Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

Ueland, Thor; Fougner, Stine Lyngvi; Godang, Kristin; Schreiner, Thomas; Bollerslev, Jens

doi:10.1530/eje.1.02285

Cited by 66 publications

(63 citation statements)

References 34 publications

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“…Bone turnover and bone area are increased in acromegaly, whereas bone mineral content seems to be unaltered, giving a relative decrease in BMD (11). The increase in bone area and thereby cortical thickness in the long bones might explain data from register studies, indicating a reduction in peripheral fractures in acromegaly (28).…”

Section: Discussionmentioning

confidence: 99%

“…The biochemical markers reflect bone resorption (CTX-1) and formation (P1NP) and together they describe bone turnover (11,27).…”

Section: Discussionmentioning

confidence: 99%

“…Following treatment, however, an opposite effect on TBS and BMD was found. Bone remodeling is coupled in as well active acromegaly as following treatment (11), in contrast to for instance endogenous Cushing's syndrome, where bone resorption and formation are uncoupled in the active state, becoming coupled following treatment and remission (36). It is therefore to be expected that disease control in acromegaly will be followed by a decrease in bone turnover and a filling of the remodeling space followed by a relative increase in BMD (11,27), as seen in other endocrine disorders with coupled bone remodeling, following treatment (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…Bone remodeling is coupled in as well active acromegaly as following treatment (11), in contrast to for instance endogenous Cushing's syndrome, where bone resorption and formation are uncoupled in the active state, becoming coupled following treatment and remission (36). It is therefore to be expected that disease control in acromegaly will be followed by a decrease in bone turnover and a filling of the remodeling space followed by a relative increase in BMD (11,27), as seen in other endocrine disorders with coupled bone remodeling, following treatment (37,38). The decrease in TBS following treatment in this study, despite the increase in BMD, reflects that the two measures describe different properties of bone, especially in other conditions than postmenopausal osteoporosis (4), but are in alignment with the observed high incidence and prevalence of vertebral fractures seen in acromegaly (5,31,32,33,34).…”

Section: Discussionmentioning

confidence: 99%

“…As BMD reflects only bone quantity, and bone quality has been shown to be altered in acromegaly (9,10), the fracture risk may be underestimated by BMD (5). Biochemical markers of bone turnover can provide further reliable information on the changes in the bone remodeling, also in a high turnover state as acromegaly (11). Accordingly, we have previously demonstrated reduced trabecular biomechanical competence in patients with active acromegaly (12), indicating that patients with acromegaly were predisposed to develop vertebral fractures independently of BMD.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Godang

Olarescu

Bollerslev

et al. 2016

European Journal of Endocrinology

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Context: Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. Objective: The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. Results: Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both P < 0.01). The changes in BMD LS and TBS were not correlated (P = 0.87). The TBS change was found to be −4.5 % (±6.7; P = 0.003) in men and −0.3 % (±6.8; P = 0.85) in women (P = 0.063 for interaction men vs women). The mean BMD LS increased in men +4.2 g/cm 2 (±4.3; P < 0.001), but not in women +1.5 g/ cm 2 (±5.6; P = 0.36); (P = 0.073 for interaction). BMD increased in the ultradistal radius and total body (both P < 0.01).The increase in BMD LS was associated with a decrease in P1NP and CTX-1 (P < 0.001) and with lower P1NP and CTX-1 at the follow-up (P < 0.02). Conclusion: Treatment of acromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control.

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Section: Discussionmentioning

confidence: 99%

“…The biochemical markers reflect bone resorption (CTX-1) and formation (P1NP) and together they describe bone turnover (11,27).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Godang

