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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Simple Summary: Cells embedded in bone, so-called osteocytes, regulate bone metabolism by releasing various factors. Mouse studies are used both to investigate the background of various diseases and during the development of drugs. This is particularly relevant for osteoporosis, a disease characterized by a reduction of bone mass and an increased risk of bone fracture. The aim of this project was to investigate the differences in the expression of factors relevant for bone metabolism by osteocytes in two different mouse strains (C57BL/6J mice with low bone mass and C3H/J mice with high bone mass). The osteocytes' expression of the investigated factors revealed strain- and age-associated differences. This study shows that the expression of specific factors by osteocytes reflects strain-related differences of bone properties. 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 mice—six animals per group—were 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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 (I 2 : 29%) or moderate (I 2 : 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Muscle and bone metabolism are both important for the healing of fractures and the regeneration of injured muscle tissue. The aim of this investigation was to evaluate myostatin and other regulating factors in patients with hip fractures who underwent hemi-arthroplasty.Methods: Serum levels of myostatin (MSTN), follistatin (FSTN), dickkopf-1 (Dkk1), and periostin (PSTN) as well as markers of bone turnover were evaluated in patients with hip fractures before surgery and twice in the 2 weeks after surgery. These parameters were also evaluated in age- and gender-matched subjects without major musculoskeletal injury.Results: MSTN was transiently reduced; its opponent FSTN was transiently increased. Dkk1, the negative regulator of bone mass, and PSTN, a marker of subperiosteal bone formation, increased after surgery. With regard to markers of bone turnover, resorption was elevated during the entire period of observation whereas the early bone formation marker N-terminal propeptide of type I collagen was elevated 12 days after surgery.Conclusions: Unexpectedly, MSTN, a negative regulator of muscle growth, was reduced after surgery compared with before surgery. As musculoskeletal markers are altered during bone healing, they do not reflect general bone metabolism after fracture or joint arthroplasty. This is important because many elderly patients receive treatment for osteoporosis. [ABSTRACT FROM AUTHOR]

Purpose Of Review: In view of the existing uncertainty about the implications of intentional weight loss in older obese adults, the present review (a) summarizes the available evidence from epidemiological and interventional studies concerning the effects of weight loss through lifestyle modifications on skeletal health parameters in older overweight/obese individuals, (b) proposes mechanisms that link weight loss to bone loss in this age group, and (c) identifies appropriate animal models. Main Findings and Future Directions: Based on prospective epidemiological studies, weight loss is associated with bone loss, impaired bone macro- and microstructure, and increased fracture risk in the elderly. Data from interventional studies confirm the negative effects of intentional weight loss achieved by lifestyle modifications on skeletal health outcomes in obese older individuals. These effects appear to be modest following a single weight loss attempt, but may persist in the longer term, and presumably, during subsequent weight loss efforts. Current evidence suggests that resistance exercise coupled with caloric restriction mitigates bone and muscle loss. However, alternative strategies do not exist for older individuals, especially those who are unable or unwilling to exercise. Clinical weight loss studies in obese older individuals and preclinical research in relevant animal models with obesity and osteoporosis are required. These will advance our understanding of the pathophysiology of weight-loss-associated skeletal alterations and provide evidence on how bone loss can be counteracted or prevented. [ABSTRACT FROM AUTHOR]

Background: Although chronic alcohol consumption in adults is an established risk factor for osteoporotic fractures, there is a huge gap in our knowledge about bone effects of binge drinking in adolescents. The aim of this pilot study was therefore to assess skeletal effects of binge alcohol drinking using prepubescent pigs as a large animal model. Methods: Piglets aged 2 months were offered alcohol orally as a mixture of hard liquor and apple juice. Those with the highest propensity to drink alcohol were included in the experiment and received 1.4 g alcohol/kg bodyweight 2 times per week for 2 months (alcohol group); control piglets received apple juice in an identical manner. At the age of 4 months, the animals were euthanized; trabecular and cortical bone samples from the femur, the tibia, the humerus, and the fourth vertebral body harvested during necropsy were assessed by microcomputed tomography and dynamic histomorphometry. In addition, blood chemistry and blood alcohol determinations were performed. Results: Blood alcohol levels assessed 1 hour after alcohol administration were 0.99‰ ± 0.15, 1.12‰ ± 0.2, and 1.14‰ ± 0.18 at the ages of 2, 3, and 4 months, respectively. In the alcohol group, serum calcium and phosphate levels were decreased. In the femur, trabecular number and connectivity density were lower in the alcohol than in the control group, and in the humerus and the fourth vertebral bodies, an opposite pattern was seen for trabecular number and connectivity density, respectively. Cortical density was higher in the humerus and trabecular density higher in the tibia of the alcohol group compared to the control group. Cortical porosity was lower in the humerus of the alcohol group. No significant differences were seen for trabecular thickness, trabecular separation, bone volume fraction, and static and dynamic histomorphometric parameters. Conclusions: In this pilot study, we have assessed skeletal effects of binge alcohol drinking by using prepubescent pigs as a promising large animal model. Binge drinking has bone effects that are site‐specific. However, these data have to be verified in a larger study population. [ABSTRACT FROM AUTHOR]

Background: Regular physical activities have a positive effect on the muscular skeletal system but overstrenuous exercise may be different. Transiently suppressed bone formation and increased bone resorption after participation in a 246-km ultradistance race has been demonstrated. Purpose: The aim of this study was to analyze effects of the Spartathlon race on novel musculoskeletal markers. Methods: Venous blood samples were obtained before and immediately after the race from 19 participants of the Spartathlon. From 9 runners who were available 3 days after the start blood was drawn for a third time. Serum levels of myostatin, an inhibitor of myogenic differentiation, and its opponent follistatin as well as sclerostin and dickkopf-1, both of them inhibitors of the wnt signaling pathway, and markers of bone turnover were determined. Results: Serum levels of myostatin were significantly higher after the race. Serum follistatin only showed a transient increase. Sclerostin levels did not significantly differ before and after the race, whereas dickkopf-1 levels were significantly decreased. At follow-up a decrement of sclerostin and dickkopf-1 levels was seen. Serum cathepsin K levels did not change. Conclusion: The increase of serum levels of myostatin appears to reflect muscle catabolic processes induced by overstrenuous exercise. After the short-term uncoupling of bone turnover participation in an ultradistance race seems to initiate a long-term positive effect on bone indicated by the low-level inhibition of the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]