Growth Hormone Therapy and Bone Quality in Pediatric Osteoporosis
Condition: Osteoporosis
MeSH terms: Osteoporosis
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary objective of this study is to test the hypothesis that growth hormone,
      administered daily by subcutaneous injection for 2 years will result in a significantly
      greater BMD Z-score over optimal standard therapy.
    

Detailed description: 
      Osteoporosis is a skeletal disorder characterized by a parallel loss of bone mineral and
      matrix which results in enhanced bone fragility and an increased risk of fractures. The
      associated fractures, and the morbidity and mortality that ensue, make osteoporosis a public
      health problem of enormous proportions. Clinical and research observations strongly suggest
      that most adult osteoporosis has its roots in childhood and have identified both genetic and
      environmental factors as central to the pathogenesis of this disorder.

      Osteoporosis is not only a major public health problem in the adult population but is
      increasingly diagnosed during childhood. Most cases are secondary to chronic illnesses
      (secondary osteoporosis). In chronically ill children several factors, in addition to the
      underlying chronic illness itself, may predispose to either reduced bone mass or impairment
      of bone quality. Osteoporosis in the otherwise healthy child (primary osteoporosis) is
      generally classified as either osteogenesis imperfecta (OI) or juvenile idiopathic
      osteoporosis (JIO).

      Optimizing Vitamin D and calcium intake as well as a weight bearing exercise program are
      central approaches in the prevention and treatment of osteoporosis. Despite increased
      awareness of this disorder in the pediatric population and more active implementation of
      these principles, an ever increasing number of children with osteoporosis present with
      symptomatic disease; that is progress to the stage of frequent peripheral fractures,
      vertebral compression fracture and/or deliberating pain. Bisphosphonates are often then added
      to the therapeutic regiment. However, it is widely acknowledged that little is currently
      known about the key factors that might predict the safe and effective use of these agents in
      this population.

      Children whose bone biopsy results indicate an adynamic form of osteoporosis and who have low
      bone turnover markers make up a significant number of the children with symptomatic
      osteoporosis. Many of these patients have in addition growth failure (due to prolonged
      glucocorticoid usage and chronic illness) and some may have low growth hormone secretion. In
      this circumstance, the agent of choice would be an anabolic agent known to increase
      osteoblast activity, normalize histomorphometric parameters and improve bone quality.
      Unfortunately, one of the most promising of these agents, recombinant PTH (Teripeptide) is
      precluded from use in pediatric patients because of concerns regarding induction of
      osteosarcoma. It is unclear to what extent antiresorptive therapy might achieve these goals,
      although it has become the therapy of choice by default.

      The Growth hormone (GH)/IGFI- axis plays a central role in longitudinal bone growth as well
      as in the acquisition and maintenance of bone mass in children. Studies, in both growth
      hormone excess and deficiency, suggest that growth hormone may be useful as an anabolic agent
      in children with osteoporosis. In acromegaly, bone turnover markers indicate activation of
      both osteoblasts and osteoclasts. Both markers correlate with circulating GH and IGF-1
      levels. IGF-1 levels are increased in cortical bone suggesting that the anabolic actions of
      GH are mediated by local production. The impact on bone density in unclear, as some studies
      show no differences from healthy controls. However, other studies indicate an increase in
      cortical bone mass while trabecular mass appears to be unchanged or somewhat reduced.
      Furthermore rates appear not to be increased.

      The Growth hormone (GH)/IGFI-axis plays a central role in the longitudinal bone growth as
      well as in the acquisition and maintenance of bone mass in children. Studies, in both growth
      hormone excess and deficiency, suggest that growth hormone may be useful as an anabolic agent
      in children with osteoporosis. Growth hormone deficiency (GHD) is recognized to result in
      reduced bone mass, decreased bone turnover markers, secondary osteoporosis and increased
      fracture rate. Epidemiological studies suggest that GHD alone may explain the increased
      fracture rate seen in these patients. Treatment of GHD patients with GH results in an
      increase in turnover markers. While short-term studies showed little improvement in bone
      mass, longer term studies with treatment periods of 2 years or more have shown significant
      increases in bone mass.
    

Intervention name(s): Vitamin D + Calcium + Exercise program; Vitamin D + Calcium + Exercise program + Humatrope
Intervention type(s): Dietary Supplement; Drug
Intervention description(s): Subjects is this arm of the study will receive a) a supplementation with vitamin D3, 1000 IU daily b) a dietary calcium intake set at DRI for age and a supplement used as needed to meet the requirement and c) a weight bearing exercise program appropriate for the underlying medical condition; Subjects in this arm will receive the same as those in arm 1 as well as Humatrope by subcutaneous infection 7 days a week at a dose of 0.05 mg.kg/day.
Other intervention name(s): Growth Hormone
Intervention MeSH terms: Calcium, Dietary; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Growth hormone; Pediatrics; Vitamin D; Calcium; Exercise