Delineating the relationship between circulating osteoprotegerin and bone health in women with a pathogenic variant in BRCA1: A cross-sectional analysis
AbstractPurposeOsteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we inv...
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| Published in | Bone Reports Vol. 22; p. 101802 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Elsevier Inc
01.09.2024
Elsevier |
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| Online Access | Get full text |
| ISSN | 2352-1872 2352-1872 |
| DOI | 10.1016/j.bonr.2024.101802 |
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| Abstract | AbstractPurposeOsteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers. MethodsWomen with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann–Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD. ResultsAmong 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement ( n = 50), low serum OPG was associated with a significantly lower BMD T-score (−1.069 vs. -0.318; P = 0.04). ConclusionOur findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers. |
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| AbstractList | Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers.PurposeOsteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers.Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann-Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD.MethodsWomen with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann-Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD.Among 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement (n = 50), low serum OPG was associated with a significantly lower BMD T-score (-1.069 vs. -0.318; P = 0.04).ResultsAmong 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement (n = 50), low serum OPG was associated with a significantly lower BMD T-score (-1.069 vs. -0.318; P = 0.04).Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers.ConclusionOur findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers. Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers. Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann–Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD. Among 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement (n = 50), low serum OPG was associated with a significantly lower BMD T-score (−1.069 vs. -0.318; P = 0.04). Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers. •High OPG associated with increased lumbar spine BMD T-scores in BRCA1 mutation carriers.•No significant difference in lumbar spine BMD by OPG level within menopausal subgroups•Unexpected positive correlation between serum OPG and FRAX scores in a young cohort of BRCA1 mutation carriers AbstractPurposeOsteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers. MethodsWomen with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann–Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD. ResultsAmong 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement ( n = 50), low serum OPG was associated with a significantly lower BMD T-score (−1.069 vs. -0.318; P = 0.04). ConclusionOur findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers. Purpose: Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the BRCA1 gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among BRCA mutation carriers. Methods: Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of major osteoporotic fracture (FRAXmajor) and hip fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann–Whitney U test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD. Results: Among 701 women with a BRCA1 mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) P < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) P < 0.0001). In a subset with BMD measurement (n = 50), low serum OPG was associated with a significantly lower BMD T-score (−1.069 vs. -0.318; P = 0.04). Conclusion: Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in BRCA mutation carriers. •High OPG associated with increased lumbar spine BMD T-scores in BRCA1 mutation carriers.•No significant difference in lumbar spine BMD by OPG level within menopausal subgroups•Unexpected positive correlation between serum OPG and FRAX scores in a young cohort of BRCA1 mutation carriers Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women with a pathogenic variant (mutation) in the gene, and thus, may be at greater risk for skeletal bone loss. Thus, we investigated the association between circulating OPG and two validated markers of bone health: 1) bone fracture risk score (FRAX) and 2) bone mineral density (BMD), among mutation carriers. Women with a blood sample and clinical data were included in this analysis. An enzyme-linked immunosorbent assay (ELISA) was used to quantify serum OPG (pg/mL) and the 10-year risk of osteoporotic fracture (FRAXmajor) and fracture (FRAXhip) (%) was estimated using a web-based algorithm. For a subset of women, lumbar spine BMD was previously assessed by dual x-ray absorptiometry (DXA)(T-score). A Mann-Whitney test was used to evaluate the association between OPG and FRAX score, while linear regression was used to assess the association of OPG and BMD. Among 701 women with a mutation, there was a significant (and unexpected) positive association between OPG levels and FRAX score (FRAXmajor: 2.12 (low OPG) vs. 2.53 (high OPG) < 0.0001; FRAXhip: 0.27 (low OPG) vs. 0.44 (high OPG) < 0.0001). In a subset with BMD measurement ( = 50), low serum OPG was associated with a significantly lower BMD T-score (-1.069 vs. -0.318; = 0.04). Our findings suggest that women with inherently lower OPG may be at risk of lower BMD, the gold standard marker of bone disease. Due to the young age of our cohort, on-going studies are warranted to re-evaluate the association between OPG and FRAX in mutation carriers. |
| ArticleNumber | 101802 |
| Author | Kotsopoulos, Joanne Uzelac, Aleksandra Lubinski, Jan Salmena, Leonardo Narod, Steven A Mokhber, Aghaghia Hall, Elizabeth Cheung, Angela |
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| Keywords | BRCA mutation carriers FRAX Osteoprotegerin (OPG) Bone mineral density |
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| Snippet | AbstractPurposeOsteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG... Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels among women... •High OPG associated with increased lumbar spine BMD T-scores in BRCA1 mutation carriers.•No significant difference in lumbar spine BMD by OPG level within... Purpose: Osteoprotegerin (OPG) plays an important role in the inhibition of osteoclast formation and bone resorption. Studies have reported lower OPG levels... |
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| SubjectTerms | Bone mineral density BRCA mutation carriers Editor Invited Review FRAX Orthopedics Osteoprotegerin (OPG) |
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| Title | Delineating the relationship between circulating osteoprotegerin and bone health in women with a pathogenic variant in BRCA1: A cross-sectional analysis |
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