Oral Bisphosphonate Treatment Research Articles

E020 Osteoporosis service improvement audit

Abstract Background/Aims Osteoporosis referrals are sent to rheumatology departments for consideration of parenteral treatments in those who are unable to tolerate oral bisphosphonates or have failed treatment. The rheumatology services at Croydon University Hospital (CUH) are oversubscribed which results in long waiting times for appointments and increased workload on clinicians. The aim of this audit is to identify the scope of osteoporosis workload, the source of referrals, to improve distribution of the osteoporosis workload in CUH and redesign the pathway for osteoporosis referrals. A secondary aim is to identify patients that could be managed without referral enabling more consultation slots within the rheumatology department for patients that present with early inflammatory arthritis. Methods Data was collected retrospectively from all the patients that had been referred to the rheumatology department, either internally or externally and offered a new osteoporosis appointment from June to mid-September 2022 (104 patients in total). A data collection sheet was created from electronic patient records. The data included the patients’ hospital number, age, sex, height, weight, BMI, race, source of referral, reason for referral, fractures sustained, admissions for fracture, prior treatment with IV/ oral bisphosphonates, which oral bisphosphonate treatment and reasons for stopping, co-prescription of calcium/ vitamin D and the follow up plan. Results Among patients who were surveyed, 33 were internal referrals. Referring departments were as follows: 18 from fracture liaison service (FLS), 7 from care of the elderly (COTE), 3 from orthopaedics, 1 from rheumatology, 1 from nephrology, 1 from endocrinology, 1 from haematology and 1 from respiratory. In the GP cohort (71 patients), many were intolerant to oral bisphosphonates due to gastrointestinal upset. Reasons for referral were as follows: 36 for intolerance to oral medication, 14 for declining BMD, 11 for restarting medication after drug holding, 9 for complexity of cases (including young age/ male/ anorexia/ osteogenesis imperfecta), 8 unspecified, 7 had sustained a fracture on treatment, 6 received breast cancer treatment, 6 had renal impairment, 6 for a second opinion and 1 for considering a drug holiday. Conclusion This audit highlights the issues associated with osteoporosis workload and suggests improvements for managing the referrals both internally and externally. GP education is important for managing patients not tolerating oral bisphosphonates before accepting referrals. We have started recommending GP to try alternative oral bisphosphonates or effervescent alendronic acid prior to referral. Some internal workload can be managed by the referring team with advice being provided by the rheumatology team in order to reallocate rheumatology appointments for other conditions. The rheumatology department at Croydon University Hospital met with stakeholders from COTE and FLS and discussed the audit results. The COTE team agreed to initiate and continue IV zoledronate to reduce the osteoporosis burden on the rheumatology department. Disclosure S. Taheri: None. R. Suresh: None. J. Burton: None. S. Adil: None. T. Ahmed: None. N. Horwood: None. R. Sathananthan: None.

THU442 A Case Of Early Medication Related Osteonecrosis Of The Jaw In Patient Receiving Intravenous Zoledronate For Treatment Of Osteoporosis

Abstract Disclosure: V. Ekpe: None. X. Au: None. M. Golson: None. L.E. McGuire: None. L.E. Aguirre: None. Introduction: Medication related Osteonecrosis of the jaw (MRONJ) is a rare side effect in patients receiving nitrogen-containing bisphosphonates intravenously and other anti-bone resorptive agents such as denosumab . The incidence is 0.1% in patients with metabolic bone disease1. Annual infusions of zoledronic acid have been recommended in order to improve patient compliance, optimize therapeutic effects and to minimize side effects in selected patients. Risk factors include history of malignancy, smoking, poor dental health, prior oral surgery, high dose exposure to zoledronic acid and longer duration of treatment with anti-resorptive therapy. Increasing usage of bisphosphonates and other antiresorptive drugs, have led to an increased incidence of MRONJ. Clinical Case: We report the case of a 63-year-old Caucasian female suffering from osteoporosis who developed early stage MRONJ. She has a history of several years of oral bisphosphonate treatment and three annual administrations of zoledronic acid. Patient presented with a new complaint of gum pain and a sore above her tooth. Prior routine dental exams have all been unremarkable. She was promptly referred and evaluated by a dental provider. Dental photographs showed a resorptive defect at the gumline. Patient was diagnosed with medication related osteonecrosis of the jaw (MRONJ) in the gum area above tooth number 9. Our patient was treated with oral amoxicillin 500mg twice daily and chlorhexidine gluconate mouth rinse twice daily. The intravenous zoledronic acid was discontinued. Her gum infection resolved. Discussion: Early detection of MRONJ is possible in patients potentially at risk for this rare complication. Providers should be aware of MRONJ and refer those patients on antiresorptive drugs to the dentist for frequent evaluation and assessment for any drug-related jaw changes.

