Intravenous Bisphosphonates Research Articles

Patterns and Predictors of Initiation of Intravenous Bisphosphonates Among Patients with Multiple Myeloma in the United States

▪Introduction:Osteolytic lesions are detected in approximately 90% of patients with multiple myeloma (MM) and increase the risk of skeletal related events (SREs), including fractures and other bone complications. Intravenous bisphosphonates (IV BPs) are recommended for patients diagnosed with MM with or without detectable osteolytic lesions to prevent SREs and possibly slow the progression of myeloma. There are limited data available describing the use of IV BPs in this population. We examined the cumulative incidence of IV BP initiation, accounting for the competing risk of death, and assessed predictors of initiation, overall and by IV BP type.Methods: An overall cohort of patients was identified using a sample of electronic health records from oncology clinics across the United States (Flatiron Health, Inc.) that linked to the MarketScan® employer-based and Medicare Supplemental administrative health insurance claims databases (Truven Health Analytics, Inc.) at any point before the MM diagnosis. Patients were aged 18 years or older and had a new MM diagnosis (ICD9, 203.00; ICD10, C90.00) between January 1, 2011 and April 30, 2016. Patients were excluded if they had an IV BP administration in the six months prior to the MM diagnosis, concurrent cancer in the 12 months prior to diagnosis, or did not have a healthcare encounter in the 30 days following the diagnosis. The cumulative incidence of IV BP initiation was estimated using competing risk models to account for death. To estimate predictors of initiation, we created a subcohort of patients who were additionally required to have continuous enrollment in MarketScan in the six months before the MM diagnosis. A multivariable generalized linear model was fit to estimate risk differences for predictors of initiation, and 95% confidence intervals (CIs) were obtained by a parametric bootstrap. Laboratory results, comorbidities, other therapies and SREs were included as time-varying variables in the model.Results: Among the 1875 patients in the overall cohort with a MM diagnosis, 60% were 65 years and older, 65% were white, and 13% had stage III MM at diagnosis. These characteristics were similar for the subcohort (N = 758). The cumulative incidence of IV BP initiation was 24% (95% CI: 22, 26%) at 30 days, 38% (35, 40%) at 90 days, and 44% (42, 46%) at 1 year. The cumulative incidence of treatment initiation was similar for patients diagnosed with MM in all calendar years of the study, but was higher for patients receiving anti-myeloma therapies. Zoledronic acid was the most commonly initiated IV BP; among those treated with an IV BP, 93% were administered zoledronic acid while only 7% were administered pamidronate. In the multivariate model, whites (compared with Blacks), patients with Stage III MM at diagnosis (compared to Stage I), patients with hypercalcemia, and patients undergoing other treatments (some anti-myeloma therapies, opioids, and glucocorticoids) were more likely to initiate an IV BP. Experiencing an SRE was the strongest predictor of IV BP initiation. Patients who had an SRE were more likely to initiate zoledronic acid, but less likely to initiate pamidronate. Patients with severely impaired renal function, defined as eGFR <30 mL/min, or patients with indicators of frailty were less likely to initiate an IV BP.Conclusions: In this study of patients diagnosed with MM who had employer-based commercial insurance or Medicare Supplemental coverage, the incidence of IV BP administration was lower than expected. Less than half of patients initiated an IV BP in the two years after diagnosis, indicating that a considerable number of patients with MM may be at increased risk for experiencing a bone complication. There are clinical reasons why patients may go untreated such as frailty or severely impaired renal function. Taking these patient characteristics into account, these real-world data revealed that an SRE was the strongest predictor of IV BP initiation, underscoring the need to manage the bone health of patients with MM more proactively. [Display omitted] DisclosuresHernandez:Amgen Inc.: Employment, Equity Ownership. Liede:Amgen Inc.: Employment, Equity Ownership. Brookhart:Amgen Inc.: Other: Scientific advisor, Research Funding; AstraZeneca: Research Funding; Merck: Other: Scientific advisor; GSK: Other: Scientific advisor; UCB: Other: Scientific advisor; Genentech: Other: Scientific advisor; TargetPharma: Other: Scientific advisor; RxAnte: Other: Scientific advisor.

Long-Term Follow-Up Outcomes of 19 Patients with Osteogenesis Imperfecta Type XI and Bruck Syndrome Type I Caused by FKBP10 Variants.

