Intravenous Zoledronic Acid Research Articles

ODP131 Zoledronic acid and red eye

Abstract Introduction Zoledronic acid, used for treatment of osteoporosis, Paget's disease of the bone, hypercalcemia of malignancy etc. is a bisphosphonate known for its anti-resorptive effect. A common adverse reaction with this medication is mild to moderate flu-like symptoms, which is transient and attributed to an acute phase reaction post zoledronic acid infusion. [1] A less common adverse reaction is ocular inflammation, including uveitis, iritis and episcleritis. [1] The incidence of ocular inflammation is 0.2 - 0.8%. [2] Development of ocular symptoms have been reported to occur between 1 to 7 days post zoledronic acid infusion. [2] We report a case of acute unilateral episcleritis following zoledronic acid infusion for treatment of osteoporosis. Clinical case: A 58-year-old female with a past medical history significant for glaucoma and gastroesophageal reflux (GERD) presented for management of osteoporosis. She could not tolerate oral bisphosphonates due to gastrointestinal side effects. She was therefore switched to intravenous zoledronic acid therapy. On day 1 post zoledronic acid infusion of 5mg dose, she developed diffuse joint and muscle pain as well as right eye pain, redness, photophobia, blurred vision and tearing. As her ocular symptoms progressed by day 5 post zoledronic acid infusion, she presented urgently to ophthalmology clinic when she was diagnosed with episcleritis of the right eye secondary to the zoledronic acid infusion. Patient was started on prednisolone acetate eyedrops twice a day. Three days after starting the eyedrops, patient reported complete resolution of her ocular symptoms. Further treatment for osteoporosis with zoledronic acid was discontinued. Conclusion We present a case of right eye episcleritis occurring 24 hours post zoledronic acid infusion leading to significant ocular discomfort and concern for the patient. Ocular inflammation is an uncommon occurrence post zoledronic acid infusion, hence is not often discussed during routine patient counseling in regards to risks and benefits of this particular treatment. We therefore stress the need for both provider and patient awareness regarding this uncommon ocular side effect related to zoledronic acid use. It is important to inform the patient and educate providers about the possibility of this acute phase reaction occurring post treatment with zoledronic acid to aid in prompt diagnosis and treatment. Our patient responded well to treatment with prednisolone acetate ophthalmologic drops. A rechallenge with zoledronic acid has not been pursued.

PSAT182 Dilemmas in the Diagnosis and Management of Osteoporosis in a patient with Alkaptonuria: Successful Treatment with Teriparatide

Abstract Introduction Diagnosis and management of osteoporosis in patients with alkaptonuria can be challenging. Coexisting arthritis involving the lumbar spine (LS) and hips can falsely elevate bone density making DXA interpretation difficult. We report a patient with alkaptonuria who was successfully treated with teriparatide in addition to bisphosphonate therapy. Case History A 69-year-old female presented for evaluation of osteoporosis. She was diagnosed with alkaptonuria at age 29 when she reported bilateral conjunctival hyperpigmentation. She was also diagnosed with arthritis requiring left knee joint replacement at the age of 57 years. Subsequently, she underwent left hip, right knee, right hip, and left shoulder joint replacement surgeries. She also sustained fragility fractures in the foot and a 2-inches height loss. Physical examination: normal vital signs. Examination of eyes and ears: bluish black discoloration of the conjunctiva and ear lobes. Heart examination showed normal S1, split S2, and IV/VI systolic murmur over the right parasternal border; the rest of the physical examination revealed limited joint movements of thoracic and lumbar spines, wrists, ankles, knees and hip joints. Laboratory: serum PTH 33 pg./mL, 25-OH vitamins 28 ng/mL, 1,25 (OH)2 vitamin D 43 pg/mL, osteocalcin 11.6 mg/mL (ref 9.4-47.4), collagen cross-linked C-telopeptide 318 pg/mL (ref 104-1008), tyrosine 79.1 umol/L (ref 31.1-118.1), 24 hours urine homogentisic acid 4.2 gms (ref 20-30 mg). Genetic testing: compound heterozygous mutation for the HGD C. 496T2T>C and HGD C.1102A < G (p.mev368Va) variants, consistent with a diagnosis of alkaptonuria. DXA scan done at the age of 56 years showed osteoporosis (T score -2.7 femoral neck, 1.8 total hip, 2.5 LS). Patient was started on alendronate 70mg PO weekly for 5 years in addition to nitisinone. While on alendronate, she sustained fragility fractures of the right radius and left ankle. After 5 years of alendronate, the patient was transitioned to teriparatide 20-mcg subcutaneously (SC) daily for 2 years followed by annual intravenous zoledronic acid. For the subsequent 7 years, the patient led a healthy, active life with no fractures. Follow-up DXA showed improvement to the osteopenic range at the radius site as degenerative arthritis made interpretation of other sites impossible.This case illustrates the challenges in the diagnosis and treatment of osteoporosis in patients with alkaptonuria. DXA can be ineffective in this condition due to the hip and LS arthritis. Measurement of trabecular bone scoreS and CT of the LS may be better alternate choices. Bisphosphonates alone are typically not effective in preventing fragility fractures in this population but use of teriparatide may be an effective treatment. Further studies are needed to assess the effectiveness of teriparatide in this population but our case shows promise that this treatment result in BMD improvement and fracture prevention. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Management of severe hypercalcaemia secondary to primary hyperparathyroidism: The efficacy of saline hydration, furosemide, and zoledronic acid.

