Soluble RANKL and risk of nontraumatic fracture.
Abstract
CONTEXT: The receptor activator of nuclear factor kappaB ligand (RANKL) is essential for osteoclast and, possibly, osteoblast activation and may represent a key link between bone formation and resorption. OBJECTIVE: To determine the relationship between serum level of RANKL and the risk of nontraumatic fracture. DESIGN, SETTING, AND PARTICIPANTS: As part of a prospective population-based study conducted in Bruneck, Italy, we recorded all fractures that occurred between 1990 and 2000 in 906 participants and classified them as traumatic (n = 115) or nontraumatic (n = 31). Serum levels of RANKL and osteoprotegerin and characteristics of bone metabolism and lifestyle were assessed in 1990 and at follow-up in 1995 and 2000. MAIN OUTCOME MEASURE: Incident nontraumatic fracture by levels of RANKL. RESULTS: Levels of RANKL did not differ between sexes and were not related to age, menopausal status, lifestyle characteristics, or data from bone ultrasound at the heel. However, RANKL emerged as a significant predictor of nontraumatic fracture. In pooled logistic regression analysis, the relative risks of nontraumatic fracture in the lowest and middle vs highest tertile for RANKL were 10.0 (95% confidence interval [CI], 2.3-43.1) and 3.9 (95% CI, 0.8-19.0) (P<.001 for trend), respectively. Patients in the highest-tertile group had a low risk of fracture even in the presence of other predisposing factors, whereas women aged 60 years or older in the lowest tertile had a 5-year rate of nontraumatic fracture greater than 7%. CONCLUSIONS: A low level of RANKL is an independent predictor of nontraumatic fracture. This finding is consistent with the hypothesis of an important role of RANKL in human bone turnover and if confirmed in future investigations may gain relevance for assessment of fracture risk.
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In one study over half of postmenopausal women had undetectable RANKL concentrations, and in another 40% of samples were below the assay detection limit.
“However, in one of the studies over half of the women (54.9%) had concentrations of RANKL that were undetectable (379), and in the other study 40% of samples were below the detection limit of the assay (385).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [385]
Serum RANKL levels in postmenopausal women have been reported not to be associated with menopausal status or BMD, but to be associated with nontraumatic fracture.
“Serum RANKL levels have also been investigated in postmenopausal women and reported not to be associated with menopausal status or BMD (379, 385) but to be associated with nontraumatic fracture (385).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [385]
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- Authors
- Schett, G.
- Affiliations
- University of Vienna (AT)
- Corresponding author
- Schett, Georg
- ORCID
- Schett, Georg
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2004-03-03
- Volume
- 291
- Issue
- 9
- Pages
- 1108
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2145245207
- Cited by
- 146
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 1
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Keywords
- RANKL, non-traumatic fracture, osteoporosis, osteoclast activation, osteoprotegerin, bone turnover, fracture risk prediction, serum biomarkers, bone metabolism, menopause, osteoblasts
- MeSH terms
- Aged, Aged, 80 and over, Bone and Bones, Female, Fractures, Spontaneous, Glycoproteins, Humans, Life Style, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Socioeconomic Factors, Biomarkers, Incidence, Multivariate Analysis, Logistic Models, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin
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