11-beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) gene expression in muscle is linked to reduced skeletal muscle index in sarcopenic patients.

BACKGROUND: Glucocorticoids play a significant role in metabolic processes and pathways that impact muscle size, mass, and function. The expression of 11-beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) has been previously described as a major regulator of skeletal muscle function in glucocorticoid-induced muscle atrophy and aging humans. Our study aimed to investigate glucocorticoid metabolism, including the expression of HSD11B1 in skeletal muscle, in patients with sarcopenia. METHODS: Muscle biopsies were taken from the vastus lateralis muscle of thirty-three patients over 60 years of age with hip fractures. Sarcopenia status was assessed according to the criteria of the European Working Group on Sarcopenia in Older People 2. Skeletal muscle mass was measured by bioelectrical impedance analysis. Cortisol and cortisone concentrations were measured in serum. Gene expression analysis of HSD11B1, NR3C1, FBXO32, and TRIM63 in muscle biopsies was performed. Serial cross sections of skeletal muscle were labeled with myosin heavy chain slow (fiber type-1) and fast (fiber type-2) antibodies. RESULTS: The study included 33 patients (21 women) with a mean age of 82.5 ± 6.3 years, 17 patients revealed sarcopenic (n = 16 non-sarcopenic). Serum cortisone concentrations were negatively correlated with muscle mass (ß = - 0.425; p = 0.034) and type-2 fiber diameter (ß = - 0.591; p = 0.003). Gene expression of HSD11B1 (ß = - 0.673; p = 0.008) showed a negative correlation with muscle mass in the sarcopenic group. A significant correlation was found for the non-sarcopenic group for NR3C1 (ß = 0.548; p = 0.028) and muscle mass. CONCLUSION: These findings suggest a pathogenetic role of HSD11B1 in sarcopenic muscle.

Exploration of mitochondrial defects in sarcopenic hip fracture patients.

Severe cases of age-related loss of muscle function and mass are clinically unique to sarcopenia. Mitochondrial dysfunction has been associated with aging and sarcopenia, but the causal connection in this context is not well eluded. Here we investigated different aspects of mitochondrial respiration in sarcopenia. Open muscle biopsies were taken from a total of 31 hip fracture patients, older than 70 years. Patients were assigned a sarcopenia Z-score based on EWGSOP2 criteria. Primary myoblast cultures were generated from the muscle tissue samples and used for real time metabolic measurement. Muscle and serum samples showed correlation of high Z-scores with reduced mitochondrial complex I activity, increased tricarboxylic acid cycle (TCA) metabolites, reduced vitamin D3 levels, and signs of an altered iron metabolism. Primary myoblast cultures gained from the same muscle biopsies did not show significant mitochondrial defects. We hypothesize that a sum of external consequences, including vitamin D3 deficiency and iron deficiency caused by disturbances in the iron metabolism, result in complex I deficiency, which in turn affects the TCA and contributes to muscle weakness and loss.

Identification of hip fracture patients at risk for postoperative mobilisation complications via handgrip strength assessment.

INTRODUCTION: Treatment of older adult hip fracture patients can be challenging and requires early postoperative mobilisation to prevent complications. Simple clinical tools to predict mobilisation/weight-bearing difficulties after hip fracture surgery are scarcely available and analysis of handgrip strength could be a feasible approach. In the present study, we hypothesised that patients with reduced handgrip strength show incapability to follow postoperative weight-bearing instructions. MATERIALS AND METHODS: Eighty-four patients aged ≥ 65 years with a proximal femur fracture (trochanteric, n = 45 or femoral neck, n = 39), who were admitted to a certified orthogeriatric center, were consecutively enrolled in a prospective study design. Five days after surgery (intramedullary nailing or arthroplasty), a standardised assessment of handgrip strength and a gait analysis (via insole forcesensors) was performed. RESULTS: Handgrip strength showed positive correlation with average peak force during gait on the affected limb (0.259), postoperative Parker Mobility Score (0.287) and Barthel Index (0.306). Only slight positive correlation was observed with gait speed (0.157). These results were congruent with multivariate regression analysis. CONCLUSION: Assessment of handgrip strength is a simple and reliable tool for early prediction of postoperative mobilisation complications like the inability to follow weight-bearing instructions in older hip fracture patients. Follow-up studies should evaluate if these findings also match with other fracture types and result in personalised adjustment of current aftercare patterns. In addition, efforts should be made to combine objectively collected data as handgrip strength or gait speed in a prediction model for long-term outcome of orthogeriatric patients.

Influence of IGF-I serum concentration on muscular regeneration capacity in patients with sarcopenia.

