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Muscle Strength/brain-mortality/after fracture & Before /
Quadriceps weakness and post-fracture mortality
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Download the PDF here
Download the PDF here
from Jules: this new study published in November finds muscle strength is associated with higher mortality, that muscle strength before & after fracture is associated with higher mortality, and that a fracture after 50 can increase muscle loss. There is a bunch of research some of which I linked to immediately below showing the importance of leg muscle strength to mortality, health in aging & brain functioning. It is very important to strengthen leg muscles. Key study below looked at master runners in their 80s and found they had stronger leg muscles. The 2nd study in twins found "Leg power predicts both cognitive ageing and global brain structure". The message: exercise, strengthen leg muscles, don't get a fracture, but ifyou do you must continue to get your muscles back to full strength!
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Association of Muscle Weakness with Post-Fracture Mortality in Older Men and Women: A 25 Year Prospective Study
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Strong Leg Muscles Improve Brain Functioning - 2 studies report: Kicking Back Cognitive Ageing: Leg Power Predicts Cognitive Ageing after Ten Years in Older Female Twins.......athletes also had almost 30 percent more motor units in their leg muscle tissue, and these units were functioning better than those of people in the sedentary group",researchers from McGill University in Canada and other schools contacted 29 world-class track and field athletes in their 80s and invited them to the university's performance lab. .....Muscles consist of fibers, each attached to a motor neuron in our spinal column by long, skinny nerve threads called axons. The fiber and its neuron are known as a muscle unit. When this muscle unit is intact, the neuron sends commands to the muscle fiber to contract. The muscle fiber responds, and your leg, eyelid, pinky finger or other body part moves....We measured MU numbersand neuromuscular transmission stability in thetibialis anterior[The tibialis anterior overlaps the anterior tibial vessels and deep peroneal nerve in the upper part of the leg.]of world champion MAs (∼80y),55 and compared the values to healthy age-matched controls (∼80y).......http://www.natap.org/2016/newsUpdates/092616_04.htm
Muscular Strength & Mortality in Men....http://www.natap.org/2008/HIV/082508_01.htm
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Association of Muscle Weakness with Post-Fracture Mortality in Older Men and Women: A 25 Year Prospective Study
"In the present study, low muscle strength was associated with higher mortality risk and absolute strength loss is much greater in men than in women."
"an intervention to increase muscle strength in the older people may be a good target for both fracture and premature mortality risk reduction."
In summary, muscle strength at quadriceps declines with advancing age but this reduction is not increased after a fragility fracture. Lower muscle strength is a determinant of premature mortality following a fragility fracture at all sites for both men and women, albeit not significantly for hip fracture in women. As low muscle strength is also associated with an increased risk of fragility fracture, early intervention to improve muscle strength in the older population may have an effect on reducing both fracture and premature mortality risk.
FNBMD: Femoral neck bone mineral density.
"We also investigated the association between post-fracture mortality risk and muscle strength measured before and after fracture. In both men and women, muscle strength before and after fracture both were associated with mortality; however, the effect size for strength before fracture was larger than that for strength after fracture (Table 6). Full adjustment for all potential predictors was not conducted due to insufficient number of events per predictor........This study, for the first time, has estimated the proportion of post-fracture mortality attributable to muscle weakness by using partial population attributable risk. Muscle weakness is attributable for 19% (95%CI: 0.11-0.27) of premature deaths after fracture in women and 27% (95%CI: 0.15-0.39) in men......In both genders, there were significant independent associations between lower muscle strength and post-fracture mortality risk as well as for advancing age, lower weight, lower FNBMD, lower BMIand low levels of physical activity"
Fall was a potential confounder as it is associated with both muscle strength and mortality. However, in the multivariable analysis, we found that fall did not alter the magnitude of association between low muscle strength and post-fracture mortality, suggesting that the association was independent off fall.
Interestingly, we have found that there was no difference in the annual loss of strength measured before and after fracture. Also, this finding did not differ between fracture types. The annual absolute loss was higher in men (0.39 kg/m) than in women (0.27 kg/m); however, as men had higher strength, they had an overall lower rate of relative loss than women (1.7% in men compared to 1.9% in women)
In women, compared to survivors, those who died were significantly older, shorter, less physically active, and also had lower weight, BMI, FNBMD and MS at baseline. These differences, except for height and physical activity, were also observed in men. Diabetes was more prevalent in men who died while respiratory disease was more prevalent in women who died.
