The why and how of sequential and combination therapy in osteoporosis. A review of the current evidence

ABSTRACT It is now well recognized that over the lifetime of a patient with osteoporosis, more than one medication will be needed to treat the disease and to decrease fracture risk. Though current gaps in osteoporosis therapy can be potentially mitigated with sequential and combination regimens, how to move seamlessly amongst the multiple treatments currently available for osteoporosis for sustained efficacy is still unclear. Data from recent studies show that an anabolic agent such as teriparatide or romosozumab followed by an antiresorptive affords maximal gain in BMD and possibly better and earlier fracture risk reduction compared to a regimen which follows the opposite sequence. Sequentially moving to a bisphosphonate such as alendronate from an anabolic agent such as abaloparatide has also been shown to preserve the fracture reduction benefits seen with the latter. This sequence of an anabolic agent followed by an antiresorptive should especially be considered in the high-risk patient with imminent fracture risk to rapidly reduce the risk of subsequent fractures. The data surrounding optimum timing of initiation of bisphosphonate therapy following denosumab discontinuation is still unclear. Though data suggests that combining a bisphosphonate with teriparatide does not provide substantial BMD gains compared to monotherapy, the concomitant administration of denosumab with teriparatide has been shown to significantly increase areal BMD as well as to increase volumetric BMD and estimated bone strength. This narrative review explores the available evidence regarding the various sequential and combination therapy approaches and the potential role they could play in better managing osteoporosis.

Controversies in the treatment of postmenopausal osteoporosis: How long to treat with bisphosphonates?

ABSTRACT Osteoporosis is a systemic skeletal disease characterized by reduced bone mass and deterioration of bone tissue microarchitecture leading to an increased risk of fractures. Fragility fractures, especially hip fractures, are associated with a significant reduction in the physical function and quality of life of affected patients, as well as increased mortality, leading to a major financial impact on health care. Many drugs have been registered for the treatment of osteoporosis and very recently, a new anabolic agent, romosozumab, has been approved in some countries. Despite the expansion of efficacious antiresorptive and anabolic therapies in recent years, a concomitant increase in concerns have been raised by physicians, patients and the lay press about the potential for adverse events, especially atypical femoral fractures (AFF) following prolonged use of bisphosphonates. Whatever the mechanism(s) may be, direct or indirect, linking prolonged bisphosphonate use to atypical femoral fractures, this adverse event is very rare in comparison to the magnitude of risk reduction of typical osteoporotic fractures. An estimated 162 osteoporosis-related fractures are prevented for each atypical femoral fracture associated with an anti-resorptive medication. Until a risk calculator for predicting risk of atypical fractures, becomes available in clinical practice, and we view this as an unlikely scenario, it is up to the physician to consider continuing or discontinuing bisphosphonate use after the critical 3-5 year period of treatment with zoledronic acid or alendronate, but close monitoring for the residual bone effects overtime should be planned. For other bisphosphonates, in which no residual effects are expected, drug holiday is usually not applied.

Design and application of "summary", "extension" and "preview" combination combined holiday counseling after the half teaching of internal medicine nursing / 中华医学教育探索杂志

Internal medicine nursing is a very important learning course for nursing students. It is divided into two semesters in our university. Because the knowledge of the course is more complex and in-volves a wide range, many students have a poor learning effect. In order to improve the teaching effect of the course, the students leave the time to build the "summary", "extension" and "preview" combined guidance method. "Summary" is on the learning content of the summary, "extension" is the effective extension of learning content to the students, "preview" is the key content of the pre term learning habit. Then, accord-ing to the final score of medical nursing in the last semester, we can flexibly design the teaching link. For students under 60 points, holiday guidance is mainly "summary", for the students between 60 points to 85 points, holiday guidance is combined with "summary" "extension" and "preview", for students above 85 points, holiday guidance is the main "extension". Thus, the students' study and holiday time are integrated into a whole to improve their overall learning efficiency.