BACKGROUND: Previous research has described a neuroprotective effect of IGF-I, supporting neuronal survival, axon growth and proliferation of muscle cells. Therefore, the association between IGF-I concentration, muscle histology and electrophysiological markers in a cohort of patients with sarcopenia dares investigation. METHODS: Measurement of serum concentrations of IGF-I and binding partners, electromyographic measurements with the MUNIX (Motor Unit Number Index) method and muscle biopsies were performed in 31 patients with acute hip fracture older age 60 years. Molecular markers for denervation (neural cell adhesion molecule NCAM) and proliferation markers (Ki67) were assessed by immunofluorescence staining of muscle biopsy tissue. Skeletal muscle mass by bioelectrical impedance analysis and hand-grip strength were measured to assess sarcopenia status according to EWGSOP2 criteria. RESULTS: Thirty-one patients (20 women) with a mean age of 80.6 ± 7.4 years were included. Concentrations of IGF-I and its binding partners were significantly associated with sarcopenia (ß = - 0.360; p = 0.047) and MUNIX (ß = 0.512; p = 0.005). Further, expression of NCAM (ß = 0.380; p = 0.039) and Ki67 (ß = 0.424; p = 0.022) showed significant associations to IGF-I concentrations. CONCLUSIONS: The findings suggest a pathogenetic role of IGF-I in sarcopenia based on muscle denervation.

Late-onset neuromuscular disorders in the differential diagnosis of sarcopenia.

BACKGROUND: Sarcopenia is the age-related loss of muscle mass and strength. Undiagnosed late-onset neuromuscular disorders need to be considered in the differential diagnosis of sarcopenia. AIM: Based on emblematic case reports and current neuromuscular diagnostic guidelines for three common late-onset neuromuscular disorders, a differential diagnostic approach for geriatric patients presenting with a sarcopenic phenotype is given. METHODS: Patients over 65 years of age with sarcopenia, amyotrophic lateral sclerosis, inclusion body myositis and myotonic dystrophy type 2 were recruited. All patients were assessed for sarcopenia based on the revised European consensus definition. Patients with neuromuscular diseases were diagnosed according to the revised El Escorial criteria and the European neuromuscular centre criteria. Phenotypes and diagnostic criteria for all patients were summarized including their specific histopathological findings. RESULTS: All patients with neuromuscular diseases were positively screened for sarcopenia and classified as severe sarcopenic by means of assessment. The clinical phenotype, the evolution pattern of weakness and muscle atrophy combined with laboratory finding including electromyography could unquestionably distinguish the diseases. DISCUSSION: Neuromuscular disorders can manifest beyond the age of 65 years and misdiagnosed as sarcopenia. The most common diseases are inclusion body myositis, amyotrophic lateral sclerosis and myotonic dystrophy type 2. A diagnostic work-up for neuromuscular diseases ensures their correct diagnosis by clinical-, electrophysiological, histopathological, and genetic work-up. CONCLUSIONS: In geriatric patients with a focal or asymmetrical muscular weakness and atrophy, sarcopenia assessment should be extended with patient's history of disease course. Furthermore, concomitant diseases, analysis of serum creatine kinase, electrophysiological examination, and in selected patients muscle biopsy and gene analysis is needed to rule out a late-onset neuromuscular disorder.

Type-2 muscle fiber atrophy is associated with sarcopenia in elderly men with hip fracture.

Sarcopenia is a common geriatric syndrome and can lead to falls and fragility fractures. It is associated with a decline of muscle fiber numbers and size. Muscle biopsies of the vastus lateralis muscle were taken from thirty-two patients with hip fracture (18 women and 14 men; mean age: 82.2 ± 6.2 years). Serial cross sections of skeletal muscle were labeled with myosin heavy chain slow (fiber type-1) and fast (fiber type-2) antibodies in order to measure the size, ratio and percentage of mixed fiber types. The presence of sarcopenia was defined according to the EWGSOP2 criteria by using BIA and handgrip strength measurement. Sarcopenia was identified in 5 patients (3 women and 2 men), probable-sarcopenia in 11 patients (4 women and 7 men). Significant differences in fiber diameter were found for fiber type-2 in men but not in women. Only 1-3% mixed fiber types were found in sarcopenic patients, indicating a final stage where reinnervation is not possible to occur anymore. Muscle fiber type-2 atrophy seems to be a histological marker for sarcopenia in men.

Weight-bearing restrictions reduce postoperative mobility in elderly hip fracture patients.

