Topographical Anatomy of the Adductor Muscle Group in the Albino Rat (Rattus norvegicus).

In comparative anatomy, the adductor muscles are said to be quite variable and to often cause difficulty in separation. The arrangement of these muscles and the possible occurrence of the adductor minimus and obturator intermedius muscles in the albino rat has not been investigated. The aim of this study was to accurately describe the adductor muscles in the albino rat (Rattus norvegicus). We hypothesized that all adductor muscles are constantly present and can be separated in a constant manner, and that the adductor minimus and obturator intermedius muscles are constant structures. Both pelvic limbs of 30 formalin-embalmed male albino rats were carefully dissected. The identification of the individual muscles was made based on their position in relation to the two branches of the obturator nerve and by comparing our results with previous findings in other species including humans. All examined rats had two gracilis muscles. The adductor longus muscle was the most superficial and smallest individual. The adductor brevis split into two parts of insertion-the femoral and genicular parts. The adductor magnus and minimus muscles could be separated constantly. The obturator intermedius muscle was a constant structure next to the obturator externus muscle. The adductor muscles of the albino rat were constantly separable and could be clearly assigned to their names. Further research is needed to investigate these muscles, especially the obturator intermedius muscle, in other species including humans.

Micronutrient intake to protect against osteoporosis during and after critical illness.

PURPOSE OF REVIEW: Improved survival from critical illness has enhanced the focus on ways to augment functional outcomes following discharge from the Intensive Care Unit. An area that is gaining increased attention is the effect of critical illness on bone health and fragility fractures following the episode. This review discusses the micronutrients that may play a role in bone metabolism and the potential benefits of their supplementation to prevent osteoporosis. These include calcium, phosphorous, magnesium, vitamin D, vitamin C, vitamin K, and certain trace elements. FINDINGS: Although there is sound physiological basis for the involvement of these micronutrients in bone health and fracture prevention, there are few clinically relevant publications in this area with calcium and vitamin D being the best studied to date. SUMMARY: In the absence of high-quality evidence in critically ill populations, attention to measurement and supplementation of these micronutrients as per current guidelines outlining micronutrient requirements in enteral and parenteral nutrition might mitigate bone loss and its sequelae in the recovery phase from critical illness.

Additive Effects of Exercise and Vitamin D Supplementation (with and without Calcium) on Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis.

Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: -0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: -0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS (I2 = 0%) and moderate for hip-BMD (I2 = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022309813.

Moderate COVID-19 Disease Is Associated With Reduced Bone Turnover.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been associated with musculoskeletal manifestations, including a negative effect on bone health. Bone formation was found to be reduced in coronavirus disease 2019 (COVID-19) patients. The aim of this case-control study was to determine whether bone metabolism is coupled or uncoupled in COVID-19 patients with moderately severe disease, the latter expressed by the requirement of hospitalization but not intensive care treatment, no need for mechanical ventilation, and a C-reactive protein level of (median [quartiles], 16.0 [4.0; 52.8]) mg/L in serum. Besides standard biochemical markers, serum levels of C-terminal telopeptide of type 1 collagen, tartrate-resistant acid phosphatase, osteocalcin, bone-specific alkaline phosphatase, sclerostin, dickkopf-1, and osteoprotegerin were evaluated in COVID-19-infected patients at the time of hospital admission, along with those of age- and sex-matched noninfected controls. The median age of the 14 female and 11 male infected patients included in the matched-pair analysis was (67 [53; 81]) years. C-terminal telopeptide of type 1 collagen was significantly lower in COVID-19 patients (0.172 [0.097; 0.375] ng/mL) than in controls (0.462 [0.300; 0.649] ng/mL; p = 0.011). The patients' osteocalcin levels (10.50 [6.49; 16.26] ng/mL) were also lower than those of controls (15.33 [11.85, 19.63] ng/mL, p = 0.025). Serum levels of sclerostin and dickkopf-1 were significantly higher in infected patients relative to controls. The remaining parameters did not differ between cases and controls. A limitation of the study was that patients and controls were recruited from different hospitals. Nevertheless, due to the geographical proximity of the two centers, we assume that this fact did not influence the results of the study. Given this limitation, the investigation showed that bone metabolism is altered but remains coupled in patients with moderately severe COVID-19. Therefore, it is important to evaluate bone turnover markers and fracture risk in these patients during the postinfection period. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The effect of aquatic exercise on bone mineral density in older adults. A systematic review and meta-analysis.