THU427 The Benefits Of Oral Bisphosphonates For Elderly Patients With A History Of Long Term Aromatase Inhibitor Use

Abstract Disclosure: L.D. Dominguez: None. S.E. Acosta: None. A.R. Alejandro: None. Aromatase Inhibitors (AI) are commonly used to treat estrogen receptor-positive breast cancer as they reduce the risk of recurrence and mortality. The AIs, however, can lead to a decrease in bone mineral density (BMD), resulting in fractures. According to the Journal of Bone Oncology (JBO), postmenopausal women on AIs with two or more risk factors for fractures should be placed on antiresorptive treatment (1). Our objective was to compare the BMD of at-risk patients that have been treated with antiresorptive treatment versus the BMD of patients not treated. An EMR chart review was conducted from 6/14/2022-8/20/2022, in which 295 patients were analyzed by the medications prescribed and their BMD. Our sample size was limited to 90 patients that had obtained DXA scores from the same GE Hologic densitometer. We hypothesized that patients on AIs and antiresorptive treatment would show more improvement in BMD than patients on AIs and not on treatment. Patients were analyzed in the comparison of their BMD. Of the 65 patients on AIs, only 17 were placed on antiresorptive treatment (26%). 94% of these patients showed improved BMD. The increase in BMD for the spine was significant (.030) as it exceeds the least significant change (LSC) of .027 g/cm^2. The improvement of .012 in the hip was not significant (.022 g/cm^2 LSC). 68.75% of patients on AI’s and not on treatment worsened by .025 in the hip (.022 g/cm^2 LSC) and by .017 in the spine (.027 g/cm^2 LSC). Alendronate (76%), Zoledronic acid (18%) and Ibandronate (6%) were commonly prescribed. The patients on Alendronate and Ibandronate, improved by .015 in the hip (.022 g/cm^2 LSC) and improved significantly by .028 in the spine (.027 g/cm^2 LSC). Patients on intravenous(IV) treatment improved significantly in the spine by .041(.027 g/cm^2 LSC) but only improved by .006 in the hip (.022 g/cm^2). Although IV administration of treatment is recommended for patients starting treatment (2), most patients showed a trend of improvement on oral bisphosphonates. Hence, to improve the care offered to at-risk patients who cannot obtain IV bisphosphonates, we can advocate for the use of oral bisphosphonate treatment.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Trends in osteoporosis care patterns during the COVID-19 pandemic in Alberta, Canada

