Intravenous Bisphosphonate Administration Research Articles

Correlation between Bone Mineral Density and Progression of Hip Osteoarthritis in Adult Men and Women in Bulgaria—Results from a 7-Year Study

Changes in clinical presentation, radiographic progression (RP), bone mineral density (BMD), bone turnover (BT), and cartilage turnover (CT) markers were compared in two groups of patients with hip osteoarthritis (HOA) over a period of 7 years. Each group consisted of 150 patients, including a control group on standard-of-care therapy (SC) with simple analgesics and physical exercises, and a study group (SG) on standard-of-care therapy supplemented by vitamin D3 and intravenous administration of zoledronic acid (5 mg) yearly for 3 consecutive years. Patient groups were homogenized regarding the following: (1) radiographic grade (RG), including 75 patients with hip OA RG II according to the Kellgren-Lawrence grading system (K/L), and 75 with RG III on K/L; (2) radiographic model (RM), as each of the K/L grades was subdivided into three subgroups consisting of 25 patients of different RMs: atrophic ('A'), intermediate ('I'), and hypertrophic ('H'); (3) gender-equal ratio of men and women in each subgroup (Female/Male = 15/10). The following parameters were assessed: (1) clinical parameters (CP), pain at walking (WP-VAS 100 mm), functional ability (WOMAC-C), and time to total hip replacement (tTHR); (2) radiographic indicators(RI)-joint space width (JSW) and speed of joint space narrowing (JSN), changes in BMD (DXA), including proximal femur (PF-BMD), lumbar spine (LS-BMD), and total body (TB-BMD); (3) laboratory parameters (LP)-vitamin D3 levels and levels of BT/CT markers. RV were assessed every 12 months, whereas CV/LV were assessed every 6 months. Results: Cross-sectional analysis (CsA) at baseline showed statistically significant differences (SSD) at p < 0.05 in CP (WP, WOMAC-C); BMD of all sites and levels of CT/BT markers between the 'A' and 'H' RM groups in all patients. Longitudinal analysis (LtA) showed SSD (p < 0.05) between CG and SG in all CP (WP, WOMAC-C, tTHR) parameters of RP (mJSW, JSN), BMD of all sites, and levels of CT/BT markers for all 'A' models and in 30% of 'I'-RMs (those with elevated markers for BT/CT at baseline and during the observation period). Conclusion: The presence of SSD at baseline ('A' vs. 'H') supported the thesis that at least two different subgroups of HOA exist: one associated with 'A' and the other with 'H' models. D3 supplementation and the intravenous administration of bisphosphonate were the treatment strategies that slowed down RP and postponed tTHR by over 12 months in the 'A' and 'I' RM with elevated BT/CT markers.

Direct Pulp Capping in Osteoporotic Rats Treated with Zoledronic Acid

Background: Osteoporosis is a metabolic bone disease, which impairs and/or delays the regenerative response of calcified tissues. Aim: The aim of this study was to assess the histopathologic response to direct pulp capping in osteoporotic rats that received a preoperative treatment with Zoledronic acid, a bisphosphonate which is currently prescribed for treating osteoporosis. Methodology: Two groups, each with 7 osteoporotic female Wistar rats (n=7) received either an intravenous dose of 100 mg/kg of Zoledronic Acid (Group 1) or the same volume of sterile saline (Group 2). One week later, the pulps of the right and left mandibular first molars of each animal were exposed and capped with Biodentine. After 20 days the animals in Group 1 received a second similar dose of Zoledronic acid and Group 2 a similar second dose of sterile saline. After 38 days the animals were euthanized and a total of 28 teeth (14 per group) were prepared for histologic analysis evaluating the following parameters: inflammation, reparative hard tissue formation, odontoblast cell layer organization, fibrous tissue, and necrosis. Results: In Group 1 the reparative hard tissue formation was scarce with preservation of the pulp tissue structure and the odontoblast cell layer. In Group 2 the pulp was preserved as a fibrous reticular-like structure. Reparative hard tissue formation was totally absent and the odontoblast cell layer was atrophic or absent. In both groups, no inflammation or necrosis was observed. Conclusions: The intravenous administration of Bisphosphonate (Zoledronic Acid) did not promote pulp healing in osteoporotic rats.

