Relationship of Sympathetic Activity to Bone Microstructure, Turnover, and Plasma Osteopontin Levels in Women
Open accessAbstract
CONTEXT: Studies in rodents have demonstrated that sympathetic activity reduces bone formation and bone mass; these effects are mediated by the noncollagenous matrix protein, osteopontin. OBJECTIVE: The objective of the study was to relate sympathetic activity (measured using microneurography at the peroneal nerve) to bone microstructure (assessed by high resolution peripheral quantitative computed tomography), bone turnover, and plasma osteopontin levels. DESIGN, SETTING, AND PATIENTS: Twenty-three women aged 20-72 yr (10 premenopausal and 13 postmenopausal) were studied in the Clinical Research Unit. RESULTS: Sympathetic activity (bursts per 100 heart beats) was 2.4-fold higher in postmenopausal as compared with premenopausal women (P < 0.001). In the two groups combined and after age adjustment, sympathetic activity was inversely correlated with trabecular bone volume fraction (r = -0.55, P < 0.01) and thickness (r = -0.59, P < 0.01) and positively correlated with trabecular separation (r = 0.45, P < 0.05). Sympathetic activity was negatively correlated with serum amino-terminal propeptide of type I collagen in postmenopausal women (r = -0.65, P = 0.015), with a similar trend in premenopausal women (r = -0.58, P = 0.082). Sympathetic activity was also negatively correlated with plasma osteopontin levels (r = -0.43, P = 0.045), driven mainly by the correlation in postmenopausal women (r = -0.76, P = 0.002). CONCLUSION: These findings represent the first demonstration in humans of a relationship between sympathetic activity and bone microstructure and circulating levels of amino-terminal propeptide of type I collagen and osteopontin. Given the critical role of osteopontin in mediating the effects of β-adrenergic signaling on bone, the inverse association between sympathetic activity and plasma osteopontin levels may reflect a negative feedback loop to limit the deleterious effects of sympathetic activity on bone metabolism. Based on the higher sympathetic activity observed in postmenopausal women, additional human studies are needed to define the role of increased sympathetic activity in mediating postmenopausal bone loss.
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P1NP and CTx in serum were quantified using validated standard assays.
“As we have established29,39,40, serum P1NP and CTx were measured with standard, validated assays: P1NP by radioimmunoassay (Orion Diagnostica, coefficient of variation <9%); and CTx by one-step ELISA (Nordic Bioscience Diagnostics, coefficient of variation <8%).”
From Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial (2024) · cites this paper as [39]
The Biochemical and bone turnover measurements section confirms that serum PINP was measured by radioimmunoassay and serum CTX by ELISA, with reported assay precision. But the cited paper names DiaSorin and Roche Diagnostics, not the Orion Diagnostica and Nordic Bioscience assays specified in the citing sentence; it also reports a between-assay CTX coefficient of variation of 8.0%, not less than 8%. (LLM, conf=0.91)
Experimental — accuracy not yet measuredA licensed X-ray technician with long experience performed the DXA scans, and phantom scans checked for drift.
“DXA scans of the lumbar spine (L1–L4), hip (femoral neck) and radius were obtained at baseline and 20 weeks (study endpoint) using the Lunar iDXA (GE Medical Systems; Encore software v.12.2) in the Mayo Clinic CRTU by a licensed X-ray technician with long-term experience29,39,40. Phantoms were scanned to detect potential drift and results were appended to a quality control database.”
From Effects of intermittent senolytic therapy on bone metabolism in postmenopausal women: a phase 2 randomized controlled trial (2024) · cites this paper as [39]
The DXA measurements section describes the scan sites and equipment but does not identify who performed the scans or mention phantom checks. The HRpQCT measurements section says a single operator performed those different scans, which does not establish the DXA technician's credentials. Searches for a licensed technician and phantom-based drift checks found no supporting passage in our copy. (LLM, conf=0.76)
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References 38 · Cited by 79
- Authors
- Farr, J. N., Charkoudian, N., Barnes, J. N., Monroe, D. G., McCready, L. K., Atkinson, E. J., Amin, S., Melton, L. J., Joyner, M. J., & Khosla, S.
- Affiliations
- Mayo Clinic (US)
- U.S. Army Research Institute of Environmental Medicine (US)
- Corresponding author
- Khosla, Sundeep
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-11
- Volume
- 97
- Issue
- 11
- Pages
- 4219-4227
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC3485606
- OpenAlex
- W2149154265
- Cited by
- 79
- References
- 38
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 6 · 2018: 8 · 2017: 3 · 2016: 1 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 1
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (RR024150, AG004875)
- National Institute on Aging (P01AG004875, AG004875)
- National Heart, Lung, and Blood Institute (HL 083947, R01HL083947)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007352)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-027065, R01AR027065)
- National Center for Research Resources (UL1RR024150)
- 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 › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- sympathetic activity, bone microarchitecture, osteopontin, bone turnover, bone formation, postmenopausal women, premenopausal women, trabecular bone volume, beta-adrenergic signaling, bone metabolism, trabecular bone
- MeSH terms
- Adult, Aged, Bone and Bones, Female, Humans, Middle Aged, Peroneal Nerve, Radiography, Sympathetic Nervous System, Bone Density, Premenopause, Postmenopause, Osteopontin
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