Study of Parameters of Osteosarcopenia in Patients With Hip Fracture

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

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.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis, Hip; Osteoporotic Fracture of Femur
• Intervention / Treatment: 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

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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Gemma Di Pompo, M.Sc.; Phone Number: +39 0516366748; Email: gemma.dipompo@ior.it

Study Locations

• Italy
  • Bologna, Italy, 40136
    • Recruiting
    • Istituto Ortopedico Rizzoli
    • Contact: Nicola Baldini, M.D.; Phone Number: +39 051 6366560; Email: nicola.baldini@ior.it
    • Sub-Investigator: Alberto C Di Martino, M.D.
    • Sub-Investigator: Giorgia Borciani, M.Sc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Hospitalized patients admitted at the 1st Orthopaedic and Traumatology Unit of the Istituto Ortopedico Rizzoli (Bologna, Italy).

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Fragility fracture; Patients who are candidates for hip replacement surgery (endo- and arthroplasty).

Diagnostic test: SARC-F questionnaire; Assessment of muscle performance based on self-reported information about grip strength, assistance with walking, rising from a chair, climbing stairs, and falls.; Diagnostic test: Bone tissue histology; Assessment of histomorphology and matrix-structure of tissue samples obtained from the bone resected during the hip prosthesis positioning.; Diagnostic test: Muscle tissue histology; 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.; Diagnostic test: Myostatin serum levels; Quantification of circulating myostatin, a muscle-specific biomarker that suppresses muscle growth and bone formation.; Diagnostic test: Insulin-like growth factor 1 (IGF-1) serum levels; Quantification of circulating IGF-1, a growth factor that promotes muscle growth and osteogenesis.; Other: Frequency food questionnaire; 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.; Other: Gut microbiota profiling; Assessment of gut microbiome composition on stool samples.

What is the study measuring?

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.
Inflammatory serum markers	Mean ± standard error of the mean, median, and min-max range of circulating IL-6, IL-8, TNF-α in patients	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	Through study completion, an average of 1 year.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of gut microbiota	The "Next Generation Sequencing" technology will be employed to characterize the overall microbiome profile in stool samples, and bioinformatics used to assess alpha-diversity (ecological diversity of a single sample according to the number of different taxa and their relative abundances) and beta-diversity (differences in microbial community composition between individuals).	Through study completion, an average of 1 year.

Collaborators and Investigators

• Sponsor: Istituto Ortopedico Rizzoli
• Investigators: Principal Investigator: Nicola Baldini, M.D., University of Bologna, Istituto Ortopedico Rizzoli

Publications and helpful links

General Publications

• Kirk B, Zanker J, Duque G. Osteosarcopenia: epidemiology, diagnosis, and treatment-facts and numbers. J Cachexia Sarcopenia Muscle. 2020 Jun;11(3):609-618. doi: 10.1002/jcsm.12567. Epub 2020 Mar 22.
• Wong RMY, Wong H, Zhang N, Chow SKH, Chau WW, Wang J, Chim YN, Leung KS, Cheung WH. The relationship between sarcopenia and fragility fracture-a systematic review. Osteoporos Int. 2019 Mar;30(3):541-553. doi: 10.1007/s00198-018-04828-0. Epub 2019 Jan 4.
• Kirk B, Al Saedi A, Duque G. Osteosarcopenia: A case of geroscience. Aging Med (Milton). 2019 Sep 8;2(3):147-156. doi: 10.1002/agm2.12080. eCollection 2019 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: January 20, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Sarcopenia; Osteoporosis; Hip prosthesis
• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Femoral Fractures; Fractures, Bone; Osteoarthritis, Hip; Osteoporotic Fractures; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: OsteoSarcopenia

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No