When analyzed by fracture type, the risk of mortality following a hip fracture was highest (67% for women and 64% for men), followed by mortality risk among individuals with a clinical vertebral fracture (37% for women and 46% for men). The risk of mortality among individuals with non–hip and non–vertebral fractures was similar to that for those with vertebral fracture.
In both genders, there were significant independent associations between lower muscle strength and post-fracture mortality risk as well as for advancing age, lower weight, lower FNBMD, lower BMIand low levels of physical activity
Muscle strength change before and after fracture
Analyses for determining muscle strength change were performed in subgroups of men and women who had at least 2 muscle strength measurements before and/or after fracture. Two parameters of muscle strength before and after fracture were estimated: predicted strength at age 70 and annual absolute loss of strength from this age, which was to calculate the relative annual rate loss.
In women, for those whose muscle strength had been taken before fracture, strength at age 70 was 14.6 kg/m (95%CI: 14.1, 15.0) and annual absolute loss was 0.27 kg/m (95%CI: -0.32, -0.23), equivalent to an annual rate loss of 1.85%/year (95%CI: -2.20, -1.57). For women whose muscle strength was measured after fracture, muscle strength loss was not significantly different from that before fracture (Table 3).
In men, all muscle parameters taken before or after fracture were greater than those in women. Before fracture, men at age 70 had a muscle strength of 22.3 kg/m (95%CI: 21.3, 23.3) and annual absolute loss of 0.40 kg/m (95%CI: -0.50, -0.29), equivalent to an annual rate loss of 1.79%/year (95%CI: -2.24, -1.30). Strength and rate of loss of strength were not significantly different between before versus after fracture (Table 3).
Subgroup analysis of those with different fracture types revealed that there were no significant differences in the absolute decline of muscle strength before and after fracture for all fracture types in both women and men (Table 4). However, among women with vertebral fracture, muscle strength after fracture was significantly lower than that before fracture while strength loss after fracture was significantly higher than the loss before fracture.
Muscle weakness as a predictor of post-fracture mortality risk
Survivalprobability was lowest in those whose muscle strength was in the lowest tertile of their gender matched group, regardless of fracture type (Figure 2).
In both genders, there were significant independent associations between lower muscle strength and post-fracture mortality risk as well as for advancing age, lower weight, lower FNBMD, lower BMIand low levels of physical activity(Table 5). Lower height and history of falls were associated with increased risk of post-fracture mortality in women but not in men. Hypertension was protective against post-fracture mortality in men (Table 5).
After adjustment for age, the association between muscle strength and post-fracture mortality was attenuated but still significant. After adjustment for other risk factors, i.e. age, FNBMD, BMI, physical activity, smoking, history of falls and the illnesses, each SD lower muscle strength was associated with increased risk of post-fracture mortality of 19% [HR(95%CI):1.19 (1.05, 1.34)] in women and 39% [HR(95%CI): 1.39 (1.18, 1.64)] in men (Figure 3).
In the most parsimonious model, predictors of post-fracture mortality risk for women were low muscle strength, older age, low femoral neck BMD, low level of physical activity and rheumatoid arthritis. If all those predictors, except age which is un-modifiable, were all eliminated, 48% of the premature mortality in these women would be delayed [PARf(95%CI): 0.48 (0.25-0.65)]. By contrast, if only low muscle strength was eliminated while other predictors stayed the same, then 15% of the premature mortality among these women would be delayed [PARp(95%CI): 0.15 (0.05-0.24)]; suggesting that muscle weakness contributes to roughly one third of the premature mortality. In men, muscle strength and age remained in the most parsimonious model. As age is un-modifiable, we obtained PAR for muscle strength only. If low muscle strength was eliminated from these men, then 23% of premature deaths [PARp(95%CI): 0.23 (0.11-0.35)] would be deferred.
We also investigated the association between post-fracture mortality risk and muscle strength measured before and after fracture. In both men and women, muscle strength before and after fracture both were associated with mortality; however, the effect size for strength before fracture was larger than that for strength after fracture (Table 6). Full adjustment for all potential predictors was not conducted due to insufficient number of events per predictor.
