Inflammation as a contributing factor among postmenopausal Saudi women with osteoporosis

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Abstract

Postmenopausal osteoporosis is an important metabolic bone disease characterized by rapid bone loss occurring in the postmenopausal period. Recently, the most prevalent form of clinically significant osteopenia and osteoporosis involves various inflammatory conditions. The aim of the study is to evaluate the association between proinflammatory markers (interleukin [IL]-1β, IL-6, TNF-α) with bone turnover markers (BTMs) in postmenopausal Saudi women with and without osteoporosis. A total of 200 postmenopausal Saudi women ≥50 years old, 100 with osteoporosis and 100 without osteoporosis (control) were recruited under the supervision of qualified physicians in King Salman Hospital and King Fahd Medical City, Riyadh, Saudi Arabia. Serum tumor necrosis factor alpha (TNF-α), IL-1, IL-4, IL-6, and parathyroid hormone (PTH) were determined using Luminex xMAP technology. N-telopeptides of collagen type I (NTx) was assessed using ELISA, 25(OH) vitamin D and osteocalcin were determined using electrochemiluminescence, serum calcium and inorganic phosphate (Pi) were measured by a chemical analyzer. Serum IL-1β, IL-6, NTx, and PTH levels in women with osteoporosis were significantly higher than controls. Although IL-4 and osteocalcin were significantly lower than controls. IL-1β and TNF-α were positively associated with NTx in osteoporosis women. TNF-α, IL-6, and TNF-α were positively correlated with IL-lβ in both groups. A significant negative correlation between osteocalcin and IL-1β in healthy women and women with osteoporosis were observed. Findings of the present study implicate a role for cytokine pattern-mediated inflammation in patients with osteoporosis.

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Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.

S C Manolagas (2000)

The adult skeleton regenerates by temporary cellular structures that comprise teams of juxtaposed osteoclasts and osteoblasts and replace periodically old bone with new. A considerable body of evidence accumulated during the last decade has shown that the rate of genesis of these two highly specialized cell types, as well as the prevalence of their apoptosis, is essential for the maintenance of bone homeostasis; and that common metabolic bone disorders such as osteoporosis result largely from a derangement in the birth or death of these cells. The purpose of this article is 3-fold: 1) to review the role and the molecular mechanism of action of regulatory molecules, such as cytokines and hormones, in osteoclast and osteoblast birth and apoptosis; 2) to review the evidence for the contribution of changes in bone cell birth or death to the pathogenesis of the most common forms of osteoporosis; and 3) to highlight the implications of bone cell birth and death for a better understanding of the mechanism of action and efficacy of present and future pharmacotherapeutic agents for osteoporosis.

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Sex steroids and the construction and conservation of the adult skeleton.

Sundeep Khosla, L. Joseph Melton, B Riggs (2002)

Here we review and extend a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) as the key hormone for maintaining bone mass and E deficiency as the major cause of age-related bone loss in both sexes. Also, both E and testosterone (T) are key regulators of skeletal growth and maturation, and E, together with GH and IGF-I, initiate a 3- to 4-yr pubertal growth spurt that doubles skeletal mass. Although E is required for the attainment of maximal peak bone mass in both sexes, the additional action of T on stimulating periosteal apposition accounts for the larger size and thicker cortices of the adult male skeleton. Aging women undergo two phases of bone loss, whereas aging men undergo only one. In women, the menopause initiates an accelerated phase of predominantly cancellous bone loss that declines rapidly over 4-8 yr to become asymptotic with a subsequent slow phase that continues indefinitely. The accelerated phase results from the loss of the direct restraining effects of E on bone turnover, an action mediated by E receptors in both osteoblasts and osteoclasts. In the ensuing slow phase, the rate of cancellous bone loss is reduced, but the rate of cortical bone loss is unchanged or increased. This phase is mediated largely by secondary hyperparathyroidism that results from the loss of E actions on extraskeletal calcium metabolism. The resultant external calcium losses increase the level of dietary calcium intake that is required to maintain bone balance. Impaired osteoblast function due to E deficiency, aging, or both also contributes to the slow phase of bone loss. Although both serum bioavailable (Bio) E and Bio T decline in aging men, Bio E is the major predictor of their bone loss. Thus, both sex steroids are important for developing peak bone mass, but E deficiency is the major determinant of age-related bone loss in both sexes.

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Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit.

Natalie Sims, T John Martin (2014)

Coupling between bone formation and bone resorption refers to the process within basic multicellular units in which resorption by osteoclasts is met by the generation of osteoblasts from precursors, and their bone-forming activity, which needs to be sufficient to replace the bone lost. There are many sources of activities that contribute to coupling at remodeling sites, including growth factors released from the matrix, soluble and membrane products of osteoclasts and their precursors, signals from osteocytes and from immune cells and signaling taking place within the osteoblast lineage. Coupling is therefore a process that involves the interaction of a wide range of cell types and control mechanisms. As bone remodeling occurs at many sites asynchronously throughout the skeleton, locally generated activities comprise very important control mechanisms. In this review, we explore the potential roles of a number of these factors, including sphingosine-1-phosphate, semaphorins, ephrins, interleukin-6 (IL-6) family cytokines and marrow-derived factors. Their interactions achieve the essential tight control of coupling within individual remodeling units that is required for control of skeletal mass.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: January 2017

Publication date (Electronic): 27 January 2017

Volume: 96

Issue: 4

Electronic Location Identifier: e5780

Affiliations

[a ]Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University

[b ]Obesity, Endocrine and Metabolism Center, King Fahad Medical City, Faculty of Medicine

[c ]College of Medicine, King Saud bin Abdulaziz University for Health Sciences

[d ]Diabetes Care Center, King Salman Bin Abdulaziz Hospital

[e ]Department of Radiology and Medical Imaging, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.

Author notes

[∗ ]Correspondence: Nasser M. Al-Daghri, Prince Mutaib Bin Abdullah Chair on Osteoporosis, Biochemistry Department, College of Science, King Saud University, PO Box, 2455, Riyadh 11451, Kingdom of Saudi Arabia (e-mail: aldaghri2011@ 123456gmail.com ).

Article

Publisher ID: MD-D-16-05507 Accession ID: 05780

DOI: 10.1097/MD.0000000000005780

PMC ID: 5287950

PubMed ID: 28121926

SO-VID: 03a00178-ee79-4291-96d2-daca43448617

License:

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

History

Date received : 4 September 2016

Date revision received : 30 October 2016

Date accepted : 8 December 2016

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Keywords: bone turnover marker,25-oh vitamin d,osteoporosis,postmenopausal,proinflammatory cytokine

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Keywords: bone turnover marker, 25-oh vitamin d, osteoporosis, postmenopausal, proinflammatory cytokine

Inflammation as a contributing factor among postmenopausal Saudi women with osteoporosis

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Arab Journal of Forensic Sciences & Forensic Medicine (AJFSFM)

Most cited references 44

Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis.

Sex steroids and the construction and conservation of the adult skeleton.

Coupling the activities of bone formation and resorption: a multitude of signals within the basic multicellular unit.

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