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NCT Number: NCT07056478

RANKL Inhibition to Combat Sarcopenia in Hip Fracture Patients

The objective of this study is to conduct a pragmatic, randomized, double-blind, active-controlled trial to assess the efficacy of receptor activator of nuclear factor-kB ligand (RANKL) inhibition in the treatment of sarcopenia in hip fractures.

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Key information

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

About this study

Objectives

  • To investigate the effect of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of physical performance and quality of life.
  • To investigate the effect of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of appendicular skeletal muscle mass and muscle strength.
  • To investigate the efficacy of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of falls, hospital re-admissions, re-fractures, and mortality.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Elderly aged 65 years or older
  • Diagnosed with sarcopenia following AWGS guidelines - low appendicular skeletal muscle mass measured by dual-energy x-ray absorptiometry (Cutoff: Male <7.0kg/m2, and female <5.4kg/m2) AND low handgrip strength (Cutoff: Male < 28kg, Female <18 kg) OR low physical performance (6-metre walk, cutoff: <1.0m/s or 5-time chair stand test >=12s)
  • Diagnosed with a hip fracture from low-energy mechanism (e.g., falling from standing height) requiring an operation
  • Willing and able to comply with study protocol including follow-up evaluations.

Exclusion criteria

  • open fracture
  • multiple fractures
  • pathological fractures e.g., tumour, infection, etc.
  • history of medication or disease affecting bone metabolism e.g., hypo/hyperthyroidism
  • malignancy
  • chairbound or bedbound (unable to perform assessments)
  • serious cognitive problems e.g., severe dementia (unable to agree for consent) - renal impairment with glomerular filtration rate <30 mL/min
  • prior anti-osteoporotic medication e.g. bisphosphonates, denosumab, etc.
  • active infection,
  • severe malnutrition i.e. Mini Nutritional Assessment < 17 points
  • serious neurological or neuromuscular conditions e.g. Parkinson's disease
  • uncontrolled chronic conditions e.g. poorly controlled diabetes mellitis
  • not anaesthetically fit for operation or conservative management

Treatment and study plan

Denosumab (Prolia)

Drug

60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly

Zoledronic acide (Aclasta)

Drug

5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months

Primary outcomes

  1. Sarcopenia and Quality of Life (SarQoL®)

    Time frame: From enrolment to 24 months after the start of treatment

    Health-related questionnaire for sarcopenia which is composed of 55 items translated into 22 questions and organized into seven domains of quality of life including physical and mental health, locomotion, body composition, functionality, activities of daily living, leisure activities, and fears. The SarQoL involves an overall score, which is the sum of seven individual domain scores, with higher scores indicating better quality of life. During the scoring process, the overall and domain scores are rescaled such that their maximum possible values become 100.

  2. Quadriceps muscle strength

    Time frame: From enrolment to 24 months after the start of treatment

    Measured on affected limb with isometric dynamometer (Baseline, Genova, Italy). Subject will sit on a chair with both feet above ground, while raising the affected leg 45° forwards. The dynamometer is placed above the ankle and subject will push the leg forward with maximum force. Measurements are repeated three times and maximum value used for evaluation

  3. Handgrip strength

    Time frame: From enrolment to 24 months after the start of treatment

    Assessed by handgrip strength with spring-type hand dynamometer (JAMAR Hand Dynamometer 5030JO; Sammons Preston, Bolingbrook, IL). The maximum reading of 2 trials using the dominant hand in a maximum-effort isometric contraction is taken. Male < 28kg, and female <18kg are cut-off for low handgrip strength

  4. Appendicular skeletal muscle mass (ASM)

    Time frame: From enrolment to 24 months after the start of treatment

    Determined with Dual-energy X-ray absorptiometry (Horizon®, Hologic, USA). Total appendicular skeletal mass (ASM) is evaluated by segmented measurement of muscle mass at four limbs by operator-defined cutlines at specific anatomical landmarks. ASM is adjusted to square of height to calculate appendicular skeletal mass index (ASMI) (kg/m2). Cutoff of low ASMI is defined as Male <7.0kg/m2, and female <5.4kg/m2.

  5. 5-time chair stand test

    Time frame: From enrolment to 24 months after the start of treatment

    The time to rise from a chair 5 times is recorded. Low physical performance is ≥ 12 seconds.

