Nutritional status and nutritional treatment are related to outcomes and mortality in older adults with hip fracture

Malnutrition is very prevalent in geriatric patients with hip fracture. Nevertheless, its importance is not fully recognized. The objective of this paper is to review the impact of malnutrition and of nutritional treatment upon outcomes and mortality in older people with hip fracture. We searched the PubMed database for studies evaluating nutritional aspects in people aged 70 years and over with hip fracture. The total number of studies included in the review was 44, which analyzed 26,281 subjects (73.5% women, 83.6 ± 7.2 years old). Older people with hip fracture presented an inadequate nutrient intake for their requirements, which caused deterioration in their already compromised nutritional status. The prevalence of malnutrition was approximately 18.7% using the Mini-Nutritional Assessment (MNA) (large or short form) as a diagnostic tool, but the prevalence was greater (45.7%) if different criteria were used (such as Body Mass Index (BMI), weight loss, or albumin concentration). Low scores in anthropometric indices were associated with a higher prevalence of complications during hospitalization and with a worse functional recovery. Despite improvements in the treatment of geriatric patients with hip fracture, mortality was still unacceptably high (30% within 1 year and up to 40% within 3 years). Malnutrition was associated with an increase in mortality. Nutritional intervention was cost effective and was associated with an improvement in nutritional status and a greater functional recovery. To conclude, in older people, the prevention of malnutrition and an early nutritional intervention can improve recovery following a hip fracture

Epidemiology of hip fracture in Belarus: development of a country-specific FRAX model and its comparison to neighboring country models

Summary Fracture probabilities resulting from the newly generated FRAX model for Belarus based on regional estimates of the hip fracture incidence were compared with FRAX models of neighboring countries. Differences between the country-specific FRAX patterns and the rank orders of fracture probabilities were modest. Objective This paper describes the epidemiology of hip fractures in Belarus that was used to develop the country-specific fracture prediction FRAX® tool and illustrates its features compared to models for the neighboring countries of Poland, Russia, and Lithuania. Methods We carried out a population-based study in a region of Belarus (the city of Mozyr) representing approximately 1.2% of the country’s population. We aimed to identify all hip fractures in 2011–2012 from hospital registers and primary care sources. Age- and sex-specific incidence and national mortality rates were incorporated into a FRAX model for Belarus. Fracture probabilities were compared with those derived from FRAX models in neighboring countries. Results The estimated number of hip fractures nationwide in persons over the age of 50 years for 2015 was 8250 in 2015 and is predicted to increase to 12,918 in 2050. The annual incidence of fragility hip fractures in individuals aged 50 years or more was 24.6/10,000 for women and 14.6/10,000 for men, standardized to the world population. The comparison with FRAX models in neighboring countries showed that hip fracture probabilities in men and women in Belarus were similar to those in Poland, Russia, and Lithuania. The difference in incidence rates between the surveys including or excluding data from primary care suggested that 29.1% of patients sustaining a hip fracture were not hospitalized and, therefore, did not receive specialized medical care. Conclusion A substantial proportion of hip fractures in Belarus does not come to hospital attention. The FRAX model should enhance accuracy of determining fracture probability among the Belarus population and help guide decisions about treatment

Development and application of a Japanese model of the WHO fracture risk assessment tool (FRAX™)

SUMMARY: The present study estimated the 10-year probability using the Japanese version of WHO fracture risk assessment tool (FRAX) in order to determine fracture probabilities that correspond to intervention thresholds currently used in Japan and to resolve some issues for its use in Japan. INTRODUCTION: The objective of the present study was to evaluate a Japanese version of the WHO fracture risk assessment (FRAX) tool to compute 10-year probabilities of osteoporotic fracture in Japanese men and women. Since lumbar spine bone mineral density (BMD) is used preferentially as a site for assessment, and densitometers use Japanese reference data, a second aim was to investigate the suitability and impact of this practice in Japan. METHODS: Fracture probabilities were computed from published data on the fracture and death hazards in Japan. Probabilities took account of age, sex, the presence of clinical risk factors and femoral neck BMD. Fracture probabilities were determined that were equivalent to intervention thresholds currently used in Japan. The difference between T-scores derived from international reference data and that using Japanese-specific normal ranges was estimated from published sources. The gradient of risk of BMD for fracture in Japan was compared to that for BMD at the lumbar spine in the Hiroshima cohort. RESULTS: The 10-year probabilities of a major osteoporosis-related fracture that corresponded to current intervention thresholds ranged from approximately 5% at the age of 50 years to more than 20% at the age of 80 years. The use of femoral neck BMD predicts fracture as well as or better than BMD tests at the lumbar spine. There were small differences in T-scores between those used for the model and those derived from a Japanese reference population. CONCLUSIONS: The FRAX mark tool has been used to determine possible thresholds for therapeutic intervention, based on equivalence of risk with current guidelines. The approach will need to be supported by appropriate health economic analyses. Femoral neck BMD is suitable for the prediction of fracture risk among Japanese. However, when applying the FRAX model to Japan, T-scores and Z-scores should be converted to those derived from the international reference

