusion. Compared with female patients without APRs, female patients with APRs had significantly higher levels of serum 25-dihydroxyvitamin D at baseline and serum C-reactive protein on the day ZA was administered (day 0). Multiple linear regression analyses showed that serum level of tartrate-resistant acid phosphatase-5b were significantly associated with an absolute decrease in serum corrected Ca from day 0 to day 7. The first infusion of ZA within one to two weeks after HF surgery was well tolerated with the combined use of antipyretic analgesics and active vitamin D analog. Higher inflammatory condition after surgery which is more likely sensitized by ZA administration may increase the risk of APRs, and high bone turnover may increase hypocalcemia risk.

Efficacy of Yigu® versus Aclasta® in Chinese postmenopausal women with osteoporosis: a multicenter prospective study

SummaryZoledronic acid (ZOL) is a therapy inhibiting bone resorption. In this study, generic ZOL (Yigu®) showed its clinical efficacy consistency with original ZOL (Aclasta®) in Chinese postmenopausal women with osteoporosis. This study provides a practical basis for the application of Yigu® in Chinese population.IntroductionYigu® has been approved its bioequivalence to Aclasta®. However, the clinical efficacy and safety of Yigu® have not been evaluated yet. Here, we compared the effectiveness and safety between Yigu® and Aclasta® in Chinese postmenopausal women with osteoporosis and assessed the efficacy of intravenous infusion of ZOL.MethodsThis was a randomized open-label, active-controlled study in postmenopausal women with osteoporosis of 14 clinical centers in China. Postmenopausal women with osteoporosis were recruited and randomized to receive a single infusion of 5 mg Yigu® or Aclasta®. The primary endpoint was the percentage change in bone mineral density (BMD) at lumbar spine after 12 months of treatment and was assessed for equivalence. The secondary endpoint was the percentage change in BMD at proximal femur after 12 months. Additional secondary endpoints were percentage changes in BMD at the above sites after 6 months of treatment and changes in bone turnover biomarkers during ZOL treatment. Safety was also evaluated and compared between two groups.ResultsA total of 458 postmenopausal women with osteoporosis were enrolled (n = 227, Yigu®; n = 231, Aclasta®). The mean percentage change in the BMD had no statistical difference at the lumbar spine (5.32% vs 5.18%), total hip (2.72% vs 2.83%), and femoral neck (2.37% vs 2.81%) between Yigu® and Aclasta® groups after 12 months of treatment. The mean difference of BMD change at the lumbar spine after 12 months between two groups was 0.15% (95% CI: − 0.71 to 1.00, equivalence margin: − 1.5%, 1.5%), demonstrating the treatments were equivalent. Meanwhile, the decreases in the P1NP and β-CTX showed no difference between two groups after 14 days and 6 and 12 months of treatment. As regards the whole sample, BMD significantly increased after 12 months of treatment. Also, serum C-terminal telopeptide of type 1 collagen (β-CTX) and procollagen 1 N-terminal peptide (P1NP) significantly decreased at each visit period. The overall adverse events were comparable and quite well between two groups.ConclusionIntravenous infusion of zoledronic acid achieved the potent anti-resorptive effects which led to significant increase in BMD of Chinese postmenopausal women with osteoporosis. Yigu® was equivalent to Aclasta® with respect to efficacy and safety.

Severe and Prolonged Hypocalcaemia Post Zoledronic Acid Infusion in a Patent with Sleeve Gastrectomy

Background: Zoledronic acid is commonly used to treat hypercalcaemia and osteoporosis, as well as to prevent skeletal complications from haematological and solid organ malignancies. Case presentation: We report the case of a 38 year old lady who presented with severe hypocalcaemia following the administration of zoledronic acid. Her significant background history included vitamin D deficiency and sleeve gastrectomy three years ago. She had prolonged hypocalcaemia requiring IV calcium replacement for two months. Her prolonged hypocalcaemia was attributed to her vitamin D deficiency at the time of zoledronic acid infusion as well as her history of bariatric surgery. Conclusion: This case emphasises the importance of ensuring vitamin D levels are replete prior to zoledronic acid infusion and ensuring the calcium levels are checked frequently in patients with a history of bariatric surgery obtaining zoledronic acid.

