Management of osteoporosis in the elderly

ABSTRACT

Background: Osteoporosis is predominantly a condition of the elderly, and the median age for hip fracture in women is approximately 83 years. Osteoporotic fracture risk is multifactorial, and often involves the balance between bone strength and propensity for falling.

Objective: To present an overview of the available evidence, located primarily by Medline searches up to April, 2009, for the different management strategies aimed at reducing the risk of falls and osteoporotic fractures in the elderly.

Results: Frailty is an independent predictor of falls, hip fractures, hospitalisation, disability and death in the elderly that is receiving increasing attention. Non-pharmacological strategies to reduce fall risk can prevent osteoporotic fractures. Exercise programmes, especially those involving high doses of exercise and incorporating balance training, have been shown to be effective. Many older people, especially the very elderly and those living in care institutions, have vitamin D inadequacy. In appropriate patients and given in sufficient doses, vitamin D and calcium supplementation is effective in reducing both falls and osteoporotic fractures, including hip fractures. Specific anti-osteoporosis drugs are underused, even in those most at risk of osteoporotic fracture. The evidence base for the efficacy of most such drugs in the elderly is incomplete, particularly with regard to nonvertebral and hip fractures. The evidence base is perhaps most complete for the relatively recently introduced drug, strontium ranelate. Non-adherence to treatment is a substantial problem, and may be exacerbated by the requirements for safe oral administration of bisphosphonates.

Conclusion: Evidence-based strategies are available for reducing osteoporotic fracture risk in the elderly, and include exercise training, vitamin D and calcium supplementation, and use of evidence-based anti-osteoporotic drugs. A positive and determined approach to optimising the use of such strategies could reduce the burden of osteoporotic fractures in this high-risk group.     

Diagnosis and treatment of osteoporosis in postmenopausal women with distal radius fracture in Germany

ABSTRACT

Objective: The aim of this study was to evaluate osteoporosis diagnosis and treatment on the basis of medical history, at hospital discharge, and 6–12 months after discharge, as well as to assess the frequency of subsequent fractures in postmenopausal women with distal radius fracture.

Research design and methods: A prospective, observational study of hospitalized women aged 55 years and older with an isolated distal radius fracture from minimal trauma. Subjects were recruited in 242 acute care hospitals in Germany.

Outcome measures: Potential risk factors for osteoporosis, frequency of osteoporosis assessment, frequency of medication treatment and subsequent fractures 6–12 months after discharge.

Results: Among 2031 patients we identified 652 appropriate postmenopausal women. Less than one-third of patient histories contained any bone density parameters, and only a minority of subjects (33%, 217) underwent bone density assessment while in hospital. Of these, 55% (119) were diagnosed with low bone density, yet only 30% of those were prescribed supplements (calcium/vitamin D) and/or specific osteoporosis medication (mostly bisphosphonates) at discharge. Six to twelve months after hospital discharge, the low rate of treatment had not changed substantially. In the interval, 4.3% had sustained a subsequent fracture from minimal trauma: 1.4% a distal radius fracture (0.3% a refracture) and 2.9% a hip joint or other fracture (not specified). A significant age difference between those with and without subsequent distal radius fractures was found (?p = 0.01) but not a significant difference between patients with or without osteoporosis medication (?p = 0.79), primarily because the case numbers were too small.

Conclusions: A substantial proportion of postmenopausal women hospitalized with distal radius fracture were not sufficiently evaluated or treated for their potential risk of osteoporosis.     

The HORIZON Recurrent Fracture Trial: design of a clinical trial in the prevention of subsequent fractures after low trauma hip fracture repair

SUMMARY

Objective: To present the novel design of a trial testing the safety and efficacy of a yearly bisphosponate, zoledronic acid, in preventing new clinical fractures in patients with recent low trauma hip fracture repair.

