Use Of Intravenous Bisphosphonates Research Articles

Impact of Osteoporosis on Autogenous Bone Graft Resorption

BackgroundOsteoporosis is a common disorder that is characterized by decreased bone density and increased bone resorption. This bone resorption may affect the grafted bone during the maxillofacial reconstruction. PurposeThis study aimed to measure the association between osteoporosis and resorption of anterior iliac crest bone grafts (AICBGs) used to reconstruct the atrophic anterior maxillae. Study design, setting, and sampleThis prospective cohort study included female patients requiring bone augmentation of the anterior maxilla. Patients with a ridge width of < 4 mm and ridge height of > 7 mm were enrolled in the study. Exclusion criteria were chronic use of corticosteroids or intravenous bisphosphonates, history of maxillofacial radiation therapy, current smoking, and underlying conditions contributing to bone metabolism (e.g., hyperparathyroidism, chronic renal failure, and hypophosphatemia). Predictor/exposure/independent variableOsteoporosis status was a predictor variable. Patients were allocated to the osteoporosis or control group based on T-scores obtained by dual-energy X-ray absorptiometry (DEXA). Mean T-scores ≤ -2.5 were assigned to the osteoporosis group. Main outcome variable(s)The outcome variable was graft resorption, defined as the difference in ridge width between measurements made immediately (T1) and six months postoperatively (T2) using cone-beam computed tomography (CBCT). CovariatesPatient age, pre-operative (T0) bone width, and the amount of bone augmentation, defined as the differences in ridge width between measurements made preoperatively (T0) and immediately after grafting (T1), were covariates of this study. ResultsThirty-two patients were included in the study (15 in the osteoporosis group and 17 in the control group). The amount of graft resorption at six-months after grafting was 2.57 ±0.59 mm in the osteoporosis group and 0.97±0.59 mm in the control group (p<0.001). A significant correlation was found between the mean T-score and graft resorption six months after grafting (p<0.001). ConclusionA significant correlation was observed between osteoporosis and graft resorption in the anterior maxilla after six months.

Investigation of the effect of oral and internal bisphosphonate use on bone density in the jaws in patients with osteoporosis in panoramic radiography

This study aims to quantitatively evaluate the effects of bisphosphonate use duration and route of administration on mandibular cortical and trabecular bone in postmenopausal women. Ninety postmenopausal women over the age of 50 were included in this study. Trabecular bone density was specified numerically by fractal dimension (FD) in the region of interest selected on the panoramic radiograph. The width of the mandibular cortical (MCW) bone under the mental foramen of the mandible was measured. Mann-Whitney U test was used for parameters that did not show a normal distribution. Spearman rho correlation test was used to determine the relationship between continuous measurement parameters. It was observed that FD and MCW of dentate and edentate individuals using bisphosphonate were statistically significantly lower than those of healthy individuals (P < .05). There was no significant correlation was found between the duration of use of bisphosphonates and the fractal values obtained from the relevant regions of the mandible (P > .05). Fractal dimension was found to be lower in oral bisphosphonate use than in intravenous bisphosphonate use. The width of the mandibular cortical bone values was found to be lower in individuals using bisphosphonate than in healthy individuals. Fractal dimension and MCW may benefit clinicians as quantitative parameters in panoramic radiography in the diagnosis of osteoporosis.

A different indication of pisphosphonates: Bone marrow edema

Abstract Introduction Bone marrow edema (BME) is an uncommonly diagnosed, reversible condition most often affecting the hip of middle-aged men. BME is characterized clinically by the onset of disabling bone pain, usually at a single skeletal site, generally in the lower limbs and most often the hip. Diagnosis is often delayed. The increased bone turnover and low bone mineral density may indicate a potential role for bisphosphonate therapy in BME. There is some evidence of the successful use of intravenous bisphosphonates in the treatment of BME of the hip. We aimed to present two cases of BME that were successfully treated with bisphosphonates. Clinical Case 1: A 41-year-old male patient presented with left inguinal pain. His past medical history was unremarkable. The visual analog scale (VAS) was 8–9. On physical examination, there was a limited range of motion (ROM) on the left hip. Laboratory results were within normal limits. Non-contrast MRI revealed signal intensity changes consistent with BME in the left femoral head and neck of the femur, which was hypointense in T1W sections and hyperintense in T2W sections. With assisted mobilization, 3 mg IV ibandronic acid, calcium and vitamin D replacement was started. Pain control was achieved one week after bisphosphonate infusion. Complete resolution of bone marrow edema was seen in the MRI taken 2 months later (Figure 1). Bisphosphonate treatment with alendronate was completed for one year. Clinical Case 2: A 59-year-old male patient presented with right hip pain that limits his walking. He was diagnosed with BME and avascular necrosis as a result of clinical and radiological evaluation in the center he applied and he underwent a right femoral core decompression operation. He was evaluated in our clinic due to ongoing pain and limitation of movement 5 months after the operation. On physical examination, there was limited ROM on right hip. All the results of laboratory tests were normal. MRI revealed signal changes consistent with bone marrow edema in the right femoral head and neck of the femur, which was hypointense in T1W sections and hyperintense in T2W sections. With assisted mobilization, 3 mg IV ibandronic acid, calcium and vitamin D replacement was started. Pain control was achieved 10 days after bisphosphonate infusion, and he returned to working life 1 month later. Complete resolution of the BME was observed in MRI performed 10 weeks later. Completion of the bisphosphonate treatment with alendronate for 1 year was planned. Conclusion The hip is the most frequently involved joint, with diffuse BME pattern in the femoral head and intertrochanteric region observed on MRI. BME may be a precursor to avascular necrosis when the diagnosis is delayed or the treatment is not well managed. Therefore, optimal timing of medical intervention is very important. Treatment with bisphosphonates is an effective and safe treatment. Additionally, providing early mobilization may prevent the risk of avascular necrosis and the workforce loss.

