Cystic Fibrosis, Osteoporosis
Conditions
Keywords
cystic fibrosis, children, adolescents, low bone mass, osteoporosis, alendronate, fractures
Brief summary
Cystic fibrosis (CF) -- an autosomal recessive genetic disease affecting about 60,000 individuals worldwide, including about 3,800 in Italy -- is often associated with low bone mineral mass. The current aggressive therapies have ensured a much longer survival of CF patients but this has led to a higher frequency of osteoporosis and bone fractures, a serious problem which not only affects quality of life, but also hinders further therapeutic measures. The aim of this study, conducted on a large group of children, adolescents and young adults with CF, has been the evaluation of bone mass changes after 1 year of a simple treatment with RDA-adjusted dietary calcium plus 25-OH vitamin D supplementation, and the feasibility and efficacy of alendronate treatment (for another year) in patients not responding to calcium + 25-OH vitamin D alone.
Detailed description
The study included 2 phases. Phase 1 (1-year open-label observational study): following baseline evaluation, bone mass changes have been studied with a simple therapy of adequate calcium intake and 25-OH vitamin D supplements in all eligible subjects (N=171). Phase 2 (1-year double-blind, randomized, placebo-controlled, parallel group study): the 128 subjects showing an insufficient response to calcium + 25-OH vitamin D alone (bone mass increase \<5%) at the end of Phase 1, were randomized into 2 groups and assigned to alendronate treatment (N=65) or placebo (N=63) (in addition to calcium and 25-OH vitamin D as during Phase 1). The study has been carried out by the Coordinator's Institution (Istituto Auxologico Italiano)in collaboration with most Regional Reference Centers for CF in Italy.
Interventions
DRUGAlendronate
As active drug, we used Alendros (Abiogen Pharma, Pisa, Italy), distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).
DRUGPlacebo
Placebo was distributed to the patients in plain bottles and boxes (bearing only the center and patient codes).
Sponsors
Fondazione Telethon
Istituto Auxologico Italiano
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* age 2-30 years * clinically stable condition * regular menses in females * low Bone Mineral Apparent Density for age (defined as BMAD Z-score ≤-2.0 if age ≤18 years or ≤-2.5 if age \>18 years).
Exclusion criteria
* two or more episodes of hypercalcemia and/or hypercalciuria * contraindications to 25-OH vitamin D or alendronate treatment * recent transplantation * other diseases or medications (glucocorticoids excepted) associated with bone loss.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone mineral density increase at lumbar spine. | up to 24 months | Bone mineral density evaluated by DXA. Bone mineral apparent density calculated to correct for bone size (growing subjects). Z-score calculated. Measurements: Phase 1 (171 subjects): Baseline, 6 months, 12 months. Phase 2 (128 subjects, randomized to 2 arms: placebo or alendronate): 18 months, 24 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in bone turnover markers. | baseline and up to 24 months | Bone turnover markers: (serum) osteocalcin (OC), bone specific alkaline phosphatase (BSAP), C-terminal telopeptide of procollagen 1 (CTx); (urine) terminal telopeptide of procollagen 1 (NTx). |
| Fracture rate. | at 12th and 24th month | Appendicular fractures were evaluated at baseline (previous fractures) and throughout the 2 years of study (incident fractures) with X-rays. Vertebral fractures were evaluated at the end of Phase 1 (12th month) and at the end of Phase 2 (24th month) with lateral thoracic and lumbar spine X-rays. |
| Adverse effects of alendronate. | continuously throughout Phase 2 (2nd year of study) | Evaluated on the basis of lab tests (calcemia, calciuria, blood cell count, liver and kidney function), FEV1 changes, and other signs/symptoms (e.g. pain, fever, etc.) |
Countries
Holy See, Italy
Outcome results
None listed