Anterior Cruciate Ligament TearPhase 1ZAPOANCT05204836
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury
A Phase 1 study testing Zoledronic Acid Injection in people with Anterior Cruciate Ligament Tear and Anterior Cruciate Ligament Rupture, run by University of Calgary at 1 site in Canada.
Trial summary
The purpose of this study is to assess if a zoledronic acid injection can alter the trajectory of joint degeneration following an acute anterior cruciate ligament (ACL) injury. Read more about this study
- Who is it for?
- Ages 25 to 45 years
- Conditions the study is for
- Anterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Injuries
- What is being tested?
- Zoledronic Acid Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteCanada
- Study dates
- 16 May 2023to 3 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical evidence of an acute unilateral ACL tear (full-thickness, complete tear) will be recruited. This age range is chosen to ensure participants have fully developed adult bone structures and to exclude participants with menopause as this could affect study results.
- Participants with combined ligament deficiencies (posterior cruciate, medial and/or lateral collateral) or meniscal injury will be included. Participants must be able to fully extend the knee while supported at the time of the baseline measurement in order to conduct the HR-pQCT scan.
- Participants with a serum calcium level in the normal range (2.10-2.60 mmol/L) and a creatinine level above 59 (reported as eGFR) will be included.
Who cannot join
- Individuals with contraindications to zoledronic acid (see below)
- Prior knee ligament and/or meniscus tears, and/or intra-articular fractures.
- Females who are pregnant or planning pregnancy within a year will not be eligible. The research team will recommend participants who are planning to become pregnant within the next five years to withdraw their participation.
- Individuals with knees larger than the CT scanner's circular field of view.
- Individuals with a history of disease and/or treatment affecting bone turnover in the past 12 months.
- Individuals with injuries or implants that are not MRI-safe.
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- Zoledronic acid is contraindicated for:
- Patients who are hypersensitive to this drug or to any ingredient in the formulation, or to any bisphosphonates or component of the container.
- Severe renal impairment with creatinine clearance <35 mL/min and in those with evidence of acute renal impairment. For this study, participants with a creatinine clearance <50 mL/min may be excluded.
- Non-corrected hypocalcaemia at the time of infusion.
- Pregnant and nursing mothers.
- Patients who are already taking another bisphosphonate (ex. for osteoporosis).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
The purpose of this study is to assess if a zoledronic acid injection can alter the trajectory of joint degeneration following an acute anterior cruciate ligament (ACL) injury.
Read the detailed description
After being informed about the study and potential risks and all participants giving written informed consent, this project will establish a cohort of young men and women who within six weeks have sustained an acute rupture of the ACL. The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection at baseline. The cohort will be followed radiographically with high resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy computed tomography (DECT), digital radiography (X-Ray), bi-planar X-ray (EOS) and magnetic resonance imaging (MRI) for eighteen months to monitor the progression of joint changes and the effects of zoledronic acid.
- Conditions
- Anterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Injuries, Osteo Arthritis Knee
- Being tested
- Zoledronic Acid Injection, Placebo
- Keywords
- acl tear, acl, acl rupture, acl injury, osteo arthritis
- Medical subject headings
- Anterior Cruciate Ligament Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic Acid InjectionDrug
Also called Taro-Zoledronic Acid, Dr. Reddy's Zoledronic Acid Injection
5 mg / 100 mL intravenous infusion
PlaceboDrug
Also called Saline
100 mL intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic Acid Injection | Experimental | Participants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid Receives: Drug: Zoledronic Acid Injection |
| Placebo | Placebo comparator | Participants will receive 1 dose 100 ml Saline. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 6 months in comparison to baseline.
Measured: Baseline, 6 months
Bone microarchitecture changes at 18 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 18 months in comparison to baseline.
Measured: Baseline, 18 months
Secondary outcomes (33)
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using a threshold-based approach BMLs will be identified, and their location and volume will be recorded in cubic millimetres (mm^3). This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in the location and volume of the BMLs will be assessed at 2 months comparison to baseline.
Measured: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of trabecular thickness which will be recorded in millimeters (mm) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in trabecular thickness will be assessed at 2 months comparison to baseline.