Research design and methods: Randomized, placebo-controlled, triple-blind study. One hundred and fifteen clinical centers worldwide are recruiting approximately 1714 subjects aged 50?years and over (no upper age limit, median age of enrolled subjects to date 79?years) who have undergone surgical repair of a low trauma hip fracture in the preceding 90?days. Patients will be assigned at random to an intervention group (5?mg zoledronic acid intravenously yearly) or a control group (placebo infusion yearly). Both groups receive a loading dose of Vitamin D2 or D3 IM or orally, followed by 800–1200?IU Vitamin D and 1000–1500?mg elemental calcium orally on a daily basis. Concomitant therapy with calcitonin, hormone replacement therapy, selective estrogen receptor modulators, tibolone, and external hip protectors are allowed.

Main outcome measures: The primary endpoint is subsequent skeletal fractures as adjudicated by a clinical endpoints committee blinded to intervention status. Secondary outcomes include delayed hip fracture healing, changes in bone mineral density, and health resource utilization. Subjects will be recruited over a 3–4?year period and will be followed until 211 primary endpoints are accrued and adjudicated.

Conclusions: This randomized clinical trial is novel among osteoporosis therapies as it (1) targets hip fracture patients, a previously understudied group, and (2) uses only clinically evident fractures as the primary outcome. Ethical and practical considerations in studying this frail population are discussed.     

Relationship between change in femoral neck bone mineral density and hip fracture incidence during treatment with strontium ranelate

ABSTRACT

Objective: Strontium ranelate (SR) increases bone mineral density (BMD) in postmenopausal osteoporotic women and reduces vertebral and non-vertebral fracture incidence. Hip fracture reduction has also been observed during 3-year treatment with SR in osteoporotic women at high risk of hip fracture. The objective of this study is to analyse the association between BMD changes and hip fracture incidence during treatment with SR.

Material and methods: In this post-hoc analysis, 465 women aged over 74 years with low BMD at the femoral neck (T-score ≤ –2.4 according to NHANES normative values) were selected from the population of a recently published study (the Treatment of Peripheral Osteoporosis Study – TROPOS). BMD was assessed at the femoral neck at baseline and after a follow-up of 3 years. Hip fractures were reported by study investigators.

Results: After adjusting for age, body mass index, femoral neck BMD at baseline and number of prevalent vertebral fractures, we found that for each 1% increase in femoral neck BMD observed after 3 years, the risk to experience a hip fracture after 3 years decreased by 7% (95% CI: 1–14%) (?p = 0.04). In patients experiencing a hip fracture over 3 years of treatment with SR, femoral neck BMD increased by (mean [SE]) 3.41 (1.02)% compared to 7.23 (0.81)% in patients without hip fracture (?p = 0.02).

Conclusion: In this post-hoc analysis of women undergoing 3 years of SR treatment, an increase in femoral neck BMD is associated with a decrease in hip fracture incidence.     

Prevalence of vitamin D inadequacy in osteoporotic hip fracture patients in London

ABSTRACT

Background: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age,?or below the normal range.

Objectives: To investigate the prevalence of vitamin D inadequacy in an elderly population with hip fractures from London (UK) and compare levels with data previously presented from Glasgow (UK).

Research design and methods: A retrospective patient audit was carried out over a 17‐month period (September 2003–January 2005). Patient records were searched for hip fracture admissions and cross matched with vitamin D analysis carried out within 3 days of the hip fracture admission. The resulting records were hand searched to exclude patients with a hip fracture resulting from high impact/trauma.

Results: There were data for 103 hip fracture patients, 79.6% of the patients were women (n = 82). The mean age at the time of fracture was 73.4 years, 100% were aged 60 years or over and 41% were aged 75 years or over. Around 20% of the patients were receiving supplementation with calcium and/or vitamin D and were not excluded from the analysis. The mean vitamin D level was 32.1?nmol/L (12.9?ng/mL), SD = 19.4 (7.8), however, it is likely that the true mean is lower since in approximately 15% of cases vitamin D levels were reported as < 12.5?nmol/L, but were transcribed at 12.5?nmol/L in order to allow a numerical value to be calculated. Ninety-nine per cent of patients had a vitamin D level < 80?nmol/L, 94.2% < 70?nmol/L and 81.6% < 50?nmol/L.

