Bone Mineralization Defect
Conditions
Brief summary
The study outlined is designed to measure and to determine whether the combined use of vitamin D2 (ergocalciferoI) and 1-alpha-hydroxyvitamin D2 (doxercalciferol)) or doxercalciferol alone will correct the mineralization defect in pediatric patients with established secondary hyperparathyroidism (2°HPT) undergoing regular peritoneal dialysis. Serum phosphorus levels will be controlled with a calcium¬-free-metal free phosphate binder; (obtained at baseline and after 8 months of treatment) sevelamer. Indices of bone mineralization obtained at baseline and after 8 months of treatment will be measured by quantitative histomorphometry in iliac crest bone biopsies after double tetracycline labeling. Immunohistochemistry will be done in specimens of bone biopsies from iliac crest to examine the expression for selected markers of bone turnover and mineralization such as FGF-23, DMP1, MEPE and OPG. Serum PTH levels will be measured with the 1st and 2nd generation immunometric assay (PTH-IMAs) and fibroblast growth factor-23 (FGF-23) will be determined by one assay with specific detection antibodies that are against epitopes within the C-terminus of FGF-23 and another assay that uses antibodies against epitopes within the N- and C-terminal portions of the molecule respectively. The value of non-invasive assessment of bone mass by quantitative computed tomography (QCT) and its relationship with vascular disease determined by ultrasound (US) of intimal carotid thickness (CIMT) will be correlated with bone histomorphometry and the different biochemical determinations.
Interventions
DRUGVitamin D2
These patients will receive standard of care vitamin D 1,25 therapy with intervention of vitamin D2
Sponsors
Children's Hospital Los Angeles
Loma Linda University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* medically stable patients * 6-21 years old * undergoing treatment with continuous cycling peritoneal dialysis * evidence of mineralization defect and secondary hyperparathyroidism
Exclusion criteria
* histopathological lesion of bone such as adynamic bone or osteomalacia * poor compliance * current treatment with prednisone or other immunosuppressives * treatment with human recombinant growth hormone * parathyroidectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement of bone mineralization defect demonstrated by bone histomorphometry | 8 months | Iliac crest bone biopsy pre and post treatment with vitamin D2 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic improvement of skeletal abnormalities associated with renal osteodystrophy | 8 months | We will compare skeletal lesions identified through radiographic studies with bone histomorphometry pre and post treatment with vitamin D2 |
Countries
United States
Contacts
Primary ContactIsidro Salusky, MD
Outcome results
None listed