Predicting the individualized risk of nonadherence to zoledronic acid among osteoporosis patients receiving the first infusion of zoledronic acid: development and validation of new predictive nomograms

Introduction:Achieving optimal adherence to zoledronic acid (ZOL) among osteoporosis (OP) patients is a challenging task. Here, we aimed to develop and validate a precise and efficient prediction tool for ZOL nonadherence risk in OP patients.Methods:We prospectively collected and analyzed survey data from a clinical registry. A total of 1010 OP patients treated for the first time with ZOL in two separate hospitals were selected for nonadherence analysis. The evaluation included a 16-item ZOL Nonadherence Questionnaire and potential risk factors for ZOL nonadherence were assessed via univariate and multivariate analyses. We next developed and validated two distinct-stage nomograms. Discrimination, calibration, and clinical usefulness of the predicting models were assessed using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA).Results:The total nonadherence rate was 20.30% after the first ZOL infusion. To generate a model predicting ZOL nonadherence risk, six predictors of 16 items were retained. Model 2 (AUC, 0.8486; 95% confidence interval [CI], 0.8171–0.8801) exhibited considerably more discrimination in desirable functional outcomes, relative to Model 1 (AUC, 0.7644; 95% CI, 0.7265–0.8024). The calibration curves displayed good calibration. DCA revealed that a cutoff probability of 5–54% (Model 1) and 1–85% (Model 2) indicated that the models were clinically useful. External validation also exhibited good discrimination and calibration.Conclusions:This study developed and validated two novel, distinct-stage prediction nomograms that precisely estimate nonadherence risk among OP patients receiving the first infusion of ZOL. However, additional evaluation and external validation are necessary prior to widespread implementation.

Characteristics Associated with Acute-Phase Response following First Zoledronic Acid Infusion in Brazilian Population with Osteoporosis.

We aimed to evaluate characteristics associated with acute-phase response (APR) following first zoledronic acid infusion in a Brazilian cohort. This retrospective cohort study enrolled all adults with osteoporosis who underwent a first zoledronic acid infusion at our centre between June 2015 and June 2019. Clinical demographics (age, sex, diabetes, smoking, body mass index, and previous oral bisphosphonate use) and laboratory data (calcium, parathyroid hormone, renal function, and serum 25-hydroxyvitamin D and carboxy-terminal crosslinked telopeptide of type 1 collagen [CTX], both before and after infusion) were compared between patients with and without APR. We evaluated association magnitude between the presence of APR and clinical variables through logistic regression. This study enrolled 400 patients (women, 80%). APR was observed in 24.5% (n = 98) of patients. The mean symptom duration in days was 3.5 ± 2.8. Patients with APR were younger (67 ± 12 vs. 71 ± 11 years; p=0.001), used oral bisphosphonates less frequently (34% × 50%; p=0.005), and had greater baseline CTX (0.535 ng/mL [0.375, 0.697] × 0.430 [0.249, 0.681]; p=0.03) and ΔCTX (−69 [−76; −50] × −54 [−72; −23]; p=0.002) than those without APR. The other variables were similar between the groups. Only ΔCTX was associated (OR, 0.62; 95% CI 0.41–0.98) with APR after accounting for age and bisphosphonate use. APR occurred in 24.5% of the cohort. Younger age and absence of prior oral bisphosphonate use were associated with APR following first zoledronic acid infusion. APR was associated with ΔCTX (but no other variables) after adjusting for these factors.

Toxicity of zoledronic acid after intravenous administration: A retrospective study of 95 dogs.