ODP112 Post-infusion ECG Changes in Patients Receiving Intravenous Bisphosphonates: a Systematic Review and Meta-Analysis

Abstract Bisphosphonates are the first-line treatment for several bone and mineral disorders. Randomized trials and cohort studies have reported increased rates of atrial fibrillation in patients receiving bisphosphonates, however, uncertainty remains as to whether other electrical disturbances are precipitated by bisphosphonates. We aimed to review the literature for studies reporting ECG findings in patients receiving intravenous bisphosphonates for any indication. We searched MEDLINE and EMBASE on 06/01/2022 for studies reporting ECG parameters following administration of intravenous bisphosphonates. We excluded studies that only reported atrial fibrillation, case reports and animal or cell-based studies. Study quality was assessed using the Newcastle-Ottawa Scale. Continuous data were meta-analysed if reported in at least two studies. Random-effects models were fitted and reported as standardized mean difference (SMD) with 95% confidence intervals (95%CI). Heterogeneity was determined by the I 2 statistic. All data were computed using R (4.1.1). We found 1,123 records of which six met our inclusion and exclusion criteria, of which five had data for meta-analysis. Studies were of low to moderate quality. Five studies used zoledronic acid while one study used pamidronate. Most studies [n=4] were conducted in postmenopausal women with osteoporosis, one study was conducted in patients with bone metastases and one study was conducted in children with cerebral palsy and osteoporosis. Most studies [n=4] reported outcomes in the sub-acute (&amp;gt;24 hours) phase. Study populations ranged from n=15 to n=116. There was a significant difference in QTc dispersion (SMD= -0.456 milliseconds [95%CI: -0.800 to -0.113]; I 2 = 0%; n= 67 patients; k= 2 studies) but no differences in heart rate, P wave (maximum), P wave (minimum), P wave dispersion, PR interval, QRS duration, QTc (maximum), QTc (minimum), or QTc. The correlation between pre- and post-infusion QTc dispersion was rho= 0.981 (p=0.866). Results were unchanged when analysing studies reporting acute or sub-acute phase ECG changes. Overall, there is insufficient and low quality evidence to support an association between intravenous bisphosphonate administration and acute phase dysrhythmias. These data underscore the importance of performing a pre-infusion ECG to evaluate potentially unreported conduction abnormalities. Presentation: No date and time listed

Computed Tomography-Based Investigation on the Effects of Intravenous Bisphosphonate Administration on Tooth Growth in a Minipig Animal Model.

Background and Objectives: The objective of this study was to evaluate the effects of bisphosphonate (BP) administration on tooth growth, using CT-data of a minipig animal model investigation. Materials and Methods: Tooth growth was evaluated in minipigs, with eight animals receiving weekly zoledronate (ZOL) and three animals serving as the control group. Tooth growth was evaluated at the right 2nd molar (M2) in the maxilla. A computed tomography-based measuring method was applied to evaluate tooth growth in the coronal-apical, buccal-oral and mesial-distal axis. Results: ZOL-administration was found to impact tooth growth in all evaluated measuring axes, with the highest effect observed in the coronal-apical axis. Conclusions: Detrimental effects of BP administration on growing teeth have been reported by a number of investigators. The results of this investigation demonstrate that intravenous ZOL affects the growth of the whole tooth within a short period of administration. With BPs being administered to a growing number of pediatric patients, further studies should be conducted to qualify and quantify the effects of BPs on developing teeth.

