Teriparatide and fracture healing

Alshaikh, Adel (2020) Teriparatide and fracture healing. PhD thesis, University of Nottingham.

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Abstract

Background: Ankle fractures are common injuries especially in the elderly that can cause morbidity. There is some evidence that Teriparatide, a drug used to treat osteoporosis, may accelerate fracture healing. To test any drug for its effect on fracture healing it is essential to assess fracture healing objectively. However, there is no optimum method for assessment of fracture healing, nor are there radiographic gold standard parameters of fracture healing.

Aims: 1-To determine if and how Teriparatide is being used by physicians to accelerate fracture healing. 2-To conduct a feasibility study in order to plan a possible future randomised control trial comparing the effect of Teriparatide treatment versus standard care on the healing of Weber B ankle fractures managed conservatively in older people.

Methods: A survey of physicians was carried out in the Kingdom of Bahrain, United Kingdom and United Arab Emirates from April 2016 to April 2017. A feasibility study of ankle fracture healing was carried out between 11th of Nov 2016 to 31st of April 2018 at Queen’s Medical Centre, Nottingham. A total of 10 participants aged 50 years and above with ankle Weber B fractures managed conservatively were recruited. Five participants were randomised into a standard care group and five participants into a Teriparatide group and followed up every 2 weeks with CT scans for a total of 12 weeks. A fracture healing score table was developed using parameters from the ankle CT scans. MatlabTM and ImageJTM software were used to quantify changes in trabecular bone region, mineralised callus and cortical bone. Patient reported outcome measures (PROMs) were recorded using Olerud Molander questionnaire for assessment of ankle function and quality of life EQ-5D-5L health status questionnaire. Additionally, an in-depth qualitative assessment of participants’ experiences in the study was carried out on the last trial visit.

Results: Of the 104 included physicians responses, 45.2% (n=47) prescribed Teriparatide, of which six prescribed it to accelerate fracture healing. The reported barriers for Teriparatide usage were: the high cost of the drug as reported in 63%(n=30); the fact that indication was off label in 36% (n=17); because the drug was only available in injection form in 19.1% (n=17). In the feasibility study, out of 81 patients screened ten participants were recruited and randomised 5 into standard care group and 5 into Teriparatide treatment group. All the ten participants completed the seven study visits without any reported drug side effects (n=5). The CT scan fracture healing score Kappa values (95% CI and P values), showed poor to moderate agreement with the percentage of agreement in the range of 34% to 78%. Internal consistency (Cronbach’s alpha) for ankle fracture healing score table for rater AA was 0.804 and for rater WAW was 0.874. In the qualitative study participants were positive about participating in the study, but had some concerns about radiation exposure and the number of trial visits, which necessitated additional travel visits to the hospital.

Conclusion: Teriparatide is being used as an off-label prescription for acceleration of fracture healing. The cost of the drug, its off-label indication and its use in an injection form are the most common barriers for prescribing the drug. This feasibility study provides some evidence for supporting a future randomised clinical trial. However, for such a study to recruit enough patients to have statistical power, it would need to be a multicentre study with improvements in the method used for CT fracture scoring. The qualitative study provided information on the perspectives of the participants participating in the study, with recommendation to reduce the number of CT scans and thus hospital visits.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Scammell, Brigitte
Wallace, Angus
Pearson, Richard
Keywords: Teriparatide, Fracture, Ankle, CT scan, Matlab, ImageJ, PROMS, Qualitative study, Fracture healing parameters, Randomised control trial, Survey Ankle fractures
Subjects: W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 63919
Depositing User: Alshaikh, Adel
Date Deposited: 04 Feb 2021 14:31
Last Modified: 04 Feb 2021 14:31
URI: http://eprints.nottingham.ac.uk/id/eprint/63919

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