Osteogenesis imperfecta type XI (OI-XI) and Bruck syndrome type I (BS1) are two rare disorders caused by biallelic variants in the FKBP10, characterized by early-onset bone fractures and progressive skeletal deformities. The patients with OI-XI, also co-segregated with autosomal-recessive epidermolysis bullosa simplex caused by KRT14 variant, have been reported. In this study, the follow-up clinical features of the patients with OI-XI and BS1 phenotypes due to biallelic FKBP10 variants are compared. The aim of this study is to investigate the follow-up findings of OI-XI and BS1 phenotypes in patients with the FKBP10 variants. A total of 19 children, ten males and nine females, from 16 unrelated families were included in the study. FKBP10 variants were investigated by next-generation sequencing (NGS) based panel gene test or Sanger sequencing. Seventeen patients were followed between 1.5 and 16.8years, and the last follow-up age was between 2 and 24.6years (median 10.7years). They received intravenous bisphosphonate infusions once every 3months in follow-up period. We identified four different biallelic FKBP10 variants, two of which are novel (c.890_897dup TGATGGAC, p.Gly300Ter and c.1256 + 1G > A) in 16 families. Five of these patients also had findings of epidermolysis bullosa simplex, and the same biallelic c.612T > A (p.Tyr204Ter) variant in KRT14, as well as FKBP10, were identified. Twelve patients were diagnosed with OI-XI; whereas, seven were diagnosed with BS1. The BS1 phenotype was late-onset and the annual fracture number was lower. After bisphosphonate treatment, bone mineral densitometry Z score at L1-L4 increased (p = 0.005) and the number of annual fractures decreased (p = 0.036) in patients with OI-XI. However, no significant effect of bisphosphonate treatment was found on these values in BS1 patients. Despite the treatment, the rate of scoliosis and long bone deformity had increased in both groups at the last examination; and, only two patients could take a few steps with the aid of a walker, while others were not ambulatory, and they used wheelchairs for mobility. We identified two novel variants in FKBP10. Families originating from the same geographic region and having the same variant suggest founder effects. Although the number of fractures decreased with bisphosphonate treatment, none of our patients were able to walk during the follow-up. This study is valuable in terms of showing the follow-up findings of patients with FKBP10 variants for the first time.

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.

Management of bone metastasis and cancer treatment-induced bone loss during the COVID-19 pandemic: An international perspective and recommendations

Optimum management of patients with cancer during the COVID-19 pandemic has proved extremely challenging. Patients, clinicians and hospital authorities have had to balance the risks to patients of attending hospital, many of whom are especially vulnerable, with the risks of delaying or modifying cancer treatment. Those whose care has been significantly impacted include patients suffering from the effects of cancer on bone, where delivering the usual standard of care for bone support has often not been possible and clinicians have been forced to seek alternative options for adequate management.At a virtual meeting of the Cancer and Bone Society in July 2020, an expert group shared experiences and solutions to this challenge, following which a questionnaire was sent internationally to the symposium’s participants, to explore the issues faced and solutions offered. 70 respondents, from 9 countries (majority USA, 39%, followed by UK, 19%) included 50 clinicians, spread across a diverse range of specialties (but with a high proportion, 64%, of medical oncologists) and 20 who classified themselves as non-clinical (solely lab-based). Spread of clinician specialty across tumour types was breast (65%), prostate (27%), followed by renal, myeloma and melanoma.Analysis showed that management of metastatic bone disease in all solid tumour types and myeloma, adjuvant bisphosphonate breast cancer therapy and cancer treatment induced bone loss, was substantially impacted. Respondents reported delays to routine CT scans (58%), standard bone scans (48%) and MRI scans (46%), though emergency scans were less affected. Delays in palliative radiotherapy for bone pain were reported by 31% of respondents with treatments often involving only a single dose without fractionation. Delays to, or cancellation of, prophylactic surgery for bone pain were reported by 35% of respondents. Access to treatments with intravenous bisphosphonates and subcutaneous denosumab was a major problem, mitigated by provision of drug administration at home or in a local clinic, reduced frequency of administration or switching to oral bisphosphonates taken at home. The questionnaire also revealed damaging delays or complete stopping of both clinical and laboratory research.In addition to an analysis of the questionnaire, this paper presents a rationale and recommendations for adaptation of the normal guidelines for protection of bone health during the pandemic.