There were no significant differences by patient age or sex, however, there were significant seasonal differences in vitamin D. In the year from September 2003 to August 2004, 82.8% of summer admissions had vitamin D levels < 70?nmol/L compared with 98.0% in winter (?p = 0.04). Mean vitamin D levels in the 30 patients with parathyroid hormone (PTH) levels above the reference range were significantly lower than levels in the 71 patients within the range: mean 19.9?nmol/L, SD = 16.2 versus mean 37.5?nmol/L, SD = 18.5 (?p < 0.0001). Furthermore, 50% of the patients with PTH levels above the reference range had vitamin D levels < 12.5?nmol/L, reflecting extremely low levels of vitamin D.

Conclusions: This study confirms almost universal vitamin D inadequacy among 103 patients admitted to hospital with hip fracture in London, although the prevalence of inadequacy is slightly lower than that seen in a similar study carried out in Glasgow.     

Efficacy and safety of alendronate and risedronate for postmenopausal osteoporosis

ABSTRACT

Introduction: This paper discusses the efficacy and safety of alendronate and risedronate in the treatment of postmenopausal osteoporosis.

Methods: The literature was searched with the PubMed from 1996 to the present, with respect to strictly conducted systematic reviews with homogeneity, meta-analyses with homogeneity, and randomized controlled trials (RCTs) with narrow Confidence Interval.

Results: According to the results of large randomized controlled trials (RCTs), bisphosphonates (alendronate, risedronate, and ibandronate), raloxifene, calcitonin, parathyroid hormone (PTH), and strontium ranelate effectively prevent vertebral fractures in postmenopausal women with osteoporosis. Because raloxifene has been shown to be effective in preventing the initial vertebral fracture in postmenopausal osteoporotic women without prevalent vertebral fractures, it is considered in the treatment of postmenopausal women with mild osteoporosis or osteopenia with some risk factors for fractures. RCTs have also demonstrated that alendronate, risedronate, PTH, and strontium are useful to prevent non-vertebral fractures and that alendronate and risedronate prevent hip fractures, thus alendronate or risedronate are primarily considered as the first-line drugs in the treatment of elderly women with osteoporosis having some risk factors for falls. While it has been suggested that PTH may be considered in patients with severe osteoporosis, the use of PTH in the treatment for osteoporosis is limited to 2 years or less, and it may be appropriate to use other anti-resorptive drugs after the completion of PTH treatment to maintain the skeletal effects gained during the treatment. RCTs have demonstrated that the incidence of gastrointestinal tract adverse events in postmenopausal osteoporotic women treated with bisphosphonates and placebo are similar, and also the long-term efficacy and safety of alendronate and risedronate.

Conclusion: The evidence derived from the literature, based on strict evidence-based medicine guidelines, suggests that there is long-term efficacy and safety with alendronate and risedronate in the treatment of osteoporosis in postmenopausal women.     

Osteoporosis management: impact of fracture type on cost and quality of life in patients at risk for fracture I

ABSTRACT

Background: Osteoporosis is a major and costly global public health problem. It is a chronic disease in which fracture is the main outcome, and the impact of these fractures can vary depending on the age of the individual and the severity of the fracture.

Scope: Using literature review, this paper discusses and summarizes the information available regarding the individual and socio-economic consequences associated with the several types of osteoporotic fractures.

Findings: Different types of osteoporotic fractures are generally associated with different age groups. The health-economic impact of vertebral and hip fractures has been extensively explored and it is well known that these fractures are associated with morbidity/disability and increased mortality; they also account for a substantial portion of the direct fracture costs. However, to accurately estimate the individual and socio-economic burden of the disease, further research is needed on the morbidity/disability, mortality, and costs associated with non-hip, nonvertebral fractures, which account for more than half of the total fractures. More data are also required on the indirect costs associated with all fracture types.

Conclusions: Understanding the socio-economic consequences of each fracture type will be important to fully estimate the burden of osteoporosis and may help clinicians tailor management plans for individual patients.     

Management of alcohol intoxication and aggressive behaviour: a tale of two cities

ABSTRACT

Background: Violence and aggressive behaviour are a growing problem in emergency departments on both sides of the Atlantic, and alcohol intoxication is often involved. A wide range of management options is available, and policies vary considerably.

Methods: We compared the management of alcohol intoxication and aggressive behaviour in four New York and four London emergency departments, using a semi-structured interview which covered 15 issues.