Severe hypercalcaemia is a life-threatening condition that should be managed urgently. The aim of this study was to assess the efficacy of saline hydration, furosemide, and zoledronic acid in the management of severe hypercalcaemia secondary to primary hyperparathyroidism (PHPT). We conducted a retrospective analysis of the management of 65 patients with severe hypercalcaemia (≥3 mmol/L) secondary to PHPT. The efficacy of each therapeutic agent was evaluated according to the variation in serum calcium level calculated as Δ calcium=initial calcium level - minimal calcium level reached after the administration of each agent. The mean age of patients was 56.4± 13.8 years. At baseline, the mean total serum calcium level was 3.42 ± 0.40 mmol/L. After normal saline hydration, calcium level decreased from 3.25 ± 0.21 to 2.98 ± 0.2 mmol/L (p < 10-3 ) in 3.1 ± 1.7 days. Normalization of calcium level did not occur in any patient. Furosemide was prescribed in 35 patients. It resulted in a serum calcium increase of 0.09 ± 0.21 mmol/L. Calcium levels did not reach the normal range in any patient. Forty-five patients received intravenous zoledronic acid. The mean maximal reduction in serum calcium level was 0.57 ± 0.27 mmol/L (from 3.25 ± 0.26 mmol/L to 2.68 ± 0.22 mmol/L, p-value <10-3 ). Normalization of calcium levels occurred in 27 patients (60%). Our results show the absence of a significant additional effect of furosemide on calcium levels in patients with severe hypercalcaemia secondary to PHPT when compared with the effect of saline hydration alone. However, zoledronic acid was more potent. Thus, appropriate normal saline hydration with immediate intravenous bisphosphonates infusion should be considered in the management of severe hypercalcaemia in patients with PHPT.

