Study of Parameters of Osteosarcopenia in Patients With Hip Fracture

Study Overview
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Brief Summary
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The study aims to assess the adequacy of a set of clinical and laboratory investigations for identifying the osteosarcopenia status in patients undergoing a hip replacement for a fragility fracture of the femoral neck. The control group will consist of patients undergoing a hip replacement for osteoarthritis, as the decrease in muscle function and bone quality is less severe in this condition than in osteoporosis.

Detailed Description
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Osteoporotic hip fractures (fragility fractures) are common in older adults, and the risk of adverse outcomes and mortality is higher in patients affected by osteosarcopenia, a geriatric syndrome in which the low bone mineral density and bone microarchitecture deterioration (osteopenia/osteoporosis) are combined with a decline in mass, strength, and functional capacity of skeletal muscle (sarcopenia). The diagnostic workup currently recommended to establish the severity of osteosarcopenia is hard to implement in individuals who arrive at the orthopedic emergency department with a fragility fracture. On the one hand, the evaluation of motility and physical performance is impracticable in bedridden patients; on the other hand, the surgical treatment priority does not allow performing all the instrumental investigations required for a proper diagnosis. In this context, reliable osteosarcopenia biomarkers could help identify most frail patients and plan for them personalized therapeutic interventions to promote postoperative recovery and reduce the risk of adverse outcomes. Based on the new knowledge on the pathophysiology of osteosarcopenia, the investigators designed a small-scale study that aims to preliminarily verify the adequacy of a set of clinical and laboratory parameters that could be easily applied in hospitalized patients undergoing hip replacement for a fragility fracture. In particular, the investigators planned to assess the following: muscle performance by SARC-F questionnaire (acronym deriving from five domains considered in the questionnaire, i.e., strength, assistance with walking, rising from a chair, climbing stairs, and falls); dietary habits through a questionnaire on the intake frequency of food categories; histological features of osteoporosis and sarcopenia in tissue samples taken from the surgical site; the serum levels of markers associated with muscle-bone cross-talk (Myostatin, Insulin-like growth factor 1); the composition of the gut microbiota. The study includes two groups of patients undergoing hip replacement, the first for a fragility fracture of the femoral neck (n = 10, cases) and the second for hip osteoarthritis (n = 10, controls). As the decrease in muscle function and bone quality is more severe in fragility fractures than in osteoarthritis, the investigators expect to find differences in laboratory and clinical parameters between the groups.

Official Title
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Study of Parameters of Bone Fragility and Sarcopenia in Patients Undergoing Surgery for Fracture of the Femoral Neck

Conditions
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Osteoporotic Fracture of Femur, Osteoarthritis, Hip

Intervention / Treatment
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* Diagnostic Test: SARC-F questionnaire
* Diagnostic Test: Bone tissue histology
* Diagnostic Test: Muscle tissue histology
* Diagnostic Test: Myostatin serum levels
* Diagnostic Test: Insulin-like growth factor 1 (IGF-1) serum levels
* Other: Frequency food questionnaire
* Other: Gut microbiota profiling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cases: fragility fracture of the femoral neck (low-intensity trauma or no trauma) to be treated surgically by endoprosthesis or hip arthroplasty. Controls: osteoarthritis of the coxofemoral joint to be treated surgically by hip arthroplasty. Exclusion Criteria: Previous osteoporotic fractures Previous prosthetic surgery for orthopedic diseases Pre-existing clinical conditions that led to permanent immobility Neoplastic diseases Autoimmune diseases Severe myopathies Chronic viral infections (HBV, HCV, HIV); Chronic treatment with anti-osteoporotic drugs, immunosuppressive drugs, and insulin Paget's disease

