Bone histomorphometry in acromegaly patients with fragility vertebral fractures

Carbonare, Luca Dalle; Micheletti, V; Cosaro, Elisa; Valenti, Maria Teresa; Mottes, Monica; Francia, Giuseppe; Davì, Maria Vittoria

doi:10.1007/s11102-017-0847-1

Cited by 59 publications

(42 citation statements)

References 36 publications

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“…However, recent work using microarchitectural and histomorphometric analysis has allowed a better understanding of the trabecular and cortical bone structural changes in acromegaly (80). Dalle Carbonare et al recently described reduced trabecular bone volume, trabecular thickness and increased trabecular separation demonstrating decreased cancellous bone; cortical thickness was increased, but the cortical bone was porous in subjects with acromegaly and VFs compared to subjects without acromegaly (81). These results were consistent with previous data reporting abnormal bone architecture and altered biomechanical competence in subjects with active acromegaly (82).…”

Section: Effects Of Gh Excess On Bone Histomorphometry and Architecturementioning

confidence: 99%

“…However, subsequent work demonstrated abnormalities in trabecular bone microstructure and strength in active acromegalic patientseven when gonadal function was normal (84,85,86). In addition to these changes in cancellous bone, the cortical bone compartment is affected, and GH excess is associated with increased cortical porosity/pore volume (81,84,87) and decreased cortical density (85).…”

Section: Effects Of Gh Excess On Bone Histomorphometry and Architecturementioning

confidence: 99%

“…VFs are not a simple radiological finding but they should be considered a marker of skeletal fragility, since an association between fractures and abnormalities in bone microstructure was found following the analysis of bone samples from individuals with acromegaly by histomorphometry, tridimensional dual-energy X-ray absorptiometry (DXA) of the proximal femur and peripheral HR-QCT of the bone structure at the distal radius (81,85,87).…”

Section: Effects Of Gh Excess On Fracture Riskmentioning

confidence: 99%

“…Recent studies hypothesized that osteoblastogenesis may be impaired in subjects with controlled acromegaly, but the studies do not offer a direct proof that osteoblast number or function is altered in these individuals (74,106,107). Dalle Carbonare et al reported decreased osteoblast number and function and reduced osteocyte number in bone samples from patients with controlled acromegaly compared to those with active disease, but the impact of these histomorphometric findings on fracture risk was uncertain since all subjects included in the study had VFs (81). Further findings to support the concept that skeletal fragility persists notwithstanding biochemical control of acromegaly are the impairment of trabecular microstructure as assessed by DXA measurement of trabecular bone score (TBS) (108) and altered tissuelevel properties of cortical bone as measured by impact microindentation in individuals with treated acromegaly (109).…”

Section: Effects Of Acromegaly Therapy On Bone Turnover Bone Structumentioning

confidence: 99%

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MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

Mazziotti

Lania

Canalis

2019

European Journal of Endocrinology

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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert physiological actions on the skeleton throughout life, by stimulating longitudinal bone growth in children, the acquisition of bone mass during adolescence and the maintenance of skeletal architecture in adults. When GH and IGF-I are secreted in excess, bone remodeling is enhanced leading to deterioration of bone microstructure and impairment of bone strength. Indeed, acromegaly causes skeletal fragility, and vertebral fractures are reported in a remarkable number of subjects exposed to GH and IGF-I excess. The management of skeletal fragility in acromegaly is a challenge, since the awareness of this complication is low, the prediction of fracture risk is difficult to ascertain, the risk of fractures remains after the control of acromegaly and the effectiveness of bone-active drugs is unknown. This review is an update on bone disorders associated with acromegaly and provides a perspective of possible therapeutic approaches based on emerging pathophysiological and clinical information.

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Section: Effects Of Gh Excess On Bone Histomorphometry and Architecturementioning

confidence: 99%

Section: Effects Of Gh Excess On Bone Histomorphometry and Architecturementioning

confidence: 99%

Section: Effects Of Gh Excess On Fracture Riskmentioning

confidence: 99%

Section: Effects Of Acromegaly Therapy On Bone Turnover Bone Structumentioning

confidence: 99%

See 2 more Smart Citations

MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

Mazziotti

Lania

Canalis

2019

European Journal of Endocrinology

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“…Simultaneous alterations of both cortical and trabecular alterations have been demonstrated in early histomorphologic studies . Bone turnover is increased in acromegaly; accordingly, cortical porosity has been found increased in patients with active disease and vertebral fractures, partly explaining the discrepancy between bone mass and strength. An association between cortical thickness in the hip and vertebral fractures was recently demonstrated .…”

Section: Discussionmentioning

confidence: 99%

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.

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Bone histomorphometry in acromegaly patients with fragility vertebral fractures

Cited by 59 publications

References 36 publications

MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

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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