Intravenous bisphosphonate therapy does not delay fracture healing in inter-trochanteric femur fractures – A randomised controlled study

Hip fractures in elderly are commonly associated with osteoporosis and surgical outcome is influenced by its concurrent management. The purpose of our study is to determine the association between timing of bisphosphonate administration in inter-trochanteric (IT) fractures and fracture healing. Patients with IT fractures (aged≥50 years) and T-score ≤ -1.5 [WHO defines osteopenia as T-score between −1 and −2.5, and osteoporosis as T-score ≤ -2.5 on DEXA scan (which was obtained post-operatively in our cohort)], who underwent proximal femoral nailing were included. Patients were divided into three groups: group 1a-intravenous bisphosphonate {ivBP [zoledronic acid (ZA)]} given within one week, group 1b-ZA at six weeks and group 2-control group. Post-operative radiographs were assessed for reduction parameters [neck-shaft angle, tip-apex distance, reduction variance]. Radiological union was determined using RUSH score and functional outcome (at one year) with Modified Harris Hip Scores. 41 (23 males), 40 (15 males) and 42 (15 males) patients were included in groups 1a, 1b and 2, respectively (no statistical difference in sex distribution among the groups; p = 0.12). Mean age in groups 1a, 1b and 2 was 71.8 ± 8.1, 75.9 ± 8.5 and 72.3 ± 10.6 years (p = 0.09). There was no significant difference in the pattern of injuries (AO classification) among the groups (p = 0.72). Mean time to union in groups 1a, 1b and 2 was 13.7,13.7 and 14.2 weeks, respectively (p = 0.69). Mean time to union in AO types A1, A2 and A3 fractures was 13.2 ± 2.1, 13.7 ± 2.8 and 16.1 ± 4.9 weeks (p = 0.01). We did not observe any association between T-scores and fracture union (hip:p = 0.52, spine:p = 0.93).The functional outcome was similar among groups (p = 0.96). Early administration of ZA did not negatively influence fracture healing in patients undergoing fixation of IT fractures. Among the various other factors analyzed, there was a statistically significant association between the fracture type (AO type A3) and longer time to fracture union.

Pre-medical dental evaluation and treatment of oral infection – a survey study among hospital-affiliated dentists in Sweden

Objective To examine how hospital-affiliated dentists assess risk and evaluate oral foci of infection in patients facing certain medical treatments, and whether the nature of upcoming medical treatment affects the choice of dental intervention. Materials and methods A survey comprising six clinical cases (50 teeth) was sent to hospital-affiliated dentists in Sweden. A treatment option for the affected tooth/teeth in each case was selected whether the patient was facing heart valve surgery, chemotherapy, radiation therapy, intravenous bisphosphonate treatment, solid organ transplantation or was diagnosed with endocarditis. Results Consensus in choice of dental treatment was high in 62%, moderate in 32% and low in 6% of the assessments. High variability of choice of treatment was seen for eight teeth whereas the remaining 42 teeth often received the same therapy regardless of medical issue. Chemotherapy and radiotherapy were thought to entail the highest risk for oral infectious sequelae with a risk ranging from 1% to 100%. Conclusion Pre-medical dental evaluations and recommended treatments are often uniform with the exception of the management of asymptomatic root canal treated teeth with persisting apical radiolucency and heavily decayed molars. In many instances, dental diagnosis has a greater impact on choice of treatment than the underlying medical issue and associated implications thereof.

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.

Benign, Malignant or Something in Between: A Rapidly Developing Atypical Parathyroid Adenoma

