Duration of treatment for osteoporosis.

Many treatments for postmenopausal osteoporosis with proven efficacy in lowering fracture risk had become available since many years now. In the last few years the issue about treatment duration has become a matter of importance. In this paper the pivotal trials for alendronate, risedronate, zoledronate and other anti reabsorptive drugs such as denosumab are revised with particular attention to the extension studies aimed to verify the effect of drug discontinuation. The results of the review highlight differences among the available drugs and the practical clinical consequences also in terms of cost-effectiveness.

Adherence to therapeutic and diagnostic recommendations in patients with femur fracture and at risk of re-fracture or death: results of an analysis of administrative databases.

The aim of the present study was to evaluate the application into clinical practice of therapeutic and diagnostic recommendations for the prevention of bone re-fracture in postmenopausal women after an hospitalization for hip fracture in clinical practice and to assess the relationship between the application of diagnostic recommendations and re-fracture or death risk. A retrospective cohort analysis was conducted. All female patients, at least 65 years old, and with an hospitalization with main or secondary diagnosis of hip fracture during the period 1 January 2006 - 31 December 2008, were included. Besides demographic characteristics and comorbidities, drug treatment prescriptions related to bone fracture or supplementary with calcium or vitamin D and prescriptions of recommended laboratory and instrumental diagnostic tests (e.g. spine radiography), were analysed. A total of 5,636 patients were included in the study. The prescription of a drug treatment aimed to reduce the risk of re-fracture was found in 16.3% of patients, among them 76.3% (699 patients) used bisphosphonates only, 17.1% (157 patients) strontium ranelate only and 4.9% (45 patients) used more than one treatment during the observation period. Among the patients who did not receive drug treatment, 17.5% made use of only supplemental calcium and vitamin D. The remaining part of patients (69.1%) received no treatment. The prescription of at least one laboratory test of first and second level was performed, respectively, on 53.7% and 43.1% of included patients, whereas the prescription of at least one instrumental test of first and second level was performed, respectively, on 5.9% and 0.8%. Although it is established that the prescription of the recommended tests and appropriate drug treatment are significantly associated with reduced risk of re-fracture and death, today the application of these recommendations is reduced.

Validation and further development of the WHO 10-year fracture risk assessment tool in Italian postmenopausal women: project rationale and description.

The threshold for pharmacological intervention for osteoporosis remains controversial. Tools predicting the future risk of new fractures are increasingly used to establish a convenient individual risk/benefit ratio for a long term treatment. FRAX® is likely to become the most widely used tool for assessing fracture risk also for the WHO endorsement. The inevitable limitations will not hamper its value. As for any tool like this a continuous process of validation and further development is highly warranted. The predictive and clinical value of FRAX® has to be tested in individual countries by exploring also the inclusion of additional specific relatively uncommon risk factors. The DeFRA project is intended to validate in a large cohort of postmenopausal women a new algorithm derived from FRAX®. Both, the coefficients of continuous variable and the gradients for clinical risk factors should not be considered as conclusive for the routine clinical use. The new tool will be offered for the routine clinical use only at the completion of the DeFRA project, requiring the prospective collection of at least 60.000 patient-years. Here we report the rational and the design of the project.

[How much does an antiinflammatory treatment cost?]. / Quanto costa una terapia con antinfiammatori?

NSAIDs are among the most popular drugs in the world for their efficacy in controlling pain and acute and chronic inflammation. The efficacy of these therapies is hampered by their safety profile, in particular regarding the gastroenteric tract. The NSAIDs' side effects may heavily influence the health of the single patient and the economy of the health systems. The pharmacoeconomic evaluation of antinflammatory treatment usually considers, in addition to the drug purchase prize, also the shadow costs. This cost is mainly due to the management and prevention of gastropathy. Coxibs, even if more expensive, may become cost-effective for their better gastronteric safety. As a matter of fact, coxib treatment can be considered equivalent to a treatment with NSAID plus PPI. However, the first requirement of these drugs, that should control pain, must be the efficacy and not only safety. In this case the NNT (Number Needed to Treat) is a good marker of efficacy. To calculate the real cost we must pay to reach the target (pain resolution in one patient), we can multiply NNT for the prize of a specific drug. The total cost will depend on drug prize (the cheaper, the better) and on the efficacy expressed by NNT (the lower, the better). In a recent meta-analysis, the NNT of several antinflammatory drugs has been calculated. When the treatment cost was adjusted for its efficacy (NNT), the difference in favour of NSAIDs became so little to disappear because of the higher safety of coxibs (especially of etoricoxiband the possibility to reach antinflammatory and analgesic doses that are difficult to obtain with NSAIDs. Moreover, if also the cost of gastroprotection is considered, the economic impact of NSAIDs can be much higher. In conclusion the pharmacoeconomic analysis of an antinflammatory therapy cannot be based only on safety issues but also on efficacy evaluation that is the main effect we ask to these drugs.

