Tooth extraction in osteoporotic patients taking oral bisphosphonates

Summary

This prospective study compares two different surgical protocols with different degrees of invasiveness for tooth extraction in patients treated with oral bisphosphonates (BPs). No intraoperative complications were observed in either of the two groups, and there was no evidence of postoperative bisphosphonate-associated osteonecrosis of the jaw in any of the extractions in the study group at follow-up (1,480 extractions). According to our data, dental extraction seems to be safe in osteoporotic patients treated with oral bisphosphonates.

Introduction

Oral bisphosphonates are drugs commonly prescribed for the treatment of osteoporosis and other resorptive bone diseases. Since 2003, there have been numerous publications relating bisphosphonate-related osteonecrosis of the jaw (BRONJ) in patients using oral bisphosphonates, such as alendronate and risedronate. Most of the BRONJ cases reported in literature show a strong correlation with dental pathologies, dental extractions, and/or oral surgical procedures.

Methods

This study was conducted on 700 consecutive patients treated with oral bisphosphonates who underwent dental extractions. A total of 1,480 extractions were involved: 864 in the mandible and 616 in the maxilla. The patients were assigned randomly to one of two groups: 334 were treated with delicate surgery and closure by primary intention (Protocol A), and the other 366 were treated with nontraumatic avulsion and closure by secondary intention (Protocol B). All patients were administered with antibiotics coverage.

Results

Seven hundred patients with required removal of compromised teeth were included in the study. No intraoperative complications were observed in either of the two groups, and there was no evidence of postoperative bisphosphonate-associated osteonecrosis of the jaw in any of the extractions in the study group at follow-up (1,480 extractions).

Conclusions

The findings of this prospective study indicate that both suggested protocols for tooth extraction in patients treated with oral BPs can provide a predictable treatment outcome (100 % success). Therefore, because atraumatic surgery is more comfortable for patients, we suggest the adoption of Protocol B, which limits trauma to both the soft and hard tissues.     

The use of Ligasure™ haemorrhoidectomy in patients taking oral anticoagulation therapy

OBJECTIVES: To assess the safety of Ligasure haemorrhoidectomy in treating patients on long-term anticoagulation therapy. METHOD: Three patients taking warfarin underwent Ligasure haemorrhoidectomy for prolapsing haemorrhoids. RESULTS: Each had a successful procedure without complications. CONCLUSION: Ligasure haemorrhoidectomy can be safely performed in anticoagulated patients and reduces in-patient hospital stay.     

Response of renal transplanted patients to oral calcium load

In a previous study we demonstrated that cyclosporin-treated renal transplanted patients have a reduced 1,25(OH)2D3 synthesis in comparison with azathioprine-treated transplanted patients. To assess the impact of this defect on intestinal calcium transport we compared the plasma calcium variation and the urinary calcium excretion in 14 cyclosporin-treated and in 12 azathioprine-treated patients, in fasting conditions and 4 hours after an oral calcium load (1 g). In ten cyclosporin patients we also correlated cyclosporin plasma values with plasma 1,25(OH)2D3 values before and after a 25(OH)D3 oral load. After the oral calcium load, plasma and urinary calcium increased significantly in the azathioprine group, while remaining unchanged in the cyclosporin group. A negative correlation between plasma concentrations of cyclosporin and the increment in 1,25(OH)2D3 after 25(OH)D3 oral load was also observed. Thus, our data suggest that cyclosporin impairs 1-alpha hydroxylase activity and alters the response to an oral calcium load.     

Outcomes of placing dental implants in patients taking oral bisphosphonates: a review of 115 cases.