Gingival swelling and diffuse mandibular osteolysis in a 57-year-old woman

A 57-year-old woman was referred from her hematologist for evaluation of a left mandibular gingival swelling of 1 week's duration. The hematologist expressed concern about odontogenic infection owing to the patient’s prolonged immunosuppressive chemotherapy for the management of treatment-resistant multiple myeloma (MM). The diagnosis of MM had been made in 2017, and since then she had received multiple rounds of chemotherapy, undergone autologous stem cell transplantation, and received intravenous zoledronic acid (Zometa; Novartis). Her health history was also significant for type 2 diabetes mellitus, hypertension, and a distant history of mandibular orthognathic surgery. Results of the extraoral examination did not indicate any pathology. The intraoral examination revealed a firm, sessile, nonmobile, 1-cm mass on the buccal gingiva between teeth nos. 21 and 22 (Figure 1). The results of pulpal and periapical testing of adjacent teeth were unremarkable. No evidence of purulent drainage or hemorrhage from the lesion was seen. A cone-beam computed tomographic scan revealed multiple missing teeth in the maxillary and mandibular right quadrants as well as hardware in place from a bilateral sagittal split osteotomy. In addition, multiple ill-defined radiolucencies were notable across the mandible, with cortical perforation apparent in the anterior and left mandible (Figures 2 and 3) without evidence of tooth resorption or displacement. An excisional biopsy was performed of the gingival soft-tissue lesion in the area of teeth nos. 21 and 22 under local anesthesia. The histopathologic examination revealed a gingival soft-tissue lesion composed of an unremarkable superficial squamous mucosa with extensive and diffuse submucosal infiltrates of mature plasma cells (Figure 4). Immunohistochemical staining showed that the plasma cells were positive for cluster of differentiation 138, and in situ hybridization for κ and λ light chains showed that the plasma cells were κ-restricted (Figure 5). 1 O’Connell F.P. Pinkus J.L. Pinkus G.S. CD138 (syndecan-1), a plasma cell marker: immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms. Am J Clin Pathol. 2004; 121: 254-263https://doi.org/10.1309/617DWB5GNFWXHW4L Crossref PubMed Scopus (214) Google Scholar Dr. Barawi is a resident, Department of Oral and Maxillofacial Surgery, University of Illinois at Chicago, Chicago, IL. Mr. Shah is a student, College of Dentistry, University of Illinois at Chicago, Chicago, IL. Dr. Cabay is an associate professor of clinical pathology, Department of Pathology, College of Medicine; a clinical associate professor, Department of Otolaryngology, College of Medicine; and an associate professor, Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, University of Illinois Hospital, University of Illinois at Chicago, Chicago, IL. Dr. Callahan is an assistant professor, Department of Oral and Maxillofacial Surgery, University of Illinois at Chicago, Chicago, IL.

Denosumab versus zoledronic acid in elderly patients after hip fracture.

Two injectable anti-osteoporosis medications, denosumab and zoledronic acid, have been widely used to treat patients with severe osteoporosis. The purpose of this study was to evaluate the real-world effectiveness and adherence of denosumab compared to zoledronic acid in geriatric patients after a hip fracture. A total of 282 patients treated with osteoporotic hip fracture between March 2014 and Aug 2022 were retrospectively reviewed. The patients were asked to select the anti-osteoporosis medication after surgery. Treatment persistence was monitored by follow-up visit to the outpatient clinic at postoperative 2years. Of 282 individuals with baseline data, 162 patients took subcutaneous denosumab and 120 patients took intravenous zoledronic acid. At postoperative 2years, the change in bone mineral density (BMD) from baseline was greater in the denosumab group compared with the zoledronic acid group (p < 0.001). The rate of persistence to denosumab was significantly higher than that for 12-months zoledronic acid (p = 0.01). Serious adverse events were similar in the two groups. Our study revealed the effectiveness and patients' persistence for two commonly used anti-osteoporosis agents after hip fracture. In this frail, elderly population, half-yearly denosumab was superior to yearly zoledronic acid in BMD and demonstrated significant higher persistence rate, indicating a potential therapeutic advantage that warrants further validation.

How zoledronic acid improves osteoporosis by acting on osteoclasts.

Osteoporosis is called a silent disease, because it is difficult to detect until comprehensive examinations for osteoporosis are performed or osteoporotic fractures occur. Zoledronic acid is currently the first-line anti-osteoporotic drug, with good efficacy and treatment compliance. A major advantage of zoledronic acid is that intravenous zoledronic acid often guarantees a therapeutic effect for up to 1 year after infusion. The reasons why zoledronic acid is effective in improving osteoporosis are that it can inhibit osteoclast differentiation and induce osteoclast apoptosis, thus suppressing bone resorption and increasing bone density. The story between zoledronic acid and osteoclasts has been written long time ago. Both the canonical receptor activator of the receptor activator of nuclear factor-κB ligand (RANKL) pathway and the non-canonical Wnt pathway are the main pathways by which zoledronic acid inhibits osteoclast differentiation. Farnesyl pyrophosphate synthase (FPPS), reactive oxygen species (ROS), and ferroptosis that was first proposed in 2012, are all considered to be closely associated with zoledronic acid-induced osteoclast apoptosis. Here, we provide a brief review of the recent progress on the study of zoledronic acid and osteoclasts, and hope to elaborate how zoledronic acid improves osteoporosis by acting on osteoclasts.

