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.     

New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion

ABSTRACT

Background: Adequate vitamin D and calcium nutrition play a critical role in the maintenance of musculoskeletal health and are considered the first step in osteoporosis treatment.

Roundtable discussion: In February 2008 Merck Sharp & Dohme sponsored a 2-day, evidence-based expert panel on the benefits of vitamin D for the patient with osteoporosis and the role of vitamin D in combination with antiresorptive therapy for the management of osteo­porosis. One of the primary objectives of the meeting was to review new data on the optimal serum 25-hydroxy­vitamin D [25(OH)D]levels. The symposium was attended by 29 researchers and clinicians from Europe and the Middle East. The discussion focused on optimizing vitamin D and calcium nutrition and reducing falls and fractures in osteoporotic patients.

Conclusions: Current evidence and expert opinion suggests that optimal serum 25(OH)Dconcentrations should be at least 50?nmol/L (20?ng/mL) in all individuals. This implies a population mean close to 75?nmol/L (30?ng/mL). In order to achieve this level, vitamin D intake of at least 20?µg daily is required. There is a wider thera­peutic window for vitamin D than previously believed, and doses of 800?IU per day, regardless of sun exposure, season or additional multivitamin use, appear to present little risk of toxicity. Apart from fracture and fall preven­tion, optimization of vitamin D status may also have additional general health benefits. Based on newly emerging data regarding calcium supplementation, and recommendations for increased vitamin D intake, the current recommendations for calcium intake in postmenopausal women may be unnecessarily high. In addition to vitamin D and calcium, treatment of patients with osteo­porosis at high risk of fractures should also include pharmacologic agents with proven vertebral and non-vertebral fracture efficacy.     

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.     

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.     

Post-fracture management of patients with hip fracture: a perspective*

ABSTRACT

Background: Hip fracture creates a worldwide morbidity, mortality and economic burden. After surgery, many patients experience long-term disability or die as a consequence of the fracture. A fracture is a major risk factor for a subsequent fracture, which may occur within a short interval.

Methods: A literature search on post-fracture management of patients with hip fracture was performed on the Medline database. Key experts convened to develop a consensus document.

Findings: Management of hip-fracture patients to optimize outcome after hospital discharge requires several stages of care co-ordinated by a multidisciplinary team from before admission through to discharge. Further studies that specifically assess prevention and post-fracture management of hip fracture are needed, as only one study to date has assessed an osteoporosis medication in patients with a recent hip fracture. Proper nutrition is vital to assist bone repair and prevent further falls, particularly in malnourished patients. Vitamin D, calcium and protein supplementation is associated with an increase in hip BMD and reduction in falls. Rehabilitation is essential to improve functional disabilities and survival rates. Fall prevention and functional recovery strategies should include patient education and training to improve balance and increase muscle strength and mobility. Appropriate management can prevent further fractures and it is critical that high-risk patients are identified and treated. To foster this process, clinical pathways have been established to support orthopaedic surgeons.

Conclusion: Although hip fracture is generally associated with poor outcomes, appropriate management can ensure optimal recovery and survival, and should be prioritized after a hip fracture to avoid deterioration of health and prevent subsequent fracture.     

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.     

The implications of a growing evidence base for drug use in elderly patients. Part 4. Vitamin D and bisphosphonates for fractures and osteoporosis

Fractures are common in elderly subjects, disabling and occasionally fatal. Their incidence increases exponentially with age, with the commonest affected sites being the wrist, vertebrae, hip and humerus. Of these, hip fractures are the most relevant in terms of morbidity and financial cost. The increase in fracture rate with age is believed to result predominantly from age-related increases in the incidence of osteoporosis and falls. This article reviews the evidence for the use of vitamin D and bisphosphonates for the prevention of bone fractures and osteoporosis in elderly patients.     

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.     

Prevalence of vitamin D inadequacy in a minimal trauma fracture population

ABSTRACT

Objective: The purpose of this analysis was to report the prevalence of vitamin D inadequacy in a population of adults with minimal trauma fractures.

Research Design and Methods: 82 adults (ages 52–97 with 63% age 80+) consecutively hospitalized with hip and extremity fractures between August 2001 and January 2002 were recruited from two St. Paul, MN hospitals. Patients came from independent living and assisted living facilities. Demographics, medical history and vitamin D supplementation were obtained by the medical record and self-report. Blood specimens were collected during hospitalization within 48 hours of admission. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were assessed using Diasorin 25-hydroxyvitamin D radioimmunoassay kit (RIA) at Mayo Clinic, Rochester, MN. Results were available for 78 patients and are included in the current analysis.