Further analysis by fracture site revealed that, after adjusting for age, each SD decrease in MS was associated with an increase in the risk of mortality following vertebral and non-hip,non-vertebral fractures for both men and women (Figure 4). However, this association was not observed for mortality following hip fractures. The adjustment for all possible risk factors was not conducted because of the small number ofdeathsin each subgroup following specific types of fracture.
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Association of Muscle Weakness with Post-Fracture Mortality in Older Men and Women: A 25 Year Prospective Study
Hanh M. Pham1,2,3, Sing C. Nguyen1, Thao P. Ho-Le4, Jacqueline R. Center1,3,
John A. Eisman1,3,5, Tuan V. Nguyen1,3,4,6*
1Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Australia; 2Thai Binh University of Medicine and Pharmacy, Vietnam; 3St Vincent's Clinical School, UNSW Australia; 4Centre for Health Technologies, University of Technology Sydney, Australia; 5School of Medicine Sydney, University of Notre Dame, Australia; 6School of Public Health and Community Medicine, UNSW Australia.
Short title: Quadriceps weakness and post-fracture mortality
Abstract
Osteoporotic fracture increases the risk of premature mortality. Muscle weakness is associated with both increased fracture risk and low BMD. However, the role of muscle strength in post-fracture mortality is not well understood. This study examines the change of muscle strength measured at quadriceps (QS) before and after fracture, and defines the relationship between muscle strength and post-fracture mortality.
The study involved 889 women and 295 men (who were participating in the Dubbo Osteoporosis Study) who had at least one low trauma fracture (ascertained from X-ray reports) after the age of 50. Median follow-up time was 11 years (range: 1-24). To determine the change in muscle strength before and after a fracture, we selected a subset of 344 women and 99 men who had had at least two muscle strength measurements before the fracture event, and a subset of 407 women and 105 men who had had at least two measurements after the fracture.
During the follow-up period, 366 (41.2%) women and 150 (50.9%) men died. The annual rate of decrease in height-adjusted muscle strength before fracture was 0.27 kg/m (1.85%) in women and 0.40kg/m (1.79%) in men. Strength loss after fracture was not significantly different from that before fracture.
In women, after adjusting for baseline age and BMD, each SD (5 kg/m) lower height-adjusted pre- and post-fracture quadriceps strength was associated with a 27% [HR(95%CI): 1.27(1.07-1.50)] and 18% [HR(95%CI): 1.18(1.01-1.38)] increase in post-fracture mortality risk, respectively.
Similarly, in men, each SD (5kg/m) lower height-adjusted pre-and post-fracture QS was associated with increased mortality before fracture [HR(95%CI): 1.33(1.09-1.63)] and after fracture [HR(95%CI): 1.43(1.16-1.78)]. Muscle weakness accounted for 15% (95%CI: 0.05-0.24) of premature deaths after fracture in women and 23% (95%CI: 0.11-0.35) in men.
These results indicate that in the older individuals, lower muscle strength is an independent risk factor for post-fracture mortality.
Introduction
From the public health view point, fragility fracture is a significant burden on the population, because it is highly prevalent and it is associated with serious consequences. In women, the lifetime risk of fracture at the hip, the most serious type of fracture, is one in six, which is higher than the lifetime risk of invasive breast cancer.(1, 2)The risk of hip fracture in aged men is about one-third of that in women.(1)More importantly, a fracture is associated with an increased risk of premature mortality in both women and men.(3) With the on-going aging of the population, the impact of fragility fracture is projected to become more pronounced.
Factors that account for this premature mortality risk following a fracture have not been well established. Studies investigating these factors have predominantly focused on hip fracture due to the high mortality incidence following this kind of fracture. Co-morbidities and low bone mineral density have been reported to be associated with post-hip fracture mortality(4, 5), but they could not explain the excess mortality post fracture.
Muscle strength declines with advancing age at the rate of 1.6% per year in the general older population.(6) This decline in muscle strength has been reported to be associated with an increased fracture risk.(6, 7) However, among those who are at risk of a fracture the pattern of muscle strength decline is not clear. Also, it is not known whether muscle strength decline is exacerbated in those who experience a fragility fracture.