Results: Differences were apparent between New York and London emergency departments in the method used for diagnosis of alcohol intoxication, the investigations carried out and discharge criteria. Chemical and physical restraints were readily and frequently used in New York in order to prevent intoxicated patients leaving the department, while in London disruptive patients tended to be ejected.

Conclusions: The marked transatlantic differences, while partly due to cultural and historic reasons, are largely due to the pressures to limit the risk of litigation in the United States and the constraints of a cost-limited health service in Britain. The management of violent and intoxicated patients deserves further refinement.     

Prevalence of vitamin D inadequacy in Scottish adults with non-vertebral fragility fractures

ABSTRACT

Background: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture are more likely to have serum vitamin D levels either lower than those of control patients of similar age, or below the normal range.

Objectives: To investigate the prevalence of vitamin D inadequacy in an elderly population presenting to the South Glasgow Fracture Liaison Service with non-vertebral fragility fractures in order to assess the extent of the problem.

Research design and methods: The retrospective arm of this study used data from an established database to identify patients aged over 50 years admitted to South Glasgow University Hospitals over the previous 4 years with hip fracture. The prospective arm identified the first 50 patients aged over 50 presenting with a clinical non-vertebral fragility fracture with osteoporosis as measured by axial spine and/or hip DEXA (T‐score < –2.5) after November 2004.

Results: In the retrospective arm, 626 patients were identified from the database: mean age 80.5 years; 94% were aged over 60 and 74% were aged over 75. Data analysis was limited to 548 patients aged over 60 years with vitamin D recordings and not receiving supplementation with calcium and vitamin D. The mean vitamin D level was 24.7?nmol/L (9.9?ng/ml) SD = 17, however, it is likely that the true mean is lower since in approximately 25% of cases vitamin D levels were reported as < 15?nmol/L (effectively unrecordable). These were transcribed as 15?nmol/L in order to permit a numerical value to be calculated. In the absence of an agreement on what should constitute a diagnostic serum level of vitamin D inadequacy, a number of thresholds were considered – 97.8% had vitamin D levels below 70?nmol/L and 91.6% had vitamin D levels below 50?nmol/L. There were no significant differences by patient sex, age or season of presentation.

The mean age of patients in the prospective arm was 65.8 years (range 50.6–83.8), 72% were aged over 60 and 16% were aged over 75. The mean vitamin D level was 44.1?nmol/L (18.4?ng/ml) SD = 25.3; 82% had vitamin D levels below 70?nmol/L and 72% had vitamin D levels below 50?nmol/L. Although numbers were too small to justify extensive subgroup analyses, the mean vitamin D level in the 13 patients with hip fracture (34.5?nmol/L) was lower than in the 37 with non-hip fractures (48.2?nmol/L).

Conclusions: This study confirms almost universal vitamin D inadequacy among 548 elderly patients admitted to hospital with hip fracture, regardless of whether a threshold of 50?nmol/L or 70?nmol/L was used. However, among a prospective subset of 50 patients with clinical fragility fractures, especially those with non-hip fractures, the prevalence of inadequacy was substantially lower. It may be that vitamin D represents a correctable risk factor for fragility fracture in the elderly, possibly specifically for the hip.     

Emerging drugs for the management of cancer treatment induced bone loss

Areas covered in this review: We focus our attention on data on the efficacy of currently available and emerging drugs for the management of cancer treatment induced bone loss (CTIBL) found in a PubMed research from 1997 till today.

Importance of the field: One of the most common and severe safety issues of the antihormonal therapy in both sexes is the CTIBL and the related fragility fractures. In postmenopausal women with estrogenic receptor positive breast cancer, the third-generation aromatase inhibitors (AIs) are the standard therapy. Observational retrospective studies have found that AIs treated patients had a high rate of bone loss and fracture risk (RR 1.3). Also in men with prostate cancer receiving androgen deprivation therapy, the increase in bone turnover and the consequent bone loss are very rapid and sustained significantly increasing the fracture risk.

What the reader will gain: The aim of our review is to provide the current evidences for the management of bone loss and fracture risk in this subpopulation.