Relationship between Eating Style and Food Intake of Healthy Female College Students during Chuseok Holidays / 대한지역사회영양학회지

OBJECTIVES: The present study was conducted to investigate associations between eating style and food intake of 45 female college students during Chuseok holidays. METHODS: A ten-day food record was obtained and divided into two parts. The first five days (September 20-24, 2015) were considered as a 'Normal Day (ND 1-5)' and the subsequent five days (September 25-29) as 'Holiday (HD6-10)'. The middle three days (September 26-28) of the holidays were considered as the 'Peak Holiday (PD7-9)'. Eating behaviors were measured using the Dutch Eating Behavior Questionnaire (DEBQ) and anthropometry was assessed in all study participants. Participants were grouped by cluster analysis according to the mean energy intake of the first three days of the Holiday. RESULTS: Participants had a low-normal range of BMI and they were carefully restricting their food intake at Normal Day. Even the food intake did not exceed 2000 kcal per day during the Peak Holiday. External eating was the most prevalent type of eating behavior, followed by restrained eating and emotional eating. Normal energy and fat intake were correlated with the external eating subscale of the DEBQ. Restrained eating was associated with the weight, BMI, fat mass, waist, and hip girth of the subjects. Compared to the Normal Day, they overate during the Holiday with different eating styles including 'restraint', 'disinhibition', and 'fluctuation'. Therefore, neither eating behaviors nor anthropometry was associated with food intake during the Holiday. Although eating behaviors and anthropometric measures were not different among eating style clusters, the food intakes of disinhibition cluster were higher than those of restraint cluster during all the study periods. CONCLUSIONS: Subjects can be classified with the restraint, disinhibition, and fluctuation clusters. However, eating behaviors and anthropometry were not different among three clusters.

Position Statement: Drug Holiday in Osteoporosis Treatment with Bisphosphonates in South Korea

Bisphosphonates have been widely used in the treatment of osteoporosis with robust data from many placebo-controlled trials demonstrating its efficacy in fracture risk reduction over 3 to 5 years of treatment. Although bisphosphonates are generally safe and well tolerated, concerns have emerged about the adverse effects related to its long-term use, including osteonecrosis of the jaw and atypical femur fractures. Because bisphosphonates are incorporated into the skeleton and continue to exert an anti-resorptive effect for a period of time after the discontinuation of drugs, the concept of a "drug holiday" has emerged, whereby the risk of adverse effects might be decreased while the patient still benefits from anti-fracture efficacy. As randomized clinical trial evidence is not yet available on who may qualify for a drug holiday, there is considerable controversy regarding the selection of candidates for the drug holiday and monitoring during a drug holiday, both of which should be based on individual assessments of risk and benefit. This statement will provide suggestions for clinicians in South Korea on the identification of possible candidates and monitoring during a bisphosphonate drug holiday.

Duration of Bisphosphonate Treatment / 대한내과학회지

Large, randomized, controlled trials have demonstrated the efficacy of bisphosphonates (BP) in terms of improving bone mineral density (BMD) and reducing fracture risk. Consequently, bisphosphonates are used widely in the treatment of osteoporosis. Recently, however, several safety issues regarding the long-term use of BP, especially BP-related osteonecrosis of the jaws and atypical fractures, have been noted and have emerged as a limitation of their clinical use. Although the absolute risk is very small, the risks could increase with the long-term use of BP. The anti-fracture efficacy of BP is not sustained after treatment for 5-10 years. Therefore, recommendations suggest that a drug holiday be considered after 5 years of treatment for patients at low risk of fracture. However, as the individual fracture risk varies, the treatment duration should be based on individual clinical risk factors and bone metabolism status. Moreover, recommendations regarding monitoring after discontinuing and reinitiating BP await further studies.

Drug holiday as a prognostic factor of medication-related osteonecrosis of the jaw

OBJECTIVES: To identify post-treatment prognostic factors for medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: We evaluated 54 MRONJ patients who visited the Department of Dentistry, Ajou University Hospital, from May 2007 to March 2014. Twenty-one patients were surgically managed with debridement or sequestrectomy and 33 patients were conservatively managed using antibiotics. Correlations of age, sex, stage, bisphosphonate duration and type, and drug holiday with the prognosis of MRONJ were investigated. Correlations were verified by logistic regression analysis and t-tests with a significance level of 0.05. RESULTS: Clinical outcomes were evaluated on the basis of both clinical and radiographic findings. Twelve out of 21 surgically managed patients showed a favorable prognosis and nine patients relapsed. Thirty-one of the 33 conservatively managed patients showed no specific change in prognosis, and two patients worsened. Statistical analyses of the conservative management group did not reveal any correlation of the above factors with the prognosis of conservative management. Drug holiday was the only prognostic factor in the surgical management group (P=0.031 in logistic regression analysis, P=0.004 in t-test). CONCLUSION: Drug holiday is a prognostic factor in the surgical management of MRONJ. Because the drug holiday in the patients of the poor prognosis group occurred 1.5 to 4 months prior to surgical management, we recommend a drug holiday more than 4 months before surgery.

