Impact of Pre-operative Sarcopenia on Functional Recovery After Hip Arthroplasty in Older Adults (HIP-REGEN)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Osteoarthritis (OA); Sarcopenia in Elderly; Hip Fracture Surgeries
• Intervention / Treatment: Procedure: Total hip replacement; Biological: Blood sampling; Biological: Muscle biopsies; Biological: Collection of joint samples derived from surgical waste; Radiation: DXA; Other: MRI; Other: Handgrip strength test

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean Baptiste Robiaud, Assistant head physician; Phone Number: +33629184092; Email: jbrobiaud@gmail.com

Study Locations

• France
  • Montpellier, France, 34090
    • University Hospital
    • Contact: Jean Baptiste Robiaud, Assistant head physician; Phone Number: +33629184092; Email: jbrobiaud@gmail.com
    • Principal Investigator: Jean Baptiste ROBIAUD, Assistant head physician

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Elderly subjects with a femoral neck fracture or severe hip osteoarthritis requiring surgery

Procedure: Total hip replacement; Hip replacement is a surgical procedure performed as part of routine care for patients with a fracture of the upper end of the femur or severe osteoarthritis of the hip.; Biological: Blood sampling; Four heparinized tubes of 5 ml of blood will be collected from each patient at inclusion. All blood samples will be stored in a biobank for subsequent analyses targeting biomarkers potentially associated with sarcopenia and muscle regeneration.; Biological: Muscle biopsies; Performed during hip arthroplasty; Biological: Collection of joint samples derived from surgical waste; Performed during hip arthroplasty; Radiation: DXA; Within 15 days following the surgical procedure, during hospitalization/rehabilitation; Other: MRI; Within 15 days following the surgical procedure, during hospitalization/rehabilitation; Other: Handgrip strength test; Measurement of handgrip strength using a hand dynamometer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Barthel Index at 3 months post-operative	A 10-point shift is the minimal clinically important difference; after hip-fracture surgery a mean 25-point decline at 3 months is anticipated.	Baseline and 3 months
Change from Baseline in the Barthel Index at 6 months post-operative		Baseline and 6 months
Measurement of hand-grip strength via dynamometry	Assessment of preoperative sarcopenia severity	Baseline
Measurement of appendicular lean mass by DXA	Assessment of preoperative sarcopenia severity	Prior to surgery or within 7 days postoperatively
Measurement of quadriceps mass by MRI	Assessment of preoperative sarcopenia severity. Because DXA cannot differentiate intramuscular fat or connective tissue, 3-D Dixon/IDEAL MRI of the quadriceps-the muscle most affected by ageing-will segment contractile tissue and compute muscle mass (volume × 1.04 kg · L-¹).	Prior to surgery or within 7 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of myoblastic progenitors at proliferation onset	Quantification, and correlation with Barthel-index at 3 month, of the number of myoblastic progenitor cells obtained after in-vitro proliferation for 3 days of primary human satellite cells isolated from ~25 mg gluteus micro-biopsies collected during surgery under general anaesthesia. The number of myoblasts will be determined by immunofluorescence staining and quantified using automated image analysis from at least five random microscopic fields per culture well (expressed as cells/mm² at day 3 of proliferation).	Intraoperative