Results: Patients were 99% Caucasian, 63% ≥ 80 years and 78% female. 97% were admitted due to hip fracture. On admission, 50% reported using at least 400?IU per day of vitamin D through supplements (including multivitamins) and 13% of all patients were taking osteoporosis medication (3 estrogen, 5 alendronate, 1 etidronate, 1 raloxifene). The mean 25(OH)D concentration was 14.2 (SD 6.6) with a range of 5–39?ng/mL (8–38?ng/mL wintertime vales in Rochester, MN). All but two of the 78 patients (97.4%) had 25(OH)D concentrations < 30?ng/mL and the majority (81%) of the patients had 25(OH)D concentrations < 20?ng/mL, including 21% < 9?ng/mL. Mean 25(OH)D concentrations were not substantially different by gender, age, or osteoporosis medication use. Patients who reported vitamin D supplementation ≥ 400?IU/day had significantly greater mean 25(OH)D concentrations, albeit suboptimal, compared to those who did not (16.4 vs. 13.7?ng/mL; p = 0.002).

Conclusions: Nearly all patients in this study hospitalized for fracture had vitamin D inadequacy. Significant opportunity exists to ensure adequate and persistent vitamin D intake in a high risk fracture patient population.     

Oral nitrogen-containing bisphosphonates: a systematic review of randomized clinical trials and vertebral fractures

ABSTRACT

Background: Vertebral fractures are the most common osteoporotic fracture. They are associated with increased morbidity and mortality, and also predict future vertebral and non-vertebral fracture risk. Bisphosphonates are the current mainstay for the treatment of postmenopausal osteoporosis. Health authority guidelines request that assessment of vertebral fracture risk reduction is part of the evaluation of bisphosphonate efficacy. In this review, we compare the published evidence for the efficacy of the nitrogen-containing oral bisphosphonates in reducing the risk of vertebral fractures.

Methods: A review of publications in the treatment of postmenopausal osteoporosis and the most frequently prescribed oral bisphosphonate therapies (alendronate, ibandronate and risedronate) was carried out using the Dialog (Embase and Medline) and Cochrane online scientific citation databases. Eligible publications were those reporting randomized, placebo-controlled trials that included vertebral fracture as the primary or secondary endpoint (any time-point).

Results: Of 159 publications identified, six studies assessing alendronate, ibandronate and risedronate met the pre-defined eligibility criteria. In total, 14?083 women were included in the studies, with 8182 patients receiving active treatment. Most studies were 3?years in duration. Discontinuation rates varied from 11 to 45%, being highest in those studies that specified one or more vertebral fracture as part of the inclusion criteria. Across these studies, the reduction in the risk of vertebral fractures ranged from 41 to 62% (44–48% for alendronate; 41–49% for risedronate; 62% for ibandronate).

Conclusions: Nitrogen-containing oral bisphosphonates effectively reduce the risk of osteoporotic vertebral fracture, with the magnitude of effect ranging from 41 to 62%.     

Persistent bisphosphonate use and the risk of osteoporotic fractures in clinical practice: a database analysis study*

ABSTRACT

Objective: This study aimed to investigate the association between persistent use of bisphosphonates and the risk of osteoporotic fractures in clinical practice.

Methods: Data were obtained from the PHARMO Record Linkage System, which includes, among other databases, drug-dispensing records from community pharmacies linked to hospital discharge records of more than two million subjects in defined areas in the Netherlands. Persistence with bisphosphonate therapy was assessed during a period of 3 years. A nested matched case control study (cases:controls = 1:10) was performed to study the association between persistent bisphosphonate use and hospitalisation for osteoporotic fractures and analysed by conditional logistic regression analysis. The analyses were adjusted for patient characteristics such as previous hospitalisations for fractures, co-morbidity and co-medication.

Results: 14?760 new female users of bisphosphonates were identified of which 541 women had a hospitalisation for osteoporotic fracture after start of bisphosphonate treatment (1–3 years follow-up). One-year persistence rates increased from 33% with alendronate daily to 48% with alendronate weekly, an increase of 15%. Similar results were obtained with risedronate daily and weekly. One year persistent use of bisphosphonates resulted in a statistical significant 26% lower fracture rate (OR 0.74; 95%CI 0.57–0.95) whereas 2 year persistent use resulted in a 32% lower rate (OR 0.68; 95%CI 0.47–0.96).

Conclusions: Persistent use of bisphosphonates decreases the risk of osteoporotic fractures in clinical practice. Approximately 6% of fractures among users of bisphosphonates could be prevented if persistence was improved by 20%. However, current persistence with bisphosphonate therapy is suboptimal and strategies that further increase persistence are likely to further prevent the number of fractures.     