Research on regularity of emergency patients visiting doctors during holidays and festival days / 中华急诊医学杂志

Objective To investigate the regularity of variation in number of emergency patients visiting doctors within each 24 h during holidays and festival days,so as to provide a scientific basis for hospital administration and the rational allocation of human resources.Methods Based on the hospital's statistical data of emergency patients visiting doctors during winters from December 2010 to February 2014,a retrospective analysis was carried out for the number and the visiting time of emergency patients on holidays (weekends,the minor long holiday of 3 days for New Year and the major long holiday of 7 days for spring festival) and on general working days (Monday to Friday),respectively.The variation in number of patients and peak time of visiting doctors were analyzed by using circular distribution method,and compared the differences in the number of emergency patients visiting doctors and peak time period between holidays and working days.Results Most of emergency patient visitors were 50-79 years old males; the number of emergency patients on holidays was significantly higher than that on general working days,especially during the seven-day spring festival (P ＜ 0.01),while the number on New Year' s day was similar to that on weekends; peak time for emergency patients' visiting doctors was from 13:05 to 0:28 during general working days.On the contrary,the peak time occurred earlier at 10:05 until 21:05 during the holidays if the hospital offers half-day outpatient service,and in the absence of outpatient service,the peak time emerged further earlier at 9:16 until 21:26 during holidays.Conclusions The ages,number and the peak time of emergency patients visiting doctors on holidays are different from those on the general working days,so medical staff on duty should be arranged reasonably to follow this regularity.

Effects of a 'Drug Holiday' on Bone Mineral Density and Bone Turnover Marker During Bisphosphonate Therapy

BACKGROUND: Recently long-term safety of bisphosphonate raises issues about the duration of therapy. We examined the effects of a drug holiday (DH) on bone mineral density (BMD) and bone turnover markers. METHODS: In Korean, 125 women of 50 years of age or older with T-score or =5 years started DH in 2006. Lumbar (L1-4), left femoral neck, total BMD, serum parameter (beta-crossLaps [CTx], phosphorus, total calcium, total alkaline phosphatase), and urinary parameter (calcium/creatinine ratio) were measured before, the time of starting, and after DH. RESULTS: After DH, lumbar, femoral neck and total BMD did not change significantly (0.757+/-0.093-->0.747+/-0.102, P=0.135, 0.567+/-0.079-->0.560+/-0.082, P=0.351, 0.698+/-0.008-->0.691+/-0.090 g/cm2, P=0.115, respectively). Serum CTx and total alkaline phosphatase were increased significantly (0.205+/-0.120-->0.791+/-0.44 ng/mL, P60.42+/-15.543 IU/L, P=0.001, respectively). Urinary calcium/creatinine ratio increased significantly (0.132+/-0.076-->0.156+/-0.093, P=0.012). CONCLUSIONS: A DH could be cautiously considered in patients with long-term use of bisphosphonate if there is a concern about severe suppression of bone turnover with respect to long-term use because insignificant changes of BMD and significant increase of bone turnover markers are shown during the period.

Prognostic Factor, for Major Trauma Patients in the Emergency Medical Service System

PURPOSE: A few studies have assessed the factors affecting the prognoses for major trauma patients and those improving the circumstances when dealing with the trauma system. In that light, we analyzed factors, such as pre-hospital factors, the time to admission, the length of stay in the emergency department (ED) and emergency operation, influencing the outcomes for trauma patients. METHODS: The patients who visited our emergency department from April 1, 2009, to February 29, 2011, due to major trauma were enrolled in the study. The inclusion criterion was a revised trauma score (RTS) or = 16. We used reviews of medical records, to analyze each step of emergency medical care with respect to patients' sex, age, visit time and visit date. Continuous variables were described as a median with an interquartile range, and we compared the variables between the survival and the mortality groups by using the Mann-Whitney U test. Fisher's exact test was used for nominal variables. Using the variables that showed statistical significance in univariate comparisons, we performed a logistic regression analysis, and we tested the model's adequacy by the using the Hosmer-Lemeshow method. RESULTS: A total of 261 patients with major trauma satisfied either the RTS score criterion or the ISS score criterion. Excluding 12 patients with missing data, 249 patients were included in this study. The overall mortality rate was 16.9%. Time to ED arrival, time to admission, time of ED stay, RTS, ISS, and visit date being a holiday showed statistically significant differences between the survival and the mortality groups in the univariate analysis. RTS, ISS, length of ED stay, and visit date being a holiday showed statistical significance in the multivariate analysis. CONCLUSION: The mortality rate did not show a significant relationship with the time to ED arrival, use of 119, on time to admission. Rather, it elicited a quite significant correlation with the trauma scoring system (RTS and ISS), the time of ED stay, and the visit date being a holiday.

