Andrea Trombetti

SURVIVAL AND POTENTIAL YEARS OF LIFE LOST AFTER HIP FRACTURE IN MEN AND AGE-MATCHED WOMEN

Abstract: Hip fracture is associated with a higher mortality rate in men than in women. However, mean age of men and women with hip fracture differs markedly. Thus, some of the differences in the clinical pattern and outcome between genders could be related to different ages. To avoid the influence of age on gender-specific outcome, we analyzed prefracture conditions and hip fracture outcome in a cohort of men and of age-matched women. Risk factors for low bone mass were recorded in 106 men (mean age ± SD, 80.3 ± 9.3 years) and 264 age-matched women (mean age 81.4 ± 8.0) with hip fracture. We compared mortality rate, survival, years of potential life lost and modification of housing conditions. These outcomes were prospectively assessed during an average 3.6 years follow-up (up to 7 years). Men with hip fracture differed from age-matched hip-fractured women by a higher alcohol and tobacco consumption, a greater frequency of living in couple, and by less prevalent fractures. Mortality rate after hip fracture was significantly higher in men (RR = 1.74, 95% CI 1.34–2.24). Since mortality is higher in the general male population, we compared reduction in life expectancy taking into account the gender-specific mortality rate. The excess mortality in each age-group of hip-fractured patients, which was measured during the whole follow-up period, and is an estimate of death attributable to fracture, did not differ between genders. Reduction in life expectancy due to hip fracture was similar in both genders (5.9 ± 4.5 and 5.8 ± 4.8 years, in men and women, respectively; NS), but the proportion of the years of life lost was higher in men (70 ± 33%) than in women (59 ± 42%, p < 0.01). It was concluded that for the same age, mortality rate after hip fracture was higher in men than in women. Although the reduction in life expectancy was similar in both genders, the proportion of the years of life lost was higher in men, suggesting a worse impact of hip fracture on survival in men, even after consideration of the higher mortality rate in the general male population.

Effect of Music-Based Multitask Training on Gait, Balance, and Fall Risk in Elderly People: A Randomized Controlled Trial

BACKGROUND Falls occur mainly while walking or performing concurrent tasks. We determined whether a music-based multitask exercise program improves gait and balance and reduces fall risk in elderly individuals. METHODS We conducted a 12-month randomized controlled trial involving 134 community-dwelling individuals older than 65 years, who are at increased risk of falling. They were randomly assigned to an intervention group (n = 66) or a delayed intervention control group scheduled to start the program 6 months later (n = 68). The intervention was a 6-month multitask exercise program performed to the rhythm of piano music. Change in gait variability under dual-task condition from baseline to 6 months was the primary end point. Secondary outcomes included changes in balance, functional performances, and fall risk. RESULTS At 6 months, there was a reduction in stride length variability (adjusted mean difference, -1.4%; P < .002) under dual-task condition in the intervention group, compared with the delayed intervention control group. Balance and functional tests improved compared with the control group. There were fewer falls in the intervention group (incidence rate ratio, 0.46; 95% confidence interval, 0.27-0.79) and a lower risk of falling (relative risk, 0.61; 95% confidence interval, 0.39-0.96). Similar changes occurred in the delayed intervention control group during the second 6-month period with intervention. The benefit of the intervention on gait variability persisted 6 months later. CONCLUSION In community-dwelling older people at increased risk of falling, a 6-month music-based multitask exercise program improved gait under dual-task condition, improved balance, and reduced both the rate of falls and the risk of falling. Trial Registration clinicaltrials.gov Identifier: NCT01107288.

Bone mineral density in lung-transplant recipients before and after graft: prevention of lumbar spine post-transplantation-accelerated bone loss by pamidronate.

