Comparative Analysis of Sarcopenia in Rehabilitation Outcomes Following Femoral Neck Fracture: a Study in Normal Weight and Obese Study Cohort

INTRODUCTION

The global population of older adults (aged 65 and above) is on the rise. In 2017, this demographic constituted 13% of the world's population, and projections indicate that by 2050, it is expected to reach 2.1 billion people. A significant aspect of human aging involves the gradual reduction of skeletal muscle mass. Numerous prospective studies indicate that muscle mass tends to decrease by around 6% per decade after reaching mid-life. Sarcopenia was considered to be purely loss of muscle (lean) mass of the extremities. In 2010, the European consensus redefined sarcopenia by incorporating the loss of function, specifically in walking speed or grip strength, along with the loss of muscle mass. Since then, several consensus groups have adopted similar definitions, now characterizing sarcopenia as the combination of both functional decline and loss of muscle mass. Sarcopenia is closely associated with frailty, physical disability, hospitalization, osteoporosis, osteoarthritis, and even mortality. Handgrip strength is a frequently employed method for assessing muscle strength, offering a straightforward, reliable, and cost-effective means to identify elderly adults who may be at risk for disability.

Older adults will represent the 20% of the population by 2030 and half of them will suffer from obesity. The prevalence of obesity has reached 30-40% of the population, and there are expectations for its incidence to continue rising in the coming decades. Obesity is linked to over 200 medical complications and poses an elevated risk of morbidity and mortality. It stands as the fifth leading cause of death globally. Obesity is marked by the excessive accumulation of white adipose tissue, not only within typical fat depots but also ectopically, a phenomenon that notably compromises physical function. The human body undergoes substantial changes in composition as age advances. Notably, muscle and bone mass show a progressive decline from the third decade of life, while fat mass tends to increase until around the age of 70. People who suffer from obesity experience weight gain and loss throughout their lives on the background of different diets, it is important to underline that diet-induced weight loss is associated with not only fat, but also muscle and bone losses and may further exacerbate age-related sarcopenia and frailty in older adults. The decline in muscle mass and strength, known as sarcopenia, is very common among older adults with obesity (sarcopenic obesity) and is closely associated with frailty. Sarcopenic obesity emerges as a significant factor contributing to physical disability.

Sarcopenia shares common physio-pathological mechanisms and is frequently linked with a high prevalence of osteoporosis. The introduction of the osteo-sarcopenia concept reflects the intersection of sarcopenia and osteoporosis, contributing to notable functional consequences, including an elevated risk of falls and hip fractures. Hip fractures have a significant impact on the daily lives of individuals aged 65 and above, as more than 40% of those who experience a hip fracture fail to regain the functional status they had before the fracture. Hip fractures are correlated with a substantial prevalence of institutionalization and mortality, with rates exceeding 35% within three years of the incident. Sarcopenia could potentially contribute to the loss of function in individuals who experience hip fractures. The prevalence of sarcopenia in older individuals admitted to acute units with hip fractures ranges from 17% to 37%. Sarcopenia serves as a significant prognostic factor for mortality among older patients admitted to acute units.

One study assessed the effect of sarcopenic obesity on ability to function in women with subacute hip fracture, and found that the presence of obesity did not worsen the negative prognostic role of sarcopenia in the short-term recovery of ability to function after hip fracture in women .Another study reviewed 222 patients who underwent orthopedic surgery and found higher prevalence of sarcopenia and sarcopenic obesity among these patients.

There is relatively limited evidence concerning the impact of sarcopenia on the survival of older individuals with hip fractures admitted to rehabilitation units more over there is no reference to obesity sarcopenia. The exclusion of older individuals from clinical trials often limits the relevance of trial results to clinical practice\[35, 36\]. Pragmatic studies that enroll real-life older participants become crucial in providing insights applicable to daily clinical practice

Muscle mass The worldwide prevalence of sarcopenia in patients with hip fractures is statistically significant. Despite established therapeutic agents and diagnostic criteria for osteoporosis, there is a lack of clear, practical criteria for diagnosing sarcopenia in the clinical setting. Few studies have reported on the evaluation and treatment of sarcopenia in patients with hip fractures. Additionally, the quality of life for postoperative hip fracture patients could be significantly enhanced through the development of precise assessments for muscle regeneration and rehabilitation.

For patients with hip fractures, diagnosis of sarcopenia is based on diagnostic criteria for acute to chronic health care settings. However, evaluation of physical ability in patients with hip fractures is not possible. Only grip strength can be measured. In addition, while measurement of muscle mass is important for patients with hip fractures, whole-body DEXA imaging before surgery is difficult due to pain and anatomical abnormalities at the fracture site.

This study aims to examine the impact of obesity on sarcopenia prevalence and severity in adults recovering from femoral neck fractures. Addressing a gap in current literature, the research endeavors to provide nuanced insights into the interplay between obesity and sarcopenia, contributing valuable knowledge for optimizing rehabilitation strategies in this patient population.