PURPOSE: In recent years, numerous cases of bisphosphonate-associated osteonecrosis of the jaw have been reported involving both intravenous and oral therapy regimens. The majority of these cases have involved intravenous bisphosphonates. Subsequently, drug manufacturers and the US Food and Drug Administration issued warnings about possible bisphosphonate-associated osteonecrosis of the jaw. The American Dental Association and the American Association of Oral and Maxillofacial Surgeons assembled expert panels to formulate treatment guidelines. Both panels differentiated between patients receiving bisphosphonates intravenously and those receiving the drugs orally. However, the recommendations were based on limited data, especially with regard to patients taking oral bisphosphonates. We wanted to ascertain the extent to which bisphosphonate-associated necrosis of the jaw has occurred in our dental implant patients. We also wanted to determine whether there was any indication that the bisphosphonate therapy affected the overall success of the implants as defined by Albrektsson and Zarb. PATIENTS AND METHODS: We identified 1,319 female patients over the age of 40 who had received dental implants at Montefiore Medical Center between January 1998 and December 2006. A survey about bisphosphonate therapy was mailed to all 1,319 patients. Responses were received from 458 patients of whom 115 reported that they had taken oral bisphosphonates. None had received intravenous bisphosphonates. All 115 patients were contacted and informed about the risk of bisphosphonate-associated osteonecrosis of the jaw. Seventy-two patients returned to the clinic for follow-up clinical and radiological evaluation. RESULTS: A total of 468 implants were placed in the 115 patients who reported that they had received oral bisphosphonate therapy. There is no evidence of bisphosphonate-associated osteonecrosis of the jaw in any of the patients evaluated in the clinic and those contacted by phone or e-mail reported no symptoms. Of the 468 implants, all but 2 integrated fully and meet criteria for establishing implant success. Implant success rates were comparable for patients receiving oral bisphosphonate therapy and those not receiving oral bisphosphonate therapy. CONCLUSIONS: Guidelines for treatment of dental patients receiving intravenous bisphosphonate treatments should be different than for patients taking the oral formulations of these medications. In this study, oral bisphosphonate therapy did not appear to significantly affect implant success. Implant surgery on patients receiving bisphosphonate therapy did not result in bisphosphonate-associated osteonecrosis of the jaw. Nevertheless, sufficient evidence exists to suggest that all patients undergoing implant placement should be questioned about bisphosphonate therapy including the drug taken, the dosage, and length of treatment prior to surgery. For patients having a history of oral bisphosphonate treatment exceeding 3 years and those having concomitant treatment with prednisone, additional testing and alternate treatment options should be considered.     

'Pulse' oral calcitriol in uraemic patients: rapid modification of parathyroid response to calcium.

We performed dynamic parathyroid function tests, with generation of parathyroid hormone/ionized calcium (PTH/iCa) response curves, obtained during sequential hypercalcaemic and hypocalcaemic dialysis, on six haemodialysis patients before and after 4-weekly 'pulse' doses of oral calcitriol. There were no significant changes in the pretreatment, 2-week and 4-week values of blood ionized calcium, serum total calcium, phosphate, and alkaline phosphatase. PTH decreased significantly after 4 weeks of treatment with calcitriol (P less than 0.03), and the post-treatment PTH/iCa curves were all displaced leftwards and downwards, indicating a marked inhibitory effect of calcitriol on parathyroid responsiveness across and beyond the physiological range of calcaemia. The mean shift of the PTH/iCa relationship was equivalent to a reduction of iCa of 0.2 mM for any given concentration of PTH, and conversely to a 70% reduction of PTH for any given blood iCa. The results suggest that wide spacing of oral 'pulse' doses of calcitriol can achieve favourable modification of the PTH/iCa relationship, and that dosing interval and dose size, rather than route of administration, may be the major determinants of the previously reported superiority of intravenous over daily oral calcitriol regimens.     

