Clinical trial NCT04498715: Trochanteric Femur Fracture Operated With Dynamic Hip Screw System (DHS) Augmented With a Biphasic Apatite Sulphate Combined With Systemic or Local Bisphosphonate
Official title: An Open-labelled Pilot Study to Evaluate Dynamic Hip Screw System (DHS) Augmented With a Biphasic Apatite Sulphate Combined With Systemic or Local Bisphosphonate for Trochanteric Femur Fracture
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Trochanteric Fracture of Femur
Keywords: Dynamic hip screw (DHS)
Biphasic apatite sulphate ceramic
bisphosphonate-zoledronic acid
Lead sponsor: Lithuanian University of Health Sciences
Sponsor class: OTHER
Collaborators: name: Lund University Hospital
First posted: 2020-08-04
Enrollment: 20
Sex: ALL
Minimum age (years): 65
Maximum age (years): 90
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to study the process of bone regeneration around a metal device in the femoral neck canal using a synthetic bone substitute Cerament bone void filler (BVF) and bisphosphonate (Zometa) locally or systemically that affects bone metabolism. Furthermore, fracture healing and implant migration will be investigated.

Detailed description: Osteoporosis associated fragility fractures in the elderly are a societal and financial burden in the western world and this burden has also started to affect developing nations. With the aging of the world's population, the age quake, hip fractures are expected to reach 2.6 million by the year 2025, and between 4.5 to 6.3 million by the year 2050. The mortality rate at 30 days after sustaining a hip fracture is up to 10%, and at one year 35% after the fracture. It is further known that almost half of the survivors are unable to reach their previous functional levels, partly related to the surgical treatment and fixation failure.

One fifth of all fragility fractures is in the hip with an almost equal ratio in in the cervical and trochanteric regions. Hip arthroplasty and internal fixation are the two most common treatment options for cervical and trochanteric femoral fractures. Healthier patients with long life expectancy have better functional recovery and lower mortality when internal fixation is used. However, dynamic hip screws (DHS) and intramedullary nails and screws are associated with high failure rates, particularly in unstable trochanteric fractures. Osteosynthesis cutout, with penetration of the cervical screw through the femoral head, preceded by a neck-shaft varus tilting, is the most common reason of failure, reported in up to 10% in trochanteric fractures, and in about 5% of neck fractures. In addition, reoperations have been reported to be as high as 30%, where treatment of dislocated femoral neck fracture with internal fixation fails and subsequently gets revised with total hip arthroplasty (THA). It is well established that salvage THA following hip fractures has significantly higher risk of complications compared to primary THA. The tip-apex distance has been defined as a strong predictor of screw cutout, while recent studies question its relevance. The bone quality, i.e. the degree of osteoporosis, on the other hand is associated with failures.\[4\] Despite the increase in clinical awareness; adoption of secondary prevention using bisphosphonates is still low, partly due to low patient adherence. Besides, even if included in a dual-energy X-ray absorptiometry surveillance program, there is a delayed response to bisphosphonate treatment, which has been deemed critical, during the first one and half years. Augmentation increasing mechanical strength of cancellous bone in osteoporotic hip fractures may lower the burden of revision, which may outweigh the related additional cost. Before the operation, deciding in whom to augment is a challenge A pilot study by Sirka et al. indicated that local delivery of a bisphosphonate, zoledronic acid (ZA), using the calcium sulphate/hydroxyapatite(CaS/HA) biomaterial enhanced bone formation in the femoral neck canal of severely osteoporotic rats. Moreover, recently, Raina et al. confirmed the findings also in a screw implant-integration model in rats. Whether these studies will show a similar potential in the clinical scenarios is a matter of speculation; however, they do provide novel methods for augmenting bone quality in osteoporosis as well as improving screw fixation. It is however important to mention that local delivery of ZA has a profound effect on cancellous bone regeneration in healthy as well as osteoporotic while the effect on cortical bone is minimal. A finite element modeling study by Kok et al. used computer simulations to predict the effect of CaS/HA augmentation in the form of injections into the human femoral heads/femoral neck canal and indicated enhanced mechanical properties by up to 25% which were dependent on volume and location of the injection. In a limited one-year follow up study, the use of an injectable ceramic applied in the trochanteric fracture bone void has been shown to lead to adequate fracture healing with minimal DHS screw migration Preliminary data from biomechanical studies in osteoporotic sawbones and donated human osteoporotic femoral heads indicates that using a biphasic apatite/sulphate material for reinforcing a fragile bone will result in an increase strength of the fixation of a fracture device inserted in the proximal femoral canal.(in house on file It is reasonable to argue that patients with high fracture and low mortality risks would benefit from an augmentation procedure far more than the ones with low fracture and high mortality risks. In a recent study, by combining the well-established fracture risk assessment tool (FRAX) and the Sernbo score to form a fracture and mortality risk evaluation (FAME) Index, one fifth of the patients could be identified as a cohort, with high risk of subsequent fracture but low risk of mortality. This group could theoretically benefit from cancellous bone augmentation during internal fixation of a fragility hip fracture. By utilizing a simple form, the FAME Index was successfully applied in the acute setting before the operation, during history taking by well-informed medical staff in less than 10 minutes.

Eligibility criteria: Inclusion Criteria:

* Patients 65-90 years of age;
* Fame classification with low mortality and high fracture risk.
* Unilateral proximal hip fracture ((AO Foundation/Orthopaedic Trauma Association (AO/OTA): A1 and A2)) caused by low energy trauma (physical condition eligible for surgery with dynamic hip screw);
* Patient with a communicative ability to understand the procedure and participate in the study and the follow-up program.

Exclusion Criteria:

* Previous hip or pelvic fractures on the same side,
* Concurrent oral treatment with corticosteroids, and/or osteoporosis medication
* Irreversible coagulopathy or bleeding disorder. Note regarding reversible coagulopathies: Patients on coumadin or other anticoagulants may participate. Investigators should follow routine practices for perioperative discontinuation and re-initiation of anticoagulants;
* Concurrent dialysis or elevated creatinine
* Hypo or hyper calcaemia
* Active treatment due to malignancy including ongoing or completed radiotherapy involving the pelvis/hip area,
* Fractures involving acetabulum
* Active systemic infection or local skin infection at the incision site
* Known hyperthyroidism or thyroid adenoma,
* History of serious reaction to iodine based radio contrast agents

Primary outcomes:
measure: Change of bone density and remodeling around the head of dynamic screw
timeFrame: 1.5, 3, 6 months
Secondary outcomes:
measure: Change of Harris Hip Score (HHS) in different group patients
timeFrame: 1.5, 3 and 6 months
measure: Change of the Screw migration by X-ray
timeFrame: 1.5, 3 and 6 months
Other outcomes:
Locations:
city: Kaunas
country: Lithuania
facility: Hospital of Lithuanian University of Health Sciences Kaunas Clinics
Study officials:
affiliation: Lithuanian University of Health Sciences
name: Sarunas Tarasevicius, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Raina DB, Markeviciute V, Stravinskas M, Kok J, Jacobson I, Liu Y, Sezgin EA, Isaksson H, Zwingenberger S, Tagil M, Tarasevicius S, Lidgren L. A New Augmentation Method for Improved Screw Fixation in Fragile Bone. Front Bioeng Biotechnol. 2022 Mar 2;10:816250. doi: 10.3389/fbioe.2022.816250. eCollection 2022.