BACKGROUND Lung-transplant recipients are at risk of osteoporosis. They may have low bone mass even before posttransplantation immunosuppressive therapy. We studied bone mineral density (BMD) before and after lung transplantation and compared the efficacy of antiresorptive therapies to calcium and vitamin D supplementation. METHODS Areal BMD was assessed in 42 patients awaiting lung transplantation and measured again after surgery at 6 (n = 29), and at 12 months (n = 20). Nineteen patients received antiresorptive therapy (30 mg pamidronate IV every 3 months (n = 14), or hormonal replacement therapy (n = 5)), and 10 patients received only calcium and vitamin D supplements. RESULTS Mean age- and gender-adjusted lumbar spine (LS) and femoral neck (FN) BMD was significantly decreased prior to transplantation (- 0.6 +/- 0.2, p< 0.01, and - 1.5 +/- 0.2 standard deviation, p < 0.001, respectively). At that time, 29% were osteoporotic (T-score < - 2.5 below the peak bone mass), while 55% were below - 1.0 T-score. Antiresorptive therapy decreased the rate of LS bone loss during the first 6 months and led to a significant increase of BMD at 1 year, with LS changes of + 0.2 +/- 0.1 vs - 0.4 +/- 0.1 Z-score in the calcium-vitamin D group (p< 0.002), and + 0.2 +/- 0.1 vs - 0.04 +/- 0.1 for FN (NS). One out of 20 patients experienced clinically evident fractures during antiresorptive therapy, and 3 out of 12 in the calcium-vitamin D group. CONCLUSION A significant proportion of patients awaiting lung transplantation was osteoporotic or osteopenic. Antiresorptive therapy (pamidronate or hormone-replacement therapy (HRT)) prevented accelerated LS bone loss after graft.

Primary hyperparathyroidism: can parathyroid carcinoma be anticipated on clinical and biochemical grounds? Report of nine cases and review of the literature.

BackgroundParathyroid carcinoma (PC) mimics benign primary hyperparathyroidism (PHP), but the diagnosis of PC is seldom available at the time of the first operation. Because PC is plagued by recurrences usually beyond cure, one may wonder whether some of these could be prevented by more extensive resections initially, i.e., if the diagnosis of PC were available at that time.MethodsOver a 25-year period, 311 consecutive patients with PHP underwent operation in our department: 302 had benign disease (adenomas or hyperplasias), and 9 had PC. Several clinical parameters, serum calcium and parathyroid hormone (PTH) levels, and the weight of the parathyroid tumor removed were compared in both groups. Receiver operating characteristic curves and logistical regression analyses were used to distinguish PC from benign PHP.ResultsEight of 9 patients with PC had symptoms, versus 238 (79%) of 302 with benign PHP (not significant). In the PC subgroup, serum calcium and PTH levels and the tumor weights of the parathyroid glands removed were significantly higher than in the benign PHP cohort, even if these three parameters were regularly flawed by low positive predictive values (14%, 20%, and 15%, respectively).ConclusionsSerum calcium, PTH levels, and tumor weights were significantly greater in the PC subgroup, even if not invariably in a discriminatory way. However, when PTH is <4 times the upper limit of normal and tumor weight is <1.9 g, the probability of PC is nil.

Effect of music-based multitask training on cognition and mood in older adults

BACKGROUND in a secondary analysis of a randomised controlled trial, we investigated whether 6 months of music-based multitask training had beneficial effects on cognitive functioning and mood in older adults. METHODS 134 community-dwellers aged ≥65 years at increased risk for falling were randomly assigned to either an intervention group (n = 66) who attended once weekly 1-h supervised group classes of multitask exercises, executed to the rhythm of piano music, or a control group with delayed intervention (n = 68) who maintained usual lifestyle habits, for 6 months. A short neuropsychological test battery was administered by an intervention-blinded neuropsychologist at baseline and Month 6, including the mini-mental state examination (MMSE), the clock-drawing test, the frontal assessment battery (FAB) and the hospital anxiety (HADS-A) and depression scale. RESULTS intention-to-treat analysis showed an improvement in the sensitivity to interference subtest of the FAB (adjusted between-group mean difference (AMD), 0.12; 95% CI, 0.00 to 0.25; P = 0.047) and a reduction in anxiety level (HADS-A; AMD, -0.88; 95% CI, -1.73 to -0.05; P = 0.039) in intervention participants, as compared with the controls. Within-group analysis revealed an increase in MMSE score (P = 0.004) and a reduction in the number of participants with impaired global cognitive performance (i.e., MMSE score ≤23; P = 0.003) with intervention. CONCLUSION six months of once weekly music-based multitask training was associated with improved cognitive function and decreased anxiety in community-dwelling older adults, compared with non-exercising controls. Studies designed to further delineate whether training-induced changes in cognitive function could contribute to dual-task gait improvements and falls reduction, remain to be conducted.

