Effect of Growth Hormone Treatment on BMD in Adults With Prader-Willi Syndrome

Compared with growth hormone (GH) treatment, one year of placebo after attainment of adult height does not decrease bone mineral density (BMD) in young adults with Prader-Willi syndrome (PWS).

However, in young adults with hypergonadism and PWS, GH treatment does not prevent decline in BMD unless it is combined with sex steroid replacement therapy (SSRT), according to a 2-year, randomized, double-blind, placebo-controlled, cross-over study published in Clinical Endocrinology.¹

The prevalence of osteopenia and osteoporosis are increased in adults with PWS.^2-4 Treatment with GH has demonstrated beneficial effects on BMD in children with PWS,^5,6 however, it is unknown whether BMD might decrease after cessation of GH treatment when adult height has been attained, whereas continuing GH treatment may be useful for maintaining BMD.

Therefore, researchers randomly assigned 27 young adults with PWS who had attained adult height to receive GH (0.67 mg/m²/day) and placebo, both during 1 year to determine the effects of GH treatment vs placebo and the effects of SSRT on BMD.¹

The investigators found that at adult height, total body BMD was significantly lower compared with that of healthy peers (P <.01), and bone mineral apparent density (BMAD) of the lumbar spine was similar. Both total body BMD and BMAD of the lumbar spine were similar during 1 year of GH treatment compared with 1 year of placebo.

In young adults with hypergonadism without SSRT, total body BMD and BMAD of the lumbar spine decreased during the 2-year study (P =.11 and P =.01, respectively), regardless of treatment with GH or placebo, whereas total body BMD increased in those who received SSRT (P <.01).

“Close monitoring of BMD in adolescents and young adults with PWS is recommended and SSRT should be considered in cases of hypogonadism and a declining BMD,” the authors concluded.¹

Disclosure: This work was supported by an investigator-initiated independent research grant from Pfizer. Anita C. S. Hokken-Koelega received the research grant from Pfizer. Pfizer provided Genotropin and identical-appearing placebo without charge.

References

1. Donze SH, Kuppens RJ, Bakker NE, van Alfen-van der Velden JAEM, Hokken-Koelega ACS. Bone mineral density in young adults with Prader-Willi syndrome: a randomized, placebo-controlled, cross-over GH trial [published online February 8, 2018]. Clin Endocrinol. doi: 10.1111/cen.13567
2. Höybye C, Hilding A, Jacobsson H, Thorén M. Metabolic profile and body composition in adults with Prader-Willi syndrome and severe obesity. J Clin Endocrinol Metab. 2002;87:3590-3597.
3. Sinnema M, Maaskant MA, van Schrojenstein Lantman-de Valk HMJ, et al. Physical health problems in adults with Prader-Willi syndrome. Am J Med Genet. 2011;155:2112-2124.
4. Butler JV, Whittington JE, Holland AJ, Boer H, Clarke D, Webb T. Prevalence of, and risk factors for, physical ill-health in people with Prader-Willi syndrome: a population-based study. Dev Med Child Neurol. 2002;44:248-255.
5. Bakker NE, Kuppens RJ, Siemensma EPC, et al. Bone mineral density in children and adolescents with Prader-Willi syndrome: a longitudinal study during puberty and 9 years of growth hormone treatment. J Clin Endocrinol Metab. 2015;100:1609-1618.
6. Duran AT, Wilson KS, Castner DM, Tucker JM, Rubin DA. Association between physical activity and bone in children with Prader-Willi syndrome. J Pediatr Endocrinol Metab. 2016;29:819-26.