In the Journals

GH therapy increases fracture risk in patients previously treated for acromegaly

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July 15, 2016

Adult patients with severe growth hormone deficiency previously treated for acromegaly saw an increased fracture risk after 6 years of growth hormone replacement therapy, whereas those previously treated for Cushing’s disease did not experience the same risk, according to a recent observational study.

Nadege C. van Varsseveld, MD, of the department of internal medicine at VU University Medical Center in Amsterdam, and colleagues analyzed data from 1,028 patients with previous nonfunctioning pituitary adenoma (NFPA; n = 783), acromegaly (n = 65) and Cushing’s disease (n = 180), identified through the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide, long-term surveillance study in patients with severe GH deficiency. Data were collected biannually from medical records through 2009. Baseline DXA measurements were available for 414 patients; 71 (17.1%) had osteoporosis at one or more of the measured sites; 147 (35.5%) had osteopenia.

During a mean follow-up of 5.2 years, researchers found that 166 of patients with previous NFPA were prescribed osteoporosis medications (21.3%), as were 69 patients with previous Cushing’s disease (38.5%) and 22 patients with previous acromegaly (33.4%). During follow-up, 39 patients experienced fractures (3.8%; 32 experiencing one fracture), including 26 patients in the previous NFPA group, eight patients in the previous Cushing’s disease group and five patients in the previous acromegaly group. The median time between baseline and first fracture was 2.4 years (mean age, 59 years).

Researchers found that fracture risk did not differ between groups before 6 years’ follow-up. Fracture risk increased in patients with previous acromegaly after 6 years’ follow-up, but not for those with previous Cushing’s disease vs. patients with NFPA. Results persisted after adjustment for multiple factors, including sex, age, fracture history and the extent of pituitary insufficiency.

The researchers noted that patients with previous Cushing’s disease were younger and more often women and had a greater history of osteopenia or osteoporosis, whereas patients with acromegaly had a longer duration between tumor treatment and the start of GH therapy and were treated more often with radiotherapy.

“During active acromegaly, increased bone turnover has been observed, but reported effects on [bone mineral density] are heterogeneous,” the researchers wrote. “It is postulated that cortical BMD increases, whereas trabecular BMD decreases or remains unaffected.

“The increased fracture risk in the present study may be a long-term effect of impaired skeletal health due to previous GH excess, even though this was not reflected by an increased occurrence of osteopenia or osteoporosis in the medical history,” the researchers wrote. – by Regina Schaffer

Disclosure: One researcher reports receiving consultancy fees from Novartis and Pfizer.