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 in | The journal of clinical endocrinology and metabolism Vol. 100; no. 2; pp. 384 - 394 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Oxford University Press
01.02.2015
Copyright by The Endocrine Society |
Subjects | |
Online Access | Get full text |
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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. |
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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 |
AuthorAffiliation_xml | – name: 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 |
Author_xml | – sequence: 1 givenname: Gherardo surname: Mazziotti fullname: Mazziotti, Gherardo 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 – sequence: 4 givenname: Maurizio surname: Spinello fullname: Spinello, Maurizio organization: 4Novartis Farma (M.S.), 21040 Origgio, Italy – sequence: 5 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 – sequence: 7 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 – sequence: 8 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 |
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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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