Measured: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of trabecular separation which will be recorded in millimeters (mm) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in trabecular separation will be assessed at 2 months comparison to baseline.
Measured: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of bone mineral density which will be recorded in milligrams of hydroxyapatite per cubic centimeter (mg HA/cm^3) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone mineral density will be assessed at 2 months comparison to baseline.
Measured: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using a threshold-based approach BMLs will be identified, and their location and volume will be recorded in cubic millimetres (mm^3). This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in the location and volume of the BMLs will be assessed at 6 months comparison to baseline.
Measured: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of trabecular thickness which will be recorded in millimeters (mm) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in trabecular thickness will be assessed at 6 months comparison to baseline.
Measured: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of trabecular separation which will be recorded in millimeters (mm) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in trabecular separation will be assessed at 6 months comparison to baseline.
Measured: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of bone mineral density which will be recorded in milligrams of hydroxyapatite per cubic centimeter (mg HA/cm^3) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone mineral density will be assessed at 6 months comparison to baseline.
Measured: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using a threshold-based approach BMLs will be identified, and their location and volume will be recorded in cubic millimetres (mm^3). This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in the location and volume of the BMLs will be assessed at 18 months comparison to baseline.
Measured: Baseline, 18 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of trabecular thickness which will be recorded in millimeters (mm) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in trabecular thickness will be assessed at 18 months comparison to baseline.
Measured: Baseline, 18 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of trabecular separation which will be recorded in millimeters (mm) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in trabecular separation will be assessed at 18 months comparison to baseline.
Measured: Baseline, 18 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
MRI data will be segmented to identify the bone surface in a similar fashion as described for HR-pQCT data. Using rigid body registration, the MRI data will be transformed to the HR-pQCT data, which allows for the analysis of bone mineral density which will be recorded in milligrams of hydroxyapatite per cubic centimeter (mg HA/cm^3) exclusively within the volume of BMLs. This analysis will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone mineral density will be assessed at 18 months comparison to baseline.
Measured: Baseline, 18 months
Knee alignment as assessed by bi-planar x-ray
Joint alignment by bi-planar x-ray (EOS) In a standing position, the baseline study visit will capture the alignment of the tibia and femur bones bilaterally so that alignment of the knee joint can be assessed. This is a standard clinical imaging device, and the software for measurement of knee alignment is built into the system.
Measured: Baseline
Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline
Patient reported outcomes at baseline will be assessed using
- ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: Baseline
Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months
Patient reported outcomes at baseline will be assessed using
- ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: 2 Months
Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months
Patient reported outcomes at baseline will be assessed using
- ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: 6 Months
Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months
Patient reported outcomes at baseline will be assessed using
- ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: 18 Months
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline
Patient reported outcomes will be assessed using
- Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Measured: Baseline
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months
Patient reported outcomes will be assessed using
- Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Measured: 2 months
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months
Patient reported outcomes will be assessed using
- Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Measured: 6 months
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months
Patient reported outcomes will be assessed using
- Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire Minimum Value: 1 (best outcome); Maximum Value: 5 (worse outcome)
Measured: 18 months
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline
Patient reported outcomes will be assessed using
- 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Measured: Baseline