FRAX- vs. T-score-based intervention thresholds for osteoporosis

Many current guidelines for the assessment of osteoporosis, including those in Kuwait, initiate fracture risk assessment in men and women using BMD T-score thresholds. We compared the Kuwaiti guidelines with FRAX-based age-dependent intervention thresholds equivalent to that in women with a prior fragility fracture. FRAX-based intervention thresholds identified women at higher fracture probability than fixed T-score thresholds, particularly in the elderly. PURPOSE: A FRAX® model been recently calibrated for Kuwait, but guidance is needed on how to utilise fracture probabilities in the assessment and treatment of patients. METHODS: We compared age-specific fracture probabilities, equivalent to women with no clinical risk factors and a prior fragility fracture (without BMD), with the age-specific fracture probabilities associated with femoral neck T-scores of -2.5 and -1.5 SD, in line with current guidelines in Kuwait. Upper and lower assessment thresholds for BMD testing were additionally explored using FRAX. RESULTS: When a BMD T-score of -2.5 SD was used as an intervention threshold, FRAX probabilities of a major osteoporotic fracture in women aged 50 years were approximately twofold higher than those in women of the same age but with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 83 years or more, a T-score of -2.5 SD was associated with a lower probability of fracture than that of the age-matched general population with no clinical risk factors. The same phenomenon was observed from the age of 66 years at a T-score of -1.5 SD. A FRAX-based intervention threshold, defined as the 10-year probability of a major osteoporotic fracture in a woman of average BMI with a previous fracture, rose with age from 4.3% at the age of 50 years to 23%, at the age of 90 years, and identified women at increased risk at all ages. Qualitatively comparable findings were observed in the case of hip fracture probability and in men. CONCLUSION: Intervention thresholds based on BMD alone do not optimally target women at higher fracture risk than those on age-matched individuals without clinical risk factors, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a 'fracture threshold' consistently target women at higher fracture risk, irrespective of age

Efficacy of weekly teriparatide does not vary by baseline fracture probability calculated using FRAX

Summary The aim of this study was to determine the efficacy of once-weekly teriparatide as a function of baseline fracture risk. Treatment with once-weekly teriparatide was associated with a statistically significant 79 % decrease in vertebral fractures, and in the cohort as a whole, efficacy was not related to baseline fracture risk. Introduction Previous studies have suggested that the efficacy of some interventions may be greater in the segment of the population at highest fracture risk as assessed by the FRAX® algorithms. The aim of the present study was to determine whether the antifracture efficacy of weekly teriparatide was dependent on the magnitude of fracture risk. Methods Baseline fracture probabilities (using FRAX) were computed from the primary data of a phase 3 study (TOWER) of the effects of weekly teriparatide in 542 men and postmenopausal women with osteoporosis. The outcome variable comprised morphometric vertebral fractures. Interactions between fracture probability and efficacy were explored by Poisson regression. Results The 10-year probability of major osteoporotic fractures (without BMD) ranged from 7.2 to 42.2 %. FRAX-based hip fracture probabilities ranged from 0.9 to 29.3 %. Treatment with teriparatide was associated with a 79 % (95 % CI 52–91 %) decrease in vertebral fractures assessed by semiquantitative morphometry. Relative risk reductions for the effect of teriparatide on the fracture outcome did not change significantly across the range of fracture probabilities (p = 0.28). In a subgroup analysis of 346 (64 %) participants who had FRAX probabilities calculated with the inclusion of BMD, there was a small but significant interaction (p = 0.028) between efficacy and baseline fracture probability such that high fracture probabilities were associated with lower efficacy. Conclusion Weekly teriparatide significantly decreased the risk of morphometric vertebral fractures in men and postmenopausal women with osteoporosis. Overall, the efficacy of teriparatide was not dependent on the level of fracture risk assessed by FRAX in the cohort as a whole

Epidemiology of fractures in Armenia: development of a country-specific FRAX model and comparison to its surrogate

