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.
Objectives 1. To investigate the effect of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of physical performance and quality of life. 2. To investigate the effect of RANKL inhibition in treating sarcopenia in hip fracture patients in terms of appendicular skeletal muscle mass and muscle strength. 3. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
130
60mg subcutaneous Denosumab (1mL solution) every 6 months and intravenous placebo (100mL normal saline) once yearly
5mg intravenous Zoledronic Acid (100mL solution) once yearly and subcutaneous placebo (1mL normal saline) every 6 months
The Chinese University of Hong Kong
Hong Kong, China
Sarcopenia and Quality of Life (SarQoL®)
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.
Time frame: From enrolment to 24 months after the start of treatment
Quadriceps muscle strength
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
Time frame: From enrolment to 24 months after the start of treatment
Handgrip strength
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
Time frame: From enrolment to 24 months after the start of treatment
Appendicular skeletal muscle mass (ASM)
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.
Time frame: From enrolment to 24 months after the start of treatment
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5-time chair stand test
The time to rise from a chair 5 times is recorded. Low physical performance is ≥ 12 seconds.
Time frame: From enrolment to 24 months after the start of treatment
6-metre walk
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
Time frame: From enrolment to 24 months after the start of treatment
Short Physical Performance Battery
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.
Time frame: From enrolment to 24 months after the start of treatment
Balancing ability
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).
Time frame: From enrolment to 24 months after the start of treatment
Balancing ability
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 (%).
Time frame: From enrolment to 24 months after the start of treatment
Balancing ability
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).
Time frame: From enrolment to 24 months after the start of treatment
Balancing ability
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 (%).
Time frame: From enrolment to 24 months after the start of treatment
Balancing ability
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 (%).
Time frame: From enrolment to 24 months after the start of treatment
Falls
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
Time frame: From enrolment to 24 months after the start of treatment
Hospital re-admissions
Documented from Clinical Management System (CMS) from Hospital Authority (public computerized system for all patients)
Time frame: From enrolment to 24 months after start of treatment
Secondary fracture
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
Time frame: From enrolment to 24 months after start of treatment
Mortality
Documented from the Clinical Management System (CMS) from Hospital Authority (public computerized system for all patients)
Time frame: From enrolment to 24 months after start of treatment
Bone mineral density (BMD)
Measured by Dual-energy X-ray absorptiometry (Horizon®, Hologic, US) at lumbar spine and contralateral hip
Time frame: From enrolment to 24 months after the start of treatment