Introduction: Although Primary Hyperparathyroidism (PHPT) is the third most common endocrine disorder, parathyroid carcinoma and atypical parathyroid adenoma are the rarest of endocrine tumours. The true incidence of atypical parathyroid adenomas has been elusive to endocrinologists since it is not possible to differentiate clinically between parathyroid carcinoma and atypical parathyroid adenomas before histological analysis. Atypical parathyroid adenoma represents a group of an intermediate form of parathyroid neoplasms with uncertain malignant potential. The majority of patients present with hypercalcaemia, however the development of atypical adenoma in patients with known PHPT is extremely rare. Clinical Case: A 78-year-old gentleman presented at the emergency department with lethargy and slurred speech which had started 1 week ago. Blood tests revealed severe hypercalcaemia. (Ca 4.98 mmol/L, PTH 114.2 pmol/L). The patient had a background of primary hyperparathyroidism which was diagnosed due to incidental mild hypercalcaemia (Ca 2.71 mmol/L, PTH 17.57 pmol/L, 25OH-vitamin D3 55 nmol/L). 2 weeks prior to presentation to the Emergency Department calcium and PTH levels were stable. On clinical examination, he was found mildly confused with no other clinical findings. No precipitating factors were identified. Hydration with IV crystalloids commenced and bisphosphonate IV was given. In view of PHPT Cinacalcet was added to treatment (30 mg BD). While the calcium levels seemed to improve initially, (lowest level achieved Ca 3.05 mmol/L) a week later they started to rise gradually. Hypercalcaemia proved refractory to medical treatment despite concomitant use of aggressive hydration, increased cinacalcet dose, second intravenous bisphosphonate, and intravenous calcitonin. Neck U/S revealed a probable parathyroid adenoma measuring 2cm axially at the inferior pole of the left thyroid lobe. In view of the severity and refractory nature of hypercalcaemia, a PET CT was requested which identified an 18 mm soft tissue mass in the left lower neck posterior to the left thyroid lobe with moderate to intense FDG uptake. There was no evidence of increased uptake elsewhere. The patient required 2 sessions of haemodialysis to maintain calcium levels around 3.5 preoperatively. He underwent parathyroidectomy with histological findings in keeping with atypical parathyroid adenoma. Gradual reduction of calcium levels was noted post-operatively with the lowest on day 10 (1.99) when he was started on oral calcium supplementation. The patient remains under follow-up with normal calcium levels 6 months postoperatively while remains on calcium and vitamin D3 supplements. Conclusion: To our knowledge, this is the only case of a patient with known primary hyperparathyroidism and mild hypercalcaemia, to develop severe parathyroid crisis with refractory to medical management hypercalcaemia within 2 weeks. Prompt surgical intervention remains of paramount importance in the management of these patients. They should have lifelong follow up in the view of uncertain malignant potential of the atypical parathyroid adenoma.

Iatrogenic Hypocalcemia With Treatment of Milk-Alkali Syndrome

Hypercalcemia is common disorder with the most likely etiology being primary hyperparathyroidism in the outpatient setting and malignancy in the hospitalized. With emergence of proton pump inhibitors and histamine blockers, milk-alkali syndrome has become a rarity. We report a unique case of hypercalcemia secondary to milk-alkali syndrome overtreated with bisphosphate therapy resulting in hypocalcemia.A 77-year-old woman with a past medical history of hypertension, gastroesophageal reflux disease presented with slurring of speech for 2 days with nausea and vomiting. Labs showed a calcium of 15.4 mg/dL, with an albumin of 4.0 g/dL. Other pertinent labs showed an ionized calcium of greater than 7.3 mg/dL, pH of 7.49, PTH of 15 pg/mL, PTHrP of 9 pg/mL, vitamin D 25-OH of 16 ng/mL, TSH of 2.16 IU/mL and acute kidney injury. Patient was started on intravenous fluids and given both calcitonin and pamidronate on presentation by the admitting team. When seen in consultation, history revealed that patient was consuming more than eight calcium carbonate antacid tablets daily and was also on hydrochlorothiazide. The calcium level decreased to 8.7 mg/dL within 48 hours. There was a concern for potential hypocalcemia due to pamidronate. Patient was advised to restart calcium carbonate 500 mg twice daily upon discharge with close follow up. However, supplementation was not started and repeat calcium was 6.7 mg/dL twelve days later. The calcium normalized within a week after starting temporary calcium supplementation.A now rare cause of hypercalcemia, milk-alkali syndrome is often overlooked in the differential diagnosis resulting in overtreatment and potentially dangerous hypocalcemia. Emergent management of intravenous hydration and bisphosphonate therapy is often immediately given by clinicians. Bisphosphonate therapy is not immediately effective and demonstrates calcium lowering effects by the second to fourth day. However, patients with milk-alkali syndrome generally improve with intravenous hydration and cessation of the causative agent. This case demonstrates the importance of obtaining a proper history with a complete list of medications and over the counter supplementations prior to treatment.