ODP107 Oral Ulcerations, A Rare Side Effect of Intravenous Zoledronic Acid

Abstract Introduction Zoledronic acid is an intravenous bisphosphonate known for its anti-resorptive effects and osteoporotic fracture risk reduction. A common adverse reaction with this medication is mild to moderate flu-like symptoms, which are transient and attributed to an acute phase reaction post treatment. A less common side effect, of oral ulcers is associated with oral bisphosphonates, attributed to incorrect oral intake but the real mechanism is still not well understood. We present a patient that developed oral ulcers after use of both oral and intravenous bisphosphonates, leading to suspicion of other underlying mechanisms other than incorrect oral intake of bisphosphonates. Case Report We present a 73 year old male with history of mild primary hyperparathyroidism and osteoporosis. Patient opted for medical management of his mild primary hyperparathyroidism in addition to having non-localizing studies. Treatment for osteoporosis was recommended due to femoral neck T score -2.4, FRAX score of 3.3% risk for hip fractures and history of low impact right foot fracture. The primary care team started treatment with alendronate 70 mg once a week, but patient developed oral blisters within a week of starting the treatment. Stopping alendronate led to resolution of the oral symptoms without any additional supportive treatment. Patient was later started on intravenous zoledronic acid, attributing the previous history of oral ulcers to a local effect of the oral bisphosphonates. Two days after the zoledronic acid infusion patient developed fatigue, fever, and oral ulcers. The oral ulcers were described as painful, located at the base and lateral aspects of the tongue. The ulcers later progressed to the buccal mucosa. No gingival ulcers were reported. Development of the oral blisters led to significant discomfort in eating and talking. Patient was treated with liquid nystatin 10,000 units/mL and lidocaine 2% viscous liquid. Patient had resolution of the painful ulcers approximately 2 weeks after the initial appearance. No recurrence of the oral ulcers has been reported, 4 months post treatment with zoledronic acid. Discussion Intuitively oral bisphosphonate induced mucosal injury is thought to be related to direct contact of the tablet with the oral mucosa or inappropriate ingestion of the medication and is not thought to be a systemic reaction. Our patient developed oral ulcers from both oral and intravenous bisphosphonates suggesting a possible systemic mechanism involved. Understanding potential side effects such as mucosal injury from intravenous bisphosphonates will be helpful for patient education and timely care. Presentation: No date and time listed

Anti-osteoporotic medication and scleroderma

Scleroderma (systemic sclerosis) represents a challenging condition, usually requiring a multi-disciplinary team due to multi-organ involvement; it is mostly considered an autoimmune disease; the signature of the malady is the extensive fibrosis at the level of skin and multiple organs, associating endothelial/vessel damage and anomalies of immune response. We point out a few aspects concerning scleroderma-related osteoporosis. This is a literature review. Patients might associate low bone mineral density (the underling mechanisms are not entirely understood), thus an increased risk of fractures; so early recognition and treatment is mandatory for a better outcome. Some data showed that particularly vertebral fractures are prone to the condition. Almost half of individuals with the malady have osteoporosis (female prevalence, especially post-menopausal) and one third of them have an osteoporotic fracture. Older age and associated vitamin D deficiency increases the risk of fracture. Vitamin D has pleomorphic distribution, also targeting the immune modulation, cytokines puzzle, and the muscle-bone crosstalk in scleroderma. Hypovitaminosis D might be expected in these patients, while general D-supplementation has controversial benefits effects. Chronic inflammatory rheumatic conditions might benefit from the TBS use as fracture risk indicator through micro-architecture evaluation. It seems that patients with systemic sclerosis and malnutrition have lower TBS; high Dkk-1 serum levels (Dickkopf-1) is correlated with reduced TBS and advanced disease; TBS is correlated to the extent of microvascular complications; exposure to glucocorticoids (certain high-dose regimes) supplementary lowers TBS. Gastrointestinal complications are presented in 90% of patients with systemic sclerosis, involving fibrosis at any level which is a poor prognostic factor; malabsorption of nutrients and weight loss correlates with reduced bone formation while esophageal and gastric anomalies contraindicate the use of oral bisphosphonates for osteoporosis. Other abnormal elements of skeleton frame include: premature ovarian failure, serotonin system anomalies, chronic inflammation, potential side effects of immunosuppressant drugs. In patients with systemic sclerosis, the choices of medication targeting osteoporosis are limited; the use of intravenous bisphosphonates remains first line option (if renal function is adequate); the consideration of skin and esophageal anomalies is mandatory in the management of osteoporosis. Overall, the landscape of bone domain in systemic sclerosis is multi-leveled and some areas are still waiting for clear answers.

