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.
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 serum levels of the following pro-inflammatory cytokines to get a clearer picture of the presence of the inflammatory state: IL-6, IL-8, TNF-α; * the serum levels of markers such as FGF-21, GDF15, soluble ST2, interesting markers of bone metabolism, indicators of bone mineral density, and modulators of osteoblast-osteoclast activity; * the composition of the gut microbiota. The study includes 100 patients who are candidates for hip replacement surgery (endo- and arthroplasty). 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.
Assessment of muscle performance based on self-reported information about grip strength, assistance with walking, rising from a chair, climbing stairs, and falls.
Assessment of histomorphology and matrix-structure of tissue samples obtained from the bone resected during the hip prosthesis positioning.
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.
Istituto Ortopedico Rizzoli
Bologna, Italy
RECRUITINGAcceptability of the SARC-F questionnaire
The number of patients able to provide answers divided by the total number of enrolled patients.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion, an average of 1 year.
Myostatin serum levels in cases (fragility fractures) and controls (osteoarthritis)
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Study Type
OBSERVATIONAL
Enrollment
100
Quantification of circulating myostatin, a muscle-specific biomarker that suppresses muscle growth and bone formation.
Quantification of circulating IGF-1, a growth factor that promotes muscle growth and osteogenesis.
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.
Assessment of gut microbiome composition on stool samples.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Within 24 hours of admission
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Through study completion, an average of 1 year.
Inflammatory serum markers
Mean ± standard error of the mean, median, and min-max range of circulating IL-6, IL-8, TNF-α in patients
Time frame: Through study completion, an average of 1 year.
Serum markers of bone metabolism
Mean ± standard error of the mean, median, and min-max range of circulating FGF-21, GDF15, ST2 in patients
Time frame: Through study completion, an average of 1 year.