A new digital case-based educational program Orthogeriatrics TeleECHO, a strategy to improve the care of fragility fracture patients.

Participation in Orthogeriatrics TeleECHO was associated with improvement in physicians' knowledge and self-confidence in managing elderly patients with fractures. PURPOSE: To develop and conduct an interactive case-based virtual TeleECHO program to expand the knowledge of healthcare professionals in the field of orthogeriatrics. METHODS: The project included twelve 90-min sessions for physicians and healthcare managers. Each session was based on real clinical cases discussed by the multidisciplinary group of faculty. The efficacy of the project was assessed using questionnaires. RESULTS: The attendance of individual sessions ranged from 129 to 224 with the total number of participants 829; 25% of participants were from remote rural regions. A survey conducted at the beginning of the project showed insufficient knowledge and ability to apply the concepts of orthogeriatrics. A final questionnaire showed that 74% of respondents participated in most sessions, with 94% wishing to continue participating in further sessions. There was a statistically significant overall improvement in confidence of caring for fragility fracture patients with an effect size of 0.75 (p<0.001). The proportion of responders who were able to apply their new knowledge in clinical practice shortly after TeleECHO showed a substantial increase (p<0.0001). CONCLUSION: The Orthogeriatrics TeleECHO program was effective in changing perceptions and self-confidence of the participants, and applying knowledge acquired to patient care. This model of learning could be applied in other countries in other languages to improve post-fracture care worldwide.

A summary of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis.

Key statements of the Russian clinical guidelines on the diagnosis and treatment of osteoporosis are summarized. They were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis and approved by the Russian Ministry of Health. PURPOSE: To summarize key statements of the Russian clinical practice guidelines for the diagnosis and treatment of osteoporosis. METHODS: The Russian clinical guidelines on the diagnosis and treatment of osteoporosis were developed by a task force representing the key Russian professional associations involved in the management of osteoporosis: These comprised the Russian Association of Endocrinologists, the Russian Association for Osteoporosis, the Association of Rheumatologists of Russia, the Association of Orthopedic surgeons and Traumatologists of Russia, the Russian Association of Gynecologists-Endocrinologists, and the Russian Association of Gerontologists and Geriatrics. The guidelines are based on a systematic literature review and principles of evidence-based medicine and were compiled in accordance with the requirements for clinical recommendations developed by the Ministry of Health of the Russian Federation. RESULTS: Key statements included in the Russian guidelines of osteoporosis approved by the Russian Ministry of Health in 2021 are summarized. The statements are graded based on levels of evidence and supported by short comments. The guidelines are focused on the current approach to screening, diagnosis, differential diagnosis, and treatment of osteoporosis. CONCLUSION: These guidelines are a practical tool for general practitioners, as well as medical specialists, primarily endocrinologists, rheumatologists, orthopedic surgeons, and other physicians who are involved in the management of patients with osteoporosis.

An experience- and preference-based EQ-5D-3L value set derived using 18 months of longitudinal data in patients who sustained a fracture: results from the ICUROS.

INTRODUCTION: EQ-5D-3L preference-based value sets are predominately based on hypothetical health states and derived in cross-sectional settings. Therefore, we derived an experience-based value set from a prospective observational study. METHODS: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) was a multinational study on fragility fractures, prospectively collecting EQ-5D-3L and Time trade-off (TTO) within two weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months thereafter. We derived an EQ-5D-3L value set by regressing the TTO values on the ten impairment levels in the EQ-5D-3L. We explored the potential for response shift and whether preferences for domains vary systematically with prior impairment in that domain. Finally, we compared the value set to 25 other EQ-5D-3L preference-based value sets. RESULTS: TTO data were available for 12,954 EQ-5D-3L health states in 4683 patients. All coefficients in the value set had the expected sign, were statistically significant, and increased monotonically with severity of impairment. We found evidence for response shift in mobility, self-care, and usual activities. The value set had good agreement with the only other experience- and preference-based value set, but poor agreement with all hypothetical value sets. CONCLUSIONS: We present an experience- and preference-based value set with high face validity. The study indicates that response shift may be important to account for when deriving value sets. Furthermore, the study suggests that perspective (experienced versus hypothetical) is more important than country setting or demographics for valuation of EQ-5D-3L health states.