Purpose/introductionThe objective of this study was to describe osteoporosis-related care patterns during the coronavirus disease 2019 (COVID-19) pandemic in Alberta, Canada, relative to the 3-year preceding.MethodsA repeated cross-sectional study design encompassing 3-month periods of continuous administrative health data between March 15, 2017, and September 14, 2020, described osteoporosis-related healthcare resource utilization (HCRU) and treatment patterns. Outcomes included patients with osteoporosis-related healthcare encounters, physician visits, diagnostic and laboratory test volumes, and treatment initiations and disruptions. The percent change between outcomes was calculated, averaged across the control periods (2017–2019), relative to the COVID-19 periods (2020).ResultsRelative to the average control March to June period, all HCRU declined during the corresponding COVID-19 period. There was a reduction of 14% in patients with osteoporosis healthcare encounters, 13% in general practitioner visits, 9% in specialist practitioner visits, 47% in bone mineral density tests, and 13% in vitamin D tests. Treatment initiations declined 43%, 26%, and 35% for oral bisphosphonates, intravenous bisphosphonates, and denosumab, respectively. Slight increases were observed in the proportion of patients with treatment disruptions. In the subsequent June to September period, HCRU either returned to or surpassed pre-pandemic levels, when including telehealth visits accounting for 33–45% of healthcare encounters during the COVID periods. Oral bisphosphonate treatment initiations remained lower than pre-pandemic levels.ConclusionsThis study demonstrates the COVID-19 pandemic and corresponding public health lockdowns further heightened the “crisis” around the known gap in osteoporosis care and altered the provision of care (e.g., use of telehealth and initiation of treatment).SummaryOsteoporosis has a known substantial care and management disparity, which has been classified as a crisis. The COVID-19 pandemic created additional burden on osteoporosis patient care with healthcare encounters, physician visits, diagnostic and laboratory tests, and treatment initiations all declining during the initial pandemic period, relative to previous years.

Utility of PINP to monitor osteoporosis treatment in primary care, the POSE study (PINP and Osteoporosis in Sheffield Evaluation).

In Sheffield (UK), we introduced the PINP monitoring algorithm for the management of osteoporosis treatment delivered in primary care. Our aims were to evaluate whether this algorithm was associated with better osteoporosis outcomes and was cost-effective compared to standard care. Inclusion criteria were referral from Sheffield GPs, BMD scans performed between 2012 and 2013 and a report advising initiation of oral bisphosphonate and PINP monitoring. 906 patients were identified and retrospectively divided into Group A (intention to monitor, with baseline PINP, n=588) and Group B (no intention to monitor, without baseline PINP, n=318). The model described by Davis and colleagues was used to extrapolate life-time costs and quality-adjusted life-years (QALYs). No differences were found in baseline characteristics between groups (age, gender, BMI, BMD and major risk factors for fractures). More patients in Group A started oral treatment (77.4% vs 49.1%; p<0.001), but there were no differences between groups in the presence of a gap in treatment >3months or in treatment duration. Patients in Group A were more likely to have follow-up DXA scan at 4-6years from baseline (46.9% vs 29.2%; p<0.000) and had a greater increase in total hip BMD (+2.74% vs+0.42%; p value=0.003). Fewer new fractures occurred in Group A but this was not statistically significant, but the numbers of fractures were small. Patients in Group A were more likely to change management (p=0.005) including switching to zoledronate (p=0.03). The PINP measurement and increased prescribing in Group A resulted in increases in both costs (£30.19) and QALYs (0.0039) relative to Group B, giving an incremental cost effectiveness ratio (ICER) of £7660 in the probabilistic sensitivity analysis. Patients monitored with PINP are more likely to start oral bisphosphonate treatment, switch to zoledronate, have follow-up DXA scans and a greater increase of hip BMD. PINP monitoring has the potential to be cost-effective in a UK NHS setting given that interventions with an ICER under £20,000 are generally considered to be cost-effective.

Real-world data of bone turnover markers to monitor oral bisphosphonate treatment

Real-world data of bone turnover markers to monitor oral bisphosphonate treatment

Bone Quality and Fractures in Women With Osteoporosis Treated With Bisphosphonates for 1 to 14 Years.

