- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05204836
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention Following an Acute Knee Injury (ZAPOA)
Altering Bone Microarchitecture and Mechanics by Off-label Pharmaceutical Intervention
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Steven Boyd, PhD
- Phone Number: 4032203664
- Email: skboyd@ucalgary.ca
Study Locations
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Alberta
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Calgary, Alberta, Canada, T2N 1N4
- Recruiting
- University of Calgary
-
Contact:
- Steven Boyd, PhD
- Phone Number: 4032203664
- Email: skboyd@ucalgary.ca
-
Principal Investigator:
- Steven Boyd, PhD
-
Principal Investigator:
- Gregory Kline, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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 (2.1-2.55 mmol/L) and a creatinine level above 50 (reported as eGFR) will be included.
Exclusion Criteria:
- 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.
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).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Zoledronic Acid Injection
Participants will receive 1 dose of 5 mg/100 mL intravenous zoledronic acid
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5 mg / 100 mL intravenous infusion
Other Names:
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Placebo Comparator: Placebo
Participants will receive 1 dose 100 ml Saline.
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100 mL intravenous infusion
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Baseline, 6 months
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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.
|
Baseline, 18 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Bone marrow lesions (BML) and soft tissue injury changes at 2 months as assessed by Magnetic Resonance Imaging (MRI)
Time Frame: Baseline, 2 months
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MRI data will be segmented to identify the bone surface in a similar fashion as described for the HR-pQCT data. Subsequently, using a threshold based approach BMLs will be identified and their locations and volumes will be recorded. Next, using rigid body registration the MRI data will be transformed to the HR-pQCT data. That allows the analysis of bone microarchitecture exclusively within the volume of BMLs. All of these analysis steps will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone will be assessed at 2 months comparison to baseline. |
Baseline, 2 months
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Bone marrow lesions (BML) and soft tissue injury changes at 6 months as assessed by MRI
Time Frame: Baseline, 6 months
|
MRI data will be segmented to identify the bone surface in a similar fashion as described for the HR-pQCT data. Subsequently, using a threshold based approach BMLs will be identified and their locations and volumes will be recorded. Next, using rigid body registration the MRI data will be transformed to the HR-pQCT data. That allows the analysis of bone microarchitecture exclusively within the volume of BMLs. All of these analysis steps will be performed using custom algorithms in Python and the visualization toolkit. The changes in bone will be assessed at 6 months in comparison to baseline. |
Baseline, 6 months
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Knee alignment as assessed by bi-planar x-ray
Time Frame: Baseline
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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.
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Baseline
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Patient reported outcomes using ACL Quality of Life Questionnaire - Baseline
Time Frame: Baseline
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Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome) |
Baseline
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Patient reported outcomes using ACL Quality of Life Questionnaire - 2 Months
Time Frame: 2 Months
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Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome) |
2 Months
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Patient reported outcomes using ACL Quality of Life Questionnaire - 6 Months
Time Frame: 6 Months
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Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome) |
6 Months
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Patient reported outcomes using ACL Quality of Life Questionnaire - 18 Months
Time Frame: 18 Months
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Patient reported outcomes at baseline will be assessed using - ACL Quality of Life Questionnaire Minimum Value: 0 (worst outcome); Maximum Value: 100 (best outcome) |
18 Months
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Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) - Questionnaire - Baseline
Time Frame: Baseline
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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) |
Baseline
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Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 2 Months
Time Frame: 2 months
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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) |
2 months
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Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 6 Months
Time Frame: 6 months
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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) |
6 months
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Patient reported outcomes using Knee injury and Osteoarthritis Outcome Score (KOOS) Questionnaire - 18 Months