PHOTODYNAMIC THERAPY AS AN ADJUVANT IN THE TREATMENT OF OSTEONECROSIS OF THE JAW: CASE REPORT

A 75-year-old woman with a history of breast cancer and use of intravenous zoledronic acid arrived at the dental office reporting upper jaw discomfort. On intraoral examination, bilateral bone exposures compatible with osteonecrosis were observed. Initially, the treatment consisted of oral antibiotic therapy (clindamycin 300 g) for 7 days, mouthwash with 0.12% chlorhexidine digluconate every 12 hours for 7 days and necrotic bone curettage. Antimicrobial photodynamic therapy (aPDT) sessions were performed with a Hand Duo Laser device, which has a continuous operation mode, a semiconductor light-emitting laser, a fixed power of 100 mW, and a spot size of 0.03 cm². The red wavelength was used for 90 seconds. 0.01% methylene blue gel was used as a photosensitizing agent. The preirradiation time was set at 5 minutes. The interval between each aPDT session was 48 hours, and after 12 sessions complete regression of the lesion was noted.

Reduction effect of oral pravastatin on the acute phase response to intravenous zoledronic acid: protocol for a real-world prospective, placebo-controlled trial

IntroductionZoledronic acid (ZA) has been used as a first-line treatment in patients with osteoporosis (OP) who receive an annual injection of 5 mg. However, side effects of bone pain and...

Denosumab versus zoledronic acid in cases of surgically unsalvageable giant cell tumor of bone: A randomized clinical trial

BackgroundGiant-cell tumor of bone (GCTB) is a relatively benign, but locally aggressive osteoclastogenic stromal tumour of the bone. Although denosumab has been approved as an monoclonal antibody against RANK ligand for the treatment of GCTB, few clinical trials of the benefit in tumor response have been conducted to prove the efficiency in Chinese population. ObjectivesIn this multicentric, random controlled, clinical trial, 160 patients were enrolled to compare the therapeutic efficacy and safety of denosumab and zoledronic acid treatment in patients with surgically unsalvageable GCTB. MethodsBetween 2nd Jan 2015 and 1st Jan 2018, 160 adults (aged ≥ 18 years) with ①surgically unsalvageable GCTB, ②surgically salvageable GCTB with planned surgery expected to result in severe morbidity were included in this randomized clinical trial. Patients received either subcutaneous denosumab (DB group; 120 mg once every 4 weeks with loading doses of 120 mg subcutaneously admininstered on days 8 and 15; n = 80) or intravenous zoledronic acid (ZA group; 4 mg once every 4 weeks; n = 80) for six cycles. Disease status, clinical benefits, treatment-emergent adverse effects, overall survival, and cost of treatment were evaluated during the follow-up period. Statistical significance was determined using 95% confidence intervals. ResultsDenosumab and zoledronic acid had similar tumor responses (p = 0.118) and clinical benefits (p = 0.574). Disease progression was observed in fewer patients in the DB group (12.5%) than ZA group (15.0%). Denosumab caused fatigue (p = 0.001) and back pain (p < 0.0001), while zoledronic acid caused hypocalcemia (p < 0.0001), flu-like symptoms (p = 0.059) and hypotension (p = 0.059). Denosumab treatment was markedly more expensive than zoledronic acid treatment (p < 0.0001). The cost to manage treatment-emergent adverse effects was the same for the ZA group and the DB group (p = 0.425). The accumulate recurrence-free survival rate at 4-year follow-up is higher in DB group (p = 0.035). ConclusionsDenosumab is a safe but costly alternative to zoledronic acid for treatment of surgically unsalvageable GCTB.

Cost-Effectiveness of Sequential Denosumab/Zoledronic Acid Compared With Zoledronic Acid Monotherapy for Postmenopausal Osteoporotic Women in China.

