Bone Turnover, Bone Mineral Density, and Fracture Risk in Acromegaly: A Meta-Analysis

Context:GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic.Objective:We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone...

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Published inThe journal of clinical endocrinology and metabolism Vol. 100; no. 2; pp. 384 - 394
Main Authors Mazziotti, Gherardo, Biagioli, Elena, Maffezzoni, Filippo, Spinello, Maurizio, Serra, Vincenza, Maroldi, Roberto, Floriani, Irene, Giustina, Andrea
Format Journal Article
LanguageEnglish
Published United States Oxford University Press 01.02.2015
Copyright by The Endocrine Society
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Abstract Context:GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic.Objective:We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly.Data Sources:We conducted MEDLINE and EMBASE systematic searches up to December 31, 2013.Study Eligibility Criteria:Studies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility.Data Extraction and Analysis:Study design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls.Results:Forty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97–2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03–2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07–1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91–23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly.Limitations:Limitations included heterogeneous study protocols with possible variability in the assessment of skeletal end-points.Conclusions:Skeletal fragility is an emerging complication of acromegaly.
AbstractList Context:GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic.Objective:We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly.Data Sources:We conducted MEDLINE and EMBASE systematic searches up to December 31, 2013.Study Eligibility Criteria:Studies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility.Data Extraction and Analysis:Study design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls.Results:Forty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97–2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03–2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07–1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91–23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly.Limitations:Limitations included heterogeneous study protocols with possible variability in the assessment of skeletal end-points.Conclusions:Skeletal fragility is an emerging complication of acromegaly.
GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic.CONTEXTGH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic.We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly.OBJECTIVEWe conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly.We conducted MEDLINE and EMBASE systematic searches up to December 31, 2013.DATA SOURCESWe conducted MEDLINE and EMBASE systematic searches up to December 31, 2013.Studies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility.STUDY ELIGIBILITY CRITERIAStudies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility.Study design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls.DATA EXTRACTION AND ANALYSISStudy design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls.Forty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97-2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03-2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07-1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91-23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly.RESULTSForty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97-2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03-2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07-1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91-23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly.LIMITATIONS included heterogeneous study protocols with possible variability in the assessment of skeletal end-points.LIMITATIONSLIMITATIONS included heterogeneous study protocols with possible variability in the assessment of skeletal end-points.Skeletal fragility is an emerging complication of acromegaly.CONCLUSIONSSkeletal fragility is an emerging complication of acromegaly.
CONTEXT:GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic. OBJECTIVE:We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly. DATA SOURCES:We conducted MEDLINE and EMBASE systematic searches up to December 31, 2013. STUDY ELIGIBILITY CRITERIA:Studies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility. DATA EXTRACTION AND ANALYSIS:Study design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls. RESULTS:Forty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97–2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03–2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07–1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91–23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly. LIMITATIONS:Limitations included heterogeneous study protocols with possible variability in the assessment of skeletal end-points. CONCLUSIONS:Skeletal fragility is an emerging complication of acromegaly.
GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies dealing with this topic. We conducted a meta-analysis of studies examining the effects of acromegaly on bone turnover, bone mineral density (BMD), and fractures. Furthermore, we evaluated the effects of sex, gonadal status, and activity of disease on skeletal end-points in acromegaly. We conducted MEDLINE and EMBASE systematic searches up to December 31, 2013. Studies conducted in patients with acromegaly and reporting at least one determinant of skeletal fragility. Study design, patient characteristics, interventions, and outcomes were independently extracted by two authors. We calculated the standardized mean difference (SMD) of bone turnover and BMD differences, whereas fractures were presented as relative frequencies in acromegaly and odds ratios between patients and controls. Forty-one studies fulfilled eligibility criteria and were therefore selected for data extraction and analysis. A total of 1935 patients were included (eight to 206 per study). Acromegaly patients had higher bone formation (SMD, 1.49; 95% confidence interval [CI], 0.97-2.01; P < .0001) and bone resorption (SMD, 1.57; 95% CI, 1.03-2.10; P < .0001) as compared to control subjects, without significant differences in lumbar spine BMD. BMD at the femoral neck tended to be higher in acromegaly patients vs control subjects (SMD, 0.67; 95% CI, 0.07-1.27; P = .03). Patients with acromegaly had high frequency of vertebral fractures (odds ratio, 8.26; 95% CI, 2.91-23.39; P < .0001), in close relationship with male gender, hypogonadism, and active acromegaly. LIMITATIONS included heterogeneous study protocols with possible variability in the assessment of skeletal end-points. Skeletal fragility is an emerging complication of acromegaly.