Introduction: Aquatic or water-based exercise is a very popular type of exercise in particular for people with physical limitations, joint problems and fear of falling. The present systematic review and meta-analysis aimed to provide evidence for the effect of aquatic exercise on Bone Mineral Density (BMD) in adults. Methods: A systematic literature search of five electronic databases (PubMed/MEDLINE, Cochrane Library, Scopus, Web of Science and CINAHL) according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) was conducted until 2022/01/30, with an update to 2022/10/07. We included controlled trials with a duration of more than 6 months and at least two study groups, aquatic exercise (EG) versus non-training controls (CG) with no language restrictions. Outcome measures were standardized mean differences (SMD) with 95%-confidence intervals (95%-CI) for BMD changes at the lumbar spine (LS) and femoral neck (FN). We applied a random-effects meta-analysis and used the inverse heterogeneity (IVhet) model to analyze the data. Results: Excluding an outlier study with an exceptionally high effect size for LS-BMD, we observed a statistically significant (p = .002) effect (EG vs. CG) of aquatic exercise for the LS-BMD (n = 10; SMD: 0.30; 95%-CI: 0.11-0.49). In parallel, the effect of aquatic exercise on FN-BMD was statistically significant (p = .034) compared to the CG (n = 10; SMD: 0.76, 95%-CI: 0.06-1.46). Of importance, heterogeneity between the trial results was negligible for LS (I2: 7%) but substantial for FN-BMD (I2: 87%). Evidence for risks of small study/publication bias was low for LS-BMD and considerable for FN-BMD. Discussion: In summary, the present systematic review and meta-analysis provides further evidence for the favorable effect of exercise on bone health in adults. Due to its safety and attractiveness, we particularly recommend water-based exercise for people unable, afraid or unmotivated to conduct intense land-based exercise programs.

Exercise effects on glucocorticoid-induced bone loss in adults: a systematic review and meta-analysis.

Objectives: Due to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy. Methods: A systematic literature search of five electronic databases included controlled trials with a duration of >6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN). Results: We identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI -0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I 2 = 71%, FN-BMD I 2 = 78%) between the study results. Conclusion: Although more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP. Registration number: PROSPERO: CRD42022308155.

Exercise training and bone mineral density in postmenopausal women: an updated systematic review and meta-analysis of intervention studies with emphasis on potential moderators.

The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I2 = 20%, TH BMD) to substantial (I2 = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur.

Exercise and the prevention of major osteoporotic fractures in adults: a systematic review and meta-analysis with special emphasis on intensity progression and study duration.

The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration. INTRODUCTION: Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic fractures in adults. METHODS: We conducted a systematic search of six literature databases according to the PRISMA guideline that included controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG) and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months). RESULTS: In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included. The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75, 95% CI: 0.54-0.94, p = .006). Although studies with intensity progression were more favorable, our subgroup analysis did not determine significant differences for diverging intensity progression (p = .133) or study duration (p = .883). Heterogeneity among the trials of the subgroups (I2 ≤ 0-7.1%) was negligible. CONCLUSION: The present systematic review and meta-analysis provided significant evidence for the favorable effect of exercise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions. PROSPERO ID: CRD42021250467.

Assessment of Bone Microstructure by Micro CT in C57BL/6J Mice for Sex-Specific Differentiation.