Objective: The primary purpose of this study was to estimate the cost-effectiveness of sequential denosumab/zoledronic acid versus zoledronic acid monotherapy for postmenopausal osteoporotic women in China. Methods: We updated and utilized a previously validated Markov microsimulation model to obtain the cost-effectiveness of two strategies for treating postmenopausal osteoporotic women. We compared the incremental cost-effectiveness ratios (ICERs) (US dollars [$] per quality-adjusted life year [QALY]) of sequential denosumab/zoledronic acid (i.e., biannual subcutaneous denosumab for 3 years followed by annual intravenous zoledronic acid for 3 years) with zoledronic acid monotherapy for 3 years in Chinese women with postmenopausal osteoporosis at ages 65, 70, 75, and 80 from the health care payer perspective. Our study’s willingness-to-pay (WTP) threshold was set to three times the value of China’s per capita GDP in 2020 ($31,512). Results: The ICERs of sequential denosumab/zoledronic acid versus zoledronic acid monotherapy were $59,389/QALY, $23,821/QALY, $22,710/QALY, and $14,027/QALY at age 65, 70, 75, and 80 years, respectively. One-way sensitivity analyses showed that the most impactful parameter was the persistence rate of the medications. If the persistence rate of denosumab or zoledronic acid was increased by 10%, sequential denosumab/zoledronic acid would be cost-effective at age 65. In probabilistic sensitivity analyses, the probabilities of sequential denosumab/zoledronic being cost-effective compared to zoledronic acid monotherapy were approximately 29.3%, 68.7%, 86.1%, and 99.4% for ages 65, 70, 75, and 80 years, respectively, at the WTP threshold of $31,512/QALY. Conclusion: Among Chinese postmenopausal osteoporosis women over 70 years old, sequential denosumab/zoledronic acid was cost-effective compared with zoledronic acid monotherapy at the pre-determined WTP threshold.

Severe Symptomatic Hypocalcaemia Associated with Zoledronic Acid in a Patient of Ca Prostate: Case Report and Literature Review

Zoledronic acid is a parenteral long acting bisphosphonate that has been used widely in the management of osteoporosis, bone metastasis and malignancy induced hypocalcaemia. Zoledronic acid is well tolerated but rarely severe hypocalcaemia and nephrotoxicity may occur. Here we report a case of 62 year male patient of metastatic Ca prostate who had severe hypocalcaemia after receiving intravenous zoledronic acid and docetaxel. Patient was hospitalized and managed with intravenous calcium supplementation and remained admitted for several days. Post recovery he was again started on zoledronic acid therapy and chemotherapy.

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update.

To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline. An Expert Panel conducted a systematic review to identify new, potentially practice-changing data. Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations. Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline.

Elucidated pathogenesis and therapeutic prospects in Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is characterized by immature dendritic cell proliferation, which is currently classified as an inflammatory myeloid neoplasm. Clinical features and outcomes vary from spontaneously regressing isolated bone disease to fatal liver, spleen, or hematopoietic system (risk organ) involvement-positive multisystem disease. LCH cells have the only mutation in the mitogen-activated protein kinase (MAPK) signaling pathway gene, represented by the BRAF V600E mutation, which is the driver mutation. The type of disease depends on the stage of hematopoietic cell differentiation at which the mutation occurs. LCH cells acquire anti-apoptosis and senescence-associated secretory phenotype by oncogene-induced senescence, with migration failure to lymph nodes. These cause LCH cell accumulation and various inflammatory cell recruitment in the lesion, resulting in severe inflammation. Tissue damage in LCH is due to this inflammation, not the LCH cell proliferation. Patients with a risk of organ involvement without the initial treatment response may be rescued by allogeneic hematopoietic stem cell transplantation after reducing the disease activity with MAPK inhibitors. Intravenous zoledronic acid and intrathecal cytarabine injections have been introduced into the ongoing clinical trial in Japan to reduce bone recurrence and prevent neurodegeneration as sequelae.

Transient osteoporosis of the hip in an old woman: a case report

Transient osteoporosis of the hip is a rare disease. It mainly affects pregnant women during the third trimester and also adult men. We report the case of an elderly patient who presented this rare pathology. A 65-year-old woman, with type 2 diabetes, with no other medical history, developed over the course of two months mechanical pain in the right hip joint with progressive loss of function, she had no fever and no other rheumatologic sign. She didn’t complain of weight loss or asthenia. Laboratory tests revealed the following results: normal erythrocyte sedimentation rate (ESR): 21mm/h, normal CRP 3.2 mg/l, a deficiency in 25-hydroxy-vitamin D: 18 µg/ml (normal > 30µg/ml). Full blood counts, liver function, renal function, parathyroid hormone and bone remodelling tests were within normal limits. Anteroposterior X-rays of the pelvis and hips showed no anomaly. The ultrasounds of hips showed synovial thickening without joint effusion at the right hip. Magnetic resonance imaging (MRI) of the pelvis showed diffuse homogenous low intensity signal on T1-weighted images and high intensity T2-weighted images of the right femoral head and neck which demonstrate a diffuse bone edema of the head and neck of the right femur, there was no sign of osteonecrosis or stress fracture of the subchondral bone. The diagnosis of Transient osteoporosis of the right hip was retained. A conservative treatment was prescribed, we recommended rest to reduce the load on the femoral head. The use of walking aid device was necessary. Physiotherapy was initiated to reduce pain. Tramadol 100 mg per day, intravenous zoledronic acid 5mg, calcium and Vitamin D were prescribed. The patient was improved and pain free by the fourth week of treatment and she could walk without crutches and up to 01 kilometers without pain or discomfort. Transient osteoporosis of the hip is a rare entity to be considered in old women. The diagnosis is based on MRI findings. This pathology need to be distinguished from avascular necrosis of the femur.

