Associations between life course longitudinal growth and hip shapes at ages 60-64 years: evidence from the MRC National Survey of Health and Development.

OBJECTIVE: We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. METHODS: Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. RESULTS: Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. CONCLUSION: Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.

Daily Pain Severity but Not Vertebral Fractures Is Associated With Lower Physical Activity in Postmenopausal Women With Back Pain.

Back pain lifetime incidence is 60%-70%, while 12%-20% of older women have vertebral fractures (VFs), often with back pain. We aimed to provide objective evidence, currently lacking, regarding whether back pain and VFs affect physical activity (PA). We recruited 69 women with recent back pain (age 74.5 ± 5.4 years). Low- (0.5 < g < 1.0), medium- (1.0 ≤ g < 1.5), and high-impact (g ≥ 1.5) PA and walking time were measured (100 Hz for 7 days, hip-worn accelerometer). Linear mixed-effects models assessed associations between self-reported pain and PA, and group differences (VFs from spine radiographs/no-VF) in PA. Higher daily pain was associated with reduced low (ß = -0.12, 95% confidence interval, [-0.22, -0.03], p = .013) and medium-impact PA (ß = -0.11, 95% confidence interval, [-0.21, -0.01], p = .041), but not high-impact PA or walking time (p > .11). VFs were not associated with PA (all p > .2). Higher daily pain levels but not VFs were associated with reduced low- and medium-impact PA, which could increase sarcopenia and falls risk in older women with back pain.

Are associations between physical activity and bone mineral density in adults sex- and age-dependent? An analysis of the UK biobank study.

Whilst physical activity (PA) is recognised as a key bone mass determinant across life, athlete studies suggest that it may be less effective in women and older individuals. This has not been explored within the general population. We aimed to address this knowledge gap using data from the UK Biobank Study, a large population-based study of middle-aged and older adults. Free-living PA data collected at 100 Hz for seven days using wrist-worn accelerometers was classified as sedentary behaviour (0-29 milligravities (mg)), light (30-124 mg) or moderate-to-vigorous PA (125 + mg). Lumbar spine and femoral neck bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Associations between PA and BMD were assessed using linear regression models, with formal assessments of sex and age interactions undertaken and adjustments made for accelerometer wear time, height, body mass index, education, ethnicity, disability, and (in women only) menopausal status. In total, 15 133 UK Biobank participants (52% women) had complete PA, bone, and covariate data. In this sample, greater overall and moderate-to-vigorous PA was associated with higher lumbar spine BMD. In women these associations were typically weaker in older individuals, for example regression coefficients in women aged ≥70y ~50% were lower than at 45-54y (age-by- PA interactions p < 0.01 in all models). Similar associations were observed in basic but not full models for femoral neck BMD. Greater sedentary time was associated with lower lumbar spine BMD in men only, and greater light PA and sedentary time were associated with higher and lower femoral neck BMD respectively in both sexes. These results suggest that associations between PA and bone health at clinically-relevant sites are weaker in older than younger women. That positive associations are evident between overall and moderate-vigorous PA and femoral neck BMD even in women ≥70y suggests that PA for bone health should still be promoted in older women.

Associations between long-term exercise participation and lower limb joint and whole-bone geometry in young and older adults.

Introduction: Features of lower limb bone geometry are associated with movement kinematics and clinical outcomes including fractures and osteoarthritis. Therefore, it is important to identify their determinants. Lower limb geometry changes dramatically during development, partly due to adaptation to the forces experienced during physical activity. However, the effects of adulthood physical activity on lower limb geometry, and subsequent associations with muscle function are relatively unexplored. Methods: 43 adult males were recruited; 10 young (20-35 years) trained i.e., regional to world-class athletes, 12 young sedentary, 10 older (60-75 years) trained and 11 older sedentary. Skeletal hip and lower limb geometry including acetabular coverage and version angle, total and regional femoral torsion, femoral and tibial lateral and frontal bowing, and frontal plane lower limb alignment were assessed using magnetic resonance imaging. Muscle function was assessed recording peak power and force of jumping and hopping using mechanography. Associations between age, training status and geometry were assessed using multiple linear regression, whilst associations between geometry and muscle function were assessed by linear mixed effects models with adjustment for age and training. Results: Trained individuals had 2° (95% CI:0.6°-3.8°; p = 0.009) higher femoral frontal bowing and older individuals had 2.2° (95% CI:0.8°-3.7°; p = 0.005) greater lateral bowing. An age-by-training interaction indicated 4° (95% CI:1.4°-7.1°; p = 0.005) greater acetabular version angle in younger trained individuals only. Lower limb geometry was not associated with muscle function (p > 0.05). Discussion: The ability to alter skeletal geometry via exercise in adulthood appears limited, especially in epiphyseal regions. Furthermore, lower limb geometry does not appear to be associated with muscle function.

