Study of Parameters of Osteosarcopenia in Patients With Hip Fracture

Recruiting

• Conditions: Osteoarthritis, Hip; Osteoporotic Fracture of Femur
• Interventions: 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

• Registration Number: NCT04730622
• Lead Sponsor: Istituto Ortopedico Rizzoli

Brief Summary

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

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.

Study Timeline

• Study Start: 2020-11-23
• Study First Submitted: 2021-01-20
• Study First Submitted QC: 2021-01-26
• Study First Posted: 2021-01-29
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Patients who came to observation with femoral neck fracture of possible osteoporotic nature (no or minimal trauma) to be treated with endoprosthesis or hip arthroplasty.
• Competent patients who have signed consent to participate in the study (see Informed Consent section of this protocol).

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Fragility fracture	SARC-F questionnaire	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).
Fragility fracture	Bone tissue histology	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).
Fragility fracture	Gut microbiota profiling	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).
Fragility fracture	Muscle tissue histology	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).
Fragility fracture	Myostatin serum levels	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).
Fragility fracture	Frequency food questionnaire	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).
Fragility fracture	Insulin-like growth factor 1 (IGF-1) serum levels	Patients who are candidates for hip replacement surgery (endo- and arthroplasty).

Primary Outcome Measures

Name	Time	Method
Presence of histological features of muscle atrophy in cases (fragility fractures) and controls (osteoarthritis)	Through study completion, an average of 1 year.	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.
Acceptability of the Frequency Food Questionnaire	Within 24 hours of admission	The number of patients able to provide answers divided by the total number of enrolled patients.
Frequency of intake of the different food categories in cases (fragility fractures) and controls (osteoarthritis)	Within 24 hours of admission	The percentages of cases (fragility fractures) and controls (osteoarthritis) who assume never/rarely or regularly the different food categories.
Acceptability of the SARC-F questionnaire	Within 24 hours of admission	The number of patients able to provide answers divided by the total number of enrolled patients.
Frequency of positive SARC-F questionnaire in cases (fragility fractures) and controls (osteoarthritis)	Within 24 hours of admission	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.
Presence of histological features of osteoporotic bone in cases (fragility fractures) and controls (osteoarthritis)	Through study completion, an average of 1 year.	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.
Myostatin serum levels in cases (fragility fractures) and controls (osteoarthritis)	Through study completion, an average of 1 year.	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.
Insulin-like growth factor 1 (IGF-1) serum levels in cases (fragility fractures) and controls (osteoarthritis)	Through study completion, an average of 1 year.	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.

Secondary Outcome Measures

Name	Time	Method
Frequency of positive SARC-F questionnaire in patients with and without muscle atrophy	Through study completion, an average of 1 year.	The percentage of patients with and without muscle atrophy who exhibit a positive (= or \> 4) or negative (\< 4) SARC-F questionnaire.
Myostatin serum levels in patients with positive and negative SARC-F questionnaire	Through study completion, an average of 1 year.	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.
Frequency of intake of the different food categories in patients with and without osteoporotic bone	Through study completion, an average of 1 year.	The percentage of patients with and without osteoporotic bone who assume never/rarely and regularly the different food categories.
Frequency of positive SARC-F questionnaire in patients with and without osteoporotic bone	Through study completion, an average of 1 year.	The percentage of patients with and without osteoporotic bone who exhibit a positive (= or \> 4) or negative (\< 4) SARC-F questionnaire.
Myostatin serum levels in patients with and without osteoporotic bone	Through study completion, an average of 1 year.	Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with and without osteoporotic bone.
Insulin-like growth factor 1 (IGF-1) serum levels in patients with and without osteoporotic bone	Through study completion, an average of 1 year.	Mean ± standard error of the mean, median, and min-max range of circulating IGF-1 (µg/L) in patients with and without osteoporotic bone.
Myostatin serum levels in patients with and without muscle atrophy	Through study completion, an average of 1 year.	Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with and without muscle atrophy.
Inflammatory serum markers	Through study completion, an average of 1 year.	Mean ± standard error of the mean, median, and min-max range of circulating IL-6, IL-8, TNF-α in patients
Insulin-like growth factor 1 (IGF-1) serum levels in patients with positive and negative SARC-F questionnaire	Through study completion, an average of 1 year.	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.
Frequency of intake of the different food categories in patients with positive and negative SARC-F questionnaire	Within 24 hours of admission	The percentage of patients with positive (= or \> 4) and negative (\< 4) SARC-F questionnaire who assume never/rarely and regularly the different food categories.
Insulin-like growth factor 1 (IGF-1) serum levels in patients with and without muscle atrophy	Through study completion, an average of 1 year.	Mean ± standard error of the mean, median, and min-max range of circulating Myostatin (µg/L) in patients with and without muscle atrophy.
Frequency of intake of the different food categories in patients with and without muscle atrophy	Through study completion, an average of 1 year.	The percentage of patients with and without muscle atrophy who assume never/rarely and regularly the different food categories.
Serum markers of bone metabolism	Through study completion, an average of 1 year.	Mean ± standard error of the mean, median, and min-max range of circulating FGF-21, GDF15, ST2 in patients

Trial Locations

Locations (1)

Istituto Ortopedico Rizzoli; 🇮🇹 Bologna, Italy