Clinical trial NCT04730622: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteoporotic Fracture of Femur
Osteoarthritis, Hip
Keywords: Osteoporosis
Sarcopenia
Hip prosthesis
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2021-01-29
Enrollment: 100
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospitalized patients admitted at the 1st Orthopaedic and Traumatology Unit of the Istituto Ortopedico Rizzoli (Bologna, Italy).

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.

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

Primary outcomes:
measure: Acceptability of the SARC-F questionnaire
timeFrame: Within 24 hours of admission
measure: Frequency of positive SARC-F questionnaire in cases (fragility fractures) and controls (osteoarthritis)
timeFrame: Within 24 hours of admission
measure: Presence of histological features of osteoporotic bone in cases (fragility fractures) and controls (osteoarthritis)
timeFrame: Through study completion, an average of 1 year.
measure: Presence of histological features of muscle atrophy in cases (fragility fractures) and controls (osteoarthritis)
timeFrame: Through study completion, an average of 1 year.
measure: Myostatin serum levels in cases (fragility fractures) and controls (osteoarthritis)
timeFrame: Through study completion, an average of 1 year.
measure: Insulin-like growth factor 1 (IGF-1) serum levels in cases (fragility fractures) and controls (osteoarthritis)
timeFrame: Through study completion, an average of 1 year.
measure: Acceptability of the Frequency Food Questionnaire
timeFrame: Within 24 hours of admission
measure: Frequency of intake of the different food categories in cases (fragility fractures) and controls (osteoarthritis)
timeFrame: Within 24 hours of admission
Secondary outcomes:
measure: Frequency of positive SARC-F questionnaire in patients with and without osteoporotic bone
timeFrame: Through study completion, an average of 1 year.
measure: Frequency of positive SARC-F questionnaire in patients with and without muscle atrophy
timeFrame: Through study completion, an average of 1 year.
measure: Myostatin serum levels in patients with positive and negative SARC-F questionnaire
timeFrame: Through study completion, an average of 1 year.
measure: Myostatin serum levels in patients with and without osteoporotic bone
timeFrame: Through study completion, an average of 1 year.
measure: Myostatin serum levels in patients with and without muscle atrophy
timeFrame: Through study completion, an average of 1 year.
measure: Insulin-like growth factor 1 (IGF-1) serum levels in patients with positive and negative SARC-F questionnaire
timeFrame: Through study completion, an average of 1 year.
measure: Insulin-like growth factor 1 (IGF-1) serum levels in patients with and without osteoporotic bone
timeFrame: Through study completion, an average of 1 year.
measure: Insulin-like growth factor 1 (IGF-1) serum levels in patients with and without muscle atrophy
timeFrame: Through study completion, an average of 1 year.
measure: Frequency of intake of the different food categories in patients with positive and negative SARC-F questionnaire
timeFrame: Within 24 hours of admission
measure: Frequency of intake of the different food categories in patients with and without osteoporotic bone
timeFrame: Through study completion, an average of 1 year.
measure: Frequency of intake of the different food categories in patients with and without muscle atrophy
timeFrame: Through study completion, an average of 1 year.
measure: Inflammatory serum markers
timeFrame: Through study completion, an average of 1 year.
measure: Serum markers of bone metabolism
timeFrame: Through study completion, an average of 1 year.
Other outcomes:
measure: Characterization of gut microbiota
timeFrame: Through study completion, an average of 1 year.
Locations:
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli
Study officials:
affiliation: University of Bologna, Istituto Ortopedico Rizzoli
name: Nicola Baldini, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.