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

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 osteoporosis

Introduction: Osteoporotic fracture is a cause of pain, loss of autonomy and excess mortality. Current drugs however, do not allow for a satisfactory non vertebral fracture risk reduction and the compliance is suboptimal.

Areas covered: Current treatments consist of mainly bisphosphonates, denosumabs, selective estrogen receptor modulators and teriparatides. All drugs currently in development will target some aspect of bone remodeling by using the recent advances in our knowledge of bone biology: cathepsin-K inhibitors (odanacatib) are antiresorptive, antisclerostin monoclonal antibodies (romosozumab and blosozumab) are anabolic agents and PTHrp 1-34 (abaloparatide) is an anabolic agent.

Expert opinion: New drugs with better tolerance and ideally with intermittent administration may improve their compliance. New drugs will have to provide higher efficiency levels with regards to reducing the risk of fractures. They may be second-line options, targeted at patients who are poor responders, or those who display contraindications to the older drugs, as a result of cost issues. In addition, some of these new drugs with potent anabolic effect may be confined to niches, for those patients at high risk of refracture after an initial severe fracture such as a hip fracture or a clinical vertebral fracture.     

Use of Medicines that Influence Falls or Fractures in a Residential Home Setting

Objective: To study the pattern of use of medicines that may contribute to, or protect against, falls and fractures in the setting of a UK residential home population, and to compare the results with a similar study conducted in 2001.Setting and method: A cross-sectional survey was conducted in 2003 in 18 residential homes. A trained community pharmacist visited the homes to retrieve information about use of medicines whilst demographic details were provided by the residential home staff.Main outcome measure: The proportion of patients who were prescribed medicines with a potential positive benefit in preventing fractures, and medicines that may cause elderly people to fall.Results: The study population consisted of 581 residents. Compared to the 2001 study, the use of both calcium and vitamin D had increased significantly (8.3% versus 2.1%). Although, the overall prescribing of psychotropics in 2003 was relatively low, there was a trend for increased prescribing of these medicines which have been identified as risk factors for falling.Conclusion: In a residential home setting in the UK, the use of psychotropic drugs is not uncommon, whereas there is limited use of drugs that have the potential for preventing morbidity associated with falls.     

Management of osteoporosis among the elderly with other chronic medical conditions

Osteoporosis is a highly prevalent chronic disease in the US and worldwide. The most serious consequence of this disorder is fractures, which have a serious negative impact on quality of life and are often the trigger for accelerated deterioration, ultimately ending in death. Despite the availability of effective preventive treatments, osteoporosis is frequently underdiagnosed and/or undertreated, particularly among the elderly, who are also at greatest risk. In addition, the presence of co-morbid medical conditions may be both a barrier to osteoporosis care and a risk factor for falls; thus individuals with multiple co-morbid conditions may be a particularly high-risk group. The management of osteoporosis involves improving bone health via adequate nutrition, calcium and vitamin D supplements, and fall prevention strategies. Although these measures are important in the management of all patients, most elderly patients are likely to need additional pharmacological therapy to adequately reduce their fracture risk. Several pharmacological treatments have been shown to significantly reduce the risk of fracture, including bisphosphonates (e.g. alendronate, risedronate, ibandronate, zoledronic acid), denosumab, raloxifene, calcitonin and teriparatide. Despite recent advances in osteoporosis care, additional action is urgently needed to improve the quality of life of osteoporotic patients in general and of elderly patients in particular, since fracture outcomes are typically poorer in older than in younger patients. This article reviews the current status of osteoporosis management, emphasizing the need to improve osteoporosis care, with a particular focus on the US, by the use of quality-improvement measures and incentives, which might result in an increased awareness and improved treatment for this debilitating disease.     

Exploring drug delivery systems for treating osteoporosis

Introduction: Osteoporosis (OP) is a major disease in elderly people; its complications and prevalence are rapidly increasing worldwide. It is associated with high fragility fracture mainly of hip, wrist and spine. With the rising lifespan worldwide, the number of hip fractures throughout globe will rise from 1.66 million in 1990 to 6.26 million by 2050. So there is a major problem in our society related to the bone diseases which needs to be addressed.

Areas covered: This review gives knowledge about OP, its symptoms and problems associated with the existing therapies. It gives idea about various drug delivery systems for bone targeting. This review also gives a comprehensive compilation of the various in vitro and in vivo studies conducted till date and US FDA approved drugs for the treatment of OP.

Expert opinion: Various drug delivery systems reduce the adverse effects of drugs and increase the availability of drugs to the target site mainly bones. Active researches are going on to improve the OP treatment, whose high prevalence and considerable functional and socioeconomic impact will raise formidable challenges in the near future. We should work on different targets rather than conventional therapies which will improve the overall treatment strategies.     

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.     

