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Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review

31 Pages Posted: 5 Mar 2021

See all articles by Marlene Chakhtoura

Marlene Chakhtoura

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Dania Bacha

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Charbel Gharios

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Sara Ajjour

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Mariam Assaad

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Yara Jabbour

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Francesca Kahale

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Aya Bassatne

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Stephanie Antoun

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Elie Akl

American University of Beirut - Department of Internal Medicine; American University of Beirut - Center for Systematic Reviews on Health Policy and Systems Research (SPARK); McMaster University - Department of Health Research Methods, Evidence, and Impact (HEI)

Roger Bouillon

Katholieke Universiteit Leuven - Department of Chronic Diseases, Metabolism and Ageing; KU Leuven - Clinical and Experimental Endocrinology

Paul Lips

Amsterdam University Medical Center - Department of Internal Medicine, Endocrine Section

Peter Ebeling

Monash University - Department of Medicine

Ghada El Hajj Fuleihan

American University of Beirut - Calcium Metabolism and Osteoporosis Program

More...

Abstract

BACKGROUND: The growing number of systematic reviews/meta-analyses (SR/MAs) on the role of vitamin D in fracture prevention has led to conflicting results and contradictory guidelines. 

METHODS: This umbrella review evaluated SR/MAs of randomized controlled trials that compare the effect of vitamin D (±calcium) to placebo/control on fracture risk in adults, as identified from 4 databases (2010-2020). We assessed the quality of SR/MAs using the latest quality tool, AMSTAR-2. We compared their results and investigated reasons for discordance using matrices and sub-group analyses (PROSPERO registration: CRD42019129540).  

FINDINGS: We included 25 SR/MAs, 21 were of critically low quality, one of low quality, and three were of moderate quality (2 were on fall-related fracture). Vitamin D combined with calcium (Ca/D) reduced the risk of hip fractures in 8/12 SR/MAs (relative risk (RR) 0.61-0.84), and the risk of any fracture in 7/11 SR/MAs (RR 0.74-0.95), on pooled analyses. Important sources of discordance in results between SR/MAs were identified. These stem from inclusion of different trials, search periods, eligibility criteria, and differences in methodology. There was a trend for sub-group effect by residency, age and vitamin D status, but none reached statistical significance. All 19 SR/MAs on vitamin D alone compared to placebo/control reported no benefit. 

INTERPRETATION: Ca/D reduces the risk of hip and any fractures, results that seem driven by findings in institutionalized subjects. Age and baseline vitamin D status may be important predictors. Individual participant data meta-analyses of older patients on Ca/D would best unravel determinants for a beneficial response to such supplementation.

FUNDING STATEMENT: This study was in part supported by internal institutional funds from the Medical Practice Plan, at the American University of Beirut Medical Center.

DECLARATION OF INTERESTS: Drs M. Chakhtoura, D. Bacha, C. Gharios, Y. Jabbour, F. Kahale, A. Bassatne, S. Antoun, E. Akl and G. El Hajj Fuleihan, and Ms S. Ajjour and M. Assaad have no conflict of interest Dr. P. Ebeling reports grants and other from Amgen, grants from Eli-Lilly, grants from Alexion, other from Sanofi, outside the submitted work. Dr. R. Bouillon reports receiving small lecture fees from FAES (Spain), Proctor &Gamble (Belgium), Abiogen (Italy), and support for attending meetings and/or travel from FAES (Spain), Abiogen (Italy). Dr P. Lips reports receiving travel cost for vitamin D workshop from Abiogen.

Suggested Citation

Chakhtoura, Marlene and Bacha, Dania and Gharios, Charbel and Ajjour, Sara and Assaad, Mariam and Jabbour, Yara and Kahale, Francesca and Bassatne, Aya and Antoun, Stephanie and Akl, Elie and Bouillon, Roger and Lips, Paul and Ebeling, Peter and El Hajj Fuleihan, Ghada, Vitamin D Supplementation and Fractures in Adults: A Systematic Umbrella Review. Available at SSRN: https://ssrn.com/abstract=3796095 or http://dx.doi.org/10.2139/ssrn.3796095

Marlene Chakhtoura (Contact Author)

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Dania Bacha

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Charbel Gharios

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Sara Ajjour

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Mariam Assaad

American University of Beirut - Calcium Metabolism and Osteoporosis Program

Beirut
Lebanon

Yara Jabbour

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Francesca Kahale

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Aya Bassatne

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Stephanie Antoun

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon

Elie Akl

American University of Beirut - Department of Internal Medicine ( email )

Beirut
Lebanon

American University of Beirut - Center for Systematic Reviews on Health Policy and Systems Research (SPARK) ( email )

Beirut
Lebanon

McMaster University - Department of Health Research Methods, Evidence, and Impact (HEI) ( email )

Hamilton, Ontario L8N 3Z5
Canada

Roger Bouillon

Katholieke Universiteit Leuven - Department of Chronic Diseases, Metabolism and Ageing ( email )

Campus gasthuisberg ON2
Herestraat 49 - bus 400
Leuven, 3000
Belgium

KU Leuven - Clinical and Experimental Endocrinology ( email )

Oude Markt 13
Leuven, Vlaams-Brabant 3000
Belgium

Paul Lips

Amsterdam University Medical Center - Department of Internal Medicine, Endocrine Section ( email )

Amsterdam, Noord Holland
Netherlands

Peter Ebeling

Monash University - Department of Medicine ( email )

Clayton, Victoria 3800
Australia

Ghada El Hajj Fuleihan

American University of Beirut - Calcium Metabolism and Osteoporosis Program ( email )

Beirut
Lebanon