176P Breast cancer treatment during the first wave of the COVID-19 pandemic at a UK centre

This study aimed to assess the impact of the first wave of the COVID-19 pandemic on treatment delivery in patients undergoing systemic anti-cancer therapy (SACT) for breast cancer at a major London Oncology centre within an acute general hospital. Patients receiving outpatient SACT for breast cancer over a two-month period from 23rd March - 17th May 2020 were included and compared to an equivalent period in 2019. The number of referrals for breast cancer diagnosis was reduced by 38%. This was primarily a result of suspended screening services and inevitably had an impact on the number of patients starting their first treatment, which was reduced by 34%. Treatment was most affected for patients receiving neoadjuvant chemotherapy, 85% (28/33) of whom were impacted. Eight-six percent (24/28) of these had surgery expedited. The treatment of 74% of adjuvant (23/31) and 57% (12/21) of palliative patients receiving chemotherapy was modified, deferred or stopped. Modifications included switching to oral or less immunosuppressive therapies, delaying anthracyclines until completion of taxanes and increased use of G-CSF. Patient preference, co-morbidities and benefit of therapy were used to guide treatment. Compared to 2019, SACT given in hospital was reduced by 39%, mainly due to a reduction in intravenous bisphosphonate administration. Recovery was evident during the 8 week period, with treatment numbers returning to near normal towards the end. Widespread COVID-19 testing was not available at this time but 1% (3/312) of patients had parenteral treatment delayed due to COVID-19 symptoms (either in themselves or a household contact) and 2 patients tested positive for COVID-19 during the study period. One of these confirmed cases died from COVID-19 infection. This study demonstrates that the first wave of COVID-19 had a significant effect on breast cancer diagnosis and treatment delivery. Future impact on survival for these patients is uncertain. Whilst recovery is now evident, better efforts must be made to ensure cancer services and patients are prioritised in future.

A Case of Paraneoplastic Arthralgias

Hypertrophic Osteoarthropathy (HOA) is a rare condition that presents with arthralgias, digital clubbing, and abnormal periosteal bone deposition seen on x rays. The secondary form of HOA may be associated with an underlying malignancy, thus highlighting the importance of early clinical recognition. We present the case of a 44-year-old woman who presented with several weeks of lower extremity swelling, arthralgias, and digital clubbing who was later found to have non-small cell lung cancer. Diagnosis can be challenging due to variable presentations that can often mimic other forms of inflammatory arthritis. Treatment is focused on addressing the underlying cause. Nonsteroidal anti-inflammatory drugs (NSAIDS) are commonly used for pain relief while intravenous bisphosphonates have been trialed with some success in case reports.

P118 Co-design of a model Fracture Liaison Service consultation: a Delphi survey with patients and clinicians

Abstract Background/Aims Fracture Liaison Services (FLSs) are recommended to deliver best practice in secondary fracture prevention. As part of the iFraP (Improving uptake of Fracture Prevention drug Treatments) research programme this study aimed to 1) co-design content for a ‘model FLS consultation’ and 2) gain consensus on the appropriateness of osteoporosis clinical guidelines in the context of FLSs. Methods Three rounds of modified Delphi survey were sent to patients with osteoporosis and/or fragility fractures, carers, and clinicians. Participants were presented with potential consultation content derived from an evidence synthesis of current guidelines, frameworks and theories of shared decision-making, communication and medicine adherence, and stakeholder consultation. Participants were asked to rate their perception of the importance of each statement on a 5-point Likert scale and elaborate using free-text boxes. In Round 2, participants were shown mean scores of importance from Round 1. Statements identified as of ‘low importance’ at the end of Rounds 1 and 2 were discussed by the study team, including patient contributors, and were removed or amended. In Round 3, participants were asked whether the statement was ‘essential’ or ‘optional’ in a time-limited FLS consultation. Percentage agreement with each statement was ranked. The threshold for ‘essential’ versus ‘optional’ was determined by the study team. Results 391 invitations to participate were sent, with 72, 49, and 52 responders to Rounds 1, 2 and 3 respectively. Throughout Rounds 1-3 participants considered 122 statements. By Round 3, 81 statements were deemed essential, with an additional 14 optional statements. Essential statements were distilled into 18 recommendations constituting the ‘model FLS consultation’. Statements related to stages of the consultation, including: introductions; gather information; consider therapeutic options; elicit patient perceptions; establish shared decision-making preferences; share information about condition and treatment; check understanding; and signpost next steps. There was consensus that FLS clinicians should discuss the benefits and risks of oral and intravenous bisphosphonates and denosumab. Optional consultation content included a statement suggesting clinicians should observe the patient to look for signs of fractures in their spine, with free-text responses suggesting that FLS clinicians may not ‘be best qualified’ to perform physical examinations. Removed statements included those relating to the discussion of Hormone Replacement Therapy, Raloxifene and Teriparatide, with free-text statements suggesting that ‘specialists’ (e.g. Rheumatologists) should discuss these medications. Additionally, statements that described the potential consequences of fracture (e.g. ‘the clinician should explain that one in ten patients with a hip fracture will die within 12 months of fracture.’) were removed. Free-text comments described these statements as potentially ‘scary’. Conclusion The Delphi survey has informed iFraP intervention development by highlighting essential and optional FLS consultation content. Findings also provide insight into aspects of current osteoporosis clinical guidelines deemed appropriate in nurse/allied health professional led FLSs. Disclosure L. Bullock: None. C. Jinks: Grants/research support; CJ is part funded by the NIHR Applied Research Collaboration (ARC) West Midlands. F. Crawford-Manning: Grants/research support; FCM is part funded by the NIHR Clinical Research Network Scholar Programme. S. Leyland: None. J. Fleming: None. E.M. Clark: None. E. Cottrell: None. J. Edwards: Grants/research support; JE is an NIHR Academic Clinical Lecturer in Primary Care (CL-2016-10-003). Z. Paskins: Grants/research support; ZP is funded by the NIHR, Clinician Scientist Award (CS-2018-18-ST2-010)/NIHR Academy.