Menopausal osteoporosis in the practice of a gynecologist

Osteoporosis represents a great healthcare challenge due to an increased risk of fragility fractures that significantly decreases quality of life, shortens life expectancy, and looms as an onerous burden on both the social environment of patients and society as a whole. Osteoporotic fractures can’t be prevented without early diagnosis of low bone mineral density in people at risk. Unfortunately, the population at risk of osteoporosis is not covered by the periodic health examination program in real practice, and involving doctors of different specialties in the prevention and treatment of this disease is one of the options for addressing the challenge. As the risk of osteoporosis is associated with age and estrogen deficiency in women, the gynecologist can and should assume responsibility for the formation of risk groups, monitoring and timely recommendations on preventive and therapeutic actions. The gynecologist’s possibilities should not be reduced solely to recommendations for correcting lifestyle and prescribing menopausal hormone therapy. Antiresorptive agents of the first-line osteoporosis therapy may also be included in the gynecologist’s drug arsenal. Among them are the most commonly used bisphosphonates that are characterized by a good efficacy and safety profile during the long-term use. However, oral administration of bisphosphonates is associated with low compliance due to adverse reactions and the need for strict observance of the rules for their administration. In contrast, intravenous administration of bisphosphonates improves compliance and allows to ensure the optimal treatment outcome. Ibandronate intended for intravenous bolus administration once every three weeks for 5 years is one of the possibilities of using parenteral bisphosphonate therapy in the practice of gynecology.

Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients.

It is yet unknown whether the intravenous administration route alone can fully account for the exacerbation of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to identify the potential role of the bisphosphonate (BP) administration route as an independent prognostic factor for non-cancerous, stage III MRONJ patients. Bone samples were retrospectively obtained from two groups of osteoporosis patients who underwent surgery for the treatment of stage III MRONJ. Among the subjects, 10 had a history of only oral BP consumption and 10 of intravenous (IV) BP administration. The samples were assessed for osteoclast morphology and immunohistochemical expression of the receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and potassium calcium-activated channel subfamily N member 4 (Kcnn4). Although the osteoclasts derived from both groups exhibited no significant differences in the mean quantity, diameter, and nuclearity, significantly attenuated tartrate-resistant acid phosphatase activity was noted among the IV BP-induced MRONJ bones compared to those of the oral BP group. Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Our results indicate the potential of the BP administration route as an independent prognostic factor for advanced-stage MRONJ, regardless of the dosage or indication for which the BP was prescribed.

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.

Absence of callus two months after surgical fixation of a hip fracture in a patient with Paget’s disease

Introduction: Paget’s disease is a disorder of bone remodeling that typically begins with excessive bone resorption followed by an increased bone formation. This misbalance into new bone formation process and osteoclastic activity leads to a structurally disorganized mosaic of bone, which is mechanically weaker, larger, less compact, more vascular, and more susceptible to fracture than normal adult bone. Case description: We report the case of a 66-year-old woman who came to us due to a nonunion two months after surgical fixation of the right femoral neck fracture. Upon admission, a pelvic radiograph revealed right femoral neck fracture with osteolysis. A biopsy of the greater trochanter demonstrated histopathological patterns of Paget’s disease. After the surgical intramedullary metallic osteosynthesis of the femoral neck, the patient left the hospital suggested for physiotherapeutic treatment with quadriceps isometric exercises. After 2 months, the pelvic X-ray revealed absence of callus, and the patient was referred to a rheumatologist. Intravenous administration of bisphosphonates (zoledronic acid), as well as oral intake of calcium and vitamin D has been prescribed. Conclusions: Besides rheumatologists and endocrinologists, clinical recognition of Paget’s disease is also very important for orthopedic surgeons in order to achieve better results for patients suffering from any kind of major osteoporotic fracture.