Time Frame: 18 months
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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) |
18 months
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Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - Baseline
Time Frame: Baseline
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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) |
Baseline
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Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 2 months
Time Frame: 2 months
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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) |
2 months
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Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 6 months
Time Frame: 6 months
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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) |
6 months
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Patient reported outcomes using 36-Item Short Form Survey (SF-36) Questionnaire - 18 months
Time Frame: 18 months
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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) |
18 months
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Patient reported outcomes using EQ-5D-5L Questionnaire - Baseline
Time Frame: Baseline
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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) |
Baseline
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Patient reported outcomes using EQ-5D-5L Questionnaire - 2 months
Time Frame: 2 months
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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) |
2 months
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Patient reported outcomes using EQ-5D-5L Questionnaire - 6 months
Time Frame: 6 months
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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) |
6 months
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Patient reported outcomes using EQ-5D-5L Questionnaire - 18 months
Time Frame: 18 months
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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) |
18 months
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Patient reported outcomes Health History Questionnaire (HHQ) - Baseline
Time Frame: Baseline
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Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale) |
Baseline
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Patient reported outcomes Health History Questionnaire (HHQ) - 2 months
Time Frame: 2 months
|
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale) |
2 months
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Patient reported outcomes Health History Questionnaire (HHQ) - 6 months
Time Frame: 6 months
|
Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale) |
6 months
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Patient reported outcomes Health History Questionnaire (HHQ) - 18 months
Time Frame: 18 months
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Patient reported outcomes will be assessed using - Health History Questionnaire (HHQ) (No scale) |
18 months
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Steven Boyd, PhD, University of Calgary
- Principal Investigator: Gregory Kline, MD, University of Calgary
Publications and helpful links
General Publications
- Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, Bridgett L, Williams S, Guillemin F, Hill CL, Laslett LL, Jones G, Cicuttini F, Osborne R, Vos T, Buchbinder R, Woolf A, March L. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014 Jul;73(7):1323-30. doi: 10.1136/annrheumdis-2013-204763. Epub 2014 Feb 19.
- Bingham CO 3rd, Buckland-Wright JC, Garnero P, Cohen SB, Dougados M, Adami S, Clauw DJ, Spector TD, Pelletier JP, Raynauld JP, Strand V, Simon LS, Meyer JM, Cline GA, Beary JF. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum. 2006 Nov;54(11):3494-507. doi: 10.1002/art.22160.
- Varenna M, Zucchi F, Failoni S, Becciolini A, Berruto M. Intravenous neridronate in the treatment of acute painful knee osteoarthritis: a randomized controlled study. Rheumatology (Oxford). 2015 Oct;54(10):1826-32. doi: 10.1093/rheumatology/kev123. Epub 2015 May 20.
- Rossini M, Adami S, Fracassi E, Viapiana O, Orsolini G, Povino MR, Idolazzi L, Gatti D. Effects of intra-articular clodronate in the treatment of knee osteoarthritis: results of a double-blind, randomized placebo-controlled trial. Rheumatol Int. 2015 Feb;35(2):255-63. doi: 10.1007/s00296-014-3100-5. Epub 2014 Aug 1.
- Laslett LL, Dore DA, Quinn SJ, Boon P, Ryan E, Winzenberg TM, Jones G. Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial. Ann Rheum Dis. 2012 Aug;71(8):1322-8. doi: 10.1136/annrheumdis-2011-200970. Epub 2012 Feb 21.
- Guermazi A, Eckstein F, Hellio Le Graverand-Gastineau MP, Conaghan PG, Burstein D, Keen H, Roemer FW. Osteoarthritis: current role of imaging. Med Clin North Am. 2009 Jan;93(1):101-26, xi. doi: 10.1016/j.mcna.2008.08.003.
- Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998 Aug;28(2):88-96. doi: 10.2519/jospt.1998.28.2.88.
- Sanders 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.
- Lohmander 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.
- Lohmander LS, Ostenberg A, Englund M, Roos H. High prevalence of knee osteoarthritis, pain, and functional limitations in female soccer players twelve years after anterior cruciate ligament injury. Arthritis Rheum. 2004 Oct;50(10):3145-52. doi: 10.1002/art.20589.
- 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.
- Noyes 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.
- Speer 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.