Diffuse sclerosing osteomyelitis of the mandible: A case‐report following the treatment over a 12‐year period

AbstractDiffuse sclerosing osteomyelitis (DSO) is a rare inflammatory disease of the bone with a poorly understood aetiology. We present a case of a 26‐year‐old female with DSO, who has been living with this condition for over 12 years. Many different therapies have been used to attempt to manage her symptoms. She is currently taking oral alendronic acid when she is symptomatic. This case report demonstrates the complexity of managing cases of DSO, as we focus on the multiple treatment modalities used in this case and the response to these. Many cases in literature discuss the use of intravenous bisphosphonates, however, this is linked with a higher risk of medically related osteonecrosis of the jaw. In addition to other reported case studies and research, this case provides further evidence to support the use of oral bisphosphonates in the management of DSO.

Use of bisphosphonates in a retrospective case series of children and adolescents with complex regional pain syndrome.

There is increasing evidence for the use of bisphosphonates to treat Complex Regional Pain Syndrome in adults. However, there are scarce data for their use in children with Complex Regional Pain Syndrome. This retrospective case series aimed to analyze the effects of intravenous bisphosphonate use in children and adolescents with Complex Regional Pain Syndrome enrolled in a multidimensional pain treatment program. We analyzed the data of 16 patients (15 females and 1 male, mean age 14±3years) who received infusions of zoledronic acid (0.015±0.0044mg/kg), pamidronate (0.72±0.17mg/kg), or both depending on their initial response between October 2014 and December 2019. The primary endpoint of the study was the patient's global impression of change. Secondary outcomes included pain intensity, physical function, role function (school attendance), need for pain medications, and adverse effects. Nine of 16 patients reported meaningful improvements (global impressions of change of 84% or higher) at a median follow-up time of 16 (8-21) months after their last infusion of bisphosphonates. There were also meaningful reductions in pain intensity and the need for pain medications. There was an increase in the proportion of patients with minimal or without physical disability, and almost all patients normalized their school activities. Thirteen patients (81%) reported adverse effects, mostly flu-like symptoms, for a few days after the infusion. The use of bisphosphonate infusions may represent an effective treatment option for children with Complex Regional Pain Syndrome, not responding to multidisciplinary pain treatment programs.

Racial Disparities in Intravenous Bisphosphonate Use Among Older Patients With Multiple Myeloma Enrolled in Medicare.

Intravenous (IV) bisphosphonates reduce the risk of skeletal-related events in patients with multiple myeloma (MM). However, data describing racial differences in IV bisphosphonate utilization outside of clinical trial settings are limited. We evaluated population-level IV bisphosphonate initiation and discontinuation among patients of age ≥ 65 years with MM. We conducted a retrospective cohort study of patients of age ≥ 65 years diagnosed with first primary MM between 2001 and 2011. Patients were identified using the SEER-Medicare linked database and followed through December 2013. Cumulative incidences of IV bisphosphonate initiation and time to discontinuation among users were compared between racial and ethnic groups. In Fine and Gray competing risk models, we estimated subdistribution hazard ratios (SHRs) and 95% CIs for initiation and discontinuation. We included 14,231 eligible patients with MM (median age, 76 years; 52% male). Over a median follow-up of 23.1 months, 54% of patients received at least one IV bisphosphonate dose. Our final analytical sample included 10,456 non-Hispanic (NH) Whites, 2,267 NH Blacks, 548 Asian and Pacific islanders, and 815 Hispanic and Latino patients. A higher proportion of White patients (56.1%) newly received IV bisphosphonates after MM diagnosis compared with NH Blacks (45.4%). Compared with White patients, NH Black patients were less likely to initiate IV bisphosphonates (SHR, 0.74; 95% CI, 0.70 to 0.79) and slightly more likely to discontinue treatment (SHR, 1.10; 95% CI, 1.01 to 1.19). Approximately half of the patients with MM of age ≥ 65 years did not receive IV bisphosphonates, with significant delay among racial minority groups. These findings highlight the need for improvement of IV bisphosphonate uptake in patients with MM of age ≥ 65 years.

Atrial fibrillation in patients treated with intravenous zoledronic or pamidronic acid: a pharmacoepidemiological study