Vitamin D status in Armenian women: a stratified cross-sectional cluster analysis.

BACKGROUND: Vitamin D plays a critical role in skeletal development and maintenance, thus sufficiency is an important goal for public health programs. Given the absence of foods fortified in vitamin D in Armenia, we hypothesized that vitamin D insufficiency would be widespread. METHODS: We conducted a random modified cluster model survey of vitamin D status of women in the country. We measured 25-hydroxyvitamin D [25(OH)D] by liquid chromatography mass spectrometry in dried blood spot samples and utilized a questionnaire to assess lifestyle factors. RESULTS: In summer, we sampled 1206 participants from 40 communities in Armenia. Mean 25-OH D level among women aged 18-24 was 20 ± 8 ng/mL; aged 25-64 was 21 ± 7 ng/mL; and >65 was 18 ± 8 ng/mL. The country-wide mean of the entire female population was 20 ± 8 ng/mL. A majority (>54%) had 25-OH D levels <20 ng/mL with nearly 13% having 25-OH D levels <12 ng/mL. Participants who reported calcium, vitamin D, or multivitamin supplementation had higher levels of 25-OH D (p values 0.004, 0.0002, and 0.03 respectively) as did pre- vs. postmenopausal women (p = 0.01), pregnant vs. nonpregnant women (p = <0.0001), and women who had experienced a sunburn in the past year (p = 0.004). CONCLUSION: In Armenia, there is a high prevalence of vitamin D insufficiency. This information provides data that can be used to inform public health directives to address this pervasive threat to optimal health.

FRAX-based intervention thresholds in eight Eurasian countries: Armenia, Belarus, Georgia, Kazakhstan, the Kyrgyz Republic, Moldova, the Russian Federation, and Uzbekistan.

Age-specific intervention and assessment thresholds based on FRAX® were developed for eight Eurasian countries participating in the EVA study (Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan). The intervention thresholds (major osteoporotic fracture) ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for people at age 50 years, and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. These thresholds enable a substantial advance in the ease of detection of individuals at high fracture risk. INTRODUCTION: The purpose of this study was to derive and compare FRAX-based intervention and BMD assessment thresholds for 8 Eurasian countries in the EVA study. METHODS: The intervention threshold (IT) was set at a 10-year probability of a major osteoporotic fracture (MOF), calculated without BMD, equivalent to a woman with a prior fragility fracture but no other clinical risk factors, and a body mass index (BMI) of 25.0 kg/m2. The lower assessment threshold was set at a 10-year probability of a MOF in women with BMI of 25.0 kg/m2, without previous fracture or other clinical risk factors. The upper assessment threshold was set at 1.2 times the IT. RESULTS: The age-specific intervention thresholds ranged from 3.6 (Armenia and Georgia) to 12.3% (Uzbekistan) for men and women at the age of 50 years and from 16 (Armenia) to 27% (Belarus) at the age of 90 years. The difference between countries was most evident at younger ages and become progressively less with advancing age. CONCLUSIONS: For the 8 Eurasian countries, the newly established FRAX-based intervention thresholds provide an opportunity to improve the clinical detection of both men and women with a high risk of fracture and improve treatment rates.

Report on the Audit on Burden of Osteoporosis in Eight Countries of the Eurasian Region: Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan.