In addition, although muscle weakness increases fracture risk (6, 7) and fracture in turn increases the risk of premature mortality,(3, 8, 9) the relationship of muscle weakness to mortality after a fracture is not well understood. People with a low-trauma hip or vertebral fracture have an increased risk of premature mortality with the highest risk during the first year after fracture, and a notably increased risk persisting for several years after the event.(3, 8, 10, 11) Muscle weakness has been shown to be associated with premature mortality in the general population.(12, 13) The excess risk of mortality in people with fracture could be contributed to by an increased prevalence of muscle weakness or anincreased effect of muscle weakness on premature mortality. Attributable risk estimates can give insight into contributors to the excess mortality in people with fragility fracture by quantifying the proportion of risk of premature mortality that is attributable to muscle weakness.
Furthermore, increased mortality after fragility fracture is gender-specific. (14) Men are about 2-fold more likely to die after fracture than women.(15) Understanding gender-specific skeletal muscle changes and their association with post-fracture mortality could help in understanding the gender difference in mortality after fracture.
In this study, we tested three hypotheses: (1) muscle strength declines in those who are progressing to a fragility fracture; (2) muscle strength loss is increased after a fragility fracture; and (3) low muscle strength (before and/or after a fragility fracture) is associated with post-fracture mortality.
Results
Fracture Cohort
Among 889 first-recorded low-trauma fractures in women, there were 89 (10.0%) hip, 298 (33.5%) vertebral and 502 (56.5%) non-hip, non-vertebral fractures. The 295 first-recorded low-trauma fractures in men were comprised of 36 (12.2%) hip, 101 (34.2%) vertebral and 158 (53.6%) non-hip, non-vertebral fractures. The mean age at fracture was 75 years (SD: 9 years) for both men and women. The mean age at baseline was 72 years (SD:7) for women and 73 (SD: 7) for men.
Compared to men, women had lower height-adjusted MS [13.2 kg/m (SD: 4.8) vs. 20.2 kg/m (SD: 5.9), P<0.0001], and lower FNBMD [0.76 g/cm2 (SD: 0.13) vs. 0.88 g/cm2 (SD: 0.15), P<0.0001]. There was no difference in the distribution of co-morbidities between women and me, except for cardiovascular disease where men had higher prevalence than women.
In the subgroups of those who had at least two measurements of muscle strength, at baseline, women in the post-fracture group were significantly older, shorter and had lower MS than those in the pre-fracture group. These differences were not observed in men (Table 1).
Incidence of mortality
During the follow-up period, 366 (41.2%) women and 150 (50.9%) men died over 10,925 and 3,186person-years at risk, respectively. These yielded an average mortality rate of 34 per 1,000 person-years (95% confidence interval (95% CI): 31, 38) in women and 47 per 1,000 person-years (95% CI: 40, 55) in men.
In women, compared to survivors, those who died were significantly older, shorter, less physically active, and also had lower weight, BMI, FNBMD and MS at baseline. These differences, except for height and physical activity, were also observed in men. Diabetes was more prevalent in men who died while respiratory disease was more prevalent in women who died. (Table 2)
When analyzed by fracture type, the risk of mortality following a hip fracture was highest (67% for women and 64% for men), followed by mortality risk among individuals with a clinical vertebral fracture (37% for women and 46% for men). The risk of mortality among individuals with non–hip and non–vertebral fractures was similar to that for those with vertebral fracture.
Muscle strength change before and after fracture
Analyses for determining muscle strength change were performed in subgroups of men and women who had at least 2 muscle strength measurements before and/or after fracture. Two parameters of muscle strength before and after fracture were estimated: predicted strength at age 70 and annual absolute loss of strength from this age, which was to calculate the relative annual rate loss.
In women, for those whose muscle strength had been taken before fracture, strength at age 70 was 14.6 kg/m (95%CI: 14.1, 15.0) and annual absolute loss was 0.27 kg/m (95%CI: -0.32, -0.23), equivalent to an annual rate loss of 1.85%/year (95%CI: -2.20, -1.57). For women whose muscle strength was measured after fracture, muscle strength loss was not significantly different from that before fracture (Table 3).
