Oral Bisphosphonate Medication Research Articles

The incidence of medication-related osteonecrosis of the jaw following tooth extraction in patients prescribed oral bisphosphonates.

Aims To determine the incidence of medication-related osteonecrosis of the jaw in patients prescribed oral bisphosphonate medication following dental extraction in a dedicated clinic within the Department of Oral Surgery of King's College Hospital. The effect of factors such as sex, duration of therapy, medical comorbidities and site of extraction, which have previously been reported to significantly affect the risk of developing osteonecrosis of the jaw, was also examined.Materials and methods Data were gathered from the dental records of patients who had extractions over an eight-year period and were included in this retrospective study. Patients with previous or current exposure to intravenous bisphosphonates, denosumab, novel-targeted chemotherapies used in the oncology setting or radiotherapy to the head and neck were excluded from this study.Results The incidence of medication-related osteonecrosis of the jaw following tooth extraction in this group of 652 was 0.8%. A significantly increased risk of developing medication-related osteonecrosis of the jaw was evident in patients prescribed oral bisphosphonates for four years or more (p = 0.02), with an incidence in this group of 1.6%.Conclusion This study demonstrates that, following dental extraction, patients who are prescribed oral bisphosphonates are at risk of developing medication-related osteonecrosis of the jaw and that this risk increases significantly when the patient has been taking the bisphosphonate for four years or more.

Community clinicians’ views about patient adherence to osteoporosis medication

Anecdotal and research evidence suggests that poor adherence and persistence with oral bisphosphonates can result in patients being at increased risk of osteoporotic fractures. Several interventions have been researched for their effectiveness with adherence and persistence, but the most effective method of supporting patients with oral bisphosphonate medications is clinician reviews, generally identified as doctors and nurses. This service evaluation aimed to explore the knowledge and views of multidisciplinary community-based clinicians about adherence and persistence with oral bisphosphonates. The results indicated a positive attitude to a multidisciplinary approach supporting patients to take their medication as prescribed, with recommendations for future research.

Primary non-adherence to bisphosphonates in an integrated healthcare setting

We estimated primary non-adherence to oral bisphosphonate medication and examined the factors associated with primary non-adherence. Nearly 30% of women did not pick up their new bisphosphonate within 60 days. Identifying barriers and developing interventions that address patients' needs and concerns at the time a new medication is prescribed are warranted. To estimate primary non-adherence to oral bisphosphonate medications using electronic medical record data in a large, integrated healthcare delivery system and to describe patient and prescribing provider factors associated with primary non-adherence. Women aged 55 years and older enrolled in Kaiser Permanente Southern California (KPSC) with a new prescription for oral bisphosphonates between December 1, 2009 and March 31, 2011 were identified. Primary non-adherence was defined as failure to pick up the new prescription within 60 days of the order date. Multivariable logistic regression models were used to investigate patient factors (demographics, healthcare utilization, and health conditions) and prescribing provider characteristics (demographics, years in practice, and specialty) associated with primary non-adherence. We identified 8,454 eligible women with a new bisphosphonate order. Among these women, 2,497 (29.5%) did not pick up their bisphosphonate prescription within 60 days of the order date. In multivariable analyses, older age and emergency department utilization were associated with increased odds of primary non-adherence while prescription medication use and hospitalizations were associated with lower odds of primary non-adherence. Prescribing providers practicing 10 or more years had lower odds of primary non-adherent patients compared with providers practicing less than 10 years. Internal medicine and rheumatology providers had lower odds of primary non-adherent patients than primary care providers. This study found that nearly one in three women failed to pick up their new bisphosphonate prescription within 60 days. Identifying barriers and developing interventions aimed at reducing the number of primary non-adherent patients to bisphosphonate prescriptions are warranted.