A quality improvement project to address the challenges surrounding zoledronic acid use in children

IntroductionZoledronic acid (ZA) is an intravenous bisphosphonate used to treat pediatric osteoporosis. Adverse events including hypocalcemia and acute phase reaction (APR) are common following first-infusion. The purpose of this report is to describe implementation of a ZA clinical practice guideline and the subsequent process changes to improve adherence to aspects of the protocol related to safety and efficacy.MethodsQuality assurance was evaluated by chart review over a 5-year period to compare the prevalence of hypocalcemia and APR to published data. A quality improvement (QI) initiative consisting of process changes including the addition of an endocrine RN to coordinate infusions and a shift to patient/family self-scheduling of infusions was conducted. The effect of the interventions on safety (completion of pre- and post-infusion bloodwork) and efficacy (receipt of all prescribed infusions) outcomes was evaluated.ResultsSeventy-two patients received 244 infusions over the period. The frequency of hypocalcemia (22%) and APR (31%) was consistent with prior reports. 99% of patients received pre-infusion bloodwork, 78% received post-first-infusion bloodwork, and 47% received all prescribed infusions. QI initiatives increased the percentage of patients receiving post-first-infusion bloodwork from 67 to 79% and those receiving all infusions from 62 to 74%, but fell short of the goal of 90%.ConclusionsThe implementation of a standardized protocol for ZA use in children was successful in confirming patient eligibility with pre-infusion bloodwork but failed to ensure that patients obtained post-first-infusion bloodwork and received all prescribed infusions. Further efforts to systematize the management of children on ZA are needed.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00774-021-01214-5.

Osteoporosis care during the COVID-19 pandemic in the Netherlands: A national survey

This is a survey study concerning osteoporosis care during the COVID-19 pandemic in the Netherlands. Respondents reported that osteoporosis care stagnated and lower quality of care was provided. This leads to the conclusion that standardization of osteoporosis care delivery in situations of crisis is needed. During the initial phase of the COVID-19 pandemic, there was no guidance of professional societies or guidelines on the organization of osteoporosis care in case of such a crisis, and treatment relied on local ad hoc strategies. Experiences from the current pandemic need to be taken into account for the near future, and therefore, a national multidisciplinary survey was carried out in the Netherlands. A survey of 17 questions concerning the continuation of bone mineral density measurements by Dual Energy X-ray absorptiometry (DXA), outpatient clinic visits, and prescription of medication was sent to physicians, nurses, nurse practitioners, and physician assistants working in the field of osteoporosis. 77 respondents finished the questionnaire, of whom 39 (50.6%) reported a decline in DXA-scanning and 36 (46.8%) no scanning at all during the pandemic. There was an increase in remote consultations for both new and control patient visits (n = 48, 62.3%; n = 62, 81.7% respectively). Lower quality of care regarding fracture prevention was reported by more than half of the respondents (n = 44, 57.1%). Treatment with intravenous bisphosphonates and denosumab was delayed according to 35 (45.4%) and 6 (6.3%) of the respondents, respectively. During the COVID-19 pandemic, osteoporosis care almost completely arrested, especially because of the discontinuation of DXA-scanning and closing of outpatient clinics. More than half of the respondents reported a substantial lower quality of osteoporosis care during the COVID pandemic. To prevent an increase in fracture rates and a decrease in patient motivation, adherence and satisfaction, standardization of osteoporosis care delivery in situations of crisis is needed.

