-
[show abstract]
[hide abstract]
ABSTRACT: Given the significant health and socioeconomic consequences of falls, to develop and promote effective falls prevention strategies among older adults represents a major issue. Jaques-Dalcroze eurhythmics is a music education program through movement method developed in Geneva, Switzerland, in the early 20th century. This new exercise form, adapted for elderly people, features various multitask exercises performed to the rhythm of improvised piano music and mainly challenge gait and balance, but also memory, attention and coordination. We report here the results of a randomized controlled trial conducted in Geneva showing that Jaques-Dalcroze eurythmics practice can improve gait performance under single and dual-task conditions, and balance, as well as reduce both rate of falls and the risk of falling in at-risk elderly community-dwellers.
Revue médicale suisse 06/2011; 7(299):1305-8, 1310.
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
In addition to PTH, elevated FGF-23 may contribute to hypophosphatemia during the early post-renal transplant period.
European Journal of Endocrinology 02/2011; 164(5):839-47. · 3.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This study examined patients' risk profiles and adherence to treatment in relation to the effect of risedronate and raloxifene on hip fracture incidence. Administrative billing data were used to follow two cohorts of women aged 65 and older after starting therapy with either risedronate (n = 86,735) or raloxifene (n = 37,726). The fracture risk profile was described using a 6-month history period before starting therapy. Effectiveness of each therapy was evaluated by comparing the incidence of hip fractures during the first 3 months with the subsequent 12 months among women adherent (medication possession ratio >80%) compared with those non-adherent to treatment. At the start of therapy, the raloxifene cohort was younger than the risedronate cohort (median age 73 vs. 76 years) and had fewer prior fractures (p < 0.01 for both). In the first 3 months of therapy, hip fracture incidence was lower in the raloxifene group (0.51 per 100 person-years) compared with the risedronate group (0.94 per 100 person-years). In the subsequent 12 months, the incidence of hip fractures decreased among patients adherent to the risedronate regimen [relative risk (RR) 0.70, 95% CI 0.59-0.84, p < 0.01] and did not change significantly among patients adherent to the raloxifene regimen (RR 1.02, 95% CI 0.73-1.44). In poorly adherent patients, neither drug decreased hip fracture risk. Risedronate treatment in adherent patients rapidly decreased the risk of hip fractures, whereas raloxifene treatment did not.
Journal of Bone and Mineral Metabolism 01/2011; 29(5):561-70. · 2.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
Archives of internal medicine 11/2010; 171(6):525-33. · 11.46 Impact Factor
-
Serge Ferrari
[show abstract]
[hide abstract]
ABSTRACT: Among the available agents for osteoporosis, anti-resorptive drugs do not increase bone formation, whereas anabolic agents do not reduce bone resorption. Strontium ranelate (SR) uniquely does both, rebalancing bone turnover in favour of bone formation. In the Spinal Osteoporosis Therapeutic Intervention (SOTI) study, a 4-year trial, SR treatment reduced vertebral fracture risk by 33% (P < 0.001), and symptomatic vertebral fracture risk by 36% (P < 0.001). SR also significantly improved quality of life as assessed by the Quality-of-Life Questionnaire in Osteoporosis (QUALIOST) instrument. In the Treatment of Peripheral Osteoporosis Study (TROPOS) study, a 5-year trial, SR significantly reduced total fracture risk by 20% (29.1 vs 33.9%; P < 0.001), total non-vertebral fracture risk by 15% (18.6 vs 20.9%; P = 0.032) and hip fracture risk by 43% (7.2 vs 10.2%; P = 0.036) in the subgroup that is at high risk for hip fracture. Analysis of pooled data from these two studies found that SR is also safe and effective in patients aged >or=80 years, reducing the risk of vertebral fracture over 5 years by 31% (P = 0.010) and non-vertebral fracture by 26% (P = 0.019). Adherence to treatment in the trials exceeded 80%, and the adverse event profile of SR was similar to that of placebo. Taken together, these long-term findings clearly demonstrate that SR is safe and effective in reducing both vertebral and non-vertebral (particularly hip) fracture risks for at least 5 years of pre-planned follow-up.
