Related Experiment Video
Updated: Sep 18, 2025
Evaluation of Amino Acid Consumption in Cultured Bone Cells and Isolated Bone Shafts
Published on: April 13, 2022
Relationship between homocysteine levels and bone quality in healthy adults - A systematic review and meta-analysis
Deepti K Sharma1, Tim Soon Cheok2, Manuela Rogers3
1Centre for Orthopaedic and Trauma Research, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia; Department of Orthopaedics and Trauma, Royal Adelaide Hospital, Adelaide, SA, Australia.
Insights
Elevated homocysteine (Hcy) impacts bone quality by increasing bone turnover and collagen crosslinking, potentially leading to reduced bone strength. This systematic review explores Hcy
Area of Science:
- Biochemistry
- Orthopedics
- Metabolic Bone Disease
Background:
- Elevated homocysteine (Hcy) is linked to increased fracture risk.
- B-vitamin supplementation lowers Hcy but has minimal effect on bone mineral density (BMD).
- Hyperhomocysteinemia may impair bone quality beyond BMD, affecting fracture risk.
Purpose of the Study:
- To systematically review the association between Hcy and bone quality outcome measures.
- Investigate Hcy's impact on bone turnover, microarchitecture, collagen crosslinks, and microdamage accumulation in healthy adults.
Main Methods:
- Systematic search of Pubmed, Embase, and Scopus up to September 30, 2024.
- Inclusion of studies with data on plasma Hcy and bone quality markers (microarchitecture, turnover, AGE pentosidine, collagen crosslinks, microdamage).
- Exclusion of patients on medications or with conditions affecting Hcy or bone health; inclusion of untreated osteoporotic patients.
Main Results:
- A significant positive correlation was found between Hcy and osteocalcin (r=0.39, p=0.023).
- Strong positive correlation between Hcy and serum pentosidine (r=0.72, p=0.020), indicating increased non-enzymatic collagen cross-linkage.
- Elevated Hcy associated with higher non-enzymatic and reduced enzymatic collagen crosslinks in bone.
Conclusions:
- Elevated Hcy negatively impacts bone quality outcome measures.
- The effect may be mediated by increased bone turnover and non-enzymatic collagen crosslinking.
- These changes likely contribute to decreased bone strength and increased fracture risk.
Background And Aims:
Patients with elevated homocysteine (Hcy) levels are associated with an increased risk of fracture. B-vitamin supplementation studies have consistently shown an ability to reduce Hcy levels but have had no or marginal effect on bone mineral density (BMD), which led us to hypothesize that hyperhomocysteinemia may increase fracture risk by altering bone quality outcome measures beyond BMD. The aim of our systematic review was to investigate the association between Hcy and bone quality outcome measures, i.e. bone turnover, bone microarchitecture, collagen crosslinks and micro damage accumulation, in healthy adults.
Methods:
A systematic search was performed on Pubmed, Embase, and Scopus from the date of inception to 30th of September, 2024. Studies were included that had sufficient data to identify the pooled relationship between plasma Hcy and at least one domain of bone quality, such as bone microarchitecture, bone turnover, advanced glycation product (AGE) pentosidine levels, collagen crosslinks, or micro damage accumulation. Studies involving patients who were on medications or had conditions affecting plasma Hcy or bone health were excluded. Osteoporotic patients were included only if they had not been treated.
Results:
Twenty-seven studies were included in our systematic review. Our meta-analysis found a significant positive correlation between Hcy and osteocalcin [Pearson's coefficient of correlation (r) = 0.39, significance value (p) = 0.023, 95 % Confidence Interval (CI) = 0.36-0.42]. No significant correlation was observed between Hcy and Procollagen type-1 N propeptide (P1NP), C-terminal telopeptide of type 1 collagen (CTX-1), or Bone-specific alkaline phosphatase (Bone ALP). Additionally, we found a strong positive correlation between Hcy and the AGE serum pentosidine [r = 0.72; 95 % CI: 0.67-0.76; p = 0.020], a molecule linked to increased non-enzymatic collagen cross-linkage. Further, two studies measured collagen-crosslinking in the bone, and both reported elevated Hcy to be associated with higher non-enzymatic crosslinks and reduced enzymatic crosslinks.
Conclusion:
Our results suggest that elevated Hcy impacts bone quality outcome measures. The effect is possibly mediated via increased bone turnover and accumulation of non-enzymatic collagen crosslinking, resulting in decreased bone strength.
Prospero Registration No:
CRD42024595870.
Related Concept Videos
01:29Bone Disorders
Bone deposition is also affected by the levels of sex hormones like estrogen and testosterone that promote osteoblast activity and bone matrix synthesis. When the level of these hormones decreases due to aging, it causes a reduction in bone deposition. As a result, bone resorption by osteoclasts...
01:25Role of Vitamins in Maintaining Bone Health
Vitamin A
Vitamin A is involved in the process of bone remodeling. Retinoic acid, the active metabolite of Vitamin A, has nuclear receptors in osteoblasts and osteoclasts, which are involved in bone remodeling.
Vitamin B12
Vitamin B12 acts as a cofactor during the formation of osteoblast-related proteins, such as osteocalcin. Vitamin B12 plays a role...
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:31Osteoclasts in Bone Remodeling
01:31Essential Minerals for Bone Health
Calcium and Phosphorus
Calcium is a critical component of bones, especially in the form of calcium phosphate and calcium carbonate. Since the body cannot make calcium, it must be obtained from the diet. However, calcium cannot be absorbed from the small intestine without...
01:17Hormones and Bone Tissue
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...