Take home message: The very high rate of bone loss and the high incidence of fractures indicate that cancer patients at risk of CTIBL need to be carefully monitored and stratified for fracture risk. Although there is a strong evidence of efficacy in prevention of bone loss and reduction of fracture risk for many drugs approved for postmenopausal osteoporosis (PMO) and male osteoporosis, for CTIBL there are actually no drugs approved for this indication.     

Lanreotide for the treatment of gastroenteropancreatic neuroendocrine tumors

Introduction: The prevalence of gastropancreatic neuroendocrine tumors (GEP-NETs), a largely sporadically occurring group of neoplasms, has rapidly increased. NET diagnoses often occur late and entail treatment challenges; treatment beyond surgical resection is typically required. Somatostatin analogs (SSAs), the cornerstone of GEP-NET therapy, target somatostatin receptors on NET cell surfaces and can ameliorate NET-related symptoms and prevent tumor progression.

Areas covered: This expert review summarizes the development of the SSA lanreotide and its role in treating NETs. Key lanreotide preclinical and clinical findings in acromegaly, carcinoid syndrome, and NETs are discussed, along with future treatment goals and therapeutic prospects.

Expert opinion: The role of SSAs in NET treatment was historically one of symptom management. Although this is a critical therapeutic component, ideal treatment would include prevention of tumor progression. As GEP-NETs are biologically diverse, progression prevention can be difficult, depending on primary tumor site and functional status. Recent data indicate that lanreotide significantly prolonged progression-free survival in metastatic GEP-NET patients. Practice patterns seem to be shifting toward using SSAs as first-line therapy. Response to SSAs has typically been categorized as either symptomatic or biochemical. However, SSA use to prevent tumor progression will lead to a new, objective response category based on tumor growth.     

Pharmacological prevention and management of restenosis

Importance of the field: The introduction of percutaneous intervention represented a major milestone in the management of obstructive arterial disease. Restenosis following intervention has been a key limitation of this therapy and, despite availability of a variety of therapeutic options, remains a challenging clinical entity.

Areas covered in this review: The aim of this review is to summarize the extensive literature regarding prevention and management of restenosis following percutaneous intervention. While systemic pharmacological approaches to reduce restenosis have not yielded convincing long-term results, drug-eluting stents (DES) have proven very effective, though their undoubted efficacy seems to be achieved at the collateral cost of delayed healing of the stented segment. The optimal management of DES restenosis remains under investigation: treatment options include repeat DES, angioplasty, brachytherapy or drug-eluting balloon.

What the reader will gain: A comprehensive overview of systemic and local drug delivery approaches for prevention and treatment of restenosis.

Take home message: Current approaches to prevent and treat restenosis are efficacious, but there remains some distance to be travelled before patients or physicians can be fully satisfied with available therapies.     

Management of varices in cirrhosis

Introduction: Acute variceal bleeding is a medical emergency and one of the main causes of mortality in patients with cirrhosis. Timely and effective treatment of the acute bleeding episode results in increased survival, and appropriate prophylactic treatment can prevent bleeding or rebleeding from varices.

Areas covered: We discuss the prevention of development and growth of varices, the primary and secondary prophylaxis of bleeding, the treatment of acute bleeding, and the management of gastric varices. We systematically reviewed studies, without time limits, identified through Medline and searches of reference lists, and provide an overview of the evidence underlying the -treatment options in the management of varices in cirrhosis.

Expert opinion: The management of variceal hemorrhage relies on nonspecific interventions (e.g., adequate fluid resuscitation, airway protection) and on specific interventions. These are routine prophylactic antibiotics, vasoactive drugs and endoscopic treatment. Procedures such as the placement of a Sengstaken–Blakemore tube or a transjugular intrahepatic portosystemic shunt (TIPS) can be lifesaving. The primary and secondary prophylaxis of bleeding is based on nonselective beta-blockers and endoscopy, even though TIPS or, less frequently, surgery have a role in selected cases.     

European women's preference for osteoporosis treatment: influence of clinical effectiveness and dosing frequency

ABSTRACT

Objective: To determine participant preference for weekly versus monthly bisphosphonate therapy for osteoporosis after being informed about differences in fracture efficacy.