It remains uncertain which skeletal sites and parameters should be analyzed in rodent studies evaluating bone health and disease. In this cross-sectional mouse study using micro-computed tomography (µCT), we explored: (1) which microstructural parameters can be used to discriminate female from male bones and (2) whether it is meaningful to evaluate more than one bone site. Microstructural parameters of the trabecular and/or cortical compartments of the femur, tibia, thoracic and lumbar vertebral bodies, and skull were evaluated by µCT in 10 female and 10 male six-month-old C57BL/6J mice. The trabecular number (TbN) was significantly higher, while the trabecular separation (TbSp) was significantly lower in male compared to female mice at all skeletal sites assessed. Overall, bone volume/tissue volume (BV/TV) was also significantly higher in male vs. female mice (except for the thoracic spine, which did not differ by sex). Most parameters of the cortical bone microstructure did not differ between male and female mice. BV/TV, TbN, and TbSp at the femur, and TbN and TbSp at the tibia and lumbar spine could fully (100%) discriminate female from male bones. Cortical thickness (CtTh) at the femur was the best parameter to detect sex differences in the cortical compartment (AUC = 0.914). In 6-month-old C57BL/6J mice, BV/TV, TbN, and TbSp can be used to distinguish male from female bones. Whenever it is not possible to assess multiple bone sites, we propose to evaluate the bone microstructure of the femur for detecting potential sex differences.

Differential Expression of Dickkopf 1 and Periostin in Mouse Strains with High and Low Bone Mass.

By expressing different genes and proteins that regulate osteoclast as well as osteoblast formation, osteocytes orchestrate bone metabolism. The aim of this project was the evaluation of the differences in the osteocytes' secretory activity in the low bone mass mouse strain C57BL/6J and the high bone mass strain C3H/J. The femura of eight- and sixteen-week-old male C57BL/6J and C3H/J mice­six animals per group­were analyzed. Using immunohistochemistry, osteocytes expressing dickkopf 1, sclerostin, periostin, fibroblast growth factor 23 (FGF23), and osteoprotegerin were detected. By means of the OsteoMeasure-System, 92.173 osteocytes were counted. At the age of eight weeks, approximately twice as many cortical and trabecular osteocytes from the C57BL/6J mice compared to the C3H/J mice expressed dickkopf 1 (p < 0.005). The number of cortical osteocytes expressing sclerostin was also higher in the C57BL/6J mice (p < 0.05). In contrast, the cortical and trabecular osteocytes expressing periostin were twice as high in the C3H/J mice (p < 0.005). The dickkopf 1 expressing osteocytes of the C57BL/6J mice decreased with age and showed a strain-specific difference only in cortical bone by 16 weeks of age (p < 0.05). In the C3H/J mice, the amount of osteocytes expressing periostin tended to increase with age. Thus, strain-related differences were maintained in 16-week-old rodents (p < 0.005). No strain-specific differences in the expression of FGF23 or osteoprotegerin in the cortical compartment could be detected. This experimental study showed that the osteocytes' protein expression reflects differences in bone characteristics and strain-related differences during skeletal maturation. Besides the osteocytes' expression of sclerostin, their expression of dickkopf 1 and periostin seems to be important for bone properties as well.

Topographical anatomy of the albino rat's ischiotrochanteric muscle group.

The obturator internus, gemelli, and quadratus femoris muscles are thought to be postural muscles. Thus, they are in the focus of research. Although these muscles are described in other species, detailed descriptions are still lacking for the albino rat. We hypothesized that the rat's ischiotrochanteric muscle group is comparable to that of humans. We aimed to provide a detailed description, and to compare the rat's condition with other species including humans. Both hind limbs of 30 adult male formalin-fixed albino rats were carefully dissected and photo documented. Our results were then compared with data for other species and descriptions of human anatomy. The gemellus muscle was one single muscle mass, originating from the lesser sciatic notch and an unnamed groove on the dorsal aspect of the ischium. The obturator internus muscle arose from the inner aspect of the tabula of ischium. Both muscles formed a continuum and inserted as one complex on the medial aspect of the greater trochanter. The quadratus femoris muscle originated from the outer aspect of the tabula of ischium and inserted on the distal portion of the intertrochanteric crest, and the dorsal aspect of the lesser trochanter. Despite minor differences, the topographical conditions of these muscles are comparable between rats and other mammals including humans.

Denosumab for Prevention of Acute Onset Immobilization-Induced Alterations of Bone Turnover: A Randomized Controlled Trial.

