Cystic Fibrosis Related Bone Disease: the Role of CFTR

Recruitment & Eligibility

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:

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

Primary Outcome Measures

Name	Time	Method
Bone Microarchitecture and Strength Measures of the Radius and Tibia	Baseline and 24 months	Change in cortical volumetric bone mineral density at the radius

Secondary Outcome Measures

Name	Time	Method
Bone Turnover Markers	Baseline and 24 months	Change in osteocalcin
Areal Bone Mineral Density as Measured by DXA	Baseline and 24 months	Change in PA spine bone mineral density