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fragility fracture<br>Patients undergoing a hip replacement for a fragility fracture of the femoral neck (n= 10). | Diagnostic Test: SARC-F questionnaire<br>* Assessment of muscle performance based on self-reported information about grip strength, assistance with walking, rising from a chair, climbing stairs, and falls.<br>Diagnostic Test: Bone tissue histology<br>* Assessment of histomorphology and matrix-structure of tissue samples obtained from the bone resected during the hip prosthesis positioning.<br>Diagnostic Test: Muscle tissue histology<br>* Assessment of histomorphology and ultrastructure of muscle biopsies taken from the upper portion of the vastus lateralis muscle, which is accessed in the surgical procedure of hip replacement.<br>Diagnostic Test: Myostatin serum levels<br>* Quantification of circulating myostatin, a muscle-specific biomarker that suppresses muscle growth and bone formation.<br>Diagnostic Test: Insulin-like growth factor 1 (IGF-1) serum levels<br>* Quantification of circulating IGF-1, a growth factor that promotes muscle growth and osteogenesis.<br>Other: Frequency food questionnaire<br>* Assessment of dietary habits based on self-reported information about the monthly- weekly- or daily-frequency consumption of main food groups, including cereals and bread, meat, fish, fruit, vegetable, legumes, dairy products, sweets and snacks, drinks, and dietary supplements.<br>Other: Gut microbiota profiling<br>* Assessment of gut microbiome composition on stool samples.<br>|
| Osteoarthritis<br>Patients undergoing a hip replacement for severe osteoarthritis (n= 10). | Diagnostic Test: SARC-F questionnaire<br>* Assessment of muscle performance based on self-reported information about grip strength, assistance with walking, rising from a chair, climbing stairs, and falls.<br>Diagnostic Test: Bone tissue histology<br>* Assessment of histomorphology and matrix-structure of tissue samples obtained from the bone resected during the hip prosthesis positioning.<br>Diagnostic Test: Muscle tissue histology<br>* Assessment of histomorphology and ultrastructure of muscle biopsies taken from the upper portion of the vastus lateralis muscle, which is accessed in the surgical procedure of hip replacement.<br>Diagnostic Test: Myostatin serum levels<br>* Quantification of circulating myostatin, a muscle-specific biomarker that suppresses muscle growth and bone formation.<br>Diagnostic Test: Insulin-like growth factor 1 (IGF-1) serum levels<br>* Quantification of circulating IGF-1, a growth factor that promotes muscle growth and osteogenesis.<br>Other: Frequency food questionnaire<br>* Assessment of dietary habits based on self-reported information about the monthly- weekly- or daily-frequency consumption of main food groups, including cereals and bread, meat, fish, fruit, vegetable, legumes, dairy products, sweets and snacks, drinks, and dietary supplements.<br>Other: Gut microbiota profiling<br>* Assessment of gut microbiome composition on stool samples.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptability of the SARC-F questionnaire | The number of patients able to provide answers divided by the total number of enrolled patients. | Within 24 hours of admission | 
| Frequency of positive SARC-F questionnaire in cases (fragility fractures) and controls (osteoarthritis) | The percentage of cases (fragility fractures) and controls (osteoarthritis) who exhibit a positive SARC-F questionnaire. The SARC-F is positive and indicates potential sarcopenia if the score point is = or > 4. For each component of the questionnaire (grip strength, assistance with walking, rising from a chair, climbing stairs, and falls), the score may be 0 (no difficulty; no falls), 1 (some difficulty), and 2 (a lot of difficulties and falls). The total score may range from 0 to 10. | Within 24 hours of admission | 
| Presence of histological features of osteoporotic bone in cases (fragility fractures) and controls (osteoarthritis) | The percentage of cases (fragility fractures) and controls (osteoarthritis) who exhibit histological features of osteoporotic bone. The presence of osteoporotic bone will be proved based on the following histological features: loss of connected trabecular bone, altered matrix mineralization, the prevalence of adipose tissue compared to bone marrow, presence of osteoclasts. | Through study completion, an average of 1 year. | 