Incidence and costs of hip fractures compared to acute myocardial infarction in the Italian population: a 4-year survey.

INTRODUCTION: Few data are available about the incidence and costs of hip fractures in Italy. We aimed to determine the impact of hip fractures vs. acute myocardial infarction (AMI). METHODS: We studied the national hospitalization database to calculate their incidence and costs in adults aged >or=45 between 1999 and 2002. RESULTS: In 2002, there were 86,719 hip fractures with a 10.0% increase over 4 years. We observed a predominance of women (77.1%) and a strong age effect: 92.7% of patients were >or=65 years old and 80% of fractures occurred in women aged >or=75, showing a clear relationship with the incidence of osteoporosis. Hospitalizations due to AMI after 45 years of age in 1999 were only 9% higher than those for hip fracture, although this difference increased over the 4 examined years up to 24%. Considering the DRGs costs, hip fractures resulted in being more expensive than AMI overall and concerning elderly people. CONCLUSIONS: This study shows that in the Italian population aged >or=45, hospitalizations following hip fracture and AMI between 1999 and 2002 were comparable, while hip fractures' direct costs were higher and grew faster than costs for AMI. Hip fractures in Italy are a serious medical problem and a leading health-cost driver.

[Incidence and socioeconomic burden of hip fractures in Italy]. / Incidenza e costi delle fratture di femore in Italia.

OBJECTIVES: The aim of this study was to evaluate the trend of the incidence and costs of hip fractures in Italy. METHODS: The incidence of hip fractures after 45 years of age in both females and males during the years 1999-2002 was obtained by analyzing the Italian Ministry of Health national hospitalization database, according to the diagnosis codes of International Classification of Diseases, Clinical Modification, 9th edition (IDC-9-CM) that indicate femoral fracture. We have computed all direct costs sustained by the National Health Service for hospitalization and treatment of hip fractures on the basis of the value of the Diagnosis Related Groups (DRG) referring to hip fractures. The expenses of rehabilitation and indirect expenses were based on estimates. RESULTS: In 2002, more than 86,000 hip fractures were registered in Italy in male and female patients over 45 years old, with 9% progression compared to 1999; 77% were female and 80% were over 75 years of age. In 2002 the direct costs of hospitalization, in the patients over 65 years alone, were almost 400 million euros, with an increase of 15% as compared to 1999. Considering also estimated rehabilitation costs, social aid and indirect costs, we estimate that hip fractures due to age-related osteoporosis created over a billion euros in expenses in 2002. CONCLUSIONS: Preventive intervention regarding the risk of hip fracture in elderly patients is urgent.

Weekly administration of alendronate: rationale and plan for clinical assessment.

OBJECTIVE: This paper describes the rationale and supporting data for once-weekly dosing of alendronate. BACKGROUND: Alendronate sodium, a bisphosphonate that potently inhibits bone resorption, has been shown to increase bone mass and substantially reduce the incidence of osteoporotic fractures, including fractures of the hip. The standard regimen of daily administration has generally been well tolerated. However, weekly administration may provide greater convenience to patients without compromising efficacy or tolerability. The pharmacokinetics of alendronate and bone remodeling theory predict similar efficacy for weekly and daily administration if the cumulative dose is the same. Bone resorption in individual remodeling units normally proceeds for approximately 2 weeks; alendronate inhibits the rate and extent of resorption. Because the half-life of residence on bone surfaces is several weeks, weekly administration of alendronate should inhibit bone resorption to an overall extent similar to that of daily dosing, thereby producing similar effects on bone mass and strength. Animal studies demonstrate that both weekly and daily parenteral administration of alendronate effectively increase bone mass and strength, but confirmation of efficacy is needed for weekly oral dosing in humans. Although daily bisphosphonates (alendronate and risedronate) elicited esophageal irritation in a canine model of gastroesophageal reflux, weekly dosing with alendronate at a higher unit dose did not. Thus, the lower frequency of weekly dosing with a higher unit dose may actually reduce the risk of upper gastrointestinal irritation compared with daily administration of a lower dose. CONCLUSIONS: Current safety and efficacy data justify further investigation of once-weekly dosing of alendronate. Two positive-control, double-blind, randomized trials of osteoporosis treatment and prevention are currently being performed to assess the comparability of weekly, biweekly, and daily dosing of alendronate with regard to effects on bone density, safety, and tolerability.