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months
Patient reported outcomes will be assessed using
- 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Measured: 2 months
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months
Patient reported outcomes will be assessed using
- 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Measured: 6 months
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months
Patient reported outcomes will be assessed using
- 36-Item Short Form Survey (SF-36) Questionnaire Questions 1, 2, 20, 22, 34, 36 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 3-12 - Minimum Value: 1 (worst outcome); Maximum Value: 3 (best outcome) Question 13-19 - Minimum Value: 1 (worst outcome); Maximum Value: 2 (best outcome) Questions 21, 23, 26, 27, 30 - Minimum Value: 1 (best outcome); Maximum Value: 6 (worst outcome) Questions 24, 25, 28, 29, 31 - Minimum Value: 1 (worst outcome); Maximum Value: 6 (best outcome) Questions 32, 33, 35 - Minimum Value: 1 (worst outcome); Maximum Value: 5 (best outcome)
Measured: 18 months
Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline
Patient reported outcomes will be assessed using
- EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: Baseline
Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months
Patient reported outcomes will be assessed using
- EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: 2 months
Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months
Patient reported outcomes will be assessed using
- EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: 6 months
Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months
Patient reported outcomes will be assessed using
- EQ-5D-5L Questionnaire Questions 1-5 - Minimum Value: 1 (best outcome); Maximum Value: 5 (worst outcome) Question 6 - Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome)
Measured: 18 months
Patient reported outcomes Health History Questionnaire (HHQ) - Baseline
Patient reported outcomes will be assessed using
- Health History Questionnaire (HHQ) (No scale)
Measured: Baseline
Patient reported outcomes Health History Questionnaire (HHQ) - 2 months
Patient reported outcomes will be assessed using
- Health History Questionnaire (HHQ) (No scale)
Measured: 2 months
Patient reported outcomes Health History Questionnaire (HHQ) - 6 months
Patient reported outcomes will be assessed using
- Health History Questionnaire (HHQ) (No scale)
Measured: 6 months
Patient reported outcomes Health History Questionnaire (HHQ) - 18 months
Patient reported outcomes will be assessed using
- Health History Questionnaire (HHQ) (No scale)
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2022
- Study start16 May 2023
- Primary completion3 Jul 2025
- Study completion3 Jul 2025
Why it stopped: Recruitment stopped due to funding shortage. The scope of the original study increased beyond what had been budgeted in the grant that funded it, and follow-up funding attempts were not successful.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for Anterior Cruciate Ligament TearStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection within 6 weeks of ACL injury.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven Boyd, PhD, Principal investigator, University of CalgaryGregory Kline, MD, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05204836
- Sponsor's protocol ID
- REB21-1109
- Acronym
- ZAPOA
- Status last verified
- Sep 2025
- First submitted
- 21 Dec 2021
- Last updated
- 2 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Dare D, Rodeo S. Mechanisms of post-traumatic osteoarthritis after ACL injury. Curr Rheumatol Rep. 2014 Oct;16(10):448. doi: 10.1007/s11926-014-0448-1.
PubMed 25182676Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007 Oct;35(10):1756-69. doi: 10.1177/0363546507307396. Epub 2007 Aug 29.
PubMed 17761605Noyes FR, Bassett RW, Grood ES, Butler DL. Arthroscopy in acute traumatic hemarthrosis of the knee. Incidence of anterior cruciate tears and other injuries. J Bone Joint Surg Am. 1980 Jul;62(5):687-95, 757.
PubMed 7391091Speer KP, Spritzer CE, Bassett FH 3rd, Feagin JA Jr, Garrett WE Jr. Osseous injury associated with acute tears of the anterior cruciate ligament. Am J Sports Med. 1992 Jul-Aug;20(4):382-9. doi: 10.1177/036354659202000403.
PubMed 1415878Spindler KP, Schils JP, Bergfeld JA, Andrish JT, Weiker GG, Anderson TE, Piraino DW, Richmond BJ, Medendorp SV. Prospective study of osseous, articular, and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy. Am J Sports Med. 1993 Jul-Aug;21(4):551-7. doi: 10.1177/036354659302100412.
PubMed 8368416Sanders TL, Maradit Kremers H, Bryan AJ, Larson DR, Dahm DL, Levy BA, Stuart MJ, Krych AJ. Incidence of Anterior Cruciate Ligament Tears and Reconstruction: A 21-Year Population-Based Study. Am J Sports Med. 2016 Jun;44(6):1502-7. doi: 10.1177/0363546516629944. Epub 2016 Feb 26.
PubMed 26920430Poulsen E, Goncalves GH, Bricca A, Roos EM, Thorlund JB, Juhl CB. Knee osteoarthritis risk is increased 4-6 fold after knee injury - a systematic review and meta-analysis. Br J Sports Med. 2019 Dec;53(23):1454-1463. doi: 10.1136/bjsports-2018-100022. Epub 2019 May 9.
PubMed 31072840Buckwalter JA. Articular cartilage injuries. Clin Orthop Relat Res. 2002 Sep;(402):21-37. doi: 10.1097/00003086-200209000-00004.