| Presence of histological features of muscle atrophy in cases (fragility fractures) and controls (osteoarthritis) | The percentage of cases (fragility fractures) and controls (osteoarthritis) who exhibit histological features of muscle atrophy. The presence of muscle atrophy will be proved based on the following histological features: decrease in size and number of type II myofibers, presence of necrosis or fibro-adipose replacement, decrease in satellite cell number. | Through study completion, an average of 1 year. | 
| Myostatin serum levels in cases (fragility fractures) and controls (osteoarthritis) | The immunoenzymatic quantification of circulating Myostatin (µg/L) will be performed on serum samples obtained from peripheral venous blood. The results will be aggregated as mean ± standard error of the mean, median, and min-max range. | Through study completion, an average of 1 year. | 
| Insulin-like growth factor 1 (IGF-1) serum levels in cases (fragility fractures) and controls (osteoarthritis) | The immunoenzymatic quantification of circulating IGF-1 (µg/L) will be performed on serum samples obtained from peripheral venous blood. The results will be aggregated as mean ± standard error of the mean, median, and min-max range. | Through study completion, an average of 1 year. | 
| Acceptability of the Frequency Food Questionnaire | The number of patients able to provide answers divided by the total number of enrolled patients. | Within 24 hours of admission | 
| Frequency of intake of the different food categories in cases (fragility fractures) and controls (osteoarthritis) | The percentages of cases (fragility fractures) and controls (osteoarthritis) who assume never/rarely or regularly the different food categories. | Within 24 hours of admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of positive SARC-F questionnaire in patients with and without osteoporotic bone | The percentage of patients with and without osteoporotic bone who exhibit a positive (= or > 4) or negative (< 4) SARC-F questionnaire. | Through study completion, an average of 1 year. | 
| Frequency of positive SARC-F questionnaire in patients with and without muscle atrophy | The percentage of patients with and without muscle atrophy who exhibit a positive (= or > 4) or negative (< 4) SARC-F questionnaire. | Through study completion, an average of 1 year. | 
| Myostatin serum levels in patients with positive and negative SARC-F questionnaire | Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with positive (= or > 4) and negative (< 4) SARC-F questionnaire. | Through study completion, an average of 1 year. | 
| Myostatin serum levels in patients with and without osteoporotic bone | Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with and without osteoporotic bone. | Through study completion, an average of 1 year. | 
| Myostatin serum levels in patients with and without muscle atrophy | Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with and without muscle atrophy. | Through study completion, an average of 1 year. | 
| Insulin-like growth factor 1 (IGF-1) serum levels in patients with positive and negative SARC-F questionnaire | Mean ± standard error of the mean, median, and min-max range of circulating IGF-1 (µg/L) in patients with positive (= or > 4) and negative (< 4) SARC-F questionnaire. | Through study completion, an average of 1 year. | 
| Insulin-like growth factor 1 (IGF-1) serum levels in patients with and without osteoporotic bone | Mean ± standard error of the mean, median, and min-max range of circulating IGF-1 (µg/L) in patients with and without osteoporotic bone. | Through study completion, an average of 1 year. | 
| Insulin-like growth factor 1 (IGF-1) serum levels in patients with and without muscle atrophy | Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with and without muscle atrophy. | Through study completion, an average of 1 year. | 
| Frequency of intake of the different food categories in patients with positive and negative SARC-F questionnaire | The percentage of patients with positive (= or > 4) and negative (< 4) SARC-F questionnaire who assume never/rarely and regularly the different food categories. | Within 24 hours of admission | 
| Frequency of intake of the different food categories in patients with and without osteoporotic bone | The percentage of patients with and without osteoporotic bone who assume never/rarely and regularly the different food categories. | Through study completion, an average of 1 year. | 
| Frequency of intake of the different food categories in patients with and without muscle atrophy | The percentage of patients with and without muscle atrophy who assume never/rarely and regularly the different food categories. | Through study completion, an average of 1 year. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoporosis, Sarcopenia, Hip prosthesis