Rheumatology (Oxford, England) 10/2009; 48 Suppl 4:iv20-4. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Bone mass and strength achieved at the end of the growth period, simply designated as 'Peak Bone Mass (PBM)', plays an essential role in the risk of osteoporotic fractures occurring in adulthood. It is considered that an increase of PBM by one standard deviation would reduce the fracture risk by 50%. As estimated from twin studies, genetics is the major determinant of PBM, accounting for about 60 to 80% of its variance. During pubertal maturation, the size of the bone increases whereas the volumetric bone mineral density remains constant in both genders. At the end of puberty, the sex difference is essentially due to a greater bone size in male than female subjects. This is achieved by larger periosteal deposition in boys, thus conferring at PBM a better resistance to mechanical forces in men than in women. Sex hormones and the IGF-1 system are implicated in the bone sexual dimorphism occurring during pubertal maturation. The genetically determined trajectory of bone mass development can be modulated to a certain extent by modifiable environmental factors, particularly physical activity, calcium and protein intakes. Prepuberty appears to be an opportune time to modify environmental factors that impinge on bone mineral mass acquisition.
Salud publica de Mexico 02/2009; 51 Suppl 1:S5-17. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Late menarche is a risk factor for fragility fractures. We hypothesized that pubertal timing-dependent alterations in bone structural components would persist from peak bone mass to menopause, independent of premenopausal bone loss. We studied the influence of menarcheal age (MENA) on femoral neck BMD (FN aBMD) by DXA and microstructure of distal tibia by HR-pQCT in healthy young adult (YAD; 20.4 +/- 0.6 [SD] yr, n = 124) and premenopausal middle-aged (PREMENO; 45.8 +/- 3.4 yr, n = 120) women. Median of MENA was 13.0 +/- 1.2 and 13.1 +/- 1.7 yr in YAD and PREMENO, respectively. In YAD and PREMENO (n = 244), FN aBMD (R = -0.29, p = 0.013), as well as total volumetric BMD (Dtot; R = -0.23, p = 0.006) and cortical thickness (Ct.Th; R = -0.18, p = 0.011) of distal tibia were inversely correlated to MENA. After segregation by the median of MENA in EARLY and LATE subgroups, the significant influences of both MENA (p = 0.004) and chronological age (p < 0.0001) were observed for FN aBMD and trabecular bone volume fraction of the distal tibia with similar differences in T-scores between LATE and EARLY subgroups in YAD (-0.36 and -0.31 T-scores) and PREMENO (-0.35 and -0.42 T-scores) women. Ct.Th was negatively influenced by MENA, whereas trabecular thickness (Tb.Th) was negatively influenced by chronological age. There was a striking inverse relationship between cross-sectional area and Ct.Th (R = -0.57, p < 0.001). In conclusion, the negative influence of late menarcheal age at weight-bearing sites as observed by the end of skeletal growth remains unattenuated a few years before menopause and is independent of premenopausal bone loss. Alterations in both bone mineral mass and microstructural components may explain the increased risk of fragility fractures associated with later menarcheal age.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 01/2009; 24(1):144-52. · 6.04 Impact Factor
-
Serge Ferrari
[show abstract]
[hide abstract]
ABSTRACT: A family history of hip fracture carries a twofold increased risk of fracture among descendants. Genetic factors indeed play a major role in the determination of bone mineral density (BMD) and osteoporosis risk. Multiple chromosomal loci have been mapped by linkage approaches which potentially carry hundreds of genes involved in the determination of bone mass and quality. Association studies based on candidate gene polymorphisms and subsequent meta-analyses, and the more recent genome-wide association studies (GWAS), have clearly identified a handful of genes associated with BMD and/or fragility fractures. Among them are genes coding for the LDL-receptor related protein 5 (LRP5), estrogen receptor alpha (ESR1) and osteoprotegerin, OPG (TNFRSf11b). However, the percentage of osteoporosis risk explained by any of these polymorphisms is small, indicating that most genetic risk factors remain to be discovered and/or that interaction with environmental factors needs further consideration.
Best practice & research. Clinical endocrinology & metabolism 11/2008; 22(5):723-35. · 3.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Shorter estrogen exposure from puberty onset to peak bone mass attainment may explain how late menarche is a risk factor for osteoporosis. The influence of menarcheal age (MENA) on peak bone mass, cortical, and trabecular microstructure was studied in 124 healthy women aged 20.4 +/- 0.6 (sd) yr.