PubMed 12218470Claes S, Hermie L, Verdonk R, Bellemans J, Verdonk P. Is osteoarthritis an inevitable consequence of anterior cruciate ligament reconstruction? A meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2013 Sep;21(9):1967-76. doi: 10.1007/s00167-012-2251-8. Epub 2012 Oct 26.
PubMed 23100047Huetink K, Nelissen RG, Watt I, van Erkel AR, Bloem JL. Localized development of knee osteoarthritis can be predicted from MR imaging findings a decade earlier. Radiology. 2010 Aug;256(2):536-46. doi: 10.1148/radiol.10090683. Epub 2010 Jun 29.
PubMed 20587644Meunier A, Odensten M, Good L. Long-term results after primary repair or non-surgical treatment of anterior cruciate ligament rupture: a randomized study with a 15-year follow-up. Scand J Med Sci Sports. 2007 Jun;17(3):230-7. doi: 10.1111/j.1600-0838.2006.00547.x.
PubMed 17501866Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, Roemer FW. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthritis Cartilage. 2011 Aug;19(8):990-1002. doi: 10.1016/j.joca.2011.05.004. Epub 2011 May 23.
PubMed 21645627Bhatla JL, Kroker A, Manske SL, Emery CA, Boyd SK. Differences in subchondral bone plate and cartilage thickness between women with anterior cruciate ligament reconstructions and uninjured controls. Osteoarthritis Cartilage. 2018 Jul;26(7):929-939. doi: 10.1016/j.joca.2018.04.006. Epub 2018 Apr 17.
PubMed 29678623Kroker A, Manske SL, Mohtadi N, Boyd SK. A study of the relationship between meniscal injury and bone microarchitecture in ACL reconstructed knees. Knee. 2018 Oct;25(5):746-756. doi: 10.1016/j.knee.2018.07.004. Epub 2018 Aug 13.
PubMed 30115589Michalak GJ, Walker R, Boyd SK. Concurrent Assessment of Cartilage Morphology and Bone Microarchitecture in the Human Knee Using Contrast-Enhanced HR-pQCT Imaging. J Clin Densitom. 2019 Jan-Mar;22(1):74-85. doi: 10.1016/j.jocd.2018.07.002. Epub 2018 Jul 19.
PubMed 30120027
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
- ClinicalTrials.gov ID
- NCT05204836
- Acronym / sponsor ID
- ZAPOA / REB21-1109
- Conditions
- Anterior Cruciate Ligament Tear, Anterior Cruciate Ligament Rupture, Anterior Cruciate Ligament Injuries, Osteo Arthritis Knee
- Keywords
- acl tear, acl, acl rupture, acl injury, osteo arthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment stopped due to funding shortage. The scope of the original study increased beyond what had been budgeted in the grant that funded it, and follow-up funding attempts were not successful.
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Study start
- 16 May 2023 (actual)
- Primary completion
- 3 Jul 2025 (actual)
- Study completion
- 3 Jul 2025 (actual)
- First posted
- 24 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess if a zoledronic acid injection can alter the trajectory of joint degeneration following an acute anterior cruciate ligament (ACL) injury.
Detailed description
After being informed about the study and potential risks and all participants giving written informed consent, this project will establish a cohort of young men and women who within six weeks have sustained an acute rupture of the ACL. The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection at baseline. The cohort will be followed radiographically with high resolution peripheral quantitative computed tomography (HR-pQCT), dual-energy computed tomography (DECT), digital radiography (X-Ray), bi-planar X-ray (EOS) and magnetic resonance imaging (MRI) for eighteen months to monitor the progression of joint changes and the effects of zoledronic acid.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- The cohort is randomized into a control and treatment group, where the treatment group receives a zoledronic acid injection within 6 weeks of ACL injury.
| Arm | Type | Receives |
|---|---|---|
| Zoledronic Acid Injection | Experimental | Drug: Zoledronic Acid InjectionParticipants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will receive 1 dose 100 ml Saline. |
Who may qualify
- Ages
- 25 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Clinical evidence of an acute unilateral ACL tear (full-thickness, complete tear) will be recruited. This age range is chosen to ensure participants have fully developed adult bone structures and to exclude participants with menopause as this could affect study results.
