Abstract
PurposeThe effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing’s disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA).MethodsFrom the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated.ResultsAt baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy.ConclusionsDuring GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.
Highlights
Severe growth hormone deficiency (GHD) in adults is an increasingly recognized clinical entity, characterized by unfavorable alterations in body composition, cardiovascular risk factors and quality of life [1,2,3]
During GH replacement therapy, an increased fracture risk was observed in severe GH deficient (GHD) adult patients previously treated for acromegaly, but not in those previously treated for Cushing’s disease (CD), compared to severe GHD adult patients using GH replacement therapy because of previous nonfunctioning pituitary adenoma (NFPA)
Of the 1028 severe GHD adult patients included in the present study, 783 (76.2 %) had previous NFPA, 180 (17.5 %) previous CD and 65 (6.3 %) previous acromegaly
Summary
Severe growth hormone deficiency (GHD) in adults is an increasingly recognized clinical entity, characterized by unfavorable alterations in body composition, cardiovascular risk factors and quality of life [1,2,3]. In a recent large observational study, the annual clinical fracture incidence was significantly lower in adult GHD patients with GH replacement therapy than in those without GH replacement therapy (1.19 vs 1.91 %) [14]. In a prospective study including GHD adult patients, 30 % of the patients developed radiological vertebral fractures during 6 years of follow-up. GH replacement therapy led to a significant decrease in vertebral fracture risk [18]. These studies may point toward a beneficial effect of GH replacement therapy on fractures in GHD patients, they show a wide variation in study design, population, follow-up duration and endpoints. The effect of GH replacement therapy on fractures in patients with specific causes of GHD has not been thoroughly investigated
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