Design: 20‐minute, semi-structured, face-to-face or telephone interviews. Two bisphosphonate choices were presented on the basis of block randomization: weekly therapy with proven efficacy to reduce fracture risk at the spine and hip, or monthly therapy with proven efficacy to reduce fracture risk at the spine but not the hip.

Subjects: Women from the UK, Germany, France, Spain and Italy, with postmenopausal osteoporosis and aged ≥ 55 years. Fifty percent were currently taking a weekly bisphosphonate; 50% had no history of taking any bisphosphonate.

Measures: An efficacy rating scale and an intention-to-use rating scale were developed for this study. The primary endpoint was preference for weekly or monthly therapy. Reasons for preference were recorded.

Results: A preference was recorded for 1248 women (1253 were recruited). More women preferred weekly to monthly therapy (82% vs. 18%, respectively; p < 0.001). Among women who preferred weekly therapy, efficacy was the most commonly cited reason (65%). Ninety-two percent of the total cohort rated the efficacy of the weekly therapy as ‘excellent/good’ versus 38% for monthly (?p < 0.001). Sixty-nine percent intended to use weekly bisphosphonates compared with 34% for monthly (?p < 0.001).

Conclusions: When informed about differences in fracture efficacy in weekly and monthly bisphosphonates, a significantly greater proportion (82%) of women preferred a weekly bisphosphonate with proven fracture efficacy at the spine and hip over a monthly bisphosphonate with proven fracture efficacy only at the spine.     

Prevention of diabetic ketoacidosis and self-monitoring of ketone bodies: an overview

ABSTRACT

Objective: Diabetic ketoacidosis (DKA) is associated with significant morbidity and mortality. Self-monitoring of ketone bodies by diabetes patients can be done using blood or urine. We compared the two self-monitoring methods and summarized recent developments in the epidemiology and management of DKA.

Methods: MEDLINE and EMBASE were searched for relevant publications addressing the epidemiology, management and prevention of DKA up to 2009. The current, relevant publications, along with the authors’ clinical and professional experience, were used to synthesize this narrative review.

Findings: Despite considerable advances in diabetes therapy, key epidemiological figures related to DKA remained nearly unchanged during the last decades at a global level. Prevention of DKA – especially in sick day management – relies on intensive self-monitoring of blood glucose and subsequent, appropriate therapy adjustments. Self-monitoring of ketone bodies during hyperglycemia can provide important, complementary information on the metabolic state. Both methods for self-monitoring of ketone bodies at home are clinically reliable and there is no published evidence favoring one method with respect to DKA prevention.

Conclusions: DKA is still a severe complication potentially arising during prolonged hyperglycemic episodes with possibly fatal consequences. Education of patients and their social environment to promote frequent testing – especially during sick days – and to lower their glucose levels, as well as to recognize the early symptoms of hyperglycemia and DKA is of paramount importance in preventing the development of severe DKA. Both methods for self-monitoring of ketone bodies are safe and clinically reliable.     

Full length parathyroid hormone,PTH(1-84), for the treatment of severe osteoporosis in postmenopausal women

ABSTRACT

Objective: To review and analyse the evidence supporting the use of full length parathyroid hormone, PTH(1-84), in the treatment of osteoporosis based on a search of several literature sources; articles selected for review were published between 1990 and 2008.

Background: PTH(1-84) is approved for the treatment of osteoporosis in postmenopausal women at high risk of fracture in Europe. It was well tolerated in clinical trials and demonstrated bone building properties and fracture prevention particularly for the lumbar spine in the treatment of postmenopausal women.

Results: The TOP clinical trial showed that PTH(1-84) treatment for 18 months resulted in a 61% reduction (p = 0.001) in new vertebral fracture incidence when compared with placebo and reduced the risk of a first vertebral fracture by 68% (p = 0.006) in women without a prevalent fracture at baseline. PTH(1-84) increased bone mineral density (BMD) at vertebral and non-vertebral sites the lumbar spine BMD increasing regardless of T-score, age, prior osteoporosis therapy or number of years post-menopause. The PaTH study showed that treatment with PTH(1-84) for 12 months increased BMD at the trabecular spine and hip. Lumbar spine BMD gains were largest with sequential administration of PTH(1-84) followed by alendronate but were smaller with concurrent administration involving anabolic and antiresorptive agents. Lumbar spine BMD increases were also seen in trials involving PTH with raloxifene and PTH in combination with hormone replacement therapy.