- Participants with combined ligament deficiencies (posterior cruciate, medial and/or lateral collateral) or meniscal injury will be included. Participants must be able to fully extend the knee while supported at the time of the baseline measurement in order to conduct the HR-pQCT scan.
- Participants with a serum calcium level in the normal range (2.10-2.60 mmol/L) and a creatinine level above 59 (reported as eGFR) will be included.
Key exclusion criteria (12 listed)
- Individuals with contraindications to zoledronic acid (see below)
- Prior knee ligament and/or meniscus tears, and/or intra-articular fractures.
- Females who are pregnant or planning pregnancy within a year will not be eligible. The research team will recommend participants who are planning to become pregnant within the next five years to withdraw their participation.
- Individuals with knees larger than the CT scanner's circular field of view.
- Individuals with a history of disease and/or treatment affecting bone turnover in the past 12 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic Acid InjectionAlso: Taro-Zoledronic Acid, Dr. Reddy's Zoledronic Acid Injection5 mg / 100 mL intravenous infusion | Drug | Zoledronic Acid Injection |
| PlaceboAlso: Saline100 mL intravenous infusion | Drug | Placebo |
Primary outcome
Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
Time frame: Baseline, 6 months
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 6 months in comparison to baseline.
Bone microarchitecture changes at 18 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT)
Time frame: Baseline, 18 months
To determine morphological parameters from HR-pQCT scans, the trabecular portion must be isolated from the cortical shell of the bone in order to analyse the components separately. This is accomplished with an already developed auto-segmentation algorithm. In addition, the raw HR-pQCT images must be converted to binary images, wherein each voxel (3D pixel) is either labelled 'bone' or 'not bone.' This segmentation is performed by an algorithm which applies either a Gaussian or Laplace-Hamming filter in addition to a threshold to the grey-scale images. The binary images can then be analysed and morphological parameters can be determined. The changes in bone microarchitecture will be assessed at 18 months in comparison to baseline.
33 secondary outcomes
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
Time frame: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
Time frame: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
Time frame: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
Time frame: Baseline, 2 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
Time frame: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
Time frame: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
Time frame: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
Time frame: Baseline, 6 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
Time frame: Baseline, 18 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
Time frame: Baseline, 18 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
Time frame: Baseline, 18 months
Bone marrow lesions (BML) and soft tissue injury changes at 18 months as assessed by MRI
Time frame: Baseline, 18 months
Knee alignment as assessed by bi-planar x-ray
Time frame: Baseline
Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline
Time frame: Baseline
Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months
Time frame: 2 Months
Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months
Time frame: 6 Months
Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months
Time frame: 18 Months
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline
Time frame: Baseline
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months
Time frame: 2 months
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months
Time frame: 6 months
Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months
Time frame: 18 months
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline
Time frame: Baseline
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months
Time frame: 2 months
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months
Time frame: 6 months
Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months
Time frame: 18 months
Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline
Time frame: Baseline
Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months
Time frame: 2 months
Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months
Time frame: 6 months
Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months
Time frame: 18 months
Patient reported outcomes Health History Questionnaire (HHQ) - Baseline
Time frame: Baseline
Patient reported outcomes Health History Questionnaire (HHQ) - 2 months
Time frame: 2 months
Patient reported outcomes Health History Questionnaire (HHQ) - 6 months
Time frame: 6 months
Patient reported outcomes Health History Questionnaire (HHQ) - 18 months
Time frame: 18 months
Results and safety
The study was stopped early (reason given: Recruitment stopped due to funding shortage. The scope of the original study increased beyond what had been budgeted in the grant that funded it, and follow-up funding attempts were not successful.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
- Background: PubMed 25182676Dare D, Rodeo S. Mechanisms of post-traumatic osteoarthritis after ACL injury. Curr Rheumatol Rep. 2014 Oct;16(10):448. doi: 10.1007/s11926-014-0448-1.