Atrial fibrillation (AF) may be triggered by intravenous bisphosphonates (IVBPs) such as zoledronic acid or pamidronic acid. Our objective was to confirm the association between AF and IVBPs in a real-life large pharmacovigilance database. A systematic analysis of VigiBase, the World Health Organization's pharmacovigilance database. Analysis of adverse events reported as 'atrial fibrillation' (according to the Medical Dictionary for Drug Regulatory Activities) associated with the use of zoledronic acid or pamidronic acid, in VigiBase, the World Health Organization's global Individual Case Safety Report (ICSR) database. All ICSRs reporting AF associated with zoledronic acid or pamidronic acid were included in a disproportionality analysis determining the lower end of the 95% credibility interval for the information component (IC025), showing a statistical association when >0. 530 ICSRs reporting on the association between AF and IVBPs were extracted. Bayesian disproportionality analysis detected a significant association between AF and use of zoledronic acid (IC025 = 1.83) and pamidronic acid (IC025 = 2.16). Further analysis of these ICSRs determined that AF was severe in 85.0% of cases and with a mortality of 17.7%. The risk of severe AF was increased (OR: 2.98 (95% CI: 1.17-7.57), P = 0.02) following zoledronic acid vs pamidronic acid, after adjustment for age and gender. This is the first VigiBase pharmacoepidemiological study confirming the association between IVBPs and AF. Most AF were severe, with a high frequency of lethal outcome. The risk of severe AF was increased following zoledronic acid use compared to pamidronic acid, advocating for a cautious use of IVBPs.

Comparison of Denosumab Versus Intravenous (IV) Bisphosphonate Use for Hypercalcemia in Multiple Myeloma

Background Hypercalcemia (HC) is a frequent complication of multiple myeloma (MM) occurring in 20-30% of patients. This is often associated with renal dysfunction and both features are important myeloma defining events resulting in significant morbidity and mortality. Denosumab, a fully human monoclonal antibody that inhibits RANKL, has been evaluated in the prevention of skeletal related events in patients with newly diagnosed MM, as well as the treatment of bisphosphonate-refractory HC of malignancy (HCM). Cases of denosumab for HCM in MM patients with renal dysfunction have been described. Both denosumab and IV bisphosphonates (IVB) represent treatment options for HC in MM. We describe a comparison of patients with MM with HC who received denosumab vs IVBs. Methods We retrospectively identified patients age ≥18 with a diagnosis of MM with HC (corrected serum calcium level [CSC] &amp;gt;10.5 mg/dL). Patients were included if they received either denosumab or IVB (zoledronic acid [ZA] or pamidronate), between April 2016 and June 2020. The primary endpoint was complete response (CR), defined as normalization of CSC to less than 10.5 mg/dL. Secondary endpoints included HC relapse (CSC &amp;gt;10.5 mg/dL) and safety. Hypocalcemia was graded per CTCAE v5. Acute kidney injury (AKI) was defined using KGIDO criteria. Patients were followed-up for 56 days. Bivariate analyses were performed. Results A total of 40 patients were included with 18 in the denosumab group and 22 in the IVB group, of whom 15 (68%) received ZA and 7 (32%) received pamidronate. Baseline characteristics are described in Table 1. Patients with newly diagnosed MM composed 33% and 55% of the denosumab and IVB groups, respectively. All patients in the denosumab group received 120 mg except one who received 60 mg, while in the IVB group, dose reductions occurred in 5/15 patients who received ZA (median dose, 4 mg; range, 3.3-4) and 4/7 patients who received pamidronate (median dose, 60 mg; range, 30-90). Most patients received HC treatment as an inpatient (58% inpatient vs. 42% outpatient). A minority of patients had received IVBs in the past 90 days. The mean CSC was 12.5 mg/dL (standard deviation [SD], 1.40) and 13.3 mg/dL (SD, 2.39) in the denosumab and IVB groups, respectively. Baseline serum creatinine (SCr) was higher and creatinine clearance (CrCl) was lower in the denosumab group (median SCr, 2.06 vs. 1.24 mg/dL, p=0.048; median CrCl, 33 vs. 48 mL/min, p=0.048). The CR rate by day 3-4 was 92% and 94% in the denosumab and IVB groups, respectively (p=NS). HC relapse occurred in 2 (12%) and 6 (29%) patients in the denosumab and IVB groups, respectively (p=0.257). Incidence of grade 1 hypocalcemia was similar between groups; however, incidence of grade ≥2 hypocalcemia was higher in the denosumab group. Incidence of new AKI was 28% (5/18) in the denosumab group 23% (5/22) in the IVB group (p=0.71). No patients in the denosumab group received an additional dose of denosumab within 14 days of initial dose. Three patients in the IVB group received an additional dose of an IVB within 14 days of initial dose. One patient, who was in the denosumab group, had refractory hypercalcemia and had not achieved CR at day 56. Conclusions We describe our experience with denosumab and IVB for the management of HC in patients with MM. The CR rate at 3-4 days was similar with either agent in our MM only population that was not bisphosphonate refractory. A higher incidence of grade 2 hypocalcemia was noted in the denosumab group. Conclusions on renal safety are limited by the small sample size and that patients in the denosumab group had a higher SCr on presentation. Denosumab and IVB represent acceptable agents for the management of HC in MM patients with further investigation necessary in those with renal dysfunction. Disclosures Lei: Fresenius Kabi USA: Consultancy; Trapelo Health: Consultancy; Bluebird Bio: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current equity holder in publicly-traded company; Clovis Oncology: Current equity holder in publicly-traded company; Blueprint Medicines: Divested equity in a private or publicly-traded company in the past 24 months. Lou:Fresenius Kabi USA: Consultancy. Raje:Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Astrazeneca: Consultancy. Yee:Karyopharm: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Denosumab is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. We describe the use of denosumab for hypercalcemia of malignancy in a multiple myeloma only patient population that is not bisphosphonate refractory. The use of denosumab for these patients was part of normal clinical practice in adherence to institutional policies and guidelines.

