The Skeletal Consequences of Growth Hormone Therapy in Dialyzed Children

Abstract

SummaryBackground and objective The effects of recombinant human growth hormone on renal osteodystrophy are unknown; thus, the effects of growth hormone (GH) on bone histomorphometry were assessed in pediatric patients with ESRD.Design, setting, participants, & measurements Thirty-three patients who underwent bone biopsy between July 1994 and May 1999 were randomly assigned to therapy with or without GH. Patients were stratified by bone formation rate; all patients with high bone turnover received intraperitoneal calcitriol. Serum biochemical values were obtained monthly, and bone biopsy was repeated after 8 months.Results Median patient age was 11.7 years (interquartile range [IQR], 7.6, 14.1 years); 45% of patients were male, and 52% were prepubertal. Median dialysis duration was 0.4 (IQR, 0.3, 0.8) year. Bone formation rate per bone surface increased from 15.0 (9.6, 21.8) to 154.6 (23.7, 174.3) mm 2 /mm 3 per year (P=0.05) in patients with low bone turnover treated with GH, decreased from 103.3 (57.0, 173.4) to 60.3 (20.3, 13.7) mm 2 /mm 3 per year in patients with high bone turnover receiving standard therapy (P=0.03), and was unchanged in the other two groups. Bone formation rates were higher with GH, irrespective of underlying bone histologic features (P=0.05). Parathyroid hormone did not differ between groups. GH therapy resulted in greater increases in height SD scores (estimated mean difference in change 6 SD, 0.32460.076; P,0.001), irrespective of underlying bone histologic features.Conclusions GH therapy improves height in pediatric dialysis patients, irrespective of underlying bone histologic features. Bone formation rates are higher in GH recipients, and GH therapy alters the relationship between circulating parathyroid hormone values and bone turnover.

Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry

“…Although this finding is promising, an R 2 of 0.38 for the model as a whole -including mCT measures of bone volume, bone mineralization, serum calcium, and serum PTH levels-suggests that these factors together predict 38% of the variation in osteoid volume, leaving another 62% of the variation unrelated to these factors. Dialysis vintage may also affect bone structure and composition, and certain treatments, including vitamin D sterols (21) and growth hormone therapy (23), have been shown to disrupt the relationship between bone turnover and PTH. In this study of patients who were relatively new to dialysis, the addition of the presence of active vitamin D sterol therapy to the model did not improve prediction of osteoid accumulation.…”

Clinical practice recommendations for growth hormone treatment in children with chronic kidney disease

“…However, the response to GH can be markedly improved by augmenting dialytic clearance with daily haemodialfiltration 55,56 . GH therapy also increases height in paediatric patients on dialysis irrespective of underlying bone histological features; bone formation rates are also higher in GH-treated patients than in controls owing to its osteoanabolic effects 57 . Although, renal transplantation does not uniformly result in catch-up growth in paediatric patients previously treated with GH, transplantation should not be withheld in these patients.…”

“…The GH dosage used in the available RCTs and observational studies was 28-30 international units (IU)/m 2 per week (equivalent to 0.045-0.05 mg/kg per day) by daily subcutaneous injections ( Supplementary Tables 2-4). Twelve RCTs compared this dosage to placebo or no treatment 28,48,57,68,[76][77][78][79][80][81][82][83] 18 cm per year (95% CI 0.52-1.84) higher increase in height velocity and a 1.48 higher (95% CI 0.03-2.93) height velocity SDS after 1 year of treatment 47 . The one study that compared 28 IU/m 2 per week with 56 IU/m 2 per week reported no significant difference between the groups in the change in mean height SDS and mean height velocity.…”

“…Aggravation of secondary hyperparathyroidism has been reported as an occasional complication of GH therapy. GH might have a direct stimulatory effect on the parathyroid gland or might have subtle effects on calcium and phosphate homeostasis, which in turn stimulate PTH secretion 57,74 . In addition, increased longitudinal bone growth by GH treatment might unmask pre-existing renal osteodystrophy 57 .…”

Ovariectomy-Induced Osteopenia Influences the Middle and Late Periods of Bone Healing in a Mouse Femoral Osteotomy Model

“…It is known that bone healing was delayed in the presence of osteoporosis in humans 10,11 . However, due to the complexities of the healing of osteoporotic fractures, animal osteoporotic / osteopenic models may be more appropriate to study the effects of osteoporosis in more details and to test drugs on the fracture repair process 12 .…”