Comparison of Local and Intravenous Zoledronic Acid on Histopathology and Recurrence Rate after Extended Curettage in Giant Cell Tumors of Proximal Tibia: A Prospective Study.

Introduction:The bone pathology-giant cell tumor (GCT) is a locally aggressive and recurrent lesion. A bisphosphonate-zoledronic acid (ZA) has been known to lower the recurrence and resorption in similar bone lesions. Hence, we evaluated the effectivity of the ZA for the GCT of the proximal tibia.Materials and Methods:We piloted a prospective clinical observational study. We included 100 subjects with GCT, who were divided into two equal groups of case (given ZA) and control (no ZA). The histopathological features and the recurrence rates along with other findings were compared with P < 0.05 deliberated as significant.Results:We observed that for in the case group, calcification and fibrosis that were beneficial were observed. Reduced giant cells and lower recurrence rate are seen in the case group. No significant variation in the functional outcome was seen between the groups.Conclusions:ZA was shown to have beneficial effect on the outcome for the treatment of the GCT.

Bisphosphonates for Post-COVID Osteonecrosis of the Femoral Head: Medical Management of a Surgical Condition.

This was a retrospective evaluation of 48 patients (88 hips) diagnosed with osteonecrosis of the femoral head at a tertiary care center after COVID-19 infection between September 2020 and May 2021. Patients received intravenous zoledronic acid (5 mg) at the initiation of therapy and oral alendronate (35 mg) twice weekly, and were followed for a minimum of 6 months. Clinical evaluation was conducted using a visual analog scale (VAS) for pain and the Harris hip score (HHS). Radiographic evaluation was performed to assess the progression of the disease and collapse of the femoral head. At a mean follow-up of 10 months, 84 (95.5%) of the hips showed good clinical outcomes, and only 4 (4.5%) of the hips required surgical intervention. The mean VAS pain score and HHS improved at 6 weeks and steadily improved on subsequent follow-ups. In 16 (18%) of the 88 affected hips, radiographic progression was observed. The mean dose of corticosteroids administered to the patients to manage COVID-19 infection was 841.3 mg of prednisolone equivalents. The mean duration between the commencement of corticosteroid therapy and the development of osteonecrosis was 179 days. Post-COVID osteonecrosis appears to be more aggressive, with COVID-19 itself contributing to its etiopathogenesis in addition to corticosteroids. However, it can be diagnosed by magnetic resonance imaging (MRI) in symptomatic patients and then effectively treated medically, especially if detected in the early stages. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Efficacy and Safety of Oral Ibandronate versus Intravenous Zoledronic Acid on Bone Metabolism and Bone Mineral Density in Postmenopausal Japanese Women with Osteoporosis.

There are no published clinical reports comparing ibandronate (IBN) treatment and zoledronic acid (ZOL) treatment in Japanese postmenopausal osteoporotic patients. This investigation therefore compared the efficacy and safety of the drugs on improving bone metabolism and bone mineral density (BMD) in Japanese postmenopausal women with primary osteoporosis. Eighty-two treatment-naïve primary osteoporotic female patients were randomly divided into IBN-treated or ZOL-treated groups. Bone turnover markers and BMD were examined immediately prior to treatment (baseline) and at 6, 12, 18, 24, and 30 months of therapy. Compared with baseline levels, the values of type 1 procollagen N-terminal propeptide, bone-specific alkaline phosphatase (BAP), urinary type-I collagen amino-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b were all significantly decreased at every time point in both groups apart from BAP at 30 months in the ZOL group, urinary NTX at 12 months in the ZOL group and at 24 and 30 months in both groups. Lumbar BMD values were significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6 and 12 months in the ZOL group compared with pre-treatment levels. Hip BMD values were also significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6, 12, and 18 months in the ZOL group compared with baseline values. The percentage changes of hip BMD at 18 and 24 months in the ZOL group were significantly higher than those in the IBN group (both p < 0.05). No remarkable adverse events were noted in either group. In conclusion, both IBN and ZOL significantly and safely improved bone turnover markers and BMD during 30 months of treatment in Japanese osteoporosis patients. The ZOL group tended to exhibit greater gains in BMD as compared with the IBN group, which merits further investigation.