The preferences and experiences of different bisphosphonate treatments in women with breast cancer

The objective of this study was to examine women's experiences with oral and intravenous (i.v.) bisphosphonate therapy, the impact that treatment had on bone pain and Quality of Life (QoL), and their preferences if choice were available between oral and i.v. administration. This was a prospective study of women with metastatic breast cancer receiving either oral or i.v. bisphosphonate therapy. Semi-structured interview techniques and QoL questionnaires were employed. Participants in the study were interviewed three times, once in person and twice by telephone. A total of 79 patients from eight UK hospitals participated in the study; 35 were receiving oral bisphosphonate medication and 44 i.v. treatments. Self-reported adherence to oral therapy was good although 21% had chosen not to take their drugs at some time. Most had adapted their lifestyle to accommodate oral therapy with 29/37(74%) completely satisfied. However 9/37(24%) expressed dissatisfaction with constraints especially the time required to stand upright after taking their tablets. By 6 months 23/25 (91%) of patients receiving (i.v.) therapies were generally satisfied with the frequency and 22/25 (88%) with the convenience especially if given concurrently with chemotherapy. Overall 25/54 (46%) patients reported improved bone pain scores on the validated FACT-BP scale from baseline to 6 months. Both oral and i.v. therapies have disadvantages but were acceptable to most patients some of whom had reduced bone pain over time. More data regarding acceptability, adherence, and patients' preference for bisphosphonate therapies are required. Until randomised trials demonstrate superior efficacy for one mode of bisphosphonate therapy over another, we suggest offering patients a choice of bisphosphonate therapy.

Predictors of Patients’ Perceived Need for Medication to Prevent Fracture

Adherence with medications to prevent fractures is suboptimal. Patients' perceived need for medication is an important predictor of medication-use behavior. Estimate the associations of patients' perceived need of medication for fracture prevention with objective indicators of fracture risk, patients' concerns about medications, and the quality of the patient-physician relationship. Cross-sectional medical record review and mailed survey. A multivariate path model was used to estimate the associations of predictor variables with perceived need for fracture prevention medication. A total of 1155 individuals were prescribed an oral bisphosphonate medication between January 1, 2006 and March 31, 2007 at a large urban multispecialty clinic in the United States. Trust in the prescribing physician, prevalent vertebral fracture on spine imaging, patients' self-reported susceptibility to and perceived severity of fractures, and medication concerns were independently associated with perceived need for medication. Bone mineral density and fracture history were only weakly associated with perceived need for medication. Trust in the physician was associated with perceived severity of fractures but not with self-reported susceptibility to fractures. Patients' perceptions that their physician communicates openly with them and their satisfaction with their physician's decision-making style are strongly associated with their trust in that physician. Documenting prevalent vertebral fracture may influence patients' perceived need for fracture prevention medication. Patients' trust in their physicians influences perceived need for fracture prevention medication. Patients' perceptions of open physician communication and their satisfaction with their physician's decision-making style are indirectly associated with perceived need for fracture prevention medication.

Association of medication attitudes with non-persistence and non-compliance with medication to prevent fractures

Our objective was to assess the association of self-reported non-persistence (stopping fracture-prevention medication for more than 1 month) and self-reported non-compliance (missing doses of prescribed medication) with perceived need for fracture-prevention medication, concerns regarding long-term harm from and/or dependence upon medications, and medication-use self-efficacy (confidence in one's ability to successfully take medication in the context of their daily life). Non-persistence (stopping medication prematurely) and non-compliance (not taking medications at the prescribed times) with oral medications to prevent osteoporotic fractures is widespread and attenuates their fracture reduction benefit. Cross-sectional survey and medical record review of 729 patients at a large multispecialty clinic in the United States prescribed an oral bisphosphonate between January 1, 2006 and March 31, 2007. Low perceived necessity for fracture-prevention medication was strongly associated with non-persistence independent of other predictors, but not with non-compliance. Concerns about medications were associated with non-persistence, but not with non-compliance. Low medication-use self-efficacy was associated with non-persistence and non-compliance. Non-persistence and non-compliance with oral bisphosphonate medication have different, albeit overlapping, sets of predictors. Low perceived necessity of fracture-prevention medication, high concerns about long-term safety of and dependence upon medication , and low medication-use self-efficacy all predict non-persistence with oral bisphosphonates, whereas low medication-use self-efficacy strongly predicts non-compliance with oral bisphosphonate medication. Assessment of and influence of these medication attitudes among patients at high risk of fracture are likely necessary to achieve better persistence and compliance with fracture-prevention therapies.