In men, all muscle parameters taken before or after fracture were greater than those in women. Before fracture, men at age 70 had a muscle strength of 22.3 kg/m (95%CI: 21.3, 23.3) and annual absolute loss of 0.40 kg/m (95%CI: -0.50, -0.29), equivalent to an annual rate loss of 1.79%/year (95%CI: -2.24, -1.30). Strength and rate of loss of strength were not significantly different between before versus after fracture (Table 3).
Subgroup analysis of those with different fracture types revealed that there were no significant differences in the absolute decline of muscle strength before and after fracture for all fracture types in both women and men (Table 4). However, among women with vertebral fracture, muscle strength after fracture was significantly lower than that before fracture while strength loss after fracture was significantly higher than the loss before fracture.
Muscle weakness as a predictor of post-fracture mortality risk
Survival probability was lowest in those whose muscle strength was in the lowest tertile of their gender matched group, regardless of fracture type (Figure 2).
In both genders, there were significant independent associations between lower muscle strength and post-fracture mortality risk as well as for advancing age, lower weight, lower FNBMD, lower BMIand low levels of physical activity (Table 5). Lower height and history of falls were associated with increased risk of post-fracture mortality in women but not in men. Hypertension was protective against post-fracture mortality in men (Table 5).
After adjustment for age, the association between muscle strength and post-fracture mortality was attenuated but still significant. After adjustment for other risk factors, i.e. age, FNBMD, BMI, physical activity, smoking, history of falls and the illnesses, each SD lower muscle strength was associated with increased risk of post-fracture mortality of 19% [HR(95%CI):1.19 (1.05, 1.34)] in women and 39% [HR(95%CI): 1.39 (1.18, 1.64)] in men (Figure 3).
In the most parsimonious model, predictors of post-fracture mortality risk for women were low muscle strength, older age, low femoral neck BMD, low level of physical activity and rheumatoid arthritis. If all those predictors, except age which is un-modifiable, were all eliminated, 48% of the premature mortality in these women would be delayed [PARf (95%CI): 0.48 (0.25-0.65)]. By contrast, if only low muscle strength was eliminated while other predictors stayed the same, then 15% of the premature mortality among these women would be delayed [PARp (95%CI): 0.15 (0.05-0.24)]; suggesting that muscle weakness contributes to roughly one third of the premature mortality. In men, muscle strength and age remained in the most parsimonious model. As age is un-modifiable, we obtained PAR for muscle strength only. If low muscle strength was eliminated from these men, then 23% of premature deaths [PARp (95%CI): 0.23 (0.11-0.35)] would be deferred.
We also investigated the association between post-fracture mortality risk and muscle strength measured before and after fracture. In both men and women, muscle strength before and after fracture both were associated with mortality; however, the effect size for strength before fracture was larger than that for strength after fracture (Table 6). Full adjustment for all potential predictors was not conducted due to insufficient number of events per predictor.
Further analysis by fracture site revealed that, after adjusting for age, each SD decrease in MS was associated with an increase in the risk of mortality following vertebral and non-hip,non-vertebral fractures for both men and women (Figure 4). However, this association was not observed for mortality following hip fractures. The adjustment for all possible risk factors was not conducted because of the small number of deaths in each subgroup following specific types of fracture.
Discussion
Post-fracture mortality remains a puzzle as debate centers on whether the relationship between fracture and mortality is causal. In this study, we have demonstrated that muscle strength declined with advancing age, and low muscle strength was associated with an increased risk of post-fracture mortality. This association was independent of baseline femoral neck BMD, BMI, history of falls, smoking, physical activity, and the number and type of co-morbidities.
Decline in skeletal muscle strength with advancing age in the general population has been previously reported,(6, 33) including in our previous study using the Dubbo Osteoporosis Epidemiology Study.(6) In that study we found that muscle strength at quadriceps declined at an annual rate of 1.6% for both older women and men. The current study extends the findings of the previous study by taking into account the fracture event so that the reduction in muscle strength can be compared before and after fracture. Interestingly, we have found that there was no difference in the annual loss of strength measured before and after fracture. Also, this finding did not differ between fracture types. The annual absolute loss was higher in men (0.39 kg/m) than in women (0.27 kg/m); however, as men had higher strength, they had an overall lower rate of relative loss than women (1.7% in men compared to 1.9% in women)
The underlining aetiology of skeletal muscle strength decline with advancing age is not well understood. One study showed that loss of muscle mass was a determinant of muscle strength reduction in older adults; however, gaining muscle mass did not prevent aging-related declines in muscle strength.(33)) Studies at the cellular and molecular levels have reported sex-specific structural alterations associated with aging. Men have been reported to have fewer fibers with large cross-section areas (CSA) while women showed reduced fiber size across the CSA range.(34) In addition,the increase of isometric tension and myofilament lattice stiffness and the reduction of phosphorylation of the fast myosin regulatory light chain and myosin actin cross-bridge kinetics are age-related molecular changes which were most notable in women.(35) These sex-specific age-related alterations may explain in part the gender differences in the age-related reduction of muscle strength.
