This single-centre, exploratory study at Montpellier University Hospital will investigate whether having low muscle mass and strength before hip-replacement surgery, a condition called sarcopenia, impact the return to everyday independence in people aged 75 years or older. About 20 volunteers, scheduled for surgery because of a recent femoral-neck fracture or severe arthritis that no longer responds to usual care, will give consent, answer brief health questionnaires, attempt simple walking and chair-rise tests if possible, and provide a small blood sample. While they are already under anaesthesia for their planned operation, the surgical team will take a tiny muscle sample through the same incision, so no extra cuts are needed. During the hospital stay or shortly after discharge, each participant will have a painless MRI scan of the thigh muscles and a very-low-dose bone scan (DXA) to measure muscle and bone health. The research team will then telephone participants at 3 and 6 months to ask about daily activities, walking ability, and any complications. The study lasts about six months for each person and does not alter their usual medical or rehabilitation care. Potential benefits include close follow-up, personalised feedback on muscle and bone results, and helping doctors learn whether pre-surgery muscle weakness predicts slower recovery-information that could guide future, more personalised exercise and nutrition programs. Extra study procedures carry only minimal risks: a routine blood draw, scans with none (MRI) or very little (DXA) radiation, and a muscle biopsy taken during surgery. Taking part is entirely voluntary, and participants may withdraw at any time without affecting their current or future care. The whole project will run for 18 months.

Hip-REGEN is an exploratory, single-centre, prospective, longitudinal pathophysiology study conducted at Montpellier University Hospital to clarify whether the degree of pre-operative sarcopenia modulates functional recovery after hip arthroplasty in patients ≥ 75 years who undergo the procedure either for a recent femoral-neck fracture or severe hip osteoarthritis.

The increasing worldwide burden of musculoskeletal diseases, represents major costs for the healthcare system. Osteoarthritis, which affects around 595 million people worldwide, and osteoporosis, defined by the WHO as a reduction in bone mineral density, are two of the main age-related musculoskeletal pathologies. In France, between 2008 and 2014, around 650,000 hip prostheses surgeries were necessary to treat severe coxofemoral osteoarthritis, and around 65,000 hip prostheses surgeries are necessary every year to treat fractures of the upper end of the femur, occuring mainly due to osteoporosis, associated with significant loss of autonomy and high one-year mortality rate (20%).

We hypothesise that lower muscle mass and strength before surgery will negatively impact the 3- and 6-month functional recovery, assessed by the Barthel Index. This association could be mediated by impaired muscle regenerative capacity and endocrine function, including myokines and related systemic circulating biomarkers. Twenty participants (10 hip fractures, 10 hip osteoarthritis) will be consecutively enrolled over 12 months, in the orthopaedic service, a sample size chosen to demonstrate feasibility and to cover the cost of ex-vivo assays while maintaining balanced sex representation. After written informed consent, baseline (Visit 1) assessments include Barthel Index, Katz ADL, Lawton IADL, physical activity (IPAQ-SF), SARC-F, comorbidity (Charlson), nutritional and cognitive screens, hand-grip dynamometry, and blood sampling for biobanking. Pre-operative sarcopenia status is classified according to EWGSOP2 thresholds for grip strength and appendicular lean mass by DXA (Visit 3), complemented by quantitative MRI (Visit 3) of the quadriceps to detect fatty infiltration that DXA may miss. All imageries will be performed either few days before or after the hip replacement for limited biais.

During the arthroplasty (Visit 2) a micro-biopsy of the gluteus medius is obtained through the surgical approach without additional incision, and bone-cartilage and synovium, normally discarded are collected and immediately transferred on ice to INSERM U1046 or U1183 for conditionning for cell culture, mechanistic assays and long-term storage (with participant opt-in for the biological collection). Within 15 days post-operatively (Visit 3) each participant undergoes a high-resolution quadriceps MRI and low-dose DXA to finalise muscle characterisation and obtain bone density. Telephone follow-ups at 3 months (Visit 4) and 6 months (Visit 5) repeat the Barthel Index and capture complications, readmissions and living arrangements; additional geriatric assessment is offered if recovery is unsatisfactory as part of routine care.

The primary endpoint is the variation in Barthel Index between baseline, 3 months, and 6 months. Key secondary analyses relate pre-operative sarcopenia metrics to: (i) in-vitro myoblast regeneration and endocrine function of skeletal muscle; (ii) circulating concentrations of muscle biomarkers (e.g. myostatin, follistatin, irisin, IL-6, IGF-1, lactate) ; and (iii) MRI-derived quadriceps composition. Laboratory procedures follow standardised culture and imaging protocols and include quality-controlled quantification of muscle satellite-cell (MuSC) proliferation, differentiation and senescence markers, as well as endocrine function including extracellular vesicle composition analysis, histological scoring of cartilage explants, and chondrocyte phenotypes and mesenchymal stem cells multipotency.

All data are entered into an electronic case-report form with automated range and consistency checks; monitoring is performed by the CHU Montpellier sponsor through on-site visits, central statistical surveillance and adherence to French Jardé Category-1 regulations (biopsy constitutes the main additional intervention). The statistical analysis plan, finalised before database lock, prespecifies descriptive statistics, non-parametric tests (Wilcoxon-Mann-Whitney, Fisher) for the primary endpoint, and exploratory Spearman correlations between sarcopenia measures, regenerative indices and functional change; given the pilot nature, 95 % confidence intervals will be reported without formal p-values.

Adverse events related to additional procedures are expected to be minimal (venepuncture, MRI without ionising radiation, DXA ≈0.001 mSv, and intra-operative muscle biopsy performed under the same anaesthesia). All events will be captured and reported according to Good Clinical Practice; a data-safety officer affiliated with the institutional vigilance unit will review safety quarterly. The study duration per participant is six months; the overall project, including analysis and dissemination, spans 18 months. Results, positive, negative or inconclusive, will be submitted to peer-reviewed journals and uploaded to ClinicalTrials.gov within one year of completion, in line with French and EU transparency requirements. By integrating in-vivo phenotyping, advanced imaging and ex-vivo regenerative testing across two complementary hip-surgery models, Hip-REGEN should generate mechanistic hypotheses and candidate biomarkers to guide future stratified rehabilitation or pre-habilitation trials in sarcopenic older adults.

Inclusion Criteria:

- Elderly subjects undergoing surgical hip replacement for fracture of the upper end of the femur or severe hip osteoarthritis.

Exclusion Criteria for both groups :

• Contraindications to MRI : pacemaker, metallic implants.
• Presence of a lower-limb prosthesis on the contralateral side to the surgery that may interfere with quadriceps mass measurements.
• Progressive high-grade neoplasia.
• Documented major cognitive disorders
• Under legal protection measures (guardianship, conservatorship, or curatorship).
• Subjects not affiliated with or not covered by a social security system.
• Participation in another ongoing study with an active exclusion period.

Exclusion criteria - Fracture group :

• Fracture with a suspicion of underlying neoplasia.
• Placement of a lower-limb prosthesis on the surgical side within the last 12 months.
• Inability to walk with or without human/technical assistance prior to fracture.

Exclusion criteria - Hip osteoarthritis group :

- Active inflammatory joint disease (rheumatoid arthritis, spondyloarthritis).