Author Serra, Vincenza
Floriani, Irene
Mazziotti, Gherardo
Spinello, Maurizio
Maroldi, Roberto
Giustina, Andrea
Maffezzoni, Filippo
Biagioli, Elena
AuthorAffiliation Endocrinology (G.M., F.M., V.S., A.G.) and Radiology (R.M.), University of Brescia, 25123 Brescia, Italy; Department of Oncology (E.B., I.F.), Instituto di Ricovero e Cura a Carattere Scientifico–Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milan, Italy; and Novartis Farma (M.S.), 21040 Origgio, Italy
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  organization: 1Endocrinology (G.M., F.M., V.S., A.G.), 25123 Brescia, Italy
– sequence: 2
  givenname: Elena
  surname: Biagioli
  fullname: Biagioli, Elena
  organization: 3 Department of Oncology (E.B., I.F.), Instituto di Ricovero e Cura a Carattere Scientifico–Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milan, Italy
– sequence: 3
  givenname: Filippo
  surname: Maffezzoni
  fullname: Maffezzoni, Filippo
  organization: 1Endocrinology (G.M., F.M., V.S., A.G.), 25123 Brescia, Italy
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  givenname: Maurizio
  surname: Spinello
  fullname: Spinello, Maurizio
  organization: 4Novartis Farma (M.S.), 21040 Origgio, Italy
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  givenname: Vincenza
  surname: Serra
  fullname: Serra, Vincenza
  organization: 1Endocrinology (G.M., F.M., V.S., A.G.), 25123 Brescia, Italy
– sequence: 6
  givenname: Roberto
  surname: Maroldi
  fullname: Maroldi, Roberto
  organization: 2Radiology (R.M.), University of Brescia, 25123 Brescia, Italy
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  givenname: Irene
  surname: Floriani
  fullname: Floriani, Irene
  organization: 3 Department of Oncology (E.B., I.F.), Instituto di Ricovero e Cura a Carattere Scientifico–Istituto di Ricerche Farmacologiche “Mario Negri”, 20156 Milan, Italy
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  givenname: Andrea
  surname: Giustina
  fullname: Giustina, Andrea
  email: a.giustina@libero.it
  organization: 1Endocrinology (G.M., F.M., V.S., A.G.), 25123 Brescia, Italy
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25365312$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
Copyright Copyright © 2015 by the Endocrine Society 2015
Copyright © 2015 by The Endocrine Society
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Snippet Context:GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of...
CONTEXT:GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of...
GH excess causes an increase in bone turnover, but the consequences in terms of skeletal fragility have long been uncertain due to the heterogeneity of studies...
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SubjectTerms Acromegaly
Acromegaly - complications
Acromegaly - diagnostic imaging
Acromegaly - physiopathology
Bone density
Bone Density - physiology
Bone growth
Bone mineral density
Bone Remodeling - physiology
Bone resorption
Bone strength
Bone turnover
Femur Neck - diagnostic imaging
Fractures
Fractures, Bone - diagnostic imaging
Fractures, Bone - etiology
Fractures, Bone - physiopathology
Humans
Hypogonadism
Long bone
Lumbar Vertebrae - diagnostic imaging
Meta-analysis
Osteogenesis
Radiography
Risk
Spine (lumbar)
Vertebrae
Title Bone Turnover, Bone Mineral Density, and Fracture Risk in Acromegaly: A Meta-Analysis
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https://www.ncbi.nlm.nih.gov/pubmed/25365312
https://www.proquest.com/docview/3164367500
https://www.proquest.com/docview/1653124958
Volume 100
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