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.

Longitudinal changes in muscle power compared to muscle strength and mass.

OBJECTIVES: The study reports longitudinal changes in grip strength, muscle mass and muscle power of lower extremities. The aim is to identify early muscular changes to improve the diagnosis and treatment of sarcopenia. METHODS: Grip strength was measured by hand dynamometer, muscle mass by dual-energy X-ray absorptiometry and muscle power by performing a chair rise test and two-leg jumps (2LJP) on the Leonardo Mechanograph®. Longitudinal changes were analysed using paired t-tests by age group and sex. Differences between groups in terms of the annual change were tested by Analysis of Variance and the Dunnett's test. Comparisons between the variables were performed using one sample t-tests. RESULTS: Six-year changes were determined in 318 randomly selected healthy participants aged 20-90 years from Berlin. 2LJP declined significantly earlier in 20-39 years old women (-3.70 W/kg) and men (-5.97 W/kg, both p<0.001). This is an absolute annual decline of -0.46 W/kg in females and -0.75 W/kg in males. In the oldest age group, 2LJP showed the highest absolute annual loss with -0.99 W/kg in women and -0.88 W/kg in men. 2LJP was significantly different compared to all variables of muscle mass and strength (p<0.01). CONCLUSIONS: The results underline the importance of assessing muscle power using 2LJP during aging.

Health Demands Moderate the Link Between Willpower Beliefs and Physical Activity in Patients with Knee Osteoarthritis.

BACKGROUND: Regular physical activity (PA) was found to alleviate pain and improve functioning among patients with osteoarthritis of the knee (OAK). Heightened health demands due to OAK severity, body mass index (BMI), and depressive symptoms may require self-regulatory strategies to engage in more PA. Research on willpower-the capacity to exert self-control-suggests that believing that willpower is a nonlimited rather than a limited resource predicts effective self-regulation specifically when demands are high. The present study examines the association of OAK patients' willpower beliefs with their daily PA as a function of health demands. METHODS: To identify the moderating role of OAK severity (WOMAC), BMI, and depressive symptoms (CES-D) on the link between willpower beliefs and objectively assessed PA over a 7-day period, baseline data of a registered randomized controlled trial with 243 patients (Mage = 65.47 years, SD = 0.49) were examined in secondary analyses. RESULTS: Moderation analyses revealed that overall positive associations of willpower beliefs with PA were further qualified by OAK severity, BMI, and depressive symptoms. When patients faced less health demands, believing that willpower is nonlimited was associated with more PA. When health demands were higher, willpower beliefs were not associated with PA. CONCLUSION: OAK patients' willpower beliefs were associated with PA. However, facing more health demands seemed to erase this beneficial link. Improving willpower beliefs by way of intervention may help to shed more light on predictive direction and ways to overcome barriers to regular physical activity.

Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial.

Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear. Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults. Design, Setting, and Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017. Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270). Main Outcomes and Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance. Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups. Conclusions and Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.

Facilitating physical activity and reducing symptoms in patients with knee osteoarthritis: study protocol of a randomized controlled trial to test a theory-based PrevOP-psychological adherence program (PrevOP-PAP).

BACKGROUND: The present randomized controlled trial, which is crossed with the "PREVenting the impairment of primary Osteoarthritis by high impact long-term Physical exercise regimen" Main Medical Trial (PrevOP-MMT), aims to evaluate a psychological adherence program (PrevOP-PAP), and is designed to support persons with knee osteoarthritis (OAK) in the uptake and maintenance of regular physical activity to reduce OAK symptoms. The PrevOP-PAP is based on the Health Action Process Approach (HAPA), a social-cognitive theory predicting health behavior change in individuals, extended here by social network characteristics and social exchange processes. It is expected that participants with OAK receiving the PrevOP-PAP will maintain higher levels of regular physical activity throughout a 24-month period and consequently report lower levels of OAK symptoms than participants of an active control condition. METHODS: A total of N = 240 participants with medically verified moderate OAK will be randomly assigned to an intervention condition (PrevOP-PAP-I; 50%) or an active control condition (PrevOP-PAP-CTRL). The PrevOP-PAP-I includes a motivational intervention, repeated self-regulation interventions, and a network creation intervention delivered over 12 months. Modes of intervention delivery include a paper-pencil motivation leaflet with a quiz, a computer-assisted face-to-face intervention, four computer assisted phone-based interventions, and activity calendars. The PrevOP-PAP-CTRL includes the motivational intervention only. Primary outcome will be OAK symptoms. Secondary outcomes include objectively and subjectively measured physical activity and indicators of quality of life. Other outcomes are HAPA-derived self-regulatory indicators as well as proposed social network and social exchange mechanisms of health behavior change. Assessments take place at baseline, 6 months, 12 months, 18 months, and 24 months following baseline. DISCUSSION: Based on the extended HAPA, this study seeks to reveal the self-regulatory and social mechanisms of the uptake and maintenance of physical activity and their relation to disease symptoms in persons with OAK. The design and evaluation of this program are intended to become a yardstick for future development and implementation of digitalized psychological adherence programs in this population. TRIAL REGISTRATION: German Clinical Trials Register; also available at http://apps.who.int/trialsearch/ ; registration number: DRKS00009677 ; date of registration: 26 January 2016.