Medication-related osteonecrosis of the jaw in a minipig model: Parameters for developing a macroscopic, radiological, and microscopic grading scheme

ObjectivesTo devise a macroscopic, radiological, and histological scale for assessing pathological changes associated with medication-related osteonecrosis of the jaw in a minipig model. Materials and methodsMedication-related osteonecrosis of the jaw was induced in Göttingen minipigs by weekly intravenous administration of bisphosphonate (zoledronic acid) combined with a tooth extraction procedure. Controls either did not receive zoledronic acid or did not undergo tooth extraction. After 20 weeks, minipigs were euthanized and underwent computed tomography and micro-computed tomography scanning. The mandible underwent additional histological examination. ResultsThe most consistent macroscopic findings in animals that had developed bisphosphonate-related osteonecrosis of the jaw (BRONJ) were necrotic, denuded bone, and formation of fistula and pus. Under radiological examination, impaired extraction socket healing, decrease in attenuation of bone beneath the extraction site, and periosteal reaction were observed. Under histological examination, demineralization of the extracellular bone matrix, denuding of bone, and osteonecrosis were recorded. ConclusionThese parameters were used to develop a scoring system for grading BRONJ.

CT imaging features of antiresorptive agent-related osteonecrosis of the jaw/medication-related osteonecrosis of the jaw.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ)/medication-related osteonecrosis of the jaw (MRONJ) include both bisphosphonate-related osteonecrosis of jaw (BRONJ) and denosumab-related osteonecrosis of jaw (DRONJ). The purpose of this study is to study radiological characteristics of ARONJ/MRONJ. These imaging features may serve as one useful aid for assessing ARONJ/MRONJ. CT scans of 74 Japanese patients, who were clinically diagnosed by inclusion criteria of ARONJ/MRONJ, obtained between April 1, 2011 and September 30, 2016, were evaluated. We investigated the CT imaging features of ARONJ/MRONJ, and clarified radiological differentiation between BRONJ and DRONJ, BRONJ due to oral bisphosphonate administration and due to intravenous bisphosphonate administration, BRONJ with respective kinds of medication, BRONJ with long-term administration and short-term administration, BRONJ with each clinical staging respectively. Fisher's exact test, χ2 test, Student's t-test and analysis of variance were performed in the statistical analyses. Unilateral maxillary sinusitis was detected in all patients with upper ARONJ/MRONJ (100%). DRONJ showed large sequestrum more frequently than BRONJ (3/4, 75 vs 3/35, 8.6%, p < 0.05). DRONJ showed periosteal reaction more frequently than BRONJ (4/10, 40 vs 7/65, 10.1%, p < 0.05). Patients of BRONJ resulting from intravenous bisphosphonate administration showed larger and more frequent buccolingual cortical bone perforations than BRONJ resulting from oral bisphosphonate administration (7/8, 87.5 vs 11/30, 36.7%, p < 0.05). There was no significant correlation between CT findings and respective kinds of medication, long/short-term administration, clinical stages of BRONJ. ARONJ/MRONJ has characteristic CT image findings which could be useful for its assessment.

Bone targeted therapies in advanced breast cancer

Bone targeted therapies are of increasing importance, not only for bone health in the clinical course of breast cancer, but recently also in the adjuvant setting as preventative, anticancer and prognosis-improving agents. It is well established that women with advanced breast cancer receive bisphosphonates or denosumab to prevent therapy-related osteoporosis. As many as 70% of these patients suffer from bone metastases and receive bone targeted agents in order to prevent skeletal related events (SREs), which are debilitating or diminish the quality of life. A number of trials provided guidance, identifying zoledronic acid as the most efficient bisphosphonate, showing that intravenous bisphosphonate administration is superior to oral intake and illustrating the different safety profile of denosumab, which has been reported to be more beneficial than zoledronic acid in delaying the time to first and subsequent (multiple) SREs. New studies have suggested that bone targeted therapies improve rates of overall survival and contribute to preventing recurrence of breast cancer at all sites. Increased bone turnover is both a consequence and a driving factor for tumour growth, expansion, formation of bone lesions and potentially also activation of disseminated tumour cells, leading to bone relapses. We review the current knowledge of bone targeted therapies in advanced breast cancer, with a focus on new insights into their bone-preserving and antitumor activity. Current guidelines, pathology of bone metastasis, mode of action and common side effects have been summarised. We also elaborate on the use of bisphosphonates and denosumab in early breast cancer, during adjuvant therapy with aromatase inhibitors.