Classification of idiopathic hypercalciuric patients by isotopic calcium absorption: A comparison with oral calcium tolerance test

Summary To test the accuracy of calcium tolerance test in estimating calcium absorption, we have measured the radioactive calcium absorption (expressed as Fx) in 27 patients with IH and renal calcium stones. The results of this test were compared with those of a standard oral calcium tolerance test. Although only seven of nine AH patients displayed normal fasting calcium excretion, they all displayed Fx values above normal and a normal parathyroid activity. Conversely, only 5 of our 18 RH patients demonstrated a hyperabsorption of radioactive calcium and an elevation in iPTH and cAMP above normal limits, yet all of them showed an increased calciuric response to an oral calcium challenge. Calcium absorption was inversely related to iPTH (r=−082;P<0.001) and cAMP (r=−064P<0.05) in AH, but directly proportional to these parameters (r=0.62P<0.001 andr=0.46P<0.05, respectively) in RH patients. In view of these results, two ratios, iPTH/Fx and cAMP/Fx were used to discriminate between the two groups of patients. Both ratios were over normal limits in all RH patients and within normal range in all but one AH patient. Furthermore, no overlap was found between the two groups. Conversely, we were unable to completely separate AH from RH subjects on the basis of the oral calcium tolerance test, since in both groups the fasting and the absolute (or percentage) changes in urinary calcium, cAMP and blood iPTH levels following oral calcium loading, overlapped in each instance. The result of this study indicates that two indices, iPTH/Fx and cAMP/Fx, may prove particularly useful in differentiating AH from RH patients. Furthermore, since only a subgroup of patients with an abnormal calciuric response to an oral calcium load manifest an increase in calcium absorption, it is concluded that the calcium tolerance test overestimates calcium absorption in IH. Supported in part by Grant No. 5T32 AM0703310     

Urinary cAMP and calcium excretion in the fasting state and their response to oral calcium loading in patients with calcium urolithiasis

Fifty-two patients with idiopathic calcareous urolithiasis (ICU) were studied with an oral calcium loading test. Twenty-one subjects were normo-calciuric with no other detectable abnormalities (NDA). Of 31 patients with hypercalciuria, 16 had elevated fasting urinary calcium excretion (UCaE) (HFC), and 15 had normal UCaE (NFC). The fasting UCaE was significantly higher and the theoretical renal threshold for phosphate (TmPO4) was significantly lower in ICU patients as compared to 19 control individuals. The mean post oral calcium loading (Post Ca) UCaE rose significantly in hypercalciuric patients compared with control subjects; however, only 18/31 (58 per cent) had values above the normal range. There was no correlation between the fasting UCaE and either the immunoreactive parathyroid hormone (iPTH) or nephrogenous cAMP (ncAMP) in ICU patients. The fasting ncAMP was normal in all subjects with ICU and 7 of 52 subjects had elevated fasting iPTH values. When ranked according to the fasting UCaE value, ICU patients formed a continuum in which the NDA and HFC groups represented the extremes. It is concluded that the responses to oral Ca loading serve no useful role in the identification of an individual ICU patient either in terms of the pathogenetic subgroup or in the differentiation from normal controls.     

Critical appraisal of oral calcium load test for indirect assessment of intestinal calcium absorption.

Two methods of oral calcium load or tolerance test for the indirect assessment of calcium absorption were compared. In 16 patients in whom the diagnosis of absorptive hypercalciuria was made independently, an exaggerated urinary total calcium excretion during four hours following calcium load, indicative of increased calcium absorption according to the method of Pak et al., was found in 15 patients. An abnormally high increment in urinary calcium during third and fourth hours post-calcium load, suggestive of enhanced calcium absorption by the criteria of Broadus et al., was encountered in 14 patients. However, an exaggerated urinary total calcium following calcium load was found in all 7 patients with renal hypercalciuria, whereas only 4 were shown to have an enhanced increment in calcium excretion. It is concluded that both methods are equally reliable in the detection of increased calcium absorption in absorptive hypercalciuria. However, the technique of Broadus et al. is probably superior to that of Pak et al. in the disclosure of increased calcium absorption in renal hypercalciuria.     

Albumin-corrected calcium and ionized calcium in stable haemodialysis patients.

