Cystic Fibrosis Related Bone Disease: the Role of CFTR

Ivacaftor, a CFTR potentiator, has recently been FDA approved for the treatment of cystic
fibrosis in patients with at least one G551D CFTR mutation. Given the possible role of CFTR
in bone, we hypothesize that this medication may also improve bone health in CF patients. The
purpose of this study is to test this hypothesis using high resolution peripheral
quantitative computed tomography, a research tool that measures bone micro-architecture and
volumetric bone density and has the ability to detect small changes in bone that might
otherwise be missed with standard bone imaging techniques such as bone density testing.

COHORT 1

Inclusion Criteria:

- Age 6 to 75 years old

- Established diagnosis of CF with at least one abnormal G551D-CFTR allele

- Eligibility for and intent to start treatment with ivacaftor or started treatment with
ivacaftor within previous 6 months

Exclusion Criteria:

- Psychiatric or mental incapacity that would preclude subject from assenting to study
participation

- Current pregnancy

- History of organ transplantation

- History of Burkholderia dolosa infection

COHORT 2:

Subjects will be grouped by gender, age and race to match subjects in Cohort 1 within two
years. Pubertal subjects will be matched by Tanner stage.

Inclusion Criteria:

- Age 6 to 75 years old

- Established diagnosis of CF

Exclusion Criteria:

- Psychiatric or mental incapacity that would preclude subject from assenting to study
participation

- Current pregnancy

- History of organ transplantation

- History of Burkholderia dolosa infection

COHORT 3:

Subjects will be grouped by gender, age and race to match subjects in Cohort 2 within two
years. Pubertal subjects will be matched by Tanner stage.

Inclusion criteria:

- Age 6 to 75 years old

- Clinically stable, deemed able to complete the screening, baseline, and scheduled
study visits.

Exclusion criteria:

- History of significant cardiac, renal, pulmonary, hepatic, or malignant disease,
current alcohol or illicit drug abuse, or major psychiatric disorder

- Current diagnoses known to affect bone metabolism, including cystic fibrosis,
osteoporosis, amenorrhea >3 months (in menstruating women who are not taking oral
contraceptives or have an IUD), hyperthyroidism, diabetes, hyperparathyroidism,
Paget's disease, kidney stones, chronic inflammatory diseases, malabsorptive
disorders, malnutrition, prolonged immobility, and skeletal dysplasias

- History of a non-digital fracture in the previous 6 months, history of one pathologic
fracture, or greater than four total lifetime non-digital fractures

- Cumulative lifetime use of oral glucocorticoids for greater than 2 months

- Current or prior use of medications known to affect bone metabolism including hormone
replacement therapy, anti-estrogens, bisphosphonates, calcitonin, fluoride, lithium,
suppressive doses of levothyroxine, or anticonvulsants.

- Pregnancy

- BMI less than 18.5 or greater than 30 kg/m2 in subjects 18 years and older, or BMI
less than 5th or greater than 95th percentile in subjects under the age of 18 years.

- Any medical or psychiatric condition or situation that would compromise subject
safety, informed consent/assent, treatment compliance, follow-up measurements, or data
quality