Hypocalcemia following Neridronate Administration in Pediatric Patients with Osteogenesis Imperfecta: A Prospective Observational Study.

The use of intravenous bisphosphonates has been linked to hypocalcemia both in children and adults with osteogenesis imperfecta (OI). The aims of this study were: (1) to investigate the incidence of hypocalcemia in the first 48 hours (T48) after neridronate infusion in a pediatric population with OI and (2) to assess any correlation between the baseline values of calcium, vitamin D (25-hydroxyvitamin D) and bone turnover markers, and the postinfusion calcium values. We conducted a prospective observational study on 37 pediatric patients. All patients were treated with a single infusion of neridronate at a dose of 1 to 2 mg/kg. The study provided two postinfusion reassessments: 24 hours (T24) and T48 after neridronate administration. Hypocalcemia was observed in 11% of patients at T24 and in 50% of patients at T48 from neridronate infusion. We observed a positive linear correlation between the baseline vitamin D values and postinfusion calcium values, both at baseline and at T24 and T48. Hypocalcemia was mild and asymptomatic in all cases. Postinfusion calcium levels were related to baseline vitamin D levels. Consequently, low vitamin D levels should be considered a significant risk factor for hypocalcemia and should be carefully investigated and treated before neridronate infusion.

SAT-524 Re-hospitalization And Mortality Outcome Following Atypical Femur Fracture

INTRODUCTION: Older women with proximal femur (hip) fractures have high morbidity and mortality; over 10% are re-hospitalized within 30 days of discharge and the overall mortality at 1 year is 20-25%. Outcomes differ for women with atypical femur fractures (AFF), although published findings have shown conflicting results. One study found a greater risk of death in patients with AFF (median survival 9 months) compared to non-AFF diaphyseal femur fractures, although AFF cases also had greater comorbidity burden (JCD 19:359-67, 2016). A second study found that mortality was much lower for patients with AFF compared to non-AFF diaphyseal fractures, with no deaths in the first year following fracture (JBMR 31:491-497, 2015). This study further examines morbidity and mortality in women who experienced an AFF, focusing on rehospitalization and all-cause mortality outcome in comparison to proximal femur fractures. METHODS: This retrospective cohort study used post-fracture outcome data from 112 women (age 67.1 ± 8.4, 63% Asian, 26% white, 11% all others) who experienced an AFF after initiating oral bisphosphonate therapy in 2002-2014. Exclusion criteria included use of intravenous bisphosphonates, teriparatide, denosumab, skeletal disorders, or advanced chronic kidney disease. Women were followed up to 1 year after the initial AFF event to determine rehospitalization outcome within 30 and 90 days of discharge. Mortality was examined at 6 months and 1 year after AFF, and results were compared to published findings for typical femur fractures occurring in the same healthcare setting. RESULTS: Among 112 women who had an AFF during 2002-2015, 38% were age 65-74 years and 22% age 75-84 years; none were age 85 and older. This contrasts with previous findings in older women with hip fracture where more than one-third were age 85 and older, the age subgroup with highest mortality (over 30%). Six women with AFF were re-hospitalized within 30 days (5.4%) and 10 within 90 days (8.9%), with principal indications for rehospitalization within 30 days relating to infection (3/6) and cardiac arrhythmia (2/6). Six-month and one-year mortality were extremely low at 0.9% overall, and by age group: 2% among age <65 years, 0% among women age 65-74 years and 0% among women age 75-84 years. These results contrast with much higher one-year mortality previously reported for women age 65-74 years (14%) and 75-84 years (18%) who experienced a proximal femur fracture within the same health plan setting. DISCUSSION: Women with AFF appear to have substantially different survival outcomes compared to women with typical femur (hip) fracture, consistent with findings reported in other studies. Whether these differences are primarily related to health status and physical function, or the relationship of chronic disease and (typical) fracture risk, should be further examined.

Current status of bone cementing and bone grafting for giant cell tumour of bone: a systemic review

Extended intralesional curettage, together with bone grafting/cementing, is considered as a surgical treatment option for giant cell tumour of the bone. This study aimed to discover the efficacy and recurrence rate with the use of bone cement in giant cell tumour and to compare it with that of bone grafting. The present systemic review is derived from the publications in the past 10 years (2009-2018). A literature search was performed via PubMed, using suitable keywords and Boolean operators database ('Giant cell tumor,' 'osteoclastoma,' 'bone,' 'bone cement,' 'bone graft' and 'curettage'). A detailed statistical analysis of the data derived from the published literature was done. The patients who underwent bone graft only exhibited significantly higher recurrence rates than those treated with polymethyl methacrylate only (risk ratio 1.90; 95% confidence interval 1.14, 3.16; overall effect Z = 2.488; P-value 0.012). The observational analysis was done in rest of the seven studies; three studies showed no recurrence rate. Only one study reported the highest recurrence rate of 42% and the remaining six had an overall recurrence rate of 20.4%. The use of bone cement was associated with a statistically significantly lower recurrence rate than bone grafting in giant cell tumour of bones. We therefore recommend the use of bone cement with extensive intralesional curettage. Adjuvant therapy like electrocautery, phenol irrigation and the use of intravenous denosumab or bisphosphonates may help in decreasing the incidence of recurrence in giant cell tumour of bone.