Hypertrophy and Explosive-Reactive Functioning in Sedentary Men After 10 Weeks of Whole-Body Vibration.

Ebing, J, Gast, U, Hauptmann, C, Felsenberg, D, and Belavý, DL. Hypertrophy and explosive-reactive functioning in sedentary men after 10 weeks of whole-body vibration. J Strength Cond Res 32(1): 27-36, 2018-The objective of this study was to determine the impact of vertical (Power-plate; POW) and side-alternating (Galileo; GAL) whole-body vibration exercise on muscle mass and lower-limb neuromuscular function. Forty-three sedentary male subjects (18-30 year) randomized into 3 groups underwent 2 upper-body exercise sessions per week for 10 weeks. Two groups of subjects underwent additional squat exercises on the GAL (N = 15) or POW (N = 14) devices. The third group was control. On magnetic resonance imaging, volume of the thigh muscles was measured. Countermovement jump, multiple one-leg hopping, drop jump, landing test, 15-m sprint, and grip strength were performed. Measurements were performed at baseline, and at 5 and 10 weeks. Significantly greater increases in vasti volume were seen in the GAL (+4.15%; p = 0.00076 vs. control) and POW (+4.81%; p = 0.0074 vs. control) groups than in the control group (-1.22%) at 10 weeks. The adductor magnus volume increased in the GAL (+2.24%; p = 0.00038 vs. baseline) and POW (+2.33%; p = 0.00038 vs. baseline) groups at 10 weeks, but this was not significantly different from the control (-0.67%; p = 0.54 vs. baseline). Hamstring volume decreased in GAL (-1.85%; p = 0.00038 vs. baseline) at 5 weeks with the reduction in the POW group at 5 weeks (-1.73%; p = 0.17 vs. baseline) not reaching significance. There were no significant differences between the POW and GAL groups (p ≥ 0.084) and no significant changes in neuromuscular performance. Twice weekly squat exercises with whole-body vibration, progressing from 3- to 5-minute time under tension, lead to thigh muscle hypertrophy but no improvements in explosive-reactive function.

Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe: prevalence, geographic variation and radiological correlates in men and women aged 50 and over.

Objectives: To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. Methods: In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results: Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Conclusion: KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.

Porcine arteriogenesis based on vasa vasorum in a novel semi-acute occlusion model using high-resolution imaging.

Bridging collaterals (BC) develop in several chronic total artery occlusion diseases, and can prevent extensive myocardial necrosis. Yet, their origin, growth process, and histo-morphology are still unclear. Since vasa vasorum (VV) may take part in collateralization, we hypothesized that VV are the basis for BCs. To comprehensively investigate this arteriogenesis process, we used high-resolution imaging, including corrosion casts, post-mortem angiography with stereoscopy, micro-CT, and immunohistology, in combination with a novel semi-acute vessel occlusion model. This porcine model was produced by implanting a copper stent minimally invasively into the left anterior descending coronary artery. To define the kinetics of arteriogenesis, pigs (n = 11) were assigned to one of the five euthanasia timepoints: day 0.5 (D0.5, n = 2), D3 (n = 2), D5 (n = 1), D7 (n = 3), or D12 (n = 3) after stent implantation. We found that (1) BCs originate from longitudinally running type 1 VV, mainly VV interna, partially also from VV externa; (2) the growth of VV to BC is rapid, occurring within 7 days; and (3) porcine BCs are likely functionally relevant, considering an observed 102% increase in the number of smooth muscle cell layers in their vascular wall. High-resolution imaging in a minimally invasive non-acute vessel occlusion model is an innovative technique that allowed us to provide direct evidence that porcine BCs develop from the VV. These data may be crucial for further studies on the treatment of angina pectoris and thromboangiitis obliterans through therapeutic stimulation of BC development.