The association between low muscle strength and mortality risk has been well established for the general population.(12, 13, 36-38) In the present study, we specifically investigated this association in a cohort of those who had sustained a fragility fracture as previous studies have shown higher premature mortality risk in this population.(3, 8, 9) In a general population of those aged 80 and above years old, those with the highest tertile of handgrip strength had a 38% lower sex-adjusted risk of all caused mortality.(13))Our study has shown that each SD decrease in quadriceps strength was associated with increased risk of mortality after a fracture by28% in women and 36% in men after adjusting for age, FNBMD and co-morbidities. The contribution of muscle weakness to post-fracture mortality could be explained in part through a falls mechanisms as muscle weakness increases the risk of falls,(39) which in turn increases the risk of fracture and fracture-related premature mortality.(3, 9, 11) However, in this study, the whole cohort had suffered fractures and there was still a strong association between muscle weakness and premature mortality.
Therefore, this association suggests a pathway independent of fracture. Fall was a potential confounder as it is associated with both muscle strength and mortality. However, in the multivariable analysis, we found that fall did not alter the magnitude of association between low muscle strength and post-fracture mortality, suggesting that the association was independent off fall.
This study, for the first time, has estimated the proportion of post-fracture mortality attributable to muscle weakness by using partial population attributable risk. Muscle weakness is attributable for 19% (95%CI: 0.11-0.27) of premature deaths after fracture in women and 27% (95%CI: 0.15-0.39) in men. From the public health perspective, an intervention which could significantly improvemuscle strength in those people to bring them to normal strength group may delay death for 2 out of every 10 women and 3 out of every 10 men.
The finding from this study provides insight into the gender difference in increased mortality risk after fragility fracture. It is well documented that while fragility fracture is less prevalent in older men than older women, mortality after fracture is more frequent in older men than in older women.(14, 15) In the present study, low muscle strength was associated with higher mortality risk and absolute strength loss is much greater in men than in women.
A novel feature of our study is that the association between muscle strength and mortality risk was examined following different types of fragility fractures. The age-adjusted association between muscle strength and mortality risk following vertebral or non-hip non-vertebral fractures was similar to that following all types of fracture. This may be explained by the finding that muscle strength and its annual rate loss did not differ between different types of fractures.
The mechanisms by which low muscle strength may be linked to increased post-fracture mortality are not known. In our previous study,(6) we reported that low muscle strength was associated with increased risk of fragility fracture. Hence, the increased risk of death following fragility fracture in those with low muscle strength may be due to low strength itself or due to an interaction between low strength and fracture. Thus, taking into account the impact of low muscle strength on fragility fracture and on mortality after a fragility fracture, an intervention to increase muscle strength in the older people may be a good target for both fracture and premature mortality risk reduction.
This study has several limitations. The participants were Caucasian so the findings may not be generalizable to different ethnicities. The morbidity data were self-reported and this could potentially introduce misclassification bias into the analysis. Moreover, there was no information concerning disease severity which could compromise the estimate of the magnitude of association. The analysis did not take into account the possible effect of vitamin D which could also be a potential confounder. The association between muscle strength andmortality found was overall independent of other risk factors, though this was not examined in detail for the different types of fracture due to the small numbers of specific types of fracture.
In summary, muscle strength at quadriceps declines with advancing age but this reduction is not increased after a fragility fracture. Lower muscle strength is a determinant of premature mortality following a fragility fracture at all sites for both men and women, albeit not significantly for hip fracture in women. As low muscle strength is also associated with an increased risk of fragility fracture, early intervention to improve muscle strength in the older population may have an effect on reducing both fracture and premature mortality risk
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