Renal Response in Carfilzomib (K)- Versus Bortezomib (V)-Treated Patients (Pts) with Relapsed or Refractory Multiple Myeloma (RRMM) in the Real-World Practice Setting

Introduction: Renal impairment (RI) is a classic clinicopathological feature of MM, is associated with poor prognosis and shorter survival (Eleutherakis-Papaiakovou Leuk Lymphoma 2007), and can complicate drug dosing and limit treatment options. In clinical trials, the proteasome inhibitors K and V have demonstrated efficacy in RRMM pts with RI, with superior efficacy observed in K-treated pts (Dimopoulos Blood 2017). K and V have also been observed to improve renal function in RRMM pts (Dimopoulos Clin Lymphoma Myeloma 2009; Dimopoulos Blood Advances 2017). However, few studies have investigated the real-world effectiveness of K- and V-based regimens in renal rescue. This study aimed to describe and compare renal response rates in RRMM pts treated with K + dexamethasone (Kd) and V + dexamethasone (Vd) in oncology clinics. Methods: The Oncology Services Comprehensive Electronic Records (OSCER) database (Lau Clin Epidemiol 2011) contains electronic medical records (EMR) from community- and hospital-affiliated oncology clinics in the United States. MM pts aged ≥18 who entered an OSCER clinic Jan 2012‒Feb 2018; initiated Kd or Vd treatment as line 2 (2L), 3L, or 4L; and had baseline renal impairment (Modification of Diet in Renal Disease Study estimated glomerular filtration rate [eGFR] Results: 543 Kd-treated and 1005 Vd-treated pts were included. Baseline characteristics were similar between cohorts, with no difference in baseline eGFR stages. More Kd pts were Conclusions: Using one of the most complete oncology EMR databases available, we found that RRMM pts with baseline RI treated with Kd had higher rates of overall and complete renal response, and were more likely to have a renal response, compared with pts treated with Vd. A limitation of the study is that we could not account for all concomitant medications or comorbidities that affect renal function, as some may not be captured in OSCER. Disclosures Kumar:AbbVie: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity9s Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity9s Board of Directors or advisory committees, Research Funding. Fu:Amgen: Employment, Equity Ownership. Mezzi:Amgen: Employment, Equity Ownership. Braunlin:Amgen: Employment. Kim:Amgen: Employment, Equity Ownership. Iskander:Amgen: Employment, Equity Ownership. Niesvizky:Amgen Inc.: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding. Jagannath:Celgene: Consultancy; Novartis: Consultancy; Merck: Consultancy; Medicom: Speakers Bureau; Multiple Myeloma Research Foundation: Speakers Bureau; Bristol-Myers Squibb: Consultancy. Boccia:Sandoz: Consultancy; Celgene: Speakers Bureau; Abbvie: Speakers Bureau; Genentech: Research Funding, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; BMS: Research Funding; Pfizer: Consultancy; AstraZeneca: Research Funding, Speakers Bureau. Raje:Celgene: Consultancy; Janssen: Consultancy; Merck: Consultancy; Takeda: Consultancy; AstraZeneca: Research Funding; Research to Practice: Honoraria; Medscape: Honoraria; BMS: Consultancy; Amgen Inc.: Consultancy.

Prevalence and Predictors of Renal Impairment Among Patients with Multiple Myeloma (MM): An Analysis of Oncology Clinic Electronic Health Records Linked to Commercial Claims in the United States