Low Lean Mass Predicts Incident Fractures Independently From FRAX: a Prospective Cohort Study of Recent Retirees

Whether low muscle mass predisposes to fracture is still poorly understood. In the diagnosis of sarcopenia, different thresholds for low lean mass have been proposed but comparative data for these criteria against hard outcomes such as fractures are lacking. This study aimed to investigate the prevalence of low lean mass according to different thresholds used in operational definitions of sarcopenia and their association with 3‐year fracture incidence in a cohort of healthy 63‐ to 67‐year‐old community dwellers. In a longitudinal analysis of 913 participants (mean age 65.0 ± 1.4 years) enrolled in the Geneva Retirees Cohort (GERICO) study, lean mass was assessed by dual‐energy X‐ray absorptiometry (DXA), and low trauma clinical fracture incidence was recorded over a 3‐year period. Prevalence of low lean mass ranged from 3.5% to 20.2% according to the threshold applied. During a follow‐up of 3.4 ± 0.9 years, 40 (4.4%) participants sustained at least one low trauma fracture. After multivariate adjustment including Fracture Risk Assessment Tool (FRAX) probability with femoral neck bone mineral density (BMD), low lean mass, as defined by Baumgartner thresholds, was associated with higher fracture risk (odds ratio [OR], 2.32; 95% CI, 1.04 to 5.18; p = 0.040). It also added significant predictive value beyond FRAX (likelihood ratio test for nested models, 4.28; p < 0.039). No significant association was found for other definition thresholds. The coexistence of sarcopenia and a T‐score <–2.5 at spine or hip was associated with a 3.39‐fold (95% CI, 1.54 to 7.46; p = 0.002) increase in low trauma fracture risk. In conclusion, low lean mass, as defined by the Baumgartner thresholds, is a predictor of incident fractures in a large cohort of healthy 65‐year‐old community dwellers, independently of FRAX probability. The increased risk is related to the threshold for low lean mass selected. These findings suggest that identification of sarcopenia should be considered in fracture risk assessment beyond usual risk factors.

Early post-transplantation hypophosphatemia is associated with elevated FGF-23 levels

BACKGROUND We examined the hypothesis that high FGF-23 levels early after transplantation contribute to the onset of hypophosphatemia, independently of parathyroid hormone (PTH) and other factors regulating phosphate metabolism. METHODS We measured serum phosphate levels (sPi), renal tubular reabsorption of Pi (TmPi/GFR), estimated GFR (eGFR), intact PTH (iPTH), calcitriol, intact (int) and C-terminal (Cter) FGF-23, dietary Pi intake and cumulative doses of glucocorticoids in 69 patients 12 days (95% confidence interval, 10-13) after renal transplantation. RESULTS Hypophosphatemia was observed in 43 (62%) of the patients 12 days after transplantation. Compared with non-hypophosphatemic subjects, their post-transplantation levels of intact and CterFGF-23 were higher (195 (108-288) vs 48 (40-64) ng/l, P<0.002 for intFGF-23; 205 (116-384) vs 81 (55-124) U/ml, P<0.002, for CterFGF-23). In all subjects, Cter and intFGF-23 correlated inversely with sPi (r=-0.35, P<0.003; -0.35, P<0.003, respectively), and TmPi/GFR (r=-0.50, P<0.001; -0.54, P<0.001, respectively). In multivariate models, sPi and TmPi/GFR were independently associated with FGF-23, iPTH and eGFR. Pre-transplant iPTH levels were significantly higher in patients developing hypophosphatemia after renal transplantation. Pre-transplant levels of FGF-23 were not associated with sPi at the time of transplantation. CONCLUSION In addition to PTH, elevated FGF-23 may contribute to hypophosphatemia during the early post-renal transplant period.