Trends and determinants of prescription medication use for treatment of osteoporosis

Trends in the use of different treatments for osteoporosis among the civilian, ambulatory U.S. population are described. Data from the Medical Expenditure Panel Survey (MEPS) were used to estimate osteoporosis prevalence and treatment rates among individuals ages 50 years and older who self-reported having osteoporosis. Specific pharmacologic treatments analyzed included oral and transdermal estrogen and estrogen and progesterone combination products in women, injectable and transdermal testosterone products in men, oral bisphosphonate medications, raloxifene, and nasal calcitonin. Predisposing characteristics included sex, age, education, income, and race. Required characteristics included the use of an oral corticosteroid medication, having a fracture in the current MEPS year, presently smoking, and self-report of fair or poor health status. Self-report of osteoporosis increased steadily from approximately 3.2 million patients in 1999 to 7.2 million patients in 2005. This was associated with an increase of the number of patients who used medication for the treatment of osteoporosis from 2.3 million in 1999 to 5.6 million in 2005. Although medication use increased over time, only 77% of people with osteoporosis reported using medication for the treatment of osteoporosis in the previous year. Only 25.4% of men, 55.6% of blacks, 64.2% of patients without a usual source of health care, and 66.8% of patients who reported their health as fair or poor used medication for the treatment of osteoporosis in the previous year. Although the MEPS data are based on patient self-report, the results from our study suggest that approximately one in four patients with osteoporosis did not receive prescription management for this condition.

Importance of microcracks in etiology of bisphosphonate-related osteonecrosis of the jaw: a possible pathogenetic model of symptomatic and non-symptomatic osteonecrosis of the jaw based on scanning electron microscopy findings

The aim of this study was to evaluate a possible role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) and to discuss an etiological model. Bone samples from 35 patients with ONJ were analyzed. Control samples were taken from five patients with osteomyelitis (OM), ten patients with osteoradionecrosis, seven patients with osteoporosis and bisphosphonate medication without signs of ONJ, and six osteoporotic elderly patients. Samples were examined using scanning electron microscopy. In 54% of the bone samples of patients with ONJ, microcracks were seen. Inflammatory and connective tissue reactions within the microcracks were evident in 82% of the cases, indicating that these cracks were not artificial. In contrast, only 29% of samples from patients with oral bisphosphonate medication without ONJ, no sample from patients with OM, none of the osteoradionecrosis group, and only 17% from patients with osteoporosis showed microcracks. Statistically significant differences could be found between the ONJ group and the group after irradiation and the group with OM, respectively. The evidence of microcracks could be a first step in the pathogenesis of bisphosphonate-related ONJ. The accumulation of these microcracks leads to a situation that could be named "non-symptomatic ONJ". Disruptions of the mucosal integrity may then allow bacterial invasion, leading to jawbone infection with exposed bone, fistulas, and pain. This state could be called "symptomatic ONJ". Furthermore, an assumed local immunosuppression as indicated by various studies could explain the severe courses of therapy-resistant ONJ as regularly observed.

The Role of Surgical Resection in the Management of Bisphosphonate-Related Osteonecrosis of the Jaws

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a poorly understood pathologic entity from the standpoints of its nomenclature, frequency, pathogenesis, and best method of treatment. In particular, numerous recommendations have been made for treatment involving nonsurgical therapy. It is the purpose of this article to specifically examine the success of resection of the necrotic bone in the mandible and maxilla in these patients. We identified 103 sites of BRONJ in 82 patients. Of these sites of osteonecrosis, 32 were in the maxilla and 71 were in the mandible. Of the patients, 30 were taking an oral bisphosphonate medication whereas 52 were taking a parenteral bisphosphonate medication. Resection was performed in 95 sites of osteonecrosis in 74 patients, whereas 8 sites diagnosed in 8 patients were not resected. A total of 27 sites of BRONJ were resected in patients treated with oral bisphosphonates, and 68 sites of BRONJ were resected in patients treated with parenteral bisphosphonates. Of the 95 resected sites, 87 (91.6%) healed in an acceptable fashion with resolution of disease. Of 27 resected sites in patients taking an oral bisphosphonate medication, 26 (96.3%) healed satisfactorily, with refractory disease developing in 1 site. Of 68 resected sites in patients taking a parenteral bisphosphonate medication, 61 (89.7%) healed satisfactorily, with refractory disease developing in 7 sites. All 29 patients (100%) undergoing resection of the maxilla related to either an oral or parenteral bisphosphonate healed acceptably. The 8 patients who had the development of refractory disease did so with a range of 7 to 250 days postoperatively (mean, 73 days). Of the 8 sites of refractory disease, 6 developed after a marginal resection of the mandible for BRONJ. Three sites of new primary disease developed in 2 patients postoperatively. Both patients were taking a parenteral bisphosphonate medication. Histologic examination of the resected specimens identified malignant disease in 4 specimens in 3 patients. Resection of BRONJ permits acceptable healing in patients taking an oral bisphosphonate medication. In addition, resection of BRONJ of the maxilla in patients taking an oral or parenteral bisphosphonate medication follows a predictable course with regard to healing. Resection of BRONJ of the mandible in patients taking a parenteral bisphosphonate medication follows a variable postoperative course, although a high degree of success is realized. Surgeons should consider resection of necrotic bone of the maxilla and mandible that develops in patients taking bisphosphonate medications. In addition, refractory disease can be successfully managed with a more aggressive resection, specifically, a segmental resection of the mandible after a marginal resection of the mandible where refractory disease developed.