Metabolic bone disease is a devastating condition in critically ill patients admitted to an intensive care unit (ICU). We investigated the effects of early administration of the antiresorptive drug denosumab on bone metabolism in previously healthy patients. Fourteen patients with severe intracerebral or subarachnoid hemorrhage were included in a phase 2 trial. Within 72 hours after ICU admission, they were randomized in a 1:1 ratio to receive denosumab 60 mg or placebo subcutaneously. The primary endpoint was group differences in the percentage change of C-terminal telopeptide of type 1 collagen (CTX-1) levels in serum from denosumab/placebo application to 4 weeks thereafter. Changes in serum levels of bone formation markers and urinary calcium excretion were secondary outcome parameters. Regarding serum levels of CTX-1, changes over time averaged -0.45 ng/mL (95% confidence interval [CI] -0.72, -0.18) for the denosumab group and 0.29 ng/mL (95% CI -0.01, 0.58) for the placebo group. The primary endpoint, the group difference in changes between baseline and secondary measurement, adjusted for baseline serum levels and baseline neurological status, averaged -0.74 ng/mL (95% CI -1.14, -0.34; p = 0.002). The group difference in changes between baseline and secondary osteocalcin measurement averaged -5.60 ng/mL (95% CI -11.2, -0.04; p = 0.049). The group difference in averaged change between baseline and secondary measurement of 24-hour urine calcium excretion was significant (-1.77 mmol/L [95% CI -3.48, -0.06; p = 0.044]). No adverse events could be attributed to the study medication. The investigation proved that a single application of denosumab early after admission to an ICU prevents acute immobilization-associated increase in bone resorption among previously healthy individuals. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Exercise Reduces the Number of Overall and Major Osteoporotic Fractures in Adults. Does Supervision Make a Difference? Systematic Review and Meta-Analysis.

The purpose of this systematic review and meta-analysis (PROSPERO ID: CRD42021250467) was to evaluate the effects of exercise on low-trauma overall and major osteoporotic fractures (hip, spine, forearm, or humerus fractures) and to determine the corresponding effect of supervision of the exercise program. Our systematic search of six literature databases according to the PRISMA guideline was conducted from January 1, 2013 (ie, date of our last search) to May 22, 2021, and included controlled clinical exercise trials with (i) individuals aged ≥45 years, (ii) cohorts without therapies/diseases related to fractures, (iii) observation periods of ≥3 months, and (iv) the number of low-trauma fractures listed separately for the exercise (EG) and control (CG) groups. We included 20 intervention studies with 21 EGs and 20 CGs comprising a pooled number of participant-years of n = 11.836 in the EG and n = 11.275 in the CG. The mixed-effects conditional Poisson regression revealed significant effects of exercise on low-trauma overall incidence (rate) ratio (IR 0.67, 95% confidence interval [95% CI] 0.51-0.87) and major osteoporotic fractures IR (0.69, 95% CI 0.52-0.92). Heterogeneity between the trials was moderate for low-trauma overall (I2 = 40%) and negligible (I2 < 1%) for major osteoporotic fractures. Supervision of the exercise program plays a significant role in the reductions of overall and major osteoporotic fractures with IR about twice as favorable in the predominately supervised (IR 0.44; 95% CI 0.27-0.73 and 0.38; 0.19-0.76) versus the predominately non-supervised exercise trials (IR 0.83; 95% CI 0.60-1.14 and 0.82; 0.64-1.05). In summary, the present study provides evidence for the positive effect of exercise on low-trauma overall and major osteoporotic fractures in middle aged to older adults. Supervision of the exercise program is a crucial aspect in exercise programs on fracture reduction. Thus, home-based exercise protocols should increasingly implement online classes to ensure widely consistent supervision and monitoring of the exercise program. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Mechanisms of Systemic Osteoporosis in Rheumatoid Arthritis.

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by the presence of symmetric polyarthritis predominantly of the small joints that leads to severe cartilage and bone destruction. Based on animal and human data, the pathophysiology of osteoporosis, a frequent comorbidity in conjunction with RA, was delineated. Autoimmune inflammatory processes, which lead to a systemic upregulation of inflammatory and osteoclastogenic cytokines, the production of autoantibodies, and Th cell senescence with a presumed disability to control the systemic immune system's and osteoclastogenic status, may play important roles in the pathophysiology of osteoporosis in RA. Consequently, osteoclast activity increases, osteoblast function decreases and bone metabolic and mechanical properties deteriorate. Although a number of disease-modifying drugs to treat joint inflammation are available, data on the ability of these drugs to prevent fragility fractures are limited. Thus, specific treatment of osteoporosis should be considered in patients with RA and an associated increased risk of fragility fractures.