  6. 6-metre walk

    Time frame: From enrolment to 24 months after the start of treatment

    The time taken to walk 6 metres without deceleration is taken. The average result of 2 trials is taken and recorded. Low physical performance is <1.0m/s

  7. Short Physical Performance Battery

    Time frame: From enrolment to 24 months after the start of treatment

    Performed by balance test (side-by-side stand, semi-tandem stand, and tandem stand), gait speed test (time for 4-meter walk), and chair stand test (5 repeats). Low physical performance is ≤ 9.

  8. Balancing ability

    Time frame: From enrolment to 24 months after the start of treatment

    The Basic Balance Master System (NeuroCom International Inc, USA) is used to measure static and dynamic ability of subjects to maintain center of balance. Subjects will stand barefoot on force plate and control location of their center-of-gravity by weight-shifting to eight different targets. Measured parameters of limits of stability test includes reaction time(s).

  9. Balancing ability

    Time frame: From enrolment to 24 months after the start of treatment

    The Basic Balance Master System (NeuroCom International Inc, USA) is used to measure static and dynamic ability of subjects to maintain center of balance. Subjects will stand barefoot on force plate and control location of their center-of-gravity by weight-shifting to eight different targets. Measured parameters of limits of stability test includes directional control (%).

  10. Balancing ability

    Time frame: From enrolment to 24 months after the start of treatment

    The Basic Balance Master System (NeuroCom International Inc, USA) is used to measure static and dynamic ability of subjects to maintain center of balance. Subjects will stand barefoot on force plate and control location of their center-of-gravity by weight-shifting to eight different targets. Measured parameters of limits of stability test includes movement velocity (degrees/s).

  11. Balancing ability

    Time frame: From enrolment to 24 months after the start of treatment

    The Basic Balance Master System (NeuroCom International Inc, USA) is used to measure static and dynamic ability of subjects to maintain center of balance. Subjects will stand barefoot on force plate and control location of their center-of-gravity by weight-shifting to eight different targets. Measured parameters of limits of stability test includes endpoint excursion (%).

  12. Balancing ability

    Time frame: From enrolment to 24 months after the start of treatment

    The Basic Balance Master System (NeuroCom International Inc, USA) is used to measure static and dynamic ability of subjects to maintain center of balance. Subjects will stand barefoot on force plate and control location of their center-of-gravity by weight-shifting to eight different targets. Measured parameters of limits of stability test includes maximum excursion (%).

Secondary outcomes

  1. Falls

    Time frame: From enrolment to 24 months after the start of treatment

    Patients self-report via fall calendar, which will be returned at each follow-up. Calendar reporting has been well proven to be reliable for fall studies

  2. Hospital re-admissions

    Time frame: From enrolment to 24 months after start of treatment

    Documented from Clinical Management System (CMS) from Hospital Authority (public computerized system for all patients)

  3. Secondary fracture

    Time frame: From enrolment to 24 months after start of treatment

    Confirmed via X-ray/radiology report and Clinical Management System (CMS). Lateral X-ray of spine also taken during follow-up to detect the often clinically silent vertebral fracture. Vertebra is assessed by Genant classification as per our previously established protocol

  4. Mortality

    Time frame: From enrolment to 24 months after start of treatment

    Documented from the Clinical Management System (CMS) from Hospital Authority (public computerized system for all patients)

  5. Bone mineral density (BMD)

    Time frame: From enrolment to 24 months after the start of treatment

    Measured by Dual-energy X-ray absorptiometry (Horizon®, Hologic, US) at lumbar spine and contralateral hip

Study contacts

Contact information is provided by the study sponsor or research team.

Ronald Man Yeung Wong

CONTACT

[email protected]

852 3505 1654

Sponsors and collaborators

Lead sponsor

Prince of Wales Hospital, Shatin, Hong Kong

Other

Registry information

Official study title

RANKL Inhibition to Combat Sarcopenia in Hip Fracture Patients: A Pragmatic, Randomized Double-blind, Active-Controlled Trial

Important dates

Study start
2026
Primary completion
2028
Study completion
2030
First posted
Jul 9, 2025
Registry last updated
Jul 9, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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