BackgroundThere is a paucity of veterinary literature on the safety or outcome of zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia.Hypothesis/ObjectivesThe primary aim was to report the adverse events in dogs receiving intravenous administration of ZA.AnimalsNinety‐five dogs with ZA use.MethodsA retrospective cohort study was performed; all dogs that received at least 1 dose of ZA and had a serum biochemistry profile performed before and after treatment were reviewed. Diagnosis, indication for treatment, adverse events and survival times were recorded.ResultsNinety‐five dogs met the inclusion criteria. Thirty‐one (33%) received multiple intravenous infusions of ZA (range, 2‐7), making a total of 166 administrations in all dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis (n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be confirmed as the cause of azotemia in any case. The change in serum creatinine concentration from dose to dose was not related to the total dose received (P = .46). Five dogs (5%) changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOG‐CTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg (range, 0.26‐0.66) was not significantly different to the group which did not change VCOG‐CTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2‐1.50; P = .93).Conclusions and Clinical ImportanceMultiple doses of ZA were well tolerated in dogs within this study. A small number of dogs developed progressive azotemia which was not associated with cumulative dose.

Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury: a randomized, controlled trial.

A single infusion of zoledronic acid (ZOL) after acute spinal cord injury (SCI) attenuates bone loss at the hip (proximal femur) and knee (distal femur and proximal tibia) for at least 6 months. The objective of this study was to examine the effects of timing and frequency of ZOL over 2 years. In this double-blind, placebo-controlled trial, we randomized 60 individuals with acute SCI (<120 days of injury) to receive either ZOL 5-mg infusion (n=30) or placebo (n=30). After 12 months, groups were again randomized to receive ZOL or placebo, resulting in four treatment groups for year 2: (i) ZOL both years; (ii) ZOL year 1, placebo year 2; (iii) placebo year 1, ZOL year 2; and (iv) placebo both years. Our primary outcome was bone loss at 12 months; compared to placebo, a single infusion of ZOL attenuated bone loss at the proximal femur, where median changes relative to baseline were -1.7% to -2.2% for ZOL versus -11.3% to -12.8% for placebo (p < 0.001). Similarly, the distal femur and proximal tibia showed changes of -4.7% to -9.6% for ZOL versus -8.9% to -23.0% for placebo (p ≤ 0.042). After 24 months, differences were significant at the proximal femur only (-3.2% to -6.0% for ZOL vs. -16.8% to -21.8% for placebo; p ≤ 0.018). Although not statistically significant, median bone density losses suggested some benefit from two annual infusions compared to a single baseline infusion, as well as from a single infusion 12 months after baseline compared to 2 years of placebo; therefore, further investigation in the 12-month to 24-month treatment window is warranted. No unanticipated adverse events associated with drug treatment were observed. In summary, ZOL 5-mg infusion after acute SCI was well-tolerated and may provide an effective therapeutic approach to prevent bone loss in the first few years following SCI. © 2021 American Society for Bone and Mineral Research (ASBMR).

