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- Publisher Website: 10.1210/clinem/dgz088
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- PMID: 31650181
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Article: Association of Genetic Variants Related to Serum Calcium Levels with Reduced Bone Mineral Density
Title | Association of Genetic Variants Related to Serum Calcium Levels with Reduced Bone Mineral Density |
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Authors | |
Keywords | adult bone density calcium blood level causality cross-sectional study |
Issue Date | 2020 |
Publisher | Oxford University Press. The Journal's web site is located at https://academic.oup.com/jcem |
Citation | The Journal of Clinical Endocrinology & Metabolism, 2020, v. 105 n. 3, p. e328-e336 How to Cite? |
Abstract | Context:
The role of serum calcium in bone metabolism is unknown, even though calcium/vitamin D supplementations have been widely used and are expected to improve bone health. We aim to determine the independent role of serum calcium in bone mineral density (BMD).
Design and setting:
Two epidemiological analyses with 5478 and 5556 participants from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2006 and the Hong Kong Osteoporosis Study (HKOS) to evaluate the cross-sectional association of serum calcium with BMD. Two-sample Mendelian randomization (MR) studies using genetic variations as instrumental variables to infer causality. Summary statistics of genome-wide association study of serum calcium (N = 39 400) and lifelong whole-body BMD (N = 66 628) were used.
Main outcome measure:
BMD measured by dual-energy X-ray absorptiometry
Results:
In NHANES 2003–6 and HKOS, each standard deviation (SD) increase in serum calcium was significantly associated with 0.036–0.092 SD decrease in BMD at various sites (all P < .05). In multivariable inverse-variance weighted MR analysis, genetic predisposition to higher serum calcium level was inversely associated with whole-body BMD after adjustment for serum parathyroid hormone, vitamin D, and phosphate (–0.431 SD per SD increase in serum calcium; 95% CI: –0.773 to –0.089, P = .014). Similar estimates were obtained in sensitivity analyses.
Conclusions:
Our study reveals that genetic predisposition to higher serum calcium level per se may have a negative impact on bone metabolism. Whether increased serum calcium caused by calcium/vitamin D supplementations would have the same negative effect on bone remains unknown, which warrants further investigation. In addition to other adverse clinical outcomes, careful use of high-dose supplementations is required. |
Persistent Identifier | http://hdl.handle.net/10722/282217 |
ISSN | 2023 Impact Factor: 5.0 2023 SCImago Journal Rankings: 1.899 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Li, GH-Y | - |
dc.contributor.author | Robinson-Cohen, C | - |
dc.contributor.author | Sahni, S | - |
dc.contributor.author | AU, PCM | - |
dc.contributor.author | Tan, KC-B | - |
dc.contributor.author | Kung, AW-C | - |
dc.contributor.author | Cheung, C-L | - |
dc.date.accessioned | 2020-05-05T14:32:19Z | - |
dc.date.available | 2020-05-05T14:32:19Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | The Journal of Clinical Endocrinology & Metabolism, 2020, v. 105 n. 3, p. e328-e336 | - |
dc.identifier.issn | 0021-972X | - |
dc.identifier.uri | http://hdl.handle.net/10722/282217 | - |
dc.description.abstract | Context: The role of serum calcium in bone metabolism is unknown, even though calcium/vitamin D supplementations have been widely used and are expected to improve bone health. We aim to determine the independent role of serum calcium in bone mineral density (BMD). Design and setting: Two epidemiological analyses with 5478 and 5556 participants from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2006 and the Hong Kong Osteoporosis Study (HKOS) to evaluate the cross-sectional association of serum calcium with BMD. Two-sample Mendelian randomization (MR) studies using genetic variations as instrumental variables to infer causality. Summary statistics of genome-wide association study of serum calcium (N = 39 400) and lifelong whole-body BMD (N = 66 628) were used. Main outcome measure: BMD measured by dual-energy X-ray absorptiometry Results: In NHANES 2003–6 and HKOS, each standard deviation (SD) increase in serum calcium was significantly associated with 0.036–0.092 SD decrease in BMD at various sites (all P < .05). In multivariable inverse-variance weighted MR analysis, genetic predisposition to higher serum calcium level was inversely associated with whole-body BMD after adjustment for serum parathyroid hormone, vitamin D, and phosphate (–0.431 SD per SD increase in serum calcium; 95% CI: –0.773 to –0.089, P = .014). Similar estimates were obtained in sensitivity analyses. Conclusions: Our study reveals that genetic predisposition to higher serum calcium level per se may have a negative impact on bone metabolism. Whether increased serum calcium caused by calcium/vitamin D supplementations would have the same negative effect on bone remains unknown, which warrants further investigation. In addition to other adverse clinical outcomes, careful use of high-dose supplementations is required. | - |
dc.language | eng | - |
dc.publisher | Oxford University Press. The Journal's web site is located at https://academic.oup.com/jcem | - |
dc.relation.ispartof | The Journal of Clinical Endocrinology & Metabolism | - |
dc.rights | Pre-print: Journal Title] ©: [year] [owner as specified on the article] Published by Oxford University Press [on behalf of xxxxxx]. All rights reserved. Pre-print (Once an article is published, preprint notice should be amended to): This is an electronic version of an article published in [include the complete citation information for the final version of the Article as published in the print edition of the Journal.] Post-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here]. | - |
dc.subject | adult | - |
dc.subject | bone density | - |
dc.subject | calcium blood level | - |
dc.subject | causality | - |
dc.subject | cross-sectional study | - |
dc.title | Association of Genetic Variants Related to Serum Calcium Levels with Reduced Bone Mineral Density | - |
dc.type | Article | - |
dc.identifier.email | Li, GH-Y: gloriali@hku.hk | - |
dc.identifier.email | Tan, KC-B: kcbtan@hkucc.hku.hk | - |
dc.identifier.email | Kung, AW-C: awckung@hku.hk | - |
dc.identifier.email | Cheung, C-L: lung1212@hku.hk | - |
dc.identifier.authority | Tan, KC-B=rp00402 | - |
dc.identifier.authority | Kung, AW-C=rp00368 | - |
dc.identifier.authority | Cheung, C-L=rp01749 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1210/clinem/dgz088 | - |
dc.identifier.pmid | 31650181 | - |
dc.identifier.scopus | eid_2-s2.0-85078685591 | - |
dc.identifier.hkuros | 309804 | - |
dc.identifier.volume | 105 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | e328 | - |
dc.identifier.epage | e336 | - |
dc.identifier.isi | WOS:000525870500033 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0021-972X | - |