Literature Review
Volume 12 Issue 10 - 2021
Research on Hip Fracture Risk in Vitamin B12 Deficient Older Adults
Ray Marks*
Department of Health and Behavior Studies, Teachers College, Columbia University, New York, NY, USA
*Corresponding Author: Ray Marks, Department of Health and Behavior Studies, Teachers College, Columbia University, New York, NY, USA.
Received: September 20, 2021; Published: September 30, 2021


Introduction: Bone diseases, such as osteoporosis, as well as falls, when combined are especially prevalent among the older population. Associated with varying degrees of bone thinning, fragility, and increased susceptibility to fracture due to sarcopenia and other neuromuscular factors, preventing hip fractures is of high importance to all populations with aging citizens. Unfortunately, relatively little has been done over time to reduce the degree of bone destruction, or thinning, among other bone and muscle associated pathological changes underpinning one or multiple hip fracture occurrences.

Aim: This mini review focuses on the topic of hip fracture risk and prevention from the viewpoint of vitamin B12, a possible unexplored correlate of clinical relevance.

Methods: Articles of any genre concerning the possible association of vitamin B12 with bone health, muscle mass and function, frailty, and falls were specifically sought.

Results: A limited volume or research both tends to support or negate a role for vitamin B12 in the context of hip fracture risk and occurrences depending on what is studied and how it is studied and interpreted.

Conclusion: Sufficient rationale for a possible moderating or mediating role for vitamin B12 in some cases among the elderly who are malnourished, have malabsorption problems, and certain cardiovascular signs appears warranted.

Keywords: Bone; Cobalamin; Elderly; Falls; Hip Fracture; Osteoporosis; Sarcopenia; Vitamin B12