Conclusions: PTH(1-84) has demonstrated effective bone building qualities and extends the therapeutic options available to osteoporotic women. The use of PTH(1-84) followed by sequential administration of an antiresorptive has proved effective at increasing trabecular BMD and points towards new treatment regimens offering improvements in BMD and fracture prevention.     

Strategies for managing cytomegalovirus in transplant recipients

Importance of the field: Cytomegalovirus (CMV) is the most important pathogen that affects transplant recipients, by directly causing clinical disease and by indirectly reducing patient and allograft survival.

Areas covered in this review: This review provides a brief overview of the direct and indirect effects of CMV disease and the traditional and newly described factors that increase the risk of disease after transplantation. Newly acquired data in the diagnostics, prevention and treatment of CMV infection are discussed, with emphasis on guidelines for management as recently endorsed by the American Society of Transplantation and the Transplantation Society.

What the reader will gain: The reader will gain up-to-date insights into the contemporary management of CMV after solid organ transplantation. Practical aspects of its diagnosis, prevention and treatment are discussed. Emerging concerns of late-onset CMV disease and antiviral resistance are also highlighted to emphasize the need to optimize CMV-prevention strategies.

Take home message: Prevention of CMV disease is an important goal in the management of solid organ transplant recipients. The efficacy of CMV prevention should be measured not only by the significant reduction in CMV incidence but, as importantly, by the improvement in long-term allograft and patient survival.     

Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies

ABSTRACT

Objective: The marketed doses of ibandronate, 150?mg once-monthly oral and 3?mg quarterly intravenous (IV) injection, produce greater increases in lumbar spine bone mineral density than treatment with the 2.5?mg oral daily dose. This meta-analysis assessed whether these doses also reduce fracture risk relative to placebo.

Study design and methods: Individual patient data from the intent-to-treat populations of the BONE, IV fracture prevention, MOBILE, and DIVA studies were grouped into three dose levels based on annual cumulative exposure (ACE), defined as the annual dose (mg) × bioavailability (0.6%, oral; 100%, IV) or placebo. Six key non-vertebral fractures (NVFs) (clavicle, humerus, wrist, pelvis, hip, and leg), all NVFs, and all clinical fractures were examined.

Results: This meta-analysis included 8710 patients. Cox proportional-hazards models estimated the adjusted relative risk (RR) for fracture with ibandronate versus placebo, and time to fracture was compared using log-rank tests. The high-dose group (ACE?≥?10.8?mg) showed significant reductions in the adjusted RR of key NVFs (34.4%, p?=?0.032), all NVFs (29.9%, p?=?0.041), and clinical fractures (28.8%, p?=?0.010) relative to placebo. The high-dose group also had significantly longer time to fracture versus placebo for key NVFs (p?=?0.031), all NVFs (p?=?0.025), and clinical fractures (p?=?0.002). Study limitations included: not all studies were placebo-controlled; a limited number of baseline characteristics were available for multivariate analyses.

Conclusion: Ibandronate at dose levels of ACE?≥?10.8?mg, which includes the marketed 150?mg once-monthly oral and 3?mg quarterly IV injection regimens, may provide significant non-vertebral and clinical fracture efficacy.     

The underuse of therapy in the secondary prevention of hip fractures

There is strong evidence to indicate that individuals who sustain a hip fracture are at a greater risk of developing another. The management of such patients should include efforts to prevent future fractures, including prescribing medications that have been shown to lower hip fracture risk. Such therapies that are currently available include calcium and vitamin D supplementation, alendronic acid and risedronic acid. In addition, there is epidemiological evidence to indicate that estrogen may also decrease the risk of hip fracture. Parathyroid hormone is another agent that has shown promise in this regard and is likely to be available for clinical use in the near future. However, the rates of utilisation of these therapies among patients with hip fractures are low. It is important to emphasise that secondary prevention of hip fractures should be an integral part of the management of individuals who sustain hip fractures.