BACKGROUND AND PURPOSE: Reduced mobility is a severe threat to the clinical outcomes and survival of elderly hip fracture patients. These patients generally struggle to comply with partial weight bearing, yet postoperative weight-bearing restrictions are still recommended by nearly 25% of surgeons. Therefore, we hypothesized that weight-bearing restrictions in elderly hip fracture patients merely leads to reduced mobility, while transposing full weight to the fractured extremity remains unaffected disregarding the prescribed aftercare. PATIENTS AND METHODS: 41 equally treated patients with pertrochanteric fractures were enrolled consecutively in a maximum care hospital in a pre-post study design (level of evidence 2). A study group of 19 patients was instructed to maintain partial weight bearing (PWB), whereas the control group of 22 patients was instructed to mobilize at full weight bearing (FWB). All patients were asked to participate in a gait analysis using an insole force sensor (loadsol®, Novel, Munich, Germany) on the fifth postoperative day. RESULTS: The postoperative Parker Mobility Score in the PWB group compared to the FWB group was significantly reduced (3.21 vs. 4.73, p < 0.001). Accordingly, a significantly lower gait speed in the PWB group of 0.16 m/s vs. 0.28 m/s was seen (p = 0.003). No difference in weight bearing was observed in between the groups (average peak force 350.25 N vs. 353.08 N, p = 0.918), nor any differences in the demographic characteristics, ASA Score, Barthel Index or EQ5D. INTERPRETATION: Weight-bearing restrictions in elderly hip fracture patients contributed to a loss of mobility, while no significant differences in loading of the affected extremity were observed. Therefore, postoperative weight-bearing restrictions in elderly hip fracture patients should be avoided, to achieve early mobilization at full weight bearing.

Weight bearing in patients with femoral neck fractures compared to pertrochanteric fractures: A postoperative gait analysis.

Early mobilization following hip fracture surgery is of superior importance especially in elderly hip fracture patients. Reduced mobilization can result in complications and increased mortality. In this study a gait analysis was performed using force-measuring insoles. We hypothesized, that patients with femoral neck fractures treated with hip replacement surgery load the affected limb more compared to patients with pertrochanteric fractures treated with fracture fixation. All patients (> 65 years) treated for a femoral neck fracture with hip replacement or a pertrochanteric fracture, respectively using fracture fixation with intramedullary nailing, were consecutively included in this study. For gait analysis, specific insole forcesensors (Loadsol®) were inserted into the footwear. Five days after surgery gait analysis was performed with a defined walking distance and all patients were instructed to transpose full weight. 20 patients following hip replacement surgery and 27 patients following intramedullary nailing were included. The hip replacement group loaded the affected limb with an average of 74.01% (SD 13.6) of bodyweight, while the fracture fixation group loaded a significantly reduced average of 62.70% (SD 8.3; p = 0.002). The results of the present study indicate that patients suffering from pertrochanteric fractures following fracture fixation are struggling to fully load the affected leg compared to patients suffering from femoral neck fractures treated with hip replacement surgery. The focus of further studies should concentrate on alternative analgesia and verify the cause of the observed difference in order to facilitate early full weight bearing especially in hip fracture patients following fracture fixation. The results indicate that in elderly patients, the fracture pattern and thus the surgical approach lead to a different weight bearing pattern. The primary therapeutic goal for elderly patients must be early mobilization at full weight bearing.

Inability of Older Adult Patients with Hip Fracture to Maintain Postoperative Weight-Bearing Restrictions.

BACKGROUND: For elderly trauma patients, a basic goal is early mobilization, as immobilization can trigger various complications, such as venous thromboembolism, pneumonia, urinary tract infections, and pressure ulcers. Although partial weight-bearing has been shown to significantly increase mortality compared with unrestricted weight-bearing, it remains a frequent recommendation of aftercare following lower-extremity fracture fixation. METHODS: An insole force sensor was used to measure true postoperative weight-bearing by patients ≥75 years of age treated for hip fracture compared with patients 18 to 40 years of age treated for ankle fracture. Both groups were instructed to maintain partial weight-bearing on the affected limb (≤20 kg) postoperatively. Following standardized physiotherapy training, gait analysis was performed. RESULTS: None of the patients in the elderly test group were able to comply with the weight-bearing restriction as recommended. We found that 69% (11 of 16) of the patients exceeded the specified load by more than twofold, whereas significantly more patients in the younger control group (>75% [14 of 18]) achieved almost the entire weight-bearing restriction (p < 0.001). Only 1 of the elderly patients was able to comply with the predetermined weight-bearing restriction, and only for a short period of time. In comparison, significantly more patients in the control group (89% [16 of 18]; p < 0.001) maintained the partial load for nearly the entire time during gait analysis. CONCLUSIONS: Elderly patients seem to be unable to maintain weight-bearing restrictions. As early mobilization of geriatric trauma patients is an important element for a successful rehabilitation, the directive of postoperative partial weight-bearing for these patients should be abandoned. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.