BACKGROUND: It is ionized calcium that is physiologically active and under homeostatic control; however, total calcium is more conveniently measured. Formulae for correction of calcium to account for albumin binding have not been validated in a dialysis setting. METHODS: We measured ionized calcium simultaneously with total calcium (t[Ca]), albumin, total protein and pH before dialysis in 50 stable outpatients and convalescent inpatients. RESULTS: Although 92% of patients were taking calcium supplements and 70% taking alphacalcidol, 11 patients (22%) had ionized hypocalcaemia. To facilitate comparison of calculated ionized calcium, measured total calcium (t[Ca]), and 'corrected' calcium (c[Ca]), with the criterion measure of ionized calcium, all measurements were converted to z scores, standardized on the normal range for each variable. Results are expressed as intraclass correlation coefficients (ICC: 0, all differences are due to error; 1, all differences are due to between patient variation). CONCLUSIONS: None of the published formulae greatly improved the test characteristics beyond simply using the total calcium. A correction formula in widespread use (Payne), quoted in reference texts, agreed less well with ionized calcium than did the unadjusted measured calcium. Correction formulae should be abandoned in favour of the use of uncorrected calcium. In cases of doubt, ionized calcium should be directly measured.     

“互联网+随访对口服利伐沙班患者服药依从性的影响

目的 探讨“互联网+护理”随访模式对口服利伐沙班的骨科老年患者服药依从性及出凝血功能的影响。方法 将74例口服利伐沙班的骨科老年患者按照入院时间分为对照组30例,观察组44例。对照组采取常规出院随访护理,观察组进行“互联网+护理”随访,随访3周后对两组利伐沙班血药谷浓度、血药浓度的离散程度、血药谷浓度的比较目标范围达标率和出凝血指标结果进行评价。结果 两组均有27例完成研究。观察组利伐沙班血药谷浓度离散程度显著小于对照组,血药谷浓度目标范围达标率显著高于对照组(均P<0.05),两组血药浓度及凝血指标比较,差异无统计学意义(均P>0.05)。结论 “互联网+护理”随访模式可以提升骨科老年患者使用抗凝药物的依从性,保持血药浓度的稳定。     

Risks and complications of transurethral resection of bladder tumor among patients taking antiplatelet agents for cardiovascular disease

Background

Urologists have not reached a consensus regarding the pre-, intra-, and postoperative management of patients taking antiplatelet agents. This study aimed to evaluate the clinical course of patients receiving antithrombotic monotherapy with acetylsalicylic acid (ASA) 100 mg who underwent transurethral resection of bladder cancer.

Methods

This study was designed to compare the surgical outcomes for 108 transurethral resections of bladder cancer performed for patients taking antiplatelet therapy and for 105 procedures performed for patients who had never taken antiplatelet agents before surgery. Antiaggregant therapy was maintained according to criteria evaluated by a urologist, surgeon, anesthesiologist, and cardiologist. Variables were described using the mean as the location index and using standard deviation as a dispersion index if continuous percentages were used elsewhere. Group comparisons were performed using the t test or the chi-square test for categorical data, and Fisher’s exact test was used where appropriate.

Results

The mean operative time for patients taking ASA was 31 min (range 10–65 min), whereas it was 26 min (range 5–60 min) for control subjects. The difference between pre- and postoperative hemoglobin values was ?0.6 g/dl in the group receiving antiplatelet therapy and ?0.8 g/dl in the control group (p = 0.0720). Transfusional support was required during four procedures performed for patients taking antiplatelet therapy and during two procedures for the control group (p = 0.242). No adverse cardiac events or anesthesia-related complications occurred. Three patients in the treatment group and two patients in the control group required reintervention to ensure hemostasis during the postoperative period. None of the patients in either group underwent rehospitalization for hematuria after leaving the hospital.

Conclusion

The current results suggest that continued use of anti-aggregant monotherapy does not increase the risk of overall bleeding or reintervention for patients undergoing transurethral resection of bladder neoplasms and that suspending aspirin before such a procedure is therefore unnecessary.     