ABSTRACTOral bisphosphonates are the primary medication for osteoporosis, but concerns exist regarding potential bone‐quality changes or low‐energy fractures. This cross‐sectional study used artificial intelligence methods to analyze relationships among bisphosphonate treatment duration, a wide variety of bone‐quality parameters, and low‐energy fractures. Fourier transform infrared spectroscopy and histomorphometry quantified bone‐quality parameters in 67 osteoporotic women treated with oral bisphosphonates for 1 to 14 years. Artificial intelligence methods established two models relating bisphosphonate treatment duration to bone‐quality changes and to low‐energy clinical fractures. The model relating bisphosphonate treatment duration to bone quality demonstrated optimal performance when treatment durations of 1 to 8 years were separated from treatment durations of 9 to 14 years. This may be due to a change in relationship of bone‐quality parameters with treatment duration. This model also showed that the effects of bisphosphonate treatment duration were most highly correlated with changes in means and standard deviations of infrared spectroscopically derived mineral and matrix parameters and histomorphometric bone turnover parameters. A second model related treatment duration to bone fracture in all 22 patients who fractured while on treatment with bisphosphonates for more than 8 years. This second model showed that bisphosphonate treatment duration, not hip bone mineral density (BMD), was the most strongly correlated parameter to these low‐energy bone fractures. Application of artificial intelligence enabled analysis of large quantities of structural, cellular, mineral, and matrix bone‐quality parameters to determine relationships with long‐term oral bisphosphonate treatment and fracture. Infrared spectroscopy provides clinically relevant bone‐quality information of which bone mineral purity is among the most relevant. Nine or more years of bisphosphonate treatment was associated with abnormal bone mineral purity, matrix abnormalities, and low‐energy fractures. These data justify limiting bisphosphonate treatment duration to 8 years. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Characteristics of patients with osteonecrosis of the jaw with oral versus intravenous bisphosphonate treatment

PurposeThis retrospective study was aimed to evaluate the clinical characteristics and treatment outcomes in patients with osteonecrosis of the jaw who were receiving oral versus intravenous (IV) bisphosphonate (BP).Materials and methodsThis retrospective study enrolled subjects who had been diagnosed with medication-related osteonecrosis of the jaw (MRONJ) during the period from July 2010 to June 2014. Information regarding the following demographic and clinical characteristics was collected: demographic data, administration route and type of BP, duration of BP medication, primary disease, number of involved sites, location of the lesion, number of surgeries, outcome of treatments, and laboratory test. All the patients were divided into oral and IV BP groups; and the between-group differences were compared.ResultsTotal 278 patients were divided into two groups as per the route of BP administration. The proportion of oral BP-related MRONJ group were more dominant over IV BP group (oral BP, n = 251; IV BP, n = 27). In the IV BP group, the average dosing duration (31.4 months) was significantly shorter than that in the oral BP group (53.1 months) (P < 0.001). The average number of involved sites in the oral BP group (1.21 ± 0.48) was smaller than that in the IV BP group (1.63 ± 0.84) (P < 0.001). The average number of surgeries was higher in the IV BP group (1.65 ± 0.95) as compared to that in the oral BP group (0.98 ± 0.73) (P < 0.001). Outcome after the surgery for MRONJ after IV BP was poor than oral BP group.ConclusionIV administration of BP causes greater inhibition of bone remodeling and could lead more severe inflammation. Therefore, even if the duration of IV administration of BP is shorter than that of oral BP, the extent of the lesion could be more extensive. Therefore, the result suggests that the MRONJ after IV BP for cancer patients needs to be considered as different characteristics to oral BP group for osteoporosis patents.

Republished: Severe hypophosphataemia following oral bisphosphonate treatment in a patient with osteoporosis

Republished: Severe hypophosphataemia following oral bisphosphonate treatment in a patient with osteoporosis

A Clinical and Histological Study about the Socket Preservation in a Patient under Oral Bisphosphonates Treatment: A Case Report.