Mean myotube surface area at differentiation end	Quantification, and correlation with Barthel-index at 3 month, of the mean surface area of myotubes at the end of the differentiation phase from primary human satellite cells isolated from ~25 mg gluteus-medius micro-biopsies collected during surgery under general anaesthesia. Myotube surface area will be determined by immunofluorescence staining and quantified using automated image analysis from at least five random microscopic fields per culture well, expressed in square micrometres (µm²).	Intraoperative
Proportion of senescent MSCs	Quantification, and correlation with Barthel-index at 3 month, of the proportion of senescent MSCs among primary MSC cultures isolated from bone fragments obtained during hip arthroplasty (surgical waste) by bone marrow flush. Senescence will be assessed using β-galactosidase staining, and the proportion of senescent cells will be calculated as the percentage of β-gal⁺ cells among total DAPI⁺ nuclei, averaged from at least five random microscopic fields per culture well (expressed as % of β-gal⁺ MSCs).	Intraoperative
Number of chondrocytes obtained from MSCs at differentiation end	Quantification, and correlation with Barthel-index at 3 month, of the number of chondrocytes obtained at the end of the differentiation phase from primary human mesenchymal stromal cells (MSCs) cultured in chondrogenic differentiation medium. Differentiated cells will be identified by immunofluorescence staining or histological coloration and quantified using automated image analysis from at least five random microscopic fields per culture well, expressed as number of cells per mm².	Intraoperative
Number of adipocytes obtained from MSCs at differentiation end	Quantification, and correlation with Barthel-index at 3 month, of the number of adipocytes obtained at the end of the differentiation phase from primary human mesenchymal stromal cells (MSCs) cultured in adipogenic differentiation medium. Differentiated cells will be identified by immunofluorescence staining or histological coloration and quantified using automated image analysis from at least five random microscopic fields per culture well, expressed as number of cells per mm².	Intraoperative
Number of osteocytes obtained from MSCs at differentiation end.	Quantification, and correlation with Barthel-index at 3 month, of the number of osteocytes obtained at the end of the differentiation phase from primary human mesenchymal stromal cells (MSCs) cultured in osteogenic differentiation medium. Differentiated cells will be identified by immunofluorescence staining or histological coloration and quantified using automated image analysis from at least five random microscopic fields per culture well, expressed as number of cells per mm².	Intraoperative
Serum concentation of myostatin	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 3 month.	Baseline and 3 month
Serum concentation of myostatin	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 6 month.	Baseline and 6 month
Serum concentation of follistatin	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 3 month.	Baseline and 3 month
Serum concentation of follistatin	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 6 month.	Baseline and 6 month
Serum concentation of irisin	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 3 month.	Baseline and 3 month
Serum concentation of irisin	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 6 month.	Baseline and 6 month
Serum concentation of IL-6	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 3 month.	Baseline and 3 month
Serum concentation of IL-6	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 6 month.	Baseline and 6 month
Serum concentation of IGF-1	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 3 month.	Baseline and 3 month
Serum concentation of IGF-1	Preoperative circulating biomarkers predictive of post-arthrosplasty recovery will be identified and validated by quantifying candidate myokines in baseline serum via ELISA and multiplex assays and correlating with Barthel-index at 6 month.	Baseline and 6 month