Comparative effectiveness of active oral vitamin D agents in patients on peritoneal dialysis

Comparative Effectiveness Research (CER) has become positioned to inform health care decision-making with passage of the health care reform law, "Patient Protection and Affordability Care Act of 2010". As the name suggests, CER attempts to understand the relative efficacy between two therapies to allow clinicians, health care providers, and others to make rational decisions when evaluating therapeutic options. This is particularly relevant in the nephrology community as the dawn of bundled payments approaches. The current evidence base for CER studies is especially curtailed as a result of limited head-to-head clinical trials in patients with end-stage renal disease. Specifically, CER for available oral vitamin D agents approved for use in ESRD is lacking. The inclusion of oral vitamin D in the bundled payment system in 2011 may lead more clinicians to examine which oral vitamin D analog to prescribe to their patients, making this an especially timely topic.     

Challenges in taking care of patients on chronic haemodialysis.

Sir, Dr Tozawa and his colleagues [1] bring out several interestingissues in their article on multiple medication use and increasedmortality in chronic haemodialysis patients. Patients on a larger number of medications had multiple co-morbidities(i.e. type 2 diabetes, Table 1). This article,     

The effect of calcium chelating or binding agents on Candida albicans.

OBJECTIVE: The aim of this study was to evaluate antifungal effects of calcium-chelating or -binding agents on Candida albicans comparing with conventional antifungal agents. STUDY DESIGN: Two clinical oral isolates and 1 standard strain of C albicans were included in the study. Test solutions were ethylenediamine-tetraacetic acid (EDTA), ethyleneglycol-tetraacetic acid (EGTA), sodium fluoride (NaF), titanium tetrafluoride (TiF4), nystatin, and ketoconazole. Minimum inhibitory and fungicidal concentrations of the solutions were determined. The results were analyzed statistically using Friedman's nonparametric 2-way ANOVA and Mann-Whitney U tests. RESULTS: All isolates demonstrated similar susceptibility patterns (P>.05). Except ketoconazole, EDTA had the highest antifungal and fungicidal activity, followed by TiF4. EGTA and NaF were the weakest agents against C albicans among all test solutions. CONCLUSION: EDTA and TiF4 may be recommended as an alternative irrigating solution particularly in persistent root canal infections and in root canals of patients having a high incidence of oral candidosis.     

Actions of ketamine and its isomers on contractility and calcium transients in human myocardium.

BACKGROUND: Ketamine has a species-dependent inotropic effect on myocardium. The authors' aim was to investigate the direct inotropic effect and the corresponding intracellular Ca2+ transients of ketamine and its isomers on human myocardium. METHODS: Right auricular myocardial strips obtained during open heart surgery were exposed to increasing concentrations (73 microM, 360 microM, and 730 microM) of racemic ketamine (n = 12), S(+)-ketamine (n = 12), or R(-)-ketamine (n = 11). Isometric force, isotonic shortening, contractility, relaxation, and time to maximal isotonic and isometric force were assessed. Ten muscle strips in each group were loaded with the calcium-sensitive fluorescent dye FURA-2/AM for simultaneous measurements of calcium transients. RESULTS: Compared with the initial control maximal isometric developed force, maximal isotonic shortening amplitude, contractility, and relaxation increased by 12.5-22.4% after perfusion with S(+)-ketamine at the concentration of 73 microM (P < 0.05). In contrast, no changes were seen after addition of 73 microM R(-)-ketamine. The effect of racemic ketamine (73 microM) was between that of the two isomers. At the highest concentration (730 microM) ketamine and its isomers decreased maximal isometric developed force, maximal shortening amplitude, contractility, and relaxation by 26.8-57.4% (P < 0.05), accompanied by a significant decrease of the intracellular calcium transient (by 21.0-32.2%, P < 0.05). CONCLUSIONS: In contrast to R(-)-ketamine, S(+)-ketamine increased isometric force, isotonic shortening, contractility, and relaxation at low concentrations (73 microM) compared with the initial control. At higher concentrations (730 microM) a direct negative inotropic action was observed after perfusion with ketamine and its isomers, which was accompanied by a decreased intracellular Ca2+ transient.     