Risk benefit statement Participation in this study carries minimal risk as all assessments and interventions are non-invasive and routinely conducted in rehabilitation settings. The potential benefits include contributing to advancements in understanding sarcopenia following femoral neck fractures, which may lead to improved rehabilitation strategies. Participants will receive comprehensive health assessments that could enhance their overall post-fracture care. The acquired knowledge may benefit not only the individual but also contribute to the broader field of geriatric orthopedics, potentially influencing future clinical practices and patient outcomes Study Objectives The aim of the current study is to evaluate the differences in sarcopenia outcomes and rehabilitation effectiveness between individuals with normal weight and those classified as obese. This investigation aims to provide crucial insights into the distinct impact of body weight on post-fracture recovery, contributing to a more tailored approach in rehabilitation strategies.

Primary endpoint The primary endpoint of this study is to assess and compare the prevalence and severity of sarcopenia between normal-weight and obese cohorts in adults recovering from femoral neck fractures.

STUDY DESIGN 1.1 Overview of the study design This prospective study focuses on hospitalized rehabilitation patients post-femoral neck fracture. After informed consent, participants undergo a comprehensive initial assessment, including demographic details, medical history, lifestyle habits, fracture information, and cognitive status. Blood samples are collected for various biochemical markers.

Upon initial assessment, patients are stratified into two groups based on body weight: normal weight and obese. Following this stratification, a series of assessments are conducted, encompassing cognitive status (MMSE), anthropometric measurements (BMI), functional independence (FIM), mobility (Up \& Go Test), frailty, hand grip strength, sarcopenia likelihood (SARC-F), muscle strength and reflexes (MSRA), and nutritional status (MNA). These assessments aim to provide a thorough evaluation of health and functional status, forming the basis for subsequent analyses on the impact of sarcopenia and obesity on post-fracture recovery.

1.2 Study population 1.2.1 Number of subjects The study population will include up to 300 participants, male and female, aged 60 - 85 years, who have been diagnosed with femoral neck fracture.

1.2.2 Inclusion criteria

* Age between 60-85 * Suffered a femoral neck fracture in the last year. * Subject willing and able to read, understand and sign an informed consent. 1.2.3 Exclusion criteria * Inability to comply with the study protocol or understand and sign an informed consent * Diagnosis of a psychiatric disorder prior to the recent femoral neck. * Active malignancy * History of other neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body Dementia (LBD), Frontotemporal dementia (FTD), Multiple sclerosis (MS), Amyotrophic lateral sclerosis (ALS), Creutzfeld Jacob disease (CJD), Multisystem atrophy (MSA), Pseudobulbar palsy (PSP), Corticobasal degeneration (CBD), Wernicke Korsakoff syndrome * Chronic Inflammatory Disorders:(e.g., rheumatoid arthritis, systemic lupus erythematosus). * Endocrine Disorders: Individuals with endocrine disorders affecting muscle metabolism (e.g., Cushing's syndrome, hyperthyroidism) * Recent Major Surgeries: Participants who had undergone major surgeries other than femoral neck fracture within the last six months were excluded * Severe Cognitive Impairment: e.g., advanced dementia were excluded to ensure reliable participation in assessments and accurate reporting of symptoms related to sarcopenia.

2 Study procedures. 2.1 Screening and baseline evaluation Upon consent, eligible participants will be invited for baseline evaluation that includes the following procedures. The evaluation will be scheduled for up to 6 weeks following consent. 1. Demographic, clinical data. 2. Mini-Mental State Examination (MMSE): Cognitive status will be evaluated using the MMSE, a widely used tool to assess orientation, memory, and other cognitive functions. 3. Anthropometric Measurements: Weight and height will be recorded to calculate the Body Mass Index (BMI) 4. Functional Independence Measure (FIM): Assessing basic functions, level of independence in activities of daily living. 5. Up \& Go Mobility Test: This test serves as an indicator of mobility and balance. 6. Frailty Assessment: Evaluating frailty will involve assessing various physical and functional aspects to gauge the patient's vulnerability and resilience. 7. Hand Grip Strength: Measuring hand grip strength will provide insights into overall muscle strength and functional capacity. 8. SARC-F:The SARC-F questionnaire will be administered to assess the likelihood of sarcopenia, focusing on strength, assistance with walking, rising from a chair, climbing stairs, and falls. 9. MSRA (Muscle Strength and Reflex Assessment): This assessment will involve evaluating muscle strength and reflexes, providing a more detailed understanding of the patient's neuromuscular function. 10. Mini Nutritional Assessment (MNA):The MNA will be utilized to assess the patient's nutritional status, helping identify individuals at risk of malnutrition. 11. Lab tests.

2.2 Post rehabilitation evaluation.

Upon completion of the rehabilitation period, subjects will undergo a comprehensive assessment to evaluate various health and functional parameters. The following tests will be conducted: * Blood Tests: chemistry panel, calcium, vitamin D, C-reactive protein (CRP), and CBC * Functional Independence Measure * Up \& Go Mobility Test * Calf Circumference * Mini-Mental State Examination * Hand Grip Strength * SARC-F questionnaire * Muscle Strength and