Summary: Fracture probabilities derived from the surrogate FRAX model for Armenia were compared to those from the model based on regional estimates of the incidence of hip fracture. Disparities between the surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal. Objective: Armenia has relied on a surrogate FRAX model based on the fracture epidemiology of Romania. This paper describes the epidemiology of fragility fractures in Armenia used to create an Armenia-specific FRAX model with an aim of comparing this new model with the surrogate model. Methods: We carried out a population-based study in two regions of Armenia (Ararat and Vayots Dzor representing approximately 11% of the country’s population). We aimed to identify all low-energy fractures: retrospectively from hospital registers in 2011–2012 and prospectively in 2013 with the inclusion of primary care sources. Results: The differences in incidence between the surveys with and without data from primary care suggested that 44% of patients sustaining a hip fracture did not receive specialized medical care. A similar proportion of forearm and humeral fractures did not come to hospital attention (48 and 49%, respectively). Only 57.7% of patients sustaining a hip fracture were hospitalized. In 2013, hip fracture incidence at the age of 50 years or more was 201/100,000 for women and 136/100,000 for men, and age- and sex-specific rates were incorporated into the new “authentic” FRAX model for Armenia. Compared to the surrogate model, the authentic model gave lower 10-year fracture probabilities in men and women aged less than 70 years but substantially higher above this age. Notwithstanding, there were very close correlations in fracture probabilities between the surrogate and authentic models ( >  0.99) so that the revisions had little impact on the rank order of risk. Conclusion: A substantial proportion of major osteoporotic fractures in Armenia do not come to hospital attention. The disparities between surrogate and authentic FRAX models indicate the importance of developing country-specific FRAX models. Despite large differences between models, differences in the rank order of fracture probabilities were minimal

Calibration of FRAX ® 3.1 to the Dutch population with data on the epidemiology of hip fractures

SummaryThe FRAX tool has been calibrated to the entire Dutch population, using nationwide (hip) fracture incidence rates and mortality statistics from the Netherlands. Data used for the Dutch model are described in this paper.IntroductionRisk communication and decision making about whether or not to treat with anti-osteoporotic drugs with the use of T-scores are often unclear for patients. The recently developed FRAX models use easily obtainable clinical risk factors to estimate an individual's 10-year probability of a major osteoporotic fracture and hip fracture that is useful for risk communication and subsequent decision making in clinical practice. As of July 1, 2010, the tool has been calibrated to the total Dutch population. This paper describes the data used to develop the current Dutch FRAX model and illustrates its features compared to other countries.MethodsAge- and sex-stratified hip fracture incidence rates (LMR database) and mortality rates (Dutch national mortality statistics) for 2004 and 2005 were extracted from Dutch nationwide databases (patients aged 50+ years). For other major fractures, Dutch incidence rates were imputed, using Swedish ratios for hip to osteoporotic fracture (upper arm, wrist, hip, and clinically symptomatic vertebral) probabilities (age- and gender-stratified). The FRAX tool takes into account age, sex, body mass index (BMI), presence of clinical risk factors, and bone mineral density (BMD).ResultsFracture incidence rates increased with increasing age: for hip fracture, incidence rates were lowest among Dutch patients aged 50–54 years (per 10,000 inhabitants: 2.3 for men, 2.1 for women) and highest among the oldest subjects (95–99 years; 169 of 10,000 for men, 267 of 10,000 for women). Ten-year probability of hip or major osteoporotic fracture was increased in patients with a clinical risk factor, lower BMI, female gender, a higher age, and a decreased BMD T-score. Parental hip fracture accounted for the greatest increase in 10-year fracture probability.ConclusionThe Dutch FRAX tool is the first fracture prediction model that has been calibrated to the total Dutch population, using nationwide incidence rates for hip fracture and mortality rates. It is based on the original FRAX methodology, which has been externally validated in several independent cohorts. Despite some limitations, the strengths make the Dutch FRAX tool a good candidate for implementation into clinical practice

FRAX™ and the assessment of fracture probability in men and women from the UK

SUMMARY: A fracture risk assessment tool (FRAX) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. INTRODUCTION: The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. METHODS: Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. RESULTS: Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m(2)) ranged from 0.2% at the age of 50 years for women without CRF's to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. CONCLUSION: The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD

Treatment of malignant hypercalcaemia with aminohexane bisphosphonate (neridronate).

Twenty patients with hypercalcaemia due to malignancy, which persisted following rehydration, were treated with the bisphosphonate, aminohexane bisphosphonate (AHBP), which is structurally similar to pamidronate. The treatment given was a single infusion of 125 mg of AHBP in 500 ml of normal saline infused over 4 h. Serum and urine biochemistry were measured before and after treatment. Acute toxicity was evaluated with particular attention to gastrointestinal symptoms, acute-phase reaction and change in renal function, as judged by serum creatinine. The infusion of AHBP induced a rapid fall apparent by day 3 (P < 0.001), with a nadir at day 7. The serum calcium remained lower at days 14 and 28 than at day 0, but the numbers followed up were low (n = 5 and n = 4). In all 20 patients there was a fall in serum calcium after treatment, and in 13 (65%) normocalcaemia was achieved. Failure to respond completely to AHBP appeared to be associated with a renal mechanism of hypercalcaemia. Treatment was associated with a significant decrease in fasting urinary calcium excretion (P < 0.05). There was no change in white cell count or renal function following AHBP and only two cases of mild pyrexia after infusion. We conclude that aminohexane bisphosphonate is an effective agent in the treatment of tumour-induced hypercalcaemia, with rapid onset of effect and low toxicity