Assessment of Awareness and Knowledge of Medication Related Osteonecrosis of Jaw among Dental Students at a Tertiary Hospital in Eastern Nepal

Introduction: The medication related osteonecrosis of jaw (MRONJ) is caused by bisphosphonates, antiresoptive or antiangiogenic drugs. It is the basic requirement for dental students to know the drugs that causing MRONJ and its management. The study was conducted to assess awareness and knowledge of MRONJ among dental students and to compare the mean knowledge score.&#x0D; Methods: A cross-sectional study was conducted among dental students at College of Dental Surgery, B. P. Koirala institute of Health Sciences. A semi-structured questionnaires consisting of sociodemographic data and questions regarding awareness and knowledge of MRONJ. Descriptive statistics like mean, standard deviation, percentage and frequency were calculated. Students “t” test was used for statistical association between the variables at P-value of 0.05 using SPSS.&#x0D; Results: Out of 191, 63 (32.98%) students were aware that drugs other than bisphosphonates can also cause osteonecrosis of jaw while only 16.23% students were able to name such drugs. Majority of the students (91.62%) failed to give proper definition of the MRONJ. More than half of the students did not know that invasive dental treatments cannot be given to patients who are currently on oral or intravenous bisphosphonates. Majority (77.5%) of the students didn’t know the treatment guideline for MRONJ. Mean knowledge score of the students was 9.068±3.092. There was statistically significant association between the score and age, marital status and academic stream of the students (P-value &lt;0.05).&#x0D; Conclusion: The study showed that students had average knowledge and awareness on MRONJ. The knowledge score was statistically associated with age, marital status and educational level. It suggests preeminent steps should be taken to educate future dental students about MRONJ at undergraduate and post graduate level of dentistry.

Interdisciplinary Management of Bisphosphonate-Related Osteonecrosis of the Jaw

Bisphosphonate (BP) Related Osteonecrosis of the Jaw (BRONJ) is one of the frequently occurring adverse reaction of BP intake, which is indicated in management of osteoporosis, Paget disease, multiple myeloma, and hypercalcemia in malignancies. The risk of osteonecrosis of the jaw relates to dose and duration of the therapy and the route of administration (i.e. more often BRONJ occurs in patients undergoing intravenous BPs therapy). At present, the management of BRONJ is a dilemma. No effective treatment has yet been developed. There is currently no gold standard of treatment for BRONJ. However, nowadays new alternative methods appear to be a promising modality of BRONJ treatment in early stages of the disease, while being safe and welltolerated, i.e. hyperbaric therapy, ozone therapy, use of platelet rich fibrine and platelet rich plasma, photodynamic therapy, low level laser therapy.

Management of glucocorticoid-induced osteoporosis.

Long-term glucocorticoid (GC) therapy is frequently indicated to treat autoimmune and chronic inflammatory diseases in daily clinical practice. Two of the most devastating untoward effects are bone loss and fractures. Doses as low as 2.5mg of prednisone for more than 3months can impair bone integrity. Population at risk is defined based on the dose and duration of GC therapy and should be stratified according to FRAX (Fracture Risk Assessment Tool), major osteoporotic fracture, prior fractures, and bone mineral density values (BMD). General measures include to prescribe the lowest dose of GC to control the underlying disease for the shortest possible time, maintain adequate vitamin D levels and calcium intake, maintain mobility, and prescribe a bone acting agent in patients at high risk of fracture. These agents include oral and intravenous bisphosphonates, denosumab, and teriparatide.