Regional and temporal variation in bone loss during the first year following spinal cord injury.

Osteoporosis is a consequence of spinal cord injury (SCI) that leads to fragility fractures. Visual assessment of bone scans suggests regional variation in bone loss, but this has not been objectively characterised. In addition, substantial inter-individual variation in bone loss following SCI has been reported but it is unclear how to identify fast bone losers. Therefore, to examine regional bone loss, tibial bone parameters were assessed in 13 individuals with SCI (aged 16-76 years). Peripheral quantitative computed tomography scans at 4 % and 66 % tibia length were acquired within 5 weeks, 4 months and 12 months postinjury. Changes in total bone mineral content (BMC), and bone mineral density (BMD) were assessed in ten concentric sectors at the 4 % site. Regional changes in BMC and cortical BMD were analysed in thirty-six polar sectors at the 66 % site using linear mixed effects models. Relationships between regional and total loss at 4 months and 12 months timepoints were assessed using Pearson correlation. At the 4 % site, total BMC (P = 0.001) decreased with time. Relative losses were equal across the sectors (all P > 0.1). At the 66 % site, BMC and cortical BMD absolute losses were similar (all P > 0.3 and P > 0.05, respectively) across polar sectors, but relative loss was greatest in the posterior region (all P < 0.01). At both sites, total BMC loss at 4 months was strongly positively associated with the total loss at 12 months (r = 0.84 and r = 0.82 respectively, both P < 0.001). This correlation was stronger than those observed with 4-month BMD loss in several radial and polar sectors (r = 0.56-0.77, P < 0.05). These results confirm that SCI-induced bone loss varies regionally in the tibial diaphysis. Moreover, bone loss at 4 months is a strong predictor of total loss 12 months postinjury. More studies on larger populations are required to confirm these findings.

Development of musculoskeletal deficits in children with cystic fibrosis in later childhood.

Cystic fibrosis (CF) is a genetic condition primarily affecting the respiratory system, with the associated progressive lung damage and loss of function resulting in reduced lifespan. Bone health is also impaired in individuals with CF, leading to much higher fracture risk even in adolescence. However, the development of these deficits during growth and the relative contributions of puberty, body size and muscular loading remain somewhat unexplored. We therefore recruited 25 children with CF (10 girls, mean age 11.3 ± 2.9y) and 147 children without CF (75 girls, mean age 12.4 ± 2.6y). Bone characteristics were assessed using peripheral quantitative computed tomography (pQCT) at 4 % and 66 % distal-proximal tibia. Muscle cross-sectional area (CSA) and density (an indicator of muscle quality) were also assessed at the latter site. Tibial bone microstructure was assessed using high-resolution pQCT (HR-pQCT) at 8 % distal-proximal tibial length. In addition, peak jump power and hop force were measured using jumping mechanography. Group-by-age interactions and group differences in bone and muscle characteristics were examined using multiple linear regression, adjusted for age, sex and pubertal status and in additional models, height and muscle force. In initial models group-by-age interactions were evident for distal tibial total bone mineral content (BMC) and trabecular volumetric bone mineral density (vBMD), with a lower rate of age-related accrual evident in children with CF. In assessments of distal tibial microstructure, similar patterns were observed for trabecular number and thickness, and cortical CSA. In the tibial shaft, group-by-age interactions indicating slower growth in CF were evident for total BMC and cortical CSA, whilst age-independent deficits in CF were observed for several other variables. Peak jump power and hop force also exhibited similar interactions. Group-by-age interactions for bone were partially attenuated at the distal tibia and fully attenuated at the tibial shaft by adjustment for muscle force. These results suggest that bone and muscle deficits in children with CF develop throughout later childhood, independent of differences in pubertal stage and body size. These diverging growth patterns appear to be mediated by differences in muscle function, particularly for bone characteristics in the tibial shaft. Given the high fracture risk in this population from childhood onwards, development of interventions to improve bone health would be of substantial clinical value.

