Fractures and Bisphosphonates: does osteoporosis treatment affect fracture healing?

ISRCTN	ISRCTN62133820
DOI	https://doi.org/10.1186/ISRCTN62133820
Protocol serial number	19403
Sponsor	University of Edinburgh (UK)
Funder	Arthritis Research UK (UK) (ref no 19403)

Submission date: 16/05/2011
Registration date: 22/06/2011
Last edited: 12/04/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Stuart Ralston
Scientific

University of Edinburgh
Institute of Genetics & Molecular Medicine
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom

Study information

Primary study design	Interventional
Study design	Double-blind randomised controlled multicentre study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Fractures and Bisphosphonates: a double-blind, randomised controlled trial on the effect of alendronic acid on healing and clinical outcomes in wrist fractures
Study acronym	FaB
Study objectives	Bisphosphonates are widely used in the treatment of osteoporosis. Although fractures often occur in patients with osteoporosis who are on bisphosphonate therapy, the effects of bisphosphonates on fracture healing have not been adequately studied in humans. Sometimes bisphosphonates are withheld because of the theoretical concern about an adverse effect on fracture healing, but sometimes bisphosphonate therapy is continued. It remains unclear whether early treatment might be advantageous or deleterious to fracture healing and clinical outcome. This study will investigate the effect of alendronic acid on radiological fracture healing in the context of a randomised placebo controlled trial. Patients aged 50 and over who have fractured their wrist and are not on bisphosphonate therapy will be invited to take part in the study.
Ethics approval(s)	Fife and Forth Valley REC, 03/08/2011
Health condition(s) or problem(s) studied	Fracture healing
Intervention	Participants are allocated to receive either 70mg alendronic acid or placebo once-weekly for 24 weeks. It will be compared against a matched placebo. Participants will take study medication for 24 weeks
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Alendronic acid
Primary outcome measure(s)	1. Comparing the fracture healing between both arms at 4 weeks using X-rays 2. Fractures will be defined as healed when the following features are present: 2.1. Bridging of three out of four cortices 2.2. Radiographic evidence of endosteal healing 2.3. Organised trabecular bridging 3. Also, a time to event analysis will also be performed to evaluate the trajectory of fracture healing from radiographs taken at 2, 4, 6 and 8 weeks
Key secondary outcome measure(s)	1. Upper limb function will be assessed by using the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Measure 2. The DASH is a validated 30-item questionnaire which has previously been shown to detect changes of disability over time after injury or surgery in patients with upper-extremity musculoskeletal disorders 3. The effect of alendronate on the DASH score during the trial will be measured by comparing the change in DASH score from initial fracture to each timepoint (baseline, 2, 4, 6, 8 and 26 weeks) for both treatment groups 4. Complex Regional Pain Syndrome type I will be assessed at weeks 6 and 26 using the clinical Budapest Criteria 5. Pain will be assessed using an 11 point (0-10) Numeric Rating Scale (NRS) and by recording the amount of analgesia used in the 24 hours prior to questioning 6. Participants will be asked rank their pain from 0 (no pain) to 10 (worst pain imaginable) 7. The difference in pain and analgesia use at baseline, weeks 2, 4, 6, 8, and 26 will be compared between both treatment groups 8. Active range of movement (AROM) and grip strength of both the affected and unaffected hand will be measured at weeks 8 and 26, using a goniometer and hand dynamometer respectively 9. The differences between the range of movement and grip strength in each hand will be used to compare the two treatment groups
Completion date	29/09/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	500
Total final enrolment	421
Key inclusion criteria	Current inclusion criteria as of 19/09/2012: 1. Patients (male and female) aged 50 years and over 2. Patients must have suffered a distal radial fracture confirmed by X-ray radiograph 3. The distal radial fracture must be: 3.1. Unilateral extra-articular or minimal articular 3.2. Displaced or un-displaced 3.3. Treated with cast/splint, external fixation or open reduction and internal fixation 4. Patients willing and able to consent and comply with study protocol Previous inclusion criteria until 19/09/2012: 3.3. Treated with cast, external fixation or open reduction and internal fixation
Key exclusion criteria	Current exclusion criteria as of 19/09/2012: 1. Any of the following: 1.1. current or previous use of zoledronic acid 1.2. current or previous use within the last 2 years of any other bisphosphonate 1.3. current or previous use within the last 6 months of strontium ranelate, calcitonin, denosumab, parathyroid hormone (PTH) or intravenous (IV), intramuscular (IM) and oral corticosteroids (inhaled corticosteroids such as asthma inhalers are acceptable) 2. Previous distal radial fracture on affected side 3. Bilateral distal radial fracture 4. Contraindications to alendronic acid, including but not limited to: 4.1. Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achlasia 4.2. Inability to stand or sit upright for at least 30 minutes 4.3. Hypersensitivity to alendronate or any of its excipients 4.4. Known hypocalcaemia 4.5. Known renal impairment 5. Women of childbearing potential not using adequate contraception 6. Pregnancy 7. The distal radial fracture is due to other pathologies e.g. Pagets Disease of Bone, metastatic bone disease etc. Previous exclusion criteria until 19/09/2012: 1. Any of the following: 1.1. Current or previous use of zoledronic acid 1.2. Current or previous use within the last 2 years of any other bisphosphonate 1.3. Current or previous use within the last 6 months of strontium ranelate, calcitonin, denosumab, parathyroid hormone (PTH) or intravenous (IV), intramuscular (IM) and oral corticosteroids (inhaled corticosteroids such as asthma inhalers are acceptable) 2. Previous distal radial fracture on affected side 3. Bilateral distal radial fracture 4. Contraindications to alendronic acid, including but not limited to: 4.1. Abnormalities of the oesophagus and other factors which delay oesophageal emptying such as stricture or achlasia 4.2. Inability to stand or sit upright for at least 30 minutes 4.3. Hypersensitivity to alendronate or any of its excipients 4.4. Hypocalcaemia at baseline (serum adjusted calcium <2.2mmol/l) 4.5. Renal impairment at baseline [estimated glomerular filtration rate (eGFR) less than 35ml/min as assessed by the Modification of Diet in Renal Disease (MDRD) formula] 5. Women of childbearing potential not using adequate contraception 6. Pregnancy
Date of first enrolment	02/04/2012
Date of final enrolment	29/09/2013

Locations

Countries of recruitment

United Kingdom
Scotland

Study participating centre

University of Edinburgh

Edinburgh
EH4 2XU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2019	12/04/2019	Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

12/04/2019: Publication reference, total final enrolment number and IPD sharing statement added.
04/04/2016: No publications found, verifying study status with principal investigator