At distal radius, areal bone mineral density (aBMD) was measured by dual-energy x-ray absorptiometry, and volumetric bone mineral density (BMD) and microstructure were measured by high-resolution peripheral computerized tomography, including: total, cortical, and trabecular volumetric BMD and fraction; trabecular number, thickness, and spacing; cortical thickness (CTh); and cross-sectional area (CSA).
Median MENA was 12.9 yr. Mean aBMD T score of the whole cohort was slightly positive. aBMD was inversely correlated to MENA for total radius (R = -0.21; P = 0.018), diaphysis (R = -0.18; P = 0.043), and metaphysis (R = -0.19; P = 0.031). Subjects with MENA more than the median [LATER: 14.0 +/- 0.7 (+/-sd) yr] had lower aBMD than those with MENA less than the median (EARLIER: 12.1 +/- 0.7 yr) in total radius (P = 0.026), diaphysis (P = 0.042), and metaphysis (P = 0.046). LATER vs. EARLIER displayed lower total volumetric BMD (315 +/- 54 vs. 341 +/- 56 mg HA/cm(3); P = 0.010), cortical volumetric BMD (874 +/- 49 vs. 901 +/- 44 mg HA/cm(3); P = 0.003), and CTh (774 +/- 170 vs. 849 +/- 191 microm; P = 0.023). CTh was inversely related to CSA (R = -0.46; P < 0.001). In LATER reduced CTh was associated with 5% increased CSA.
In healthy young adult women, a 1.9-yr difference in mean MENA was associated with lower radial aBMD T score, lower CTh without reduced CSA, a finding compatible with less endocortical accrual. It may explain how late menarche is a risk factor for forearm osteoporosis.
Journal of Clinical Endocrinology & Metabolism 07/2008; 93(7):2594-601. · 6.50 Impact Factor
-
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 06/2008; 23(5):770; author reply 771. · 6.04 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In 232 healthy prepubertal boys, increased physical activity was associated with greater BMC at both axial and appendicular sites under high-protein intake.
Physical activity is an important lifestyle determinant of bone mineral mass acquisition. Its impact during childhood can be modulated by nutrition, particularly by protein and calcium intakes. We analyzed the relationship between physical activity levels and protein compared with calcium intake on BMC.
In 232 healthy prepubertal boys (age: 7.4 +/- 0.4 [SD] yr; standing height: 125.7 +/- 5.9 cm; body weight: 25.3 +/- 4.6 kg), physical activity and protein and calcium intakes were recorded. BMC was measured by DXA at the radial metaphysis, radial diaphysis, total radius, femoral neck, total hip, femoral diaphysis, and L(2)-L(4) vertebrae.
In univariate analysis, the correlation coefficients r with BMC of the various skeletal sites were as follows: physical activity, from 0.26 (p = 0.0001) to 0.40 (p = 0.0001); protein intake, from 0.18 (p = 0.005) to 0.27 (p = 0.0001); calcium intake, from 0.09 (p = 0.181) to 0.17 (p = 0.007). By multiple regression analysis, the beta-adjusted values remained correlated with BMC, ranging as follows: physical activity, from 0.219 (p = 0.0007) to 0.340 (p < 0.0001); protein intake, from 0.120 (p = 0.146) to 0.217 (p = 0.009). In contrast, it was not correlated for calcium intake: from -0.069 (p = 0.410) to 0.001 (p = 0.986). With protein intake (mean = 2.0 g/kg body weight/d) above the median, increased physical activity from 168 to 321 kcal/d was associated with greater mean BMC Z-score (+0.6, p = 0.0005). In contrast with protein intake (mean = 1.5 g/kg body weight/d) below the median, increased physical activity from 167 to 312 kcal/d was not associated with a significantly greater mean BMC Z-score (+0.2, p = 0.371). The interaction between physical activity and protein intake was close to statistical significance for mean BMC Z-score (p = 0.055) and significant for femoral neck BMC (p = 0.012). In keeping with the results derived from multiple regression analysis, the increased physical activity on mean BMC Z-score was not influenced by difference in calcium intake above (mean = 945 mg/d) and below (mean = 555 mg/d) the median.