P10 Treating osteoporosis, facing reality – adopting a holistic approach

Case report - IntroductionOsteoporosis is a significant health problem; globally around 200 million women are affected. In Europe, osteoporosis is responsible for a higher disability encumber than cancer (with the exception of lung cancer). The treatment of osteoporosis is quite exacting. Although understanding of the diagnosis and treatment of osteoporosis has broadened considerably over the last few years, lack of bridging information still exists with guidance lacking on the appropriate management of complex comorbid clinical scenarios.Here we will present a scenario of a patient with osteoporosis and multiple risk factors and comorbidities, where choice of suitable anti osteoporotic treatment was quite challenging.Case report - Case descriptionAn 84-year-old lady with known osteoporosis with history of T-12 fracture (in 2009), sarcoidosis, coeliac disease (confirmed on duodenal biopsy), chronic hepatitis, history of acute kidney injury secondary to zoledronic acid infusion and urosepsis in 2017 was re-referred to the rheumatology clinic from respiratory team for optimisation of her bone protection.She was previously on risedronate for almost 5 years without any improvement of bone mineral density. She was last seen in rheumatology in 2018, because of ineffectiveness and intolerance to alendronate (gastritis) and intravenous zoledronate – a discussion about subcutaneous denosumab was had, but the patient refused that option because of needle phobia. So, the plan was to maintain her on optimisation of vitamin D and calcium level. She was discharged from the clinic. Her GP advised her against vitamin D or calcium supplements because of episodes of hypercalcaemia secondary to sarcoidosis. For the last 3 years she was not on any bone protection or even calcium or vitamin D supplements.Recently she noticed a worsening of exertional dyspnoea. She was reviewed by the respiratory team. Her lung function test showed slow progression of restrictive lung disease with FEV1/FVC ratio is 100.4%. In December 2020, she was started on prednisolone 30mg, which gradually stepped down; at the moment, she is on 15mg and will continue it as maintenance.The patient was an ex-smoker, and drinks alcohol at about 10 unit/week. Her mobility is slightly better compared to the last few years. She trys to keep active and is enjoy gardening in the sunny weather. It was difficult to convince her for blood tests; however, we succeeded after repeated counselling. Her blood tests showed microcytic anaemia, with normal inflammatory markers mild renal impairment with eGFR of 67, corrected calcium 2.19, alkaline phosphatase 78, vitamin D 49 (sub optimal) albumin 32.Case report - DiscussionConsidering her age, comorbidities, frailty, intolerance and doubt about the efficacy, selecting an appropriate bone protection for her was fairly hard. Starting denosumab had more risk than benefit and in future if it need to stop there is an increased chance of rebound fracture. Besides this, she re-expressed her reluctance to the subcutaneous option. Moreover, calcium and vitamin D level were low in her recent blood tests. She did not fulfil the criteria for considering teriperatide. We reviewed her DEXA scan in 2018, which showed an overall 19% reduction of BMD compared to 2009 (1.6% per year). She was on risedronate intermittently for about 4 years that time; however, she had not experienced any new fracture at that point. She had multiple hospital admissions during those years. Bone protection was withheld multiple times. Poor mobility, frailty status and other comorbidities during that period were also responsible for BMD decline. Her case was discussed with a consultant with special interest in metabolic bone disease. Treatment decisions should be individualised; risk versus benefit needs to be considered to ensure the best outcome for the patient. We have decided to put her back on risedronate for at least 3 years. She tolerated only this medication in the past. We have requested bone markers and a repeat DEXA scan. Case report - Key learning pointsComorbidities adversely affect the management of osteoporosis. A comprehensive assessment of the comorbid list is necessary before considering changing a medication which suits the patient well and when there is limited option. Obstacles to offer high quality service are knowledge, expertise, and critical thinking from healthcare professionals, and knowledge and compliance to treatment from patients. Facing those challenges and treating patients judiciously will help to reduce the potential health and economic burden of osteoporosis.

Thyroid dysfunction with Zoledronic acid infusion for osteoporosis

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Correlation Analysis of Adverse Reactions of Antiosteoporosis Drugs by Different Mechanisms with Bone Turnover and Vitamin D.

Objective The risk factors for the most common adverse reactions of two types of antiosteoporosis drugs in the first treatment of postmenopausal osteoporosis were analyzed to investigate the relationship between the occurrence of adverse reactions and different bone transition states and vitamin D levels. Methods A total of 381 postmenopausal women who were diagnosed with osteoporosis in the Osteoporosis Clinic of Ningxia Medical University General Hospital from January 2017 to June 2020 were enrolled. A telephone follow-up survey was conducted on the mentioned subjects. According to the survey results, the mentioned subjects were selected according to their first use of antiosteoporosis drugs. They were divided into zoledronic acid and teriparatide acetate groups. The subjects in the two groups were divided into two groups according to the presence or absence of adverse reactions after medication and according to vitamin D level and P1NP level, and the correlation between the two factors and the occurrence of adverse reactions was analyzed. Results Among the 307 patients treated with zoledronic acid for antiosteoporosis, 99 patients developed acute phase adverse reactions (APR+), accounting for 32.2% of the total subjects. 56.7 percent of the subjects had vitamin D deficiency. The 25(OH)D level of the APR + subjects was 16.75 ± 9.20 ng/mL, significantly lower than that of the APR− patients (23.68 ± 10.67 ng/mL). Serological P1NP level in APR+ patients was 73.95 ± 34.50 ng/ml, significantly higher than that of APR− patients with 55.80 ± 36.91 ng/ml. Musculoskeletal symptoms were observed in 14 of the 74 subjects treated with teriparatide acetate, accounting for 18.9% of the total subjects. The 25(OH)D level was deficient in 59.5% of the subjects. The 25(OH)D level of the subjects with musculoskeletal symptoms was 15.96 ± 8.17 ng/ml, while that of the subjects without musculoskeletal symptoms was 20.86 ± 8.52 ng/ml, which showed no statistical significance. The reason was considered to be related to the small sample size included in the study. The P1NP level of subjects with musculoskeletal symptoms was 96.85 ± 58.52 ng/ml, significantly higher than the P1NP level of subjects without musculoskeletal symptoms (55.28 ± 27.87 ng/ml). Conclusions The 25(OH)D level in vivo was negatively correlated with the acute phase adverse reactions after the first infusion of zoledronic acid. When the rate of bone formation is increased and osteoblasts are active, the risk of acute phase adverse reactions is increased with the use of zoledronic acid as antiosteoporosis therapy. There was no significant correlation between 25(OH)D levels and musculoskeletal symptoms after teriparatide acetate treatment of osteoporosis. When the rate of bone formation is increased and osteoblasts are active, the risk of adverse reactions to musculoskeletal symptoms is increased with antiosteoporosis treatment with teriparatide acetate.