Olarescu

Bollerslev

et al. 2016

European Journal of Endocrinology

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Hip Structure Analyses in Acromegaly: Decrease of Cortical Bone Thickness After Treatment: A Longitudinal Cohort Study

et al. 2019

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Long‐standing growth hormone (GH) excess causes the skeletal clinical signs of acromegaly with typical changes in bone geometry, including increased cortical bone thickness (CBT). However, a high prevalence and incidence of vertebral fractures has been reported. The aim of this study was to assess the course of cortical bone dimensions in the hip by comparing patients with acromegaly and clinically nonfunctioning pituitary adenomas (NFPAs) at baseline and 1 year after pituitary surgery (1‐year PO) in a longitudinal cohort study. DXA was performed in patients with acromegaly (n = 56) and NFPA (n = 47). CBT in the femoral neck (CBTneck), calcar (CBTcalcar), and shaft (CBTshaft) were determined by hip structural analysis (HSA). CBT at baseline and the change to 1‐year PO were compared. Test results were adjusted for differences in gender distribution, age, and gonadal status. Cortical thickness analyses showed higher values [mm] at baseline in patients with acromegaly compared with NFPA: CBTneck median [25th; 75th] 6.2 [4.7; 8.0] versus 5.1 [4.1; 6.4] (p = 0.006), CBTcalcar 4.8 [4.2, 5.7] versus 4.0 [3.2, 4.5] (p < 0.001), CBTshaft 6.2 [5.1, 7.2] versus 5.2 [4.6, 6.0], (p = 0.003). In acromegaly, GH was correlated with CBTneck (r = 0.31, p = 0.020), whereas IGF‐1 was correlated with CBTcalcar (r = 0.39, p = 0.003) at baseline. In acromegaly, CBTneck decreased by 11.2%, p = 0.002 during follow‐up. Finally, the decrease in CBTneck and CBTcalcar in acromegaly was significant compared with NFPA (p = 0.023 and p = 0.017, respectively). Previous observations of increased CBT in acromegaly were confirmed with DXA‐derived HSA in a large, well‐defined cohort. The decline in CBT in acromegaly could contribute to the increased fracture risk in acromegaly despite increased bone dimensions and disease control. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Endocortical Trabecularization in Acromegaly: The Cause for the Paradoxically Increased Vertebral Fracture Risk?

Heck,

Godang,

Lekva

et al. 2023

JBMR Plus

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Growth hormone (GH) is nonphysiologically increased in acromegaly, stimulating target tissues directly and indirectly via insulin‐like growth factor type 1 (IGF‐1). Despite GH having anabolic effects on bone growth and renewal, the risk of vertebral fractures is paradoxically increased in acromegaly. We hypothesized that bone tissue compartments were differentially affected by hormonal alterations in active and controlled acromegaly. We aimed to study the effect of sex and gonadal status on long‐term outcome of bone mass and structure to understand the biomechanical competence of bone. We followed 62 patients with newly diagnosed acromegaly longitudinally (median 4.8 years after pituitary surgery) to investigate changes assessed by dual X‐ray absorptiometry (DXA), trabecular bone score (TBS), and hip structure analysis (HSA). At diagnosis, patients had increased bone mineral density (BMD) in most compartments compared with normative data (Z‐scores). Conversely, TBS Z‐score was decreased (Z = −0.64 (SD 1.73), p = 0.028). Following treatment of acromegaly, BMD increased further in compartments containing predominantly trabecular bone, such as the lumbar spine, in eugonadal and male subjects, while compartments with predominantly cortical bone, such as the hip and femoral neck, were unchanged. Total body measurements showed further increase in BMD independent of sex and gonadal status. TBS did not change. HSA revealed a significant decrease in cortical thickness in both sexes independent of gonadal status, whereas the overall size of bone (hip axis length and neck width) did not change over time. In conclusion, patients with acromegaly had increased bone mass and dimensions by DXA. Following normalization of disease activity, BMD increased mainly in compartments rich in trabecular bone, reflecting a closure of the remodeling space. However, HSA revealed a significant decrease in cortical thickness, implying endocortical trabecularization, potentially explaining the increased risk for incident vertebral fractures following treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

show abstract

Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

Cited by 66 publications

References 34 publications

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Hip Structure Analyses in Acromegaly: Decrease of Cortical Bone Thickness After Treatment: A Longitudinal Cohort Study

Endocortical Trabecularization in Acromegaly: The Cause for the Paradoxically Increased Vertebral Fracture Risk?

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