Relationship of sympathetic activity to bone microstructure, turnover, and plasma osteopontin levels in women

Joshua Farr, Nisha Charkoudian, Jill N. Barnes, David G Monroe, Louise K. McCready, Elizabeth J. Atkinson, Shreyasee Amin, L. Joseph Melton, Michael Joseph Joyner, Sundeep Khosla

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4219-4227
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume97
Issue number11
DOIs
StatePublished - Nov 2012

Fingerprint

Osteopontin
Bone Remodeling
Bone
Plasmas
Microstructure
Bone and Bones
Peroneal Nerve
Postmenopausal Osteoporosis
Osteogenesis
Adrenergic Agents
Rodentia
Tomography
Metabolism
Volume fraction
Demonstrations
Serum
Research
Feedback
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Relationship of sympathetic activity to bone microstructure, turnover, and plasma osteopontin levels in women. / Farr, Joshua; Charkoudian, Nisha; Barnes, Jill N.; Monroe, David G; McCready, Louise K.; Atkinson, Elizabeth J.; Amin, Shreyasee; Melton, L. Joseph; Joyner, Michael Joseph; Khosla, Sundeep.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 97, No. 11, 11.2012, p. 4219-4227.

Research output: Contribution to journalArticle

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AU - Farr, Joshua

AU - Charkoudian, Nisha

AU - Barnes, Jill N.

AU - Monroe, David G

AU - McCready, Louise K.

AU - Atkinson, Elizabeth J.

AU - Amin, Shreyasee

AU - Melton, L. Joseph

AU - Joyner, Michael Joseph

AU - Khosla, Sundeep

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N2 - 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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