Descriptive analysis of concomitant prescription medication patterns from 1999 to 2004 among US women receiving daily or weekly oral bisphosphonate therapy

To improve medication-taking behavior, it is important to identify factors that may contribute to suboptimal compliance and persistence with osteoporosis medications. The purpose of this descriptive analysis was to identify concurrent prescription medication use (number and type) among women receiving daily or weekly oral bisphosphonate therapy. Patient prescription data were collected from November 1999 to June 2004 from a US patient claims database accessed through Wolters Kluwer Health (formerly NDC Health), which represents >65 million patients annually. Women aged >or=50 years who were receiving daily or weekly oral bisphosphonate medication during the study months were included. Concomitant medications were defined based on >or=14 days of prescription supply in the same month as bisphosphonate therapy. Data were examined to determine the frequency with which certain drugs and drug classes were prescribed concomitantly with bisphosphonates. Each study month was treated independently to assess concomitant medication use. Over the study period, the number of female bisphosphonate recipients in the database increased from 78,909 to 250,286. At the end of the study, 16.2%, 12.2%, 8.7%, and 19.1% of bisphosphonate recipients were prescribed 3, 4, 5, or >or=6 concomitant medications, respectively. The most commonly prescribed concomitant drug classes were cholesterol reducers, diuretics, beta-blockers, calcium channel blockers, synthetic thyroid hormones, angiotensin-converting enzyme inhibitors, systemic analgesics/anti-inflammatory drugs, and antispasmodics/antisecretory drugs. From July 2001 until the end of the study, the number of concomitant medications was higher for women receiving daily bisphosphonates than for those receiving weekly bisphosphonates, 4.16 versus 3.77 as of June 2004. In addition, the mean number of concomitant medications prescribed increased with age: in the aged 50 to 64 years cohort, the aged 65 to 74 years cohort, and the aged >or=75 years cohort, the mean number was 3.09, 3.62, and 3.97, respectively, as of June 2004. This analysis suggests that women prescribed bisphosphonates have a high medication burden, with the majority of patients (56%) taking >or=3 concomitant prescription medications.

Differences in persistence among different weekly oral bisphosphonate medications

We evaluated the differences in persistence with weekly oral bisphosphonate therapy according to the initial drug. Persistence to weekly oral preparations remains suboptimal, particularly in patients who receive generic alendronate. Alternative solutions are needed to improve the real life effectiveness of osteoporosis therapies. Poor persistence is widespread with oral osteoporosis (OP) therapy. The objective of this study was to evaluate the persistence among OP patients started on weekly oral bisphosphonates (BP). Patients newly initiated on branded risedronate, branded alendronate, or generic alendronate once weekly were selected from the Régie de l'Assurance Maladie du Québec databases. The cohort included patients with and without a previous OP fracture. The probability and the risk factors for early discontinuation were estimated using Cox regression models. The study cohort included 32,804 patients. After 1 year, a significant difference in persistence on oral BP therapy was found. The patients started on branded risedronate were 11% more likely to stop OP therapy than patients started on branded alendronate. Risk of discontinuation doubled in patients initiated with generic alendronate compared to patients started on branded alendronate. Male gender was associated with a 25% increase risk of early discontinuation. No statistical association was found between previous OP fracture and early discontinuation. This study provides further evidence of poor persistence to newly initiated oral weekly BP therapies, particularly for the patients started on generic alendronate.

