Fracture Incidence in GH-Deficient Patients on Complete Hormone Replacement Including GH
Abstract
Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. Introduction: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. Materials and Methods: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. Results: A more than doubled risk (IRR, 2.29; 95% CI, 1.23–4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34–0.86) was recorded in AO GHD men. Conclusions: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH–IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.
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Patients with isolated GH deficiency and with multiple pituitary deficiencies usually have low BMD.
“Patients with isolated GH deficiency (GHD) and with multiple pituitary deficiencies usually have low BMD.”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
GH may play a role in the achievement of peak bone mass.
“which may present the potential role of GH in the achievement of peak bone mass [44–49].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
GHD itself is crucial for the development of osteopenia in hypopituitary patients.
“Studies have shown that GHD itself is crucial for the development of osteopenia in hypopituitary patients [44, 49, 51].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
GHD and hypopituitarism are associated with increased fracture risk.
“It has been reported that GHD and hypopituitarism are associated with increased fracture risk [17, 44, 51, 55].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
In patients with childhood onset GHD, there is a clear reduction in BMD.
“In patients with childhood onset (CO) GHD there seems to be a clear reduction in BMD, which may present the potential role of GH in the achievement of peak bone mass [44–49].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
In adult onset GHD men on complete hormone replacement therapy, a significantly decreased incidence of fractures was observed.
“In contrast, a significantly decreased incidence of fractures was observed in AO GHD men.”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
The findings on fracture incidence in GHD patients on complete hormone replacement therapy are justified by the interaction between oral estrogen and the GH-IGF-1 axis in women and by the adequate substitution of testosterone and GH in men.
“These findings were justified by the interaction between oral estrogen and the GH-IGF-1 axis in women and by the adequate substitution of testosterone and GH in men [44].”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
Women with childhood onset GHD on complete hormone replacement therapy had more than doubled risk for nonosteoporotic fractures.
“They demonstrated that women with CO GHD had more than doubled risk for nonosteoporotic fractures.”
From Pituitary Disorders and Osteoporosis (2015) · cites this paper as [44]
The study design of Holmer et al. limited the possibility of separately evaluating the effects of untreated and treated GHD on fracture incidence, because the person-years risk before starting rhGH therapy was too low for a reliable interpretation of GHD-specific fracture risk.
“The study design limited the possibility of separately evaluating the effects of untreated and treated GHD on fracture incidence, because the person-years risk before starting rhGH therapy was too low for a reliable interpretation of GHD-specific fracture risk.”
From Pituitary Diseases and Bone (2018) · cites this paper as [441]
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- Authors
- Holmer, H., Svensson, J., Rylander, L., Johannsson, G., Rosén, T., Bengtsson, B.-Å., Thorén, M., Höybye, C., Degerblad, M., Bramnert, M., Hägg, E., Engström, B. E., Ekman, B., Thorngren, K.-G., Hagmar, L., & Erfurth, E.-M.
- Affiliations
- Skåne University Hospital (SE)
- Sahlgrenska University Hospital (SE)
- Lund University (SE)
- Karolinska University Hospital (SE)
- Department of Endocrinology, University Hospital, Malmö, Sweden
- University Hospital of Umeå (SE)
- Uppsala University Hospital (SE)
- Linköping University Hospital (SE)
- Corresponding author
- Erfurth, Eva-Marie
- ORCID
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-12-01
- Volume
- 22
- Issue
- 12
- Pages
- 1842-1850
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2037472576
- Cited by
- 66
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 4 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 7 · 2013: 4 · 2012: 4
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Pfizer
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- growth hormone deficiency, fracture risk, growth hormone therapy, hormone replacement therapy, childhood-onset growth hormone deficiency, adult-onset growth hormone deficiency, sex differences, oral estrogen, IGF-I axis
- MeSH terms
- Adolescent, Adult, Child, Female, Humans, Hypopituitarism, Male, Risk Factors, Sex Factors, Sweden, Testosterone, Incidence, Human Growth Hormone, Hormone Replacement Therapy, Fractures, Bone
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