The audit provides a detailed analysis of the burden of osteoporosis and differences between Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan with regard to prevalence of osteoporosis and incidence of osteoporotic fractures, future demographic changes, diagnostic resources, and treatment availability. PURPOSE: This paper describes the results of the Audit on Burden of Osteoporosis in Armenia, Belarus, Georgia, Moldova, Kazakhstan, the Kyrgyz Republic, the Russian Federation, and Uzbekistan. METHODS: We carried out a review of the available literature and a survey of the representatives of the national osteoporosis societies. All the information available in English, Russian, or national languages including the publications of local or regional importance was analyzed. RESULTS: The expected number of osteoporosis patients varies from 240,000 in Armenia to 16 million in Russia. Low-energy fractures are a serious health problem in all countries with the highest incidence in Kazakhstan and Russia. The rate of hip fracture patients' hospitalization in the majority of countries is low (33-80%). In the coming decades the populations, in particular, in Uzbekistan, Kazakhstan, and Kyrgyzstan, will continue to show increases in life expectancy with a corresponding increase in the number of fractures in older people. Thus, in 2050, the number of hip fractures in these countries will increase by 2.5-3.5 times. However, the availability of DXA devices in the region is low (0.2-1.3 per million), and DXA tests are expensive. Almost all modern treatments for osteoporosis are available, but the costs are high even for alendronate. Urgent action is needed at the national level in each country including recognition of osteoporosis as a priority health issue. CONCLUSION: Osteoporosis is an important health problem in the countries of the Eurasian region that will only get worse in the future due to expected demographic changes.

Treatment of high fracture risk patients in routine clinical practice.

A retrospective cohort study determined the high incidence of recurrent fractures in osteoporotic patients with high fracture risk during the observation. The strategy of starting treatment with more potent regimens (zoledronic acid, denosumab and/or teriparatide) seems to have the best secondary fracture prevention efficacy. OBJECTIVE: This paper describes the various medical therapy regimens prescribed to osteoporotic patients with high fracture risk and the result of treatment. METHODS: We carried out a retrospective cohort study in selected Osteoporosis Centers. Patients were considered to have high fracture risk in case of a history of a low-energy hip fracture or two or more vertebral or other site fractures. A total of 812 subjects (768 women and 44 men) aged 36-95 years were included. The observation period was 2285.1 patient-years. Demographic data, clinical findings, and BMD data obtained by DXA, as well as a history of fractures that had occurred during the follow-up, were included in the analysis. RESULTS: Overall, at baseline, there were 637 non-vertebral fractures including 104 hip fractures. A total of 590 patients had vertebral fractures; of these, 69% suffered multiple fractures. Being on treatment, 119 (14.7%) patients developed new vertebral and non-vertebral fractures. The incidence of new non-vertebral fractures and hip fractures was 39.4 and 13.1 per 1000 patient-years. The total number of vertebral fractures increased by 24.8% from 1353 to 1689. The best results of the treatment were achieved in patients who were started on zoledronic acid, denosumab, or teriparatide and had an adequate duration of treatment. Although these patients had significantly lower BMD values at the time of diagnosis compared with other patients, they showed a lower incidence of new vertebral and hip fractures, during the follow-up. CONCLUSION: Therapy of patients at high risk of fractures started with more potent treatment regimens (zoledronic acid, denosumab and/or teriparatide) of adequate duration was more effective in terms of prevention of new vertebral and hip fractures as compared with other treatment options. However, treatment appears to be challenging given the number of recurrent fractures in patients on treatment and the frequency of drug withdrawal or replacement.

Quality of life after fragility fracture in the Russian Federation: results from the Russian arm of the International Cost and Utility Related to Osteoporotic Fractures Study (ICUROS).