The impact of osteoporosis medication beliefs and side-effect experiences on non-adherence to oral bisphosphonates

ABSTRACTObjective: Non-adherence to oral bisphosphonate medications is a pervasive problem that blunts their potential to prevent fractures. Using multivariate modeling, we assessed the unique contribution of six classes of variables as drivers of non-adherence to bisphosphonates: (1) beliefs about osteoporosis and its prescription drug treatment, (2) ratings of the affordability of the prescription osteoporosis medications, (3) evaluations of the convenience of the bisphosphonate dosing frequency, (4) reports of troublesome side effects, (5) ratings of aspects of the bisphosphonate dosing regimen, and (6) risk factors for fracture. These categories of predictor variables were selected for investigation because they have been suggested by clinical-trial, survey, and observational studies in osteoporosis as reasons for non-adherence among patients taking prescription osteoporosis therapy.Methods: Women aged 45 or older who filled a prescription for an oral bisphosphonate in January or February of 2006 were identified through a dispensing database of 3300 US retail pharmacies. Subjects received a mailed pre-notification letter from the retail pharmacy chain informing them that someone would be calling them to invite them to participate in a telephone survey about osteoporosis medications. Trained interviewers used a standardized telephone script to recruit patients. Our definition of adherence was provisionally based on database records across a 7-month period and then cross-validated using patient self-report during the telephone recruitment. We measured beliefs regarding bisphosphonate effectiveness and safety, osteoporosis health concerns, concerns regarding drug costs, dosing frequency convenience, and experienced side effects using multi-item scales. Data were collected by telephone interview. Bivariate analyses were conducted using χ2 and t-tests, and multivariate analyses were conducted using logistic regression.Results: Of the 3274 women contacted for study participation, 1092 (33%) completed the interview and 1015 had analyzable data. Multivariate analyses showed that those most symptomatic in terms of side effects and those with the most skeptical beliefs in drug effectiveness and drug safety had odds ratios for non-adherence of 6.78 (95% CI 4.67–9.86), 5.70 (95% CI 3.65–8.92), and 2.26 (95% CI 1.49–3.42), respectively. In multivariate models, osteoporosis health concerns, dosing frequency convenience, and concerns regarding medication costs were not statistically associated with non-adherence to bisphosphonate therapy.Conclusions: The experience of troublesome side effects and patient beliefs regarding the effectiveness and safety of oral bisphosphonate medications prescribed for them are strongly associated with bisphosphonate non-adherence. Improving adherence to oral bisphosphonates may require providers to solicit and address patients’ medication beliefs and to proactively address side effects. Limitations of our study include: (1) the study sample is not likely to be a national random sample of bisphosphonate users, and (2) some evidence of non-response bias was observed.

Necrosis of the jaws under bisphosphonate therapy

Bisphosphonates are widely used in the treatment of cancer patients with hypercalcemia and bone metastases or in osteoporosis therapy. Current reports have focused on therapy-resistant osteonecrosis of the jaws as a possible side effect of bisphosphonates. Official German drug committees have recently warned about the possibility of these side effects. So far we have experience with 12 patients showing therapy-resistant osteonecrosis of the mandible under bisphosphonate medication, three of whom received oral bisphosphonates for osteoporosis treatment. Presentation of these three cases provides more information on this clinically important side effect of oral bisphosphonate medication, also in osteoporosis therapy.

Oral Bisphosphonates to Treat Disuse Osteopenia in Children With Disabilities

Children with congenital conditions who are nonambulatory have been observed to have pathologic fractures due to disuse osteopenia. Data support the use of intravenous bisphosphonates to treat this in children with disabilities, but there are no data to guide the use of oral bisphosphonate medication. Ten nonambulatory children with disuse osteopenia secondary to either static brain injury or spina bifida were started on alendronate. Investigators completed a chart review of each subject. There were 17 fractures before starting alendronate and 1 fracture in the follow-up period. All children with nociceptive behavior or pain complaints (5/10) had their symptoms resolve after treatment. Despite the presence of gastrointestinal comorbidities (7/10 with a history of gastroesophageal reflux disease, 5/10 taking reflux medication, and 4/10 with PEG tubes), only 1 of the 10 children discontinued the medication secondary to gastrointestinal complaints. This case series offers evidence that disabled nonambulatory children tolerate alendronate, and it may decrease fractures in those at risk from severe disuse osteopenia.