Fibrous dysplasia of thoracic and lumbar spine: A case report

IntroductionFibrous dysplasia (FD) is a rare genetic disease characterized by development of dysplastic bone tissue leading to pain, deformities and compressive complications. Spinal involvement is rare particularly for the polyostotic form. Case reportHerein, we present a case of 52-year-old man presented with isolated low back pain who received non-steroidal anti-inflammatory drugs (NSAIDs) with partial pain relief. On examination, the thoracic and lumbar spines were tender. Lumbar spine movements, attested by Shöber’s test and finger-to-floor test, were limited. There was no radicular pain and neurological examination was normal. The erythrocyte sedimentation rate was 20 mm/1st hour, C- reactive protein 2 mg/l and white blood cell count, serum calcium, phosphorus, alkaline phosphatase and parathormone were normal. Plain x-ray lumbar and thoracic spine and hips were normal. X-ray cervical spine and peripheral bone showed no lesions. Computed tomography (CT) and magnetic resonance imaging showed multiple osteolytic lesions with ground-glass opacity and sclerotic rims of thoracic and lumbar (L1 and L2) spine. Investigations to rule out malignancy or infections were negative. CT guided biopsy of a lumbar vertebra was performed and showed the presence of abnormal fibrous matrix surrounding an irregular shaped immature bone. The diagnosis of polyostotic FD of the spine was made. Zoledronic acid infusion was introduced and the patient felt better thereafter with no additional osteolytic lesions or new pain localization reported for 2 years on follow up. ConclusionThoracic and lumbar spine FD is a rare localization that should be considered in the differential diagnosis of back pain.

Relationship Between Changes in Serum Levels of Intact Parathyroid Hormone and Sclerostin After a Single Dose of Zoledronic Acid: Results of a Phase 1 Pharmacokinetic Study

Although changes in serum sclerostin levels at 12 months after infusion of zoledronic acid have been reported, the changes in sclerostin levels at earlier time points are poorly understood. We reanalyzed the study data of a previous phase 1 pharmacokinetic study and investigated the correlation between changes in sclerostin levels and relevant factors in calcium metabolism. A total of 24 Japanese female subjects with primary postmenopausal osteoporosis were administered a single 4- or 5-mg dose of zoledronic acid. Serum and urine samples were collected on days 15, 29, 90, 180, and 365 after administration. Serum levels of calcium, phosphate, intact parathyroid hormone (iPTH), and sclerostin were measured. Levels of serum sclerostin were unchanged from baseline on days 15 and 29, but increased significantly on day 90, subsequently decreased significantly on day 180, and returned to baseline levels on day 365. A significant negative correlation was observed between changes in iPTH levels at early time points and sclerostin levels at later time points. This suggests that sclerostin was negatively regulated by iPTH, and the decrease in sclerostin may indicate the start of bone formation during later time points after zoledronic acid injection.