Changes in health-related quality of life (QoL) due to hip, humeral, ankle, spine, and distal forearm fracture were measured in Russian adults age 50 years or more over the first 18 months after fracture. The accumulated mean QoL loss after hip fracture was 0.5 and significantly greater than after fracture of the distal forearm (0.13), spine (0.21), proximal humerus (0.26), and ankle (0.27). INTRODUCTION: Data on QoL following osteoporotic fractures in Russia are scarce. The present study evaluated the impact of hip, vertebral, proximal humerus, distal forearm, and ankle fracture up to 18 months after fracture from the Russian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study. METHODS: Individuals age ≥ 50 years with low-energy-induced humeral, hip, clinical vertebral, ankle, or distal forearm fracture were enrolled. After a recall of pre-fracture status, HRQoL was prospectively collected over 18 months of follow-up using EQ-5D-3L. Multivariate regression analysis was used to identify determinants of QALYs loss. RESULTS: At 2 weeks, patients with hip fracture (n = 223) reported the lowest mean health state utility value (HSUV) compared with other fracture sites. Thereafter, utility values increased but remained significantly lower than before fracture. For spine (n = 183), humerus (n = 166), and ankle fractures (n = 214), there was a similar pattern of disutility with a nadir within 2 weeks and a progressive recovery thereafter. The accumulated mean QoL loss after hip fracture was 0.5 and significantly greater than after fracture of the distal forearm (0.13), spine (0.21), proximal humerus (0.26), and ankle (0.27). Substantial impairment in self-care and usual activities immediately after fracture were important predictors of recovery across at all fracture sites. CONCLUSIONS: Fractures of the hip, vertebral, distal forearm, ankle, and proximal humerus incur substantial loss of QoL in Russia. The utility values derived from this study can be used in future economic evaluations.

Epidemiology of osteoporotic fracture in Moldova and development of a country-specific FRAX model.

Retrospective population-based survey in 2 regions of the Republic of Moldova determined the incidence of fractures at the hip, proximal humerus and distal forearm. The estimated number of such fractures nationwide for 2015 was 11,271 and is predicted to increase to 15,863 in 2050. The hip fracture rates were used to create a FRAX model to help guide decisions about treatment. OBJECTIVE: This paper describes the epidemiology of osteoporotic fractures in Republic of Moldova that was used to develop the country-specific fracture prediction FRAX® tool. METHODS: We carried out a retrospective population-based survey in 2 regions of the Republic of Moldova (Anenii Noi district and Orhei district) representing approximately 6% of the country's population. We identified hip, forearm and humerus fractures in 2011 and 2012 from hospital registers and primary care sources. Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for Moldova. Fracture probabilities were compared with those from neighbouring countries having FRAX models. RESULTS: The incidence of hip fracture applied nationally suggested that the estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 3911 and is predicted to increase by 60% to 6492 in 2050. Hip fracture incidence was a good predictor of forearm and humeral fractures. FRAX-based probabilities were higher in Moldova than neighbouring countries (Ukraine and Romania). CONCLUSION: The FRAX model should enhance accuracy of determining fracture probability among the Moldavan population and help guide decisions about treatment.

Quality of life after hip, vertebral, and distal forearm fragility fractures measured using the EQ-5D-3L, EQ-VAS, and time-trade-off: results from the ICUROS.

INTRODUCTION: The International Costs and Utilities Related to Osteoporotic fractures Study is a multinational observational study set up to describe the costs and quality of life (QoL) consequences of fragility fracture. This paper aims to estimate and compare QoL after hip, vertebral, and distal forearm fracture using time-trade-off (TTO), the EuroQol (EQ) Visual Analogue Scale (EQ-VAS), and the EQ-5D-3L valued using the hypothetical UK value set. METHODS: Data were collected at four time-points for five QoL point estimates: within 2 weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months after fracture. Health state utility values (HSUVs) were derived for each fracture type and time-point using the three approaches (TTO, EQ-VAS, EQ-5D-3L). HSUV were used to estimate accumulated QoL loss and QoL multipliers. RESULTS: In total, 1410 patients (505 with hip, 316 with vertebral, and 589 with distal forearm fracture) were eligible for analysis. Across all time-points for the three fracture types, TTO provided the highest HSUVs, whereas EQ-5D-3L consistently provided the lowest HSUVs directly after fracture. Except for 13-18 months after distal forearm fracture, EQ-5D-3L generated lower QoL multipliers than the other two methods, whereas no equally clear pattern was observed between EQ-VAS and TTO. On average, the most marked differences between the three approaches were observed immediately after the fracture. CONCLUSIONS: The approach to derive QoL markedly influences the estimated QoL impact of fracture. Therefore the choice of approach may be important for the outcome and interpretation of cost-effectiveness analysis of fracture prevention.

