Electronic Letters to:

Endocrine Care: Omar Ali, Melanie Shim, Eileen Fowler, Marcia Greenberg, Donna Perkins, William Oppenheim, and Pinchas Cohen Growth Hormone Therapy Improves Bone Mineral Density in Children with Cerebral Palsy: A Preliminary Pilot Study J Clin Endocrinol Metab 2007; 92: 932-937 [Abstract] [Full text] [PDF]

eLetters: Submit a response to this article

Electronic letters published:

Growth hormone or Bisphosphonate for Cerebral Palsy related Osteoporosis

John R Porter, Nicholas J Shaw   (19 January 2007)

Growth hormone or Bisphosphonate for Cerebral Palsy related Osteoporosis 19 January 2007
John R Porter, Paediatric Endocrinology Registrar Birmingham Children's Hospital, Nicholas J Shaw Send letter to journal: Re: Growth hormone or Bisphosphonate for Cerebral Palsy related Osteoporosis jporter{at}doctors.org.uk John R Porter, et al.	We read with interest the article by Ali et al. (1). We have several concerns about this study, and the implication that growth hormone may be acceptable first-line treatment for osteopenia in cerebral palsy. The authors have made selective use of the literature in this study. We were surprised that bisphosphonates are not mentioned, as their use is well established in childhood osteogenesis imperfecta, and has shown beneficial effects on BMD in studies of children with spastic cerebral palsy, including a randomized control trial (2-5). The use of height age to calculate BMD Z scores appears to have been an afterthought, as subjects were originally recruited on the basis of Z scores calculated for chronological age. If height age had been used initially, several subjects would not have passed the entry criterion of BMD <1.0 standard deviation. We were surprised that BMD was not corrected for volume throughout, especially as the online calculator used in the method has this facility. Of further concern is that the normative BMD data used is for a different scanner (Hologic QDR1000) than that used in the study (Hologic QDR4500), an approach that leads to discrepancies (6). It is unclear which lumbar vertebrae were used to measure BMD, and no mention has been made of using distal femoral BMD as an alternative technique (4). The statistics presented mean values, not medians, which are not representative of the skewed distributions of age and mobility in the groups. When medians are used there appears to be a trend towards increased mobility and decreased age in the treated group, both of which would potentially influence bone density. Although the differences between the groups are non-significant even when non-parametric statistics are used, this is not surprising with such small numbers. The authors suggest that the increase in urinary N-telopeptide seen may relate to transient decrease in bone mineral density with growth hormone treatment. We suggest that this is more likely to be due to the increase in growth velocity, and therefore bone turnover due to growth hormone. Finally, as the authors acknowledge, the main risk of osteopenia in cerebral palsy is peripheral long bone fracture, so a longer study looking at fracture risk, which has been shown to be reduced with bisphosphonates (3), would be more useful. We do not feel the published study justifies the use of growth hormone to improve BMD in children with cerebral palsy. There is potentially more evidence for use of bisphosphonates either orally or intravenously, which would be more cost effective and acceptable to patients than daily growth hormone injections. Further randomized studies of treatments to reduce fracture risk in addition to improving BMD are required in this patient group. References 1. Ali O, Shim M, Fowler E, Greenberg M, Perkins D, Oppenheim W, Cohen P. 2006. Growth Hormone Therapy Improves Bone Mineral Density in Children with Cerebral Palsy: A preliminary pilot study. J Clin Endocrinol Metab DOI jc.2006-0385v1 2. Shaw NJ, White CP, Fraser WD, Rosenbloom L. 1994. Osteopenia in cerebral palsy. Arch Dis Child 71:235-238 3. Grissom LE, Kecskemethy HH, Bachrach SJ, McKay C, Harcke HT. 2005. Bone densitometry in pediatric patients treated with pamidronate. Pediatr Radiol 35:511-517 4. Henderson RC, Lark RK, Kecskemethy HH, Miller F, Harcke HT, Bachrach SJ. 2002. Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial. J Pediatr 141:644-651 5. Plotkin H, Coughlin S, Kreikemeier R, Heldt K, Bruzoni M, Lerner G. 2006. Low doses of pamidronate to treat osteopenia in children with severe cerebral palsy: a pilot study. Dev Med Child Neurol 48:709-712 6. Leonard MB, Propert KJ, Zemel BS, Stallings VA, Feldman HI. 1999. Discrepancies in pediatric bone mineral density reference data: potential for misdiagnosis of osteopenia. J Pediatr 135:182-188