In healthy prepubertal boys, the impact in increased physical activity on BMC seems to be enhanced by protein intake within limits above the usual recommended allowance.
Journal of Bone and Mineral Research 01/2008; 23(1):131-42. · 6.37 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The contribution of leptin to bone mass acquisition in humans remains unclear. We investigated the association of the Gln223Arg polymorphism in the leptin receptor gene (LEPR) with bone mineral content (BMC) and areal bone mineral density (aBMD) in prepubertal boys and LEPR interaction with vitamin D receptor (VDR) genotypes (Bsm1 and Fok1).
In a cross-sectional design with a longitudinal follow-up, dual-energy x-ray absorptiometry measurements at the lumbar spine, hip, femoral diaphysis, and radius were performed at baseline (mean age 7.4 +/- 0.4 yr) and 2 yr later in 222 healthy Caucasian males.
LEPR genotypes were significantly associated with baseline BMC at the hip (P = 0.017), femur diaphysis (P = 0.019), and radius (P = 0.007) and with height (P = 0.041) as well as with physical activity (P = 0.016). Associations with height and BMC at femur diaphysis and radius remained significant after 2 yr. Significant differences in 2-yr bone mass gain at the spine and femur neck were also found among LEPR genotypes. In contrast, adjusting BMC for projected bone area (aBMD) and/or weight, height, and physical activity resulted in a weak association only at the femur (P = 0.014-0.054). VDR polymorphisms were not associated with BMC or aBMD, but significant interactions occurred between VDR Fok1 and LEPR genotypes.
The LEPR Gln223Arg polymorphism was associated with bone mass in growing boys. The association, however, was markedly dependent on bone area, body size, and physical activity, in addition to VDR genetic variation, suggesting that the leptin system may modulate bone mass in humans mostly through indirect mechanisms.
Journal of Clinical Endocrinology & Metabolism 12/2007; 92(11):4380-6. · 6.50 Impact Factor
-
Serge Ferrari
[show abstract]
[hide abstract]
ABSTRACT: Vitamin D is essential for intestinal calcium absorption, bone mineralisation and plays an important role in neuromuscular functions. Vitamin D insufficiency is highly prevalent among postmenopausal women with osteoporosis and in the elderly. In turn, supplements of vitamin D3 (cholecalciferol), and to a lesser extent vitamin D2 (ergocalciferol), may decrease falls and fracture risk by 25%. Despite some recent negative studies, the actual question is not to know whether vitamin D is necessary, but rather how much vitamin D is sufficient to prevent secondary hyperparathyroidism, falls and fractures. Moreover, the risk of osteoporosis and of fragility fractures may be influenced by genetic variation in the vitamin D receptor (VDR).
Revue médicale suisse 07/2007; 3(115):1515-6, 1518-20.
-
[show abstract]
[hide abstract]
ABSTRACT: The amount of bone mineral mass acquired at the end of growth, the so-called 'peak bone mass', is considered to be a major risk factor for the occurrence of fragility fractures during adult life. Many interrelated factors can influence the accumulation of bone mass during growth, including genetics, sex, ethnicity, nutrition (e.g. calcium, vitamin D, protein), hormonal factors (e.g. sex steroids, insulin-like growth factor I), physical activity and exposure to various risk factors (e.g. alcohol, smoking, certain medications). Family and twin studies have estimated that up to 60-80% of the variance in peak bone mass is attributable to genetic factors. It can be predicted from epidemiological studies that a 10% increase in peak bone mass would reduce the risk of fragility fractures after the menopause by 50%. Intervention studies testing the effects of increasing either calcium intake or physical activity during growth provide evidence that modifying environmental factors can positively influence peak bone mass. Nevertheless, there is large interindividual variability in the response suggesting gene-environment interactions. A few studies have reported associations between some bone-related gene polymorphisms and the osteogenic response to loading or calcium supplementation. Identifying the functionally implicated genes interacting with mechanical loading and/or specific nutrients represents a formidable but hopefully not intractable challenge.
Medicine and sport science 02/2007; 51:64-80.