Intravenous aminophylline in patients already taking oral theophylline: effect on calculated dose of knowledge of serum theophylline concentration on admission.

Measurement of serum theophylline concentration is usually recommended before intravenous aminophylline is given to patients taking oral theophylline. Fifty patients with worsening airflow obstruction, all of whom were taking oral theophyllines and who had no contraindication to the use of parenteral aminophylline, were randomly allocated into two groups before treatment was given. The dose of aminophylline was calculated without (group A) and with (group B) knowledge of admission serum theophylline concentration. In group A a regimen incorporating corrections to account for factors affecting theophylline clearance was used in an attempt to represent a "knowledgeable" approach; in group B a formula incorporating the known serum theophylline concentration at the time of admission was used. All loading doses were given over 30 minutes as "mini infusions." The two groups were well matched for age, blood gas tensions, and severity of airflow obstruction. The results for four patients (one from group A and three from group B) were excluded from analysis after completion of the study. In each group the mean admission serum theophylline concentration measured (group A: 8.4 (SD 6.0)mg/l; group B: 7.2 (5.7)mg/l) and the aminophylline doses used (group A: loading bolus 172 (45.5)mg, infusion 815 (198)mg; group B: loading bolus 233(189)mg, infusion 788(214)mg) were similar. Mean serum theophylline concentrations during 24 hours' aminophylline treatment, number of patients with a serum theophylline concentration greater than 20 mg/l, symptoms of toxicity, and outcome were also similar in the two groups. Although satisfactory use of parenteral aminophylline was achieved for most patients without knowledge of serum theophylline concentration at the time of admission to hospital (with the aid of a "knowledgeable" clinical approach and constant infusion pumps), prompt measurement of serum theophylline concentration at the time of admission identified patients with either suboptimal or potentially hazardous theophylline concentrations.     

Effect of early surgery in high surgical risk geriatric patients with femoral neck fracture and taking antiplatelet agents

AIM: To investigate the effect of early surgical intervention on the high surgical risk elderly patients who sustained femoral neck fracture (FNF) and taking concomitant antiplatelet agents.METHODS: Between 2010 and 2012, a prospective study was conducted on 49 geriatric patients, who took antiplatelet agents, sustained FNF and underwent surgery within 72 h [early surgery (ES) group], and these were compared with a retrospective consecutive case series of patients with similar characteristics (45 cases) who had delayed surgery (DS group) after 72 h during an earlier 3-year period. Postoperative outcomes were followed for one year and compared.RESULTS: There were non-significant differences in perioperative blood loss, blood transfusion, intensive care unit requirement and postoperative mortality (P > 0.05 all). There were 2 patients (4%) in the DS group who died after surgery (P = 0.23). However, the ES group showed a significantly better postoperative outcome in terms of postoperative complications, length of hospital stay, and functional outcome (P < 0.05 all).CONCLUSION: Early hip surgery in geriatric hip fracture patients with ongoing antiplatelet treatment was not associated with a significant increase of perioperative blood loss and postoperative mortality. Moreover, ES resulted in a better postoperative surgical outcome. In early hip surgery protocol, the antiplatelet agents are discontinued and the patient is operated on within 72 h after admission, which is safe and effective for the medically fit patients.     

糖尿病肾病患者口服降糖药应用进展

糖尿病肾病已成为全球终末期肾病的最主要病因之一。严格控制血糖可以有效减少糖尿病肾病发生及疾病进展;然而随着肾功能减退,会出现体内降糖药物蓄积,增加药物毒副反应及低血糖事件,所以糖尿病肾病患者如何有效且安全的使用口服降糖药物至关重要。本文主要讨论各类口服降糖药物包括胰岛素促泌剂、非胰岛素促泌剂及新型口服降糖药物在糖尿病肾病中的应用。