- Spindler 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.
- Poulsen 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.
- Buckwalter JA. Articular cartilage injuries. Clin Orthop Relat Res. 2002 Sep;(402):21-37. doi: 10.1097/00003086-200209000-00004.
- Claes 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.
- Huetink 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.
- Meunier 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.
- Hunter 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. Erratum In: Osteoarthritis Cartilage. 2011 Sep;19(9):1168.
- Bhatla 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.
- Kroker 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.
- Michalak 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.
- Kroker A, Bhatla JL, Emery CA, Manske SL, Boyd SK. Subchondral bone microarchitecture in ACL reconstructed knees of young women: A comparison with contralateral and uninjured control knees. Bone. 2018 Jun;111:1-8. doi: 10.1016/j.bone.2018.03.006. Epub 2018 Mar 8.
- Kroker A, Besler BA, Bhatla JL, Shtil M, Salat P, Mohtadi N, Walker RE, Manske SL, Boyd SK. Longitudinal Effects of Acute Anterior Cruciate Ligament Tears on Peri-Articular Bone in Human Knees Within the First Year of Injury. J Orthop Res. 2019 Nov;37(11):2325-2336. doi: 10.1002/jor.24410. Epub 2019 Jul 23.
- She G, Zhou Z, Zha Z, Wang F, Pan X. Protective effect of zoledronic acid on articular cartilage and subchondral bone of rabbits with experimental knee osteoarthritis. Exp Ther Med. 2017 Nov;14(5):4901-4909. doi: 10.3892/etm.2017.5135. Epub 2017 Sep 19.
- Spector TD, Conaghan PG, Buckland-Wright JC, Garnero P, Cline GA, Beary JF, Valent DJ, Meyer JM. Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial [ISRCTN01928173]. Arthritis Res Ther. 2005;7(3):R625-33. doi: 10.1186/ar1716. Epub 2005 Mar 24.
- Adami S, Pavelka K, Cline GA, Hosterman MA, Barton IP, Cohen SB, Bensen WG. Upper gastrointestinal tract safety of daily oral risedronate in patients taking NSAIDs: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc. 2005 Oct;80(10):1278-85. doi: 10.4065/80.10.1278.
- Vaysbrot EE, Osani MC, Musetti MC, McAlindon TE, Bannuru RR. Are bisphosphonates efficacious in knee osteoarthritis? A meta-analysis of randomized controlled trials. Osteoarthritis Cartilage. 2018 Feb;26(2):154-164. doi: 10.1016/j.joca.2017.11.013. Epub 2017 Dec 6.
- Kuttapitiya A, Assi L, Laing K, Hing C, Mitchell P, Whitley G, Harrison A, Howe FA, Ejindu V, Heron C, Sofat N. Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation. Ann Rheum Dis. 2017 Oct;76(10):1764-1773. doi: 10.1136/annrheumdis-2017-211396. Epub 2017 Jul 13.
- Cai G, Aitken D, Laslett LL, Pelletier JP, Martel-Pelletier J, Hill C, March L, Wluka AE, Wang Y, Antony B, Blizzard L, Winzenberg T, Cicuttini F, Jones G. Effect of Intravenous Zoledronic Acid on Tibiofemoral Cartilage Volume Among Patients With Knee Osteoarthritis With Bone Marrow Lesions: A Randomized Clinical Trial. JAMA. 2020 Apr 21;323(15):1456-1466. doi: 10.1001/jama.2020.2938.
- Aitken D, Laslett LL, Cai G, Hill C, March L, Wluka AE, Wang Y, Blizzard L, Cicuttini F, Jones G. A protocol for a multicentre, randomised, double-blind, placebo-controlled trial to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change and knee pain over 24 months in knee osteoarthritis patients - ZAP2. BMC Musculoskelet Disord. 2018 Jul 18;19(1):217. doi: 10.1186/s12891-018-2143-2.