BackgroundAlthough incurable, MM is responsive to treatment, and the prognosis of MM patients has improved dramatically over the past two decades. This has led to increased recognition of the importance of effective long-term management of the classic clinicopathological features of MM. Renal impairment (RI) is a defining hallmark of active myeloma. While it is known that RI is associated with poor survival and can complicate drug dosing and limit treatment options, patterns of renal function and risk factors of RI in MM are poorly characterized. This study seeks to characterize the natural history and risk factors of RI in MM using a unique real-world dataset that links patient-level electronic health records (EHR) to healthcare insurance claims.MethodsThe Oncology Services Comprehensive Electronic Records (OSCER) database contains EHR data from community and hospital-affiliated oncology clinics in the U.S. The MarketScan (MS) database contains healthcare claims information from large employers, managed care organizations, Medicare, and Medicaid programs. This study used a subset of MM patients with overlapping data from OSCER and MS, allowing the analysis of EHR-based serum creatinine and claims-based comorbidity data in the same patient.Patients ≥ 18 with a MM diagnosis between 2011 and February 28, 2016 in an OSCER clinic; had at least 6 months of continuous MS benefits coverage; no MM diagnosis in MS in the 3 months prior to OSCER MM diagnosis; and no evidence of another malignancy prior to MM diagnosis were included in the study. Index date was the date of OSCER MM diagnosis and patients were followed up until February 28, 2017. Baseline (BL) patient characteristics and potential risk factors of RI, including demographics, BMI, ECOG, ISS stage, and comorbidities (e.g., hypertension, diabetes, hypercalcemia, etc.) were assessed in the 6 months prior to index. Intravenous bisphosphonate (IV BP) use was assessed during follow-up. Renal function was assessed using the MDRD eGFR method or CKD stage diagnosis codes, with RI defined in this study as eGFR < 60 or stage 3+ CKD. BL eGFR was assessed using the serum creatinine measurement closest to the index in the interval 1 month before and 1 month after index.The prevalence of RI in the year following diagnosis was calculated based on the average number of at-risk patients during this period. Change in renal function for up to 4 years post-diagnosis was assessed by BL renal function and was characterized based on the worst recorded estimate of renal function during this period. A multivariate Cox model was used to assess the impact of BL risk factors and IV BP use during follow-up on progression to RI in patients without RI at BL (eGFR ≥ 60 and CKD diagnosis). Follow-up IV BP use (dose count) was treated as a time-dependent variable.ResultsThe median number of eGFR values recorded per patient during follow-up was 18 (range: 7-36). Among newly diagnosed MM patients (n = 625), 69% (95% CI: 65-73%) experienced ≥ 1 episodes of eGFR < 60 ml/min or stage 3+ CKD diagnosis (RI) within 1 year of diagnosis, with 16% (13-20%) experiencing an episode of eGFR 15-29 or stage 4 CKD and 15% (11-18%) experiencing an episode of eGFR < 15 or stage 5 CKD.Among patients without RI at diagnosis (n = 281), 37% (31-43%) subsequently experienced at least one episode of RI during follow-up (Figure 1). In addition, 26% (20-32%) of patients with BL eGFR 30-59 or stage 3 CKD experienced progression to an episode of eGFR < 30 or stage 4+ CKD, and 31% (20-42%) of patients with BL eGFR 15-29 or stage 4 CKD progressed to an episode of eGFR < 15 or stage 5 CKD.In our multivariate Cox model, use of the IV BP zoledronic acid (ZA) during follow-up; ECOG; baseline eGFR; known predisposing conditions, including autoimmune diseases, vascular conditions, and infections of the kidney were found to be associated with higher risk for experiencing an episode of RI in patients with high BL renal function (Figure 2). In our sample, 12 doses of ZA was associated with a 2.4-fold (1.2-4.8) increase in risk of RI. A baseline ECOG of 1 vs. 0 was also associated with a 2.4-fold (1.1-5.2) increase in risk of RI.ConclusionsUsing a unique EHR-insurance claims linked data source, we found that two-thirds of patients experienced at least one episode of renal impairment within the first year of MM diagnosis. Repeated exposure to zoledronic acid and poor performance status may increase the risk of RI in patients without renal impairment at diagnosis. DisclosuresBlock:Amgen, Inc.: Consultancy. Fu:Amgen: Employment, Equity Ownership. Wade:Wade Outcomes Research and Consulting: Employment, Equity Ownership. Jaramillo:Amgen, Inc.: Consultancy; SimulStat: Employment. Bhatta:Amgen, Inc.: Employment, Equity Ownership. Raskin:Amgen, Inc.: Employment, Equity Ownership. Hernandez:Amgen, Inc.: Employment, Equity Ownership.

1022P - Population-based use of intravenous bisphosphonates in patients newly diagnosed with symptomatic multiple myeloma in Denmark in 2005-2015: Impact of patient characteristics

1022P - Population-based use of intravenous bisphosphonates in patients newly diagnosed with symptomatic multiple myeloma in Denmark in 2005-2015: Impact of patient characteristics

Osteonecrosis of the jaws in a patient with multiple myeloma - a case report

Objetivo: este artigo relata um caso de osteonecrose dos maxilares associada ao uso de bisfosfonatos intravenosos (BRONJ) após a extração da maxila primeiro e segundo molares direito. Relato de caso: Paciente do sexo masculino, 53 anos, com diagnóstico de mieloma múltiplo em tratamento no Instituto Arthur Siqueira Cavalcanti (HEMORIO), com bisfosfonato endovenoso (ácido zoledrônico), realizou extrações dentárias em clínica privada. Aproximadamente um mês depois, ele se queixou de dor no local da extração dentária e foi encaminhado pelo oncologista para o serviço odontológico do hospital. O exame clínico intraoral revelou extensa área com características de necrose óssea e a radiografia panorâmica revelou área radiolúcida sugestiva de sequestro ósseo. A combinação de achados clínicos e radiográficos confirmou o diagnóstico de osteonecrose dos maxilares relacionada aos bisfosfonatos (BRONJ). Conclusão: os pacientes em uso regular e contínuo de bisfosfonatos devem ser alertados sobre o possível desenvolvimento de BRONJ após procedimentos odontológicos invasivos e devem ser fornecidas orientações adequadas.