Lower limb bone geometry in adult individuals with X-linked hypophosphatemia: an observational study.

We assessed lower-limb geometry in adults with X-linked hypophosphatemia (XLH) and controls. We found large differences in multiple measures including femoral and tibial torsion, bowing and cross-sectional area and acetabular version and coverage which may contribute to clinical problems such as osteoarthritis, fractures and altered gait common in XLH. PURPOSE: Individuals with X-linked hypophosphatemia (XLH) are at risk of lower-limb deformities and early onset of osteoarthritis. These two factors may be linked, as altered biomechanics is a risk factor for osteoarthritis. This exploratory evaluation aims at providing clues and concepts for this association to facilitate future larger-scale and longitudinal studies on that aspect. METHODS: For this observational study, 13 patients with XLH, aged 18-65 years (6 female), were compared with sex-, age- and weight-matched healthy individuals at a single German research centre. Femoral and hip joint geometry, including femoral and tibial torsion and femoral and tibial shaft bowing, bone cross-sectional area (CSA) and acetabular version and coverage were measured from magnetic resonance imaging (MRI) scans. RESULTS: Total femoral torsion was 29° lower in individuals with XLH than in controls (p < 0.001), mainly resulting from lower intertrochanteric torsion (ITT) (p < 0.001). Femoral lateral and frontal bowing, tibial frontal bowing, mechanical axis, femoral mechanical-anatomical angle, acetabular version and acetabular coverage were all greater and tibial torsion lower in individuals with XLH as compared to controls (all p < 0.05). Greater femoral total and marrow cavity CSA, greater tibial marrow cavity CSA and lower cortical CSA were observed in XLH (all p < 0.05). DISCUSSION: We observed large differences in clinically relevant measures of tibia and particularly femur bone geometry in individuals with XLH compared to controls. These differences may plausibly contribute to clinical manifestations of XLH such as early-onset osteoarthritis, pseudofractures and altered gait and therefore should be considered when planning corrective surgeries.

Fibula response to disuse: a longitudinal analysis in people with spinal cord injury.

Fibular response to disuse has been described in cross-sectional but not longitudinal studies. This study assessed fibular bone changes in people with spinal cord injury. Fibular bone loss was less than in the tibia and was not correlated together. This might explain low fibular fracture incidents in these patients. PURPOSE: Cross-sectional studies suggest that the fibula responds differently to loading and disuse compared to the tibia. Whilst tibial bone changes following spinal cord injury (SCI) have been established in longitudinal studies, fibular changes remain unexplored. METHODS: Fibular and tibial bone parameters were assessed in 13 individuals with SCI (aged 16-76 years). Peripheral quantitative computed tomography scans were acquired at 4%, 38% and 66% distal-proximal tibia length at 5 weeks and 12 months post-injury. Changes in 4% site total bone mineral content (BMC), total cross-sectional area (CSA) and bone mineral density (BMD), and 38% and 66% sites total BMC, total CSA, cortical BMD and cortical CSA were assessed using paired T-tests. Relationships between bone loss in the two bones at equivalent sites were assessed using paired T-tests and correlation. RESULTS: At the 4% site, fibular total BMC and BMD losses were less than tibial losses (- 6.9 ± 5.1% and - 6.6 ± 6.0% vs - 14.8 ± 12.4% and - 14.4 ± 12.4%, p = 0.02 and p = 0.03, respectively). Similarly, at the 66% site, fibular BMC losses were less than those in the tibia (- 2.0 ± 2.6% vs - 4.3 ± 3.6%, p = 0.03), but there was no difference at 38% (- 1.8 ± 3.5% vs - 3.8 ± 2.1%, p = 0.1). No correlation was observed for BMC changes between the two bones (all p > 0.25). CONCLUSION: These results support cross-sectional evidence of smaller disuse-related bone loss in the fibula compared to the tibia. These results may in part explain lower incidence of fibula fractures in individuals with chronic SCI. The lack of association between losses in the two bones might point to different underlying mechanisms.

Circulating testosterone and dehydroepiandrosterone are associated with individual motor unit features in untrained and highly active older men.

