Fracture (FX) Improvement With Teriparatide: FiX-IT Study (FiX-IT)

This open label comparison study examines the hypothesis that teriparatide given immediately following repair of an atypical subtrochanteric or diaphyseal femoral shaft fracture will enhance healing and improve bone mineral density compared to delayed treatment (after six months) with teriparatide or no treatment with teriparatide (patients who refuse therapy or for whom teriparatide is contraindicated). Patients with up-front teriparatide in addition will have greater quality of life measures and less pain compared to those with delayed or no therapy.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Atypical Femoral Fracture
• Intervention / Treatment: Drug: teriparatide

Detailed Description

Up to 24 postmenopausal women with osteoporosis who have been on bisphosphonate therapy for one year or more at any point prior to fracture and have sustained an atypical subtrochanteric or diaphyseal fracture will be enrolled. Subjects randomized to the two intervention arms will self-administer a daily SQ injection of the study medication for 12 months. The primary objective is to demonstrate greater radiologic evidence of healing at 10 weeks in patients on immediate teriparatide compared to those on delayed teriparatide who receive therapy six months after fracture. Secondary end points include (1) radiologic healing at 2, 6, 24, and 46 weeks; (2) increased bone density at 6 and 12 months as assessed by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, and femoral neck; (3) quality of life improvements at 10 weeks and 6 months as assessed by quality of life questionnaire and pain score; and (4) differences in biochemical markers of bone turnover in patient with upfront therapy compared to patients with delayed therapy and patients who refuse therapy or for whom teriparatide is contraindicated.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh, Osteoporosis Prevention & Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• postmenopausal women
• with osteoporosis who have been on bisphosphonate therapy for one year or more (all bisphosphonates will be included such as alendronate, risdedronate, ibandronate, or zoledronic acid).
• Patients will also be included if they are on glucocorticoids or other medications known to affect bone mineral metabolism as these are often found in patients with these types of fractures.
• sustain an atypical subtrochanteric or diaphyseal femoral shaft fracture as defined by the the 2010 ASBMR task force. An atypical fracture must include all of the following: (1) a location in the femur distal to lesser trochanter; (2) no trauma or minimal trauma as a fall; (3) transverse or short oblique configuration; (4) noncomminuted; and (5) complete fracture extends through both cortices and may be associated with a medial spike; incomplete fractures involve only the lateral cortex. Patients who have an incomplete fracture can be included if they fall into the 2010 ASBMR task force definition.

Exclusion Criteria:

• men
• children
• those who have had radiation therapy
• Paget's disease
• treatment with teriparatide for two year in the past
• metastatic bone disease
• active cancer
• hypercalcemia
• hyperparathyroidism
• metabolic disease other than osteoporosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immediate teriparatide; Open label teriparatide given immediately following surgical repair of fracture	Drug: teriparatide; 20 microgram once-daily subcutaneous injection; Other Names: Forteo
Experimental: Delayed teriparatide; Open label teriparatide given six months following surgical repair of fracture	Drug: teriparatide; 20 microgram once-daily subcutaneous injection; Other Names: Forteo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiologic Evidence of Bone Healing	The radiologic indices of fracture healing included (1) cortical continuity on two of four cortices, (2) persistence of alignment, (3) decreased conspicuity of fracture line, and (4) increased callus formation. For each of these indices, healing was graded on a scale of 1 to 4 with 1 = no change (less than 25%), 2 = minimum healing (25-50%), 3 = moderate healing (50-75%), and 4 = complete healing (greater than 75%). A composite score was calculated by summing the subscale scores for the 4 indices. Composite score scale ranged from 4 to 16 with higher scores indicating more complete healing. The primary grading was performed by a radiologist with expertise in musculoskeletal radiology, then independently repeated by a second radiologist, both of whom were blinded to the study allocation.	6, 12 months of treatment
Radiologic Evidence of Healing	Number of participants with persistence of alignment as determined by a radiologist.	at 10 weeks for immediate teriparatide group

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiologic Healing		at 2, 6, 24, and 48 weeks
Increased Bone Density	Percent change in Bone Mineral Density (BMD) as assessed by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, distal 1/3 radius, and femoral neck	at 6 and 12 months
Quality of Life Improvements	Assessed by quality of life questionnaire (SF-36). There are 8 subscales each ranging from 0-100 with higher scores indicating better quality of life.	at 12 months
Difference in Biochemical Markers of Bone Turnover	upfront therapy group compared to delayed therapy group and no therapy group	intervals over 12-18 months depending on treatment group

Collaborators and Investigators

• Sponsor: Susan L. Greenspan
• Collaborators: Eli Lilly and Company; University of Pittsburgh
• Investigators: Principal Investigator: Susan L. Greenspan, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: October 9, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 12, 2012

Study Record Updates

• Last Update Posted (Actual): December 12, 2017
• Last Update Submitted That Met QC Criteria: November 6, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: osteoporosis; postmenopausal women; bone loss; atypical femoral fractures; prior bisphosphonate treatment
• Additional Relevant MeSH Terms: Metabolic Diseases; Wounds and Injuries; Leg Injuries; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Femoral Fractures; Fractures, Bone; Osteoporosis; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Teriparatide
• Other Study ID Numbers: PRO12040560 (FiX-IT)