The aim of the present study is to assess the clinical and histological healing of a post-extractive alveolus following the procedure for socket preservation, in a patient receiving oral bisphosphonates for more than 6 years. After the extraction, enzymatically-deantigenated horse bone granules and an equine pericardium membrane were used to preserve the tooth socket. The patient was placed on a monthly follow-up in order to monitor the healing process. A 3 mm trephine bur was used to drill the bone for implant site preparation and to collect the bone sample. No signs and symptoms related to osteonecrosis of the jaws were reported. Histological data showed that, after 5 months, the mean percentages of trabecular bone, bone marrow and residual bone graft were respectively 45.74 ± 0.09%, 48.09 ± 0.08%, and 6.16 ± 0.01%. The residual graft material appeared to be osteointegrated and none of the particles appeared to be encapsulated. The present case report supports the guidelines that assume that patients undergoing oral bisphosphonate therapy can be eligible for surgical therapy. More clinical studies with larger sample sizes are needed to support this clinical evidence.

Bisphosphonates for the treatment of fibrous dysplasia of bone

Fibrous dysplasia of bone (FD) is a rare congenital bone disease, due to a somatic mutation of GNAS. This mutation results in a defect of osteoblast differentiation and mineralization and also an increase in bone resorption by large active osteoclasts. Bone pain is present in half of patients and is the main determinant of quality of life of patients with FD. Bisphosphonates are known to reduce bone pain and reduce the risk of fracture in patients with bone metastases or Paget's disease. Bisphosphonates may have similar effects in FD. In this article, we have reviewed the therapeutic potential of bisphosphonates to reduce bone pain due to FD, improve bone strength and reduce the occurrence of fracture. We have reviewed 234 articles examining the effect of bisphosphonates on FD/McCune Albright Syndrome with no date limit, in PubMed and selected the articles with highest quality of methodology. Pamidronate therapy significantly decreased bone pain and bone resorption (urinary NTX, urinary and serum CTX). Pamidronate may improve radiological lesions of FD patients (filling of osteolytic lesion and/or cortical thickening). This data with intravenous pamidronate, however, has been obtained from observational studies and no randomized controlled trial is available. Randomized placebo-controlled trials of oral bisphosphonates (alendronate or risedronate) have failed to demonstrate a significant decrease in bone pain over placebo. Several studies including one randomized controlled trial have shown an increase in bone mineral density (BMD) at FD sites with oral and intravenous bisphosphonate treatment. No effect on occurrence of fracture has been reported. In conclusion, intravenous bisphosphonates may be proposed to treat persistent, moderate to severe bone pain of FD, e.g., according to the guidelines from the FD/MAS International Consortium. Oral bisphosphonates should not be used in this indication.

Vertebral fracture assessment (VFA) for osteoporosis screening in US postmenopausal women: is it cost-effective?

To evaluate the cost-effectiveness of VFA as a screening tool to reduce future fracture risk in US community-dwelling women aged ≥ 65years. An individual-level state-transition cost-effectiveness model from a healthcare perspective was constructed using derived data from published literature. The time horizon was lifetime. Five screening strategies were compared, including no screening at all, central dual-energy X-ray absorptiometry (DXA) only, VFA only, central DXA followed by VFA if the femoral neck T-score (FN-T) ≤ - 1.5, or if the FN-T ≤ - 1.0. Various initiation ages and rescreening intervals were evaluated. Oral bisphosphonate treatment for 5-year periods was assumed. Incremental cost-effectiveness ratios (2017 US dollars per quality-adjusted life-year (QALY) gained) were used as the outcome measure. The incorporation of VFA slightly increased life expectancy by 0.1years and reduced the number of subsequent osteoporotic fractures by 3.7% and 7.7% compared with using DXA alone and no screening, respectively, leading to approximately 30 billion dollars saved. Regardless of initiation ages and rescreening intervals, central DXA followed by VFA if the FN-T ≤ - 1.0 was most cost-effective ($40,792 per QALY when the screening is initiated at age 65years and with rescreening every 5years). Results were robust to change in VF incidence and medication costs. In women aged ≥ 65years, VFA is cost-effective when it was incorporated in routine screening for osteoporosis. Our findings support the National Osteoporosis Foundation (NOF) guidelines for the diagnostic use of VFA as an important addition to fracture risk assessment.