Case-Based Review of Osteonecrosis of the Jaw (ONJ) and Application of the International Recommendations for Management From the International Task Force on ONJ.

Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.

Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest.

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Normocalcaemic hypoparathyroidism: prevalence and effect on bone status in older women. The OPUS study.

OBJECTIVE: There are no consistent data on the prevalence and bone status of normocalcaemic hypoparathyroidism (NHYPO) as defined by normal adjusted calcium and low PTH level. Our aim was to determine the prevalence and the metabolic bone profile of NHYPO in older women, assessing its evolution over time. The second objective was to evaluate the prevalence of other calcium metabolic disorders. DESIGN: The Osteoporosis and Ultrasound Study (OPUS) is a 6-yr prospective study of fracture-related factors. PARTICIPANTS: A total of 2419 older women (age 55-79 yrs) and 258 younger women (age 30-40 yrs) participated. Complete follow-up data were available in 1416 subjects. MEASUREMENTS: After calculating the adjusted calcium according to James' formula, we identified 'abnormal' calcium and PTH using Mahalanobis distances and allocated older women into different pathological categories using reference intervals from the healthy young women. RESULTS: We identified 57 subjects with NHYPO (2·4%). These women had lower than expected bone turnover as assessed by bone alkaline phosphatase (-14·5%, 95% CI: -26·2 to -3·0, P = 0·007), CTX (-66·3%, 95% CI: -74·0 to -56·4, P < 0·001) and osteocalcin (-36·8%, 95% CI: -45·6 to -26·6, P < 0·001). After 6 years, of the 35 NHYPO subjects with follow-up data, none developed overt hypoparathyroidism and only 15 (0·6%) subjects had persistent evidence of NHYPO. We also identified 86 subjects (3·6%) affected by hyperparathyroid hypercalcaemia. CONCLUSION: This is the first large population-based study to investigate NHYPO in older women. NHYPO is fairly common, not always persistent and is characterized by low bone turnover.

Disuse deterioration of human skeletal muscle challenged by resistive exercise superimposed with vibration: evidence from structural and proteomic analysis.

In the present bed rest (BR) study, 23 volunteers were randomized into 3 subgroups: 60 d BR control (Ctr); BR with resistive exercise (RE; lower-limb load); and resistive vibration exercise (RVE; RE with superimposed vibration). The aim was to analyze by confocal and electron microscopy the effects of vibration on myofibril and filament integrity in soleus (Sol) and vastus lateralis (VL) muscle; differential proteomics of contractile, cytoskeletal, and costameric proteins (TN-C, ROCK1, and FAK); and expression of PGC1α and atrophy-related master genes MuRF1 and MuRF2. RVE (but not RE) preserved myofiber size and phenotype in Sol and VL by overexpressing MYBPC1 (42%, P ≤ 0.01), WDR1 (39%, P ≤ 0.01), sarcosin (84%, P ≤ 0.01), and CKM (20%, P ≤ 0.01) and prevented myofibrillar ultrastructural damage as detectable by MuRF1 expression. In Sol, cytoskeletal and contractile proteins were normalized by RVE, and TN-C increased (59%, P ≤ 0.01); the latter also with RE (108%, P ≤ 0.01). In VL, the outcomes of both RVE (acting on sarcosin and desmin) and RE (by way of troponinT-slow and MYL2) were similar. RVE appears to be a highly efficient countermeasure protocol against muscle atrophy and ultrastructural and molecular dysregulation induced by chronic disuse.

Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk.

Osteoporotic fracture is a major cause of morbidity and mortality worldwide. Low bone mineral density (BMD) is a major predisposing factor to fracture and is known to be highly heritable. Site-, gender-, and age-specific genetic effects on BMD are thought to be significant, but have largely not been considered in the design of genome-wide association studies (GWAS) of BMD to date. We report here a GWAS using a novel study design focusing on women of a specific age (postmenopausal women, age 55-85 years), with either extreme high or low hip BMD (age- and gender-adjusted BMD z-scores of +1.5 to +4.0, n = 1055, or -4.0 to -1.5, n = 900), with replication in cohorts of women drawn from the general population (n = 20,898). The study replicates 21 of 26 known BMD-associated genes. Additionally, we report suggestive association of a further six new genetic associations in or around the genes CLCN7, GALNT3, IBSP, LTBP3, RSPO3, and SOX4, with replication in two independent datasets. A novel mouse model with a loss-of-function mutation in GALNT3 is also reported, which has high bone mass, supporting the involvement of this gene in BMD determination. In addition to identifying further genes associated with BMD, this study confirms the efficiency of extreme-truncate selection designs for quantitative trait association studies.