Long-term exercise training has been considered as an effective strategy to counteract age-related hormonal declines and minimise muscle atrophy. However, human data relating circulating hormone levels with motor nerve function are scant. The aims of the study were to explore associations between circulating sex hormone levels and motor unit (MU) characteristics in older men, including masters athletes competing in endurance and power events. Forty-three older men (mean ± SD age: 69.9 ± 4.6 years) were studied based on competitive status. The serum concentrations of dehydroepiandrosterone (DHEA), total testosterone (T) and estradiol were quantified using liquid chromatography mass spectrometry. Intramuscular electromyographic signals were recorded from vastus lateralis (VL) during 25% of maximum voluntary isometric contractions and processed to extract MU firing rate (FR), and motor unit potential (MUP) features. After adjusting for athletic status, MU FR was positively associated with DHEA levels (p = 0.019). Higher testosterone and estradiol were associated with lower MUP complexity; these relationships remained significant after adjusting for athletic status (p = 0.006 and p = 0.019, respectively). Circulating DHEA was positively associated with MU firing rate in these older men. Higher testosterone levels were associated with reduced MUP complexity, indicating reduced electrophysiological temporal dispersion, which is related to decreased differences in conduction times along axonal branches and/or MU fibres. Although evident in males only, this work highlights the potential of hormone administration as a therapeutic interventional strategy specifically targeting human motor units in older age.

Age-Related Declines in Lower Limb Muscle Function are Similar in Power and Endurance Athletes of Both Sexes: A Longitudinal Study of Master Athletes.

The age-related decline in muscle function, particularly muscle power, is associated with increased risk of important clinical outcomes. Physical activity is an important determinant of muscle function, and different types of physical activity e.g. power-based versus endurance-based exercise appear to have differential effects on muscle power. Cross-sectional studies suggest that participation in power-based exercise is associated with greater muscle power across adulthood but this has not been investigated longitudinally. We recruited eighty-nine male and female power and endurance master athletes (sprint and distance runners respectively, baseline age 35-90y). Using jumping mechanography, we measured lower limb muscle function during a vertical jump including at least two testing sessions longitudinally over 4.5 ± 2.4y. We examined effects of time, discipline (power/endurance) and sex in addition to two- and three-way interactions using linear mixed-effects models. Peak relative power, relative force and jump height, but not Esslingen Fitness Index (indicating peak power relative to sex and age-matched reference data) declined with time. Peak power, force, height and EFI were greater in power than endurance athletes. There were no sex, discipline or sex*discipline interactions with time for any variable, suggesting that changes were similar over time for athletes of both sexes and disciplines. Advantages in lower limb muscle function in power athletes were maintained with time, in line with previous cross-sectional studies. These results suggest that improvements in lower limb function in less active older individuals following power-based training persist with continued adherence, although this requires further investigation in interventional studies.

Development of tibia & fibula bone deficits in children with neurofibromatosis type I - A longitudinal case-control comparison.

Neurofibromatosis type 1 (NF1) is associated with lower bone mass and increased risk of fracture. Children with NF1 display faltering growth from mid-childhood. However, to date tibia bone development in children with NF1 across childhood and the role of body size have not been explored. Therefore, we recruited 24 children with NF1 (12 girls, mean age 8.2 ± 1.1y) and 104 children without NF1 (52 girls, mean age 11 ± 1.7y). Tibia and fibula bone characteristics were assessed at 4% and 38% distal-proximal tibia length in all children at baseline using peripheral quantitative computed tomography (pQCT). Longitudinal scans were obtained in 21 children with NF1 (12 girls) over 3.4 ± 0.3y and 71 children without NF1 (34 girls) over 1.1 ± 0.1y, such that at follow-up mean age of both groups (NF1 10.9 ± 1.3y, controls 11.4 ± 1.4y) were similar. Effects of group (NF1/control) on bone outcomes as well as group-by-age interactions, indicating differences in rate of change in bone outcome bone outcomes were assessed via linear mixed effects models with adjustment for sex, age, pubertal status and in additional models with adjustment for height and weight Z-scores. Group (NF1/control)-by-age interactions indicated a slower rate of tibia and fibula bone mass accrual in children with NF1 at all measured sites. These associations were attenuated by 25-50% by adjustment for height and weight Z-scores. At the 4% site, deficits in bone mass at older ages were related to slower trabecular BMD accrual. At the 38% site, group-by-age interactions suggested that bone mass deficits resulted from poorer accrual of cortical CSA and to a lesser extent cortical BMD. Lower limb bone mass deficits evident in children with NF1 appear to be progressive and emerge in mid-childhood. In part, they are related to development of a similar pattern of deficits in longitudinal growth and body weight in NF1. Interventions promoting muscle development or physical activity may be partially effective in attenuating bone mass accrual deficits in this population.