Oral bisphosphonate treatment in patients with Duchenne muscular dystrophy on long term glucocorticoid therapy

Osteoporosis is a major problem in patients with Duchenne muscular dystrophy (DMD), due to glucocorticoid therapy and muscle weakness. Evidence on which to base optimal prevention and treatment strategies, including bisphosphonate use, in DMD are limited. Our objective was to describe bone health outcomes of oral alendronate treatment in patients with DMD and glucocorticoid-induced osteoporosis. We retrospectively studied 54 patients treated between 2005 and 2017, and assessed changes in dual-energy x-ray absorptiometry (DXA) whole body and lumbar spine bone mineral density and content, and lateral distal femur bone mineral density. We also examined vertebral fracture development in a subset with serial spine radiographs. Pre-alendronate DXA Z-score trajectories decreased progressively. Over three years post-alendronate initiation, Z-score trajectories improved (p<0.01) at most sites compared with pre-alendronate trajectories. Height-adjusted Z-score trajectories for lumbar spine bone mineral density (p = 0.01) and whole body bone mineral content (p = 0.0004) also improved. The positive trajectories did not seem to be sustained long term in those treated up to 6 years. Radiographic vertebral findings in 43 patients appeared stable. In conclusion, oral bisphosphonate therapy using alendronate was associated with improvement of DXA bone health indices during the first three years of treatment, and may help mitigate progression of osteoporosis in glucocorticoid-treated patients with DMD.

Adherence with brand versus generic bisphosphonates among osteoporosis patients: a new-user cohort study in the French National Healthcare Insurance database

Several studies documented declines in treatment adherence with generic forms of oral bisphosphonates in osteoporosis compared to branded forms, while others did not support this relation. Our aim was to compare medication adherence with brand versus generic forms of oral bisphosphonates. A new-user cohort study was conducted using routinely collected administrative and healthcare data linked at the individual level extracted from a nationwide representative sample of the French National Healthcare Insurance database. We included all patients aged 50 and older, new users of oral bisphosphonates for primary osteoporosis between 01/01/2009 and 31/12/2015. Two components of adherence were measured: implementation (continuous multiple-interval measure of medication availability version 7; CMA7) and persistence (time to discontinuation). The sample was composed of 1,834 in the “brand bisphosphonate” group and 1,495 patients in the “generic bisphosphonate” group. Initiating oral bisphosphonate treatment with brand was associated with a higher risk of discontinuation within 12 months (Hazard Ratio = 1.08; 95%CI = [1.02;1.14]). The risk of good implementation (CMA7 ≥ 0.90) was significantly lower in “brand bisphosphonate” group (Risk Ratio = 0.90; 95%CI = [0.85; 0.95]). We did not find any evidence to support the hypothesis of a lower adherence to generic bisphosphonates. In fact, prescribing of generic bisphosphonates led to a higher persistence rate and to better implementation at 1 year.

Risk assessment of bisphosphonate-related osteonecrosis of the jaw based on CBCT scans