P11 Multiple insufficiency fractures in rheumatoid arthritis

Abstract Case report - Introduction Rheumatoid arthritis (RA) is an autoimmune inflammatory arthropathy with systemic manifestations. It is 4-times more common in females. RA is recognised to induce bone loss and decrease in bone mineral density (BMD). Management may include corticosteroids (CS) for new presentations, acute flares, and more rarely longer-term management, which increases bone fragility. Patients are at 30—50% increased risk of developing osteoporosis with a 30% increase in fracture risk. This risk rises with the level of persistent disease inflammation. We present a case of a lady with longstanding RA, who sustained multiple bone fractures without significant osteoporosis on bone density scanning. Case report - Case description Our patient is a 64-year-old headteacher who took early retirement due to reduced mobility after 20 years of seropositive RA. She had received multiple disease modifying drugs (DMARDs) and biologics therapies, requiring repeated alterations primarily due to treatment failure. She was commenced on alendronic acid due to osteopaenia of the hip but 2 years later sustained a fractured neck of femur and was switched to risedronate. A year later she presented with acutely painful and swollen right foot and ankle without history of trauma. X-rays showed progressive degenerative change whilst inflammatory markers were normal. Ultrasound demonstrated sub-clinical synovitis. Her medication was optimised but the ankle swelling persisted, rendering her wheelchair-reliant. MRI revealed multiple stress fractures involving calcaneum, talus and 5th proximal phalanx. She was treated with 16 weeks of an Aircast boot. An old right upper medial tibial fracture was also identified. Repeat dual energy X-ray absorptiometry (DEXA) scan showed osteopaenia but with improvement from the previous scan (T score of -2.1 total hip and -1.6 lumbar vertebra). She smoked 1 cigarette a day, did not drink alcohol and there was no parental history of fractures. No evidence of malabsorption or endocrine disorder was identified. Unusually, she had received tamoxifen in her late 20s for cancer prevention based on breast fibroadenosis and she experienced early menopause aged 36 years. Inflammatory markers, calcium, parathyroid hormone, and immunoglobulins were normal. Vitamin D3 levels were insufficient at 40.3 nmol/l and replacement was initiated, following which she was switched to intravenous zoledronic acid. After one infusion of zolendronate, she twisted her right ankle and sustained a new malleolar fracture. She was converted to 6-monthly denosumab injections along with calcium and vitamin D, which has been continued. Her RA remains active, and she has recently commenced JAK2 inhibitors. Case report - Discussion Inflammatory arthropathies such as RA predispose to significant morbidity and disability. An earlier age of diagnosis poses a longer inflammatory response in body, with a higher incidence of bone health complications. A treat-to-target strategy in RA aids optimal disease management and reduces fracture risk. Studies have shown the risk of osteoporosis in RA is not just disease dependent but also affected by certain medications. Treatment challenges arise when a patient sustains fracture despite a BMD above osteoporosis risk criteria, leading us to consider other variables. She was further investigated for secondary causes of osteoporosis, including endocrine causes, and was found to be vitamin D insufficient, which was replaced prior to further antiresorptive treatment. Our case also highlights a diagnostic dilemma given that our patient presented with a single swollen joint assumed to be due to active RA. Multiple insufficiency fractures were only identified after MRI was performed. As per EULAR criteria, our patient had difficult to treat RA with a long disease duration. She showed intolerance to a several DMARDs and treatment failure with multiple biologic therapies. She had required local joint injections and repeated short courses of oral steroids. These factors are likely to have played a considerable role in her fracture development. RA is an independent risk factor for fracture in both men and women with disease duration and CS use being important clinical variables. Bisphosphonates are considered vital in fracture risk reduction. The compliance is an important factor for both primary and secondary prevention of fracture. They are associated with decreased bone remodelling and have been well studied for atypical femoral fractures; however, whether there is any link with stress fractures in the feet requires further studies. Long-term use (&amp;gt;5years) hasn’t shown to be beneficial in preventing hip fractures. Case report - Key learning points