Trabecular bone score: a noninvasive analytical method based upon the DXA image.

The trabecular bone score (TBS) is a gray-level textural metric that can be extracted from the two-dimensional lumbar spine dual-energy X-ray absorptiometry (DXA) image. TBS is related to bone microarchitecture and provides skeletal information that is not captured from the standard bone mineral density (BMD) measurement. Based on experimental variograms of the projected DXA image, TBS has the potential to discern differences between DXA scans that show similar BMD measurements. An elevated TBS value correlates with better skeletal microstructure; a low TBS value correlates with weaker skeletal microstructure. Lumbar spine TBS has been evaluated in cross-sectional and longitudinal studies. The following conclusions are based upon publications reviewed in this article: 1) TBS gives lower values in postmenopausal women and in men with previous fragility fractures than their nonfractured counterparts; 2) TBS is complementary to data available by lumbar spine DXA measurements; 3) TBS results are lower in women who have sustained a fragility fracture but in whom DXA does not indicate osteoporosis or even osteopenia; 4) TBS predicts fracture risk as well as lumbar spine BMD measurements in postmenopausal women; 5) efficacious therapies for osteoporosis differ in the extent to which they influence the TBS; 6) TBS is associated with fracture risk in individuals with conditions related to reduced bone mass or bone quality. Based on these data, lumbar spine TBS holds promise as an emerging technology that could well become a valuable clinical tool in the diagnosis of osteoporosis and in fracture risk assessment.

Congress Report: 5th Central and Eastern Europe (CEE) Summit on Osteoporosis in Bratislava, 2-3 December 2011.

Major aims of the 5th Central and Eastern Europe (CEE) Summit on Osteoporosis held in Bratislava, Slovakia, on 2 and 3 December 2011, were to provide participants with state-of-the-art knowledge in the fields of osteoporosis research, diagnosis, and therapy and to evaluate, compare, and discuss the very heterogeneous health care situations and related challenges in the different countries in CEE and elsewhere. The summit was attended by 70 delegates from 15 countries. State-of-the-art lectures given by international authorities on osteoporosis covered a broad spectrum of topics ranging from osteoporosis in the male population, novel therapies in osteoporosis such as cathepsin K and sclerostin inhibitors, and the implementation and use of FRAX® in CEE, to an update on denosumab for the management of osteoporosis. Workshops organized to enable the exchange of individual experiences addressed the importance and current availability of osteology training for physicians and the impact of patient training programs on therapy compliance. Furthermore, the availability of and need for standardized quality controls and therapy guidelines in different CEE countries were discussed. Finally, based on a questionnaire, a very up-to-date analysis of all participating countries regarding incidences of osteoporosis, commonly used diagnostic and therapeutic measures, the number of specialists and specialized hospitals, and differences in the reimbursement situation in the different countries was generated and presented. On the whole, the very authentic contributions and the synergistic exchange of ideas allowed the identification of both positive developments as well as still existing issues and needs in diagnosis and therapy of osteoporosis.

Epidemiology of fracture in the Russian Federation and the development of a FRAX model.

UNLABELLED: The incidence of hip, forearm and humeral fractures was studied in two cities from the Russian Federation. Fracture rates were used to create a FRAX model for Russia and to estimate the current and future burden of fracture. PURPOSE: There is scant information on the epidemiology of fracture in Russia. The aim of the study was to determine the incidence of major fractures in order to populate a new FRAX model and to characterise the burden and future burden of fractures. METHODS: The number of hip, forearm and humeral fractures was determined in two Russian cities with a well-defined catchment population over a 2-3-year period. Incidence rates for the two cities were merged and used to populate a FRAX model for Russia. Incidence rates were also applied to the general population in 2010 and 25 years later in 2035. RESULTS: A total of 6,012 fractures were documented. For hip fracture, 27 % of cases in Pervouralsk and 1.8 % in Yaroslavl were not registered in the hospital data base. The incidence of index fractures increased with age and was higher in women than in men. The lifetime probability of hip fracture at the age of 50 years was 4 % in men and 7 % in women. The total number of hip fractures estimated in 2010 (112,000) is expected to rise to 159,000 in 2035. The estimated number of major fractures will rise from 590,000 to 730,000 over the same time interval. CONCLUSIONS: Fragility fractures pose a serious health care problem in Russia. Urgent steps are needed to improve the acute management of hip fracture and long-term care of other osteoporotic fractures.

Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

Diagnostic performance of amyloid A protein quantification in fat tissue of patients with clinical AA amyloidosis.

OBJECTIVE: Amyloid A protein quantification in fat tissue is a new immunochemical method for detecting AA amyloidosis, a rare but serious disease. The objective was to assess diagnostic performance in clinical AA amyloidosis. METHODS: Abdominal subcutaneous fat tissue of patients with AA amyloidosis was studied at the start of an international clinical trial with eprodisate (NC-503; 1,3-propanedisulfonate; Kiacta), an antiamyloid compound. All patients had renal findings, i.e. proteinuria (> or =1 g/day) or reduced creatinine clearance (20 - 60 ml/min). Controls were patients with other types of amyloidosis and arthritic patients without amyloidosis. Amyloid A protein was quantified by ELISA using monoclonal antihuman serum amyloid A antibodies. Congo red stained slides were scored by light microscopy in a semiquantitative way (0 to 4+). RESULTS: Ample fat tissue (>50 mg) was available for analysis in 154 of 183 patients with AA amyloidosis and in 354 controls. The sensitivity of amyloid A protein quantification for detection of AA amyloidosis (>11.6 ng/mg fat tissue) was 84% (95% CI: 77 - 89%) and specificity 99% (95% CI: 98 - 100%). Amyloid A protein quantification and semiquantitative Congo red scoring were concordant. Men had lower amyloid A protein values than women (p < 0.0001) and patients with familial Mediterranean fever had lower values than patients with arthritis (p < 0.001) or other inflammatory diseases (p < 0.01). CONCLUSIONS: Amyloid A protein quantification in fat tissue is a sensitive and specific method for detection of clinical AA amyloidosis. Advantages are independence from staining quality and observer experience, direct confirmation of amyloid AA type, and potential for quantitative monitoring of tissue amyloid over time.

Eprodisate for the treatment of renal disease in AA amyloidosis.

BACKGROUND: Amyloid A (AA) amyloidosis is a complication of chronic inflammatory conditions that develops when proteolytic fragments of serum amyloid A protein (SAA) are deposited in tissues as amyloid fibrils. Amyloid deposition in the kidney causes progressive deterioration in renal function. Eprodisate is a member of a new class of compounds designed to interfere with interactions between amyloidogenic proteins and glycosaminoglycans and thereby inhibit polymerization of amyloid fibrils and deposition of the fibrils in tissues. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of eprodisate in patients with AA amyloidosis and kidney involvement. We randomly assigned 183 patients from 27 centers to receive eprodisate or placebo for 24 months. The primary composite end point was an assessment of renal function or death. Disease was classified as worsened if any one of the following occurred: doubling of the serum creatinine level, reduction in creatinine clearance by 50% or more, progression to end-stage renal disease, or death. RESULTS: At 24 months, disease was worsened in 24 of 89 patients who received eprodisate (27%) and 38 of 94 patients given placebo (40%, P=0.06); the hazard ratio for worsening disease with eprodisate treatment was 0.58 (95% confidence interval, 0.37 to 0.93; P=0.02). The mean rates of decline in creatinine clearance were 10.9 and 15.6 ml per minute per 1.73 m(2) of body-surface area per year in the eprodisate and the placebo groups, respectively (P=0.02). The drug had no significant effect on progression to end-stage renal disease (hazard ratio, 0.54; P=0.20) or risk of death (hazard ratio, 0.95; P=0.94). The incidence of adverse events was similar in the two groups. CONCLUSIONS: Eprodisate slows the decline of renal function in AA amyloidosis. (ClinicalTrials.gov number, NCT00035334.)