Leukocyte-derived ratios are associated with late-life any type dementia: a cross-sectional analysis of the Mugello study.

Immunosenescence, vascular aging, and brain aging, all characterized by elevated levels of inflammatory markers, are thought to share a common pathogenetic pathway: inflamm-aging. Retrospective cross-sectional analysis was conducted using data from the Mugello study (Tuscany, Italy), a representative Italian cohort of free-living nonagenarians. to assess the association between specific peripheral inflammation markers derived from white blood cell counts, and the diagnosis of dementia. All the variables of interest were reported for 411 subjects (110 males and 301 females) out of 475 enrolled in the study. Anamnestic dementia diagnosis was obtained from clinical certificate and confirmed by a General Practitioner, whereas leukocyte ratios were directly calculated from white blood cell counts. Body mass index and comorbidities were considered potential confounders. Diagnosis of any type dementia was certified in 73 cases (17.8%). Subjects affected by dementia were older, more frequently reported a previous stroke, had lower body mass index, and lower Mini-Mental-State-Examination score. Moreover, they had a higher lymphocyte count and lymphocyte-to-monocyte ratio compared to the non-demented nonagenarians. We found that higher levels of lymphocyte counts are cross-sectionally associated with a clinical diagnosis of dementia. Furthermore, lymphocyte-to-monocyte ratio is directly associated with any type of dementia, independently of age, sex, lymphocyte count, and comorbidities. Lymphocyte-to-monocyte ratio may be considered a marker of immunological changes in the brain of dementia patients; moreover, it is low-cost, and easily available, thus enabling comparisons among different studies and populations, although the timeline and the extent of lymphocyte-to-monocyte ratio role in dementia development must be further investigated.

Sedentary behaviour is an independent predictor of diabetic foot ulcer development: An 8-year prospective study.

AIMS: To prospectively explore the association between sedentary time (SED-time) and the development of diabetic foot ulcer (DFU) in people with diabetic peripheral neuropathy (DPN). METHODS: 175 DPN individuals who attended the annual evaluation for the SAMBA Study (2012-2019) were included. Main outcome measure was the first diagnosis of DFU. SED-time was measured by the PAS 2.1 questionnaire. Nerve function was evaluated by nerve conduction studies. Vascular function was assessed by Ankle-brachial index (ABI) and pedal pulses. Foot deformity and skin dryness were examined by visual inspection. RESULTS: 62 participants (35.5%) developed a DFU during the study. SED-time was significantly higher in people who developed DFUs (12.8 ± 3.0 vs 9.4 ± 3.1 h/day). Logistic regression showed that among several nervous (motor amplitude, OR 0.33, 95% CI, 0.18-0.60; sensory amplitude, 0.85, 0.77-0.94) and vascular parameters (ABI, 0.23, 0.1-0.61; pedal pulses, 2.81, 0.12-0.63) and foot characteristics (deformity, 2.63, 1.30-5.32; skin dryness, 2.04, 0.95-4.37), SED-time was one of the strongest variables contributing to the development of DFUs (2.95, 1.45-6.44). CONCLUSIONS: SED-time is an independent predictor of the risk of DFU in people with DPN. The monitoring of SED-time with strategies aimed at reducing it should be included in the standard care of diabetic patients.

Lifelong exercise is associated with more homogeneous motor unit potential features across deep and superficial areas of vastus lateralis.

Motor unit (MU) expansion enables rescue of denervated muscle fibres helping to ameliorate age-related muscle atrophy, with evidence to suggest master athletes are more successful at this remodelling. Electrophysiological data has suggested MUs located superficially are larger than those located deeper within young muscle. However, the effects of ageing and exercise on MU heterogeneity across deep and superficial aspects of vastus lateralis (VL) remain unclear. Intramuscular electromyography was used to record individual MU potentials (MUPs) and near fibre MUPs (NFMs) from deep and superficial regions of the VL during 25% maximum voluntary contractions, in 83 males (15 young (Y), 17 young athletes (YA), 22 old (O) and 29 master athletes (MA)). MUP size and complexity were assessed using area and number of turns, respectively. Multilevel mixed effects linear regression models were performed to investigate the effects of depth in each group. MUP area was greater in deep compared with superficial MUs in Y (p<0.001) and O (p=0.012) but not in YA (p=0.071) or MA (p=0.653). MUP amplitude and NF MUP area were greater, and MUPs were more complex in deep MUPs from Y, YA and O (all p<0.05) but did not differ across depth in MA (all p>0.07). These data suggest MU characteristics differ according to depth within the VL which may be influenced by both ageing and exercise. A more homogenous distribution of MUP size and complexity across muscle depths in older athletes may be a result of a greater degree of age-related MU adaptations.