Abnormalities in Tooth Formation after Early Bisphosphonate Treatment in Children with Osteogenesis Imperfecta

Treatment with intravenous bisphosphonate (BP) in children and adolescents with osteogenesis imperfecta (OI) started in Sweden in 1991. No human studies on the role of BP therapy in development of disturbances in tooth mineralization or tooth morphology have been published. The study cohort comprised 219 individuals who were divided into four groups: group 1, BP treatment onset before 2 years of age (n = 22); group 2, BP treatment onset between 2 and 6 years of age (n = 20); group 3, BP treatment onset between 6 and 10 years of age (n = 13); and a control group of patients with OI who had not received BP therapy (n = 164). The chi-square test was used in between-group comparisons of the prevalence of tooth agenesis. The prevalence of tooth agenesis was significantly higher in children who began BP treatment before the age of 2 years (group 1; 59%,) compared to the controls (10%; p < 0.001) and to children who had begun BP therapy between ages 2 and 6 years (group 2; 10%; p = 0.009) or between ages 6 and 10 years (group 3; 8%; p = 0.003). Different types of disturbances in the enamel formation were seen in 52 premolars, where 51 were seen in those who began BP treatment before the age of 2 years. To conclude, starting BP treatment before the age of 2 years increases the risk of abnormalities in tooth formation manifesting as morphological aberrations, tooth agenesis, and enamel defects.

"The use of bisphosphonates to treat skeletal complications in solid tumours".

The skeleton is the most common site of secondary disease in breast cancer and prostate cancer, with up to 80% of patients with advanced disease developing bone metastases (BM). The proportion is also substantial in advanced lung cancer (20%-40%). Because of the high prevalence of cancers of the breast, prostate and lung, these cancers account for more than 80% of cases of metastatic bone disease occurring in solid tumours. Metastatic bone disease is associated with greatly increased bone resorption by osteoclasts, leading to moderate to severe pain and other skeletal complications, with major impact on quality of life (QoL). Skeletal Related Events (SREs) have been defined as: pathological long bone or vertebral fractures; spinal cord compression; need for radiation for pain relief or to prevent fracture/spinal cord compression, need for surgery to bone and hypercalcaemia. More recently, Symptomatic Skeletal Events (SSEs) have been defined to monitor QoL. Although there are currently no curative treatments for metastatic bone disease, patients with breast or prostate cancer and BM are now surviving for several years and sometimes longer, and prevention of SREs is the key aim to optimization of QoL. Since their discovery 50years ago and their introduction more than 30years ago into the field of metastatic bone disease, a range of oral and intravenous bisphosphonate drugs have made a major contribution to prevention of SREs. Large trials have clearly demonstrated the clinical value of different bisphosphonate-based drugs (including the oral drugs ibandronate and clodronate and intravenous agents such as zoledronate and pamidronate), in treatment of hypercalcaemia of malignancy and the reduction of SREs and SSEs in a range of cancers. Despite the success of denosumab in reducing osteolysis, bisphosphonates also remain mainstay drugs for treatment of metastatic bone disease. Recognizing the 50th Anniversary of the discovery of bisphosphonates, this review focuses on their continuing value in BM treatment and their future potential, for example in providing a bone-targeting vehicle for cytotoxic drugs.

Antiresorptive medication in oncology: the clinical and dental profile of patients in a reference center.

ObjectivesThe aim of this study was to evaluate the profile of patients on antiresorptive therapies for cancer treatment and assess presence of oral lesions, oral hygiene status, and knowledge regarding medication-related osteonecrosis of the jaw (MRONJ).Materials and MethodsThis was an observational cross-sectional study that evaluated patients treated with antiresorptive medication at a single cancer hospital. Clinical data were collected and oral examination was performed to assess patient oral health.ResultsFrom July 2017 to December 2018, 90 patients were assessed; 64 were female and 26 were male, and the mean age was 61 years. The most common drug was an intravenous bisphosphonate, zoledronic acid. Among the 90 patients, 47 presented with some type of oral disease, isolated or associated. Among these 47 patients, 9 patients (10%) developed osteonecrosis. Oral hygiene was evaluated, and most patients, with or without MRONJ, presented with regular to poor condition. Regarding patient knowledge of the risks of MRONJ and the risks associated with dental surgery, 60% stated that they were not aware of the risks.ConclusionIdentifying the profile of patients and their needs facilitates not only the preventive process, but also the emergence of new therapeutic options. Our study shows that most patients are weakened both by metastatic disease and antineoplastic treatment as well as by issues associated with aging because most were over 60 years of age. Collectively, this information should be considered for management of preventive and therapeutic measures.