Increased Growth after Long-Term Oral 1α,25-Vitamin D₃in Childhood Renal Osteodystrophy

Abstract

We evaluated oral 1,25-vitamin D3 for as long as 26 months in six prepubescent children with renal osteodystrophy previously treated with vitamin D2. Therapy was given at 14 to 41 ng per kilogram per day to correct hypocalcemia and reverse bone disease. Serum levels of 1,25-vitamin D3 were initially reduced at 15 +/- 5 pg per milliliter (mean +/- S.E.M.) and after treatment rose to 54 +/- 13. Serum calcium rose from 7.5 +/- 1.6 mg per deciliter (mean +/- S.D.) to 9.8 +/- 0.6 after one month (P less than 0.02). Alkaline phosphatase activity fell from 536 +/- 298 to 208 +/- 91 IU per liter after 12 months (P less than 0.05). Serum immunoreactive parathyroid levels fell from 900 +/- 562 microliter eq per milliliter 411 +/- 377. Healing of rickets and subperiosteal erosions was found. Remineralization of bone was demonstrated by the photon absorption technic. In four patients growth velocity, evaluated for 12 months before and after therapy, increased from 2.6 +/- 0.8 to 8.0 +/- 3.2 cm per year. Growth velocity per year increased from less than third percentile in each to the 10th to 97th percentile after therapy. Height increment ranged from 27 to 113 per cent of that expected for change in chronologic age and 40 to 114 per cent expected for change in bone age after therapy. This trial demonstrates that oral 1,25-vitamin D3 can reverse renal bone disease and increase growth in uremic children.

A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

“…Whereas early case series of bone biopsy results in children on maintenance dialysis reported high-turnover bone disease (osteitis fibrosa and mild lesions of secondary hyperparathyroidism) in the vast majority of patients [8][9][10], more recent series identified adynamic bone in a substantial proportion (27-33%) of children and adolescents [11][12][13]. The implications of low bone turnover for bone structure and strength during growth are not known; however, this bone lesion is associated with increased fracture risk in adults [14] -perhaps due to impaired microfracture repair.…”

Long-Term Use of Recombinant Human Growth Hormone (rhGH) in Children with Chronic Renal Insufficiency (CRI)

“…The precise etiology for the growth retardation in children with CRI remains unknown despite 5 international symposia devoted to delineate the relationship (1)(2)(3)(4)(5). Multiple factors have been implicated including early age at onset of CRI (6), persistent fluid and electrolyte abnormalities (7), concomitant acidosis (8), inadequate nutritional (caloric) intake (9), and unresolved or progressive renal osteodystrophy (ROD) (10). Despite corrections of fluid electrolyte disturbances and acidosis, provision of optimal caloric intake and correction of ROD, growth retardation frequently persists.…”

The Skeletal Consequences of Growth Hormone Therapy in Dialyzed Children

“…In pediatric patients with CKD stages 2-4, supraphysiologic doses of recombinant growth hormone overcome growth plate resistance to growth hormone, thus increasing growth and improving final adult height (2)(3)(4); however, the response to growth hormone in patients with ESRD (CKD stage 5) varies (5)(6)(7)(8)(9). The precise mechanism behind decreased responsiveness to growth in dialysis patients is incompletely understood and is probably multifactorial, but because both high and low bone turnover increase the severity of growth retardation (10,11), alterations in trabecular bone turnover may contribute.…”