Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease

a Systematic Review and Meta-Analysis

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Purpose of Review: Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD. Methods: EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3–5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools. Recent Findings: Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21–3.38) and femoral neck (SMD 3.29; 95% CI 3.21–3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. Summary: There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.

Original languageEnglish
Pages (from-to)674-692
Number of pages19
JournalCurrent Osteoporosis Reports
Volume16
Issue number6
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • Bone mineral density
  • Chronic kidney disease
  • Fractures
  • Hormone replacement therapy
  • Hypogonadism
  • Selective oestrogen receptor modulators

Cite this

@article{ceb75556b6eb46f9872ec3c0a5b8829b,
title = "Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease: a Systematic Review and Meta-Analysis",
abstract = "Purpose of Review: Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD. Methods: EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3–5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools. Recent Findings: Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95{\%} CI 3.21–3.38) and femoral neck (SMD 3.29; 95{\%} CI 3.21–3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. Summary: There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.",
keywords = "Bone mineral density, Chronic kidney disease, Fractures, Hormone replacement therapy, Hypogonadism, Selective oestrogen receptor modulators",
author = "Jasna Aleksova and Rodriguez, {Alexander J.} and Robert McLachlan and Peter Kerr and Frances Milat and Ebeling, {Peter R.}",
year = "2018",
month = "12",
day = "1",
doi = "10.1007/s11914-018-0483-3",
language = "English",
volume = "16",
pages = "674--692",
journal = "Current Osteoporosis Reports",
issn = "1544-1873",
publisher = "Springer-Verlag London Ltd.",
number = "6",

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T1 - Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease

T2 - a Systematic Review and Meta-Analysis

AU - Aleksova, Jasna

AU - Rodriguez, Alexander J.

AU - McLachlan, Robert

AU - Kerr, Peter

AU - Milat, Frances

AU - Ebeling, Peter R.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Purpose of Review: Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD. Methods: EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3–5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools. Recent Findings: Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21–3.38) and femoral neck (SMD 3.29; 95% CI 3.21–3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. Summary: There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.

AB - Purpose of Review: Patients with chronic kidney disease (CKD) have a greatly increased fracture risk compared with the general population. Gonadal hormones have an important influence on bone mineral density (BMD) and fracture risk, and hormone therapies can significantly improve these outcomes. Gonadal dysfunction is a frequent finding in patients with CKD; yet, little is known about the impact of gonadal hormones in the pathogenesis and treatment of bone health in patients with CKD. This systematic review and meta-analysis aimed to examine the effects of gonadal hormones and hormone therapies on bone outcomes in men and women with CKD. Methods: EMBASE, MEDLINE, SCOPUS, and clinical trial registries were systematically searched from inception to February 14, 2018 for studies that assessed gonadal hormones or hormone treatments with bone outcomes in patients with CKD stage 3–5D. Two independent reviewers screened the titles and abstracts of search results according to inclusion criteria and assessed study quality and risk of bias using validated assessment tools. Recent Findings: Thirteen studies met the inclusion criteria. Six moderate-to-high quality observational studies showed inconsistent association between any gonadal hormone and bone outcomes, limited by significant study heterogeneity. Five moderate-high risk of bias interventional studies examined treatment with selective oestrogen receptor modulators in post-menopausal women (four using raloxifene and one bazedoxifene) and demonstrated variable effects on BMD and fracture outcomes. Meta-analysis of raloxifene treatment in post-menopausal women demonstrated improvement in lumbar spine (SMD 3.30; 95% CI 3.21–3.38) and femoral neck (SMD 3.29; 95% CI 3.21–3.36) BMD compared with placebo. Transdermal oestradiol/norethisterone in pre-menopausal women receiving dialysis (n = 1 study), demonstrated BMD improvement over 12 months. Testosterone treatment for 6 months in dialysis-dependant men (n = 1 study) did not improve BMD. Summary: There is evidence that raloxifene treatment may be beneficial in improving BMD in post-menopausal women with CKD. There is insufficient evidence for other hormone treatments in men or women. Despite high fracture rates and frequent gonadal dysfunction in patients with CKD, significant evidence gaps exist, and well-designed studies are required to specifically assess the impact of gonadal status in the pathogenesis of CKD-related bone fragility and its treatment.

KW - Bone mineral density

KW - Chronic kidney disease

KW - Fractures

KW - Hormone replacement therapy

KW - Hypogonadism

KW - Selective oestrogen receptor modulators

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U2 - 10.1007/s11914-018-0483-3

DO - 10.1007/s11914-018-0483-3

M3 - Review Article

VL - 16

SP - 674

EP - 692

JO - Current Osteoporosis Reports

JF - Current Osteoporosis Reports

SN - 1544-1873

IS - 6

ER -