Bone mineral density declines after cessation of growth hormone treatment

By Will Boggs MD

NEW YORK (Reuters Health) - Bone mineral density increases during long-term growth hormone treatment but decreases after cessation of treatment in young adults born small for gestational age, researchers from The Netherlands report.

"After cessation of growth hormone (GH) due to adult height attainment, bone mineral apparent density (BMAD) of the lumbar spine deteriorates and there is a trend towards a deterioration of bone mineral density (BMD) of the total body in males,” Dr. Carolina C. J. Smeets from Erasmus University Medical Center, Rotterdam, The Netherlands told Reuters Health. “Important to note is that BMD remains within the normal range and almost all participants had a BMD above -2 SDS, which is, of course, reassuring.”

BMD and BMAD peak between ages 18-20 in girls and 18-23 in boys and are the main determinants of bone strength in later life. GH treatment improves BMD and BMAD in short children born small for gestational age (SGA) in the short term.

Dr. Smeets and colleagues investigated BMD and BMAD longitudinally in young adults born SGA who were treated with GH during childhood and had attained an age of 21 years. They compared these results with those of young adults born SGA with persistent short stature who were never treated with GH and with those of healthy young adults born at an appropriate size for gestational age.

At the end of growth hormone treatment, estimated BMD (expressed as standard deviation score) was within the normal range but significantly lower than 0 SDS for both males (-0.40) and females (-0.51). These levels were significantly better than BMD measured at the onset of treatment.

In the six months following GH cessation, males experienced a slight improvement in BMD (to -0.30) followed by a slow decline in the ensuing five years (to -0.59).

BMD in females did not change significantly in the five years after GH cessation, the authors reported July 5th online in The Journal of Clinical Endocrinology and Metabolism.

BMAD at the lumbar spine did not change in the six months after GH cessation in either males or females, but it started to decline 18 months thereafter in males and two to five years thereafter in females, so that five years after GH cessation it was -0.38 in males and -0.55 in females.

At five years after GH cessation, only 1.3% of the study group had a BMD SDS of -2 or lower, which was similar to the expected proportion in the reference population. Similarly, the proportion of patients with a BMAD of the lumbar spine SDS of -2 or lower did not differ significantly from the expected.

At the end of the study, previously GH-treated SGA young adults also had similar BMD and BMAD as controls born SGA who remained untreated.

“These findings are reassuring for adults born SGA since their risk for osteoporosis does not seem to be increased,” Dr. Smeets concluded. “However, futures studies should aim at investigating how BMD of the total body and BMAD of the lumbar spine progress when they progress further into adulthood, and what the long-term clinical implications will be.”

Dr. Nicholas Tritos from Massachusetts General Hospital and Harvard Medical School in Boston told Reuters Health by email, "Growth hormone is anabolic to bone, so it is not surprising that withdrawal of therapy would lead to a gradual decline in bone density.”

As for the clinical implications of these findings, he said they "are simply unknown. The present findings are hardly surprising and cannot inform current practice. Clearly, more study is needed."

Dr. Natasha M. Appelman-Dijkstra from Leiden University Medical Center, Leiden, The Netherlands, who conducted a similar study in adult GH-deficient patients, told Reuters Health by email, "More measures on lifestyle advices (for healthy bones and adiposity) should be initiated in these patient groups.”

In her study, body fat percentage increased significantly after GH cessation, making attention to adipose tissue an important part of ongoing follow-up, she said.

SOURCE: http://bit.ly/2uD40gx

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