- Background: PubMed 17761605Lohmander LS, Englund PM, Dahl LL, Roos EM. The long-term consequence of anterior cruciate ligament and meniscus injuries: osteoarthritis. Am J Sports Med. 2007 Oct;35(10):1756-69. doi: 10.1177/0363546507307396. Epub 2007 Aug 29.
- Background: PubMed 7391091Noyes FR, Bassett RW, Grood ES, Butler DL. Arthroscopy in acute traumatic hemarthrosis of the knee. Incidence of anterior cruciate tears and other injuries. J Bone Joint Surg Am. 1980 Jul;62(5):687-95, 757.
- Background: PubMed 1415878Speer KP, Spritzer CE, Bassett FH 3rd, Feagin JA Jr, Garrett WE Jr. Osseous injury associated with acute tears of the anterior cruciate ligament. Am J Sports Med. 1992 Jul-Aug;20(4):382-9. doi: 10.1177/036354659202000403.
- Background: PubMed 8368416Spindler KP, Schils JP, Bergfeld JA, Andrish JT, Weiker GG, Anderson TE, Piraino DW, Richmond BJ, Medendorp SV. Prospective study of osseous, articular, and meniscal lesions in recent anterior cruciate ligament tears by magnetic resonance imaging and arthroscopy. Am J Sports Med. 1993 Jul-Aug;21(4):551-7. doi: 10.1177/036354659302100412.
- Background: PubMed 26920430Sanders TL, Maradit Kremers H, Bryan AJ, Larson DR, Dahm DL, Levy BA, Stuart MJ, Krych AJ. Incidence of Anterior Cruciate Ligament Tears and Reconstruction: A 21-Year Population-Based Study. Am J Sports Med. 2016 Jun;44(6):1502-7. doi: 10.1177/0363546516629944. Epub 2016 Feb 26.
- Background: PubMed 31072840Poulsen E, Goncalves GH, Bricca A, Roos EM, Thorlund JB, Juhl CB. Knee osteoarthritis risk is increased 4-6 fold after knee injury - a systematic review and meta-analysis. Br J Sports Med. 2019 Dec;53(23):1454-1463. doi: 10.1136/bjsports-2018-100022. Epub 2019 May 9.
- Background: PubMed 12218470Buckwalter JA. Articular cartilage injuries. Clin Orthop Relat Res. 2002 Sep;(402):21-37. doi: 10.1097/00003086-200209000-00004.
- Background: PubMed 23100047Claes S, Hermie L, Verdonk R, Bellemans J, Verdonk P. Is osteoarthritis an inevitable consequence of anterior cruciate ligament reconstruction? A meta-analysis. Knee Surg Sports Traumatol Arthrosc. 2013 Sep;21(9):1967-76. doi: 10.1007/s00167-012-2251-8. Epub 2012 Oct 26.
- Background: PubMed 20587644Huetink K, Nelissen RG, Watt I, van Erkel AR, Bloem JL. Localized development of knee osteoarthritis can be predicted from MR imaging findings a decade earlier. Radiology. 2010 Aug;256(2):536-46. doi: 10.1148/radiol.10090683. Epub 2010 Jun 29.
- Background: PubMed 17501866Meunier A, Odensten M, Good L. Long-term results after primary repair or non-surgical treatment of anterior cruciate ligament rupture: a randomized study with a 15-year follow-up. Scand J Med Sci Sports. 2007 Jun;17(3):230-7. doi: 10.1111/j.1600-0838.2006.00547.x.
- Background: PubMed 21645627Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, Roemer FW. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthritis Cartilage. 2011 Aug;19(8):990-1002. doi: 10.1016/j.joca.2011.05.004. Epub 2011 May 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven Boyd, PhD principal investigator
University of Calgary
Gregory Kline, MD principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zoledronic Acid Injection in people with Anterior Cruciate Ligament Tear and Anterior Cruciate Ligament Rupture, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment stopped due to funding shortage. The scope of the original study increased beyond what had been budgeted in the grant that funded it, and follow-up funding attempts were not successful.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bone microarchitecture changes at 6 months as assessed by high resolution peripheral quantitative computed tomography (HR-pQCT) (time frame: Baseline, 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05204836, which also lists 45 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.