Study of Parameters of Osteosarcopenia in Patients With Hip Fracture

Official title

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

Overview

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.

Interventions

• 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.

Primary outcome measures

• Acceptability of the SARC-F questionnaire [Time frame: Within 24 hours of admission]
• Frequency of positive SARC-F questionnaire in cases (fragility fractures) and controls (osteoarthritis) [Time frame: Within 24 hours of admission]
• Presence of histological features of osteoporotic bone in cases (fragility fractures) and controls (osteoarthritis) [Time frame: Through study completion, an average of 1 year.]
• Presence of histological features of muscle atrophy in cases (fragility fractures) and controls (osteoarthritis) [Time frame: Through study completion, an average of 1 year.]
• Myostatin serum levels in cases (fragility fractures) and controls (osteoarthritis) [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) [Time frame: Through study completion, an average of 1 year.]
• Acceptability of the Frequency Food Questionnaire [Time frame: Within 24 hours of admission]
• Frequency of intake of the different food categories in cases (fragility fractures) and controls (osteoarthritis) [Time frame: Within 24 hours of admission]

Secondary outcome measures (12)

• Frequency of positive SARC-F questionnaire in patients with and without osteoporotic bone [Time frame: Through study completion, an average of 1 year.]
• Frequency of positive SARC-F questionnaire in patients with and without muscle atrophy [Time frame: Through study completion, an average of 1 year.]
• Myostatin serum levels in patients with positive and negative SARC-F questionnaire [Time frame: Through study completion, an average of 1 year.]
• Myostatin serum levels 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 [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 [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 [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 [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 [Time frame: Within 24 hours of admission]
• Frequency of intake of the different food categories in patients with and without osteoporotic bone [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 [Time frame: Through study completion, an average of 1 year.]
• Inflammatory serum markers [Time frame: Through study completion, an average of 1 year.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Italy · 1 center

• Istituto Ortopedico Rizzoli — Bologna

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. PMID 32202056
• 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. PMID 30610245
• 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. PMID 31942528

Identifiers

NCT: NCT04730622 · OsteoSarcopenia

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