Impact of skeletal-related events on multiple myeloma treatment.

e20009 Background: Skeletal-related events (SREs), sequelae of bone lesions, are common and devastating complications in patients with multiple myeloma (MM).This study assessed the impact of SREs on progress to Next line of anti-MM Therapy (NT), a proxy for disease progression. Methods: In this retrospective cohort study, adults with ≥1 inpatient or ≥2 outpatient MM diagnoses claims between 01/01/2010 and 03/31/2016 were identified from the Truven Health MarketScan Commercial and Medicare databases. The index date was the first anti-MM treatment date post-MM diagnosis. All patients had ≥6-months of continuous enrollment pre- and post-index. SREs were identified during 6 month pre-index period and during first anti-MM treatment post-index. The impact of SREs on progress to NT was assessed, using Cox proportional hazard regression analysis, with occurrence of post-index SREs and renal impairment as time-varying covariates. Results: A total of 5,580 patients met the study criteria, 1,362 (24.4%) of them had SREs pre-index. A total of 1,175 (21.1%) patients experienced SREs during first anti-MM treatment post-index [mean age: 64.3 (±11.8) years, mean Charlson Comorbidity Index score: 3.9 (±2.6), opioid use: 80.4%]. Occurrence of post-index SREs was significantly associated with NT [Hazard ratio (HR): 1.25 {95% confidence interval (CI): 1.13-1.37}] (Table 1). Conclusions: Occurrence of post-index SREs was significantly associated with 25% higher likelihood of progressing to next line of anti-MM therapy, suggesting that SREs may indicate disease worsening in patients with MM. Table 1: Impact of Skeletal-Related Events (SREs) on Progress to Next Line of Therapy in Multiple Myeloma: Cox Proportional Hazard Regression Model Results Patient Characteristics Hazard Ratios (95% Confidence Interval) P-values Post-index SREs 1.25 (1.13-1.37) < 0.0001 Pre-index SREs 0.96 (0.87-1.07) 0.4787 Pre-index Renal impairment 0.83 (0.73-0.95) 0.0050 Post-index Renal Impairment 1.05 (0.95-1.17) 0.3354 Bone lesion 1.14 (1.04-1.25) 0.0066 Hypercalcemia 1.30 (1.15-1.46) < 0.0001 The model was adjusted for age, gender, health plan type, index year, region, comorbidity score, osteoporosis, use of intravenous bisphosphonates, corticosteroids, and opioids

Severe osteonecrosis of the jaw with attempted near total mandibular exfoliation

AbstractThis report describes an unusual and extreme case of osteonecrosis of the jaw (ONJ) affecting the entire mandible, which was attempting to self exfoliate. A 76‐year old male presented clinically with all aspects of the mandible, except the condylar heads, necrotic and exposed in the oral cavity. The mandible had elevated out of the mucosa and was attempting to exfoliate through the mouth. As it was obstructing his oral cavity, the necrotic mandible was sectioned posteriorly allowing the patient to speak and eat comfortably, as well regain an oral seal. The use of intravenous bisphosphonates for metastatic prostate cancer coupled glucocorticosteroids, diabetes mellitus and hyperlipidaemia are likely to have contributed this extensive medication related ONJ. This complication is well‐recognised in association with bisphosphonates, however, this case is unique due to its severity, its spontaneous occurrence and the oral cavity's natural response to manage it, through near complete self exfoliation.

SIRT1/HERC4 Locus Associated With Bisphosphonate-Induced Osteonecrosis of the Jaw: An Exome-Wide Association Analysis.

Osteonecrosis of the jaw (ONJ) is a rare, but serious drug side effect, mainly associated with the use of intravenous (iv) bisphosphonates (BPs). The purpose of this study was to identify genetic variants associated with ONJ in patients of European ancestry treated with iv BPs using whole-exome sequencing (WES). The WES phase 1 included 44 multiple myeloma patients (22 ONJ cases and 22 controls) and WES phase 2 included 17 ONJ patients with solid tumors. Multivariable logistic regression analysis was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CI), adjusting for age, sex, and principal components for ancestry. Meta-analysis of WES phase 1 and 2 was performed to estimate the combined ORs. In silico analyses were then performed to identify expression quantitative loci (eQTL) single-nucleotide polymorphisms (SNPs) that are in high linkage disequilibrium (LD) with the top SNPs. The associations of the potentially functional SNPs were replicated and validated in an independent case-control study of 48 patients of European ancestry treated with iv BPs (19 ONJ cases and 29 controls). The top SNPs in the exome-wide association meta-analysis were two SNPs on chromosome 10: SIRT1 SNP rs7896005 and HERC4 SNP rs3758392 with identical OR of 0.07 (0.01-0.46; p = 3.83 × 10-5 ). In the in silico functional analyses, two promoter region SNPs (rs7894483 and rs3758391) were identified to be in high LD with the index SNPs and are eQTLs for SIRT1 gene in whole blood in the GTEx database. The ORs were 0.30 (0.10-0.88), 0.26 (0.12-0.55), and 0.26 (0.12-0.55) for the WES top SNP rs7896005 and two promoter SNPs rs7894483 and rs3758391, respectively, in the replication sample. In summary, we identified the SIRT1/HERC4 locus on chromosome 10 to be associated with iv BP-induced ONJ and two promoter SNPs that might be the potential genetic markers for this association. © 2017 The Authors.Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.