  1. McLean RR., et al. “Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women”. Journal of Clinical Endocrinology and Metabolism6 (2008): 2206-2212.
  2. Dai Z and Koh WP. “B-vitamins and bone health--a review of the current evidence”. Nutrients5 (2015): 3322-3346.
  3. Mithal A., et al. “Nutrition Working Group. “Impact of nutrition on muscle mass, strength, and performance in older adults”. Osteoporosis International 24 (2013): 1555-1566.
  4. Tanaka K., et al. “Insufficiency of B vitamins with its possible clinical implications”. Journal of Clinical Biochemistry and Nutrition1 (2000): 19-25.
  5. Swart KM., et al. “A randomized controlled trial to examine the effect of 2-year vitamin B12 and folic acid supplementation on physical performance, strength, and falling: additional findings from the B-PROOF Study”. Calcified Tissue International1 (2016): 18-27.
  6. Wolffenbuttel BHR., et al. “Association of vitamin B12, methylmalonic acid, and functional parameters”. Netherlands Journal of Medicine1 (2020): 10-24.
  7. Wee AK. “Serum folate predicts muscle strength: a pilot cross-sectional study of the association between serum vitamin levels and muscle strength and gait measures in patients >65 years old with diabetes mellitus in a primary care setting”. Nutrition Journal1 (2016): 89.
  8. Bulut EA., et al. “Vitamin B12 deficiency might be related to sarcopenia in older adults”. Experimental Gerontology 95 (2017): 136-140.
  9. Gedmantaite A., et al. “Associations between diet and handgrip strength: a cross-sectional study from UK Biobank”. Mechanisms of Ageing and Development 189 (2020): 111269.
  10. Macêdo LLG., et al. “Vitamin B12, bone mineral density and fracture risk in adults: a systematic review”. Journal of the Brazilian Medical Association9 (1992): 801-809.
  11. He T., et al. “The association of homocysteine, folate, vitamin B12, and vitamin B6 with fracture incidence in older adults: a systematic review and meta-analysis”. Annals of Translational Medicine14 (2001): 1143.
  12. Torbergsen AC., et al. “Micronutrients and the risk of hip fracture: case-control study”. Clinical Nutrition2 (2017): 438-443.
  13. Gjesdal CG., et al. “Plasma homocysteine, folate, and vitamin B12 and the risk of hip fracture: the Hordaland Homocysteine Study”. Journal of Bone and Mineral Research 5 (2007): 747-756.
  14. Tucker KL., et al. “Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study”. Journal of Bone and Mineral Research 1 (2005): 152-158.
  15. Inoue T., et al. “Undernutrition, sarcopenia, and frailty in fragility hip fracture: advanced strategies for improving clinical outcomes”. Nutrients12 (2020): 3743.
  16. Buesing S., et al. “Vitamin B12 as a treatment for pain”. Pain Physician 1 (2019): E45-E52.
  17. Matteini AM., et al. “Transcobalamin-II variants, decreased vitamin B12 availability and increased risk of frailty”. Journal of Nutrition Health and Aging 1 (2010): 73-77.
  18. Meyer M., et al. “Impact of malnutrition and vitamin deficiency in geriatric patients undergoing orthopedic surgery”. Acta Orthopaedica3 (2021): 358-363.
  19. Young J. “Rapid response to: prevention of falls in older people living in the community”. British Medical Journal 353 (2016): i1419.
  20. Watson J., et al. “Consequences of inadequate intakes of vitamin A, vitamin B 12, vitamin D, calcium, iron, and folate in older persons”. Current Geriatrics Reports2 (2018): 103-113.
  21. Shipton MJ and Thachil J. “Vitamin B12 deficiency - a 21st century perspective”. Clinical Medicine 2 (2015): 145-150.
  22. Pannérec A., et al. “Vitamin B12 deficiency and impaired expression of amnionless during aging”. Journal of Cachexia, Sarcopenia, and Muscle1 (2018): 41-52.
  23. Van Wijngaarden JP., et al. “Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses”. Journal of Nutrition and Metabolism 2013 (2013): 486186.
  24. Herrmann W and Obeid R. “Causes and early diagnosis of vitamin B12 deficiency”. Deutsches Ärzteblatt International40 (2008): 680-685.
  25. Calderón-Ospina CA and Nava-Mesa MO. “B vitamins in the nervous system: current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin”. CNS Neuroscience and Therapy1 (2020): 5-13.
  26. Green R., et al. “Vitamin B12 deficiency”. Nature Reviews: Disease Primers 3 (2017): 17040.
  27. Soh Y and Won CW. “Association between frailty and vitamin B12 in the older Korean population”. Medicine (Baltimore)43 (2020): e22327.
  28. O’Leary F and Samman S. “Vitamin B12 in health and disease”. Nutrients3 (2010): 299-316.
  29. Wolffenbuttel BHR., et al. “The many faces of cobalamin (vitamin B12) deficiency”. Mayo Clinic Proceedings: Innovations, Quality, and Outcomes2 (2019): 200-214.
  30. Stone KL., et al. “Effect of combination folic acid, vitamin B6, and vitamin B12 supplementation on fracture risk in women: a randomized, controlled trial”. Journal of Bone and Mineral Research12 (2017): 2331-2338.
  31. Dokuzlar O., et al. “Association between serum vitamin B12 level and frailty in older adults”. Northern Clinics of Istanbul1 (2017): 22-28.
  32. Van Dijk M., et al. “Reduced dietary intake of micronutrients with antioxidant properties negatively impacts muscle health in aged mice”. Journal of Cachexia, Sarcopenia, and Muscle1 (2018): 146-159.
  33. Egan W., et al. “Vitamin B12 deficiency-induced neuropathy secondary to prolonged recreational use of nitrous oxide”. American Journal of Emergency Medicine9 (2018): 1717.e1-1717.e2.
  34. Verlaan S., et al. “Nutritional status, body composition, and quality of life in community-dwelling sarcopenic and non-sarcopenic older adults: a case-control study”. Clinical Nutrition1 (2017): 267-274.