Age Related Osteoporosis: Targeting Cellular Senescence.

Age-related chronic diseases are an enormous burden to modern societies worldwide. Among these, osteoporosis, a condition that predisposes individuals to an increased risk of fractures, substantially contributes to increased mortality and health-care costs in elderly. It is now well accepted that advanced chronical age is one of the main risk factors for chronical diseases. Hence, targeting fundamental aging mechanisms such as senescence has become a promising option in the treatment of these diseases. Moreover, for osteoporosis, the main pathophysiological concepts arise from menopause causing estrogen deficiency, and from aging. Here, we focus on recent advances in the understanding of senescence-related mechanisms contributing to age-related bone loss. Furthermore, treatment options for senile osteoporosis targeting senescent cells are reviewed.

Effects of Hormone Therapy and Exercise on Bone Mineral Density in Healthy Women-A Systematic Review and Meta-analysis.

CONTEXT: There is some evidence that an adequate "anabolic hormonal milieu" is essential for the mechanosensitivity/transduction/response of bone tissue. OBJECTIVE: This work aimed to determine whether enhancing hormone therapy (HT) with exercise increases the isolated effect of HT on bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN). METHODS: A comprehensive search of 6 electronic databases according to the PRISMA statement up to April 28, 2021, included controlled trials longer than 6 months with 3 study arms: (a) HT, (b) exercise, and (c) HT plus exercise (HT + E). Apart from HT, no pharmaceutic therapy or diseases with relevant osteoanabolic or osteocatabolic effect on bone metabolism were included. The present analysis was conducted as a random-effects meta-analysis. Outcome measures were standardized mean differences (SMD) for BMD changes at the LS and FN. RESULTS: Our search identified 6 eligible studies (n = 585). Although the effect of HT + E was more pronounced in the LS (SMD: 0.19; 95% C,: -0.15 to 0.53) and FN-BMD (0.18; -0.09 to 0.44) compared to the HT group, we did not observe significant differences between the 2 groups. We observed a low (I2: 29%) or moderate (I2: 49%) level of heterogeneity between the trials for FN or LS. CONCLUSION: We do not observe a significant effect of HT + E vs HT alone. We largely attribute this result to varying HT supplementation and hormonal status. Bearing in mind that synergistic/additive effects between HT and mechanical stimulation can only be expected in situations of hormonal insufficiency, further clinical studies should consider baseline endogenous estrogen production but also HT dosing more carefully.

Circulating bioactive sclerostin levels in an Austrian population-based cohort.

BACKGROUND: Circulating serum sclerostin levels are supposed to give a good estimation of the levels of this negative regulator of bone mass within bone. Most studies evaluating total serum sclerostin found different levels in males compared to females and in older compared to younger subjects. Besides an ELISA detecting total sclerostin an ELISA determining bioactive sclerostin has been developed. The aim of this study was to investigate serum levels of bioactive sclerostin in an Austrian population-based cohort. METHODS: We conducted a cross-sectional observational study in 235 healthy subjects. Using the bioactive ELISA assay (Biomedica) bioactive sclerostin levels were evaluated. RESULTS: Serum levels of bioactive sclerostin were higher in men than in women (24%). The levels correlated positively with age (r = 0.47). A positive correlation could also be detected with body mass index and bone mineral density. CONCLUSION: Using the ELISA detecting bioactive sclerostin our results are consistent with data in the literature obtained by different sclerostin assays. The determination of sclerostin concentrations in peripheral blood thus appears to be a robust parameter of bone metabolism.

The effect of different training frequency on bone mineral density in older adults. A comparative systematic review and meta-analysis.