Model citizens. Outsourcing helps start-up Medicare HMO.

UNLABELLED: Health Plans of Pennsylvania (HPP), the managed care arm of Crozer-Keystone Health System, in Media, Pa. PROBLEM: Selecting the information systems and building the infrastructure to support the start-up of a new Medicare HMO product. SOLUTION: HPP chose to outsource the information systems needed to integrate all the components of managed care administration into a cost-effective and cohesive program. RESULTS: Because of its aggressive programming and start-up of the MedCarePlus product offering, HPP became the first plan in the country to submit Medicare claims data electronically for encounter reporting to the Health Care Financing Administration (HCFA). KEYS TO SUCCESS: "Through an integrated team approach, an organization truly can benefit from the economies of scale gained through outsourcing."

Computed radiographic absorptiometry and morphometry in the assessment of postmenopausal bone loss.

The best method for the diagnosis of osteoporosis and assessment of fracture risk is currently considered to be bone densitometry. The most commonly used dual-energy X-ray absorptiometry (DXA) methods may sometimes not predict bone mass accurately in every skeletal site, are expensive and not widely available. The recent development of computed analysis of a plain radiograph of the hand might provide a practical, inexpensive and rapid method for evaluation of bone mineral status. In this study we evaluated 20 healthy premenopausal and 660 postmenopausal women. In 36 of these subjects a second evaluation was carried out after 2 years of therapy with calcium supplements. The internal and external diameters of the second metacarpal and the metacarpal and ultradistal radial bone density were evaluated using a technical device developed in our laboratory and marketed by NIM, Verona, Italy (Osteoradiometer). The radiographic images, captured by a video camera, were digitized and studied by computed analysis. In 150 subjects bone density at the level of the lumbar spine, femur, and ultradistal and proximal radius was also measured by DXA techniques. Both external (D) and internal (d) diameters increase significantly with age and years since menopause (YSM), whereas metacarpal index (D--d/D) and metacarpal and ultradistal radial bone density decrease significantly with age and YSM. The ratio between metacarpal bone mineral content and the cortical area (volumetric metacarpal bone density) did not change with age. Significant correlations were found between radiometric findings and DXA measurements. The best correlation coefficients were between bone density measured at the level of the ultradistal radius by DXA and radiographic absorptiometry. In the 2-year follow-up study, a 4.9% and 6.2% decline in radial metacarpal bone density respectively were observed, but the difference was statistically significant only for the latter. In conclusion, computed radiogrammetry is closely correlated with all DXA measurements and may be useful in screening of large populations, providing a simple, inexpensive and sufficiently precise method for evaluation of bone mineral status. Further studies are warranted for assessing the accuracy of radiogrammetry for longitudinal investigations and its capacity to predict fracture risk.

The radiological assessment of vertebral osteoporosis.

The traditional skeletal X-ray is of little help in quantifying osteopenia in the spine, and indirect criteria, such as increased lucency, loss of horizontal trabeculae and reduction in end-plate thickness with relatively increased opaqueness, can be misleading. However, the clinical expression of osteoporosis is fracture, which can be identified by radiography. Any reduction in the anterior, middle, or total height of the vertebral body should be classified as vertebral fracture. In mild cases, such fractures are not easily detectable, particularly when previous radiographs are not available for comparison. Thus several objective methods for fracture identification have been developed. Most of these methods are based on the ratio between posterior and anterior or middle height (wedge or biconcave deformity, respectively) and on the ratio between posterior height of adjacent vertebrae or with a single vertebral reference (T4). Some of these indices are referred to normal ranges in order to take into account intervertebral and interindividual variability. In 36 women with postmenopausal osteoporosis we have compared the lateral radiographs of lumbar and thoracic spine to similar X-ray pictures taken by chance at least five years before menopause. By defining a fracture as any decrease in vertical height above 1 mm, we found 77 deforming events in 29 out of 36 patients. We then applied some of the methods to identify objectively fractures in our postmenopausal radiographs: the sensitivity of the various systems ranged from 50 to 100%; however there was a large overlap between false positives and false negatives and the methods with the highest sensitivity lack specificity and vice versa.