  35. Takahashi F., et al. “Vitamin intake and loss of muscle mass in older people with type 2 diabetes: a prospective study of the KAMOGAWA-DM cohort”. Nutrients 7 (2021): 2335.
  36. Kalimeri M., et al. “Folate and vitamin B-12 status is associated with bone mineral density and hip strength of postmenopausal Chinese-Singaporean women”. JBMR Plus 10 (2020): e10399.
  37. Ao M., et al. “Relationship between homocysteine, folate, vitamin B12 and physical performance in the institutionalized elderly”. Journal of Nutritional Science and Vitaminology 1 (2019): 1-7.
  38. Behrouzi P., et al. “Dietary intakes of vegetable protein, folate, and vitamins B-6 and B-12 are partially correlated with physical functioning of Dutch older adults using copula graphical models”. Journal of Nutrition 3 (2020): 634-643.
  39. Lewerin C., et al. “Low holotranscobalamin and cobalamins predict incident fractures in elderly men: the MrOS Sweden”. Osteoporosis International1 (2014): 1311-1340.
  40. Majumder A., et al. “Causes and consequences in skeletal muscle myopathy”. Journal of Cell Biochemistry8 (2017): 2108-2117.
  41. Franques J., et al. “Characteristics of patients with vitamin B12-responsive neuropathy: a case series with systematic repeated electrophysiological assessment”. Neurology Research6 (2019): 569-576.
  42. Mizrahi EH., et al. “Low borderline levels of serum vitamin B12 may predict cognitive decline in elderly hip fracture patients”. Israel Medical Association Journal5 (2017): 305-308.
  43. Berlie HD and Garwood CL. “Diabetes medications related to an increased risk of falls and fall-related morbidity in the elderly”. Annals of Pharmacotherapy4 (2010): 712-717.
  44. Gwathmey KG and Grogan J. “Nutritional neuropathies”. Muscle Nerve1 (2020): 13-29.
  45. Singh P., et al. “Maternal vitamin B12 in mice positively regulates bone, but not muscle mass and strength in post-weaning and mature offspring”. American Journal of Physiology: Regulatory, Integrative, and Comparative Physiology6 (2020): R984-R993.
  46. Pawlak R. “Vitamin B12 status is a risk factor for bone fractures among vegans”. Medical Hypotheses 153 (2021): 110625.
  47. Meyer HE., et al. “Association of high intakes of vitamins B6 and b12 from food and supplements with risk of hip fracture among postmenopausal women in the Nurses' Health Study”. JAMA Network Open5 (2019): e193591.
  48. Dhonukshe‐Rutten., et al. "Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people”. Journal of Bone and Mineral Research6 (2005): 921-929.
  49. Jatoi S., et al. “Low vitamin B12 levels: an underestimated cause of minimal cognitive impairment and dementia”. Cureus2 (2020): e6976.
  50. Tangney CC., et al. “Vitamin B12, cognition, and brain MRI measures: a cross-sectional examination”. Neurology13 (2011): 1276-1282.
  51. Dharmarajan TS., et al. “Vitamin B12 deficiency. Recognizing subtle symptoms in older adults”. Geriatrics (Basel, Switzerland)3 (2003): 30-34.
  52. Mosen DM., et al. “Food insecurity associated with self-reported falls among medicare advantage members”. Population Health Management6 (2019): 536-539.
  53. Allen LH., et al. “Biomarkers of Nutrition for Development (BOND): vitamin B-12 review”. Journal of Nutrition4 (2018): 1995S-2027S.
  54. Marks R. “Hip fracture epidemiological trends, outcomes, and risk factors, 1970-2009”. International Journal of General Medicine 3 (2010): 1-17.
  55. Langan RC and Goodbred AJ. “Vitamin B12 deficiency: recognition and management”. American Family Physician6 (2007): 384-389.
  56. Ng TP., et al. “Homocysteine, folate, vitamin B-12, and physical function in older adults: cross-sectional findings from the Singapore Longitudinal Ageing Study”. The American Journal of Clinical Nutrition6 (2012): 1362-1368.
  57. Vincenti A., et al. “Perspective: practical approach to preventing subclinical b12 deficiency in elderly population”. Nutrients6 (2021): 1913.
  58. De Martinis M., et al. “Hyperhomocysteinemia is associated with inflammation, bone resorption, vitamin B12 and folate deficiency and mthfr c677t polymorphism in postmenopausal women with decreased bone mineral density”. International Journal of Environmental Research and Public Health12 (2020): 4260.
  59. Stone KL., et al. “Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study”. Journal of Clinical Endocrinology and Metabolism3 (2004): 1217-1221.
  60. Tardy AL., et al. “Vitamins and minerals for energy, fatigue and cognition: a narrative review of the biochemical and clinical evidence”. Nutrients1 (2020): 228.
  61. Spence JD. “Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke”. Nutrition Research 2 (2016): 109-116.
  62. Health Quality Ontario. “Vitamin B12 and cognitive function: an evidence-based analysis”. Ontario Health Technology Assessment Service 23 (2013): 1-45.
  63. Porter K., et al. “Causes, consequences and public health implications of low B-vitamin status in ageing”. Nutrients 8 (2016): 725.
  64. Van de Lagemaat EE., et al. “Vitamin B12 in relation to oxidative stress: a systematic review”. Nutrients 11 (2019): 482.
Citation: Ray Marks. “Research on Hip Fracture Risk in Vitamin B12 Deficient Older Adults”. EC Orthopaedics 12.10 (2021): 60-72.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

November Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the November issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before December 15, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.