Bisphosphonate-related osteonecrosis of the jaw is a condition that severely affects the quality of life, therefore an early diagnosis is of utmost importance (both from a general and a surgical point of view), alongside with an accurate assessment of the risk of emergence of the disease. Estimation of the prognosis is not resolved; among several radiological options those used in dentistry seem the most fit for the purpose, with cone-beam computed tomography (CBCT) being superior in this task. Assessment of the risk of BRONJ developed following orally applied bisphosphonate is unemphatic in most case studies - these focus more on the intravenous application carrying a greater risk of BRONJ. In contrast with the studies published so far, we performed our measurements on preoperative CBCT scans, thereby directly studying the possibility of risk assessment. Our measurements were conducted through evaluating CBCT scans. We chose the frontal section in the midline of the mental foramen as the representative area. We measured density and thickness of the cortical bone on several given points; the diameter of the mental foramen was also measured. In the first group, we examined patients suffering from osteoporosis who had developed BRONJ following oral bisphosphonate treatment. In the second group, we looked at patients suffering from osteoporosis, who had received oral bisphosphonate therapy for this condition but did not develop BRONJ after oral surgery. As control group, we chose patients suffering from osteoporosis who had not received any of the medications known to cause BRONJ. Based on our results, it is clear that there is no significant difference in the bone density of those patients who developed BRONJ and those who did not, examining the preoperative CBCT scans. Using CBCT scans (and thereby submitting the patient to radiation exposure) in order to estimate the possibility of BRONJ following oral bisphosphonate treatment for osteoporosis is not recommended. It is important not to expose patients to more radiation than strictly necessary to predict BRONJ following oral bisphosphonate treatment in accordance with the ALARA (as low as reasonably achievable) principle. Orv Hetil. 2020; 161(21): 867-872.

Determinants of Oral Bisphosphonate Use Beyond 5 Years.

Few studies have examined factors that determine bisphosphonate (BP) continuation beyond 5 years in clinical practice. To investigate factors associated with BP continuation among women who completed 5 years of BP therapy. Women who received 5 consecutive years of oral BP treatment entered the cohort during 2002-2014 and were followed up to 5 additional years. Multivariable logistic regression was used to evaluate the association of demographic and clinical factors with adherent treatment continuation. The cohort included 19,091 women with a median age of 72 years. Baseline and time-varying factors associated with increased odds of BP continuation after 5 years were (a) most recent bone mineral density (BMD) T-score -2 to -2.4 (OR = 1.31, 95% CI = 1.25-1.38), T-score -2.5 to -2.9 (OR = 1.48, 95% CI = 1.39-1.57), and T-score ≤ -3.0 (OR = 1.57, 95% CI = 1.47-1.68) versus T-scores above -2.0; (b) index date before 2008 (OR =1.35, 95% CI = 1.29-1.41); and (c) diabetes mellitus (OR = 1.08, 95% CI = 1.01-1.16). In contrast, factors associated with decreased odds of BP continuation were (a) recent hip (OR = 0.61, 95% CI = 0.52-0.71) or humerus (OR = 0.79, 95% CI = 0.66-0.94) fracture or fracture other than hip, wrist, spine, or humerus (OR = 0.90, 95% CI = 0.84-0.97); (b) Charlson Comorbidity Index score > 2 (OR = 0.91, 95% CI = 0.84-0.98); (c) history of rheumatoid arthritis (OR = 0.89, 95% CI = 0.80-0.99); (d) Hispanic (OR = 0.89, 95% CI=0.85-0.94) or Asian (OR = 0.90, 95% CI = 0.85-0.94) race/ethnicity; and (e) use of proton pump inhibitors (OR = 0.65, 95% CI = 0.59-0.71). Patient age and fracture before BP initiation were not associated with treatment continuation. Clinical factors predicting continued BP treatment beyond 5 years include low BMD T-score, absence of recent fracture, and earlier era of treatment. Use of proton pump inhibitors was associated with lower likelihood of BP continuation. Other clinical and demographic factors were also noted to have variable effects on BP treatment continuation. This study was supported by a grant from the National Institute on Aging and National Institute of Arthritis, Musculoskeletal and Skin Diseases at the National Institutes of Health (NIH; R01AG047230, S1). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or Kaiser Permanente. Lo has received previous research funding from Amgen and Sanofi, unrelated to the current study. Adams has received previous research funding from Merck, Amgen, Otsuka, and Radius Health, unrelated to the current study. Ettinger has served as an expert witness for Teva Pharmaceuticals, unrelated to the current study. Ott previously attended a scientific advisory meeting for Amgen but declined the honorarium. The other authors have nothing to disclose. These data were presented at the 2018 Annual Meeting of the American Society of Bone and Mineral Research (ASBMR), September 28-October 1, 2018, Montreal, Quebec, Canada.