Osteonecrosis of the Mandible Associated with Bisphosphonate Treatment

This study analyzes 35 patients with bisphosphonate-related osteonecrosis of the mandible (BRONJ) diagnosed and treated in the Oral and Maxillofacial Surgery Clinic of St. Spiridon Hospital Iasi. The inclusion criteria were in line with the recommendations of the American Association of Oral and Maxillofacial Surgery (AAOMS). The analysis included the underlying disease, the type of bisphosphonate and the route of administration, the duration of treatment as well as the osteonecrosis triggering factor. Surgery was consistent with the condition of the disease, ranging from debridement and sequestrectomy to alveolar marginal and even segmental bone resections. The results of the study were similar with the data from the literature suggesting that the condition is more common in the lower jaw compared to the upper jaw, and the main risk factors are dental extraction and intravenous bisphosphonate administration.

Innovation of bisphosphonates for improvement of adherence.

Bisphosphonates are standard medicine for treatment of osteoporosis, and have been inovated to overcome complicated rules for their appropriate administration or their poor intestinal absorption. Not only weekly but also monthly oral bisphosphonates have been available. Furthermore, we are now allowed to choose intravenous administration of bisphosphonates for osteorporosis. Good persistance and adherence is another critical and essential issue to be solved to achive the aim of osteoprosis treatment with bisphosphonates. Variable formulations of bisphosphonate are now able to bring patients closer to a goal of reduction in fragile fracture due to osteoporosis.

Medication-Related Osteonecrosis of the Jaws (MRONJ) Induced by Incompatible Complete Removable Denture: A Case Report

Multiple myeloma is a malignant, hematological neoplasia affected plasma cells. It causes anemia, leads to increased susceptibility to infections by compromising immune response and severe pain is raised as a result of osteolytic lesions. For medical therapy of this condition, bisphosphonates (BPs) can be prescribed. Despite its great benefits in Multiple Myeloma (MM), in particular intravenous administration of BPs can lead to Medication-related osteonecrosis of the jaws (MRONJ). A 61-year-old female patient refers to our department for complaint of difficulty on usage of her prosthesis. In medical history, it was learned that her chemotherapy for multiple myeloma has been continued for 5 years and skull radiographs showed characteristic punched-out lytic lesions. With clinical and radiological examinations, this condition diagnosed as Stage II MRONJ. The aim of this study is to report the case of MRONJ within the reason of incompatible prosthesis by this way to be directive about preventive management.

Exposed necrotic bone in 183 patients with bisphosphonate-related osteonecrosis of the jaw: Associated clinical characteristics.

BackgroundThe main objective of our study was to identify oral symptoms and signs most likely to be associated with the exposure of necrotic bone in bisphosphonate-related osteonecrosis of the jaw (BRONJ).Material and MethodsThe study group consisted of 183 patients with BRONJ. We recorded data on the underlying disease, bisphosphonate used, location of osteonecrosis, symptoms, pain, fistula development, suppuration, infection, exposed necrotic bone, and BRONJ stage.ResultsThe mean age of the patients was 68.22 ± 12.19 years. The sample included 118 (64.5%) women. Breast cancer and multiple myeloma were the most common underlying diseases, and 50 patients received oral bisphosphonates for osteoporosis. Dental extractions (69.4%) and mandibular location (74.3%) predominated. The only two variables influencing the possibility of necrotic bone exposure were intravenous bisphosphonate administration and the presence of an intraoral fistula (p >0.05).ConclusionsIntravenous bisphosphonate use and intraoral fistula presence were associated with a major predisposition to bone exposure in patients with BRONJ. Key words:Bisphosphonate, Osteonecrosis, Jaw.

Intravenous pamidronate versus oral and intravenous clodronate in bone metastatic breast cancer: a randomized, open-label, non-inferiority Phase III trial.