Cost-effectiveness of zoledronic acid compared with sequential denosumab/alendronate for older osteoporotic women in Japan

SummaryAmong hypothetical cohorts of older osteoporotic women without prior fragility fracture in Japan, we evaluated the cost-effectiveness of two treatment strategies using a simulation model. Annual intravenous zoledronic acid for 3 years was cost-saving compared with biannual subcutaneous denosumab for 3 years followed by weekly oral alendronate for 3 years.PurposeOsteoporosis constitutes a major medical and health economic burden to society worldwide. Injectable treatments for osteoporosis require less frequent administration than oral treatments and therefore have higher persistence and adherence with treatment, which could explain better efficacy for fracture prevention. Although annual intravenous zoledronic acid and biannual subcutaneous denosumab are available, it remains unclear which treatment strategy represents a better value from a health economic perspective. Accordingly, we examined the cost-effectiveness of zoledronic acid for 3 years compared with sequential denosumab/alendronate (i.e., denosumab for 3 years followed by oral weekly alendronate for 3 years, making the total treatment duration 6 years) among hypothetical cohorts of community-dwelling osteoporotic women without prior fragility fracture in Japan at ages 65, 70, 75, or 80 years.MethodsUsing a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life-year [QALY]) from the public healthcare and long-term care payer’s perspective over a lifetime horizon with a willingness-to-pay of ¥5 million (or $47,500) per QALY.ResultsIn the base case, zoledronic acid was cost-saving (i.e., more effective and less expensive) compared with sequential denosumab/alendronate. In deterministic sensitivity analyses, results were sensitive to changes in the efficacy of zoledronic acid or the cumulative persistence rate with zoledronic acid or denosumab. In probabilistic sensitivity analyses, the probabilities of zoledronic acid being cost-effective were 98–100%.ConclusionsAmong older osteoporotic women without prior fragility fracture in Japan, zoledronic acid was cost-saving compared with sequential denosumab/alendronate.

P53-5 Severe hypercalcemia in renal cell carcinoma: The diverse manifestations of genitourinary malignancies

Hypercalcemia of malignancy is a common paraneoplastic syndrome among patients with renal cell carcinoma (RCC), affecting up to 20% of patients. We report a case of metastatic RCC in a man presenting with severe hypercalcemia. A 76-year-old gentleman presented with 2 weeks of lethargy and dyspnea. He had a 50 pack-year smoking history. Examination revealed diminished breath sounds. Abdomen was soft with mild left flank tenderness. Blood tests revealed severe hypercalcemia (corrected calcium 4.09 mmol/L, range: 2.10-2.60 mmol/L), with a concurrent suppressed parathyroid hormone (PTH) level (0.5 pmol/L, range: 1.3-7.6 pmol/L), consistent with non-PTH mediated hypercalcemia. Chest X-ray showed bilateral pleural effusions with nodular opacities. A CT demonstrated an 8cm mass arising from the superior pole of the left kidney suspicious for a renal cell carcinoma, with innumerable pulmonary nodules, large bilateral pleural effusions, as well as mediastinal, hilar and para-aortic lymphadenopathy. Iatrogenic hypercalcemia and multiple myeloma were excluded. 1,25-dihydroxyvitamin D level was normal. Measurement of parathyroid hormone-related peptide was not feasible. Following treatment with intravenous fluid and zoledronic acid, his calcium level normalized twelve days later. He underwent a therapeutic and diagnostic thoracentesis. His radiological findings and pleural fluid cytology result were in keeping with metastatic renal cell carcinoma. He was commenced on pazopanib. He required bilateral long-term indwelling pleural catheter insertion for recurrent bilateral pleural effusions. He was discharged home after 4 weeks of hospitalization but was readmitted to hospital 6 weeks later with worsening dyspnea. CT showed progression of pulmonary metastases. He died 12 weeks after his initial presentation. RCC has protean manifestations and hypercalcemia is the most common paraneoplastic complication of RCC.