Real-world persistence and adherence with oral bisphosphonates for osteoporosis: a systematic review

ObjectivesThis study examined patient adherence and persistence to oral bisphosphonates for the treatment of osteoporosis in real-world settings.MethodsA systematic review was completed according to the Preferred Reporting Items for Systematic...

PMS88 - REAL WORLD PERSISTENCE AND ADHERENCE WITH ORAL BISPHOSPHONATES FOR OSTEOPOROSIS - A SYSTEMATIC REVIEW

Osteoporosis is a chronic global health condition, characterised by low bone density. Bisphosphonates are a common medication used to treat this condition. This study examined patient adherence and persistence with oral bisphosphonates for the treatment of osteoporosis. A systematic review was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). MEDLINE, CINAHL, AMED, DARE, HTA and NHS EED databases were searched for studies published in English language up to 11th August 2017. We used a detailed list of search terms related to persistence and adherence of oral bisphosphonate treatment. In order to assess the quality of the studies we used the Newcastle – Ottawa quality assessment scale [NOS]. The search yielded 532 published studies, of which 89 were deemed relevant and were included in this review. The mean age of patients included within the studies ranged between 53 to 80.8 years, and the follow-up varied from 6 months to 14 years. The mean persistence of oral bisphosphonates for 6 months, 1 year and 2 years ranged from 38% to 79%, 12.6% to 77.6%, and 9.5% to 41.8%, respectively. The mean medication possession ratio (MPR), a measure of adherence, ranged from 58% to 92%. All the included studies scored the maximum applicable score of between 6 to 8 on the NOS. The determinants of adherence and persistence to oral bisphosphonates included geographic residence, marital status, tobacco use, educational status, income, race, hospitalisation and medication type and dosing frequency. The findings of this review suggest that patients’ persistence with treatment was poor and dropped notably over the first two years. Overall, adherence was sub optimal. In order to maximize adherence and persistence to oral bisphosphonates it is important to consider their possible determinants including characteristics of the patients.

Exposure to alendronate is associated with a lower risk of bone metastases in osteoporotic women with early breast cancer

BackgroundBisphosphonate (BP) treatment to prevent bone loss in breast cancer patients is already well established. However, data on the association between oral BP exposure before cancer diagnosis and disease outcomes in patients with early breast cancer are still scarce. Limited information is available on alendronate, the most common oral agent for the treatment of post-menopausal osteoporosis, regarding the association with bone metastases. AimTo examine the association between oral bisphosphonate exposure before cancer diagnosis and the risk of bone metastases in osteoporotic women diagnosed with early breast cancer. Subjects and methodsThis historical cohort study was conducted at the oncology division at Tel Aviv Medical Center. The study population included post-menopausal women with early breast cancer, diagnosed between 2002 and 2012. Data on cancer characteristics, diagnosis of osteoporosis, prior bisphosphonate exposure and outcome were collected from medical files. ResultsAmong 297 osteoporotic women identified, 145 (49%) were treated with bisphosphonates (alendronate in 90% of the cases) before cancer diagnosis. BP-treated women were significantly older than the BP-naïve ones (67.9 years vs 64.6 years, p = 0.01), but comparable in risk factors and disease characteristics. Over a mean follow up of 5.6 years, nine cases of bone metastases were identified, eight of them among BP-naïve patient (cumulative incidence of 9.9%) and one among BP-treated patients (0.7%). In a multivariable Cox's proportional hazards survival model the use of BP prior to cancer diagnosis was associated with a hazard ratio of 0.04 (95%CI:0.004–0.403, p = 0.006) for bone metastasis. The HR remained similar after further adjustment for tumor stage and cancer therapy. ConclusionsHistory of alendronate use is associated with a lower likelihood of bone metastases in postmenopausal women with early breast cancer. Oral bisphosphonate treatment could be sufficient for reducing the risk of bone metastases.