PurposePatients with metastasized breast cancer often suffer from discomfort caused by metastatic bone disease. Thus, osteoprotection is an important part of therapy in breast cancer metastasized to bone, and bisphosphonates (BPs) are a major therapeutic option. In this study, our objectives were to compare the side effects of oral versus intravenous BP treatment and to assess their clinical effectiveness.Patients and methodsIn this prospective randomized, open-label, non-inferiority trial, we enrolled breast cancer patients with at least one bone metastasis and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were randomly assigned to one of the three treatment groups: A, 60 mg pamidronate intravenously q3w; B-iv, 900 mg clodronate intravenously q3w; and B-o, 2,400 mg oral clodronate daily. Assessments were performed at baseline and every 3 months thereafter.ResultsBetween 1995 and 1999, 321 patients with confirmed bone metastases from breast cancer were included in the study. At first follow-up, gastrointestinal (GI) tract side effects were most common, and adverse effects on the GI tract were more frequent in the oral treatment group (P=0.002 and P<0.001, respectively). There were no statistically significant differences among the treatment cohorts for other documented side effects (skin, serum electrolytes, urinary tract, immune system, and others). No significant differences in clinical effectiveness of BP treatment, as assessed by pain score, were detected among the groups; however, pathologic fractures were more effectively prevented by intravenous than oral BP administration (P=0.03). Noncompliance rates were similar among the study cohorts.ConclusionWe conclude that oral BP treatment is significantly associated with higher rates of adverse GI side effects. Additionally, our data indicate that intravenous BP administration is more effective than oral treatment in prevention of pathologic fractures; hence, oral administration should be considered with caution.

Identification of Risk Factors for Bisphosphonate-Associated Atypical Femoral Fractures and Osteonecrosis of the Jaw in a Pharmacovigilance Database.

Atypical femoral fractures (AFs) and osteonecrosis of the jaw (ONJ) are well-known adverse drug reactions (ADRs) associated with bisphosphonates. To prevent these ADRs and to aid in the search for pathogenic mechanisms, knowledge of risk factors can be helpful. To identify risk factors for bisphosphonate-related ONJ and AF. In this case-control study of reports of bisphosphonate-related ADRs from February 16, 1984, to October 16, 2013, in the Swedish national database of ADRs, we compared characteristics for cases of ONJ (n = 167) and AF (n = 55) with all other bisphosphonate-related ADRs (n = 565) with regard to demographic variables, clinical characteristics, and concomitant drug treatments. We adjusted for multiple comparisons with Bonferroni correction. Time to onset of ADRs differed statistically significantly between cases of AF and controls (2156 vs 111 days). For ONJ versus controls, differences were statistically significant for time to onset (1240 vs 111 days), intravenous administration (40% vs 20%), dental procedures (49% vs 0.2%) and prostheses (5% vs 0%), cancer disease (44% vs 12%), multiple myeloma (21% vs 1%), rheumatoid arthritis (14% vs 5%), and treatment with antineoplastic agents and oxycodone. These results lend further evidence to previously identified risk factors for ONJ-that is, intravenous bisphosphonate administration; invasive dental procedures and dental prostheses; cancer disease, in particular multiple myeloma; and possibly, long-term bisphosphonate treatment. A putative further risk factor is rheumatoid arthritis. Only long-term bisphosphonate treatment was more common among AF cases. The lack of overlap of risk factors between ONJ and AF suggests different pathogenic mechanisms.