Exercise frequency is a key aspect of exercise protocols. In this systematic review and meta-analysis, we determined the effect of training frequency on (areal) bone mineral density (BMD) at lumbar spine (LS) and hip. Reviewing seven electronic databases up to April 2021, we conducted a systematic review of the literature according to the PRISMA statement. Inclusion criteria were (a) controlled exercise trials (b) with at least two study arms that compared low versus high exercise frequency, (c) an intervention ≥6 months and (d) BMD assessments at lumbar spine (LS) or hip. The analysis was conducted as a mixed-effect meta-analysis and used "type of exercise" and "study duration" as moderators in subgroup analyses. Standardized mean differences (SMD) for LS- and hip-BMD changes were defined as outcome measures. Seven studies with 17 exercise groups were included in the analysis. We observed significantly higher effects of high (≥2 sessions/week) vs. low net training frequency (1-<2 sessions/week) exercise on LS- (SMD 0.55, 95%-CI: 0.20-0.90) but not hip-BMD (0.19, -0.06 to 0.45). Study duration was found to be a significant moderator for the effect of training frequency at LS- but not hip-BMD. In parallel, the type of exercise moderately influences the effect of training frequency on LS- but not on hip-BMD. We observed a superior effect of higher net training frequency on BMD. Longer exercise exposition increases this effect. Considering e.g. holidays, indisposition or other temporary absence, exercise programs on osteoporosis should provide at least 3 sessions/week/year to allow a net training frequency of more than two sessions/week. STUDY REGISTRATION: PROSPERO (CRD42021246804).

Exercise Effects on Bone Mineral Density in Men.

In contrast to postmenopausal women, evidence for a favorable effect of exercise on Bone Mineral Density (BMD) is still limited for men. This might be due to the paucity of studies, but also to the great variety of participants and study characteristics that may dilute study results. The aim of the present systematic review and meta-analysis was to evaluate the effect of exercise on BMD changes with rational eligibility criteria. A comprehensive search of six electronic databases up to 15 March 2021 was conducted. Briefly, controlled trials ≥6 months that determined changes in areal BMD in men >18 years old, with no apparent diseases or pharmacological therapy that relevantly affect bone metabolism, were included. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) and femoral neck (FN) were considered as outcomes. Twelve studies with 16 exercise and 12 control groups were identified. The pooled estimate of random-effect analysis was SMD = 0.38, 95%-CI: 0.14-0.61 and SMD = 0.25, 95%-CI: 0.00-0.49, for LS and FN, respectively. Heterogeneity between the trials was low-moderate. Funnel plots and rank and regression correlation tests indicate evidence for small study publication bias for LS but not FN-BMD. Subgroup analyses that focus on study length, type of exercise and methodologic quality revealed no significant difference between each of the three categories. In summary, we provided further evidence for a low but significant effect of exercise on BMD in men. However, we are currently unable to give even rough exercise recommendations for male cohorts.

Myostatin and markers of bone metabolism in dermatomyositis.

BACKGROUND: In dermatomyostis (DM) patients, inflammation, reduced activity, and medication have a negative impact on the musculoskeletal system. Several endocrine factors are involved in muscle growth and bone turnover. OBJECTIVE: We aimed to investigate factors regulating myogenesis and bone metabolism and to evaluate possible associations between these endocrine factors, muscle strength, and functional tests in DM patients. METHODS: We conducted a cross-sectional study in 20 dermatomyositis patients. Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf 1 (Dkk1), sclerostin (SOST), periostin (PSTN), the receptor activator nuclear factor kB ligand (RANKL):osteoprotegerin (OPG) ratio and fibroblast growth factor 23 (FGF23) were determined. Physical function was evaluated by hand-held strength measurement, chair rising test, timed up and go test and the 3-min walking test. RESULTS: Serum MSTN and FGF23 levels (2.5 [1.9; 3.2] vs. 1.9 [1.6; 2.3] and 2.17 [1.45; 3.26] vs. 1.28 [0.79; 1.96], respectively; p <  0.05) were significantly higher in DM patients than in controls. Dkk1 was significantly lower (11.4 [6.9; 20.0] vs. 31.8 [14.3; 50.6], p <  0.01). Muscle strength and physical function tests correlated with each other (e.g. hip flexion - timed up and go test: r = - 0.748, p < 0.01). CONCLUSION: In DM patients, biochemical musculo-skeletal markers are altered and physical function shows deficits. All these tests reflect independent of each other different deficits in long-term DM patients which is important for the assessment of DM patients as well as planning of therapeutic interventions in clinical routine.