Prevalence of vitamin D inadequacy in patients attending a metabolic bone clinic in Medway

ABSTRACT

Background: It is well established that vitamin D levels are sub-optimal in the elderly and that adults with fragility fracture have low levels of serum vitamin D.

Objectives:?To investigate the prevalence of vitamin D inadequacy in Medway, Kent in patients attending a metabolic bone clinic and in patients with fragility fractures and to compare levels with data previously presented from Glasgow.

Research design and methods:?Retrospective patient records audit of patients attending the metabolic bone clinic from 1998 to 2005.

Results:?There were data for 870 patients, 77.5% of the patients were women (n = 674) and 48.2% (n = 420) of patients had a fragility fracture. The mean age was 61.6 years (SD = 14.12), 56.4% were aged 60 years or over and 17.7% were aged 75 years or over. The mean vitamin D level was 47.7?nmol/L (19.1?ng/mL), SD = 25.8 (10.3). Of the patients 88.7% had a vitamin D level < 80?nmol/L, 81.4% < 70?nmol/L and 59.1% < 50?nmol/L.

Of the 420 patients with fragility fracture, 78.1% were women and the mean age was 66.6 years (SD = 12.22). The mean vitamin D level was 45.3?nmol/L (18.1?ng/mL), SD = 25.8 (10.3). In patients not receiving supplementation (n = 222) the mean vitamin D level was 40.5?nmol/L (16.2?ng/mL), SD = 20.9 (8.4) and 95.9% of patients had a vitamin D level < 80?nmol/L, 89.6% < 70?nmol/L and 71.2% < 50?nmol/L.

In order to compare data from Medway with previously published data from Glasgow, a subset of 198 patients with fragility fracture, aged over 50 years, attending the metabolic bone clinic and not receiving supplementation with calcium and/or vitamin D was analysed. There were 76.6% women and the mean age was 68.6 years (SD = 9.1). The mean vitamin D level was 40.0?nmol/L (16.0?ng/mL), SD = 21.5 (8.6). Of these patients 96.4% had a vitamin D level < 80?nmol/L,89.7% < 70?nmol/L and 73.2% < 50?nmol/L.

Data on the month of vitamin D assessment were available for 499 patients. The mean vitamin D in the summer (April–September) months (n = 217) was significantly higher than in the winter (October–March) months (n = 281): 53.2?nmol/L (SD = 29.4) versus 47.3 (SD = 24.9), p = 0.02.

Parathyroid hormone (PTH) levels were available for 289 patients. Mean vitamin D levels in the 47 patients with PTH levels above the reference range were significantly lower than vitamin D levels in the 238 patients within the reference range for PTH: mean 31.1?nmol/L, SD = 21.1 versus mean 46.5?nmol/L, SD = 24.8 (?p = 0.000092). Four patients had PTH levels below the reference range.

Conclusions:?The prevalence of vitamin D inadequacy is high in patients attending a metabolic bone clinic, in particular in those patients with fragility fractures. The prevalence of inadequacy is comparable with that seen in Glasgow.     

New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion

BACKGROUND: Adequate vitamin D and calcium nutrition play a critical role in the maintenance of musculoskeletal health and are considered the first step in osteoporosis treatment. ROUNDTABLE DISCUSSION: In February 2008 Merck Sharp & Dohme sponsored a 2-day, evidence-based expert panel on the benefits of vitamin D for the patient with osteoporosis and the role of vitamin D in combination with antiresorptive therapy for the management of osteoporosis. One of the primary objectives of the meeting was to review new data on the optimal serum 25-hydroxy vitamin D [25(OH)D] levels. The symposium was attended by 29 researchers and clinicians from Europe and the Middle East. The discussion focused on optimizing vitamin D and calcium nutrition and reducing falls and fractures in osteoporotic patients. CONCLUSIONS: Current evidence and expert opinion suggests that optimal serum 25(OH)D concentrations should be at least 50 nmol/L (20 ng/mL) in all individuals. This implies a population mean close to 75 nmol/L (30 ng/mL). In order to achieve this level, vitamin D intake of at least 20 microg daily is required. There is a wider therapeutic window for vitamin D than previously believed, and doses of 800 IU per day, regardless of sun exposure, season or additional multivitamin use, appear to present little risk of toxicity. Apart from fracture and fall prevention, optimization of vitamin D status may also have additional general health benefits. Based on newly emerging data regarding calcium supplementation, and recommendations for increased vitamin D intake, the current recommendations for calcium intake in postmenopausal women may be unnecessarily high. In addition to vitamin D and calcium, treatment of patients with osteoporosis at high risk of fractures should also include pharmacologic agents with proven vertebral and non-vertebral fracture efficacy.