The FIM® instrument to identify patients at risk of falling in geriatric wards: a 10-year retrospective study

OBJECTIVES the main objective was to evaluate if the admission functional independence measure (FIM) score could be used to predict the risk of falls in geriatric inpatients. DESIGN a 10-year retrospective study was performed. SETTING the study was conducted in a 298-bed geriatric teaching hospital in Geneva, Switzerland. SUBJECTS all patients discharged from the hospital from 1 January 1997 to 31 December 2006 were selected. MAIN OUTCOME MEASURES measures used were FIM scores at admission using the FIM instrument and number of falls extracted from the institutions fall report forms. RESULTS during the study period, there were 23,966 hospital stays. A total of 8,254 falls occurred. Of these, 7,995 falls were linked to 4,651 stays. Falls were recorded in 19.4% of hospital stays, with a mean incidence of 7.84 falls per 1,000 patients-days. Although there was a statistically significant relationship between total FIM score, its subscales, and the risk of falling, the sensitivity, specificity, positive predictive value and negative predictive value obtained with receiver operating characteristic curves were insufficient to permit fall prediction. This might be due in part to a non-linear relationship between FIM score and fall risk. CONCLUSION in this study, the FIM instrument was found to be unable to predict risk of falls in general geriatric wards.

Reliability and minimal detectable change of gait variables in community-dwelling and hospitalized older fallers

PURPOSE Gait variables may constitute surrogate outcomes for fall risk. Their reliability in a specific population of older fallers has not been fully established, which limits their research and clinical applications. This study aimed to determine test-retest reliability and minimal detectable change (MDC) values for selected fall-related gait variables in older adults with a recent fall history. METHODS Community-dwelling (n=30) and hospitalized (n=30) fallers aged≥65 years were assessed twice using an instrumented pressure-sensitive walkway, under single- and dual-task gait conditions. Intraclass correlation coefficient (ICC(2,1)), standard error of measurement (SEM; SEM%) and MDC at 95% confidence level (MDC95; MDC95%), were used as reliability estimates. RESULTS The ICC(2,1) for gait velocity was greater than 0.84 across all gait conditions and groups; SEM% and MDC95% did not exceed 6.5% and 18.1%, respectively. Gait variability measures returned lower ICC(2,1) (range 0.18-0.79), and markedly higher SEM% (16.3-31.9%) and MDC95% (45.3-88.3%). Overall, hospitalized fallers exhibited larger SEM and MDC95 values for variability measures compared to community-dwellers in all gait conditions, while larger values were found for all variables while dual-tasking compared to single-tasking in both groups. CONCLUSIONS Gait velocity was found to be highly reliable and likely to be sensitive to change over repeated sessions in community-dwelling and hospitalized older fallers, both under single- and dual-task conditions. Gait variability measures showed lower reliability, irrespective of gait condition or group, displaying consistently larger measurement error, particularly under dual-task conditions. Clinicians should consider MDC95 values before using gait variability variables as evaluative outcome measures at patient level.

Selective Determinants of Low Bone Mineral Mass in Adult Women with Anorexia Nervosa

We investigated the relative effect of amenorrhea and insulin-like growth factor-I (sIGF-I) levels on cancellous and cortical bone density and size. We investigated 66 adult women with anorexia nervosa. Lumbar spine and proximal femur bone mineral density was measured by DXA. We calculated bone mineral apparent density. Structural geometry of the spine and the hip was determined from DXA images. Weight and BMI, but not height, as well as bone mineral content and density, but not area and geometry parameters, were lower in patients with anorexia nervosa as compared with the control group. Amenorrhea, disease duration, and sIGF-I were significantly associated with lumbar spine and proximal femur BMD. In a multiple regression model, we found that sIGF-I was the only significant independent predictor of proximal femur BMD, while duration of amenorrhea was the only factor associated with lumbar spine BMD. Finally, femoral neck bone mineral apparent density, but not hip geometry variables, was correlated with sIGF-I. In anorexia nervosa, spine BMD was related to hypogonadism, whereas sIGF-I predicted proximal femur BMD. The site-specific effect of sIGF-I could be related to reduced volumetric BMD rather than to modified hip geometry.