Osteoporosis after spinal cord injury: aetiology, effects and therapeutic approaches.

Osteoporosis is a long-term consequence of spinal cord injury (SCI) that leads to a high risk of fragility fractures. The fracture rate in people with SCI is twice that of the general population. At least 50% of these fractures are associated with clinical complications such as infections. This review article presents key features of osteoporosis after SCI, starting with its aetiology, a description of temporal and spatial changes in the long bones and the subsequent fragility fractures. It then describes the physical and pharmacological approaches that have been used to attenuate the bone loss. Bone loss after SCI has been found to be highly site-specific and characterised by large inter-variability and site-specific changes. The assessment of the available interventions is limited by the quality of the studies and the lack of information on their effect on fractures, but this evaluation suggests that current approaches do not appear to be effective. More studies are required to identify factors influencing rate and magnitude of bone loss following SCI. In addition, it is important to test these interventions at the sites that are most prone to fracture, using detailed imaging techniques, and to associate bone changes with fracture risk. In summary, bone loss following SCI presents a substantial clinical problem. Identification of at-risk individuals and development of more effective interventions are urgently required to reduce this burden.

Thyroid hormone signaling is associated with physical performance, muscle mass, and strength in a cohort of oldest-old: results from the Mugello study.

Thyroid hormones (THs) play a crucial role in the homeostasis of muscle function, such as myogenesis and energy metabolism, suggesting that the thyroid may be also involved in the entropic processes of muscle aging. The aim of the present study is to evaluate the effect of TH signaling on physical performance, muscle mass, and strength in a cohort of community-dwelling oldest-old subjects (> 90 years). The study population was selected in a rural area of central Italy (Mugello, Tuscany), and the design was cross-sectional. Four hundred seventy-five subjects (130 males and 345 females) were enrolled, representing about 65% of all the nonagenarians living in the Mugello area. After adjusting for multiple confounding factors (sex, age, diabetes, and levothyroxine administration), the lowest quartile of FT3/FT4 ratio distribution showed lower physical performance compared to the other quartiles (ß ± SE: - 0.49 ± 0.12; p < 0.001), whereas the highest quartile of FT3/FT4 ratio was associated with higher skeletal muscle index (ß ± SE: 1.11 ± 0.42; p = 0.009). In addition, the lowest quartile of FT4 showed a statistically significant higher handgrip strength (ß ± SE: 1.78 ± 0.68; p = 0.009) compared to all other quartiles. This study demonstrates that nonagenarians with higher FT3/FT4 ratios had better preserved muscle function, therefore successfully overcoming the imbalance of homeostatic and entropic processes involved in muscle aging. However, we could not establish a cause-effect relationship due to the cross-sectional design of the study.

Peripheral quantitative computed tomography (pQCT) in 12- and 24-month-old children - Practical aspects and descriptive data.