-
[show abstract]
[hide abstract]
ABSTRACT: Most mu-opioid receptor agonists recruit beta-arrestin2, with some exceptions such as morphine. Surprisingly, however, the acute analgesic effect of morphine is enhanced in the absence of beta-arrestin2. To resolve this paradox, we examined the effects of morphine and fentanyl in acute brain slices of the locus coeruleus and the periaqueductal gray from beta-arrestin2 knockout mice. We report that, in these mice, presynaptic inhibition of evoked inhibitory postsynaptic currents was enhanced, whereas postsynaptic G protein-coupled K(+) (Kir3/GIRK) currents were unaffected. The frequency, but not amplitude, of miniature inhibitory postsynaptic currents was increased in beta-arrestin2 knockout mice, indicating a higher release probability compared to WT mice. The increased release probability resulted from increased cAMP levels because of impaired phosphodiesterase 4 function and conferred an enhanced efficacy of morphine to inhibit GABA release. Thus, beta-arrestin2 attenuates presynaptic inhibition by opioids independent of mu-opioid receptor-driven recruitment, which may make beta-arrestin2 a promising target for regulating analgesia.
Proceedings of the National Academy of Sciences 03/2005; 102(8):3034-9. · 9.68 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Both late menarcheal age and low calcium intake (Ca intake) during growth are risk factors for osteoporosis, probably by impairing peak bone mass. We investigated whether lasting gain in areal bone mineral density (aBMD) in response to increased Ca intake varies according to menarcheal age and, conversely, whether Ca intake could influence menarcheal age. In an initial study, 144 prepubertal girls were randomized in a double-blind controlled trial to receive either a Ca supplement (Ca-suppl.) of 850 mg/d or placebo from age 7.9-8.9 yr. Mean aBMD gain determined by dual energy x-ray absorptiometry at six sites (radius metaphysis, radius diaphysis, femoral neck, trochanter, femoral diaphysis, and L2-L4) was significantly (P = 0.004) greater in the Ca-suppl. than in the placebo group (27 vs. 21 mg/cm(2)). In 122 girls followed up, menarcheal age was recorded, and aBMD was determined at 16.4 yr of age. Menarcheal age was lower in the Ca-suppl. than in the placebo group (P = 0.048). Menarcheal age and Ca intake were negatively correlated (r = -0.35; P < 0.001), as were aBMD gains from age 7.9-16.4 yr and menarcheal age at all skeletal sites (range: r = -0.41 to r = -0.22; P < 0.001 to P = 0.016). The positive effect of Ca-suppl. on the mean aBMD gain from baseline remained significantly greater in girls below, but not in those above, the median of menarcheal age (13.0 yr). Early menarcheal age (12.1 +/- 0.5 yr): placebo, 286 +/- 36 mg/cm(2); Ca-suppl., 317 +/- 46 (P = 0.009); late menarcheal age (13.9 +/- 0.5 yr): placebo, 284 +/- 58; Ca-suppl., 276 +/- 50 (P > 0.05). The level of Ca intake during prepuberty may influence the timing of menarche, which, in turn, could influence long-term bone mass gain in response to Ca supplementation. Thus, both determinants of early menarcheal age and high Ca intake may positively interact on bone mineral mass accrual.
Journal of Clinical Endocrinology & Metabolism 01/2005; 90(1):44-51. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Dietary Ca2+ is essential for the development and maintenance of bone mineral mass. The vitamin D endocrine system plays a fundamental role in the regulation of Ca2+ homeostasis, and mutations affecting genes implicated in vitamin D metabolism or vitamin D receptor (VDR) functions are responsible for severe alterations in skeletal growth. In addition, vitamin D is also implicated in the pathophysiology and treatment of adult bone disorders associated with impaired mineralization of bone matrix. Very recently, common polymorphisms in the 3′- and 5′-end region of the VDR gene have been suggested as possible determinants of bone mineral mass and, hence, of the risk of osteoporosis. None of these polymorphisms appear to be associated unequivocally with bone mineral mass or biochemical variables of Ca2+ and phosphate metabolism, except perhaps VDR 3′-end polymorphisms before puberty. As these associations are so inconsistent, interactions with environmental factors, particularly dietary intake, and with other polymorphisms have to be considered.
Trends in Endocrinology and Metabolism 10/1998; · 8.11 Impact Factor