Muscle X-ray attenuation is not decreased during experimental bed rest.

INTRODUCTION: Muscle X-ray attenuation (MXA) in Hounsfield units (HU) is decreased in dystrophy, aging, and immobilization. We hypothesized a decrease also during bed rest (BR). METHODS: Twenty-five healthy men performed BR for 90 days, 8 of whom performed flywheel exercise 2-3 times per week. Muscle cross-sectional area (CSA) and MXA were assessed by computed tomography. RESULTS: In the control group, calf muscle CSA decreased during 89-day BR by 26.6 (SD 3.8) %, while MXA increased by 1.2 HU on day 28 and almost reached baseline values on day 89. Changes were mitigated in the flywheel group for the calf (P < 0.001). All changes were reversed within 90 days after BR. CONCLUSIONS: Results contradict the initial hypothesis. Increased intramuscular blood content, interstitial fluid space shrinkage, and reduction of intramuscular lipid stores are possible explanations for the moderate increase in MXA during the initial phase of bed rest.

Expression and regulation of Homer in human skeletal muscle during neuromuscular junction adaptation to disuse and exercise.

Protein calcium sensors of the Homer family have been proposed to modulate the activity of various ion channels and nuclear factor of activated T cells (NFAT), the transcription factor modulating skeletal muscle differentiation. We monitored Homer expression and subcellular localization in human skeletal muscle biopsies following 60 d of bedrest [Second Berlin Bedrest Study (BBR2-2)]. Soleus (SOL) and vastus lateralis (VL) biopsies were taken at start (pre) and at end (end) of bedrest from healthy male volunteers of a control group without exercise (CTR; n=9), a resistive-only exercise group (RE; n=7), and a combined resistive/vibration exercise group (RVE; n=7). Confocal analysis showed Homer immunoreactivity at the postsynaptic microdomain of the neuromuscular junction (NMJ) at bedrest start. After bedrest, Homer immunoreactivity decreased (CTR), remained unchanged (RE), or increased (RVE) at the NMJ. Homer2 mRNA and protein were differently regulated in a muscle-specific way. Activated NFATc1 translocates from cytoplasm to nucleus; increased amounts of NFATc1-immunopositive slow-type myonuclei were found in RVE myofibers of both muscles. Pulldown assays identified NFATc1 and Homer as molecular partners in skeletal muscle. A direct motor nerve control of Homer2 was confirmed in rat NMJs by in vivo denervation. Homer2 is localized at the NMJ and is part of the calcineurin-NFATc1 signaling pathway. RVE has additional benefit over RE as countermeasure preventing disuse-induced neuromuscular maladaptation during bedrest.

Adverse reactions and drug-drug interactions in the management of women with postmenopausal osteoporosis.

The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug-drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug-drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.

The effects of rehabilitation on the muscles of the trunk following prolonged bed rest.

Microgravity and inactivity due to prolonged bed rest have been shown to result in atrophy of spinal extensor muscles such as the multifidus, and either no atrophy or hypertrophy of flexor muscles such as the abdominal group and psoas muscle. These effects are long-lasting after bed rest and the potential effects of rehabilitation are unknown. This two-group intervention study aimed to investigate the effects of two rehabilitation programs on the recovery of lumbo-pelvic musculature following prolonged bed rest. 24 subjects underwent 60 days of head down tilt bed rest as part of the 2nd Berlin BedRest Study (BBR2-2). After bed rest, they underwent one of two exercise programs, trunk flexor and general strength (TFS) training or specific motor control (SMC) training. Magnetic resonance imaging of the lumbo-pelvic region was conducted at the start and end of bed rest and during the recovery period (14 and 90 days after re-ambulation). Cross-sectional areas (CSAs) of the multifidus, psoas, lumbar erector spinae and quadratus lumborum muscles were measured from L1 to L5. Morphological changes including disc volume, spinal length, lordosis angle and disc height were also measured. Both exercise programs restored the multifidus muscle to pre-bed-rest size, but further increases in psoas muscle size were seen in the TFS group up to 14 days after bed rest. There was no significant difference in the number of low back pain reports for the two rehabilitation groups (p=.59). The TFS program resulted in greater decreases in disc volume and anterior disc height. The SMC training program may be preferable to TFS training after bed rest as it restored the CSA of the multifidus muscle without generating potentially harmful compressive forces through the spine.