BACKGROUND: Peripheral quantitative computed tomography (pQCT) is a useful tool to assess detailed bone characteristics. Its utility in infants is however limited due to lack of reference data and technical challenges. The purpose of this study was to provide data on length- and weight-adjusted pQCT values and to present a quality grading system for healthy children aged 12 and 24 months. MATERIAL AND METHODS: As a part of the Vitamin D intervention in Infants (VIDI) trial, we collected pQCT and anthropometric data from 855 children at 12 months and from 784 children at 24 months. Bone mineral content (BMC; mg/mm), volumetric bone mineral density (vBMD; mg/cm3), cross-sectional area (CSA; mm2), polar-moment of inertia (PMI; mm4), and periosteal circumference (PsC; mm) were assessed for total bone at 20% distal site of the left tibia using pQCT (Stratec XCT2000L). We evaluated the impact of scan quality on bone measures. Total bone parameters were assessed for boys and girls separately. The means of the bone parameters were also compared in relation to age. The associations between bone parameters and weight, length, sex and scan quality were analyzed. RESULTS: We included scans with sufficient quality (Grade 1-5) in the final analyses: 679/855 (79%) at 12 months and 709/784 (90%) at 24 months. Altogether 39% of the scans at 12 months and 51% at 24 months were of good or excellent quality (Grade 1-2). Scan quality had an impact on BMCs at 12 and 24 months (p = 0.001 and p = 0.017, respectively) but not on other bone parameters. Boys presented greater total bone BMC, CSA, PMI and PsC values at 12 and 24 months but vBMDs were similar. All bone parameters showed a significant increase between 12 and 24 months for both sexes. When adjusting bone parameters for weight, length and scan quality, differences between sexes disappeared. Weight was the strongest modifier of BMC, CSA, PMI and PsS at 12 and 24 months. CONCLUSIONS: This study increases our understanding on bone parameters in young children and demonstrates the suitability of pQCT in bone research in infants. The described pQCT data and scan quality grading system should prove useful in evaluating data reliability in research settings. CLINICAL TRIAL REGISTRATION NUMBER: NCT1723852.

Associations between prenatal indicators of mechanical loading and proximal femur shape: findings from a population-based study in ALSPAC offspring.

OBJECTIVES: Hip development is influenced by mechanical loading, but associations between prenatal loading and hip shape in later life remain unexplored. METHODS: We examined associations between prenatal loading indicators (gestation length, oligohydramnios (OH) and breech) obtained from obstetric records and hip shape modes (HSMs) generated using dual-energy X-ray absorptiometry images taken at age 14- and 18-years in participants from the UK Avon Longitudinal Study of Parents and Children (ALSPAC). These associations were examined in 2453 (30 OH, 105 breech) and 2330 (27 OH, 95 breech) participants with complete data at age 14- and 18-years respectively using confounder-adjusted models. RESULTS: At 14 years HSM2 was 0.59SD lower in OH males, and HSM5 (-0.31SD) and HSM9 (-0.32SD) were lower in OH in both sexes. At 18 years HSM1 (-0.44SD) and HSM2 (-0.71SD) were lower and HSM6 (0.61SD) and HSM8 (1.06SD) were higher in OH males, whilst HSM5 was lower in OH in both sexes. OH appeared to be associated with a wider femoral neck and head, and larger lesser/greater trochanters. Only weak associations were observed between gestation length/breech and HSMs. CONCLUSIONS: These results suggest that prenatal skeletal loading, in particular oligohydramnios, may influence adolescent joint shape with associations generally stronger in males.

Greater maintenance of bone mineral content in male than female athletes and in sprinting and jumping than endurance athletes: a longitudinal study of bone strength in elite masters athletes.

We investigated longitudinal changes in tibia bone strength in master power (jumping and sprinting) and endurance (distance) athletes of both sexes. Bone mass but not cross-sectional moment of inertia was better maintained in power than endurance athletes over time, particularly in men and independent of changes in performance. OBJECTIVE: Assessment of effects of sex and athletic discipline (lower limb power events, e.g. sprint running and jumping versus endurance running events) on longitudinal changes in bone strength in masters athletes. METHODS: We examined tibia and fibula bone properties at distal (4% distal-proximal tibia length) and proximal (66% length) sites using peripheral quantitative computed tomography (pQCT) in seventy-one track and field masters athletes (30 male, 41 female, age at baseline 57.0 ± 12.2 years) in a longitudinal cohort study that included at least two testing sessions over a mean period of 4.2 ± 3.1 years. Effects of time, as well as time × sex and time × discipline interactions on bone parameters and calf muscle cross-sectional area (CSA), were examined. RESULTS: Effects of time were sex and discipline-dependent, even following adjustment for enrolment age, sex and changes in muscle CSA and athletic performance. Male sex and participation in power events was associated with better maintenance of tibia bone mineral content (BMC, an indicator of bone compressive strength) at 4% and 66% sites. In contrast, there was no strong evidence of sex or discipline effects on cross-sectional moment of inertia (CSMI, an indicator of bone bending and torsional strength-P > 0.3 for interactions). Similar sex and discipline-specific changes were also observed in the fibula. CONCLUSIONS: Results suggest that male athletes and those participating in lower limb power-based rather than endurance-based disciplines have better maintenance of bone compressive but not bending and torsional strength.