- Davis AM, Kennedy D, Wong R, Robarts S, Skou ST, McGlasson R, Li LC, Roos E. Cross-cultural adaptation and implementation of Good Life with osteoarthritis in Denmark (GLA:D): group education and exercise for hip and knee osteoarthritis is feasible in Canada. Osteoarthritis Cartilage. 2018 Feb;26(2):211-219. doi: 10.1016/j.joca.2017.11.005. Epub 2017 Nov 13.
- Maetzel A, Li LC, Pencharz J, Tomlinson G, Bombardier C; Community Hypertension and Arthritis Project Study Team. The economic burden associated with osteoarthritis, rheumatoid arthritis, and hypertension: a comparative study. Ann Rheum Dis. 2004 Apr;63(4):395-401. doi: 10.1136/ard.2003.006031.
- Burt LA, Liang Z, Sajobi TT, Hanley DA, Boyd SK. Sex- and Site-Specific Normative Data Curves for HR-pQCT. J Bone Miner Res. 2016 Nov;31(11):2041-2047. doi: 10.1002/jbmr.2873. Epub 2016 Jun 9.
- Campbell GM, Buie HR, Boyd SK. Signs of irreversible architectural changes occur early in the development of experimental osteoporosis as assessed by in vivo micro-CT. Osteoporos Int. 2008 Oct;19(10):1409-19. doi: 10.1007/s00198-008-0581-7. Epub 2008 Mar 29.
- Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, Engelke K, Bouxsein ML. Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int. 2020 Sep;31(9):1607-1627. doi: 10.1007/s00198-020-05438-5. Epub 2020 May 26.
- Mattap SM, Aitken D, Wills K, Laslett L, Ding C, Pelletier JP, Martel-Pelletier J, Graves SE, Lorimer M, Cicuttini F, Jones G. How Do MRI-Detected Subchondral Bone Marrow Lesions (BMLs) on Two Different MRI Sequences Correlate with Clinically Important Outcomes? Calcif Tissue Int. 2018 Aug;103(2):131-143. doi: 10.1007/s00223-018-0402-8. Epub 2018 Feb 13.
- Kroker A, Zhu Y, Manske SL, Barber R, Mohtadi N, Boyd SK. Quantitative in vivo assessment of bone microarchitecture in the human knee using HR-pQCT. Bone. 2017 Apr;97:43-48. doi: 10.1016/j.bone.2016.12.015. Epub 2016 Dec 27.
- Compston J. Pathophysiology of atypical femoral fractures and osteonecrosis of the jaw. Osteoporos Int. 2011 Dec;22(12):2951-61. doi: 10.1007/s00198-011-1804-x. Epub 2011 Oct 14. Erratum In: Osteoporos Int. 2012 Feb;23(2):793.
- Mohtadi N. Development and validation of the quality of life outcome measure (questionnaire) for chronic anterior cruciate ligament deficiency. Am J Sports Med. 1998 May-Jun;26(3):350-9. doi: 10.1177/03635465980260030201.
- Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. 2007 Oct;41(4):505-15. doi: 10.1016/j.bone.2007.07.007. Epub 2007 Jul 18.
- Kemp TD, de Bakker CMJ, Gabel L, Hanley DA, Billington EO, Burt LA, Boyd SK. Longitudinal bone microarchitectural changes are best detected using image registration. Osteoporos Int. 2020 Oct;31(10):1995-2005. doi: 10.1007/s00198-020-05449-2. Epub 2020 May 19.
- Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat JB, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. 2014 Jun;63:147-57. doi: 10.1016/j.bone.2014.03.001. Epub 2014 Mar 12.
- Arias-Moreno AJ, Hosseini HS, Bevers M, Ito K, Zysset P, van Rietbergen B. Validation of distal radius failure load predictions by homogenized- and micro-finite element analyses based on second-generation high-resolution peripheral quantitative CT images. Osteoporos Int. 2019 Jul;30(7):1433-1443. doi: 10.1007/s00198-019-04935-6. Epub 2019 Apr 17.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- REB21-1109
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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