Patellar tendinopathy in master track and field athletes: influence of impact profile, weight, height, age and gender.

PURPOSE: Patellar tendinopathy causes significant morbidity in professional and recreational athletes. Despite the relevance of the problem, its causative factors remain poorly understood. The purpose of this cross-sectional study is to evaluate the influence of age, gender, weight, height and impact profile on developing patellar tendinopathy in master track and field athletes. METHODS: During the European Veterans Athletics Championships in Poznan in July 2006, 174 athletes (103 men and 71 women; mean age: 53.8 (SD 11.4) years, range 35-82 years) were evaluated with the VISA-P questionnaire. A fully trained orthopaedic surgeon made a diagnosis of patellar tendinopathy according to clinical criteria. RESULTS: There was no effect of gender upon the presence of patellar tendinopathy (n.s.). No significant track and field specialty effect upon the frequency of patellar tendinopathy was found on the VISA-P questionnaire scores. There was no effect of track and field specialty on the VISA-P score. No evidence of a statistically significant association was found between age and VISA-P score (n.s.). There was no statistically significant difference in either prevalence of patellar tendinopathy or VISA-P score between high-impact and low-impact athletes (n.s.). CONCLUSION: In master track and field athletes, impact profile, weight, height, age and gender did not exert any influence on developing patellar tendinopathy.

Regular exercise counteracts circadian shifts in core body temperature during long-duration bed rest.

With NASA's plans for the human exploration of Mars, astronauts will be exposed to mission durations much longer than current spaceflight missions on the International Space Station. These mission durations will increase the risk for circadian misalignment. Exercise has gained increasing interest as a non-pharmacological aid to entrain the circadian system. To assess the potential of exercise as a countermeasure to mitigate the risk for circadian disorders during spaceflight, we investigated the effects of long-term head-down tilt bed rest (HDBR) with and without exercise on the circadian rhythm of core body temperature. Core body temperature was recorded for 24 h using a rectal probe in sixteen healthy men (age: 30.5 ± 7.5 years (mean ± SD)) after 7 days and 49 days of HDBR. Five participants underwent HDBR only (CTR), five participants underwent HDBR and performed resistive exercises (RE), and six participants underwent HDBR and performed resistive exercises superimposed with vibrations (RVE). The exercise was scheduled three times per week. CTR showed a phase delay of 0.69 h. In contrast, both exercise groups were characterized by a phase advance (0.45 h for RE and 0.45 h for RVE; p = 0.026 for interaction between time and group). These findings suggest that resistive exercise (with or without vibration) may also serve as a countermeasure during spaceflight to mitigate circadian misalignments. The results could also be important for increasing awareness about the role of circadian disorders in long-term bedridden patients.

Quantitative assessment of the lumbar intervertebral disc via T2 shows excellent long-term reliability.

Methodologies for the quantitative assessment of the spine tissues, in particular the intervertebral disc (IVD), have not been well established in terms of long-term reliability. This is required for designing prospective studies. 1H water T2 in the IVD ("T2") has attained wider use in assessment of the lumbar intervertebral discs via magnetic resonance imaging. The reliability of IVD T2 measurements are yet to be established. IVD T2 was assessed nine times at regular intervals over 368 days on six anatomical slices centred at the lumbar spine using a spin-echo multi-echo sequence in 12 men. To assess repeatability, intra-class correlation co-efficients (ICCs), standard error of the measurement, minimal detectable difference and co-efficients of variation (CVs) were calculated along with their 95% confidence intervals. Bland-Altman analysis was also performed. ICCs were above 0.93, with the exception of nuclear T2 at L5/S1, where the ICC was 0.88. CVs of the central-slice nucleus sub-region ranged from 4.3% (average of all levels) to 10.1% for L5/S1 and between 2.2% to 3.2% for whole IVD T2 (1.8% for the average of all levels). Averaging between vertebral levels improved reliability. Reliability of measurements was least at L5/S1. ICCs of degenerated IVDs were lower. Test-retest reliability was excellent for whole IVD and good to excellent for IVD subregions. The findings help to establish the long-term repeatability of lumbar IVD T2 for the implementation of prospective studies and determination of significant changes within individuals.