69-Year-Old Woman With Confusion and Fatigue

Resident in Internal Medicine, Mayo School of Graduate Medical Education, Rochester, MN (H.M.K.); Advisor to resident and Consultant in Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN (A.E.K.). A 69-year-old woman presented to her primary care physicianwith a 4-day history of fatigue and dizziness. She was 45 minutes late for her appointment because she had trouble driving to the office. She reported no motor or sensory deficits but had difficulty with coordination. Review of systems was positive for dysuria and urinary frequency. She did not have fever, chills, weight or appetite changes, respiratory, cardiac, or gastrointestinal symptoms, or recent head trauma. The patient’s medical history was remarkable for hypertension, hyperlipidemia, type 2 diabetes mellitus, osteoporosis, and gastroesophageal reflux disease. Medications included metoprolol tartrate, lisinopril with hydrochlorothiazide, lovastatin, cholecalciferol, and as-needed calcium carbonate. She had smoked half a pack of cigarettes per day for 40 years but had quit smoking 6 years previously. She didnot use alcohol or illicit drugs. On examination, the patient was afebrile with a blood pressure of 104/67 mm Hg, heart rate of 76 beats/min, respiratory rate of 17 breaths/min, oxygen saturation of 94% while breathing room air, and body mass index (calculated as weight in kilograms divided by height inmeters squared) of 39 kg/m. Shewas alert and oriented to person, place, and time. Her speech was dysarthric, and she had difficulty following simple commands. Her coordination was impaired with symmetric dysmetria on finger-to-nose testing, heel-kneeshin testing, and rapid alternating movements. Cranial nerves II through XII were intact. Results of motor and sensory examinations were within normal limits. Reflexes were symmetric. Lymph node, thyroid, cardiac, respiratory, gastrointestinal, musculoskeletal, and skin examinations identified no abnormalities.

A comparative study between intravenous and oral alendronate administration for the treatment of osteoporosis.

It has recently been reported that bisphosphonates are the most common treatment for osteoporotic patients. However, they are many problems, including poor bioavailability and adherence, as well as adverse drug reactions. Therefore, intravenous administration of bisphosphonates has been developed to resolve these problems. In Japan today, alendronate and ibandronate have been approved for intravenous administration, and they have advantages, such as good adherence and better gastrointestinal tolerability, compared to oral administration. We attempted to confirm the effects of administration of intravenous alendronate, which is not inferior to oral administration, for osteoporotic patients in earlier research. 200 consecutive Japanese over 70 years-old postmenopausal women who visited the first author’s orthopedic clinic and had femoral neck or lumbar spine bone mineral density (BMD) values more than 2.5 SD lower than the reference values were randomly enrolled in this study. 100 subjects were recruited for administration of intravenous alendronates because of their poor adherence, no respond of treatment status, and gastrointestinal adverse effects. Furthermore, 10 of these subjects were excluded due to discontinuation, and a total of 90 subjects were eligible for the intravenous group. The remaining 50 patients received oral alendronate. The present study also showed no significant difference between intravenous and oral administration with respect to BMD, biochemical bone turnover markers, and the incidence of fractures. These results show that intravenous administration of alendronate is not inferior to oral alendronate for the treatment of osteoporosis. Therefore, intravenous administration of alendronate can be recommended if patients do not tolerate or adhere to oral bisphosphonates.

Evaluation of dental implants as a risk factor for the development of bisphosphonate-related osteonecrosis of the jaw in breast cancer patients.

It remains unclear whether dental implants are a risk factor for the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We retrospectively evaluated the status of dental implants in patients given intravenous bisphosphonates (BPs) in a breast cancer cohort to elucidate the risk for BRONJ at the implant site. We established a BRONJ oral monitoring program for 247 breast cancer patients given intravenous BP in our institution. The 3-year cumulative incidence rate was determined. The systemic and local risk factors of 44 patients who completed comprehensive oral examinations were evaluated by logistic regression analysis. The 3-year cumulative incidence rate of the 247 patients was 0.074% (8/247, 95% CI 0.0081-0.014). In the 44 orally examined patients, 6 (13.6%: 6/44) had dental implants. Of these 6 patients, 1 developed BRONJ at the implant site. There were no significant differences in the age, total BP treatment period, number of residual teeth, time of regular oral monitoring, oral hygiene level, or dental implant insertion. Although a case of ONJ was identified, dental implants which were inserted before intravenous BP administration were not a risk factor for the development of ONJ in breast cancer patients.