Ingeniería ritual en la comunicación de masas: a propósito de los JJ. OO. de Río de Janeiro 2016 / Ritual engineering in the comunication of the masses: purpose of the JJ.OO. of Rio de Janeiro 2016

La próxima celebración, en Río de Janeiro, de los JJ.OO., donde anualmente se celebran los más conocidos carnavales, permite reflexionar sobre la ingeniería ritual en la comunicación de masas con la que están construidos estos espectáculos, realizada por los gobiernos para afirmar la identidad nacional, de cara a los propios ciudadanos y de cara, también, al mundo entero, sin olvidar la propaganda implícita de su "ethos burocrático". Los JJ.OO., tienen una estructura ritual, un sentido de fiesta y hasta son una religión civil, siendo la sinergia de estos tres componentes una poderosa fuerza de conducción y nacionalización de las masas.

The next celebration, in Rio de Janeiro, of JJ.OO., where every year are celebrate the most knows carnivals, make possible think about the ritual engineering in the communication of the masses, with that are building this spectacles. This ritual engineering is doing for the governments to confirm the national identity, for the own citizens and for, too all over the world, without forget the inside advertising of his "bureaucratic ethos". The JJ.OO., have a ritual structure, a sense of holiday and even a civil religion, being a synergy of this three components one powerful force of control and nationalization of the masses.

Epidemiological features of emergency calls around the spring festival holiday in past 5 years / 中国基层医药

Objective To explore the epidemiologic al features of emergency calls around the spring festival holiday in past 5 years,so as to guide emergency medical services during holldays.Methods An investigation was made into emergency calls around the spring festival holiday in 2001～2005(1～7 of the first month of the lunar year) as well as one week before and after the holiday.Results The person-times to emergency during the spring festival holiday was correspondly stabilize in the recent 5 years,compared to the datas of the previous and subsequent 1 week,the person-times of emergency and the patients needed to rescue at first significantly increased,and the patients to pediatric emergency increased most significantly.The most part of the person-times to emergency were internal medicine.Conclusion It is essential to do a good job of health education and disease prevention,especially among high risk groups of people,and to reinforce the establishment of the emergency medical services system so as to effectively guarantee the the development of holiday economy.

Application of grouping statistic of working day and holiday through functions of SQL in Oracle / 医疗卫生装备

Objective To calculate workload according to working day and holiday separately.Methods Functions of SQL in Oracle were used to separate working day and holiday.Results The method could accomplish holiday's workload statistics expediently.Conclusions Statistics of holiday's workload are becoming ordinary work,so the separated analysis for them has practical value.

Epidemiological features of emergency calls around tbe National Day holiday in the past three years / 中华医院管理杂志

Objective To find out about the epidemiological features of emergency calls around the National Day holiday so as to guide emergency medical services during holidays. Methods An investigation was made into e-mergency cases during the National Day holiday in 2002 (October 1-October 7) as well as one week before and after the holiday and comparison was made between the numbers of emergency cases in the past three years. Results In the past three years, the number of emergency cases around the National Day holiday has been going down year by year whereas at the same time the number of hospitalized patients and patients admitted to the observation ward has been going up. During the National Day holiday in 2002, the number of emergency cases, hospitalized patients and patients admitted to the observation ward increased markedly compared with those before and after the holiday, with the most remarkable increase in the number of pediatric emergency cases and the biggest number of emergency cases in internal medicine. Conclusion It is essential to do a good job of health education and disease prevention, especially among high risk groups of people, and to reinforce the establishment of the emergency medical service system so as to effectively guarantee the development of holiday economy.