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier

Publications and helpful links

General Publications

• Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012 Apr 3;8(8):457-65. doi: 10.1038/nrendo.2012.49.
• Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: epidemiology and therapy. Osteoarthritis Cartilage. 2020 Mar;28(3):242-248. doi: 10.1016/j.joca.2020.01.002. Epub 2020 Jan 13.
• Fox KM, Magaziner J, Hawkes WG, Yu-Yahiro J, Hebel JR, Zimmerman SI, Holder L, Michael R. Loss of bone density and lean body mass after hip fracture. Osteoporos Int. 2000;11(1):31-5. doi: 10.1007/s001980050003.
• Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014 Jul;10(7):437-41. doi: 10.1038/nrrheum.2014.44. Epub 2014 Mar 25.
• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169.
• GBD 2021 Osteoarthritis Collaborators
• Stein H, Perren SM, Cordey J, Kenwright J, Mosheiff R, Francis MJ. The muscle bed--a crucial factor for fracture healing: a physiological concept. Orthopedics. 2002 Dec;25(12):1379-83. doi: 10.3928/0147-7447-20021201-16. No abstract available.
• Brzeszczynska J, Meyer A, McGregor R, Schilb A, Degen S, Tadini V, Johns N, Langen R, Schols A, Glass DJ, Roubenoff R, Ross JA, Fearon KCH, Greig CA, Jacobi C. Alterations in the in vitro and in vivo regulation of muscle regeneration in healthy ageing and the influence of sarcopenia. J Cachexia Sarcopenia Muscle. 2018 Feb;9(1):93-105. doi: 10.1002/jcsm.12252. Epub 2017 Dec 6.
• Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A. Muscle mass and functional recovery in men with hip fracture. Am J Phys Med Rehabil. 2007 Oct;86(10):818-25. doi: 10.1097/PHM.0b013e318151fec7.
• Maden-Wilkinson TM, Degens H, Jones DA, McPhee JS. Comparison of MRI and DXA to measure muscle size and age-related atrophy in thigh muscles. J Musculoskelet Neuronal Interact. 2013 Sep;13(3):320-8.
• Fuchs CJ, Kuipers R, Rombouts JA, Brouwers K, Schrauwen-Hinderling VB, Wildberger JE, Verdijk LB, van Loon LJC. Thigh muscles are more susceptible to age-related muscle loss when compared to lower leg and pelvic muscles. Exp Gerontol. 2023 May;175:112159. doi: 10.1016/j.exger.2023.112159. Epub 2023 Mar 31.
• Vergara I, Vrotsou K, Orive M, Gonzalez N, Garcia S, Quintana JM. Factors related to functional prognosis in elderly patients after accidental hip fractures: a prospective cohort study. BMC Geriatr. 2014 Nov 26;14:124. doi: 10.1186/1471-2318-14-124.
• Gielen E, Dupont J, Dejaeger M, Laurent MR. Sarcopenia, osteoporosis and frailty. Metabolism. 2023 Aug;145:155638. doi: 10.1016/j.metabol.2023.155638. Epub 2023 Jun 20.
• Di Monaco M, Vallero F, Di Monaco R, Tappero R. Prevalence of sarcopenia and its association with osteoporosis in 313 older women following a hip fracture. Arch Gerontol Geriatr. 2011 Jan-Feb;52(1):71-4. doi: 10.1016/j.archger.2010.02.002. Epub 2010 Mar 5.
• Haute Autorité de Santé. Prothèses de hanche. Saint-Denis La Plaine: HAS; 2013.
• Clynes MA, Gregson CL, Bruyere O, Cooper C, Dennison EM. Osteosarcopenia: where osteoporosis and sarcopenia collide. Rheumatology (Oxford). 2021 Feb 1;60(2):529-537. doi: 10.1093/rheumatology/keaa755.
• Candel-Parra E, Corcoles-Jimenez MP, Del Egido-Fernandez MA, Villada-Munera A, Jimenez-Sanchez MD, Moreno-Moreno M, Carrion-Gonzalez M, Denia-Cortes A. [Independence in activities of daily living 6 months after surgery in previously independent elderly patients with hip fracture caused by a fall]. Enferm Clin. 2008 Nov-Dec;18(6):309-16. doi: 10.1016/s1130-8621(08)75853-4. Spanish.
• Maravic M, Taupin P, Landais P, Roux C. Change in hip fracture incidence over the last 6 years in France. Osteoporos Int. 2011 Mar;22(3):797-801. doi: 10.1007/s00198-010-1255-9. Epub 2010 Jun 2.
• Desmond Curran, et al. Épidémiologie des fractures liées à l'ostéoporose en France : revue de la littérature, Revue du Rhumatisme, Volume 77, Issue 6, 2010, Pages 579-585,ISSN 1169-8330
• Putman S, et al. Épidémiologie des prothèses de hanche en France : analyse de la base nationale du PMSI de 2008 à 2014, Revue de Chirurgie Orthopédique et Traumatologique,Volume 103, Issue 7, Supplement, 2017, Page S90, ISSN 1877-0517

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: September 1, 2025
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Rehabilitation; Functional Recovery; Osteoarthritis (OA); Hip Fracture Surgeries; Sarcopenia in Elderly
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Arthroplasty, Replacement; Arthroplasty; Orthopedic Procedures; Plastic Surgery Procedures; Prosthesis Implantation; Blood Specimen Collection; Arthroplasty, Replacement, Hip
• Other Study ID Numbers: RECHMPL23_0348; 2024-A02779-38 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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